Vitamin D, boron and other nutritional supplements to protect against severe COVID-19 symptoms; Concerns about NSAIDs, ibuprofen, aspirin & paracetamol / acetaminophen; Potassium gluconate solution instead of blood pressure medication

Robin Whittle  2020-05-27 14:00 UTC  Please reload this page in the next day or two since I am updating it progressively.  I haven't yet got to the main vitamin D and boron sections below, but I am on the case.

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. 

Introduction

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, man 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 likelihood 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 #2016-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 an effective vaccine.  Immunity to coronaviruses after infection - or which might be elicited by a vaccine - is 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.  Humans 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, with a total D3 cost of USD$10, and I guess USD$100 manufacturing cost, would be good for one adult for a hundred years.

The trouble is that, 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 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.



Coming soon -  a new website

I am working on 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.

Recent articles concerning COVID-19 and vitamin D

Two studies from Indonesia and the Philippines are of particular interest.

#2020-Raharusun
Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
Prabowo Raharusun et al. 2020-04-30
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561

COVID-19 death rates by vitamin D (25OHD) levels of hospitalised patients:

25OHD  Death rate
ng/ml

> 30     4.2%    
 
20-30   49.1%  

< 20   
46.7%    

The death rates for all people infected with COVID-19 would be somewhat different, with the rate for > 30ng/ml (greater than 75nmol/L) people not in hospital vastly lower, since only the sickest subset of them are in hospital and so included in this research.

With proper in-hospital care, according to Paul Marik's Protocol or the Front Line COVID-19 Critical Care Working Group's Protocol, both involving intravenous vitamin C and corticosteroids, the death rates would be much lower than these.

#2020-Alipio
Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019)
Mark Alipio  2020-04-08
Davao Doctors College; University of Southeastern Philippines
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3571484

Hospitalised COVID-19 patients were classified into Mild (without pneumonia), Ordinary (CT confirmed pneumonia with fever and respiratory symptoms), Severe (hypoxia and respiratory distress) and Critical (respiratory failure).  Here are the number of cases in these categories, grouped by their vitamin D (25OHD) levels, which remained generally stable during the course of the disease. 

25OHD  All Mild Ordinary Severe Critical
ng/ml

> 30    55   47        4      2        2    
 
20-30   80    1       35     23       21  

< 20    77    1       20     31       25


46 ng/ml is the average of African herders and hunter-gatherers - and can be attained, on average, in normal weight people with 4000IU vitamin D3 a day.


Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics
Dieter De Smet et al. 2020-05-05
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).
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)
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:

#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.


#2016-Stagi
By mid-May 2020 it has become clear that some children are suffering severe symptoms from COVID-19 - and some of them are dying.  The inflammatory symptoms are similar to Kawasaki disease.  Here is a 2016 article of interest 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 (2016)
https://link.springer.com/article/10.1007/s10067-015-2970-6  (Paywalled.)
https://sci-hub.tw/10.1007/s10067-015-2970-6

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 severe 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 10% to 20% 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 supplements so they never have to suffer and die like this!  Why are so many doctors resistant to vitamin D supplementation when most people, without supplements are deficient?

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 they too were already struggling with extremely low 25OHD levels.

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 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?  What is wrong with the doctors and/or the education of the parents?  There are no-doubt numerous triggers for Kawasaki disease, with COVID-19 being a novel, widespread and effective 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).  However, see Alipio et al. above who noted that the levels during COVID-19 severe symptoms were generally consistent with those measured months or years before.

It is obvious that 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, they 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 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.  Assuming it was given with meals, I can't imagine how a child so supplemented could have such low 25OHD as to be at risk of Kawasaki syndrome/disease.

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 (2016)
https://sci-hub.tw/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 

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:

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

Dr Robert Baker of New Jersey https://robertbakermdhealthnewsletter.blogspot.com  wrote, 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)

By the way, my parents Jeff and Ruth are doing pretty well in their early 90s.  For years, as advised by their doctor, they have been taking 4300IU D3 a day.

