Vitamin D & other nutritional supplements to protect against severe COVID-19 symptoms

This is the only way we can cope with COVID-19 without the twin disasters of the suffering, harm and death caused by some people's weakened and dysregulated immune response to SARS-CoV-2  infection and the comparably deadly, disastrous, lockdowns which are currently government's only way of protecting people from harm and death.

For links to research articles on how vitamin D supplementation and blood levels, please see:  https://aminotheory.com/cv19/d3/ .


Robin Whittle  rw@firstpr.com.au 2020-10-10 10:30 UTC  Please reload this and the other pages since I update them frequently.   The structure is less than ideal since I have been adding material since late March.

Be sure to read the Disclaimer below: #disclaimer which is followed by contact and copying details.  I am not a doctor.  Even if I was, I have not examined you.   The updates/ page lists all the significant updates to these cv19 pages.  Be sure to see the list of recent research articles #lr !

If you are a researcher, MD or nurse with vitamin D expertise, please consider joining an email  discussion list https://groups.google.com/g/vitamindcovid19/ of other such people who are working on an open letter to world leaders, public health officials and MDs regarding robust vitamin D supplementation.  This would bring numerous health benefits, starting with greatly reduced COVID-19 severity and viral shedding - and so a great reduction in it spreading, even without lockdowns, social distancing and masks.   The list is run by Gareth Davies https://www.gruffdavies.com and Karl Pfleger https://agingbiotech.info/vitamindcovid19/.

Please also consider joining the Nutrition for Immune System Health (NISH) email discussion list, which I run: https://nish.groups.io .

Quick intro

If everyone supplemented with sufficient vitamin D3 to achieve ancestral blood levels (25OHD, the form needed by immune cells and created from D3 in the liver) of 40 to 60ng/ml (100 to 150nmol/L = one part in 25 million to 16.7 million) then the autocrine signaling processes (explained below) inside many types of cell, especially immune cells, would function properly. 

With lower levels (such as 8 to 28ng/ml - which is typical for people who do not supplement and who do not receive much high elevation sunlight on their skin - the autocrine signaling cannot work properly, so immune responses are both weak and dysregulated.   "Dysregulation" means overly-aggressive, pro-inflammatory and destructive - responses which drive the cytokine storm which is the fundamental mechanism of COVID-19 severe symptoms and sepsis.

To achieve these target levels of 40 to 60ng/ml, average weight adults need 0.125mg (5000IU = 1/8000 gram) of D3 a day - and it is fine to take this average amount once every week or two.   This is about ten times the intake many governments recommend.  For instance the UK government recommends 0.01mg (400IU) D3 a day with vitamin D deficiency being defined as below 10ng/ml (25nmol/L) - less than a quarter of what we need.
 
0.125mg is a gram every 22 years, and the ex-factory price of pharmaceutical D3 is USD$2.50 a gram.   So the cost of this 45 milligrams of D3 a year is about US 13 cents a year.  (It just needs to be made into 52 weekly capsules of 0.875mg D3.)  Overweight people need more than this and obese people should take at least twice as much.  (See the d3/ page for details.)   Toxicity is possible at levels above 150ng/ml, but this can only be attained by weeks or months of ingesting ten or more times this.

If everyone aimed for these this 40 to 60ng/ml definition of vitamin D repletion, and most people achieved this (there's not enough doctors or labs to be continually testing the world's population for their 25OHD blood vitamin D levels), some would have less than this and quite a few would have more, which is fine.  It would double or triple most people's current levels.  Assuming this was achieved, then, all year round, no matter how dark a person's skin, and no matter how little their skin is exposed to high elevation sunlight:
Consequently:

There would be no need for lockdowns, social distancing, masks or vaccines.  COVID-19 would probably spread slowly to the majority of the population, and a much smaller number of people -  those people with other serious health concerns, including obesity and old age - would need medical care if they were infected.

It would not matter how the SARS-CoV-19 virus mutated.  The virus can mutate to a different form which is not affected by immunity gained from prior current strain infection, or from vaccines targeting current stains.  Such mutations wouldn't alter the protection from severe symptoms given by adequate vitamin D levels.

There are many chronic and acute diseases which are in small or large part caused by vitamin D deficiency.  These would become less prevalent.  See #kp below for some of these listed.

Other major benefits of ending the global vitamin D deficiency pandemic include:

There would be no need for influenza vaccines.  As with COVID-19, transmission and severity would both be greatly reduced, all year round. 

There would be a great reduction in incidence of sepsis - a suddenly occurring, difficult to diagnose quickly, immune dysregulation disorder which harms and kills within hours.

Likewise ARDS (Acute Respiratory Distress Syndrome) and, in children and adolescents, and Kawasaki disease and Multisystem Inflammatory Syndrome, both of which are triggered by COVID-19, but only in children and adolescents with very low vitamin D levels. 

Most doctors are unaware of the importance of vitamin D to immunity.  For instance, despite excellent Italian research in 2015 #2015-Stagi showing that Kawasaki disease children have very low levels of vitamin D, and those with the lowest levels have the most severe symptoms (coronary artery aneurysms), most doctors have no idea that low vitamin D levels are a precondition for KD.  So they don't supplement KD children with D3, beyond whatever low level is in hospital food.  The children generally recover - perhaps in part due to gaining D3 from the plasma transfusions they are typically given.

Most people assume that most doctors are up-to-speed with all the pertinent research for whatever condition they are being treated for.  In the case of many diseases caused by inadequate vitamin D, this is tragically not the case.   A handful of doctors and researchers have been trying to educate the majority of doctors about vitamin D for decades, with limited success.  The need for this has long been critical, since millions of people die from sepsis, influenza, ARDS and other conditions which result in large part from inadequate vitamin D.  The COVID-19 crisis makes this education campaign far more urgent.

Doctors and nurses have a very difficult job.  They acquire knowledge and experience of thousands of biological processes and human diseases.   They know all sorts of things, from resuscitation, minor surgery, and ear cleaning to very complex diagnostic criteria and drug interactions

They are generally not very well trained in nutrition and they are constantly schmoozed by pharmaceutical companies.  So they are generally overly enamoured of drugs and acute interventions, and do not know enough about nutrition, the immune system and prevention of disease.   There is a vast and at times bewildering array of research and doctors absolutely cannot keep up with this.  They rely on guidelines developed by committees - and these are often out of date and influenced by pharmaceutical companies.   Furthermore, many patients - unwisely - expect their doctors to give them a pill or a vaccine or whatever to specifically fix their current ailment.

Instead, doctors and patients should pay a lot more attention to nutrition and prevention.   Please ask your doctor to read this site, especially the sections on autocrine signaling in immune cells #vitd-autocrine and the latest research on vitamin D and other nutrients regarding COVID-19 #lr .


2020-09-29 update: Please see this excellent video presentation at VitaminDUK.com :

Vitamin D – BIG news about Coronavirus



1 BIG numbers – Analysis of 190,000 tests

Professor Michael Holick MD, Boston University - the world's foremost vitamin D researcher.

2 BIG view – Overview of 15+ trials
William Grant PhD, San Francisco - another long time vitamin D researcher.

3 BIG data – Causal Inference from 240 locations
Gareth Davies PhD, physicist, UK.

4 BIG questions – Bradford Hill’s Criteria
David Grimes MD, gastroenterologist, UK.  This is a great presentation on all the criteria required to "prove" (in science, establish the veracity of, beyond reasonable doubt) a medical hypothesis - in this case that good vitamin D levels are essential for good general health and for protecting against severe COVID-19 symptoms.

5 BIG answers – Next steps?
Rufus Greenbaum, citizen scientist, UK.


Vitamin D supplementation guide - especially concerning COVID-19

The d3/ page links to the best research articles on desired vitamin D blood levels - 40 to 60ng/ml, and reproduces a diagram which shows the amounts of supplemental vitamin D3 which are needed to achieve this, on average, for people with underweight, normal, overweight and obese body types.

This is intended to be applicable to all people - not just those who can access a doctor and pathology lab to test their vitamin D levels.

See also 3-reasons/ why I want everyone in the world to have good nutrition for immune system health.  The first is general and simple.  The second and third are unique to the COVID-19 crisis.



#mn-xover

Mother Nature's crossover trial of summer and winter vitamin D levels

2020-08-28: Please see the 5th comment at:

https://quillette.com/2020/08/27/covid-19-returns-to-new-zealand/

which is a good introduction to the material on this and other pages here.

2020-08-28, updated 2020-09-10:

I argue against the common idea that the drop in new cases per day in the UK and some other northern hemisphere countries, from about April-May, is due to herd immunity.  I argue that it is partly due to lockdown, which is continuing, and mainly due to the summer peak of vitamin D levels which somewhat reduces the chance of contracting the disease for any given viral insult, but most importantly reduces the severity of the disease AND reduces the amount of viral shedding, on average.  I propose that this lower level of shedding (which as far as I known has never been measured) greatly reduces transmission and caused the drop in new cases per day per million people, graphed below. 





Link to the latest version of the above graph from Our World in Data.

We see that "new cases" are rising again in several these and some other countries further north than about 35°.   At the same time, it does not appear that deaths are increasing.  (I don't know of graphs for hospitalisation.)





Link to the latest version of the above graph from Our World in Data.


We are now entering a new phase of Mother Nature's crossover trial, in which vitamin D is dropping - or will drop after September see #2004-UK-vit-D below - in countries 40 to 60 degrees north of the equator.  So viral shedding, rates of infection and (I assume) severity are - or will in or after September - all increasing as 25OHD vitamin D blood levels descend again towards their winter nadir around February.

A possible explanation other than lockdowns and summer vitamin D levels:

It is possible that the upswing in daily “new cases” is partly or wholly caused by increased use of antibody (and perhaps antigen) tests in the last month or two. The original PCR tests detected viral RNA and so indicated current or recent (weeks) infection. Assuming no false positives, antibody tests are positive for people who were previously infected. A positive antibody test for a person who was not previously PCR tested, or who was and tested negative, may be counted as a “new case” even though their infection may have been months ago.

For this pattern to significantly add to the “new cases” count, significant numbers of such people – who are presumably no longer symptomatic, and who may never have had more than mild symptoms – would need to be presenting for an antibody test. To the extent that antibody tests are widely deployed for such people and the results counted in this way, the rise in “daily new cases” does not generally represent people who were infected in the last week or so.

This explanation is advanced by biochemical engineer Ivor Cummings, better known as https://thefatemperor.com in this 2020-08-12 video: Crucial Viewing – to truly understand our current Viral Issue #Casedemic https://www.youtube.com/watch?v=FU3OibcindQ .  He points to graphs of rising new cases with no matching rise in deaths.  I am unsure to what extent this explains the upswings in "new cases".

If summer vitamin D levels did suppress transmission significantly, such as by reducing viral shedding, then the coming months - October to December 2020 and to March 2021 - will show this, because genuinely new cases will rise inexorably as average vitamin D levels drop, (as will death rates) unless there is a return to extreme lockdowns and perhaps in spite of those lockdowns. While some extra vitamin D supplementation is presumably occurring now, it is not enough to protect entire populations from winter declines in vitamin D levels.

2020-08-31 update:  BBC-2's Newsnight reports https://www.bbc.co.uk/programmes/p08pz1fm on a leaked SAGE (Scientific Advisory Group for Emergencies) report with a worst-case prediction for 81,000 excess deaths directly attributed to COVID-19 and 27,000 excess deaths not related to COVID-19.  Greg Fell, Public Health Director for Sheffield said: "We know cases will rise into the autumn and winter.  There's no doubt about that."  However, there is no mention of vitamin D or the precise mechanisms which make COVID-19, influenza or various common cold viruses (some of which are also coronaviruses) seasonally more active in winter and spring.

He said that the reason the death rate remains low while new cases are rising is that in the first wave, the mean age was in the mid to high 60s.  (I assume he is talking about people who needed medical care, but perhaps he means confirmed cases, which would be skewed by low testing rates in younger people who felt they were not at risk of bad outcomes.)  Now the mean age is in the mid 30s to the early 40s.  Fewer people need to be hospitalised and "almost zero" need intensive care.  (I don't have a clear idea of what is going on here or why the average age has dropped.)


#kp

The case for worldwide vitamin D supplementation

For links to the latest research into vitamin D, immunity and COVID-19, please see the next section

See also the section #vaccines below where I argue that a COVID-19 vaccine is absolutely the wrong approach.  It doesn't even solve the right problem.  This virus is not the problem.   The problem is people's weakened and dysregulated immune systems - and this already causes far more trouble than COVID-19 would cause even if everyone in the world contracted the disease with their currently generally weak and dysregulated immune responses.

The most concise, well-referenced, business and moral case for an urgently implemented worldwide program of vitamin D supplementation is Karl Pfleger's frequently updated essay.  This was written and is maintained entirely independently of this aminotheory.com material - so the vision of supplementation it presents is not the same as what I am proposing.

Low Vitamin D Worsens COVID-19
http://agingbiotech.info/vitamindcovid19/

While high vitamin D levels may protect somewhat against infection, this is insignificant in the face of the highly contagious SARS-CoV-2 virus. 

The first critical point is that vitamin D deficiency is the most important, easily correctable, cause of the immune system weakness and dysregulation which drives COVID-19 harm and death

The second critical point is that vitamin D deficiency is the most important, easily correctable, cause of high rates of viral shedding and so of rapid spread of SARS-CoV-2 infection.

A worldwide program of vitamin D repletion can reasonably be expected to play a decisive and essential role in improving everyone's immune system health, so as to render COVID-19 at most a nuisance, and (except perhaps for a some people with lung injuries or other severe health conditions) no longer the serious, disastrous, cause of suffering, hospitalisation, harm and death which it is today

Population-scale vitamin D supplementation can and should be implemented sooner than any safe, effective, well-tested vaccine could be widely deployed, with much greater safety , greater health benefits, and lower cost.


You are reading a very long web page which has grown since late March.  Here is my attempt at summarising the urgent need for worldwide vitamin D supplementation, aiming for all babies, children, adolescents and adults to have 40 to 60ng/ml vitamin D levels, with no great concerns that some people's levels will be twice these.

There is a growing body of epidemiological, clinical and cellular evidence which shows that low vitamin D levels are a major cause of the weakened and dysregulated (overly-aggressive, hyper-inflammatory, self-destructive) immune responses which, in some people, cause the severe symptoms of COVID-19, including the endothelial cell (blood vessel lining) damage which causes the body to make the blood thick and hyper-coagulative.  This hypercoagulative state drives most of the resulting damage, with microembolisms (tiny blood clots) forming in the lungs, brain, heart, liver kidneys etc. along with heightened risk of large blood clots in the brain (stroke) or the coronary arteries (heart attack).  Lasting harm and organ damage typically results from this hypercoagulative state, which sometimes begins even in the presence of relatively mild symptoms.

For decades, a growing body of research has documented the global vitamin D deficiency pandemic.  Since 2008 vitamin D specialist researchers and MDs have recommended that everyone should try to attain vitamin D blood levels (25 hydroxy vitamin D, produced in the liver from ingested or UVB produced D3) of 40 to 60ng/ml (100 to 150nmol/L) all year round.  100ng/ml is considered the the high end of normal, but some people are perfectly healthy - indeed with healthier regarding reductions in asthma and other diseases - with higher levels.  Toxicity - hypercalcemia which damages bone and  blood vessels - bone is possible above 150ng/ml but is most likely to begin at higher levels still.   Such levels cannot be attained through sun or artificial UVB light exposure. 

Without supplements most people's year-round average 25OHD levels are in the 10 to 25ng/ml range and are lower still in winter.  The best estimate we have of the 25OHD levels of our ancestors is 46ng/ml - the average levels of traditionally living East African Maasai herders and Hadzabe hunter gatherers: https://www.ncbi.nlm.nih.gov/pubmed/22264449 .  The internal (autocrine) signaling systems of many of our cells evolved to work with this supply of 25OHD.

As you can read below, some groups of people have 25OHD levels disastrously below 10ng/ml.  Yet UK government standards state that 10ng/ml is an adequate level and many other countries, including the USA define vitamin D repletion as 20ng/ml 25OHD.  The UK and US recommended supplemental D3 intake for adults is 0.01mg (400IU) and 0.015mg (600IU), which are about a 10th of what normal weight adults, on average, need to attain 40ng/ml
The Endocrine Society's standard for repletion is 30ng/ml.

Food - including fortified foods and drinks - and multivitamins contain only small amounts of vitamin D.  Pharmaceutical grade vitamin D3 (cholecalciferol) is produced industrially mainly in China and India.  The ex-factory 1kg lot price is around USD$2.50 a gram.  0.125mg (5000IU) a day is sufficient to raise most normal weight adults' 25OHD levels to at least 40ng/ml.  At this rate, a gram lasts for 22 years.  So raw cost of this healthy level of supplementation is  USD$0.12 a year.  D3 need only be taken every week or two, so it would suffice to supply it as 52 capsules a year, each containing 0.875mg (35,000IU).  Babies and children need less, according to body weight.  Overweight and obese people need significantly more due to their greater body weight and because D3 is absorbed by their greater proportion of adipose tissue.

Ideally, all people would have ready and affordable access to their own personal doctor who advises them according to the best research, and who is able to order blood tests to monitor their 25OHD levels every year or two.  However, this is impossible for all 7.8 billion humans, and the costs would vastly exceed those of the D3 supplements.  Many doctors are either unaware of the best vitamin D research and/or are constrained by government, professional association, hospital and insurance rules and guidelines regarding 25OHD testing and the ideal blood levels and supplementation intakes they can advise for their patients.

Dozens of chronic and acute diseases are caused by weak and dysregulated (over-inflammatory) immune systems, as listed below.

One primary cause of immune system dysregulation is - with considerable genetic variation between individuals - that our immune systems evolved to be more aggressively inflammatory than is desirable, because our ancestors were all infected with helminths (intestinal worms), which produce a variety of compounds which downmodulate many immune responses.  Now, with most humans being free of helminthic infection, some of our immune responses are self-destructive.  For instance, patients with Crohn's disease (auto-immune destruction of the intestines) go into remission when infected with the relatively benign pig whipworm.  #helminthsgone .  Some people, such as those with life-threatening asthma, infect themselves (helminthic therapy) to obtain relief.  There is ongoing research into pharmaceutical approaches to mimicking at least some of the helminths' downmodulatory effects, but commercially available products for this are a long way off.

The other primary cause of weakened and dysregulated immune systems is nutritional deficiencies - and, arguably, an excess of salt.  Vitamin D deficiency is the best researched, most important and easiest to correct of these.  Inadequate omega 3 fatty acids (as found in fish and algae oils) is probably the second most important, and can easily be corrected - though the quantities needed and the annual cost is much greater than for vitamin D.

Inadequate boron #08-boron is also known to drive overly inflammatory immune system dysregulation.  Boron supplementation is widely used to treat arthritis, and boron, as borax, is appearing in some mass market multivitamins.  However, despite decades of research showing its importance to humans, and its routine use in preventing bone and joint problems in pigs and other agricultural animals, according to conventional (textbook and nutritional guideline) understanding, boron has no role in the nutrition of animals. 

Boron, as borax, is readily available, inexpensive and very safe to use in the 6 to 12mg per day range which would probably lead to repletion (there are no standards for this, yet) and significant health benefits over the typical 1mg daily intake of most adults. 

Boron's half-life is ~22 hours, so small quantities need to be taken each day.  12mg a day would require 36 grams of borax per year, and it costs less than USD$0.01 per gram.  Borax is a sodium oxygen salt of boron.  Large deposits of this mineral are mined in Turkey and California, with relatively simple crystallisation purification at the mine site,

Despite the vast amount of vitamin D research, many doctors remain unaware of the benefits of repletion to at least 40ng/ml, or wary about such levels because of outdated and overly cautious concerns about toxicity.  The pharmaceutical industry has no interest in promoting vitamin D, since worldwide repletion would greatly reduce the global burden of disease which drives most of its sales of high-profit, patented, drugs.  Boron research is generally unknown to doctors and even to most vitamin D researchers.

Even in diseases where research has clearly established very low vitamin D levels to be a distinctive - and no-doubt largely causative - factor, including the childhood immune dysregulation disorder Kawasaki disease #2015-Stagi (now being triggered with much greater frequency by COVID-19), many doctors remain unaware #kdarticles that vitamin D deficiency is involved, so they fail to test or replete their patients' vitamin D levels.

Potassium deficiency, especially in the context of excessive salt, is a global problem which research shows beyond any doubt is the primary avoidable cause of hypertension and stroke kna/ .   Potassium supplementation is challenging because of the quantities involved - such as 2.5 grams potassium a day to approximately double the normal intake.   This is possible, at the cost of around USD$100 a year, with potassium gluconate solution, which has a very mild taste.   However I have never encountered a doctor who is aware of this.  So many or most people my age (I am a 1955 model) take expensive hypertension drugs, all of which have significant ill-effects - and sometimes additional drugs to counter those ill effects.  Potassium supplementation and modest avoidance of salt solves the problem of K / Na ionic balance in all cells of the body, removes the primary causes of hypertension and stroke, and provides numerous other benefits - no-doubt including immune system strength and regulation.

Iron is a well known nutritional deficiency, and many people are deficient in vitamin C, magnesium and zinc.   Here is a table of the five nutrients whose common deficiency most contribute to immune system dysfunction and general ill-health.  A future website, to be known as Five Neglected Nutrients, will cover these in greater detail than is possible here. 

Ideally we would replete all five, for all people on Earth, as a matter of urgency - and that was the situation before COVID-19.  Since COVID-19 harm and death results only from a subset of the population having weakened and dysregulated immune systems (in combination wit genetic variation, obesity, advanced age and several comorbid conditions) it is absolutely imperative that governments and doctors work together to replete vitamin D and ideally some of the others, with an urgency which only occurs in times of war.

Nutrient
Medical profession knowledge of mechanisms of the nutrient's benefits, and so of the problems caused by deficiency.

(Most doctors receive inadequate training in nutrition.)
Medical profession consensus on supplementation.
Practicality for global repletion in the coming months to render COVID-19 no longer a threat.
Vitamin D
Vast amount of research, yet not very well known except to a subset of doctors who are well aware.
General disinterest and some controversy - with a small, growing, number of doctors adamantly promoting vitamin D repletion for general health and protection from COVID-19 harm and death.
Practical, safe, inexpensive and absolutely vital for general health and for reducing COVID-19 severe symptoms and the rate at which the disease spreads.  New D3 factories are urgently required.
Omega 3 oils
Good research on immune system benefits, though not very widely known.
General disinterest and some controversy - again with some doctors in favor.  No controversy about safety - so should be used by all who have it available.

Would surely help with COVID-19, but there is no research to quantify this.
Impossible to quickly scale up fish or algae oil production to meet needs of grams a day per 7.8 billion persons.  2g/day 6 billion adults = 4.4 million tonnes / year.
Boron
Good research, but precise cellular mechanisms not yet well understood.

Not recognised as a nutrient.  Most doctors have never heard of it, although it is used to reduce or prevent arthritis.

See #08-boron .
Only a handful of doctors are aware of it. 

Would surely help with COVID-19, but there is no research to quantify this.
Readily available as borax, very inexpensive, safe and easy to ingest in water solution.

However, doctor's general ignorance of this and widespread misconceptions about its toxicity make boron supplementation challenging in the short time frame we have to render COVID-19 no longer a threat.
Vitamin C
Very well researched and recognised.
Controversy about dosage, with some high dose protocols probably unnecessary for most people, while providing benefits for some. 

Dr Paul Marik's 10g/day IV vitamin C MATH+ protocol for ICU patients, including especially those with COVID-19, remains controversial despite obvious benefits.
Production could be increased somewhat, but I suspect it would be best to keep limited vitamin C in reserve for people who are COVID-19 positive so they can use multi-gram quantities a day and hopefully stop the virus from infecting their lungs.
Potassium
Excellent research on hypertension and stroke, but not widely known.

Fundamental importance to ionic balance of all cells is well established, but not widely recognised by doctors.

See kna/ .
Virtually all doctors and, as far as I know, most researchers assume that potassium supplementation is impossible due to the strong taste of the salts.  They do not know about potassium gluconate's mild taste.

Doctors are coached heavily in the dangers of excessive intravenous potassium supplementation since the body can only handle limited quantities at any one time.  Overdoing it, including by drinking excessive potassium gluconate at any one time, will raise blood potassium too much before the cells absorb it and so cause potentially deadly heart problems.
No prospect of ramping up potassium gluconate for global needs except over many years.

There are safety concerns with such supplementation being taken too quickly, so it needs to be spread throughout the day.

These problems - and many doctors being alarmed at the prospect of patients drinking a potassium solution - mean that progress towards global potassium repletion needs to be made cautiously and not at all in the current crisis.

See also this article on vitamin B: https://www.maturitas.org/article/S0378-5122(20)30348-0/ .

The best, post-COVID-19, review article on vitamin D recommends 40 to 60ng/ml 250HD levels.  It is co-written by Michael Holick MD, who has been researching vitamin D since 1971, and is the foremost vitamin D researcher, with Google Scholar reporting 129,193 citations of his articles:

Immunologic Effects of Vitamin D on Human Health and Disease
Nipith Charoenngam, Michael F. Holick 2020-07-15
Nutrients 2020, 12(7), 2097

https://doi.org/10.3390/nu12072097

From a 2019 article (24 citations):

Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience
Patrick J.McCullough, Douglas S.Lehrer, Jeffrey Amend
Journal of Steroid Biochemistry and Molecular Biology V189, May 2019

https://www.sciencedirect.com/science/article/abs/pii/S0960076018306228 (Paywalled.)
https://sci-hub.se/10.1016/j.jsbmb.2018.12.010

Vitamin D is essential for internal (autocrine) signaling in may cell types, including especially those of the immune system which both attack pathogens and regulate such actions:

The exact number of gene products controlled by vitamin D3 is unknown, but the active hormone form of vitamin D3 was recently found to bind via its receptor to 2776 distinct binding sites in a human cell line, many of which were located near autoimmune and cancer associated genes.

Both these articles list diseases for which vitamin D is a significant contributing cause (or at least of severe symptoms, as with COVID-19).  The two lists combined result in:

Alzheimer’s disease.

Asthma.

Atopic dermatitis.

Autoimmune diseases such as Cohn’s disease, inflammatory bowel disease, multiple sclerosis, psoriasis, posoriatic arthritis, rheumatoid arthritis and ulcerative colitis.

Cancers including breast, colon, prostate, sarcomas and skin cancer.

Chronic pain.

COVID-19 - hyperinflammatory response.

Dementia = neurodegeneration.

Depression.

Diabetes types 1 and 2.

Epilepsy.

Falls, fractures and muscle weakness.

Fibromyalgia.

Hypertension.

Muscle pain and proximal muscle weakness.

Osteoarthritis.

Parkinson’s disease.

Pregnancy complications including premature birth and death.

Respiratory infection.

Rickets (Failure to develop strong bones in childhood.)
Osteomalacia (Softening of bones, mainly in children and young adults.)
Osteoporosis (Low bone density, mainly in old age.)

Schizophrenia.

Seasonal affective disorder.

Sepsis.

Tuberculosis.

Urticaria.

Vitiligo.

Wheezing disorders.

So there has long been an urgent need for global vitamin D repletion.   COVID-19 makes it the most urgent and important step humanity can take to combat the disastrous severe complications which COVID-19 elicits in a substantial subset of the population whose immune systems are weak and dysregulated.


#lr

Latest research concerning COVID-19, immune system regulation, vitamin D and other nutrients

These are sorted roughly with the most significant articles first.  Please see the dates if you are looking for updates since you last viewed this list.


http://aminotheory.com/cv19/#2020-Castillo     2020-09-02

A Cordoba, Spain, vitamin D supplementation trial for hospitalised COVID-19 patients used fast-acting 25OHD calcifediol instead of they usual D3, which takes some days to be converted to 25OHD in the liver.  Without vitamin D, 50% of patients needed intensive care and 4% died.   With vitamin D, only 2% (one of 50) needed intensive care and none died.

I think this is the most significant vitamin D supplementation COVID-19 trial and that it should lead doctors all over the world to implement vitamin D3 supplementation programs for their patients and the general public, as well as early supplementation with immediately available 25OHD calcifideol for patients entering hospital. 


http://aminotheory.com/cv19/#2020-Mardani     2020-09-02

Iranian research finds respiratory patients who died of COVID-19 had only 8.2ng/ml while those who did not have COVID-19 averaged 30.2ng/ml.

http://aminotheory.com/cv19/icu/#2020-McGregor

Th1 lymphocytes isolated from the lungs of patients with severe COVID-19 symptoms have an autocrine signaling pathway which should be activated, to turn the cells off their hyper-inflammatory program which produces pro-inflammatory IL-17 and instead make them produce the anti-inflammatory cytokine IL-10.  However, this anti-inflammatory pathway is not working, due to lack of vitamin D

See also http://aminotheory.com/cv19/#2020-Fabbri for why 40ng/ml or more 25OHD is required for these autocrine signaling systems to function properly.

http://aminotheory.com/cv19/#2020-Panagiotou

In Newcastle upon Tyne, hospitalised COVID-19 patients had low vitamin D levels on admission.  Some of the predominantly white patients had levels below the 3.2ng/ml detection limit!

Those assigned initially to the ICU had lower levels than those initially assigned to the general wards.  


http://aminotheory.com/cv19/#2020-Merzon

Israeli researchers find a modest difference in average 25OHD levels between COVID-19 PCR positive patients who need hospital treatment and those who don't.   This is much more statistically significant than the difference found in the Newcastle upon Tyne study.


http://aminotheory.com/cv19/#2020-Maghbooli

Iranian researchers, with Michael Holick as co-author, report highly significant correlations between "vitamin D insufficient" < 30ng/ml 25OHD and "sufficient" >= 30ng/ml levels in respect of symptom severity, inflammatory biomarkers and death.


http://aminotheory.com/cv19/#2015-Stagi
Italian researchers in 2015 report that children with Kawasaki Disease were, on average, "severely vitamin D deficient".

The patients were 21 girls and 58 boys, average age 5.8 years.  Their average 25OHD levels were 9.2ng/ml, while age-matched controls averaged 23.3ng/ml.  In the patients who developed coronary artery abnormalities, the average 25OHD level was 4.9ng/ml (sd 1.36).

These children were struggling to live with vitamin D 25OHD in their bloodstream 20% to 11% of what is normal (46ng/ml) for hunter gatherers in Africa.  https://www.ncbi.nlm.nih.gov/pubmed/22264449 - the best estimate we have for the 25OHD levels of our ancestors, in which our current immune systems evolved.

http://aminotheory.com/cv19/#kdarticles
In June I found 18 articles on Kawasaki disease and COVID-19.   None of them mentioned vitamin D.   It seems that many or most doctors cannot imagine that vitamin D deficiency is an essential causative element in KD, even though they should all know that vitamin D deficiency causes immune system dysregulation and that KD is immune system dysregulation.


http://aminotheory.com/cv19/#2020-Baktash   2020-08-29

Researchers in Slough, west of London, find elderly COVID-19 patients have median 25OHD levels of only10.8ng/ml.



http://aminotheory.com/cv19/#2020-Shakoor   2020-08-29

Vitamin B1 thiamine, B2 riboflavin, B3 nicotinamide / niacin, B4 pantothenic acid, B6 pyridoxine, B9 folic acid / folate and B12 cobalamin play important roles in the immune system and so are important in reducing COVID-19 severity.


http://aminotheory.com/cv19/#SAAD
UK BAME doctor's recognise 25OHD below 20ng/ml as a risk factor for severe COVID-19 symptoms. 


http://aminotheory.com/cv19/#haplotypes

A haplotype on chromosome 3 confers a high risk of severe COVID-19 symptoms.  It is apparently inherited from Neanderthals, rare in Africans, common in Europeans and most prevalent in Bangladeshis.


http://aminotheory.com/cv19/obesity/


http://aminotheory.com/cv19/icu/#2020-Bilezikian

A 2020-08-04 review article on Vitamin D and COVID-19 observations and mechanisms.

Here are some brief notes on research I intend to write about more when I have time:

2020-08-07 

Linda L. Benskin's 77 page review of this research is available as a preprint (for the journal Frontiers In Public Health):

A Basic Review of the Preliminary Evidence that COVID-19 Risk and Severity is Increased in Vitamin D Deficiency

Researchgate 


News and updates

2020-07-14: If you are seriously interested in vitamin D and COVID-19 - and more broadly in Nutrition for Immune System Health - please consider subscribing to this private email discussion list, with web-based searchable archives.  This is the NISH list at groups.io:

https://nish.groups.io

This is intended for doctors, nurses, researchers, health authority advisers etc. as well as people such as myself with no formal qualifications or direct involvement in healthcare.  It is for people who actively seek out, evaluate and discuss the latest research and wish to work with others to facilitate research and understanding of the likely role vitamin D supplementation has in reducing the risk of COVID-19 severity.  (Vitamin D supplements will not significantly affect the risk of infection but will probably reduce the rate of viral shedding, and so the chances of infecting others.) 


Please see these excellent pages listing the latest vitamin D and COVID-19 researchhttp://agingbiotech.info/vitamindcovid19/ and  https://github.com/GShotwell/vitamin_d_covid .  The authors of these pages are keeping up with developments faster than I can. 

The first of these, by Karl Pfleger, is much more than a list of research articles.  It is a detailed, coherent, argument for vitamin D supplementation for many well researched reasons of enormous importance to health, with COVID-19 making this need even more crucial and urgent.   (However, it is tricky to print: Neither Firefox or Chrome would print it.  I had to select the whole page, copy it into Word, make a narrower right margin and then resize come graphics before I could print it.)

2020-07-22: Th1 lymphocytes isolated from the lungs of patients with severe COVID-19 symptoms have an autocrine (internal to the cell W) signaling pathway which should be activated, to turn the cells off their hyper-inflammatory program and instead make them produce the anti-inflammatory cytokine IL-17.  However, this anti-inflammatory pathway is not working, due to lack of vitamin D.  Please see icu/#2020-McGregor for a summary and a link to the research article.


