Vitamin D, boron and other forms of nutritional supplement to reduce deadly sepsis inflammation with coronavirus COVID-19; Concerns about NSAIDs, ibuprofen, aspirin & paracetamol / acetaminophen; Potassium gluconate solution instead of blood pressure medication

Robin Whittle rw@firstpr.com.au   2020-03-21  Last update 2020-04-01 22:20 AEDT


Below (and in the fever/ and kna/ pages) you will find an updated version of an email I sent to a number of COVID-19 researchers and clinicians, starting on 21st March 2020.  It contains suggestions for advice I believe they should be giving regarding what people can do to cope, at home, without relying on hospitals (which will soon be completely overloaded) with COVID-19 induced inflammation (sepsis) which causes life-threatening pneumonia, organ damage and failure (heart, liver, kidneys) and so, potentially, permanent disability or death.

Clinicians (doctors and nurses) have vast knowledge and often extraordinary skills.  However, in general, they are not properly informed about research into nutrition.  Their  view of medicine and health can be unduly influenced by drug companies - who are only interested in substances they can patent and profit from.

On 21st March 2020 I thought some prominent COVID-19 researchers and clinicians needed a pep talk about all this.  I was also concerned that many people would take fever-reducing drugs at home, and so reduce their body's ability to combat the virus.

I am an electronic technician and computer programmer. I created this website http://aminotheory.com in 2011 primarily for my new observations and etiological theory of Restless Legs Syndrome:

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.)

I update the text below 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 .

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.  The fact that I think these are good ideas should not affect your own decisions about healthcare for yourself and your loved ones.  You should read and consult very widely.  A list of coronavirus links is at the end of this page: #links .

By all means direct your doctor, nurse or naturopath to read what follows.

If your decisions are influenced by what you read below, it should be because you have evaluated the arguments, followed the links and read the research articles I cite and because you take responsibility for your own life.

The text following #msg is written for people with medical training.  If you can't understand it clearly, please rely on the judgment of someone who can.

I have expanded on a few acronyms with fuller text and.or [WP] Wikipedia links, which were not in the emails I sent.  I have also boldfaced and highlighted some text and added headings.

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.

Paracetamol (Panadol) is the same as acetaminophen (Tylenol etc.)  It reduces fever and is generally not regarded as an NSAID [en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug] - a class of drugs which includes aspirin and ibuprofen.


#key

Key points of the message to clinicians and researchers below

These points are stripped of arguments and references, and are a guide to the message below #msg , which would ideally be a much longer exposition.  Please read the message, with the research it cites AND read the disclaimer above that you shouldn't act on suggestions regarding health from an electronic technician unless you have researched the arguments to your satisfaction, read and ideally consulted very widely indeed and take full responsibility for your decisions.




#msg

Updated version of the message I wrote to clinicians and researchers

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 Canadian graph www.crsociety.org/topic/11678-vitamin-d-recommendations/ 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.




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.)

Vitamin D deficiency causes the overly inflammatory process of acne PMC5997051 - and I suspect that boron supplementation alone would probably resolve this and many of the more serious conditions, since it enables the body to make better use of limited vitamin D.   Since acne is clearly visible, this might be helpful for clinicians in assessing the need for dietary advice and the risk of developing chronic diseases and sepsis.


#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-why-the-medical-community-is-recommending-that-if-folks-get-sick-with-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-%20boron%20on%20plasma%20steroid%20hormones%20and%20proinflammatory%20cytokines.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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