Please also see Irish doctors debating how much supplemental vitamin D3 should be given, with one group (and these are the good guys) arguing for 2500IU a day (which 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 Philippino work (Alipio et al.)  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, or in how these tragic, disastrous, patterns of ill-health can be largely or completely 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, 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.

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:


Vitamin D levels in US women are too low.  2500IU D3 helps, but still some do not attain 30ng/ml, which is at the low end of what could be considered replete.  4000IU or more would be better.

Fortunately, there are doctors all over the world, who - like Robert Baker - recommend high enough D3 intakes that their patients are 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 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 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 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!

Meanwhile 21 authors, in an article finalised on 2020-04-29, support the official 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, or to the severe vitamin D deficiency observed in, and obviously causing (in combination with some infectious insult) Kawasaki Disease (above) were sufferers averaged 9.2ng/ml.

Nor is there any mention of the work of #2020-Alipio (3 weeks before their final version) and #2020-Raharusun (a day after) showing vastly greater risk of serious COVID-19 symptoms and death with 25OHD levels below 30ng/ml.

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.

On the ICU page icu/ please see two 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.


COVID-19 would cause little or no harm if everyone's immune system was working well

#helminthsgone
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.

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

(Here is the link to the PDF of Multiple sclerosis and the hygiene hypothesis.   The Inkscape .svg file his here.
 
There is little up-to-date information on helminth infection prevalence by country.  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.)

We cannot easily fix this, though relatively benign helminth infections - or in the future drugs which mimic the downregulating chemicals they produce - will be part of the solution.  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 non-omega-3 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.

Other pages here

For information of interest to Critical Care workers, including the early use of vitamin C and corticosteroids to avoid the need for invasive ventilation, based on the Marik Protocol:

http://aminotheory.com/cv19/icu/

I reviewed the research regarding antipyretics, NSAIDs, paracetamol etc. for dealing with fever:

http://aminotheory.com/cv19/fever/

All the research I can find indicates that fever, in general, should not be lowered.  There are specific exceptions such as for stroke, neurological injury and heart disease.  There is an urgent need for the WHO and health authorities to warn people of the dangers of using these drugs at home when they contract COVID-19 with fever.

I wrote what was intended as in introduction on another page, mainly concerning the global problem of obtaining sufficient vitamin D3 in weeks, rather than months:  

http://aminotheory.com/cv19/intro/

I haven't updated in in mid-May.  I will present an updated version in the forthcoming new website.

My notes on supplementation with potassium gluconate are:

http://aminotheory.com/cv19/kna/


#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.  I am not selling anything.  I never got around to getting the certificates etc. for encrypted https.  These web pages set no cookies in your browser.


Contact

I update this material according to new information and any feedback I receive from clinicians, researchers, or anyone at all. 

Please email your 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.

Nutrition and better guidance regarding fever

(This section written 2020-05-26.  I will fine tune it in a few days and then work on the next section concerning vitamin D.)

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: 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%).  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: 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: 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 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].

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 macronutrients omega-3 fatty acids P15 and potassium P16 and 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 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.

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.

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.  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. 

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 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.

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 are at 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.

S3: Directly to P7 and P8, and so 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 weeks and 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.

Since we can't slow the spread of the disease sufficiently - so that the 20% or so of people who do get lung infections can all go immediately to hospital - fully achieving S4 would be  an important but only partial solution to P2c.

In order to achieve S4, 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 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 protect them against 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 no 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 30n/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.

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.  We probably need 6 to 12mg a day to be boron replete.

In trying to solve these problems, the material (below, I am working on a completely revised version) at this website 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 am working on now.  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.

Here is a trial giving ICU patients high 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, 50,000 IU vitamin D
3 or 100,000 IU vitamin D3 daily for 5 consecutive days.

There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 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 two of these 50,000IU capsules a month.  We also get some vitamin D in multivitamins.


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

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.

The nutritional requirements are the same, except for more melatonin for hospitalised patients.