2020-07-25:  Please see the Newcastle upon Tyne (northern England) article #2020-Panagiotou below.  It is the first report I read showing the correlation between low vitamin D levels in hospital patients and more severe COVID-19 symptoms.

Also, an Israeli article #2020-Merzon reporting lower 25OHD levels for COVID-19 PCR positive people who need to be hospitalised vs. those with milder or no symptoms.  Neither of these articles reports a dramatically strong association, but in the scheme of things, with millions of people being infected, the difference between low and moderate levels of vitamin D makes a big difference, and raising the 25OHD levels of the population, before infection, to something healthy, such as 40 to 60ng/ml would surely result in a still greater reduction in symptom severity.  The Israeli sample is larger and the correlation is much more significant (p < 0.001) then in the Newcastle sample (p = 0.3).

In the UK, NICE have released their report which states there is no reason to believe that low vitamin D levels are causing severe COVID-19 symptoms: COVID-19 rapid evidence summary: vitamin D for COVID-19, Evidence summary [ES28] 2020-06-29:

https://www.nice.org.uk/advice/es28/evidence

This is obviously mistaken.  I plan to write a response here, but I have to give priority to paying work.  Dr David Grimes has a critique of the NICE report (but I consider the  Filipino and Indonesian articles he mentions are fake: #2020-Alipio).

#Fauci
2020-09-11:  In a report on a 2020-09-10 Instagram interview (viewed by 1.7 million two days later) with Dr Fauci, he states that he takes vitamin D and vitamin C:

If you're deficient in vitamin D, that does have an impact on your susceptibility to infection. I would not mind recommending, and I do it myself, taking vitamin D supplements.  The other vitamin that people take is vitamin C because it's a good antioxidant, so if people want to take a gram or so of vitamin C, that would be fine.


#haplotypes
I have only briefly looked at this article The major genetic risk factor for severe COVID-19 is inherited from Neandertals https://www.biorxiv.org/content/10.1101/2020.07.03.186296v1 which suggests that a Neanderthal gene haplotype [W] drives an overly-inflammatory response which is known to cause severe COVID-19 symptoms, and that this haplotype is much more common in some races (though they do not use this term).   This haplotype is rare in Africans, moderately prevalent in Europeans, and common in some South Asian populations:

The highest frequency occurs in Bangladesh, where more than half the population (63%) carries at least one copy of the Neandertal risk variant and 13% is homozygous [has both of their chromosome 3s carrying it] for the variant.

This does not relate directly to vitamin D (as far as I know - though perhaps the haplotype mediates its ill-effects partly via low vitamin D levels), but when considering low vitamin D as a cause of severe COVID-19 symptoms, which is very common in people with brown or black skin, who live far from the equator, we should consider that genetic factors such as this may also play a role.  

The above URL also has extensive comments on the article.  The article in which this haplotype is identified as a risk factor in patients in Italy and Spain is: Ellinghaus et al. (over 100 co-authors): https://www.nejm.org/doi/10.1056/NEJMoa2020283  .


2020-07-02: I have been unable to disprove my hypothesis that two widely-cited non peer reviewed articles concerning vitamin D and COVID-19, from the Philippines and Indonesia, are invalid.  - and I found lots of evidence to support it.  Likewise a third article from India.   See my new site:

https://researchveracity.info

for a detailed account of why I believe these articles are fabricated.  Please do not take my word for it - read the above account and make up your own mind.  I am not an authority.

#vitd-basics

Vitamin D basics:

Since 2008, four dozen medical doctors and researchers have been advocating for 40 to 60ng/ml (100 to 150ng/ml) 25OHD vitamin D levels to be recognised as necessary for health in general - and particularly regarding the immune system.  This is the Call to D*Action:

https://www.grassrootshealth.net/project/our-scientists/

A recent review also supports 40 to 60ng/ml 250HD levels:

Immunologic Effects of Vitamin D on Human Health and Disease
Nipith Charoenngam, Michael F. Holick 2020-07-15
Nutrients 2020, 12(7), 2097

https://doi.org/10.3390/nu12072097

Also, Barbara A Gilchrist's 2008 article Sun exposure and vitamin D sufficiency on why sun exposure of artificial ultraviolet light capable of raising vitamin D always involves DNA damage and so increased risk of cancer.  Exposure to about 1/3 the UVB light required to produce a little sunburn is all that is required each day to maximise vitamin D production in the skin.  In general, it is best to avoid sun or other UVB exposure and instead rely on nutritional supplements, since there is not enough vitamin D in food to achieve vitamin D repletion. 

She argues for a lower target than 40 to 60ng/ml - but that was before 2012 research which provides the best estimate we have for the 25OHD levels of our African ancestors - the level which our immune systems evolved to work with.  The average vitamin D level of traditionally living East African Maasai herders and Hadzabe hunter gatherers is 46ng/ml (115nmol/L): https://www.ncbi.nlm.nih.gov/pubmed/22264449

As you will read below, there is a relationship between low vitamin D levels and severe symptoms, lasting harm and death among adults with  COVID-19.  This is surely a significant reason contributing to the greater toll of harm and death suffered by people with dark and black skin especially when they are living far from the equator.  The same is true of children who suffer from Kawasaki disease, which can be triggered by numerous viral and bacterial infections, including especially COVID-19.  Italian research #2015-Stagi shows they have very low vitamin D levels: 9.2ng/ml - and 4.9ng/ml for those with coronary artery artery damage.  Most doctors have been unaware of this important research.

One of the Call to D*Action researchers, William B. Grant PhD, wrote an article in 2018 about what he - and I guess his colleagues - perceive as a series of unfair actions and biases frustrating their efforts to have official guidelines about vitamin D supplementation doses and desired 25OHD blood levels revised to match what is now known about vitamin D and health, especially immunity:

Vitamin D acceptance delayed by Big Pharma following the Disinformation Playbook
William B. Grant  Orthomolecular Medicine News Service, 2018-10-01
http://orthomolecular.org/resources/omns/v14n22.shtml

I think that "orthomolecular" is an awkward term for a field in which nutrition is given greater prominence for disease prevention and perhaps cure than is common in Western medicine.  While there may be some arguments in this field which I consider not properly based on observations or experiments, the fundamental tenet is obviously sound.  

In electronic engineering, the equivalent tenet would be "Battery voltages, external power voltages and all internal power supply voltages must remain with specified ranges before the equipment can be expected to perform reliably".
 
"Orthomolecular" medicine is only necessary because Western medicine - as practiced by many, probably most, but not all doctors - has such blind-spots regarding nutrition, and such a keen eye for using drugs instead.  


#vitd-autocrine

Vitamin D in autocrine signaling:

The following is the best effort of an electronic technician to introduce how autocrine signaling differs from the endocrine / hormonal mechanisms by which vitamin D is involved in calcium and bone metabolism.

For more in-depth material, a good place to start might be articles which cite a 2010 article,  Autocrine and Paracrine Actions of Vitamin D by  Howard A Morris and Paul H Anderson. Also: Vitamin D metabolism and signaling in the immune system (2012), Vitamin D and immune function: autocrine, paracrine or endocrine (2013)  and Vitamin D and immune function (2013). 


The importance of proper (at least 40ng/ml = 100nmol/L = 1 part in 25 million by mass) levels of 25OHD is not widely enough known, especially by doctors.   While lower values may be sufficient for the hormonal actions of vitamin D, we need at least this level of 25OHD for numerous types of cell - especially immune cells - to function correctly. 

Many people think of vitamin D, at least in the 1,25OHD form which most activates receptors, as a hormone.  This is true for its calcium and bone functions, but this is just one function in the body for which vitamin D is crucial.  Hundreds - perhaps thousands - of different cell types rely on vitamin D for their autocrine (internal) signaling.  This has nothing to do with the circulating levels of 1,25OHD, and depends entirely on the circulating levels of 25OHD.  This circulating 25OHD is not, to my understanding, operating as a hormone.  So it is not really functioning as part of the endocrine system.  It is the feedstock for hundreds or thousands of separate autocrine signaling systems - most of them completely unrelated to calcium and bone metabolism.

So the old skin/food > liver > kidneys > receptor story is completely inadequate for understanding vitamin D's role in the the body, especially regarding the immune system.  Once you understand this, and how low most people's 25OHD levels are compared to ancestral levels, which were about what we need now to be healthy, it will be no surprise that a great number of chronic and acute conditions would happen much less frequently, or not at all, if everyone had 25OHD levels above about 40ng/ml.  (I doubt there is an absolute threshold - some people with particular health challenges such as obesity and COVID-19 probably need as much 25OHD as they can get,  I guess for some, that 100ng/ml would be better than 90ng/ml.)

Three forms of vitamin D are of interest (D2 behaves like D3, but D3 works better):

D3 cholecalciferol. [W]   Produced by UV-B light acting on 7-dehydrocholesterol in the skin, or ingested in food or supplements.  While this does have some direct actions in some cells, its major role in the body is to be converted in the liver, over a period of days, by the enzyme vitamin D 25-hydroxylase (encoded by the CYP2R1 gene, a name sometimes given to the enzyme itself) to 25OHD.  (Another enzyme encoded by the CYP27A1 gene does the same thing and so produces some of the 25OHD.)

25OHD calcifediol = 25 hydroxy vitamin D = cacldiol [W].  This has an OH hydroxyl group at the 25 position.  This is what is measured in blood tests.  25OHD circulates in the blood, mainly bound to the vitamin D carrier protein and albumin.  It is also absorbed into fatty tissue, as is D3.  25OHD and perhaps D3 may also be stored in the liver.  (Has anyone got references on this?)

Neither D3 nor 25OHD bind strongly to the vitamin D receptor [W]. 

1,25OHD calcitriol [W] = 1, 25 dihydroxy vitamin D = 1,25(OH)2 vitamin D, is produced by a second enzyme encoded by the CYP27B1 which adds an OH hydroxyl group at the 1 position to 25OHD.   This happens in the kidneys and inside many types of cells, including immune cells.

1,25OHD binds strongly to, and so activates, the vitamin D receptor.

(There is another enzyme CYP24A1 which can add an OH hydroxyl group to  25OHD and 1,25OHD, which is an irreversible process.  The resulting molecules are degraded and excreted.)

The conversion of circulating 25OHD to circulating 1,25OHD in the kidneys is regulated with the parathyroid hormone.  This circulating 1,25OHD acts as a hormone  - it is a signaling molecule emitted in one part of the body and carried in the bloodstream to all other parts of the body, where it activates the vitamin D receptors on or inside cells, causing various actions primarily concerning calcium metabolism and bone maintenance.    The long-range nature of the signaling interaction makes this a hormonal = endocrine process [W].  So in this context, 1,25OHD is a hormone, 25OHD is a pro-hormone and D3 is a pro-pro-hormone.

1,25OHD exists, in circulation, at much lower concentrations than 25OHD.  It has a relatively short half life (5 to 8 hours in adults) compared to the half-life of 25OHD, which is weeks or a month or two at low concentrations, and shorter at higher concentrations, by way of degradation to 24,25OHD, in a self-regulating, concentration-dependent manner.  (This accounts for the curves in the 25OHD by weight and D3 intake graph below.  This self-regulation makes it very hard to attain toxic 25OHD levels, which may occur above 150ng/ml.)

The level of 1,25OHD in the bloodstream is tightly regulated as part of the calcium and bone system.  This circulating, hormonal, 1,25OHD is not particularly important to various types of cell which use vitamin D for autocrine signaling.  I think this is partly due to the low circulating levels compared to the (I assume) higher levels which can be produced by the autocrine signaling system and also due to the relative stability of this circulating level.

Autocrine [W] means "inside the cell".  A substance is produced inside the cell and has its actions there.  This is the opposite of endocrine (hormonal) signaling.  Autocrine signaling involving vitamin D is used by many cell types, and it is particularly important in immune system cells.

There are two other types of cell signaling, which are also be a part of how some types of immune cell affect the operation of other types of immune cell which are nearby:

Paracrine signaling [W],  This involves a cell emitting a substance which travels a short distance - implicitly by diffusion, rather than in the blood or lymphatic fluid - where it affects the behaviour of other cells.

Juxtracrine signaling [W] is similar, but just for adjacent cells.

Both these may result from 1,25OHD produced in the autocrine process leaving the cell it is produced in and affecting nearby cells.  Both these mechanisms are important in immunity and development.

Generally, the autocrine production of 1,25OHD in cells (apart from those in the kidney) does not lead to sufficient release of 1,25OHD into the circulation to significantly effect 1,25OHD levels there.   I am aware of to pathological exceptions to this:

Sarcoidosis and some other granulomatous diseases.  Here, immune cells are scuffling with each other, clumping together all over the body and behaving in other dysregulated ways.  (See the end of the d3/ page for an article on sarcoidosis.)

Particular tumors.

Are there any others?  

I have an article here somewhere with a good diagram of vitamin D autocrine signaling.  When I find it I will link to it here and show the diagram. 

Here is an example from:

An autocrine Vitamin D-driven Th1 shutdown program can be exploited for COVID-19
Reuben McGregor et al. 2020-07-19
https://www.biorxiv.org/content/10.1101/2020.07.18.210161v1

which I discuss at icu/#2020-McGregor.  This is my best effort in describing particular immunological processes - please remember I am not an immunologist!

This example concerns CD4 [W] (T-helper cells, T4 cells) which emit various cytokines to signal to other types of immune cells actions which destroy pathogens directly, destroy infected cells (cytotoxic) or take other actions.

Autocrine signaling with vitamin D has presumably evolved to be used in many cell types, due to each cell type being able to upregulate and/or downregulate particular genes in very flexible ways by attaching various promoters next to particular genes, in a manner with is specific to each cell type.

This is a Mouse Trap (video) approach go biology - Rube Goldberg [W] engineering when we might be able to imagine something simpler to do the job.  I guess its internal complexity gives rise to flexibility and multiple control inputs which have caused the same basic plan to have evolved for many different types of cell.

Our Th1 (T Helper 1) cells start off on a pro-inflammatory program, referred to in the article as T-effector.  In this mode, they produce the inflammatory cytokine IFN-γ interferon gamma [W].

This autocrine signaling system has evolved so that when it is activated, the Th1 cell switches to a second mode of operation (program) in which it instead emits the anti-inflammatory cytokine IL-10 [W].   The above article discusses how this does not happen in Th1 cells from hospitalised COVID-19 patients, due to lack of 25OHD while it works fine in TH1 cells from healthy controls.  (Unfortunately the authors do not report blood 25OHD levels from these patients.)

"Complement" here refers to a number of proteins which form an important part of immune system signaling [W].   High levels of complement occur in the lungs with severe COVID-19.

The switch from effector T cells, important for pathogen clearance, into IL-10 producing cells reduces collateral damage and is a natural  transition in a T cell’s life-cycle. This suggests that IL-10 is produced by cells that are successfully transitioning into the Th1 shut down program. . . . We asked whether prolonged Th1 responses in COVID-19 patients are due to the failure in initiating this Th1 shutdown program.

This article is a beauty.  It gets down to brass tacks with the molecular processes of one aspect of the cytokine storm of immune dysregulation which is crucial to the development of severe COVID-19

The high levels of complement activate the CD46 [W] transmembrane receptor.  This induces (leads to more of) 24 transcription factors [T].  Transcription factors are molecules which bind to specific locations on the DNA where they enhance or reduce (turn on or off) the transcription of particular genes into messenger RNA [W].  The exact mechanisms of these transcription factors depend on epigenetic [W] changes to the DNA, which would be specific to the particular cell type.  Two of these transcription factors upregulate the mRNAs for the vitamin D receptor [W] (hereafter VDR) and for the CYP27B1 enzyme

In the vitamin D autocrine signaling system of other cell types, some other receptors would be activated initially, in response to some other stimulus than high levels of complement.  This would result in the induction of different transcription factors - and I guess some of these would do part of the work required for the cell to respond properly to the stimulus.  However, two of those transcription factors would again be for VDR and the CYP27B1 enzyme, just as in this particular example.

The next few steps are for this example, and more generally for the vitamin D autocrine functions of other cell types.

These two sets of mRNAs migrate from the nucleus and (for simplicity ignoring any post-translational modifications) find ribosomes in the cytosol [W], which work their way along each mRNA and produce a protein according to the instructions encoded in the mRNA.  So, (ignoring any other processing steps) the cytosol now contains a lot more VDRs and CYP27B1 enzyme molecules than it did before.

The next step is what should happen, but did not happen or did not happen enough in the Th1 cells isolated from the lungs of hospitalised COVID-19 patients.  

25OHD from the bloodstream migrates into the the interstitial fluid [W] and from there it migrates into the cytosol (AKA cytoplasm - the main body of the cell).  I recall that there are no specific transporters for 25OHD, but I haven't researched it.   Most 25OHD in the blood is bound to vitamin D binding protein or albumin, and I recall that relatively small proportion which is free is that which can migrate into cells - though I think the binding to albumen is much weaker than to the vitamin D binding protein, meaning that albumin-bound 25OHD is also free to migrate into cells.

So the initial and continuing 25OHD levels in the cytosol of our TH1 cells are determined primarily or solely by passive diffusion from the concentration in the blood. 

I don't' know what the cytosol 25OHD concentration is before the CYP27B1 enzyme is produced there, but for simplicity I think of it as being the same as some (free, rather than bound) fraction of the ideally 40ng/ml 25OHD in the blood.  Some people have 2 to 4 times this, or more.  Many people have less, such as less than 10ng/ml for children with the worst symptoms of Kawasaki disease.  This is 1 part in 100 million by mass, whereas to be healthy, we need at least 1 part in 25 million.

By random bouncing around a 25OHD molecule finds its way into the active site of a CYP27B1 enzyme molecule, which, with co-factors, attaches an OH hydroxyl group onto it and releases it as 1,25OHD calcitriol.   There are a limited number of these enzyme molecules.  Assuming the co-factors are in good supply, the actual rate of production of 1,25OHD depends primarily on the time taken to add the hydroxyl group and how long it takes for another 25OHD molecule to find its way into the the enzyme's active site.   The lower the 25OHD level in the blood, the lower the concentration in the interstitial fluid and cytosol and so the longer it will take before another 1,25OHD molecule can be produced.  According to #2020-Fabbri 40ng/ml 25OHD is the level at which the production of 1,25OHD flattens out, due to to the enzyme not having to wait very long for another input molecule, the substrate, 25OHD, to find its way into its active site.

The newly created 1,25OHD bounces around in the cytosol, as do all small molecules, until it finds itself correctly oriented in the binding site of a VDR molecule, to which it has a very strong affinity.  This pairing is the "activated" state of the VDR.  The VDR molecule changes its behaviour and the entire complex of VDR and its bound ligand, 1,25OHD, migrates to the nucleus, where it binds to particular transcription factors attached to particular parts of the DNA.  The particulars of these transcription factors differ  between the various cell types which use vitamin D autocrine signaling.

These now-activated transcription factors upregulate one or more genes and may downregulate others.  The resulting new mRNAs (and potentially reductions in previously produced mRNAs) are worked on by ribosomes and so result new proteins (or less of of other proteins) in the cytosol which cause the cell to complete the action for which this autocrine signaling system has evolved.

In this particular example, the cells action includes shutting down pro-inflammatory IFN-γ production and ramping up inflammatory IL-10 production.

This does not occur to the degree it should in the cells the researchers isolated from the lungs of COVID-19 patients - but it did when they added sufficient 25OHD for the CYP27B1 enzyme to work on.

This is one example of a specific vitamin D autocrine signaling system in one particular type of immune cell.  The following article discusses the evolutionary basis and other details of 189 human genes know to be regulated in an autocrine / paracrene manner by vitamin D in monocytes [W], which are a subset of leucocytes [W], which are a subset of immune cells which are a subset of the cell types in the body which use their own particular version of vitamin D autocrine / paracrine signaling. 

Primary Vitamin D Target Genes of Human Monocytes 
Veijo Nurminen, Sabine Seuter and Carsten Carlberg
Frontiers of Physiology 2019-03-15
https://www.frontiersin.org/articles/10.3389/fphys.2019.00194/full

I don't want to imply that I have read this, or that I would be able to understand it without weeks of work.  I cite it as an easy way of expanding upon this one concrete example which surely plays a crucial role in severe COVID-19 (and see #2020-Castillo for how oral 25OHD for hospitalised patients causes most of them to get much better, very quickly) to indicate how important this general principle of vitamin D autocrine signaling is.   None of these systems will work very well if the circulating 25OHD (or more particularly the unbound fraction of it) is less than (to the best of our knowledge) 40ng/ml (100nmol/L).


Now a study of 4.6 million Israelis:

The link between vitamin D deficiency and Covid-19 in a large population
Ariel Israel et al. 2020-09-07
https://www.medrxiv.org/content/10.1101/2020.09.04.20188268v1

here are graphs depicting the distribution of 25OHD levels in Israel.  The top graph is for men and the bottom for women.   The red bars are the proportion of the population with that narrow range of 25OHD levels who test positive for COVID-19 and the grey bars are for those who do not. 




If you see Fig 1 of that article, it is clear that the excessive (compared to men) number of women with very low (below 15ng/ml) 25OHD levels is due entirely to Arab women.  (Ultra-Orthodox men and women both tend to have lower 25OHD levels, but there is an extreme peak towards the low end for Arab women only.)  This is clearly due to clothing coverage preventing sunlight from reaching almost all their skin.

(This indicates, by the way, that low vitamin D leads to a marginal increase in risk of being infected for any given viral load.  However a complete analysis shows that the total effect seen in this regard (the peak of red bars being for lower 25OHD levels than for the grey bars) is also due to these individuals generally mixing with like individuals with lower vitamin D levels, and so, it is reasonable to expect, higher rates of viral shedding than for high 26OHD levels.  Also, larger families, less respect for lockdown, masks etc. may be higher in the Ultra-Orthodox people and perhaps the Arabs, and both these groups tend to have lower 25OHD and so, I assume, greater rates of shedding and so are more likely to infect the people they mix with.   So I expect the proclivity of low 25OHD to lead to greater chance of infection for any given viral insult is likely to be even less than the small effect indicated in these graphs.

Very few of these people have 25OHD levels of 40ng/ml or above.  The average is about half this. For Arab women, the average (Fig 1 in the above article) the average is even lower.  Table 2 shows 59.1% of Arab women in Israel have average 25OHD less than 30nmol/L, which is  just 12ng/ml.  These are terribly low levels.   The best figures are for ordinary Israeli men: 34% below 20ng/ml, 24% above 30ng/ml and the rest, 42%, between 20 and 30ng/ml.  

See below #2020-UK-vit-D-BAME for a UK chart showing even lower average levels, and still lower levels coming out of winter.


Despite the tens of thousands of words on this page, the situation looks real simple to an electronic technician like me:
  1. One human operating requirement is enough vitamin D3 to provide at least 40ng/ml 25OHD.  Without this, hundreds and probably thousands of types of cell cannot work properly.

  2. Most people do not get enough D3 to achieve this, even in Israel which has few people with black or really dark skin, and which is only about 31° from the equator .

  3. To a technician, this is much the same as most people on the planet running around with flat batteries.  So for heaven's sake lets charge them!   45mg of D3 a year, for an  average weight adult, will do the trick.   There are other deficient nutrients as well, but vitamin D is the big one, with such a small, inexpensive, safe, quantity needed for repletion.

Other pages here

icu/
Doctors!  Be sure to see the sections on this page on the Marik Protocol and the closely related MATH+ Protocol for ICU treatment of COVID-19 patients.  It results in higher survival rates than the techniques used in most hospitals today.  This page also has more detailed discussion of COVID-19 endothelial pathology in the lungs and the importance of good vitamin D levels to ensure our immune responses are both strong and well regulated.
obesity/
Fat cells (adipocytes) in obesity are known to increase inflammatory responses and so worsen the cytokine storm which characterises COVID-19 with severe symptoms.  This is true of visceral adipocytes around the heart and other organs in the abdomen.  Ectopic (growing where they shouldn't) adipocytes in the lungs are also a problem.  Furthermore, adipocytes may express the ACE2 receptor and so be subject to infection by SARS-CoV-2. 

Obesity is perhaps the biggest single risk factor for severe COVID-19 symptoms, and so for death or lasting harm from microembolisms and resulting organ damage for those who survive.  On one hand, it could be argued that repleting all relevant nutrients to ensure good immune function - including vitamin D to achieve at least 40ng/ml 25OHD - will help immune system function in general, but that these excess adipocyte problems will remain.  On the other hand, as far as I know, the problematic behaviour of these adipocytes is generally only observed in patients whose vitamin D levels have been low for years, and remain low.  So there's a chance that with nutrient repletion, their potentially destructive role in the immune response will be significantly less than is normally the case.
d3/
Links to the best research articles on desired vitamin D blood levels and what amounts of supplemental vitamin D3 are needed to achieve this, on average, for underweight, normal, overweight and obese body types. 

Links to (and in the future discussion of) the most pertinent research on the vexed question of vitamin D toxicity - in general and for individuals with particular genetic makeups, particular tumors or granulatomous diseases such as sarcoidosis. 
3-reasons/ Three reasons I want everyone in the world to have good nutrition for immune system health, to greatly reduce the chances of their immune responses being weak and/or dysregulated.
crisis-diy/
(I haven't written this yet.) If demand for pharmaceutical vitamin D greatly exceeds supply (as I expect it will once most people recognise they need substantial supplements to stop their immune system causing harm and death when responding to the SARS-CoV-2 virus), what are we going to do for people who cannot get the supplemental D3 they need or good, high-elevation sun exposure most days?   Firstly, access some of the vitamin D3 used for agricultural feed, which is where about 75% of D3 production goes.  Secondly, use boron - which is worth using anyway for its anti-inflammatory and other immune-system benefits. Thirdly, find UV light sources which can drive D3 synthesis in our skin - this is tricky.

Finally, build vitamin D3 factories in our own countries - skunkworks-style as in war-time, since our lives depend upon it.  Regarding this, for now please refer to this excellent description of industrial production of vitamin D3 cholecalciferol by Arnold L. Hirsch in 2010 : https://sci-hub.se/10.1016/B978-0-12-381978-9.10006-X .
prisons/
About 10 million people are confined in prisons and jails. They and the prison staff are at high risk of COVID-19 infection.  While (in the USA, so far, 2020-06-22) rates of prison harm and death per confirmed case from COVID-19 are generally lower than in the outside world, this is primarily due to few prisoners being over the age of 60.  The number of confirmed cases is generally higher - which may be partly due to better testing in prisons. 

The rate of harm and death for younger prisoners may be higher than in the outside world - in part because prisoners in general have even lower vitamin D levels than free living people. 

There is an urgent need to give all these people substantial vitamin D supplements - and more generally the full range of vitamins, minerals and omega-3 fatty acids.  The health and other benefits have already been shown to far exceed the small cost of providing these - and COVID-19 infection is close to  inevitable in the months to come.
kna/
Decreasing sodium (salt) consumption and boosting potassium intake - including with supplements in the form of potassium gluconate solution drinks - reduces the incidence of high blood pressure and stroke.
fever/
Links to research articles indicating that in general, with certain exceptions, fever (at least in the initial stages) should not be lowered because it is an important part of the body's defense against viral and bacterial infection.  Also links to some research which may indicate there is little harm and perhaps some benefit of lowering fever with COVID-19 with particular drugs. 


Contents of this long page

#intro Introduction.
#othersites Some other sites of interest.
#cv19vitd Recent articles concerning COVID-19 and vitamin D.
#2015-Stagi Severe vitamin D deficiency in Italian children with Kawasaki disease.
#pandend Ending the global vitamin D deficiency pandemic by aiming for at least 40ng/ml 25OHD.  This is the only way we can ensure that COVID-19 causes far less harm and fewer deaths.
#cvkd COVID-19 induced Kawasaki disease in children and babies AKA Paediatric multisystem inflammatory syndrome.
#uk-bame Discussion of the high rate of harm and death to black, Asian and minority ethnic people in the UK has generally not mentioned their very high rates of vitamin D deficiency.
#pep-talk Pep-talk for doctors regarding the need for robust vitamin D supplementation to protect against severe COVID-19 symptoms.  Written specifically for BAME doctors, but really to all doctors - and not just because of COVID-19.
#2020-Baker-a Articles concerning vitamin D supplementation to protect against harm and death from COVID-19, including research which shows that 40ng/ml or more 25OHD is required for proper immune system functioning.  Also a list of other articles of interest I have not read or written about yet.
#low-verylow Irish doctors debate whether to use low or ridiculously low doses of vitamin D3.
#21authors 21 authors advise very low levels of D3 supplementation, aiming for a minimum 25OHD level of only 10ng/ml.
#weak-sys COVID-19 pathology - weak and dysregulated immune systems.  The icu/ page has all the details.
#helminthsgone Weak and dysregulated, over-inflammatory, immune responses are caused by lack of helminths, individual genetic variation, dietary excesses and several common nutritional deficiencies.
#vaccines
A safe, effective, reasonably long-lasting vaccine to protect against COVID-19 may never be devised.  Even if it is, it will take a long time and be much more expensive and risky than vitamin D and other nutritional supplements which will actually, to a substantial degree, solve, the immune system weakness and dysregulation which drives COVID-19 severe symptoms.
#disclaimer I am not a doctor etc.  About these pages.  Contact and copying information.
#plan Global plan for better nutrition for immune system health, and for better guidance regarding fever.  Written for people who are fusspots for detail.
#msg This section is older, and not so recently updated.  It is based on the email I sent out to doctors, researchers etc. starting on 22 March 2020.  This has a section on boron: #08-boron .



#intro

Introduction

For an introduction written in late August, please see the 5th comment at: https://quillette.com/2020/08/27/covid-19-returns-to-new-zealand/  .

In general, people infected with COVID-19 only suffer serious harm, or are killed, due to their immune system being weak and/or being dysregulated - their immune response is overly-aggressive, proinflammatory, generally ineffective against the virus and most importantly, damaging to the self.  

The same is true of influenza, but COVID-19 is much worse because it is highly infectious and - when the dysregulated immune system allows the virus to infect the lungs - the loss of ACE2 receptors there raises angiotensin II, which causes vasoconstriction of the pulmonary capillaries and a highly coagulative state, which leads to micro-embolisms and larger blood clots there and in other parts of the body.  Both the vasoconstriction and the clots reduce the ability of the lungs to exchange oxygen and carbon dioxide.  Without hospital care, including oxygen (though ideally not mechanical ventilation, which tends to make things worse), the patient will be seriously injured or killed through lack of oxygen.

Direct viral and/or dysregulated immune responses damage endothelial cells in the lung - and presumably elsewhere - and the body responds to this blood vessel damage by making the blood hypercoagulative.  This hypercoagulative state drives most of the harm which results, with micro-embolisms and/or larger blood clots anywhere in the body, including the lungs, brain, spinal cord, heart, kidney and liver.  This can lead to death via stroke, heart attack and kidney failure.

There are evolutionary reasons why our immune systems are dysregulated - as explained below, we (in developed countries) lack the helminths (intestinal worms) our ancestors had.  Our immune system evolved to counter helminthic downmodulation of many immune responses.  Without helminths, many of our immune responses are overly-inflammatory and self destructive.

There is also considerable genetic variation between individuals.

Finally, common nutritional deficiencies and excesses both weaken our immune system, and reduce its ability to regulate its potentially excessive actions.  The focus of this web page, and others which lead from it, is to correct these nutritional problems - most importantly by way of vitamin D3 supplements.  If all humans do this, then our general health will improve in many ways, and COVID-19 will cause us little trouble.

This is the only way we can deal with the threat of harm and death from COVID-19, and likewise with the rising incidence of numerous chronic and acute health problems which result from our generally weakened and dysregulated immune systems.

We can't stop the spread of the SARS-CoV-2 virus which causes COVID-19 illness.  Antivirals have never stopped the spread of any virus.  The common hope or expectation that a vaccine could stop it, by being proven effective and safe, and administered to most people in the world, is unlikely in any time frame - and impossible to achieve in the next few months or year.

It is likely that drugs will be developed which reduce the ability of the virus to replicate, and so cause serious symptoms.  These will be welcome, but are unlikely to be tested and made available en-masse any time soon.  It makes no sense to be using drugs like this while it is easier, safer and less expensive to improve our immune system's strength and ability to regulate itself by correcting nutritional deficiencies.

We cannot continue to contain the spread of the virus by lockdowns, social distancing etc.  These measures have unsustainable social, economic and health costs.  For now, we should certainly try to slow its spread - but only when most people's immune systems are working properly will it be possible to relax these constraints, and so let the virus spread without causing much harm or death.

Giving humans their proper operating conditions - at least regarding nutrition for general health and strong, well-regulated immune systems - is necessary for numerous other reasons (reducing asthma, neurodegeneration, inflammatory bowel disease, diabetes etc.) and is urgently needed so we can cope with COVID-19 without the twin disasters of widespread harm and death (as is occurring now) and of all the so-far uncounted costs, harm and death which results from lockdowns.


Even children can be affected, with the coronavirus causing their dysregulated immune system to attack the self in a pattern similar to that of Kawasaki disease.  In pre-COVID research #2015-Stagi, it was shown all children with this disease were severely vitamin D deficient.  The children with the lowest vitamin D levels had the worst outcomes - their vitamin D levels averaged about 1/10th of the levels of African herders and hunter gatherers.

So when children are now, tragically, harmed and killed by COVID-19 in ways which resemble Kawasaki disease, it is reasonable to assume that this is only occurring due to their extremely low vitamin D levels (no-doubt combined with genetic and other factors) - and (in the absence of evidence to the contrary) that their parents and treating doctors were unaware of the need to provide them with adequate vitamin D supplementation.

There is no reason to believe that there ever will be a vaccine which is effective against COVID-19.  Immunity to coronaviruses after infection - or which might be elicited by a vaccine - may only likely to last a few years.   Vaccines can cause much worse symptoms in some or many people when the antibodies they raise attach to the virus and are recognised by receptors other than ACE2, which enables the virus to infect other types of cells.  (Contrary to this gloomy outlook, see the research mentioned in points 1, 2 and 3 of this  nymag.com article: people who test positive a second time are not infectious; SARS-CoV antibodies seem to be effective up to 17 years later and a SARS-CoV antibody is effective, in vitro, against SARS-CoV-2.)

SARS-CoV-2 will continue to mutate.  We all have to live indefinitely with current and/or future strains.  Fortunately, this virus does not cause serious trouble for people with properly functioning immune systems.  Other viral diseases do - for instance smallpox, or ebola.  We will be in serious trouble - no matter how good our nutrition and strong our immune systems - if a novel virus emerges which is as deadly as these whilst also being highly infectious.

Unfortunately, for various reasons - most of them spurious - most (but not all) doctors are excessively wary of nutritional supplements.  This wariness is part of the reason we have such widespread vitamin D deficiencies.  The official vitamin D guidelines are recognised by many researchers and some doctors as being woefully inadequate in terms of desired 25OHD levels and regarding maximum safe dosages of vitamin D3.

This global problem of inadequate nutrition will only be solved by people choosing to take supplements regularly.  Ideally this would happen as a result of most or all doctors recognising that their guidance, which lead to the current disastrous situation, was wrong and that they need to accept and promote the regular use of nutritional supplements in quantities sufficient to make most people replete - generally without the need for medical supervision and blood tests, which are more expensive than the supplements themselves.

For instance, an adult taking 4000IU a day of vitamin D3 needs a gram every 27 years.  The ex-factory, kilogram lot, price of pharmaceutical D3 is USD$2500. At that rate, the annual cost is USD$0.09 per year.  All that is needed is a capsule or tablet a week, so 5,200 such capsules, with a total D3 cost of USD$10, and I guess USD$100 manufacturing cost, would be good for one adult for 100 years.

For various reasons - not all of them good - doctors are extremely resistant to changing their thinking.   In order to avoid a catastrophic continuation of the current harm and death, they will need to change their minds fast - since I can't imagine most people, with the support of their governments (to handle the logistics of obtaining and distributing the nutrients), achieving this level of supplementation without the support of most doctors.

Even if COVID-19 disappeared, we still need to give all humans their proper operating conditions as a matter of urgency, since the same nutritional problems, against a background of genetic variation, drive the growing burden of chronic and acute disease, including: diabetes, neurodegeneration (Alzheimer's, Parkinson's diseases etc.), hypertension, stroke, multiple sclerosis, inflammatory bowel disease (Crohn's disease and others), sepsis, osteoporosis and so on.

Here is a chart depicting vitamin D blood levels in relation to body weight and D3 dosage.   The Kawasaki disease figures come from research before COVID-19 elicited a similar, deadly, condition in some children, especially in the UK.  You can read below #2016-Caprio research which indicates that 40ng/ml is the minimum 25OHD level for proper immune system functioning.  Yet some experts #21authors advise the public that they should supplement to attain merely 10ng/ml.  This is very close to the 9.2ng/ml average 250HD levels of children with Kawasaki disease #2015-Stagi .

#2014-Ekwaru


See the d3/ page where this is part of the guide to vitamin D supplementation.  This graph is my adaptation of the original from:

The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers
John Paul Ekwaru et al. PLoS One 2014
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111265


#2014-Palacios
Here is a world map which depicts some estimates of vitamin D deficiency, where deficiency is defined as 25OHD levels in the blood below 30ng/ml.   However, the best research indicates we should be aiming for 40 to 60ng/ml. as shown in the chart above.   So by that, realistic, standard, the prevalence of vitamin D deficiency is much greater than depicted in the following map.

World map of vitamin D deficiencies countries

Larger versions of the above: 1300x948 & 2644x1926 .  This is from:

Is vitamin D deficiency a major global public health problem?
Cristina Palacios & Lilliana Gonzalez J Steroid Biochem Mol Biol. 2014 Oct
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018438/

The light grey percentages are for people with less than 30ng/ml, which is the threshold of vitamin D sufficiency adopted by the Endocrine Society and some other organisations.  Below you can read research from the Philippines and Indonesia which indicates that the risk of severe symptoms and death from COVID-19 is very much greater for people whose levels are below 30ng/ml than for those with higher levels.

Although these figures are incomplete, and based on research at least 6 years old, it is easy to see what that vitamin D deficiency is a profound problem in most, if not all countries.  Jordanian men are doing pretty well, but not Jordanian women or any of the other populations surveyed.  Among the most alarming results are women in Bangladesh (80% below 20ng/ml, the UK with 47% below this in winter, and 78% of Scots below 20ng/ml - and  35% below 12ng/ml.

So about 1/3 of Scots have about 1/4 of 46mg/ml average vitamin D blood levels of traditionally living African herders and hunter-gatherers (https://www.ncbi.nlm.nih.gov/pubmed/22264449).  Everyone's immune system evolved to work with these 40 to 60ng/ml 25OHD levels.


#2004-UK-vit-D
The next chart depicts seasonal variations in vitamin D levels in the UK.  See below for another chart which separates out White and BAME levels.



Larger version 1868x1616 .  This is from:

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors
Elina Hyppönen and Chris Power Am J Clin Nutr 2007;85:860 – 8
https://academic.oup.com/ajcn/article/85/3/860/4633120

The graph shows month-by-month average 25OHD levels in white men and women in the UK, all aged 45.  Most of the time the 25OHD levels of most people fall under the 30ng/ml threshold below which the Endocrine Society defines vitamin D insufficiency or deficiency.

16% of these people used modest ~200IU supplements which raised their levels 3ng/ml on average.  This contributes only about 0.16ng/ml to the average - so the graph is very close to the averages of non-supplementing individuals.  Vitamin D from food made only a slight contribution to these levels.

Scots and the obese had lower levels than average.  African and Asian people who do not supplement would have significantly lower levels.  None of these averages come close to the 40ng/ml minimum level required for proper immune system functioning - according to several research articles cited below, including:  #2016-Caprio & #2020-Baker-a and to the Scientists' Call to D*Action link, which was originally made in 2008. 

The initial phase of COVID-19 infection, harm and death in the UK occurred in March to May 2020 - when 25OHD levels were close to their lowest.


#2020-UK-vit-D-BAME
Here is another graph of seasonal vitamin D levels in the UK, with separate curves for men and women, white and BAME (black, Asian, minority ethnic) - which means UK residents with black or brown skin.



Vitamin D levels 25OHD in the UK by season for white and Black (African and Caribbean), Asian (Indian, Pakistani, Bangladeshi) Chinese and mixed race people

Larger version 1453x1255 .  If these graphs don't make you gasp at the tragedy of harm and death resulting from easily correctable nutritional deficiency, then you are not paying attention.  This is from:

Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank
Zahra Raisi-Estabragh et al.  Journal of Public Health 2020-06-19
https://academic.oup.com/jpubhealth/..../doi/10.1093/pubmed/fdaa095/5859581

The data is from 4,510 people, 1,326 of whom were SARS-CoV-2 RNA positive.   Despite the article's title, I found nothing in it regarding COVID-19 severity.  No-one is seriously suggesting that robust vitamin D supplements will significantly affect the chance of being infected with the SARS-CoV-2 virus.  The lower vitamin D levels of BAME men compared to women coming out of winter probably contributes to their higher incidence of severe symptoms and death compared to BAME women.

There is no numeric mention of the averages for white and BAME people, but the dotted lines evidently show these: 48 and 32 nmol/L respectively.  Divide by 2.5 to get ng/ml:
These BAME figures are averages for multiple ethnic groups.  It is reasonable to assume the Africans, with the darkest skin, have still lower average 25OHD levels.  Now consider UK African males, coming out of winter, take the 20% of these with the lowest vitamin D levels and I guess you would find hundreds of thousands of men with 25OHD levels 6 to 9ng/ml.  Now consider all you read below and on the icu/ page about 40ng/ml being the minimum vitamin D level required for proper immune system functioning, and how weakened and dysregulated immune responses (of which low vitamin D is the primary easily avoidable cause) are the cause of harm and death with COVID-19. 


Very High Prevalence of 25-hydroxyvitamin D Deficiency in n 6433 UK South Asian adults: analysis of the UK Biobank Cohort
Andrea L. Darling, David J. Blackbourn, Kourosh R. Ahmadi and Susan A. Lanham-New
British Journal of Nutrition 2020-07-22
https://doi.org/10.1017/S0007114520002779  (PDF hard to access.)
https://sci-hub.se/10.1017/S0007114520002779

This research also shows alarmingly low vitamin D levels among South Asians in the UK.


Very low vitamin D levels in BAME South Asians from Bangladesh Indian and Pakistan place them at very high risk of COVID-19 severe symptoms, harm and death.


Yet the researchers recommend only 0.01mg (10 micrograms = 400IU) vitamin D3 a day, in the hope that this will raise 25OHD levels above 25ng/ml - about half of what is recommended for immune system health.   These disastrously low vitamin D levels are averages.  In winter, in men, in the overweight and obese, and in those living in Scotland, the averages are lower still, and about half the people have less than the averages.


More on COVID-19 severe symptoms of BAME people in the UK below: #uk-bame .

Most people the world over are vitamin D deficient.  This is especially so of people who spend most of their time indoors, or protecting themselves from sunburn (as they should) and all the more so of people with brown and dark skin who are living far from the equator.

For instance (BMJ response), Somalis make up 0.84% of the population of Stockholm County, but but of the 15 deaths to 2020-03-24, 6 were Somali.  This is a death rate 48 times that of non-Somalis.

#othersites

Other sites concerning Vitamin D, the immune system and COVID-19

http://agingbiotech.info/vitamindcovid19/
 
Karl Pfleger's article  Low Vitamin D Worsens COVID-19  Immediate eradication of inadequate vitamin D levels is needed links to and discusses many research articles including some not mentioned here.


https://github.com/GShotwell/vitamin_d_covid

Gordon Shotwell's excellent list of research articles.

An extensive, long-established sites concerning vitamin D and other nutrients: https://vitamindwiki.com .   This is the work of retired electronics engineer and now vitamin D researcher Henry Lahore.  Vitamin D Wiki has many pages mentioning boron.  See also the pages on the APOE4 allele which is a risk factor for  Alzheimer's disease and numerous other conditions [W] due in part to it reducing the level of omega 3 fatty acids in the brain.  However, it boosts 25OHD levels, which is generally a benefit.

(I have been informed by Henry Lahore that the site www.vitad.org is an unauthorised, illegal, not updated, copy of vitamindwiki.com.)

Some pages at VitaminDWiki:

Loading doses - large initial doses.
Vitamin D intervention trials for COVID-19.
COVID-19 risk factors including obesity.
Farm animals and some pets get better vitamin D nutrition than most humans

https://www.grassrootshealth.net

This is a long established vitamin D advocacy organisation, whose International Scientists Panel includes many of the most prominent vitamin D research article authors.  Since 2008 they have advocated (the Call for D*action) for 40 to 60ng/ml 25OHD to be regarded as the optimal vitamin D level - well above most of the standards which persist to this day.

They offer test kits for vitamin D, omega-3 fatty acids and other nutrients, since there is 25OHD levels vary greatly between individuals using the same supplementation amount.  (Some of that variation will be due to their weight and whether or not the supplement is taken with a fatty meal.  So I think the graph there, with its extremes from large samples, depicts more variation than would be expected if a person scales their D3 dose to their body weight, and takes it with a fatty meal.)

https://www.powerofd.org

Dr Ken Redpath and colleagues do a great job of promoting robust vitamin D supplementation, especially for people in the USA with brown or black skin.

The main page and an interview emphasise the importance of aiming for 40 to 60ng/ml .  However, both these refer to a graph by Lorenz Borsche purportedly of data from a supposed Indonesian researcher "Dr Raharusun".  The graph depicts no deaths with patients whose 25OHD (vitamin D blood levels) are 34ng/ml and most of the patients dying if their levels were below 27ng/ml.  The sharpness of this relationship is completely unrealistic.  As you can read here, the supposed author does not exist.  The research never took place.  The "data" is completely fake and so is the graph.  I wrote to Dr Redpath and his scientific advisors about this on 2020-08-20 and three weeks have passed without a reply or the misleading information being removed.


https://vitaminduk.com/2020/05/30/black-asian-minority-ethnic-why-the-health-differences/

Rufus Greenbaum has been advocating better vitamin D nutrition in the UK since at least 2011.

http://www.drdavidgrimes.com/2020/06/covid-19-vitamin-d-progress.html

Dr David Grimes has written about vitamin D since at least 2006 (Are statins analogues of vitamin D?) He is from Blackburn, Lancashire in the North of England.  He reports that many BAME doctors are now prescribing vitamin D.

https://scotsneedvitamind.com 

They certainly do!

2020-06-11: The New York Times published an article https://www.nytimes.com/2020/06/10/well/live/coronavirus-vitamin-d-immunity.html which  concerns vitamin D and COVID-19.  It mainly focuses on whether or not this protects against getting the illness - but there is little evidence for this.  It also discusses its effect on the severity of symptoms, which is far more important and which is supported by evidence you can read below.  I commented, pointing to the #2015-Stagi research on vitamin D deficiency and Kawasaki disease.

If you want to read an academic article and you can't find a non-paywalled version of it from Google Scholar , or using the UnPaywall browser plugin then there's a good chance you can find it, ideally using its DOI, from https://sci-hub.se .   If this URL doesn't work, try here or here to find another URL which is currently working. (sci-hub.tw stopped working in late September 2020.)  SciHub is created and run by Alexandra Elbakyan and thrives on donations.

Sometime in the future - a new website

I plan a more extensive and better organised site 5 Neglected Nutrients, concerning five nutrients which most people do not get enough of, causing not just potentially deadly responses to COVID-19, but lifelong problems with the immune system, hypertension, stroke, bone and dental health:
Further down this page you will find information on these.

Research in the last few decades shows that boron has numerous functions regarding proper immune system regulation and bone health.  The mechanisms by which it works in the body are not well understood and most doctors do not regard it as an essential nutrient.  However, it is inexpensive, safe (below 20mg/day) and in doses such as 6 to 12mg a day helps reduce arthritis and problems caused by inadequate vitamin D. 

Modern diets typically provide only about 1mg boron a day.  Like vitamin D, it improves immune system regulation by reducing the overly-aggressive, pro-inflammatory response, which drives the cytokine storm response some people have to COVID-19.


#2020-Davies

Recent articles concerning COVID-19 vitamin D and other nutrients



#2020-Castillo

Spanish  vitamin D (calcifediol = 25OHD) intervention trial provides dramatic reduction in COVID-19 severity and deaths

This study from Cordoba, Spain is a highly significant:

Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study
Marta Entrenas Castillo, Luis Manuel Entrenas Costa, José Manuel Vaquero Barrios, Juan Francisco Alcalá Díaz, José López Miranda, Roger Bouillon, José Manuel Quesada Gomez.  Journal of Steroid Biochemistry and Molecular Biology  (Prepress accepted 2020-08-24)
https://www.sciencedirect.com/science/article/pii/S0960076020302764

This is a randomized, open label, double masked vitamin D intervention trial involving hospitalised COVID-19 patients.  Instead of supplementing with vitamin D3 cholecalciferol, which must be converted over a few days or so in the liver to circulating 25OHD (AKA calcifediol & calcidiol), the patients were supplemented with oral 25OHD which goes straight into circulation.  If you search this page for "autocrine" you will find other articles on how 40ng/ml 25OHD (as measured in vitamin D blood tests) is required for proper operation of the autocrine (with the cell) signaling systems of many kinds of immune system cell.

So this is a faster way of raising people's 25OHD level, without relying on liver function.

76 patients admitted to hospital with confirmed COVID-19 were randomly split into two groups:

26 patients in the control group received no calcifediol.

50 patients in the vitamin D supplementation group received 0.532mg (21,280IU) calcifideol on day 1, 0.26mg (10,640IU) on days 3 and 7, and then 0.26mg every week until discharge.

All patients received hydroxychloroquine and azithromycin.  Here are the results:


Patients
Did not need intensive care
Number Percentage
ICU
Died in ICU
Control
26
13 50%
13 50%  2 8%
Vitamin D
50
49 98%  1  2%

Initial and later 25OHD blood levels were not measured.  However the authors mention that greater than or equal to 40ng/ml is "a guide to the serum levels of 25OHD3 to be achieved in our trial .".   They also mention that in late winter and early spring, the average 25OHD level of adults in the Cordoba region is 16ng/ml.  Cordoba is 37° from the equator, as is Melbourne Australia, Auckland, Seoul, San Francisco, Washington DC and Athens.  This is a lot closer than the northern USA, Canada, Ireland, the UK, Germany and Poland

The randomisation produced a greater proportion of hypertensive and diabetic patients in the control group, but the authors state that their analysis shows that the protective effects of the calcifediol supplementation remained significant.  Age, sex and other comorbidities were in general much the same in the two groups.  The only significant comorbidity not recorded was obesity.

If the control group outcomes are extrapolated to the 50 other patients, we would expect 26 of these 50 to have needed intensive care if not for the vitamin D supplementation and that 4 of them would have died.


To my knowledge (2020-09-02) this is the first vitamin D hospital intervention trial to show such such success in reducing symptom severity and deaths.  Two major features of it are the use of substantial initial doses (though not as much as the several hundred thousand IU D3 doses used in other trials mentioned here) AND the use of direct-acting 25OHD calcifideol.

COVID-19 patients who need hospital care are in serious trouble.  There's no time to be waiting for their likely distressed liver to convert D3, so I think it is absolutely valid to use 25OHD instead.

With stark success like this, I think there can be no justification for:
  1. Further vitamin D hospital trials with a control arm.   We know from this and others trials that higher vitamin D levels are associated with (and are presumably the cause of) less severe COVID-19 symptoms and fewer deaths AND we have numerous theoretical reasons for expecting this to be the case.

    In this trial 12 or all 13 of the control patients who needed intensive care probably would not have if they had been given, in total, about 1mg of vitamin D in their first week, and just a quarter of that each week thereafter.   Likewise, two people died in this trial who probably wouldn't have died if they had recieved vitamin D supplements.

    The researchers had good reason for believing their intervention would save lives.  I expect they ran the trial with a control arm with heavy hearts knowing that they would not be giving the best treatment to some of their patients.   They chose to make the control arm 34% rather than the traditional 50%.

    I expect that the researchers conducted this trial for the benefit of millions of people who will contract COVID-19 in the future - to show beyond reasonable doubt that robust, especially directly absorbed, vitamin D supplementation reduces harm and suffering and saves lives in a hospital setting, so that doctors can proceed with confidence to treat people this way, rather than calling for further randomized controlled trials, review papers for such trials, etc. etc, while patients suffer and die for want of two or so cubic, millimetres of vitamin D.

  2. Hospital treatment with ordinary D3 whenever 25OHD calcifediol is available.   Time is precious and the D3 takes a few days to deliver its benefit.

I believe that the sacrifice made by the patients in the control arm should be honored by all doctors, in all countries, by rapidly implementing vitamin D supplementation programs in hospitals, and more importantly in the general population to reduce the chances of them needing to go to hospital at all.


#2020-Mardani

Vitamin D 25OHD levels of Iranian patients without COVID-19, with COVID-19 who survived and of those who died due to COVID-19

Association of vitamin D with the modulation of the disease severity in COVID-19
Mardani R, Alamdary A, Mousavi Nasab S.D, Gholami R,  Ahmadi N Virus Research 2020-08-28
https://www.sciencedirect.com/science/article/pii/S0168170220310558

In March 2020 123 outpatients aged 18 to 78 (median age 42) were referred to hospital with respiratory symptoms and/or a CT scan showing ground glass opacity in the lungs (X-ray absorption broadly consistent with pneumonia).  63 patients these were confirmed by PCR test as suffering from COVID-19 and 4 of these subsequently died.

Here are the averages of the initial 25OHD levels of these three groups of patients, bearing in mind that the COVID-19 positive group is all the 63, including the 4 who died:


Not COVID-19
COVID-19 positive total
COVID-19 positive who died
Patients
60
63
 4
25OHD
ng/ml
30.2
18.5
8.2

Fig 1 shows a three bar graph with a different figure for "positive", being 19.25ng/ml.  I think this refers to the average 25OHD levels of the 59 COVID-19 positive people who survived.



#2020-Gennari

Milan study: Vitamin D levels correlate inversely with COVID-19 severity

This report in Healio of a conference paper by Luigi Gennari MD, PhD, associate professor in the department of medicine, surgery and neurosciences at the University of Siena, Italy:
Low vitamin D levels independently associated with severe COVID-19 cases, death (2020-09-11) reports on analysis of 25OHD levels in 155 people:



The hospitalized COVID-19 group had lower 25OHD levels (mean, 18.2 ng/mL) than the group with mild symptoms (30.3 ng/mL) or the control group (25.4 ng/mL; P < .0001 for both).

Compared with COVID-19 cases who survived, those who died had lower 25OHD levels (mean, 13.2 ng/mL vs. 19.3 ng/mL; P = .03).


#2020-Panagiotou

Newcastle upon Tyne  (UK)  COVID-19 patients are vitamin D deficient - and the ICU patients are more deficient

Here is the first substantial report I know of regarding low vitamin D levels correlating with COVID-19 severity.  However, I have not yet had time to look carefully at this 2020-06-10 Singaporean article: https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v2 .

See also the next item #2020-Merzon for an Israeli study reporting a similar relationship between low vitamin D levels and symptom severity, but with greater statistical significance.


Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.
Grigorios Panagiotou, Su Ann Tee, Yasir Ihsan, Waseem Athar, Gabriella Marchitelli, Donna Kelly, Christopher S. Boot, Nadia Stock, Jim Macfarlane, Adrian R. Martineau, Graham Paul Burns, Richard Quinton  2020-06-25  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.06.21.20136903v2

164 primarily Caucasian hospital inpatients with COVID-19 had their 25OHD levels tested on admission, prior to a selective vitamin D supplementation trial - more on this below.

92 were in the general wards and 42 in the ICU.  (I am not sure how this assessment was made, since patients can be transferred between these.)  The most directly interesting findings were that the general ward patients averaged 30.6ng/ml 25OHD while those in the ICU averaged 24.4ng/ml .  This looks like a significant difference to me, but, probably due to the wide range of values in each group, analysis revealed that the p value was only 0.3, meaning that that with the observed scatter of values, even if there was no actual link between the ward/ICU observation and the measured levels, that on average, once in every 3.333 trials we would see a deviation like this.

However, some of the other observations point more strongly to a strong correlation between low vitamin D levels and COVID-19 severity.   No-one is seriously suggesting that the low 25OHD levels result entirely or largely from the severity of COVID-19, so most of this relationship presumably reflects low vitamin D levels causing the increased severity.  For this not to be the case, some more complicated hypothesis would need to be accepted, such as an unmeasured condition causing both the low 25OHD levels and the severity.  This is not out of the question to some degree, but when we consider how far these 25OHD levels are below the 40 to 60ng/ml levels recommended as optimal, it is hard to avoid the conclusion that low vitamin D levels are a major causative factor of COVID-19 severity.

The first observation is that the general ward group was, on average, older (76.4 years) than the ICU group (61.1).  This is highly statistically significant: p less than or equal to 0.001.   This means that if there really was no relationship, then such a deviation would be observed on average only once in 1000 or more trails.

Since greater age is generally associated with worse disease outcomes (the association is causative from age to outcomes, since the outcomes can't affect age!) the fact that the ICU patients were younger makes us think that some common factor, such as low vitamin D, might be having a stronger ill effect with these people, than if the average ages of both groups were the same.

Moreover, many comorbid conditions (pre-existing conditions generally associated with worse COVID-19 outcomes) were marginally less prevalent in the ICU group.  The two exceptions were obesity (how defined?) with ward/ICU percentages 6.3% / 25.7% and hypertension (how defined) 40.5% / 686.6%, both of which were p <= 0.01, and so highly significant.  However, I am puzzled by the hypertension finding, since the ICU average blood pressures were lower than the ward average.

C-reactive protein levels were much higher in ICU patients than in the ward patients.  This is expected since this is marker of increased inflammation.

The researchers defined "normal" 25OHD levels as 20ng/ml or above.  This may be normal in the far north of England, but it is half the bottom of the 40 to 60ng/ml range recommended by the D*action MDs and researchers.  The ward/ICU percentages of patients with less than 20ng/ml 25OHD were 61% / 81% (p = 0.02.)  This is a very coarse level of analysis.

Overall, the patients (here the ward and ICU patients are considered all together) had low vitamin D levels:
Even more horrifying, the researchers mentioned that an unspecified number of patients' 25OHD levels were below the 3.2ng/ml detection limit!  This threshold is 7% of the 46ng/ml average of East African herders and hunter gatherers.

This is a highly preliminary report, as part of a program in which COVID-19 patients with sufficiently low 25OHD levels recieved supplemental vitamin D3.

Sidebar:  I am just a . . . .   If I was a . . . .

I am just an electronic technician, and I think of low 25OHD levels like a sagging power supply voltage or a flat battery.  I would see patients suffering and dying for lack of this vital nutrient and I would move fast to fix it.   So I would be supplementing these patients to get their 25OHD levels well into the 40ng and higher range.  I would use oral or perhaps IV 25OHD (calcifideol) itself, since this goes straight into the bloodstream, while D3 takes days to a week or so to be converted into 25OHD - and that assumes normal liver function, which is unlikely to be the case.

I would also recommend that everyone on Earth supplement to get their 25OHD levels up to 40ng/ml at least.   To me, this is just like telling my musical instrument customers to use fresh alkaline batteries, not old ones, or ordinary carbon-zinc batteries.  The cost of these batteries and of vitamin D supplements is vastly lower than the cost of batteries being flat, or 25OHD being low.

These researchers considered patients with 30ng/ml or more as not needing any vitamin D supplementation. 

No hypercalcemia resulted from any of these bolus doses, which is not surprising. 

The authors write that vitamin D levels are so low in the UK in part due to poor promotion of vitamin D supplements to the public.  They don't mention that this 400IU dose is 10% or less of what most people need to get to 40ng/ml or so.  The note that in Scandinavia, vitamin D prescription is promoted to the public in winter, and result in better outcomes.

My overall view of the UK, being hit by COVID-19 as the country came out of winter, is that almost everyone has dangerously low 25OHD levels, and that this is in part due to the high latitude and to the scandalously low standards of dosage and adequate 250HD level recommended by the UK government.   I regard these low levels as being the biggest single easily avoidable cause of COVID-19 suffering, harm and death in the UK.  A similar pattern plays out in all countries - but the UK government recommendations are, in my view, just to be  very clear, dangerously and irresponsibly low.


#2020-Merzon

Israeli COVID-19 positive patients who require hospital treatment have lower vitamin D levels than those who don't

Here is a report which passed peer review in late July 2020:

Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population based study
Eugene Merzon et al. Federation of European Biochemical Societies (FEBS) Journal 2020-07-23
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15495

From an initial population of 14,000 people, 7,807 had had their vitamin D (25OHD) levels tested in February, March or April 2020 - due to some health concern.  Of these, 782 (10.1%) tested COVID-19 positive with a PCR (viral DNA, not antibody) test.  There was a marginal difference in 25OHD levels between those who tested negative (20.55mg/ml) and those who tested positive (19.00ng/ml).  With the large numbers of subjects, this was highly significant - P < 0.001, meaning that if there was no actual relationship, such a difference would only occur once in more than 1,000 trials. 

While it is not particularly surprising that higher vitamin D levels might reduce rates of infection with SARS-CoV-2, no-one is seriously suggesting that any level of vitamin D in the blood will provide reliable protection against infection.

Of much greater interest is the average 25OHD levels of those COVID-19 positive people who were not hospitalised (20.45ng/ml) vs. the levels of those who were (18.38ng/ml).  This is not a particularly dramatic relationship, and it shows that there is no particular level, at least in these ranges, of vitamin D which will completely protect against symptoms severe enough to warrant hospitalisation.

The value of this research is that it involves many more subjects than the Newcastle upon Tyne research.   While the two studies both relate different levels of symptom severity - the Newcastle one in hospitalised patients between needing general ward or ICU treatment, and the Israeli one between not needing hospital treatment and needing it - we see the same association with low vitamin D and greater symptom severity. 

In the Newcastle research, it could be argued that the COVID-19 symptoms, severe enough to warrant hospitalisation, may have reduced the vitamin D blood levels (directly, or by causing people to spend less time in the sun, ingest less food or supplements etc.) by the time they were tested, upon admission to hospital.  The Israeli research is less subject to such concerns about reverse causality, because the 25OHD levels were generally, as far as I can tell, taken before the onset of any symptoms or the COVID-19 PCR tests. 

While, due to low numbers of subjects and the (I assume) wide scatter of the 25OHD levels in both groups, the Newcastle trend was only significant to p = 0.3, the Israeli research reports a similar trend with very high significance p < 0.001.



#2020-Maghbooli

Iranian COVID-19 patients' symptom severity, inflammatory biomarkers and death rate correlate with low vitamin D levels

Here a preprint, from ten authors in Iran with co-author Michael Holick of Boston University - arguably the best known and most prolific vitamin D researcher.

Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients
Zhila Maghbooli PhD, Mehdi Ebrahimi MD, Arash Shirvani MD PhD, Mehrad Nasiri, Marzieh Pazoki MD, Samira Kafan MD, Hedieh Moradi Tabriz MD, Azar Hadadi MD, Mahnaz Montazeri MD, Mohammad Ali Sahraian MD, Michael F. Holick PhD MD.  Lancet preprint 2020-07-14
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3616008

The PDF date of of this preprint (v1) is 2020-05-28.  It reports on clinical observations up to 2020-05-01 (red, below), from Sina Hospital, Tehran, towards the end of the first wave of infections in Iran (from Worldometer) which began at the end of winter.   Tehran is at 35.4 degrees north, closer to the equator then most of Europe.




Of the 611 COVID-19 patients at Sina Hospital, this study concerns 235 who had 25OHD levels tested upon hospitalisation.  There is no mention of vitamin D or any other nutritional supplementation in hospital.  All patients were 18 years or older with mean age 58.7.  37.4 were over were 65+.   No patients 40 years or younger died.

30ng/ml was defined as vitamin D sufficient, according to Endocrine Society and other standards - not the UK standard which is 10ng/ml (which vitamin D researchers and clinicians have been protesting for years).

However, the observations show that for COVID-19 sufferers, 30ng is not sufficient, replete or whatever - since, as best I understand the analysis, bad outcomes were inversely proportional to vitamin D levels for most or all of the cohort of patients, not just those with 25OHD levels below 30ng/ml.

Sidebar on Iranian research:

I read a lot of research from all over the world, and I frequently encounter excellent research from Iran, Turkey, Iraq and (in at least one case) Kurdistan regarding nutrition, especially regarding vitamin D and boron.  

I wonder why, in the midst of a disastrous wave of COVID-19, and operating under numerous other difficulties, these Iranian clinicians were able to measure the 25OHD levels of 38% of their COVID-19 hospital patients AND conduct a detailed study, in April, when months later, in the whole rest of the world - with Western hospitals operating under far fewer difficulties - is very rare to find any research study of all those concerning with COVID-19 that even mentions vitamin D.

In the West, most doctors would look at you blankly at the mention of boron as a nutrient.  Even the vitamin D researchers rarely mention it.

My working hypothesis is that whatever the cause of the unknowing, unreasonable, lack of interest regarding nutrition which seems to be a hallmark of much of Western medicine, many clinicians and researchers in these countries have done well to avoid this stifling trend.

Some key points, with my paraphrasing:
This shows there is a downwards slope in symptom severity with increasing 25OHD levels, but no magic safety zone above any particular value which protects people from severe symptoms, as is depicted in the widely circulated, and still cited, Raharusun article (withdrawn in late June 2020, which I now believe is fictional: #2020-Raharusun) and from which the steep slope graph you can see here:  https://borsche.de/res/Patterns_of_COVID_19_Mortality_and_Vitamin_D_An_Indonesian_Study.pdf
was supposedly derived from.  This steep slope graph, which I used to have on this page, is also widely cited, at least on Twitter, blog posts and the like.

Ideally we would have age and 25OHD data for the population from which the patients came, with such data for those who were known to be infected.  Then we would be able to estimate, for different age groups, to what extent high vitamin D levels were protective against being hospitalised, having severe symptoms or dying, rather than having few enough symptoms not to need to go to hospital.  However, we don't have this data.

From the article, here are some of the most significant differences in outcome between the 158 patients with less than 30ng/ml 25OHD and the 77 patients with 30ng/ml or more. 

Clinical outcomes
< 30ng/ml
N = 158
>= 30ng/ml
N = 77
P value
Deaths
20.0%  (26)
9.0%  (7)
0.04
Unconsciousness
8.3%  (13)
1.3%  (1)
0.03
Hypoxia
39.2%  (62)
19.4% (15)
0.004
CFP > 40ng/L
77·2% (122)
61.0% (47)
0.01
Lymphocytes < 20%
60·1%  (95)
45·5% (35) 0.03
Severe - critical
 77·2% (122)
 63·6% (49)
0.02

In late July 2020, as I write this, we might have reasonably expected clinicians and researchers, starting in China, to have been measuring vitamin D levels and their correlation with symptoms since January of February, with a rich set of studies being published by March or April.  Yet, here we are, with only a handful of studies - and all of them which we can easily imagine being more detailed.

In this context, I take some interest in the following diagram.  It depicts all patients in this Iranian study, denoting those who died.   (I compacted the legends a little and moved the horizontal line at the bottom to the 0ng/nl position.)



It is notable that quite a few people with 40ng/ml or more 25OHD needed to go to hospital.  The five people who died with the highest vitamin D levels included one with about 54ng/ml, one with about 48ng/ml and three with about 40ng/ml.

Ignoring the two outliers with over 100ng/ml, there is a general trend towards people being hospitalised and dying with higher vitamin D levels according to their greater age. 