The prophylaxis recommendations are, implicitly, for all adults in the current (early April) state of expecting to be infected with COVID-19 in the weeks or months to come.   The intention is to either prevent infection (I think this is unlikely to be achieved) or to reduce the severity of the infection when it occurs, by preparing the body with nutritional and other items.  I believe these are a very good thing!
Please see #marik below for a link to the latest version of the document, and for some quotes from the document which explain the purpose of some of the items listed above.  For instance, melatonin is believed to have antiviral properties.

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 below #marik .


#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 below #marik - 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.


 Since mid March, our supermarket has been sold out 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 below #marik, 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

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.)

Laundry borax is available by the kilogram in most supermarkets.  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.


#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, in the first week or so of April.

(On 2020-03-31, Paul Marik's protocol recommends 5000IU vitamin D a day for adults, before infection and after, for mild symptoms.  I think this is an excellent development.  I hope that intakes such as this will soon be recommended by national health authorities and/or the WHO.)




#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 .

1.  We are all inhabitants of the same planet and we are all in this together. The medical community needs to get off their "high pedestal" and act decisively and right now; there is no time to lose.   

2.  It is likely that 40-80% of the population across the world will become infected with this virus. It is therefore unrealistic for us to expect this will just go away. Our goal should therefore to reduce the mortality in those who are at greatest risk of dying. This requires that those at risk to "socially" isolate themselves. Once they become infected, we should treat aggressively to prevent disease progression.

3.  The course of the disease is quite predictable. Acute respiratory failure occurs on day 6-8 (due to cytokine storm). In those patients requiring supplemental oxygen, we need to be very aggressive to prevent progression to ARDS. Once ARDS develops the mortality is high.

4.  This is not your "typical" ARDS. Chest CT shows bilateral, discreet, irregular, multi-lobar infiltrates and not the typical dependent air-space consolidation (“sponge lung”) characteristic of the usual ARDS. Physiologically "COVID-19 ARDS" is different; our preliminary data suggests that lung water (EVLWI) is only marginally increased. Furthermore, lung compliance is quite good yet severe hypoxia (due to shunting). Cause unclear?? Microvascular thrombosis.  

7.  Zinc (Zn++ ) inhibits viral RNA dependent RNA polymerase (replicase). Chloroquine and hydroxychloroquine are potent Zn ionophores that increase intracellular Zn concentrations.

8.  Ascorbic acid (vitamin C) has numerous proven biological properties (anti-inflammatory, anti-oxidant, immune enhancing, antiviral) that are likely to be of benefit in patients with COVID-19 disease.

9.  Very recent data suggests that in addition to being a potent ant-oxidant, melatonin may have direct antiviral effects against COVID-19. In healthy people, melatonin levels plummet after the age of 40 years. This may partly explain the increased risk of death in patients with COVID-19 who are over the age of 40. Melatonin may therefore have a role in both the prevention and treatment of COVID-19.

10. Vitamin D has important immune enhancing effects. Much of the population, especially the elderly have sub-optimal vitamin C levels, particularly during the winter months. Low vitamin D levels have been shown to increase the risk of developing viral upper respiratory tract infections. Therefore, prophylactic vitamin D should be considered especially in the elderly.  

11. Quercetin is a plant phytochemical. Experimental and early clinical data suggests that this compound has broad antiviral properties (including against coronavirus) and acting at various steps in the viral life cycle. Quercetin is a potent inhibitor of heat shock proteins (HSP 40 and 70) which are required for viral assembly. This readily available and cheap plant derived compound may play a role in the prophylaxis of COVID-19 in high risk populations. 

A 2018 article about this by Paul Marik and colleagues: Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation  www.ncbi.nlm.nih.gov/pmc/articles/PMC6206928/ contains a big diagram and explanation.
Humans (and anthropoid apes) have lost the ability to synthesize vitamin C and therefore have an impaired stress response. The inability to produce vitamin C has serious implications in septic humans. Treatment with vitamin C appears to restore the stress response and improve the survival of stressed humans
"My colleagues, when I told them what was going on, thought it was the biggest load of nonsense they had ever seen.  But then they actually saw that none of our patients were dying.  And then our CEO saw that none of the patients were dying.  So this has become instituted through the whole healthcare system.

"We were going to do a randomised clinical trial, but we couldn't - because it would have been unethical."



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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