Assuming that people under 50 also have a wide range of 25OHD levels, and that these people suffered similar rates of COVID-19 infection, we can see that:
Assuming that the vitamin D level - severity/death correlations for these Iranians can be extrapolated to other populations, including those where vitamin D levels are generally (without supplementation) generally lower but where quite a few people have levels above 40 or 50 due to robust supplementation (I assume most people stay out of the sun) then I propose that in this data we see evidence of a relationship with both COVID severity and mortality which slopes downward over a range of vitamin D levels, from 0 to 60ng/ml at least.

#hazard

Contemplating a COVID-19 suffering, harm and death hazard curve according to vitamin D levels

Assuming for the moment that this is the case, I would depict this curve, or line, representing severity (and so the level of suffering and lasting harm) and of the risk of death, vs 25OHD levels, as sloping downwards from top left to bottom right, in the range of interest, at least to 60ng/ml, and probably somewhat beyond.

Here is an all-cause mortality graph from a recent UK BIOBANK research article.  It has nothing to do with COVID-19.

Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank
Xikang Fan et al. The Journal of Clinical Endocrinology & Metabolism, dgaa432 2020-07-04
https://doi.org/10.1210/clinem/dgaa432 (Paywalled despite being based on publicly funded data.)
https://sci-hub.se/10.1210/clinem/dgaa432



This results from an average 8.9 year follow-up time for 365,530 UK adults who reported no cardiovascular disease (CVD), cancer or diabetes at baseline, 2006 - 2010.

The 1.0 starting point is the all cause mortality risk for the 10% of the cohort with the lowest 25OHD levels ("lowest decile 10.0 to 22.7nmol/L) - a range of 4 to 9ng/ml.   46ng/ml (115nmol/L) is the average level for traditionally living Maasai herders and Hadzabe hunter gatherers.

See the chart above #2020-UK-vit-D-BAME (also derived from BIOBANK data) showing that, depending on season, sex and white / BAME, people in the UK mainly had 25OHD levels in the ~7 to ~27ng/ml range.

The rise in the risk of death shown above about 30ng/ml is primarily due to the risk of cancer and could be due to people who were ill at baseline taking vitamin D supplements, and later dying due to their pre-existing illness.  (The survey asked about vitamin D supplementation, but not the dose, and did not include anyone with a cancer diagnosis at baseline.)  See pages 16 and 17 of the article for their discussion of this small rise in risk beyond 30ng/ml not being reported in all other comparable studies, and not necessarily reflecting actual risks.

As noted above, vitamin D specialists recommend 25OHD levels of 40 to 60ng/ml for proper health.

There's a difference between what we all aim for - robust good health in numerous respects, as close as possible to what our bodies are capable of with good nutrition and care - and death, which is the failure to have any health at all.

Consider neurodegeneration - Alzheimers disease, Parkinson's disease, dementia with Lewy bodies etc.  They are all much the same, with minor differences in detail.  Excessive inflammation (which would be reduced by adequate vitamin D, omega 3 fatty acids* and I think boron) drives protein agglomeration and further immune responses which damage and kill neurons, subtly at first, and then vastly, degrading quality of life - and eventually extinguishing it.

* VitaminDWiki has thousands of pages on this topic.

This and many other degradations of quality of life don't show up as death until we have been suffering them for decades.  So all-cause mortality is some kind of guide as to what we want to avoid, but our goals are to thrive, not just survive.

Consider this curve, and for now assume it is flat beyond 30ng/ml.  

If you know for a fact that your 25OHD level is consistently 30ng/ml, it would be tempting to keep it there, since it looks like it would need to go as low as 15ng/ml before there was a noticeable increase in risk of death.  Some people who recovered from cancer or MS with much higher levels of vitamin D would tell you their experience is different - but lets assume you will never be in their position (though you may be).   In terms of CVD, cancer and all other causes experienced by these BIOBANK people, it looks like there's no health advantage to raising your 25OHD levels beyond 30ng/ml.

But this is mid-to-late 2020 and it is reasonable to assume that most of us are going to get COVID-19 in the months or year or so to come.   There are several conditions other than COVID-19 which test of our immune system's initial strength and its proper regulation - which fails spectacularly in sepsis, ARDS, influenza-driven pneumonia etc.

Most people think - not always correctly - that these things won't happen to them.

COVID-19 is a much more rigorous test of our immune systems than influenza  - and it is spreading rapidly, with most of us having no immunity, and no chance of protection via vaccines, antivirals (except perhaps if we can get into hospital, which is not assured) etc.

Now, back to the Iranian data.  The following are my thoughts, and I have no medical training - so consider everything carefully and don't take my word for anything.

It seems that the Iranian cohort had a much wider range of vitamin D levels than the UK BIOBANK data.  Most of the UK people, as far as I know,  have vitamin D levels below 30ng/ml.  They are living 50 to 58 degrees north, which is totally different from the Iranian experience at 36 degrees.

Yet there are quite a few Iranians - at least those older than 40 - in hospital due to COVID-19.  (Iran health is probably suffering since the country is subject to trade sanctions and faces other difficulties.)

IF we assume that the Iranian data is broadly applicable to all people - at least those older than 40 (and still with some  relevance to a smaller proportion of younger people and children, according to genetic and other factors), AND since we know that in the Iranian cohort, the inverse relationship between vitamin D level and severity/death is strong well into the range above 30ng/ml, then, at least for people over 40, we can draw another line very approximately, on a chart such as the above, depicting the continuing benefits of improving one's vitamin D levels even if they are 30ng/ml, assuming that one is going to get COVID-19 sooner or later.   Perhaps the benefits of increasing vitamin D levels, in terms of coping well with COVID-10, continue well into the 40, 50 and 60ng mil range, at least for a subset of the population with one or more risk factors for COVID-19 severe symptoms, such as advanced age, obesity, lung injuries, diabetes, particular haplotypes etc.

On the above speculative basis here is the same chart, but with a line I drew in, based on a WAG (a SWAG [W] not necessarily expert or rigorously scientific) of what the risk of suffering,  lasting harm and death would look like, for people aged 40 and above, according to vitamin D levels AND COVID-19 infection, considering all the comorbid conditions which tend to accumulate with age (though most would accumulate much more slowly if everyone had > 40ng/ml 25OHD):




While this is highly speculative, the Iranian data indicates clearly that COVID-19 patients in hospital who have less then 30ng/ml vitamin D do significantly worse than those with more than this. 

So even if the pre-COVID-19 hazard rate for death curve really did flatten out above 30ng, and the hazard curve for suffering and harm (which as far as I know is not calculated, since it is very hard to define and measure) did the same, then the the fact that the COVID-19 curve continues to provide better health above 30ng/ml means we should raise our levels more.

Its not radical to aspire to 60 or even 100ng/ml (the high end of normal, according to the Endocrine Society).  But such a statement will make many doctors twitch, especially those in the UK

Even if the pre-COVID-19 hazard curves, for suffering, harm and death really do go slightly upwards beyond 30ng/ml, if the curves for COVID-19 go down more over that range of 25OHD levels, which would not be surprising, then we would again do well to raise our vitamin D levels.

Of course, if we have already had COVID-19, did OK with it, believe correctly that we are never going to get it again, or if we get a vaccine soon and are very sure it is going to protect us, then the COVID-19 hazard curve is irrelevant and we can, according to theory, rest on our laurels at 30ng/ml.



#2020-Baktash

Baktash et al. in Southern England: Elderly COVID-19 patients have low vitamin D levels

Researchers in Slough, west of London, report on a cohort of 105 elderly (65 years and greater, av. age 81) hospital patients with symptoms matching those of a viral infection in March and April 2020.

Vitamin D status and outcomes for hospitalised older patients with COVID-19
Vadir Baktash1, Tom Hosack1, Nishil Patel1, Shital Shah1, Pirabakaran Kandiah1, Koenraad Van Den Abbeele1, Amit K J Mandal1, Constantinos G Missouris
BMJ Postgraduate Medical Journal 2020-08-01

https://pmj.bmj.com/content/early/2020/08/26/postgradmedj-2020-138712

The 35 patients not diagnosed with COVID-19 had median 25OHD vitamin D levels of 20.8ng/ml and the 70 who were diagnosed with COVID-19 had mean 25OHD levels of 10.8ng/ml.  There is no data on the levels of aged matched healthy controls.

In these observations, interquartile range (IQR) is a measure of the distribution of values such that 25% of subjects have levels below the first value and 25% have levels above the second value.  So this range encompasses the values of half the patients.

The interquartile ranges of the non-COVID-19 patients was 12.6 to 28.6ng/ml.  The COVID-19 patients range was 8.0 to 18.8ng/ml.   The significance of these mean and IQR differences was p = 0.0008, which means that if there really was no mechanism for such a relationship, observations with this divergence would only be made about once in 1250 trials.

The patients were 76% Caucasian, with 21 South Asian, 2 East Asian and 4 Afro-Caribbean.  The COVID-19 group were 60% men and on average 3.2 years younger then the non-COVID-19 group, who were 57% women.  Eyeballing the chart above #2020-UK-vit-D-BAME I estimate that at this time of year, in the whole of the UK, much of which is more northerly, the average 25OHD levels for an ethnicity and sex mix matching the COVID-19 group would be about 15ng/ml.  However, this is for all adults and people in their 80s typically have lower levels unless they supplement with D3 at higher levels than the very small 0.01mg (400IU) day recommended by the UK government.

Like many MDs in the UK, these researchers considered the threshold of vitamin D repletion to be only 12ng/ml, and gave patients with levels below this a 0.01mg (400IU) supplemental dose of vitamin D3.  (This article cites the fake Alipio article.)   Some quotes:

Vitamin D has been shown to condition the innate immune reaction against both bacterial and viral infections. Calcitriol 1,25OH, the active form of vitamin D, modulates macrophage activity by inhibiting the release of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, IL-12 and tumour necrosis factor-alpha.  Vitamin D shifts the adaptive immune reaction from a Th1 to a Th2 phenotype, downregulating differentiation of naïve T cells into pro-inflammatory Th17 cells, and promotes T regulatory cell induction.  Dysregulation of both innate and adaptive immunity, as a result of vitamin D deficiency, may therefore be central to precipitating the "cytokine storm" seen in COVID-19 infection.

In addition to anti-inflammatory properties, vitamin D also exerts a protective effect on human alveolar epithelial cells by promoting wound repair.  Vitamin D has also been shown to preserve endothelial integrity and deficiencies result in increased vascular permeability and leak.

Vitamin D also increases the expression of ACE2.  While increased ACE2 expression in the early pandemic was predicted to increase the risk of infection, paradoxically, ACE2 has also been shown to protect against acute lung injury.



#2020-Shakoor

Shakoor et al. Be well: A potential role for vitamin B in COVID-19

The B vitamins are rarely mentioned in articles concerning immunity and COVID-19, but vitamin B1, Thiamine, is a key feature of Paul Marik's ICU protocol, which predates COVID-19 by several years, and is the basis for the MATH+ protocol: icu/#Marik-protocol , https://covid19criticalcare.com as explained in an article MATH+ Protocol for the Treatment of SARS-CoV-2 Infection: The Scientific Rationale Paul E. Marik, Pierre Kory, Joseph Varon, Jose Iglesias & G. Umberto Meduri. 

Here is an article focusing on the B vitamins:

Be well: A potential role for vitamin B in COVID-19
Hira Shakoor, Jack Feehan, Kathleen Mikkelsen, Leila Cheikh Ismail, Lily Stojanovska, Vasso Apostolopoulos.  Maturitus 2020-08-14
https://www.maturitas.org/article/S0378-5122(20)30348-0/fulltext



Low levels of vitamins D and C result in coagulopathy and suppress the immune system, causing lymphocytopenia. Evidence has shown that the mortality rate is higher in COVID-19 patients with low vitamin D concentrations. Further, vitamin C supplementation increases the oxygenation index in COVID-19 infected patients.  Similarly, vitamin B deficiency can significantly impair cell and immune system function, and lead to inflammation due to hyperhomocysteinemia.

There is a need to highlight the importance of vitamin B because it plays a pivotal role in cell functioning, energy metabolism, and proper immune function.  Vitamin B assists in proper activation of both the innate and adaptive immune responses, reduces pro-inflammatory cytokine levels, improves respiratory function, maintains endothelial integrity, prevents hypercoagulability and can reduce the length of stay in hospital.


Regarding B vitamins used with vitamin D research projects dealing with specific conditions, with 25OHD targets above the 40 to 60ng/ml range unrecommended by recent research articles mentioned above (and so even further above many MD's 12 to 30ng/ml standard of repletion) please see this Vitamin D Wiki page, which results from 2019 interviews with researchers:

https://vitamindwiki.com/Comparing+High-dose+vitamin+D+therapies

They all use magnesium, vitamin K2, omega 3 fatty acids and one or more of the B vitamins.  Two also use boron, zinc and C0-Q 10.

The majority of Italian COVID-19 patients are vitamin D deficient

Here are some quotes from a 2020-06-24 News-Medical.net interview The Role of Nutrition in Recovery from COVID-19  with Dr Riccardo Caccialanza of San Mateo Hospital, Pavia, Northern Italy.

It might seem obvious, but unfortunately, nutrition is still widely overlooked in the hospital setting.

Our preliminary analysis clearly shows that the majority of patients admitted with COVID-19 have a vitamin D deficiency.

I hope that COVID-19 and that research, such as my own and the other studies, are seen and taken as our chance to develop a well-designed preventive campaign that puts nutrition and tailored vitamin supplementation at the core of preventative medicine.


Latitude and COVID-19 severity - solar UV exposure and vitamin D

I have not yet had time to read this article, but it looks interesting:

Evidence Supports a Causal Role for Vitamin D Status in COVID-19 Outcomes
Gareth Davies, Attila R Garami, Joanna C Byers 2020-03-13  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v3

Death rates correlate with high northern latitude.  There is too little data at southern high latitudes to be significant.






There is also a critique of RCTs (Randomized Clinical Trials), citing the work of several other researchers on this topic - regarding some RCTs not meeting proper requirements and their results incorrectly being being ascribed greater validity than observational studies.

#az-trial

Arizona State University trial of vitamin D to reduce COVID-19 severity

This trial is due for completion on 2020-08-18.  It involves robust vitamin D3 supplementation with the aim of determining whether this reduces the severity of COVID-19 symptoms:

https://clinicaltrials.gov/ct2/show/NCT04407286?cond=COVID-19&cntry=US&state=US%3AAZ&draw=2

https://pitchfunder.asufoundation.org/project/21360

The supplementation levels are high enough to effect significant change in 25OHD levels, though this will depend on absorption and on how fast the liver converts the D3 to 25OHD:


Take a vitamin D supplement daily for two weeks, at a dosage of 10,000 IU/day (0.25mg) b.i.d. (age 18-69 years) or 15,000 IU/day (0.375mg) t.i.d. (age 70+)

After two weeks of taking vitamin D, return to SCNM for a blood draw to remeasure levels of vitamin D, comprehensive metabolic panel, and complete blood count with differential. If vitamin D levels are still below 30 ng/ml, continue the dosage for 3 more weeks. If vitamin D levels are 30-49 ng/ml, continue at a dosage of 5000 IU/day. If vitamin D levels are 50+ ng/ml, stop supplementation.

This medical abbreviation (acronyms?) decoder http://www.cwladis.com/math104/lecture5.php tells us that "b.i.d" means twice a day and "t.i.d" means three times a day, so this would refer to frequency of taking 0.15mg (5000IU) capsules.


#veracity   #2020-Raharusun  #2020-Alipio

Reports of research from Indonesia and the Philippines which I previously accepted and quoted are, in my opinion now, completely fictitious

Please see my new site:

https://researchveracity.info

for all the reasons I now believe these two articles (and one other not cited here) concerning vitamin D and COVID-19 are fabricated.   Please read the material there and make up your own mind, rather than taking my word for it.  I am not an authority..

Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
Prabowo Raharusun et al. 2020-04-30  (Not peer-reviewed.)
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561 (Withdrawn in late June.)
It is available at: https://archive.org/details/ssrn-id-3585561 and
https://borsche.de/res/...COVID_19_Mortality_and_Vitamin_D_An_Indonesian_Study.pdf


Important update 2020-07-27:  See the following article in which three Indonesian MDs find no trace of the purported authors of the above article.  This includes searching the Indonesian Medical Council database and contacting the hospital mentioned in the article :

COVID-19 and Misinformation: How an Infodemic Fueled the prominence of Vitamin D
Joshua Henrina, Michael Anthonius Lim and Raymond Pranata
British Journal of Nutrition 2020-07-27
https://doi.org/10.1017/S0007114520002950


Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019)
Mark Alipio  2020-04-08  (Not peer-reviewed.)
Davao Doctors College; University of Southeastern Philippines
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3571484

I apologise for not scrutinising these articles more carefully at first.  I had no idea that anyone would write completely fictional documents posing as academic articles.


#2020-Pinzon
Vitamin D Deficiency Among Patients with COVID-19 : Case Series and Recent Literature Review
Rizaldy Taslim Pinzon et al.  2020-05-06  (Not peer-reviewed.)
https://www.researchgate.net/publication/341559270_Vitamin_D..COVID-19...

23% of the Indonesian population is vitamin D "deficient" (25OHD < 20ng/ml). "The examination of Vitamin D status is not a routine in Indonesian clinical setting."  Of 10 COVID-19 patients average age 49.6 in Bethesda Hospital Yogyakarta, 9 were deficient and 1 was "insufficient" (20 to 29ng/ml).   Their levels were (patients sorted by age):

Pt.     25OHD  Comorbidities (HT = hypertension.)
   Age  ng/ml                 Symptoms (Fever, Fatigue.)

 7 14F   8.3                   -
 3 17M  20.5                   -
 4 40M  11.9                   Fa, Fe, dry cough
 
1 49F  <8.1                   Fa
 2 51M  10.6  Diabetes         Fe, diarrhea
 8 54F  10.1                   Fa, headache
10 64F  <8.1  HT, post stroke  Fe, dry cough
 5 65F  11.6  HT               Fa, Fe, headache
 9 69M  <8.1  HT               Fa, dry cough
 
6 73M  12.4  HT COPD          Fa, Fe, dry cough

All patients received 2000IU oral D3 a day.

Singapore trial of 1000IU vitamin D3, B12 and magnesium

On 2020-06-10 the results of a small trial in Singapore were published:

#2020-Tan
A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients
Chuen Wen Tan et al. 2020-06-10  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v2

The patients were all over 50 years old, not requiring oxygen therapy.  The control group of 26 were admitted before the trial began.  The intervention group of 17 patients received, daily, on average for 5 days:
The intervention group was younger than the control group (average 58.4 to 64.1) and had a greater number of comorbidities (14 over 17 patients, compared to 49 over 26 control patients).  The intervention group required less oxygen therapy (3 = 17.6% to 16 = 61.5%) and only one of them required ICU treatment, compared to 8 of the control group.  Of the 3 intervention group patients who required oxygen therapy, 2 had only been treated for one day.

This is a small, non-randomized, non-blinded trial, conducted under "difficult dynamic circumstances" with modest vitamin D3 and magnesium doses and with no record of 25OHD levels.  The authors claim that after correcting for age and comorbidities, that the DMB intervention was associated with significantly better outcomes - and this includes with the two patients who were only treated for one day.

Research from Belgium, Louisiana, a homeless shelter in Boston . . .

Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics
Dieter De Smet et al. 2020-05-05  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.05.01.20079376v1

In this Belgian retrospective study, male but not female COVID-19 hospital patients had lower 25OHD levels than controls whose levels were sampled at the same time of year.  However, the controls were all "diseased" in that they were attending or admitted to hospital too.

In males, but not females, there is a clear correlation between low vitamin D and COVID-19 disease severity:



There's no record of to what extent any of these patients or controls were supplementing with vitamin D3.  Nor are there data on 25OHD levels for age matched non-hospitalised controls.

Vitamin D Insufficiency is Prevalent in Severe COVID-19
Lau, F.H. (2020).  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.04.24.20075838v1

There are numerous items of interest here, including:

In Louisiana, African Americans account for 70% of COVID-19 deaths despite representing only 32% of the population. In a Boston homeless shelter, 100% of 147 COVID-19 positive  subjects were asymptomatic.

COVID-19 hospital patients in ICU, on average, have lower vitamin D levels than those not in ICU.  Of these 19 ICU patients, 17 are African American. 17 of these patients have 26ng/ml 25OHD or less.


COVID-19 outbreak at a large homeless shelter in Boston: Implications for universal testing
Travis P. Baggett et al. (2020)  (Not peer-reviewed.)
https://www.medrxiv.org/content/10.1101/2020.04.12.20059618v1

408 people in a homeless shelter in Boston were PCR tested and 36% were positive for COVID-19.  Their average age was 53.1. They had no serious symptoms, and a remarkably low incidence of minor symptoms: 7.5% cough, 1.4% shortness of breath and 0.7% fever - and these rates hardly differed from those who tested negative, average age 50.8.

Homeless people are more exposed than average to sun, and therefore might be expected to have higher than average vitamin D levels, even without supplements. They also get more exercise - and I suspect few of them are as old as those in their 70s and 80s who suffer the worst harm from COVID-19.  They are probably less likely to use drugs to lower fever, though I guess they would often find it harder to keep warm and so sustain any fever which was helping them fight the coronavirus.

Also, perhaps they smoke more - and there is some evidence of smoking being protective:

. . . . France (nicotine?), Ireland . . .


#nicotine

Low incidence of daily active tobacco smoking in patients with symptomatic COVID-19
Makoto Miyara et al.  2020-05-09
https://www.qeios.com/read/WPP19W.4

File this under "COVID-19 curve-ball":  25.4% of the French population smoke.  4.4% of a COVID-19 inpatient group smoke and 5.3% of an outpatient group.

Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection
J.L. Faul et al. Ir Med J; Vol 113; No. 5; P84 (2020)
http://imj.ie/wp-content/...Vitamin-D-Deficiency...SARS-CoV-2-Infection.pdf

A large survey of Irish males 40 to 60 yo revealed they had a median 25OHD level of 18.8ng/ml.  25% of them had 16.4ng/ml or less!  25% of them had 26ng/ml or more.  So, assuming for the moment that the Indonesian and Philippino reports above are relevant to Irish men (and ignoring any nicotine use) most of these Irish men are at much higher risk of serious harm and death from COVID-19 than if they supplemented with vitamin D3 to bring their 25OHD levels well above 30ng/ml - say to the 40 to 50 range.

The report concerns 33 males 40yo and above with COVID-19 pneumonia and respiratory failure.  None of them suffered from cancer, diabetes, CVD or had received chronic immunosuppressive therapy.  12 were placed on mechanical ventilators and four of these men died.  The 21 who did not need mechanical ventilation had mean 25OHD 16.4ng/ml, while the 12 who needed this had mean 25OHD 10.8ng/ml.  All these levels are very low. indeed.


#2015-Stagi

2015: Severe vitamin D deficiency in Italian children with Kawasaki disease

By mid-May 2020 it has become clear that some children are suffering severe symptoms from COVID-19 - and some of them are suffering serious harm or are dying.  The inflammatory symptoms are similar to Kawasaki disease and it is reasonable to regard such cases as instances of Kawasaki disease [W]. 

However, due to some specific disease features - presumably due to particular characteristics of the SARS-CoV-2 infection - and its sudden wide prevalence, a new diagnostic category has been created for this condition when triggered by COVID-19:
Paediatric multisystem inflammatory syndrome [W].  Here I will use "KD" and "Kawasaki disease" to include both diagnostic categories.

Here is a 2015 article of crucial importance from Italy:

Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities?
Stefano Stagi et al. Clinical Rheumatology volume 35, pages 1865–1872 (2015)
https://link.springer.com/article/10.1007/s10067-015-2970-6  (Paywalled.)
https://sci-hub.se/10.1007/s10067-015-2970-6

Google Scholar 13 citations (2020-05-29)

On 2020-05-30, as best I could tell, none of the numerous academic journal articles concerning Kawasaki disease and COVID-19 cite this one.   See below #kdarticles below for a link to the list of such articles.  I wrote to the corresponding authors of all these articles pointing them to this Stefano Stagi et al. 2015 article.

Every such article should cite this one, because there is no other way of understanding the etiology of Kawasaki disease, how to prevent it, or how to cure it, if the central and surely causative role of vitamin D deficiency is not fully recognised.  This is true whether it is triggered by COVID-19 or any other condition. 


The patients were 21 girls and 58 boys, average age 5.8 years.  Their average 25OHD levels were 9.2ng/ml, while age-matched controls averaged 23.3ng/ml.  In the patients who developed coronary artery abnormalities, the average 25OHD level was 4.9ng/ml (sd 1.36).

These children, due to the decisions made by adults, were struggling to live with vitamin D 25OHD in their bloodstream 20% to 11% of what is normal for hunter gatherers in Africa.  https://www.ncbi.nlm.nih.gov/pubmed/22264449

These children are severely vitamin D deficient.  What is hard about this?  For heaven's sake give children vitamin D supplements so they never have to suffer and die like this!  All children before they get ill, and especially these KD children who have such low levels. Why are so many doctors resistant to vitamin D supplementation when most people, without supplements are deficient?

More on Kawasaki disease  in sections following the next one.


#pandend

Ending the global vitamin D deficiency pandemic

Inadequate vitamin D levels - such as 25OHD levels below 40ng/ml (100nmol/L) - are a slippery slope leading to multiple forms of ill-health, disease and sometimes death.   This is a global pandemic.  See the Google search results for vitamin D deficiency pandemic .

We are now living in what I hope will be the last months or year or so of the Vitamin D Dark Ages

Future generations will look back in bewilderment that we had such sophisticated technology, hospital care and social and scientific achievements - yet still expected most people to live with inadequate nutrition, including especially vitamin D.  This will be clumped together with other health-horrors-now-thankfully-and-firmly-in-the-past:  The days before sewerage systems;  hand-washing and basic sanitation;  antibiotics; vaccines;  anesthetics; chemical analysis of blood and tissue samples; X-ray and MRI machines; Internet access to health information and lively discussions like this one . . . .   The days when many people, including many doctors, smoked.  (They still do in China.)

It is not practical to repeatedly test the 25OHD levels of every person on Earth.  This would be far more trouble and expense than the vitamin D supplements themselves.  There are some concerns about vitamin D toxicity (link) among a small fraction of the population, which I want to analyse and write more about later - but in general everyone needs to get their 25OHD to 40ng/ml or more in order that their immune system works correctly.   This goal is at odds with the advice given by some, such as #21authors, that we should aim for 25OHD levels merely above 10ng/ml (25nmol/L).

Here are some arguments for robust vitamin D supplementation to ensure 25OHD levels above 40ng/ml which will ensure, in most people, strong initial immune responses to infections and well-regulated later responses with good resolution mechanisms - not the overly-aggressive, pro-inflammatory, self-destructive responses which cause the harm in Kawasaki disease, COVID-19 and many other conditions.

I am using Kawasaki disease (see the article linked to in the previous section) in children as an example, but the principles apply to people of all ages, and for all sorts of conditions - of which COVID-19 is the one which most urgently demands our attention.

The estimated vitamin D intakes of the KD children did not differ significantly from those of  the control group.  The numbers in brackets are the standard deviation [W].   Significance [W] values show the probability that this difference would occur by chance due to random differences even if there was no actual relationship between the two variables.  NS means the difference is not statistically significant - in this article, below 0.05.  NS means that there is a greater than 1 in 20 chance the difference in these observations could occur due to random variation rather than due to a real cause. 


Control KD Significance
Vitamin D from diet IU/day
micrograms
209(43)
5.2
220(49)
5.5
NS
Vit D supplementation in prior 6 months
10.7% 11.4% NS
25OHD vit D ng/ml
KD children with heart damage
23.3(10.6) 9.17(4.9)
4.92(1.4)
< 0.0001

Only about 11% of the children had received vitamin D supplements in the past 6 months.  We don't know how much they were given, or how these children's 25OHD levels differed from those who were not supplemented.  The control group's 23OHD level of 23.3ng/ml is (I guess) about the same as for many adolescents and adults.  However, older people, and those with darker skins would have generally lower levels.

A simplistic analysis of this might be that the KD children had the same (or slightly more) vitamin D intake as the controls (their sunlight exposure and sunscreen use was about the same too) and that a viral or bacterial infection trigger caused their 25OHD levels to plummet in the course of their illness.  In this basis, there might be no argument for greater vitamin D supplementation to prevent illness. 

There are, of course, strong arguments for supplementing these children with vitamin D once they are ill.  However I have not found any reports of doctors doing this.  It seems that most doctors are unaware of these low vitamin D levels, or consider them insignificant or at least not amenable to change once in hospital.  I am not a doctor, but it seems obvious to me that these children should get oral, intravenous or intramuscular 25OHD (25 dihyhdroxy vitamin D = calcifediol = Rayaldee) supplements as a matter of urgency, since this will directly raise the blood 25OHD their immune system relies upon. Failing this, they should at least get oral vitamin D3, which will take some days to be converted by their livers into the circulating 25OHD.

It is possible that the viral infection (and the direct, helpful - even if weakened - immune response to it) and/or the KD disease process itself (which is a self-destructive dysregulated immune response) depletes 25OHD levels.  I am still researching this, but I think there is limited evidence for substantial declines like this in any illness. 

The half-life of 25OHD in adults is weeks, but I guess it might be shorter in children.  Being ill, they may have been out of the sun for a month or so by the time they were admitted to hospital, and they may have not been eating well, absorbing vitamin D3 or converting it in their livers to 25OHD in the bloodstream.   So even without direct effects of the viral or KD illnesses, we might expect these children's 25OHD levels to drop a few percent to 30% (my guess) over this month or so of ill-health.

(Whatever small amount of boron they might have had from their normal food - fruits, vegetables and nuts mainly - would be rapidly depleted if they stopped eating this due to illness.  The half life in adults is less than a day.  Hospital food probably has little or no boron, since it is not recognised as a nutrient.)

Accepting that some non-trivial fraction of the difference between 25OHD levels of the control and KD children is caused by the viral illness and the immune system's subsequent attack (all the KD literature indicates that KD occurs weeks after the peak of viral replication), here is my attempt to explain the causative role of vitamin D deficiency in Kawasaki disease in general, KD or anything like it in children due to COVID-19 and more generally severe symptoms from COVID-19 in adults

For completeness, this explanation also attempts to cover severe outcomes for adolescents whose disease progression differs significantly from that of KD and of adult COVID-19.  Adult COVID-19 severe symptoms result from viral replication in the lungs driving endothelial damage and a resulting hypercoagulative state.  icu/  KD does not seem to involve the lungs so much, and most of the harm is observed in mid-sized arteries - especially those supplying the heart muscles - though I think stroke is also a cause of harm and death.

We start with a population of children of suitable age for KD, before any disease trigger.  We assume that the dietary vitamin D estimates and those for sunlight are valid and that the 23.3ng/ml average 25OHD levels of the control group apply to this whole group.

The first thing to note is that although the Endocrine Society regards levels of 30ng/ml or as being replete, 23.3ng/ml is too low by a factor of about 2.  It is half the average level of 25OHD in African herders and hunter gatherers.  See #2020-Baker-a and #2016-Caprio below for why we should aim for 40 to 60ng/ml. 

Assuming (for simplicity in this example) a Gaussian distribution [K] the 10.6 standard deviation indicates that 16% of these children have 25OHD levels below 12.7ng/ml, which is very low.  Let's take these children and call them subset AA.  The reasons for these low levels include some mixture of:
Now, by some magical means, we sort these children AA according to their genetic proclivity to mount an overly-aggressive pro-inflammatory immune response to infection even if they were replete in all nutrients including vitamin D and any we currently know little about (such as boron) which affect immune functioning.  This proclivity is due to numerous types of genetic variation concerning their immune system cells, on top of the general human tendency for our inflammatory immune response to be overly-aggressive due to the fact that we have no intestinal worms.  (See #helminthsgone below.)  Let's pick the 20% of these AA children with the most destructively dysregulated immune responses, and call them group BB.

BB are 3.2% of the initial group of children whose age made them possibly at risk of KD.

Now I will assume that 5% of these BB children - group CC - are infected with SARS-CoV-2.  This is 0.16% of the initial set of children. 

Ignoring, for simplicity, genetic variations in the virus, some children will get a mild initial dose and others will get a large initial viral load, which is inherently more difficult to fight.  There could be 100 to 1 variations in the viral load these children get.

Some of these SARS-CoV-2 infected children will develop a fever.  Of these, a fraction will be given drugs to lower that fever.  As far as I know, from all the research fever/ I found regarding viral infection fevers in general  - not specific to COVID-19 - this is a bad idea, and is likely to cause a weakened innate and adaptive antiviral response, and so a greater chance that the infection will worsen and so increase the likelihood of triggering KD.

Assuming the lack of helminths and genetic variations in overly-aggressive pro-inflammatory responses are not important in the initial stages of the infection (in the throat, or perhaps the eyes), there will be some inherent genetic variation in how strongly the children can fight the virus, even if they were replete in all nutrients. 

However, all of group AA, BB and CC are very low in vitamin D (less than or equal to 12.7ng/ml in this example), and this greatly reduces the ability of their innate (at first [K]) and later adaptive [K] immune systems to fight the virus directly.  So we expect some fraction of the CC children not to stop the viral infection in the first few days.

I will assume this is 20%.  For these children, group DD, the virus replicates in large numbers in their lungs, blood vessels or wherever else it is active in a way which tends to stimulate a self-destructive immune response we later diagnose as Kawasaki disease.  This is group DD - now 0.16 * 0.5 * 0.05 * 0.20 = 0.08% of the whole initial group of children - one in 1,250.

These children are in trouble - and these are the ones who, in general, get Kawasaki disease or whatever else their condition might be called - severe symptoms with possible lasting damage the heart and other organs, triggered by COVID-19. 

The short version of this story is that a SARS-CoV-2 viral infection has triggered KD in a relatively small subset of all children, according to the combined effects of various circumstances as just described.  I have assumed a sharp cutoff of 25OHD 12.7ng/ml to denote the children at risk of KD.  In fact, there is no sharp cutoff.  Some children with higher levels will get KD - presumably due to some bad combination of all the variables just mentioned.  Still, for discussion, this 12.7ng/ml sharp threshold is good enough.

Now lets re-run the situation with one major change.  This change is easier to make than changing lifestyle, urban shadowing, culturally driven patterns of clothing and sunscreen use, or food choices.  This change is also a hell of a lot easier than coping with the situation described above, in which some children - thousands to hundreds of thousands in any one country as COVID-19 affects almost the entire population - suffer illness, lasting harm and perhaps death, with all the efforts at treatment etc.

The change is that with the support of most doctors and the government, the great majority of parents recognise the need to get their children's 25OHD levels safely at or above 40ng/ml.  This means lifelong robust vitamin D supplementation (except perhaps if, as adults, they spend a lot of time all-year round in UVB rich sunlight without clothing or sunscreen protection).  It also requires robust vitamin D supplementation for  women in general and especially women of childbearing age, since their baby's 25OHD levels depend entirely on their own before birth, and frequently after when they rely on breast feeding.

(This will also significantly reduce the incidence of autism and probably numerous other health conditions.  Low vitamin D in-utero and/or early life seems to be a significant cause of autism: https://www.scientificamerican.com/article/vitamin-d-and-autism/ .)

The whole set of children now average 46ng/ml 25OHD.  The proportion of them with dangerously low 25OHD levels is now reduced.  So the incidence of KD in general, and in response to COVID-19, will be correspondingly lower.  Likewise adolescents and adults regarding severe symptoms from COVID-19 and numerous other chronic conditions and acute diseases.

If doubling the average level also doubled the standard deviation, then:

Ave.      SD       Proportion below
25OHD              12.7ng/ml

23.3    10.6      15.9%  
calc

46.6    21.2       5.5%   calc

in theory, 65% (1 - (5.5 / 15.9))of the children at risk of KD in the first scenario due to low vitamin D levels would no longer be at risk.  Likewise any other diseases which strongly depend on low 25OHD levels.

If everyone supplemented about the same amount, to double the average levels, the standard deviation would probably increase by less than a factor of 2, as I have assumed here.  The bell curve would be narrower and the proportion of children with less than 12.7ng/ml 25OHD would be even less than this.  If the SD was 16, only 1.7% of the children would have 25OHD levels below 12.7ng/ml - a reduction of 89% from 15.9%.

In this future era of ubiquitous vitamin D awareness, any children diagnosed with KD or similar conditions would be quickly treated with extra vitamin D, ideally 25OHD, and any other nutrients which would improve their immune system dysregulation.  At present, this does not occur, and hospital treatment relies on transfusions of donated plasma with antibodies, anti-inflammatory drugs, aspirin and (as far as I know - and though the doctors may not recognise this) probably a low level of vitamin D3 which may be in the food or IV drips the children receive once in hospital.

The same reductions in severe disease should apply for adolescents and adults with COVID-19, sepsis, severe symptoms from influenza etc.

Come the revolution we will all have  generally good levels of vitamin D supplementation, generally good (40ng/ml) 25OHD levels and so a great reduction in the incidence of severe disease states, with prompt repletion as soon as such states are diagnosed.


#cvkd

COVID-19 induced Kawasaki disease in children and babies

Further to the two sections above:

It is reasonable to assume that when children infected with COVID-19 have severe symptoms and sometimes die from a condition closely resembling Kawasaki disease, that in most cases they too were already struggling with extremely low 25OHD levels. 

According to these newspaper reports, on 2020-04-16, Alexander Parsons became the youngest person in the UK to die due to COVID-19.  He was 8 months old:

https://www.mirror.co.uk/news/uk-news/baby-dies-coronavirus-related-kawasaki-22039416

https://www.dailymail.co.uk/...Baby-dies...Kawasaki-disease-aged-eight-months.html

(In mid May 2020, Google reports 6,050 pages on this child's tragic death.)

In the Daily Mail comments, VV, Cheshire wrote:
 
My daughter's immunologist told me they had 200 cases in 6 weeks in the U.K. because of the instance in initially Asymptomatic COVID-19 in children.  There's usually only 300 cases of Kawasaki in an entire year.

"Only 300 cases" a year?  There are numerous bacterial and viral triggers for Kawasaki disease, with SARS-CoV-2 being a novel, widespread and potent one.  But these extremely low 25OHD levels can at best be only partly explained as a result of the disease (there are some suggestions in research that the levels drop due to inflammation).

It is obvious that most of these 300 children a year would not be suffering Kawasaki disease if their 25OHD levels were not so extremely low.  While individual levels do vary, for any given body weight and intake, surely if these children were properly supplemented, most of them would not have this disease, no matter what triggering condition they have which might have set it off in children with very low 25OHD levels.

#NHS-advice
NHS advice https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-d/ is that babies to 1 year should take 240 to 400IU vitamin D3 a day. This seems like a reasonable amount considering their small bodies.

mickyfin of Leeds wrote:

I also read recently that around 40% of covid patients recovering from treatment were also diagnosed with dangerous blood clots.

The comments are full of sorrow, grief and people apparently resigned to all that is happening - both COVID-19 and the decades old pattern of Kawasaki disease.   I saw no mention of vitamin D or any other preventative measures.

I am an electronic technician and computer programmer.  I want things to work properly - including especially people's bodies!  I wrote this comment to both newspapers, but in neither case did the moderators approve it:

It is reasonable to assume that children suffering severe symptoms from COVID-19 - especially those with a condition resembling Kawasaki disease - are struggling with extremely low vitamin D levels:

Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities? Stefano Stagi et al. Clinical Rheumatology volume 35 (2015)
https://sci-hub.se/10.1007/s10067-015-2970-6

The patients were 21 girls and 58 boys, average age 5.8 years.  Their average 25OHD (vitamin D) levels were 9.2ng/ml, while age-matched controls averaged 23.3ng/ml.  In the children who developed severe coronary artery abnormalities, the average 25OHD level was 4.9ng/ml.   These children, due to the decisions made by adults, were struggling to live with vitamin D in their bloodstream about 10% to 20% of what is normal for hunter gatherers in Africa: 46ng/ml (115nmol/L):
https://www.ncbi.nlm.nih.gov/pubmed/22264449 

#kdarticles
On 2020-05-30 I searched Google Scholar for articles concerning this disease and COVID-19.  I found none which mentioned the Stefano Stagi et al. 2015 article #2025-Stagi .  I think this article is the key to understanding, preventing and treating Kawasaki disease, no matter what triggers it.

This outrigger page:

http://aminotheory.com/cv19/kd/

lists those 15 articles, with a few notes about the contents of some of these articles.  See also below another 3 articles and the email I sent to the corresponding authors: #more-KD-articles-1 .

I may have missed one or two, but I think this is the great majority of the articles written about COVID-19 and Kawasaki disease.  None of them mention:
The general picture presented by all of them is that the etiology is Kawasaki disease is unknown, except that there is usually a viral or bacterial infection trigger and that the fact that only some children get it is explained by currently unknown genetic factors.

This is despite some of the articles observing a disproportionate number of sufferers being dark skinned (living in Paris, for instance) and that in Japan, the peak incidence coincides with winter.  

The average person would quickly link these observations to the possibility that vitamin D deficiency was a significant contributing cause to the disease.

However, these doctors do not think of this.  Some studies included lab tests on numerous  compounds associated with general health and inflammation, but 25OHD was never mentioned.

I know there is a problem with the volume of research, but any academic article concerning Kawasaki disease is affecting matters of life and death, and so should be based on the best available knowledge of the cause of the condition, and of measures to prevent and cure it.

The Stefano Stagi et al. 2015 article is good research of immense importance.  Perhaps some contributing reasons to it being only occasionally cited are that it is  behind a paywall and that it is in a rheumatology journal - and so may not be seen by the heart and vascular specialists who tend to work on Kawasaki disease.

#2019-Meyer
A 2019 article on Kawasaki disease does mention vitamin D and cites Stagi et al. 2016:


Breastfeeding and vitamin D supplementation reduce the risk of Kawasaki disease in a German population-based case-control study
K. Meyer et al.  BMC Pediatrics volume 19, Article number: 66 (2019)
https://link.springer.com/article/10.1186/s12887-019-1438-2

This is a retrospective study of Kawasaki disease in German children, with a control group made up largely of children who were in similar families - often friends of the families of the KD children.

The researchers had no information on vitamin D levels in any of the children.  They drew on medical records of the KD cases, which included various details of their condition and treatment.  This indicates that in general, the doctors treating these Kawasaki disease children had no interest in their vitamin D status

The researchers attempted to find a correlation between the incidence of KD and the length of vitamin D supplementation from birth and of breastfeeding.  Some correlation was found, but I think it is of little interest, since the median age of KD onset was 30 months and vitamin D supplementation ended on average after 5 months.  Of the 79% of KD patients who were supplemented, 27% were "irregularly" supplemented, and there is no information on the dosages.  Breastfeeding data was even less precise, with 21% of KD patients being breastfed for less than 2 weeks and no data on how long the remainder were breastfed.  Nor was there any information on the mothers' 25OHD levels, or those of the milk itself.

By 2.5 years, there would be no effect of that breastfeeding or vitamin D supplementation on actual 25OHD levels.  There might however be some correlation with the children's general nutrition and/or some lasting effects of the original breastfeeding and vitamin D supplementation on the children's immune systems.

In Germany, vitamin D supplementation generally is recommended for the first year of life.

As you will read in these pages, to safely reach or exceed 40ng/ml 25OHD - which seems to be the minimum required for proper immune system functioning - all people, from birth, need supplements, with the possible exception of those who spend so much time in the sun all year round that they produce enough D3 themselves.

The 1 year recommendation is obviously too short, but it did did result in more than half of the children being supplemented for 5 or so months to start with.

#more-KD-articles-1
On 2020-06-11 I found two more articles concerning Kawasaki disease and COVID-19, both with clinical details, plus another two discussing these.  I could probably have found more if I searched assiduously.

Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2
Elizabeth Whittaker et al. JAMA 2020-06-08
https://jamanetwork.com/journals/jama/fullarticle/2767209

Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City
Eva W. Cheung et al.  JAMA 2020-06-08
https://jamanetwork.com/journals/jama/fullarticle/2767207

SARS-CoV-2–Related Inflammatory Multisystem Syndrome in Children Different or Shared Etiology and Pathophysiology as Kawasaki Disease?
Brian W. McCrindle, Cedric Manlhiot JAMA Editorial 2020-06-08
https://jamanetwork.com/journals/jama/fullarticle/2767205

COVID-19–linked syndrome in kids new, distinct, studies suggest
Mary Van Beusekom CIDRAP News 2020-06-09
https://www.cidrap.umn.edu/news-perspective/2020/06/covid-19...kids...

The first three are written by 28 medical doctors and one PhD.  There is NO mention of vitamin D!!   It should be obvious to anyone with an understanding of immune dysregulation and vitamin D, and who is aware of the low 25OHD levels in child (KD) and adult COVID-19 patients with severe symptoms, that these symptoms are both, in large part, caused by inadequate vitamin D.

Of all the things I have ever researched, this is the greatest mystery: Why are so many doctors so ignorant of, so blind to, or whatever, the importance (generally causative) of inadequate vitamin D and a these two acute conditions which are affecting hundreds of thousands and soon millions of adults and children all around the world?

On 2020-06-11 I wrote to the corresponding authors of these articles, and of the 15 mentioned above, a message you can read here: kd/#msg .  I won't mention details of any correspondence, but will add a note here if and when I receive any replies.  (5 days later . . . . nothing.)

#uk-bame

UK discussion about BAME community susceptibility to severe COVID-19 symptoms generally ignores vitamin D

In mid-June 2020, the tide is turning and more people are seriously considering the low vitamin D levels of Black, Asian, Minority Ethnic (black and brown skinned) people in the UK regarding their much greater share of COVID-19 harm and death.  So hopefully the above heading will soon be be a footnote in history, rather than referring to tragic reality.

Please see the graph I added on 2020-06-20 above #2020-UK-vit-D-BAME which shows seriously low vitamin D level for UK White people and disastrously low levels for BAME people.

Here is an article, one of many concerning the much greater death toll among Black, Asian and Minority Ethnic people in the UK - especially among doctors and other healthcare workers.

Inequality in our ethnic minorities: we must act before the next pandemic
Dipesh P Gopal and Sonia Adesara BMJ Opinion 2020-06-02
https://blogs.bmj.com/bmj/2020/06/02/inequality-in-our-ethnic-minorities.../


I wrote a response to this. 

I wanted to write a similar response to an article in Unherd, concerning a hypothesis, which I disagree with, that the majority of people are already immune to the virus without being infected. 

Karl Friston: up to 80% not even susceptible to Covid-19
Freddie Sayers 2020-06-04
https://unherd.com/2020/06/karl-friston-up-to-80-not-even-susceptible-to-covid-19/


However, Unherd's discussion system, like that of the above BMJ page, is controlled by Disqus, and I am concerned that by writing something similar, the Disqus system will regard me as a spammer.

My response is on a separate page here: bmj-gopal-response/

On 2020-06-15 I was happy my comment, the first, was accepted for this Conversation.com article on the BAME COVID-19 tragedy, which does mention nutrition for immune system:

BAME people need a better chance of fighting off coronavirus – here's what can be done now
Anil Gumber, Senior Health Economist, Sheffield Hallam University 2020-06-15
https://theconversation.com/bame-people-...-140354


#SAAD

This 2020-05-26 article http://www.pulsetoday.co.uk/.../20040871.article * reports on a team of doctors north of Manchester (Dr Mohammed Jiva and colleagues, Rochdale and Bury LMC staff.php) who developed a Safety Assessment and Decision scorecard (SAAD), which commemorates their colleague, Dr Saad Al-Dubbaisi, who died of COVID-19. (Article on hundreds lining the streets for his funeral procession.) 

* I was able to access this article at first, but not a second time.  Clearing my browser's cookies for www.pulsetoday.co.uk enabled me to see it again.

Side note on geography and music:

Bury is 53.6° north of the equator. So is Wigan, where my father Jeff was born - and Wigan gets a mention in the KLF's Its Grim Up North .  This is like living  900km south of the southern tip of the South Island of New Zealand, with its glaciers and all.  Heaven help the Scots!

Here's a live performance of Justified & Ancient, with Tammy Wynette, Maxine Harvey and Ricardo da Force all warming this world immeasurably - the last two BAME, though I think the term didn't exist in 1991: https://www.youtube.com/watch?v=f1PNnDagj6s . This is my absolute favourite.

Here is my adaptation of the SAAD scorecard, with 25OHD levels in both ng/ml and (x 2.5) nmol/L:

Safety Assessment and Decision scorecard (SAAD) COVID-19 vitamin D UK BAME medical staff doctors nurses at risk

Here is a bigger version: SAAD_table--ng-per-ml--1000x620.png .

They only consider low vitamin D levels a risk factor for COVID-19 severe symptoms and death if 25OHD is below 20ng/ml.  See #2016-Caprio below for arguments for raising 25OHD levels to at least 40ng/ml.

Low vitamin D levels may be thought of as a risk factor along with other conditions like age, but unlike all the other factors listed in the above table, it can be changed within a week or so with substantial vitamin D3 supplementation - far more than the paltry 400IU/day recommended by the UK government.  If anyone has 25OHD below 40ng/ml, according to all the research I can find, there is are very good arguments why they should raise that by robust vitamin D supplementation as a matter of great urgency - to at least 40ng/ml, to approximate, to the best of our knowledge, the levels our African ancestors had when our immune systems evolved.

This would apply to virtually all people in the UK who were not already taking substantial (4000IU or more) vitamin D3 supplements.   Low vitamin D levels in the UK population in general, and in BAME communities in particular, have been recognised for years:

COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities
Eyad Abuelgasim et al. Curr Probl Cardiol. 2020-05-08 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207142/

This recent article assumes a 20ng/ml threshold for vitamin D deficiency and cites 2013 research: 

Vitamin D Deficiency Amongst Minority Ethnic Groups in the UK: A Cross Sectional Study
Jeetesh V Patel et al.  Int J Cardiol 1;167(5):2172-6
2013-09-01
https://pubmed.ncbi.nlm.nih.gov/23140614/ (Paywalled.)
https://sci-hub.se/10.1016/j.ijcard.2012.05.081

which found that, of 45 years and older people recruited at medical clinics, with South Asian (India, Pakistan and Bangladesh) and Black African-Caribbean, background, Male and Female, the following percentages of people had 25OHD levels: 

25OHD                        
ng/ml = nmol/L  SA-M  SA-F  BAC-M BAC-F 

 
> 20    > 50     7%   11%    13%   30%
12-20   30-50    17%   13%    34%   33%
 6-12   15-30    36%   31%    41%   38%
  < 6    < 15    40%   44%    14%   11%

These are "age adjusted" figures which I rounded to the nearest integer.  The article explains that for some conditions, SA and BAC people seem to be able to cope with lower 25OHD levels than people of European ancestry.  Still, these levels are frighteningly low for general immune health, and are clearly a significant factor in the higher rates of harm and death among these people due to COVID-19.

These extremely low vitamin D levels, and their generally causative association with a plethora of illnesses, have been known for decades.  I don't understand why governments, at the urging of most doctors have not not implement programs to get everyone's 25OHD levels at least to above 30ng/ml.  To this day (#21authors, below), some in the UK use 10ng/ml (25nmol/L) as the threshold above which they consider 25OHD levels to be sufficient.

The past record of ill-health hasn't prompted this push for adequate supplementation.  Even now (mid-June 2020) with the deaths of so many UK doctors, nurses and other health workers from their weak and dysregulated immune system responses to SARS-CoV-2, there are just murmurings about vitamin D, and lots more fuss about more difficult-to-correct factors such as crowded homes and workplaces.  These affect the likelihood of contracting the virus, while vitamin D levels have a profound effect on the incidence of severe symptoms.  Density of housing, use of PPE etc. are not decisive, because within months most people will be infected anyway.  The lockdowns necessary to really slow transmission are not sustainable for more than a few months.

There are many reasons to believe that a truly safe, effective, vaccine for SARS-CoV-2 in all its variations will never be possible.  Even if it was, it would take years to develop, test, refine and put into billion-dose scale production.  Individuals and governments waiting for a vaccine to save the day any month now are completely mistaken.

Robust population-scale vitamin D supplementation will be safer, cheaper and vastly more effective than all the current investment in drugs or vaccines.

The British Medical Association has a page devoted to the threat posed by COVID-19 to BAME medical workers: 

https://www.bma.org.uk/advice-and-support/covid-19/your-health/covid-19-the-risk-to-bame-doctors

It doesn't mention vitamin D.

Dr David Grimes, from Blackburn, north of Bury, wrote on 2020-05-07 that all the doctors in Blackburn  had recently begun prescribing vitamin D and taking it themselves - perhaps in part due to an impromptu video lecture he did while buying fuel for his chainsaw being widely circulated on Facebook. 

http://www.drdavidgrimes.com/2020/06/covid-19-vitamin-d-progress.html

He also writes that the deaths of (mainly BAME) doctors in the UK is slowing and that this was due in large part to vitamin D awareness being spread by social media and local newspapers.

A 2020-04-19 article in the BMJ Is ethnicity linked to incidence or outcomes of covid-19?
https://www.bmj.com/content/369/bmj.m1548 briefly mentioned vitamin D.  Most of the 24 (2020-06-15) responses concerned vitamin D.

The response from veteran vitamin D researcher William B. Grant mentions, among many other things, that winter 25OHD levels were 15.2ng/ml for vegans and 25.2 for meat eaters, which he attributed to meat containing both vitamin D3 and 25OHD.   Leslie Lewis mentions 1999 research into South Asian ethnicity and polymorphisms in the ACE (not ACE2) enzyme.  Robert A. Brown and numerous colleagues from the McCarrison Society wrote at length about vitamin D.

#pep-talk

Pep-talk for doctors regarding the need for robust vitamin D supplementation to protect against severe COVID-19 symptoms

DOCTORS!!!!  What is it about vitamin D deficiency that you just don't see, or accept in some fatalistic manner?  

The page you are reading and the icu/ page link to plenty of research showing the need for proper - 40 to 60ng/ml (100 to 150nmol/L) 25OHD levels to prevent the weakened and dysregulated immune response which is harming and killing millions of people due to COVID-19 - and has been doing so for decades at a slower rate with numerous other acute diseases and chronic conditions.

What is it about vitamin D toxicity (link) which makes you so wary of recommending robust supplementation of 4000IU and more for adults to achieve these levels?

If this catastrophic level of harm and death to your patients doesn't prompt you do do this, and the harm and death to your colleagues

Some of the Black, Asian, African and ethnic minority medical staff in the UK who have been killed by their own weakened, dysregulated, immune response to the SARS-CoV-2 COVID-19 virus - most or all of which would never have occured if they had been vitamin D replete, such as 40ng/ml (100nmol/L) 25OHD.

doesn't prompt you to do this, what will?

Doctors are subject to enormous pressures to conform, not to make wild claims, not to do anything which might cause harm.  Your ability to practice your profession requires you not to do anything which might make people think of you in terms of the sound made by ducks.  

Non-doctors all around the world are figuring out the need for robust vitamin D supplementation - sometimes with the help of doctors who recognise the need for this.  I am an electronic technician in Australia.  As far as I know, I have never seen a person infected with SARS-CoV-2.

Since March it was obvious to me that vitamin D deficiency was driving much of the harm and death from COVID-19.  Before I established these web pages on 2020-03-22 I wrote to numerous doctors and other responsible people about this.  The first version of the email went to the WHO
Strategic and Technical Advisory Group for Infectious Hazards (STAG-IH) :

Email-to-WHO-STAG-IH--COVID-19-vitamin-D-boron-fever-etc--2020-03-22.pdf

Since I figured out the urgent need for a global program of vitamin D supplementation program in March this year, when the Wordometer looked like this (2020-03-17):



I expect everyone else to have figured it out by now (13.5 weeks later 2020-06-13):



with 120,000 new confirmed cases and 4000 deaths a day.

Remember, the ex-factory cost of pharmaceutical grade vitamin D3, in 1kg lots, is USD$2.50 a gram.  At this rate, 4000IU a day costs USD$0.09 a year.  If all adults in the world took this, there would be little serious harm or death from COVID-19, or influenza and a great reduction in numerous chronic diseases.  Some people, especially those overweight, need twice this (see the next section).

We don't need blood tests, doctors consultations, double-blind placebo controlled randomized clinical trials etc. etc.  We need a program to get everyone's vitamin D levels safely above 40ng/ml, ideally within weeks - but it will take months with all the best efforts and full support of most doctors and governments.  It won't work for everyone, since it will be voluntary, but it will help most people escape harm from the COVID-19 infections they are bound to get in the months to come.  Fortunately, for the northern hemisphere, it will be summer.

Dr David Grimes, from Blackburn, north of Bury, reports (2020-06-07) http://www.drdavidgrimes.com/2020/06/covid-19-vitamin-d-progress.html that many BAME doctors are prescribing and taking vitamin D, and that the death rate among BAME healthcare workers is declining, at least in his area.

#2020-Baker-a

Articles concerning vitamin D supplementation to protect against harm and death from COVID-19

You can see the vitamin D supplementation naysayers (who want RCT trials of COVID-19 patients before they would recommend supplements, though a few say it would do little harm) debating with doctors and nurses who recognise how important it is to supplement vitamin D, in the comments to this article:

Does Vitamin D Protect Against COVID-19?
JoAnn E. Manson, MD, DrPH 2020-05-11
https://www.medscape.com/viewarticle/930152

Dr Manson, who has lead vitamin D supplementation research, proposes further work on the value of vitamin D supplementation in anticipation of COVID-19 infection.

I found two interesting comments:  Dr Robert Baker of New Jersey https://robertbakermdhealthnewsletter.blogspot.com  wrote (my boldface), on 2020-05-14:

I have tested over 12,000 patients for a vitamin D level since 2004.  A number of patients told me when tested that they take 1000 or 2000IU a day of vitamin D.  In spite of that almost all of those people come back with a result in the 20's.  Seldom over 30ng/ml. 

Most adults need 5000 units a day to reach a level of 40 to 50 ng.  Some actually need double that.  The only way to tell for sure is to test at 6 months and yearly.  It would be a waste to do a study that is only going to raise the level to high 20's or 30's.

How does one get someone to fund an RCT to document what so many clinicians have observed in the field for decades? The correlation of dramatically reduced incidence and severity of respiratory infections in hundreds of thousands of patients who replete serum vitamin D levels to 50ng/ml or more is not ‘anecdotal.’ It’s reams of unpublished potential case studies that could save lives.

Studies on the effects of vitamin D on various forms of immunity are probably being designed right now with the same pathetically insufficient doses to support healthy immune system function. Such a waste. Mostly over misplaced fear of Hypercalcemia. Most average weight patients would need to take 10,000 IU daily for a year to begin to see a rise in serum calcium levels.

Benefit - Risk Assessment of Vitamin D Supplementation
Heike A. Bischoff-Ferrari1 et al. Osteoporosis Int. 2010 July ; 21(7): 1121–1132
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062161/

Mike Vidler wrote:

80 yr old British born; user for 25 years, southern USA. No degenerative illnesses. NO infections in 20 yr.

Prepared to accept the consequences of my decision whatever they may be!)..
Typical dose 10,000 IU. (10 years)Typical 25(OH)d 70 mg/dL (175 nMol/L)


2400IU (0.06mg) a day D3 raises the 25OHD levels of most, but not all, white women in the USA above 30ng/ml - but few have their levels raised to the 40 to 60ng/ml range required for optimum health

Vitamin D supplementation in young White and African American women.
Gallagher JC1, Jindal PS, Smith LM. J Bone Miner Res. 2014 Jan;29(1):173-8

https://www.ncbi.nlm.nih.gov/pubmed/23761326

Here is my adaptation of one of the charts.  Each circle represents the vitamin D level of one woman in one of the five study groups after 12 months.  The first study group received no vitamin D supplements, so their vitamin D levels result only from sun exposure and the small amounts of vitamin D in food, with some foods containing small supplemental levels.

This chart shows the levels of the white women studied.  African American women, without supplementation, had still lower levels: on average 11.6ng/ml.


US white women need substantial vitamin D supplementation to reach 40 to 60ng/ml. African American women probably need more.


https://www.grassrootshealth.net/project/our-scientists/
 
https://www.mdpi.com/2072-6643/12/4/988

https://sci-hub.se/10.1007/s40519-016-0312-6

https://doi.org/10.1016/j.mayocp.2015.03.015

https://doi.org/10.3389/fendo.2018.00550

https://pubmed.ncbi.nlm.nih.gov/22264449/

Doctors advising vitamin D supplementation in sufficient quantities to raise 25OHD to 40 to 60ng/ml, which they regard as being vitamin D replete

Since 2008, with the Scientists' Call to D*Action link, doctors and researchers have been advocating 40 to 60ng/ml as the healthy standard for vitamin D 25OHD levels. 

While they may be in the minority, there are doctors all over the world, who - like Robert Baker #2020-Baker-a - recommend high enough D3 intakes that their patients will be vitamin D replete:

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
William B. Grant et al. Nutrients 2020, 12(4), 988
https://www.mdpi.com/2072-6643/12/4/988

It is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d [0.25mg a day] of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d  [0.125mg per day]. The goal should be to raise 25(OH)D concentrations above 40 to 60 ng/mL (100–150 nmol/L).

In comments regarding an article in lifting levels in government vitamin D advice: https://scitechdaily.com/vitamin-d...severity-in-covid-19..government-to-change-advice/ Sonia wrote, on 2020-05-13:

I had back surgery in October 2019 and my Dr. recommended to start taking D3 4000IU [0.1mg] every day + vit. E 1000 to help absorbed D3, I had the surgery and I was walking the same day. I also had COVID-19 in February and I didn’t know I had it until I recovered and no fever ever I was just very tired for 1 1/2 week.  I‘m 76 yrs. Old and doing great!

#2016-Caprio
Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects
Massimiliano Caprio et al. 2016-08-23
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity v 22, pp 27–41
https://link.springer.com/article/10.1007/s40519-016-0312-6 (Paywalled.)
https://sci-hub.se/10.1007/s40519-016-0312-6

This article has a good review of "high dose" (compared to recommendations such as 2000IU a day) vitamin D supplementation, including with oral and intramuscular 25OHD (calcifideol).  A 6 month trial with relapsing-remitting multiple sclerosis patients, of 800IU and 10,400IU D3 (cholecalciferol) per day:

. . . achieved 25OHD levels between 40 and 60ng/ml, which was considered the optimal target for patients with MS. In addition, only in the high-dose group, there was a reduction in the proportion of IL17+ CD4+ T cells, considered a major contributor to the immunopathogenesis of MS, with a concomitant increase in the proportion of central memory CD4+ T cells and naıve CD4+ T cells, concluding that high-dose cholecalciferol therapy exhibits in vivo pleiotropic immunomodulatory effects in MS. Adverse events were minor and did not differ between the two groups, indicating that 10,400 IU cholecalciferol daily is a safe and well-tolerated therapy in patients with MS.  [0.2mg].

A Brazilian pilot study by Finamor et al. on the efficacy and safety of prolonged high-dose vitamin D3 therapy in patients with psoriasis and vitiligo suggested that an oral daily dose of 35,000 IU [0.875mg] D3 for 6 months, associated with preventive measures (low-calcium diet and a daily hydration of at least 2.5 L daily), is a safe and effective therapeutic strategy for reducing disease activity. All nine patients with psoriasis and 14 out of 16 with vitiligo recruited in the study received benefit from the treatment, showing a decreased disease activity with no side effects. Altogether these studies indicate that 25OHD blood levels below 100ng/mL are safe.

Nevertheless, there are groups of individuals in which high doses of vitamin D over a long period could be detrimental in terms of developing hypercalcemia and rapid deterioration of kidney function, such as patients with primitive hyperparathyroidism or those with chronic granulomatous diseases, which are prone to elevated extrarenal synthesis of 1,25OHD.  Moreover, even healthy subjects with mutations in CYP24A1 - the mitochondrial enzyme responsible for the deactivation of 1,25OHD - are susceptible to developing hypercalcemia, hypercalciuria, and kidney stones when exposed to high vitamin D doses. 

Therefore, to avoid toxicity, all patients eligible for a high-dose treatment should be previously screened for hypercalcemia and hypercalciuria, while serum and urinary calcium levels should be monitored during the vitamin D treatment itself.

To date, it can be established that vitamin D dose up to 2000 IU/day, or more recently, 4000 IU/day [0.1mg] should be considered safe above the age of 9.  This dose should be corrected according to non-pharmacological intake of the vitamin D.
 


The question of potential vitamin toxicity for particular groups of people is a frequent argument for limiting supplement does for all people.  I plan to research this assiduously when writing the forthcoming website, using the best available research on vitamin D toxicity such as this .  I have an article here somewhere arguing that patients with granulomatous diseases do better with higher doses of vitamin D.  (These are immune system disorders in which the troops fuss and fight, mistake each other for the enemy, and bind to each other in numerous small clumps throughout the body.  Some immune cells in these clumps have been observed to convert 25OHD into 1,25OHD in such quantities perhaps due to intracellular bacterial infection - that it diffuses into the bloodstream, potentially disturbing calcium metabolism.)

Massimiliano Caprio and colleagues cite several lines of research indicating the need for 40ng/ml or more 25OHD to avoid various illnesses:

At least 40ng/ml 25OHD vitamin D needed for various aspects of health


#2020-Fabbri

Editorial – Vitamin D status: a key modulator of innate immunity and natural defense from acute viral respiratory infections
A. Fabbri, M. Infante, C. Ricordi Eur Rev Med Pharmacol Sci 2020; 24 (7): 4048-4052 2020-04-05
https://www.europeanreview.org/article/20876

They mention that 40 to 60ng/ml circulating 25OHD is required for the autocrine signaling system of immune cells to function properly.  25OHD in the bloodstream (from food, supplements or UVB-irradiated skin), for instance at a concentration by mass of 1 part in 25 million (40ng/ml) diffuses into the cytoplasm of the cell where it is the input (substrate) molecule for the CYP27B1 enzyme which converts it to 1,25OHD, which immediately complexes with vitamin D receptor molecules.  The complexes then migrate to the nucleus find a promoter molecule bonded to DNA near the start of a gene, and there activate the process of transcribing that gene into an RNA molecule containing the gene's instructions. 

That messenger RNA molecule - or rather multiple such molecules produced by this transcription mechanism - goes into the cytoplasm were ribosomes work along it, using its instructions to build a molecule of protein from the specified amino acids.  

The enzyme and receptor genes are both upregulated by a process driven by external conditions according to the cell type.  Likewise, the one or more genes upregulated (and some can be downregulated) by the 1,25)HD-vitamin-D-receptor complex vary according to cell type.

With blood concentrations of 40 to 60ng/ml or above, the rate of 1,25OHD synthesis becomes "substrate independent" - that is, the enzyme does not spend long waiting for another 25OHD molecule to fall into its active site for conversion.  Below this concentration, it takes longer, on average, for a new 25OHD molecule to engage, so this lowers the enzyme molecule's output of 1,25OHD and so limits this entire autocrine signaling pathway, reducing the cell's ability to respond as it should to all its conditions.  In the case of various types of immune system cell, this leads to both weakness in direct responses to the infection, and also to weak regulatory actions, which are intended to release anti-inflammatory cytokines and so reduce overly aggressive, self-destructive, hyper=inflammatory actions (AKA cytokine storm) by other immune cells.

So it is not surprising that low 25OHD levels make it more likely that SARS-CoV-2 will progress to the lungs, and once there, trigger an overly-aggressive, destructive, hyper-inflammatory cytokine storm.  This leads to destruction of endothelial cells lining the blood vessels and so to hyper-coagulatory blood which causes micro embolisms all over the body.

We also believe that maintenance of circulating 25-hydroxyvitamin D levels of 40 - 60ng/ml would be optimal, since it has been suggested that concentrations amounting to 40ng/ml represent the beginning point of the plateau where the synthesis of the active form calcitriol becomes substrate-independent [2011-Hollis err] [2018-Wagner].

Additionally, serum 25-hydroxyvitamin D levels of approximately greater than or equal to 40ng/ml could provide protection against acute viral respiratory infections, as demonstrated in a prospective cohort study published in PLoS One and conducted on 198 healthy adults [2020-Sabetta].  To reach these concentrations in adults, a dietary and/or supplemental intake of vitamin D up to 6000 IU/day – deemed to be safe – is required.  However, elderly subjects, overweight/obese and diabetic patients, patients with malabsorption syndromes, and patients on medications affecting vitamin D metabolism may require even higher doses under medical supervision.



Dr David Ajibade of the Nigerian based Brain and Body Foundation (bio) stated, on 2020-07-25 in an interview

In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.   (0.25mg a day.)
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/

#Maharashtra-police

Indian Police receive substantial vitamin D supplementation

Here is an example of the action governments and particular organisations and companies can take in this time of crisis to make a real difference to people's health through nutrition:



https://www.expresspharma.in/....vitamin-d3-dv-60k-for-250000-maharashtra-police-personnel/

Fermenta Biotech is one of the biggest producers of vitamin D3 cholecalciferol for both pharmaceutical use and for agricultural feed.  They have cholecalciferol factories in Kullu and Dahej:




Fermenta Biotech and Indchemie Health Specialities have jointly committed to supplying Maharashtra Police personnel 250,000 strips of DV 60K, each strip containing sufficient dosage for an individual’s recommended regime of 60,000 IU of Vitamin D3 per week for two months.

The state of Maharashtra includes Mumbai and has a population of 112 million people.   Its 250,000 personnel will use these oil-filled minicaps once a week to provide 8571IU (214ug) vitamin D3 per day.

Other articles not yet mentioned

I don't have time to report in detail on a number of vitamin D COVID-19 articles.  Here are the URLs.  I hope to return to these at a later date, probably on the new website, since this page is getting very long:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150529/

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.15764

https://journals.physiology.org/doi/full/10.1152/ajpendo.00138.2020

https://www.metabolismjournal.com/article/S0026-0495(20)30115-3/fulltext

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194616/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276741/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239633/

https://nutrition.bmj.com/content/early/2020/05/20/bmjnph-2020-000096.full

https://www.frontiersin.org/articles/10.3389/fpubh.2020.00135/full

https://www.europeanreview.org/wp/wp-content/uploads/4035-4039.pdf

Supplement vitamin D only if 25OHD is below 12.5ng/ml!

https://www.preprints.org/manuscript/202004.0023/v1

https://www.maturitas.org/article/S0378-5122(20)30292-9/fulltext

https://clinicaltrials.gov/ct2/show/NCT04344041

Single oral D3 dose 50,000 or 200,000IU.


#low-verylow

Irish doctors debate whether to use low or ridiculously low doses of vitamin D3

You may be interested to read Irish doctors debating how much supplemental vitamin D3 should be given, with one group (and these are the good guys) arguing for 2500IU (62.5ug) a day - which, above,  Robert Baker  wrote was nowhere near enough - and the other group arguing for 800IU (20ug) or so a day, which is 10% to 20% of what people actually need.  These are two of several articles in a Vitamin D Debate section of the May 2020 edition (index):

Covid-19, Cocooning and Vitamin D Intake Requirements
M.J.McKenna, M.A.T.Flynn
http://imj.ie/covid-19-cocooning-and-vitamin-d-intake-requirements/

They are concerned about supplements of 2000IU (50ug) being "high".

They were responding to an article by McCartney et al, here, citing the Filipino work (#2020-Alipio) I now regard as fake, with suggestions of up to 2500IU/day.   

Likewise a doctor who cites the Philippino and Indonesian research mentioned above, and who for some reason thinks that 600IU/day D3 is sufficient: (link) until RCTs demonstrate that more is needed for COVID-19 patients.

The central mystery for me, in all this, is not what is happening in COVID-19 patients, or in people who are suffering from a wide range of diseases, nor in how these tragic, disastrous, patterns of ill-health can be largely resolved by supplementation.  The central mystery, which I am slowly coming to elucidate, is why many doctors (at least in the West - and I haven't seen such a trend in nurses) are so ignorant and/or unreasonably wary of nutritional supplements in general and of vitamin D in particular.

I will write up my thoughts some other time, but for now, I regard many doctors' extreme reluctance to advise robust, safe, doses of vitamin D3 is  contributing to the immense toll of harm and death due to immune system dysfunction.

#21authors

21 authors advise very low levels of D3 supplementation, aiming for a minimum 25OHD level of only 10ng/ml

Meanwhile 21 authors, in an article finalised on 2020-04-29, support the official UK guidance on vitamin D intakes, cautioning strongly against exceeding 4000IU/day on account of unspecified dangers (though kidney disease was mentioned in passing):

Vitamin D and SARS-CoV-2 virus/COVID-19 disease
Susan A Lanham-New et al. bmjnph 2020;0

https://nutrition.bmj.com/content/early/2020/05/15/bmjnph-2020-000089

They advocate daily, midday sunshine as an important part of maintaining vitamin D levels - despite the sun not always shining and not being at a high enough angle in the sky to be useful, even if direct sunlight can be found in dense urban environments in which many people are confined due to shelter at home laws.  There's no mention of skin area to be exposed, but their "season appropriate clothing" description implies scarves and gloves, with little skin to be exposed, in winter.

They explicitly support the official recommendations for 400IU/day D3 (UK) and 600IU/day (USA and for >70 yo Europeans).  They note that the UK standards are intended to ensure the majority of the population have 25OHD levels above 10ng/ml (UK) or 12 to 20ng/ml (USA).  There is no reference to hunter-gatherer levels of 46ng/ml (https://www.ncbi.nlm.nih.gov/pubmed/22264449), or to the severe vitamin D deficiency observed in, and obviously causing (in combination with some infectious insult) Kawasaki Disease (#2015-Stagi above) were sufferers averaged 9.2ng/ml.

Historical note: I initially complained here "Nor is there any mention of the work of #2020-Alipio (3 weeks before their final version) and #2020-Raharusun (a day after) showing much greater risk of serious COVID-19 symptoms and death with 25OHD levels below 30ng/ml." but in late June I recognised these to be fake, so these Susan Lanham-New et al,  were right not to cite these. 

21 highly qualified people went to some trouble to write an article which gave people completely false assurances about the desirability of such low levels of vitamin D supplementation and 25OHD levels, whilst warning strongly against dosages which are actually, as mentioned above, at the low end of what is necessary to achieve vitamin D repleteness regarding immune system functioning.

I regard work such as this as a fundamental part of the problem we are trying to solve - and that it directly contributes to the suffering, harm and death caused by dysregulated immune system responses to SARS-CoV-2.

I wrote a comment to this article on 2020-05-20.  Despite assurances via email that the were attending to this, no comments have been published.  Meanwhile, the article has been widely reported in the press along the lines of experts advising that there is no reason to believe that vitamin D supplementation will help with COVID-19 symptoms - while suggesting that their low doses should be taken anyway, with an absolute upper limit of 4000IU/day.

#weak-sys

COVID-19 pathology - weak and dysregulated immune systems

On the ICU page icu/ please see these items:

Firstly, Farid Jalali's beautiful detective work icu/#2020-Jalali-b - an etiological hypothesis of COVID-19 lung injury, which explains may observations which are unique to this disease.  One of is diagrams:



Secondly a link
icu/#2020-Kim to a recent article Vitamin D and Endothelial Function which shows how important vitamin D is for enabling endothelial cells to vasodilate (and COVID-19 makes them vasoconstrict) and to resist inflammation.

If you are are a researcher or doctor - or if you still doubt how essential it is to make everyone vitamin D replete - please see the icu/ page for more detailed descriptions of COVID-19 lung and pathology and the role vitamin D deficiency plays in this.


Please see the ICU page icu/#2020-Tay for a link to an article which makes it clear how much severe COVID-19 symptoms are a result of weakened and dysregulated, overly-aggressive, proinflammatory immune responses.  A diagram from the article:




#helminthsgone

Weak and dysregulated, over-inflammatory, immune responses are caused by lack of helminths, individual genetic variation, dietary excesses and several common nutritional deficiencies

This is my account of this important question.  I haven't read it like this in any one academic article, but I cite such articles which support the various parts of my explanation.

The primary reason for the immune dysregulation which makes COVID-19 potentially harmful and deadly is that our immune systems evolved to be overly-aggressive due to the presence of intestinal worm (helminth) infestations which downregulated many aspects of our immune response.  Now - in developed countries - without such helminths, our immune system is overly-aggressive in several important ways, which contributes enormously to a plethora of acute and chronic inflammatory and autoimmune diseases, including asthma, MS (multiple sclerosis), inflammatory bowel disease, osteoporosis etc. etc.

Multiple sclerosis and the hygiene hypothesis
John O. Fleming and Thomas D. Cook,  Neurology 67 Dec 2006 page 2085
https://pdfs.semanticscholar.org/c3ad/39654adf2b578768482576bb0ad81f03d268.pdf
Google Scholar 186 citations

Prevalence of Multiple Scherosis is inversely proportion to the prevalence of helminth infections

(The Inkscape .svg file of the above chart his here.)
 
Some information on helminth infection prevalence by country and within countries is available at http://www.thiswormyworld.org/maps/find-a-map and PMC6114701

It would not be surprising if people with such infections had less trouble with COVID-19 than those in developed nations where we got rid of helminths decades ago.  However, many of these people suffer numerous health problems and have little access to hospital care.  They may also be deficient in vitamin D, boron and other nutrients, so this is not a cause for complacency or even much hope.  As far as I know, COVID-19 will spread inexorably through all countries and will cause a great deal of harm and death unless and until most people take supplements to fix their most pressing nutritional deficiencies.

#Ethiopia
That said, please consider these two items concerning Ethiopia:

Trend of Soil Transmitted Helminths in Ethiopian children: A Systematic Review and Meta-analysis (2000-2018)
Getaneh Alemu1 et al. (No journal - not peer reviewed) PDF date 2020-02-08
https://assets.researchsquare.com/files/.../v1/Manuscript.pdf

51% prevalence of helminths.  I haven't scrutinised the article, but it is clear from many other articles that helminths are more prevalent in Ethiopia than in most other countries.  Also, this advice for travelers (iamat.org) states Risk is present in urban and rural areas of Ethiopia.  Fleming et al. state that since school age children are the most likely hosts, and that infection in childhood may provide protection from MS for life, that relatively low (such as for most children being infected at some stage, rather than the whole population) levels of helminth infection may provide good protection for most of the population. 

Is COVID-19 as infectious and fatal in Ethiopia? Perhaps not
Daniel Hailu Ethiopia Insight 2020-05-28
https://www.ethiopia-insight.com/2020/05/28/is-covid-19-as-infectious-and-fatal-in-ethiopia-perhaps-not/

Numerous factors are discussed which might explain the low rate of spread and severity in Ethiopia.  Vitamin D is mentioned briefly, but not helminths.

We cannot easily fix the overly-aggressive immune systems we inherited.  Helminthic therapy https://helminthictherapywiki.org is sometimes used for severe asthma, Crohn's disease etc.  There is a lot of research into compounds which replicate of mimic the downregulating chemicals helminths exude. 

One dramatic demonstration of the importance of this evolutionary overshoot to inflammatory diseases is that Crohn's disease patients went into remission when infected with the relatively benign pig whipworm:

Trichuris suis therapy in Crohn’s disease
R W Summers, D E Elliott, J F Urban Jr, R Thompson and J V Weinstock  Gut 2005
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774382/

There is, of course, considerable genetic variation between individuals.  For instance, sensitivity to Crohn's disease has a strong genetic component.  Yet pig whipworm infection causes many Crohn's sufferers to go into remission.

The second set of reasons for this immune system dysregulation is nutritional deficiencies - and dietary excesses, such of salt and some fats.  These weaken many initial immune responses and are an additional cause of dysregulation which drives overly-aggressive inflammatory responses, which harm the self while failing to destroy the virus, bacteria or whatever it is which is causing the infection.

These nutritional deficiencies can be fixed - and fixing them for most humans is the only way we can coexist with COVID-19 without further disastrous harm and death and without the need for the disastrously harmful and deadly lockdowns. 

However difficult it may seem, fixing these deficiencies will be vastly easier, less expensive and better for everyone's health than the current approach of trying to hold back the tide of infection, while accepting a terrible toll of harm and death on a significant subset of the population as they contract COVID-19.



#vaccines

COVID-19 vaccines and immunity - robust vitamin D supplementation will be far superior to even the most perfect vaccine

(This section was added on 2020-08-31.)

This article: Jeffrey Seow et al. 2020-07-11 https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1
reports that antibody levels are proportional to COVID-19 disease severity and that, irrespective of severity, the antibody levels decline rapidly.  However, https://www.cell.com/immunity/pdf/S1074-7613(20)30183-7.pdf reports that T and/or B memory cells for COVID-19 antibodies  provide more lasting protection. 

According to Not just antibodies: B cells and T cells mediate immunity to COVID-19 (2020-08-24)  https://www.nature.com/articles/s41577-020-00436-4

Studies of patients who became infected with SARS-CoV in 2003 suggested that the infection induced durable T cell responses lasting for 6 years but no long-term memory B cells.  Importantly, these T cells were shown to cross-react with the SARS-CoV-2 virus 17 years later, but the extent to which they can provide protection is not known.
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/

Here are some quotes from the detailed Lessons for COVID-19 Immunity from Other Coronavirus Infections (2020-08-18) by Alan Sariol and Stanley Perlman  https://www.sciencedirect.com/science/article/pii/S1074761320303125 .

This recurrent theme [referring to vaccines for coronaviruses in cats, other domestic animals, agricultural animals and species used in vaccine research] of waning immunity and need for periodic boosts following initial infection or vaccination is relevant to our understanding of human respiratory coronaviruses and has implications for vaccine strategies against these viruses, especially SARS-CoV-2, in humans.
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/

The authors discuss mutations which can occur during persistent infection with a normally mild feline coronavirus which cause it to infect macrophages in addition to the usual intestinal epithelial cells.  The mutated form - Feline infectious peritonitis virus (FIPV) - is universally fatal.  Vaccination or prior infection with the coronavirus can give rise to antibodies which instead of protecting the cat, enable the virus to infect cells which develop into a particular type of lymphocyte.  (More details here.)  This process of antibodies enabling the virus to infect different types of cell than it normally does is Antibody-Dependent Enhancement - ADE.

ADE in the context of FIPV vaccination raises concerns about the same phenomenon occurring after SARS-CoV-2 vaccination.
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/

The Wikipedia article on ADE has a section on ADE complicating betavirus vaccine development, with examples of non-human animal research into vaccines for MERS_CoV and SARS-CoV (the virus which caused the 2003 disease SARS).

A Google Scholar search for ADE SARS-CoV-2 returns over a thousand articles.  The most highly cited article suggests that SARS-CoV-2 infections maybe worsened by ADE from antibodies raised by previous coronavirus infections - and that is may be an important reason why particularity populations have worse outcomes than other populations.

More on ADE:

A widely cited 2014 article demonstrated ADE in-vitro with dilute neutralising antibodies to SARS-CoV spike protein. Antibodies from a prior Dengue virus infection can lead to ADE on a second infection (Stat 2017) with consequent cytokine storm.  A 2020-07-22 Global Virus Network article on ADE and SARS-CoV-2 links to research articles including this one from 2015, in which a monoclonal neutralising antibody attaches to the MERS (another coronavirus) spike protein, changing its shape.  The antibody then attaches to the Fc receptor [W] of lymphocytes and other immune system cells which are intended to activate phagocytic (pathogen destroying) or cytotoxic (killing infected cells) actions, but in this case brings the attached virus into the immune cell, infecting it.  The GVN article mentions interactions with common cold coronaviruses and states:

Epidemiological studies investigating ADE in individuals with multiple SARS-CoV-2 infections or cross-reactivity to common-cold-causing CoVs will likely take several years. 
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/
In my opinion, the best way for black people to get adequate levels of vitamin D is by supplementation. And the research shows that adults should be getting no less than 10,000 IUs a day.

Read more at: https://www.vanguardngr.com/2020/07/vitamin-d-crucial-in-management-of-covid-19-sickle-cell-disorders-dr-david-ajibade/

Most members of the public, and of governments - and probably quite a few doctors - have a vision of a vaccine being a safe, well-tested, highly effective means of creating lasting immunity - akin to a magic bullet.   However, the safety of any vaccine cannot be known until it has been used in hundreds of thousands of people, since even rare incidences of ACE making subsequent SARS-CoV-2 infection much worse are a serious matter.  For more on this, click the aforementioned search link and see Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19 (2020-06-240 https://www.sciencedirect.com/science/article/pii/S1286457920301246 .

I don't have time to read these articles and I doubt of you do either.   However, if you think that a safe, effective, vaccine for SARS-CoV-2 can be developed and tested without years of work, then you should at least cast your eyes over the Lessons and frying pan articles.

Also, some of these COVID-19 vaccines - including the Oxford one the Australian government is so keen to get - work by injecting an artificial virus which can infect cells but not reproduce.   The infected cells produce parts of the virus's spike protein, which together with adjuvants, causes the immune system to recognise these as other and mount an immune response, just like in a real infection.  

How do the virus creators know which cells are going to produce these fragments?  What happens if the vaccine is given to someone who has already been infected with COVID-19?  They may not know it, and we can't give everyone an antibody test before vaccination to prevent this.  Let's imagine this person having an overly twitchy immune response - strong immunity from antibodies and/or memory cells AND genetic differences making them prone to dysregulation AND lousy vitamin D, boron, omega 3 fatty acid etc. intakes.  Why wouldn't their immune system go bananas with this sudden explosion of spike proteins and adjuvant and so cause extreme hyper-inflammatory reactions, including cytokine storm damage to endothelial cells?  This would lead to the same deadly coagulopathy which harms and kills most or all of the people who are killed by their immune system's response to a real COVID-19 infection.


Most doctors, ordinary people  and governments are operating according to the following "conventional wisdom":
  1. Infection with SARS-CoV-2 is potentially very harmful or deadly.

  2. Without a vaccine it can only be stopped with extreme and unsustainable lockdowns, social distancing etc. or by herd immunity.   (There are numerous arguments that the early, low-dose use of hydroxychloroquine and some other drugs are safe, highly protective and inexpensive - and that some government bodies are unreasonably restricting their use to the advantage of companies which make vaccines and more expensive drugs.   I tend to agree with this view.  I mention it because there is a growing body of opinion that the early and ICU care of COVID-19 patients could be much better than it is, so rendering the threat posed by the virus significantly lower than many people believe it is.   I think there is merit in this, but that vitamin D repletion is a much more powerful, safer and more generally useful approach than band-aid approaches involving drugs once people are infected.)

  3. Herd immunity (something like 70 to 90% or more people being immune) will stop, or dramatically slow, the spread of the virus, so even those with no immunity are completely or largely protected.

  4. Few, if any, governments aim for herd immunity to be achieved via most of their population being infected, so they have their populations living in fear, isolation, locked down etc. waiting for a population-scale vaccination program to achieve herd immunity with minimal direct infections.  This is personally, socially, economically and politically extremely destructive.
Consequently governments and populations alike, are, in general, doing their civil duty by  enforcing and complying with lockdowns etc. while eagerly awaiting the boffins to develop, test and mass-produce their magic bullet vaccines, ready for a bevy of hypodermic equipped nurses to administer to the great majority of the population.   This is reckless and at odds with all we know about vaccine development and testing, which normally takes many years.

A growing number of people are becoming alarmed and bitterly frustrated with this mainstream government approach, as supported by most doctors.   There are numerous websites devoted to this.  Tucker Carlson's 2020-08-24 video When do we get America back? encapsulates quite a bit of this frustration which I think is well founded and doesn't depend at all on avoidant themes such as the virus being a hoax.  I would really like to bring him and numerous other influential people up to speed on nutrition for immune system health!


Let's imagine the best case outcome for COVID-19 vaccination:
Even with these ideal conditions, vaccination against COVID-19 is absolutely the wrong approach.  

It is an attempt to solve the wrong problem.

The problem is not the virus.

The problem is that many people's immune systems are weak and dysregulated. 


There are three sets of reasons for this, considering a whole population of individuals:
  1. Humans now, with rare exception, are no longer infested with helminths (intestinal worms), which in our ancestors downmodulated several immune responses.  Our immune systems evolved with helminths and so some aspects of our systems' operation are dysregulated: overly aggressive, hyper-inflammatory and so (without helminths downmodulating these responses) cause the cytokine storm which is a crucial step in the development of severe COVID-19.  See #helminthsgone .   (Lack of helminths lead to dysregulation, not immune system weakness.)

    We can't easily fix this, since helminths are at least somewhat pernicious and many are extremely harmful.

  2. Individual genetic variations on the average human genetic pattern which cause some people to have weaker and/or more dysregulated immune responses than average.

    Again, we can't fix this.

  3. Nutritional deficiencies and some excesses (such as salt, high-fructose corn syrup, excessive omega 6 and trans fatty acids).  We can and must fix these since the health benefits vastly exceed the costs of doing so.

    The most important and best researched deficient nutrient is vitamin D.   Only tiny quantities, at very low cost, are required to bring everyone's 25OHD levels safely into the 40 to 60ng/ml range.  See #kp above and #plan below for details of the other deficient nutrients.
A country-wide, ideally global, program of vitamin D repletion will be much easier, less expensive and safer than any vaccine program.   Although it will take some months to build new vitamin D3 factories to produce the quantities we need, these quantities and costs are very small compared to vaccines.  An average weight person needs 1/22 of a gram D3 per year - and it costs about USD$2.50 a gram.

The same principle applies to influenza vaccines: influenza only causes serious harm to people with weakened and dysregulated immune systems.   This weakness and dysregulation has  several contributing causes, but in most people it can be largely or completely overcome with vitamin D supplementation to achieve 25OHD levels of 40 to 60ng/ml.

There is well-known seasonality driving influenza and common cold respiratory infections:



This is from:

Epidemic influenza and vitamin D
J J Cannell, R Vieth, J C Umhau, M F Holick, W B Grant*, S Madrionich, C F Garland and E Giovannucci  Epidemiology & Infection 2006
https://doi.org/10.1017/S0950268806007175

* Member of the NISH discussion mailing list.

The next chart is from correspondence regarding the above article:

Epidemic Influenza and Vitamin D [with Reply]
John F. Aloia and Melissa Li-Ng 2007
https://www.jstor.org/stable/4621170





The seasonality of the spread of influenza - and no-doubt COVID-19 - can be explained in terms of two potentially variable items, assuming the population mixes and behaves reasonably consistently throughout the year.  (For simplicity I am ignoring other factors like dry air leading to exhaled droplets drying into 0.12 micrometre virus particles which stay airborne for longer than the droplets would in humid air.   I am also ignoring sickness keeping people at home, and so spreading the virus less - which is probably not much affected by the season.)

I For a given viral insult, the average chance that a person becomes infected.

S  The total number of viruses an infected person sheds, at least when in the company of others who have not yet been infected.

The product of these two variables (I x S) has an enormous effect on the spread of the infection.  The number of viruses shed is likely to scale with the severity of the infection.   So even if I did not alter throughout the year, we could explain the wide seasonal variation in spread rate in terms of seasonal changes to the second variable alone:  S.

The first chart above - seasonality of influenza by latitude - does not enable us to distinguish the degree to which I or S varies, but we know the product of them varies a lot with summer / winter in locations about 30° or more from the equator, and not much for locations closer to the equator.   (There is, of course, no summer or winter at the equator.)

The two most obvious mechanisms by which I and S vary at locations 30° or more from the equator (and each could be affected completely differently by these two mechanisms) are:

W - Summer warmth and comparative dryness vs. winter coldness and wetness, with rain and perhaps snow.

D - Variations in vitamin D synthesis in the skin due to the Sun shining more directly downwards in summer, compared to at a shallow angle from the horizon in winter.  (Also, people exposing more skin in the warmer months.)  This directly affects the average vitamin D level of most of the population.  (Even those who get no sun exposure are caught up in winter waves of infection, due to that year's somewhat novel flu strain being passed around in most of the population during winter.)

The second chart is evidence for the hypothesis that the dominant mechanism for changing (I x S)  is D, because the women were still subject to strong W summer / winter temperature changes in New York State (40.6° north) and those who took the relatively small 0.02mg (800IU) D3 had hardly any more episodes of flu or common cold in winter than in any other season.

This second graph also enables us to distinguish whether it I or S which changed most, going high in winter and low in summer.  Since all the women in the trial were a tiny proportion of the population, their viral exposure was essentially unaffected by being part of the trial, including when half of them were taking vitamin D.   So, on average, the intervention group suffered the same number of viral insults, with the same seasonality, as the control group.   This trial's outcomes are unaffected by the viral shedding of its subjects.  So this data supports the hypothesis that, at least for these women, the variation in their vitamin D alone, and its effect on their susceptibility to infection alone, was sufficient for them to escape infection during the winter when they are most subject to the viral shedding of everyone else.

This doesn't tell us that viral shedding is unaffected by vitamin D, or by any other seasonal variable.  Maybe they are - and it is obvious that a person who is very sick for a long time will shed more viruses than someone who has few, if any, symptoms, for a shorter time.

Since these infections were self-reported - not detected by any medical examination or blood tests - we don't know to what degree the women were infected with too few symptoms for them to notice as the flu or a common cold.

What is clear from this data (and there are various other research studies on vitamin D levels and respiratory diseases, with a range of outcomes) is that even low levels of vitamin D supplementation greatly reduced the subjective experience of illness in whatever infections the women actually had.   It is also worth noting that African American women living in New York state are likely to be generally very low in vitamin D, especially in winter, in the absence of supplementation.   So even small supplemental quantities could make a significant difference to the 25OHD levels and to to improving the strength and regulation of their immune systems.

We also see that 0.05mg (2000IU) vitamin D provided much greater protection from noticeable infection than 0.02mg (800IU).   This is not surprising.

With SARS-CoV-2, being so infectious and with most people (as far as we know, and research is continuing on levels of pre-existing immunity), I doubt if the proclivity to be infected due to a given viral insult varies a lot between people with low and high 25OHD levels.

The enormous drop in reported flu / cold infections in this trial, due to 0.05mg (2000IU) D3 a day may not be representative of all people, but there are numerous research studies indicating that influenza and viral respiratory tract infections in general (and COVID-19 starts off, and ideally ends, in the respiratory tract) are made much less likely and/or severe, for any given viral insult, by higher levels of vitamin D.  For more such research:

https://vitamindwiki.com/tiki-index.php?page_id=1304

I believe that the severity of symptoms and so the degree of viral shedding will vary enormously between a person with very low 25OHD levels, such as of these women in New York State in winter without supplements (perhaps 10ng/ml or less) and such a person having taken 0.05mg (2000IU) D3 a day for a year.  We would expect 0.125mg (5000IU) a day to be still more effective at reducing the chance of infection and/or the severity of infection and so the amount of viral shedding.

I am advocating all people - or as many as choose do so with good information, access their choice of quality supplements at suitably low cost, and without coercion or unreasonable cajoling or pressure - take enough vitamin D3 to get their 25OHD levels to the 40 to 60ng/ml range.  This is what we aim for - but there's no time or money, and not enough labs or doctors, to do 25OHD tests for most of these people.

The solution needs to scale globally, since I don't know of a single country where average 25OHD levels are in this range.  As you can read above, this is the range of our ancestors, the range our immune systems evolved to work from, the level needed for proper autocrine signaling within immune system cells, and the range recommended by the best researchers.

By scaling the intake with bodyweight - and probably at a higher multiplier for weights much beyond average, which indicate overweight or obesity - we can aim to get people's average 25OHD levels into this safe and healthy range, without prior knowledge or subsequent testing of their levels.  Some will arrive at levels below 40ng/ml and some will get to levels well above 60ng/ml, which is OK.  See the d3/ page.  This is the best we can do without global testing, which is vastly more expensive than the actual D3 supplements.  The 150ng/ml threshold above which toxicity might be a problem can only be reached with much higher intakes than are needed when aiming for 40 to 60ng/ml.

It is no good advocating a scheme which works for middle-class people in developed countries, but not for their poor, remote and/or indigenous people, or not for developing countries with limited health infrastructure.  The plan has to work for all people.

It need not be expensive - its just a few cents a year per person of D3, packaged into weekly or fortnightly capsules.   Average weight (say 55 to 75kg): get a pack of 52 capsules each with 0.125mg (5000IU) and take one a week.   Other sizes would be made for children and young adolescents, and for overweight and obese people.  Morbidly obese people need medical care urgently, so their doctor can sort out their vitamin D and numerous other nutritional and medical needs.   Sick people need medical care too.  The mainstream program would be to make such capsules, independently tested, available from multiple manufacturers with good advice about how to use them.   In these quantities, they need not cost much.   However, new pharma grade D3 factories will need to be built.

As you can read in https://sci-hub.se/10.1016/B978-0-12-381978-9.10006-X , in 2010 about 90 tonnes of vitamin D3 (cholecalciferol) was manufactured.  About 20 tonnes of this was refined for human pharmaceutical use and the rest was for agricultural animals.  This 20 tonnes is about 0.009 milligrams (360IU) a day per person, though of course most of it went to only a few people.   Pharmaceutical grade vitamin D costs about USD$2.50 a gram ex-factory in 1kg lots.  So 0.125mg (5000IU) a day, would cost USD$0.12 a year.

Assume 0.125mg/day (1/8000th of a gram) for 7 billion adults (more for the overweight, less for children, and some people will choose not to take it)  = 875kg/day = 320 tonnes a year.   So we need new D3 factories.  There's no reason to expect the major factories in China and India to export to other countries once everyone realises how their current production meets only part of the needs of their own people.

Even a fraction of this would make a big difference, since (as far as I can tell, based on limited research to date) the people most at risk have very low vitamin D levels, and even small daily doses would raise these levels significantly and so reduce the chance they would suffer serious harm or be killed by their body's own weakened and dysregulated immune response to what is, for most people, the relatively benign SARS-CoV-2 virus.

The difficulty, disruption (to medical care, with so many doctors and nurses vaccinating rather than working in their regular roles), expense etc. of a global vaccination program can be imagined.   It is far, far, beyond the cost and difficulty of the D3 repletion plan I propose.

For the sake of the argument, lets assume that global scale vaccination was about as easy as D3 repletion.  Let's assume it is a single injection and that there is usually no need for medical supervision or care to deal with serious side-effects.

Here are the arguments which show that even then, vaccination is vastly inferior to D3 repletion - and why D3 repletion makes vaccination for both COVID-19 and influenza unnecessary.   This is not a generalised argument against vaccination.   There are good reasons for vaccinating against other diseases which are still deadly or exceedingly harmful with perfectly good immune responses and all the best nutrition.   Its just that COVID-19 and influenza are generally benign viruses (or at least not seriously harmful, in the case of influenza) and that the whole reason people want to vaccinate against them is because a small subset of people can be harmed or killed by the disease AND because that subset is harmed due to inadequate vitamin D (most importantly, of several nutrients) causing their immune systems be weakened and dysregulated.

So here we contemplate a vaccination scheme as lightweight as giving most people about 1/22 of a gram of D3 a year, in weekly capsules, without need for direct medical supervision.


Vaccination
D3 repletion aiming for 40 to 60ng/ml 25OHD
COVID-19 current and very similar strains
Assumed to be effective at stopping infection, or greatly reducing its severity, to the point where there would be almost no serious symptoms if people were infected AND there would be very few people infected anyway, due to herd immunity.  In reality, there are dangers of adverse reactions, inadequate immunity, variations in how many years immunity lasts and potentially serious outcomes if the vaccine causes Antibody-Dependent Enhancement in some people.
In the case of infection, will generally lead to no or mild symptoms, and will make serious symptoms, harm, and death unlikely except in rare cases where people have multiple serious comorbidities and immune dysregulation which remains a problem even with adequate vitamin D.  The generally low levels of viral shedding by most people, if they are infected, means that the disease cannot spread very far except in the most extreme situations of close personal contact.  
A new strain of COVID-19 which evades the immunity elicited by the vaccine
The current strains will be under strong selection pressure to evolve a spike protein which still attaches to ACE2 but which is not recognised by the antibodies which vaccinated people produce.  Given the global scale of the disease, this cannot be ruled out.  On the other hand, coronaviruses mutate less than flu viruses and there is at least some cross reactivity between antibodies raised by SARS-CoV and the SARS-C0V-2 spike protein, which is functionally different and superior in how it attaches to ACE2.
People will handle all new strains of COVID-19 as they do the current ones, unless the new strain has evolved to cause far more symptoms with increased viral shedding.  The virus is already highly infectious for a given viral insult, so there's not a lot of scope for it improving its performance in this respect.  There should be no problems unless the virus develops an entirely new mode of operation, evading healthy, strong, well-regulated innate defenses so it causes lots of shedding, presumably stronger symptoms and so it gets to the lungs and causes damage there even with well regulated, strong responses,

The virus already attaches strongly to ACE2.  Even if it attaches more strongly, it will be basically the same disease and D3 replete people will be infected briefly, with the infection being halted in the upper respiratory tract, at it is for most people today.
Influenza
No protection against infection or serious symptoms and death.
All the above applies to influenza as well.
Common cold and other respiratory diseases
No protection.
All the above applies.
Sepsis and ARDS
No protection.
All the above replies.  Hardly anyone - except those with profoundly damaging pre-existing conditions - will get sepsis or ARDS.  (Still, those who smoke and abuse their bodies may harm their lungs.)
Numerous other chronic and acute diseases
No protection.
Partial or very substantial protection against dozens of diseases and chronic conditions. See the list above at the end of the #kp section.  See also the long list of diseases on the left of the Vitamin D Wiki main page.
Need for medical personnel, syringes, hypodermic needles, refrigerated transport, privacy invasive record keeping etc. to fan out over whole cities and sparsely populated areas?
Yes.
No, but there needs to be good, well-labeled, inexpensive (or zero cost through government subsidy) supplement capsules and drops for babies, with a really good, multi-lingual, education campaign funded by the government and either approved by or paralleled by similar educational campaigns by internationally and locally trusted NGOs.  This must not be seen as a purely government initiative, and there must be no coercion, or any other crap such as only allowing people to travel or work if they do a 25OHD blood test to prove they are replete.

The same education and supply programs could also support increased intake of omega 3 fatty acids, boron, vitamin C, B vitamins, zinc, iron etc.
Longer term maintenance
Ongoing program for children and any new arrivals from overseas if not already vaccinated.   At present we have no idea of how long vaccine elicited immunity would last for.   Since it will be impractical to test people individually, research will show, for particularly sub-groups of the population, how often vaccination needs to be repeated.  Maybe it will last a lifetime - but this seems unlikely.
D3 supplementation needs to be maintained from birth (except for babies breastfed by replete mothers).
Other opportunities
If medical teams comb the countryside and reach most settlements, there would be opportunities for medical checkups and other healthcare services.
No such medical contact, except perhaps to reach particularly vulnerable people in remote areas.
Overall health benefits for people, and so reduced health costs for governments and better national productivity
No improvement on the pre-COVID-19 situation, which is very poor compared with the levels of health which can and should be achieved with proper nutrition.
There will be profound, long-term, improvement in health in numerous respects, so boosting happiness, productivity, reducing health care expenditure, taxation, poverty and crime.
Dependence upon or government?
As currently conceived, most national vaccination plans seem to be the work of government, though middle-class and wealthy people might have the opportunity to choose between multiple vaccines if such vaccines exist, are sold in their country and have made it through government approval mechanisms.  Otherwise, this is likely to be a highly government -centric operation, with all the privacy problems this entails, and profound resistance by many people (myself included) against getting injected with some concoction because the government says it is good.
I envisage government support, but multiple sources of D3, all independently tested and available at low or perhaps government subsidised zero cost.

There's no need for privacy invasive record keeping or medical involvement for the vast majority of people.

In chaotic third-world countries, it is possible that NGOs might do a lot of the work even if the government is not supportive.

There is technically no need for government support, other than to allow the sale of this nutrient in the quantities required.  For instance, in Australia, the maximum D3 content of any one capsule is 0.025mg (1000IU) which would make proper supplementation awkward and expensive.


#disclaimer

Disclaimer!

I am not a doctor.  I have no medical training.  I have not even done a first aid course, though I think everyone should learn this in high school.  My positive view of the research and ideas you read here should not affect your own decisions about healthcare for yourself and your loved ones .  You should read and consult very widely.

By all means ask your doctor, nurse or naturopath to read this material.

Through their training and day-to-day work, medical professionals develop a vast knowledge of interrelated considerations about human health, and use this for your benefit after individually assessing your condition. 

Their knowledge may be incomplete.  The medical conventions they rely upon may be out of step with current research.  They may be excessively wary of supplements and more confident about using drugs, due to the constant schmoozing of drug companies.  Their patients may be generally tired of dietary advice, and expect quick drug fixes for whatever ails them.  For reasons of professional liability insurance, and to protect their reputation, doctors may be reluctant to do anything different from what the main body of medical professionals seem to be doing - so many of them are bound by a strong herd mentality.

I provide information by way of linking to and quoting from research articles and - in some instances which I intend to make very clear - with my own interpretations and hypotheses.  But even if I knew all there was to know about your individual condition, I do not have the knowledge and experience to do what medical professionals normally do so well: give reliable guidance tailored to your particular situation - because I lack their training and experience.  Furthermore, I don't want that sort of responsibility.

If your decisions are influenced by what you read below, it should be because you have evaluated the arguments, read the research articles I cite and because you take responsibility for your own health.

If you don't understand what you read here, please rely on the judgment of someone who does - someone with a broad knowledge of science in general, biology, nutrition and human health to evaluate the observations and arguments in the broadest possible context.

I have expanded on a few acronyms with fuller text and/or [WP] Wikipedia links.

Paracetamol (Panadol) is the same as acetaminophen (Tylenol etc.)  It reduces fever and is generally not regarded as an NSAID https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug - a class of drugs which includes aspirin and ibuprofen.

About

I am an electronic technician working with electronic musical instruments http://www.firstpr.com.au/rwi/dfish/ . I also work in computer programming: C++ for mine schedule optimisation, continuing the work of my father Jeff Whittle.  My wife Tina and I live in Daylesford, north west of Melbourne, Victoria, Australia.

I created this website http://aminotheory.com in 2011 primarily for my new observations and etiological theory of Restless Legs Syndrome / Periodic Limb Movement Disorder, which I suggest should be known as Restless Limbs Sensorimotor Disorder:

http://aminotheory.com/rlsd/briefsumm/

This is not a commercial site.  It generates no revenue.  These web pages set no cookies in your browser.  It is a static site made with KompoZer.


Contact

I update this material according to new information and any feedback I receive from clinicians, researchers, or anyone at all. 

Please email constructive critiques to rw@firstpr.com.au .

Copying

Please quote selected passages in your social media feeds, discussion forums etc. - always with a link to this page's URL:

http://aminotheory.com/cv19/

Please do not copy the entire page, or substantial parts of it, to other sites, since I may update the text at any time, and I don't want out-of-date versions of this text floating around the Web.

#plan

Plan for better nutrition and guidance regarding fever

(This section was written 2020-05-26 and revised a little on 2020-06-15.)

We insist on proper operating conditions (fuel, oil, water, tyre pressure, ignition timing etc.) for our cars.  We insist on feeding our cats a diet which makes them replete in all known nutrients (though boron is not yet recognised as one of them).  We insist the AA batteries which run our devices are 1.5 volts, not 1.3.

Yet only a small fraction of 7.79 billion humans get their proper operating conditions, which begin with adequate quantities of dozens of nutrients.

Primary problems concerning immunity, health in general and COVID-19 in particular

Problems and Solutions:

P1: COVID-19 spreads quickly unless unsustainable - and ultimately harmful and deadly - lockdown measures are enforced.  If the disease only caused a week or two of suffering and inability to function properly, this would not be such a serious matter.

I have broken P2 into three sub-types.  All these are strongly associated with very low levels of vitamin D and of other nutrients.  However, there is much more to the interrelated set of health problems we are trying to solve than lack of vitamin D.

P2c: Coagulation.  With current (generally inadequate) approaches to nutrition and hospital care, a significant number of people who contract COVID-19 die (0.5 to 5%) or suffer serious harm (5 to 20%).  (2020-06-15: The UK death rate is 14% of the confirmed cases!  While the latter is surely an underestimate, the death rate will rise even if new infections stopped today.) Most of these are elderly people with known health problems, but there are lots of people in middle age, in their 20s and 30s - and some children - who are suffering lasting harm and death. 

The main reason for all this harm is the SARS-CoV-2 virus' ability, once it is replicating in the lungs (which would not occur if the immune system successfully fought it in the throat), to elicit a dysregulated immune response which damages the epithelium (inner lining of blood vessels and capillaries) in the lung.  The fragments of epithelial cells cause the blood to become hypercoagulative - the natural, evolved, response to these signs of broken blood vessels. 

This hypercoagulopathy causes blood clots (including thousands or millions of micro-embolisms) to form in the lungs.  These, plus the viral and immune system damage, reduces oxygen and CO2 exchange progressively over a week or so.  Beyond a certain point, unless their breathing is assisted in hospital (with oxygen via nasal canula, trying as much as possible to avoid mechanical ventilation, with its sedation, invasive plumbing and lung damage) the person will die.

Even without significant breathing difficulties, the hypercoagulative state causes blood clots all over the body, resulting in permanent harm or death.

P2i: Inflammation.  Many people, particularly as we age, suffer serious harm or are killed by a long list of chronic and acute illnesses caused by excessive inflammation.  These include diabetes (type 2 and type 1 which strikes in childhood), asthma, inflammatory bowel disease, neurodegeneration (dementia), some forms of cancer and the mechanisms by which it metastasizes, multiple sclerosis, coeliac disease etc.

P2s: Sepsis.  Many bacterial and viral diseases - and some injuries such as near-drowning and burns - if severe enough, can prompt the immune system to respond in an overly-aggressive, pro-inflammatory way known as sepsis.  This develops rapidly and even with ICU hospital care, often leads to permanent disability and death.  (Though see the Marik Protocol in icu/ for techniques which achieve better outcomes, in part by fixing the extreme vitamin C deficiency which afflicts sepsis and most other patients who need critical care.)

Most deaths caused by influenza are due to sepsis, in the form of Acute Respiratory Distress Syndrome (ARDS), in which the lungs are flooded (pneumonia) due to over-inflammation.  This fluid reduces the ability to breathe, potentially killing the person.  Even if this inflammation does not kill, it may lead to later bacterial infection - bacterial pneumonia - which again can flood the lungs, damage other organs and kill.

(Initially, it was assumed that COVID-19 produced a similar form of sepsis and ARDS.  We now know that the virus's direct harm to the epithelium of the lung, together with the overly-inflammatory response there, drives an extremely destructive hypercoagulative state, which is not found in traditional sepsis or ARDS.)

P2c and P2s are caused to some extent by existing illness and injuries, such as to the lungs, but are primarily caused by P3w and P3d:

P3w: The immune system has one or more of its many antiviral, antibacterial, antifungal or antiparasite mechanisms weakened.  This causes no direct harm to the self.

P3d: The immune system has one or more of these mechanisms dysregulated.   Overly aggressive, overly inflammatory, immune responses ensue, often  taking place at the wrong time or the wrong place.  These responses are  typically ineffective at combating the pathogen, but the most important result of this immune system dysregulation is inappropriate inflammation, including destruction of cells of the body which do not really need to be destroyed in order to stop viral or bacterial replication.

P2i is caused primarily by:
P4 The noxious properties of gluten proteins in wheat and related grains.  Rice and oats are fine.

These grains evolved sulphur cross-links in the protein of the wheat grain to make them difficult to digest by birds, animals and insects which would otherwise eat the grain.  These links give rise to wheat's dough's unique stretchy nature which is essential to bread-making.   The linked sections of protein cannot be broken into separate amino acids by our digestive enzymes.  The resulting protein fragments (the most notorious one is called 33-mer, with 33 amino acids) disturb the lining of the intestine and trigger an immune response there.  The whole intestinal lining is in a constant state of inflamed preparedness, to accept food and defend against pathogens.  This opens gaps in the tight junctions between the brush-border cells [W], allowing lumen (digestive juices, food fragments and bacteria) to enter the bloodstream, so causing inflammation and other problems throughout the body.  For instance, in some people, wheat causes neurological problems, such as gluten ataxia [W] even though the problems in their digestive tract to not result in any noticeable symptoms.

While the sourdough processes used for all bread until the early 20th century reduces this disturbance by breaking down the noxious protein fragments, our taste for wheat condemns many of us to a lifelong struggle against the ill-effects of these indigestible fragments. 

Other plants we eat contain noxious substances too.  Wheat gluten would still cause us some harm even if our immune system was working perfectly.  Today, due to human genetic variation and unknown triggers, some people suffer intense harm with coeliac disease, while most of us other wheat-eaters suffer more subtle forms of harm over a lifetime of eating non-sourdough wheat products.

There are several contributing causes to P3w (weak immune responses) and P3d (dysregulated, overly-aggressive, proinflammatory responses):

P5: P3w - Generally poor nutrition (including the separately listed problems of inadequate intake of macronutrients omega-3 fatty acids P15 and potassium P16 and of multiple micronutrients, such as vitamin D and boron P14), lack of exercise and lack of other essentials for health and happiness including clean air and water, sunshine, close friends and loving relationships, social contact, good medical support when needed etc.

P6: P3w - Prior injuries and illnesses

P7: P3w & P3d - Nutritional excesses, such as salt, omega-6, saturated and trans fatty acids.

P8: P3w - Use of recreational drugs which harm health in general and immunity in particular, including alcohol and no-doubt tobacco, cannabis, cocaine etc.  (Though there are suggestions that nicotine has anti-inflammatory effects which protect against severe problems with  COVID-19: #nicotine .)

P9: P3w - The use of prescription drugs which weaken immune responses (immunosuppresants are helpful in some medical conditions, often due to our lack of helminths) or which cause particular problems with COVID-19.   There has been discussion about particular hypertension drugs making things worse for COVID-19 patients.  Some drugs such as hyroxychloroquine (for lupus) or others which dampen down excessive immune responses, such as for asthma or Crohn's disease, may be protective against severe COVID-19 symptoms.  (Mehra et al. 2020-05-22 report (hydroxy)chloroquine apparently causing heart arrhythmia and being associated with higher death rates and an earlier RCT showed no antiviral or other benefits.) Prescription drugs should be continued unless advised by your doctor.

P10: P3w - Some people seriously curtail their body's initial attempts to fight the virus by lowering their temperature when they have a fever.  See the fever/  page.

P11: P3w and P3d - Individual immune responses differing from from the norm due to genetic variations.   These variations are primarily in the codons of our DNA, but there is also an epigenetic [W] component, in which long lasting (and impossible to change, as far as we know) methylation and other additions to the DNA occur due to life experience - including especially in-utero - affect how our bodies interpret the genes we inherited from our parents.

P12: P3d - Assuming that the person does not have any helminth infections (intestinal worms, as described in the previous section),  some aspects of their immune system, due to evolution, being set up for overly-aggressive actions which are not being downmodulated by the helminths our ancestors had.  See above:  #helminthsgone .  This is the condition of essentially all people in developed countries - our immune systems, in general, are primed to respond in damaging, overly-aggressive, proinflammatory ways to many stimuli, including especially SARS-CoV-2 infection of the lungs. 

P13: P3w and P3d - People with helminth infections face P12 in general, but to some extent these P3d excesses will be moderated by the chemicals their helminths exude.  These people may have weak responses to the virus due to helminthic downmodulation of normally effective immune responses.  Their (without helminths) overly-aggressive responses may persist, may be downmodulated to being about optimal, with a good balance between fighting infection and harming the self.  These responses may also be downregulated below the point of optimality - being ineffective against the virus, and hopefully being still less  harmful to the self.

P14: P3w and P3d - Deficiencies in nutrients which cause significant weakening and/or dysregulation of the immune system.  Of course all nutrition affects general health and so the immune system, but there are a number of micronutrients which are important here:  vitamin D, boron, vitamin C, zinc, magnesium and probably quite a few others. 

There are also two macronutrients of interest in this regard - macro because we need grams of them per day, not milligrams or micrograms: omega-3 fatty acids and potassium.

Most of what follows on this page, and in the forthcoming 5 Neglected Nutrients website, concerns vitamin D, boron, vitamin C, omega-3 fatty acids and potassium.  These are all of widely neglected, but are vital to immune system functioning and to avoiding hypertension and stroke.

This article is highly relevant, but I haven't read it yet.  It mentions vitamins A, D, C, E, B6, and B12, folate, zinc, iron, copper, and selenium.

A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection
Adrian F. Gombart, Adeline Pierre and Silvia Maggini Nutrients 2020, 12(1), 236 2020-01-16
https://www.mdpi.com/2072-6643/12/1/236


P15: P3w and P3d - We generally don't eat enough omega-3 fatty acids

These are synthesized by algae and eaten by fish - so with oily fish, fish-oil capsules and/or algae oil capsules, we can obtain decent amounts of omega-3 fatty acids.  Most of the fat we eat in food other than fish contains mainly, or exclusively omega-6 and saturated fatty acids.  Fats are controversial, but as far as I can tell, we generally eat too much omega-6 and saturated fat and too little omega-3 fatty acids.

Omega-3 fatty acids [W] perform at least two crucial functions.  Firstly, they are used to make some of the prostaglandins (others are made from omega-6s) and other compounds, which are necessary for proper immune system regulation. 



Effects of Omega-3 Fatty Acids on Immune Cells
Saray Gutiérrez, Sara L Svahn, and Maria E Johansson
Int J Mol Sci. 2019 Oct; 20(20): 5028.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834330/

Secondly, the two-fatty-tail phospholipids [W] - which make up (with cholesterol) the lipid bilayer cell membrane of all our cells - have their fatty tails composed of oily tails from the fats we eat.  So the ratio of omega-3 tails to other types of tails in our cell membranes reflects what we have been eating in the last few months or year or so.  These tails' mechanical properties vary, and the exact mechanical properties of the lipid bilayer affect the operation of the complex transmembrane proteins through which many molecules and ions enter and leave the cell and which form many types of receptor.  These effects are directly mechanical on these major transmembrane proteins and by way of altering other transmembrane proteins which, ideally, sit alongside the major ones.

So the exact, mechanical, electrical and chemical behaviour of all our cells' membrane-bound receptors, calcium channels etc. depend, in some ways on the ratio of omega-3 to other fatty acids in our diet.  This is especially true of our neurons.  So the ratio of the various types of fat in our diet affects every aspect of our emotions mood and cognition.  Most people in the West would benefit from less omega-6s [W], saturated fatty acids [W] and especially trans-fats [W]and more omega-3s in our diet.  

This article describes the importance of dietary omega-3 fatty acids for improving immune system regulation, including by decreasing excessive inflammation, by way of these fatty acids forming part of lipid rafts which support the transmembrane proteins of CD4+ T-helper lymphocytes [W], which play an important role in regulating inflammation, by their secretion of anti-inflammatory cytokines:

The science behind dietary omega-3 fatty acids
Marc E. Surette CMAJ. 2008 Jan 15; 178(2): 177–180
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174995/
Google Scholar Cited by 176


P15: P3w and P3d - Except for hunter gatherers, some vegetarians and perhaps some people with modern diets who eat lots of yams, sweet potatoes etc. none of us get enough potassium in our diet.  This is exacerbated by the fact that we generally consume excessive amounts of salt. 

The following account is written from memory after partially reading a large box full of research articles on salt and potassium metabolism, hypertension, stroke etc. and especially this excellent book from 2001:

The High Blood Pressure Solution: A Scientifically Proven Program for Preventing Strokes and Heart Disease
Richard D. Moore MD Healing Arts Press; 2nd edition 2001-06-15
https://www.amazon.com/dp/0892819758

Our ancestors found it very hard to obtain enough sodium (and so chloride) through salt, so their tastes (now ours) evolved to included a strong liking for salt - and our body has evolved to conserve it.  Potassium was plentiful in the ancestral diet (going back to common ancestors with chimps etc.), with a potassium to sodium ratio (by mass) of 20 to 40.  We have no taste for potassium and our bodies do not conserve it.

Every cell in our body relies on pumping potassium ions into the cells and sodium ions out for its trans-membrane voltage, and ionic balance.  This voltage and the two opposing ionic concentration gradients powers the operations of many trans-membrane proteins.  So the exact voltage and concentrations of the two ions on either side of the membrane constitute some of the most important operating conditions for each cell.  Some cells, such as neurons, devote 70% or so of their entire energy budget to pumping these ions, with various transmembrane proteins powering their operation by letting sodium ions back in and the potassium ions out again.

Now salt is easy to obtain (actually almost impossible to avoid, since it is needed in bread-making, and is in most manufactured foods), we eat lots of it. 

Potassium is primarily found in vegetables and fruits. There is little in grains, eggs, dairy, fish, poultry or meat. 

Consequently, many people ingest 2 to 4 grams of sodium a day, and only 2 grams or so of potassium.  Ideally we would have 1 to 2 grams of sodium and 5 or more grams of potassium.

The very low - below 1.0 for many people - potassium to sodium ratio in our diet directly drives ill health in general and hypertension and stroke in particular.  For more information on this, with research references, and for the little known option we have for supplementing potassium via potassium gluconate solution, please see the kna/ page.

COVID-19 is causing stroke in many people, including younger people who do not get particularly severe symptoms.  A contributing factor to this is surely excessive sodium and insufficient potassium.  I advocate reducing salt, but not, in the short term, supplementing potassium.  While it is surely better to supplement potassium, and so avoid hypertension and so hypertension drugs, and to reduce reduce the risk of stroke, there are some tricky aspects to it and I an not suggesting people rush into this without their doctor's supervision. 

Unfortunately, I think most doctors are unaware this ability to supplement with 2 or 3 grams of potassium a day - and quite a few would find the prospect alarming.   Richard D. More explains that in medical school, it is impressed upon all the trainee doctors, how careful they must be with intravenous potassium - because excessive input (faster than the cells can absorb it) will raise blood levels and so cause potentially deadly heart disturbances.

We can't stop the virus spreading, or change the genes which evolved in our ancestors

We can't stop the virus from spreading to most people, in all countries, since:
We can't change people's DNA or its epigenetic attachments.

We can't stop the virus from causing a substantial proportion of the population to suffer fever, cough and other moderate symptoms for a few weeks.

Nor can we coexist with COVID-19 by using vaccines, antivirals or lockdowns

Even if there were drugs with powerful antiviral or inflammation-dampening properties, we can't manufacture or distribute them in sufficient quantities, with sufficient medical oversight, to most people in the world in a few months - or probably over years.

We can - and must - improve nutrition to correct many of the failings which cause people's immune systems to be weak and/or dysregulated

Problems and Solutions:

S1
: The public should be advised, in general (with whatever exclusions properly apply) that they should not lower their fever, with drugs or other means.  This is potentially a complete solution to P10

However, since it is impossible and generally undesirable to advise people to do this against the wishes of most doctors in general, and their doctor in particular, and since many doctors (I don't know the proportion - I guess 20% to 80%) still support the use of anti-pyretic drugs in general, and so I guess with COVID-19, this could only be fully achieved if we somehow solve another problem:

P20: How to convince the great majority of doctors of the need for this advice, in the next few weeks, so their united position will cause health authorities to promptly issue the required advice to the public, with the backing of almost all doctors.   There is an urgent need for this, since the next wave of COVID-19 infections are coming, with lockdowns impossible to extend.  (At least in the northern hemisphere, I hope people will get some sunlight on their skin over their summer and so boost their vitamin D levels a little.)

In principle this could be done by having them all read the research, such as that which I found and link to at the fever/ page.  However, there are challenges regarding doctors changing their minds, rapidly, about a matter on which they have long held a contrary position.  Arguments against lowering fever with antipyretics have been controversial for decades, and some doctors recognise the essential role fever plays in fighting infections.  There is a long way to go, and here we run into numerous reasons - not all of them good - for the great resistance to change and new information which for many or most members of the medical profession constitutes a profound herd mentality.

Ideally there wouldn't be any urgency, and the doctors who still advocate lowering fever could be gently cajoled and convinced of the need to (generally) let fever do its work, over decades.  This would be the polite thing to do, and would respect doctors' dignity and professionalism.

The trouble is, that with COVID-19 inducing protective fever in a large fraction of the population in the months to come, waiting and hoping for doctors to change their mind would vastly increase suffering, harm and death.

I think P20 is insoluble.  Therefore, any improvement on the currently parlous situation - (P10) of people lowering their fever and so frequently suffering a more prolonged illness with more harmful and deadly hypercoagulation - will result from partial or full solutions to P21 and/or P22:

P21: How to convince health authorities to issue good advice against lowering fever for COVID-19 and perhaps other diseases, with suitable exceptions) despite a lack of consensus on this among doctors. 

I regard P21 this as insoluble, since authorities generally would only advise according to broad consensus among doctors, and since many people would not accept such advice even if it was contrary to their understanding of doctors' consensus views.

P22: How to convince most people to ignore the opinion of many doctors, including perhaps their own AND the absence of suitable guidance by health authorities, with them placing more trust in the advice of particular doctors they know to be respected, and who advise (with suitable exceptions) against lowering fever for COVID-19 and/or in general.

This can probably be achieved to some limited extent, with Internet communications.  It would be a pretty dodgy for this to be done by people like me who lack medical training, so I hope that the solution will be along the lines of:

S2: Directly to P22, indirectly to P21 and P20 and so towards fully achieving S1:    Well-respected doctors and nurses communicate their advice on letting fever (in general, with suitable exceptions) do its work - primarily to the public, and secondarily to other doctors and nurses

You know who you are.  Blog!  Write opinion pieces for news websites!  Turn on your cellphone camera and talk to the public via YouTube and the like!  Your place in history: one day wayward, impressionable, tragically optimistic doctors gone astray; the next day (or year or decade): celebrated, righteous rebel who gave the best advice contrary to cranky old paradigms now consigned to history's dustbin.

This article by Josh Farkas is pertinent:

https://emcrit.org/pulmcrit/pulmcrit-american-research-infrastructure-is-killing-us-
the-misbegotten-battle-between-the-ivory-tower-academics-and-the-rogue-cowboys/



On paper, the Ivory Tower Academics [who want RCTs before introducing any new treatment] will always look better.  Their arguments are technically impeccable.  It’s easy for them to paint themselves as the paragon of scientific virtue, while shaming others as irresponsible dilettantes.  However, the closer one gets to the bedside struggle against COVID-19, the less compelling these intellectual arguments become.  Thus, I daresay that among frontline providers actually caring for patients with COVID-19, the rogue cowboy mentality [who use RCT-unproven therapies which seem safe and effective] often has greater appeal.

I think emcrit.org articles and discussions I have read are the very heights of erudition, thoughtfulness and pertinence.

However, see Dr Roger Seheult's Update 74 in which he cites a CNN interview with YouTube CEO Susan Wojcicki, who states that videos which contradict the WHO's COVID-19 advice contravene YouTube's Terms of Service - so raising the spectre of academic censorship in the middle of a crisis.

S3: Directly to P7 and P8, and so in part to P3w & P3d - Everyone should be advised not to drink alcohol (or at least not to drink it regularly or to the point of intoxication) or use excessive salt - and of course not to harm their immune systems with other recreational drugs. 

This is basic, uncontroversial, medical advise which can safely be given to everyone.  So there should be no problems with changing doctor's thinking, or any controversy.

Again, it is unseemly for non-medicos such as me to be leading the charge here.  So doctors and nurses should communicate directly and urgently with the public, and with their patients, as well as advocating health authorities to issue suitable directives.

Only a subset of people will take any notice, but it will help.

(There is a suggestion that some cannabis compounds might reduce COVID-19 severity.  Maybe so, but this is of no interest to me since there's no way of deploying such compounds or any other drugs to the population in general in any time frame, let alone the months we have to cope with the second wave of COVID-19 infections.)

S4: We can and should urgently reduce the toll of harm and death for hospitalised patients, even within the currently poor nutritional arrangements by which most people live.  See the Marik Protocol icu/ .  

However, this would only relevant for the general population if all the people who start to develop the hypercoagulative state are able to be treated in hospital very promptly.  People at home with symptoms continuing beyond a week or so, beyond the throat infection stage, with the virus replicating in their lungs, develop this hypercoagulative state and so are at high and ever-increasing risk of serious harm or death from blood clots forming in their lungs, brain, spinal cord, heart, liver, kidneys etc.  People at home are suffering permanent neurological damage, stroke, heart attack etc.  Children and babies are suffering and dying from a form of Kawasaki disease.

Generally (New Zealand potentially excepted) national governments can't slow the spread of the disease sufficiently to ensure that the 20% or so of their people who do get lung infections can all go immediately to hospital.  If they could, then in principle it would be possible to fully achieving S4, which would have huge benefits and largely solve P2c.

In order to achieve S4 (ignoring for the moment that we can't generally slow the infection rate as just mentioned) we face problems regarding conservatism, herd mentality and getting changes made to departmental guidelines in a hurry similar to those mentioned above regarding fever (S2).  As with S2 and S3 it would be unseemly for non-medicos like me to be advocating change, so it is vital that doctors and nurses work within their professions, and by communicating to the public in general, about the need for hospital treatment protocols such as those pioneered by Dr Marik, which result in far less harm and death than is the norm in most hospitals so far (to May 2020 at least).

However, even if S4 was fully achieved, this is only relevant for the general population to the extent that all the people who start to develop the hypercoagulative state are able to be treated in hospital very promptly

People at home with symptoms continuing beyond a week or so, beyond the throat infection stage, with the virus replicating in their lungs, develop hypercoagulopathy and so are at high and ever-increasing risk of serious harm or death from blood clots forming in their lungs, brain, spinal cord, heart, liver, kidneys etc.  People at home are suffering permanent neurological damage, stroke, heart attack etc.  Children and babies are suffering and dying from a form of Kawasaki disease.

The Marik protocol works, in part, by solving a severe nutritional deficiency, of vitamin C, by way of intravenous vitamin C (ascorbic acid) around 10 grams per day.

I believe these techniques could be improved by repleting patients' deficiencies of vitamin D, boron and other nutrients as well.

However, the earlier all these nutritional deficiencies are fixed, the better - so that the people don't get seriously ill and never need to go near a hospital.

Other solutions having been highlighted, we now focus on nutrition to improve the function of the immune system, general health and to reduce hypertension and the risk of stroke

So the remaining solutions to the problem of COVID 19 - beyond sustainable hand-washing, social distancing etc. - all concern improving the nutrition of adults and children so that their immune systems are strong and well-regulated, to solving, to the greatest extent possible:
Unfortunately, we can't fix the fact that human immune systems are bound to be dysregulated in the absence of helminths.  I believe that for most people, a great deal of currently lacking immune system regulation can be restored by repletion of micronutrients, especially vitamin D and boron, even though are genes predispose us to overly-aggressive inflammatory responses.

There are several levels on which this can be achieved:
  1. As individuals and families, deciding to take the relevant supplements, being able to do so (the supplements being available and affordable) - either due to personal decisions or in accordance with advice from doctors or health authorities.   Initially, this will need to be in accordance with the subset of doctors who advocate such supplementation, since I have no idea how long it will take for most doctors and authorities to overcome their long-established pattern of avoidance and ignorance of nutritional supplements. 

    The extent to which doctors' caution about supplementation is valid (is) will be the subject of a section below.  There are reasons to be concerned, but overall, I believe these concerns are blown out of all proportion, especially given the urgent need to deal with COVID-19 triggering a billion or so people's dysregulated immune system into harming and killing them.

  2. At the level of individual doctors, clinics or hospitals and so their their patients, including especially those at home who need to prepare for COVID-19 infection in the weeks and months to come.

  3. At the level of countries, where governments act decisively to facilitate the practical, educational and other aspects (medical guidance, identification of individuals with unusual nutritional needs etc.) of a campaign to get all their citizens replete in the nutrients they need to protect them from COVID-19 harm and death.

    I am not advocating mandatory supplementation - just clear advice and logistical and economic support for the entire population to become replete in these nutrients, in the hope that most people will follow this advice.
 
So S5 is the project which these web pages are intended to facilitate:  Getting people - individuals, families, countries and ideally all humans - replete in the nutrients which are essential for proper health, in particular immune health. 

This will largely protect them against the worst symptoms of COVID-19, so we can let the virus run and do away with unsustainable measures which attempt to slow the spread of the virus.  This will also greatly reduce the death toll from influenza - so reducing the need for vaccinations.  This will also greatly reduce the prevalence of chronic illnesses due to immune system dysregulation.  This is a far bigger problem, in the long run, than COVID-19.

In order to achieve this, there are a number of problems to solve:

P30: Identify which nutrients are required, and in what quantities in general - and for particular individuals and people with particular medical conditions.

P31: Entwined with P30, get enough doctors to agree on this, since - except for a few individuals and families who trust either their own judgment or that of remote (via the Internet) doctors who advocate proper supplementation - most people and all governments will take the required actions only when there is broad consensus to do so among doctors.

P32: Entwined with P30 and P31, review all available research and arguments and come to the right conclusions regarding what the nutritional advice should be, despite this differing significantly from the consensus view of the medical profession in recent decades. 

For instance, the dosages of vitamin D3 we need for COVID-19 survival (and for general health, avoiding to the greatest extent possible, without helminths, the plethora of inflammatory disorders) exceed not just the recommended dosages many doctors and government health authorities recommend, but their maximum tolerable doses too.

Likewise the desired 25OHD levels.  Some doctors are happy to aim for getting most people above 12ng/ml (30nmol/L).  This might be enough to avoid rickets, but to make people safe from COVID-19, we need to get everyone safely over 40ng/ml.  So we should be aiming for 40 to 80ng/ml.  Toxicity may occur, for most people, above 150ng/ml, which can only be achieved by long-term usage of much higher doses of D3 than are required to get most people to > 40ng/ml.   There may also be problems with the subset of people with unusual genetics for vitamin D enzymes, with granulomatous diseases or tumors. 

In the case of boron, only some researchers and a few doctors recognise it as nutrient - though it has long been recognised as safe in daily doses up to 20mg.  As far as I know, we probably need 6 to 12mg a day to be boron replete.  (Tina and I take 12mg.)

In trying to solve these problems, the material at this website (below, I will work on completely revised versions for vitamin D and boron) is concerned with biological reality, as best we can understand it from all research and observations AND the beliefs of most doctors - not least because their general wariness about nutritional supplementation has some basis in reality, at least for some subsets of the population.



Recent updates are above this point.

Below is what I will work on next, when I get time.  All that follows will soon be greatly revised and reorganised:





#msg

Updated version of the message I wrote to clinicians and researchers in late March

Contents

#00-survival
Poor survival rate once people need breathing assistance
#01-fever
Clear guidance regarding paracetamol, ibuprofen, aspirin and NSAIDs in general
#02-sepsis
Reducing the cytokine storm of sepsis
#03-vit-d

#03-vit-d-dose
Vitamin D3

Doctor's recommended vitamin D3 doses for COVID-19
#04-omega-3
Omega 3 PUFAs
#05-zinc
Zinc
#06-vit-c
Vitamin C
#07-vit-b1
Vitamin B1
#08-boron
Boron
#09-salt
Salt
#10-exercise
Exercise
#11-ht-drugs
Potassium gluconate solution is superior to blood pressure medication
#12-blind-spots
Overcoming Western Medicine's blind spots in the next week or two


#00-survival

Poor survival rate once people need breathing assistance

Most people's battle against the virus will be lost or won at home, not in hospitals or doctors' clinics.  Zhou et al. (below) report that of 34 patients receiving invasive mechanical ventilation or ECMO [WP], only 1 survived.  The survival rate for non-invasive ventilation was 2/26 and for nasal breathing support, 8/41.  Antivirals and antibiotics help, but we will soon run out of these. 

Coronavirus home remedies as suggested here - nutritional supplements to enhance immune system function, especially by reducing the overly-aggressive pro-inflammatory responses which  cause sepsis - can make a  substantial contribution to public health in this disastrous situation, given doubling times of half a week, and the impossibility of retaining sufficient social distancing for 6 months or more.


#01-fever

Clear guidance regarding paracetamol, ibuprofen, aspirin and NSAIDs in general

Please see the separate page on this:  http://aminotheory.com/cv19/fever/ .





#02-sepsis

Reducing the cytokine storm of sepsis

The cytokine storm, lead by IL-6, TNF-alpha and other pro-inflammatory cytokines is the primary or sole cause of death - and probably of pneumonia and so most hospital admissions.  The graphs in Fei Zhou et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study 

www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

Pro-inflammatory cytokines in COVID-19 - from Zhou et al.

show that those who survived usually did so without radically elevated IL-6 levels, and that those whose IL-6 levels kept on rising died.  Thrombosis (D-dimer) increased progressively in those who died, but not in survivors.  These averages are extremely divergent.  Serum ferritin kept rising in those who died, indicating not iron overload, but (www.bmj.com/content/351/bmj.h3692.full) excessive inflammation.

The real enemy with COVID-19 is not the virus itself, but the excessive and inappropriate inflammatory response to it -  the same thing which drives sepsis, neurodegeneration (Alzheimers, Parkinsons), osteoporosis, diabetes etc.  One probable cause of this is that some aspects of our immune system are far more aggressive than they should be, due to them evolving in the presence of ubiquitous infection with intestinal parasites and/or H. pylori, both which attenuate these mechanisms.  However, now is not the time for helminthic therapy. (Google search for helminthic therapy.)

Another set of causes, which can be fixed - and must be fixed in the next few weeks in order to prevent millions of deaths - are nutritional deficiencies, particularly in vitamin D, boron, omega 3 PUFAs and probably other nutrients such as vitamin C.  For brevity I state the following arguments as if they were facts.

The overly-aggressive inflammatory response which drives sepsis is supposedly not understood: www.sepsis.org/sepsis-basics/what-is-sepsis/ .  However, a Google scholar search for inflammation and helminths makes it clear that our lack of intestinal parasites now plays a major role in the excessive, inappropriate, inflammatory response which drives asthma, Alzheimers / Parkinsons disease (and other forms of neurodegeneration), osteoporosis , Crohn's disease, periodontal disease, atherosclerosis etc. etc. 

It is also clear, as you will read below, that common nutritional deficiencies also drive this inflammation. 

Perplexed sidebar:

Why, given all this research, do so many disease support groups, clinicians and some researchers fail to recognise that inadequate nutrition (and with salt, inappropriate nutrition) drives our overly-aggressive inflammatory response? 

Electronic technicians make sure power supply voltages are correct before attempting serious fault-finding.  Motor mechanics don't work on poorly performing engines without checking the fuel.  Farmers fix problems with their animals by feeding them correctly.  For instance lameness in pigs is routinely fixed with borax: 2005 article Boron Supplementation Prevents Osteochondrosis in Growing Swine.

Why do doctors put so much effort into drugs and acute interventions and so little into nutrition to ensure the body works well in the first place?

A possible answer is that highly skilled clinicians, researchers and disease support group people dedicate their lives to helping people with complex, devastating diseases and can't believe that the primary or sole cause of the disease is several well-researched nutritional deficiencies and excesses which can be fixed


I have no problem believing this.  Electronic devices can misbehave in all sorts of complex and perplexing ways due to simple causes such as electrical leakage on the circuit board, temperature sensitive intermittent failure inside an integrated circuit etc.  Many fault symptoms are complex, and there is usually one or sometimes two simple (once you find them) underlying problems which explain it all.  Electronics is complex, but it is child's play compared to cell biology, multicellular life forms, genetics, immunology, neuroscience etc.

It makes perfect sense to me that human health is terribly impacted due to one or more nutritional conditions not being met for most people in our normal lifestyle.  We have hundreds of operating conditions and if only one of them is outside of a proper range, bad things will happen.  There's probably dozens of inputs not being adequately met.  I believe boron is the nutrient most people are most deficient in. Then vitamin D, potassium, omega 3 fatty acids.  After that are the better known deficiencies such as iron.

It is so much easier to fix these things than live with the consequences.  The fix can't be achieved entirely with food - we need supplements. 

Most people wouldn't tolerate such ill-care for their car.  It would be unethical for a mechanic to be changing valves and pistons on the engine, adding additives to the oil etc. in an attempt to solve the problems caused by a fuel or air blockage, or contaminated fuel or lubricating oil.

There can be enormous inertia in some areas of medicine.  See the section #ssc below for 22 pulmonologists raising 6,267 signatures in a petition to change what they argue is damaging guidance on treating sepsis from a major international sepsis treatment authority.

Starting in March 2020 and peaking in May, June and beyond, billions of people will contract COVID-19 and a substantial fraction of them will be pushed into sepsis-induced pneumonia, respiratory distress and organ failure - with a high risk of lasting disability and death.

Doctors, nurses and health organisations have an urgent responsibility to read the research and make the connections so they can advise everyone on readily available nutritional supplements which will reduce the incidence of sepsis in the  months to come.  These levels of nutrition are known to be safe.  There is no need, or time, for RCTs.



#03-vit-d

Vitamin D3

Please see the section below #03-vit-d-dose which lists doctor's vitamin D3 recommended doses for prophylaxis and for those with COVID-19 infection.  Dr Paul Marik recommends 5000IU in both cases.

Vitamin D deficiency is a major causative factor for Acute Respiratory Distress Syndrome, which is what kills most people with COVID-19.

This boldly titled open access article makes it abundantly clear that very low levels of vitamin D3 are an essential precondition for most cases of ARDS.  This is cited by 62 other articles.

Dancer RCA, Parekh D, Lax S, et al.
Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS)
Thorax 2015;70:617-624.
thorax.bmj.com/content/70/7/617

Patients with and at risk of ARDS are highly likely to be deficient, and severity of vitamin D deficiency relates to increased epithelial damage, the development of ARDS and survival.

Following adjustment for gender, age, diagnosis, staging data, and pack-years
[smoking], patients with vitamin D3 less than 20 nmol/L had a 4.2-fold higher odds of ARDS than patients with vitamin D3 greater than 20 nmol/L (p=0.032).

20nmol/L = 8 ng/ml.  This is a very low vitamin D level.

Many of these people are dying due to an easily correctable, extreme, nutritional deficiency!  Every supermarket has vitamin D3 capsules.  If they took one or two of these a day they probably wouldn't be in hospital at all.





COVID-19 kills most of its victims due to ARDS (WP).  This results from the same overly-aggressive pro-inflammatory sepsis which kills people with heart, kidney or liver failure even if their lungs fail and they are on a ventilator or ECMO.

COVID-19 is just another triggering condition, one of many, for ARDS.  However, it may have unique characteristics which make it a particularly severe trigger.  One such mechanism, which it shares with SARS, is that the virus attaches to ACE2 (WP) transmembrane proteins in particular types of cells in the lungs, liver and other organs.  When it attaches it causes the ACE2 molecule to be pulled into the cell, with the virus still attached.

COVID-19 sufferers surely have significantly fewer active ACE2 molecules available to play their role as an enzyme in the renin-angiotensin system, where moderates processes which increase blood pressure and have numerous other local effects in particular organs  A 2008 explanation of this system is: journals.physiology.org/doi/pdf/10.1152/physrev.00036.2005 .

The extremely low vitamin D level of ARDS sufferers might, in part, be explained as an effect of ARDS or of other processes which accompany or drive it.  A much more important explanation for this relationship is that vitamin D deficiency directly causes or at least significantly contributes to the sepsis - the overly-aggressive pro-inflammatory response - which in this scenario manifests as the condition we know as ARDS.

A Google Scholar search for ARDS and vitamin D turns up plenty of articles, but none yet on an RCT involving vitamin D supplementation.

Another perplexed sidebar 2020-03-31 - this time really perplexed:

With its current rate of spread, and the health and vitamin D status of the population as it is now, this disease can be expected to kill millions of people in these ways in the next few months.

Research clearly shows that ARDS sufferers - due to a variety of causes other than COVID-19 - are highly deficient in vitamin D3. 

There's no reason to think that the subset of people who COVID-19 kills in this way are not also, on average, highly vitamin D3 deficient. 


We are now 3 months into this global pandemic.

Why hasn't the WHO told everyone to supplement vitamin D3?

If they had issued such advice, it would have been followed very widely by now, and would probably save millions of people's lives in the next few months.

The causative role of vitamin D in ARDS is no secret.  See below for articles which confirm it.

Vitamin D is not controversial, obscure, expensive or dangerous.

It is not a drug with side-effects.  It is safe and very well researched nutrient.  So there's no need for an RCT to prove beyond reasonable doubt that supplementation would reduce the incidence of ARDS deaths and disability due to COVID-19.

ARDS isn't the only lung problem caused by vitamin D deficiency. 

Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system (2017)
www.nature.com/articles/s41598-017-03474-6

Vitamin D deficiency (VDD) is closely associated with lung diseases, including asthma, cystic fibrosis, interstitial lung disease, chronic obstructive pulmonary disease (COPD) and respiratory infections.


#2015-Han

Here is a 2016 placebo-controlled double-blind RCT giving ICU patients substantial loading (bolus) doses of vitamin D3.  Of course it would have been better still if they had taken vitamin D supplements all their lives.  Then they probably would not be in ICU at all.

High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial (2016)
www.sciencedirect.com/science/article/pii/S2214623716300084

There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency = less than  20 ng/mL (see above and below, this is a very low level) and increased hospital length of stay, readmission rate, sepsis and mortality.

Subjects were administered either placebo, 1.25mg (50,000 IU) vitamin D
3 or 2.5mg (100,000 IU) vitamin D3 daily for 5 consecutive days.

There was a significant decrease in hospital length of stay over time in the 6.25mg = 250,000 IU and the 12.5mg = 500,000 IU vitamin D3 group, compared to the placebo group:

25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively.
(p = 0.03).
(This means that an outcome would only have occurred by chance once in 33 such trials.)
 

With the knowledge from this trial, how is it ethical to admit people to hospital like this and not give them 500,000IU (12.5mg) vitamin D3 in the first 5 days?

Its not expensive, or risky.

Tina and I take one of these 1.25mg (50,000 IU) capsules a week.  We also get some vitamin D in multivitamins and calcium citrate tablets.  (We also take magnesium citrate, B complex, zinc multivitamins and 4 grams of fish oil a day.)


They are made by Bio-Tech in the USA.  The cost is USD$30 for 100 capsules.  The cost of giving ICU patients 500,000 IU vitamin D (12.5mg) is USD$3.00.  To save:

  36 - 18 = 18 days in hospital

So the cost of avoiding one day in hospital, with vitamin D supplementation = USD$0.17.

If the drug companies found a patentable compound with this effectiveness and safety profile, they would be selling it for $100 per capsule AND they would be advertising it to doctors and the public AND everyone would think it was a modern marvel and be very happy to pay good money for it.

Instead, because it is a cheap nutrient, which no-one makes much money from, hardly anyone sings its praises - and year after year, people suffer grave illness and death, with billions of dollars of hospital and drug costs, since only a subset of the population use it. 

Doctors do, at times, advise their patients to take vitamin D3, omega 3 fatty acids and other nutrients.  However, it is my impression that the dosage can be rather low, such as 2000IU or less, when research (below) indicates that about twice this would better protect against numerous diseases.

Vitamin D3 is exceedingly inexpensive.  At PureBulk a powder made up of 0.2549% vitamin D3 sells for USD$93 per kilogram.  This contains 2.549 grams of vitamin D3, at a cost of USD$36.48 per gram.  At 4000IU a day, this would last for 69 years.  At this rate, the 5 million IU (125mg) in the above bottle would cost USD$4.56.

At this price, the cost of saving 18 days in hospital would be USD$0.46.

In bulk, a kilogram of pharmaceutical grade vitamin D3 (colecalciferol USP) costs USD$13,553 from a US supplier (link), or USD$2500 from a Chinese manufacturer (link). 

100 years supply at 4000IU a day is 3.7 grams, which is USD$9.25 at the Chinese wholesale price.  So, not counting the cost and effort of splitting it into 5,200 weekly capsules (there's no need to take it every day), a vast array of diseases and chronic conditions could be largely or entirely avoided, for 9 cents a year.

It is clear that vitamin D deficiency plays a crucial, causative, role in many lung diseases.  It is reasonable to assume that it plays a crucial role in most of the suffering and death caused by COVID-19.  The same would be true of the most serious consequences of influenza.

If everyone in the world took a decent amount of vitamin D, such as 4000IU, it would be reasonable to expect that COVID-19 wouldn't be such a big deal.  It would be a new virus, which makes some people ill for a while, and it would cause few if any deaths worldwide.

So the entire human world is being disrupted, and hundreds of thousands or millions of people are going to die because they didn't take an adequate vitamin D supplement?

As far as I can see, this is true.

So why are our health authorities not urging everyone to take vitamin D?  Now?  Or years ago?  Hopefully they will.

There would be far less work for doctors and hospitals, and billions of dollars less spent on drugs.  One can imagine a conspiracy of drug companies suppressing vitamin D, boron etc. but I don't think they are doing this.

It is as if the medical profession is focussed on sick people, the complexities of their illnesses, and the costly, difficult and sophisticated acute interventions they have learned to help these people get well again. 

Yet it is easy and inexpensive to fix these nutritional deficiencies such as for vitamin D - which would save so much suffering.  It is a easier than supplementing with potassium, (see kna/ ) but that is easier and better than using blood pressure drugs.  It is a lot easier than getting people to give up smoking.  And that is easier than having to cope with the damage smoking causes.

A 2014 article PMC4220998  relates blood levels to vitamin D3 supplement quantities for underweight, normal, overweight and obese people.  For normal weight people, 4000 IU/d provides 117 nmol/L, which is 47 ng/ml.  Toxicity (PMC6158375) occurs with blood levels more than three times this.


Vitamin D3 vs. blood level graph adapted from 2014 Ekwaru et al. The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

If all adults (who wisely have little UVB exposure) took 4000IU vitamin D3 a day (a gram every 27 years) then they would avoid most of the diseases caused by vitamin D deficiency.    This chart from Garland et al. 2014 PMC4103214 shows the importance of achieving at least 40ng/ml.


Vitamin D health benefits - from Garland et al. 2014

A chart from one of the co-authors, (vitamindwiki.com/Chart%20of%20Vitamin%20D%20levels%20vs%20disease%20-%20Grassroots%20Health%20June%202013) labels the various conditions:

(Right click the image to see it at full size.)


Vitamin D health benefits by blood levels of D3

Numerous peer-reviewed journal articles showing adequate vitamin D reduces inflammation AKA sepsis can be found at:

vitamindwiki.com/Inflammation

vitamindwiki.com/Vitamin+D+reduces+sepsis

www.ncbi.nlm.nih.gov/pmc/articles/PMC4070857/  (Vitamin D and inflammatory diseases, 2014.  Google reports 227 citations.)



#03-vit-d-dose

COVID-19 Vitamin D dose recommendations from doctors

See the d3/ page for supplemental intake quantities according to body weight.

Please let me know any published recommendations not listed here, from doctors or health authorities - for the public in general, and especially for the public preparing for COVID-19 infection.  These are implicitly for adults, since children seem not to have much trouble with COVID-19.

Both the article and the comments are interesting - however, I think vitamin D will at best slow down the progression of the infection, rather than prevent it, and that its real value will be in reducing or eliminating the overly-aggressive pro-inflammatory immune response which causes the sepsis. 

In the comments, Donna Hurlock MD recommends 4000IU to 5000IU.  There is discussion of magnesium, calcium, vitamin K2 and other nutrients.

To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful.

The highest recommendation is 10ug, which is only 400IU.


#04-omega-3

Omega 3 PUFAs

The same is true of omega 3 fatty acids.  I believe that if the WHO et al. recommended adults take 2 grams of fish oil a day and 4000IU vitamin D3, that this - to the extent that people were willing and able to comply - would significantly reduce disease severity and death for hundreds of millions of people, especially those with a Western, indoor, lifestyle.

openheart.bmj.com/content/5/2/e000946 Importance of maintaining a low omega–6/omega–3 ratio for reducing inflammation (2018)

A systematic review of 26 randomised controlled trials (RCTs) concluded, ‘Dietary omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower levels of inflammation and endothelial activation in cardiovascular disease and other chronic and acute diseases, including chronic renal disease, sepsis and acute pancreatitis’.

Indeed, supplementing with fish oil is known to inhibit inflammatory cytokines such as TNF-alpha and IL-1 beta and  proinflammatory/proaggregatory eicosanoids such as thromboxane-2 and prostaglandin E2.


(2017) N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2
www.tandfonline.com/doi/full/10.1080/15548627.2017.1345411

#05-zinc

Zinc

It may be best to recommend zinc supplements, since Zn++ in the cytoplasm inhibits viral RNA synthesis - including zinc lozenges to slow the initial infection in the throat, before it gets into the lungs.  Zinc is needed for hundreds of enzymes. Please see what Google scholar returns for zinc inflammation immune.

Another potential reason for advising people take, for instance, 25mg zinc per day as chelate is that oral zinc 225mg a day (as best I understand it) is recommended for patients who do not yet need breathing support. Paul Marik's COVID-19 Treatment Strategy - see icu/#Marik-protocol  .


#06-vit-c

Vitamin C

I suggest you recommend a substantial but safe level of vitamin C oral supplementation, since it is known to reduce respiratory infections and to reduce sepsis when used intravenously.   A vet reports IV vitamin C is routinely used for saving animals from sepsis (medium.com/@anmldoc/i-really-do-not-know-d657e669e749).  She cites Paul Marik MD (www.pilotonline.com/news/health/article_7a3063e5-24cf-56c1-b25c-142731604196.html) who uses IV vitamin C and hyrdocortisone with success against sepsis in humans.

Paul Marik's COVID-19 Treatment Strategy - see icu/#Marik-protocol  - recommends 500mg oral vitamin C 2 or 3 times a day for patients who do not require breathing support, and for those in ICU, intravenous vitamin C 3 grams every 6 hours.  From (2017) Vitamin C and Immune Function :

Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections.

Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels.

In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.


Soon, hundreds of millions of people with COVID-19 breathing difficulties will be at home, unable to access care in hospitals or doctors' clinics.  Should uninfected people be advised to take 250mg vitamin C a day, and those with fever, sore throats and/or breathing difficulties (sepsis induced pneumonia) be advised to take 1000mg or more, subject to concerns about diarrhea?  (I assume that for the duration of the illness kidney stones are not a significant concern: www.ncbi.nlm.nih.gov/pmc/articles/PMC4769668/ )

Intravenous vitamin C 1500mg 3 or 4 times a day (with hydroxychloroquine, azithromycin and other drugs) is helping COVID-19 patients in New York: nypost.com/2020/03/24/new-york-hospitals-treating-coronavirus-patients-with-vitamin-c/
Dr Andrew G. Weber said:

The patients who received vitamin C did significantly better than those who did not get vitamin C.  “It helps a tremendous amount, but it is not highlighted because it’s not a sexy drug.

Vitamin C levels in coronavirus patients drop dramatically when they suffer sepsis, an inflammatory response that occurs when their bodies overreact to the infection.  It makes all the sense in the world to try and maintain this level of vitamin C.




#07-vit-b1

Vitamin B1 thiamine

(Not to be confused with theanine, as found in green tea.)

I have not studied thiamine (WP), but a Google Scholar search for thiamine inflammation turns up plenty of articles, such as:

(2014) The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis
link.springer.com/article/10.1186/1476-9255-11-11

This begins with numerous references regarding thiamine deficiency and critically ill patients, neurodegeneration etc.

My reason for including it here is that vitamin B1 is a component of the
Paul Marik's COVID-19 Treatment Strategy - see icu/#Marik-protocol , though not for patients with mild symptoms.  Those with breathing difficulties, in ICU, are given 200mg thiamine every 12 hours, orally or intravenously.  This seems a lot, considering the RDA is 1.0 to 1.2mg.   This search turns up various relevant articles. 

www.ncbi.nlm.nih.gov/pmc/articles/PMC6206928/ (2018) Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation

The ordinary retail B complex tablet my wife Tina and I take every day has 15mg of vitamin B1. Our multivitamin has 2.2mg.  Given the correlation between low vitamin B1 and sepsis, it seems prudent to take ordinary vitamin B1 supplements, especially since it is "relatively nontoxic" www.drugs.com/monograph/thiamine-hydrochloride.html .


#08-boron

Boron

2020-06-15: I have a box of boron research papers and am keen to write them up as an annotated bibliography.  I don't know when I will have the time for this.  I will do it on the new website.

For now, please start by reading this excellent review article from 2018, which has a lot of links to research on boron's role in the immune system, especially regarding inflammation.

The importance of boron in biological systems
Irem Uluisik, Huseyin Caglar Karakaya, Ahmet Koc
Journal of Trace Elements in Medicine and Biology v45, Jan 2018, pp 156-162
https://openaccess.iyte.edu.tr/bitstream/handle/11147/7059/7059.pdf

In this section I want to raise your awareness of boron as an essential nutrient which could save hundred of millions of people from sepsis-induced illness and death with COVID-19.  Please take a look at a recent review article:

PMC4712861/ Nothing Boring about Boron (2015)

the work of long-time US Department of Agriculture boron researcher, Forrest Nielsen, such as:

www.researchgate.net/publication/254082639_Growing_Evidence_for_Human_Health_Benefits_of_Boron (2011, cited by 60.) 

scholar.google.com/scholar?q=Forrest+Nielsen+boron 
and the research cited at: ods.od.nih.gov/factsheets/Boron-HealthProfessional/ .

One advantage of boron over the other micronutrients mentioned here is that while supplies of the others could easily be snapped up if everyone wanted them, there is plenty of boron for the whole population sitting on supermarket shelves, in the form of laundry borax.

It is a scandal that boron is not officially recognised as an essential nutrient.  Most people turn their noses up at the thought.  The word sounds like "boring" and rhymes with "moron". They know borax is used in laundry, as a welding flux, as an ant and cockroach poison and in children's slime.  Many people recoil at the idea of ingesting boron, because they see borax is the active ingredient of Ant Rid (8.5% borax).  But boron is in many foods, and vitamin D3 is a widely used rat and mouse poison.  (See my second comment at quillette.com/2020/03/22/covid-19-statistical-and-science-update-for-march-22/ .)

The naturally pure mineral borax -  sodium tetraborate - is mined at large scale in Turkey and California, and then refined into the bright crystals sold in supermarkets.  USP boron is used in nutritional supplements and medication, but it is difficult to obtain at a retail level. 

If a drug company found a patentable compound with boron's health benefits and safety profile - including especially its ability to restrain the body's overactive, sepsis-causing, inflammatory response - then we would all be singing its praises and paying top dollar for it.

Borax, 100mg a day, in water solution, provides 11.36mg boron a day, and I believe this will significantly reduce the inflammation which is killing COVID-19 patients.   (I have a box of journal articles on boron, and no time now to write up an annotated bibliography of boron nutrition.)

Side note on borax regulation in the EU, including the UK:

I have not yet fully researched this, but as best I can tell, the EU banned borates, including borax for many purposes including laundry, around 2010.  A laundry borax substitute sodium sesquicarbonate is sold in its place. 

Yet according to http://www.caviarfactory.ro/en/caviar-preservative-borax/ borax is authorised as a food additive E285 for preserving caviar in the EU, but not in the USA.  An extensive 2013 report .

Laundry borax is available by the kilogram in most supermarkets in Australia and the USA.  My wife Tina and I use this - plain laundry borax is plenty pure enough. (The Eti mine in Turkey, which produces 47% of the world's borax, specifies its technical grade borax to have no more than 15ppm Fe:  www.etimaden.gov.tr/storage/uploads/2018/01/10-2017-Borax_Deca_Powder.pdf)  We use: www.blants.com.au/product/natural-pure-borax-900g/

Our 12mg boron a day greatly improves on the typical 1mg a day in the average American diet (ods.od.nih.gov/factsheets/Boron-Consumer/ & ods.od.nih.gov/factsheets/Boron-HealthProfessional/), and is well within the tolerable maximum of 20mg a day (nap.edu/10026/):




From Nothing Boring about Boron:

A number of papers have indicated that boron reduces levels of inflammatory biomarkers. In a recent human trial involving healthy male volunteers (n = 8), a significant increase in concentrations of plasma boron occurred 6 hours after supplementation with 11.6 mg of boron, coupled with significant decreases in levels of hs-CRP and TNF-α. One week of boron supplementation 10 mg/d resulted in a 20% decrease in the plasma concentration of TNF-α [tumor necrosis factor alpha], from 12.32 to 9.97 pg/mL, and in remarkable decreases (approximately 50%) in plasma concentration of hs-CRP [high-sensitivity C-reactive protein], from 1460 to 795 ng/mL, and of
IL-6, from 1.55 to 0.87 pg/mL.

Is boron adequacy important? Consider that elevated hs-CRP is associated with an increased risk for breast cancer, obesity and metabolic syndrome (MetS) in children, atherosclerosis, unstable angina, insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metastatic prostate cancer, lung cancer, adult depression, depression in childhood and psychosis in young adult life, coronary heart disease, and stroke.

An assessment of high hs-CRP levels in www.ahajournals.org/doi/10.1161/JAHA.119.012638 is:

Most patients with myocardical infarction [heart attack] exhibit elevated hsCRP levels. Besides identifying populations at high-inflammatory risk, this study extends the prognostic validity of this biomarker from trial evidence to real-world healthcare settings. 

Please take a look at vitamindwiki.com/Vitamin+D+and+Boron which links to articles such as M R Naghii et al. 2011:

Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and pro-inflammatory cytokines
tahomaclinic.com/Private/Articles1/SHBG/Naghii%202011%20.pdf

10mg boron per day raised Vitamin D levels and reduced inflammatory cytokine levels.

As far as I know, 12mg / day boron is safe for most people, but it is probably best to start with 3mg and increase from there.  The two possible adverse reactions I am aware of are:

3mg boron capsules are readily available, but in the current emergency, I think it would be good to instruct people to get a heaped teaspoon of borax (about 8 grams), divide it by 4, and dissolve each quarter in 2 litres of water.  Two 50ml drinks a day provides 11.36 mg boron.

500 grams of borax is enough for 5,000 days at this rate, so a single borax purchase would help a dozen or so households through the current crisis.

#boron-ra
While searching Google Scholar for "rheumatoid arthritis" and "boron" I found an interesting article from 2012:

Serum boron concentration in rheumatoid arthritis: correlation with disease activity, functional class, and rheumatoid factor
Ziad S. Al-Rawi, Faiq I. Gorial (GS), Wejdi A. Al-Shammary, Fadhil Muhsin, Ahmed S. Al-Naaimi, Sa’ad Kareem 2012-12 Journal of Experimental and Integrative Medicine 3(1):9-15
researchgate.net/publication/264119179_Serum_boron_....


These Iraqi researchers measured boron concentrations in the blood with an atomic absorption spectrophotometer.  (Boron is not one of the normal blood tests run by pathology labs.)  They found the average boron levels in 107 RA patients was 21.8ng/ml (standard deviation 8.6) while for 214 age- and sex-matched healthy control subjects, the average was about twice this: 43.5ng/ml (SD 9.8).  For this difference p < 0.001, which means that if there really was no underlying relationship, then based on the random differences between the measured values, such a deviation would only occur on average once per more than a 1000 trials.  They also found some other significant inverse correlations between boron levels and RA disease severity.

Some notes about this article and the journal it was published in:

The journal Journal of Experimental and Integrative Medicine is now defunct.  I am not sure that it was ever recognised as a legitimate open-access journal, so it may have been predatory.  The first two authors seem to have a good publication history in legitimate journals.  I found little or no history for the other three, but some searches produced numerous matches for similar names, and I did not scrutinise all the results.

I assume that the article is based on real research and that the authors choice of journal was mistaken.  This article was cited in 2017 by Forrest Nielsen of the US Department of Agriculture , who is perhaps the most prolific and widely cited boron nutrition researcher:
Historical and recent aspects of boron in human and animal health

I think it is common for researchers from non-English speaking countries, with limited funds, to choose open access journals with lower fees than the mainstream, non-predatory, legitimate journals.  There are also quite a few Western, including English speaking, researchers who publish in predatory journals, presumably not being wise to what they are doing.

Two later articles, also from Iraq, mention boron and other mineral levels in RA patients: 2015-05 and 2015-07  .  In both cases the RA patients' boron  levels were also about half of those of the control subjects.  These two are in a well-known predatory journal: the Pakistan-based, so-called: American Journal of Internal Medicine.   I regard these articles as probably being based on real research, but not really citable due to the journal they appear in. 


Boron supplement capsules and tablets are available from numerous companies, usually with 3mg boron.  This is suitable for taking two a day, since this gives 6mg a day, and the half-life of boron in the bloodstream is a little less than a day.  An eBay search for boron and 3mg showed products from obscure companies and major ones such as Now, Solgar, Life Extension and Solaray.  The best deal I found was 250 3mg capsules for USD$6 or less: swansonvitamins.com .

I have noticed small amounts of boron, such in some Australian supplement tablets containing other compounds for arthritis:

2.5mg as borax: https://www.blackmores.com.au/products/collagen-protect-joint-and-bone
1.0mg as borax: https://www.blackmores.com.au/products/joint-formula-advanced
1.5mg as borax: https://thompsonsnutrition.com.au/.../...chondroitin-with-boron/

I was pleasantly surprised to see boron in some mass-market (larger supermarkets all over Australia) multivitamin capsules, from Cenovis: https://cenovis.com.au/?s=boron :

1mg as borax: Men's MultiWomen's Multi , Women's Multi + Energy Boost & Men's Multi + Performance .

3mg as boric acid: 50+ Multi


#09-salt

Salt

Everyone knows that most people consume too much salt.  See some journal article links below #salt concerning excessive salt consumption driving pro-inflammatory immune responses - and so sepsis.

Faced with the threat of imminent sepsis, I think many people could be convinced by consistent medical advice to go easy on salt.   This should go along with the obligatory warnings to reduce or eliminate smoking and alcohol.


#10-exercise

Exercise

Regular moderate exercise helps build a robust and well-regulated (against sepsis) immune system.  This 2018 article argues against the view that intense exercise decreases immune competency: pubmed/29713319

Epidemiological evidence indicates that regular physical activity and/or frequent structured exercise reduces the incidence of many chronic diseases in older age, including communicable diseases such as viral and bacterial infections, as well as non-communicable diseases such as cancer and chronic inflammatory disorders.

The challenge is to maintain or increase regular exercise in a time of social distancing and shelter-in-place.



#11-ht-drugs

Potassium supplementation with potassium gluconate solution is superior to blood pressure medication

Please see the separate page on this:  http://aminotheory.com/cv19/kna/ .


#12-blind-spots

Overcoming Western Medicine's blind spots in the next week or two

Conventional Western medicine excels at surgery and other acute interventions, but has blind-spots regarding nutrition and chronic diseases.

Since there is no money to be made from the nutrients mentioned above, their full benefits are known only to some clinicians and researchers.  In the developed world, most people are deficient in potassium, vitamin D and especially boron.  This leads to illness with aging, diabetes, stroke, CVD, sepsis etc.

As best we know, SARS-CoV-2 will induce debilitating and potentially deadly sepsis in 5 to 20% of the population in April, May and June.  The terrible toll which is likely to come from this is due, in large part, to easily corrected nutritional inadequacies.  These they can be solved, since the necessary nutrients are widely available. 

It is not right for me to be making such recommendations to the public at large, since I have no medical training.  I am an electronic technician, computer programmer and amateur neuroscientist: aminotheory.com/rlsd/briefsumm/To the extent that advice such as the above is valid, it needs to come from clinicians and health authorities.





#links

COVID-19 and sepsis resources for healthcare professionals

The Surviving Sepsis Campaign is a blight on modern, evidence-based medicine[2018-ref]. ​  It's been clear for some years that its fundamentals were flawed (centering around rapid, large-volume fluid resuscitation).  Rather than adapt guidelines to modern evidence, the campaign recently doubled down on immediate administration of fluid and antibiotics within one hour.  This provoked widespread protest, including a petition to retire the Surviving Sepsis Campaign that garnered over 6,000 signatures.[ref]   Whether or not to retire the campaign was openly debated in the journal CHEST.​​

Change takes time, meanwhile the Surviving Sepsis Campaign continues to lumber forward.  One consequence of this is that recommendations in the one-hour sepsis bundle have started to creep into other literature.  If 30 cc/kg fluid and antibiotics are good for septic shock, then perhaps they're beneficial for other patients?  One example of collateral damage from these guidelines is their mis-application to viral pneumonia.

See also (2020) PMC7024750 .



COVID-19 and sepsis links:

Instead of temporarily overreacting, people are hesitating, preparing less and taking fewer precautions than the knots in their stomachs say they should – beset by self-doubt that maybe they’re wrong and fear of embarrassment that maybe others will mock them. Perhaps the most challenging job public health officials face right now is helping us bear these feelings and ambivalences – and, of course, bearing their own.






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