18 Comments
Jan 31, 2022Liked by Robin Whittle

Fantastic article and as someone that recently got COVID, i am grateful i had read this early enough. I got away with only 2 days of symptoms, no loss of taste symtom or any other left over. Plus ivermectin of course and the FLCCC protocol.

Expand full comment
Jan 23, 2022Liked by Robin Whittle

I've been looking for this exact information for a couple months now. Thank you SO MUCH for providing it and for all the links, as well.

Expand full comment
Dec 21, 2021Liked by Robin Whittle

Thank you Robin for your thorough explanation. Now we need to get the word out to doctors.

Expand full comment

Very useful and practical information!

As a Queenslander (with Scots ancestry and skin pigmentation), I have resisted the idea that I might need supplemental Vitamin D - until I had a blood test last November. Even then, it took me until recently to figure out that the 69 nmol/L level of my test results - technically within normal range - was at best considered moderate, and in fact equivalent to about 27.5 ng/ml (the use of these 2 different measurement options still confuses me!)

And it wasn't until I read Dr David Grimes' blog that I came to understand that as you age, your skin no longer produces enough enzyme to synthesise adequate Vitamin D from sunlight, even for those living in the sub-tropics and getting a fair bit of sun exposure all year round.

http://www.drdavidgrimes.com/2021/12/covid-19-and-vitamin-d-strong-evidence.html

However, I am thinking that COVID is not the only illness we need to protect against, and for those who have this information ahead of time, the most sensible strategy is not to try to get hold of a supply of either calcifediol or cholecalciferol (D3) to stockpile for future need, but to start supplementing immediately - perhaps with a high dose initially to boost blood levels quickly in the first instance, but anyway, to take preventative action.

Expand full comment

I think that calcitriol is of some use. See Grimes - http://www.drdavidgrimes.com/2021/09/ & the RCT referred to - https://pubmed.ncbi.nlm.nih.gov/34508882/

Expand full comment
author

Hi Ko12, I agree with Dr Grimes on many things (we are both on a Google group devoted to vitamin D) but I disagree with him on calcitriol. The Elamir et al. article: "A randomized pilot study using calcitriol in hospitalized COVID-19 patients", Bone, 2021-09-08, showed moderately significant (p = 0.14) benefits in length of hospital stay and a reduction in deaths for which they did not report a significance.

Marginally boosting circulating, hormonal, 1,25-dihydroxyvitamin D might have some benefits, such as if this level was too low due to illness and/or low 25-hydroxyvitamin D supply to the kidneys (neither would be surprising). However, an immediate (4 hour) boost of ~~20ng/ml or less (typical in hospitalised patients, and these researchers did not measure these levels) would enable the kidneys to maintain hormonal 1,25-dihydroxyvitamin D levels better and so attain the same benefits. That hormonal level sets calcium levels which is a crucial and necessarily tightly controlled foundation for all bodily processes. That hormonal level cannot be forcibly raised by oral calcitriol very much before calcium levels are raised to dangerous levels.

The researchers have no idea how the immune cells use 25-hydroxyvitamin D, or how each such cell needs good levels of this to produce its _own_ intracellular, 1,25-hydroxyvitamin D at a _particular_ times due to that individual cell's particular circumstances. Raising circulating, hormonal, 1,25-hydroxyvitamin D levels can't help with this, in part because those levels are so much lower - such as 0.045ng/ml - than those inside the cell with autocrine signaling: ~~1ng/ml: https://vitamindstopscovid.info/02-autocrine/#02-nothorm.

At https://vitamindstopscovid.info/05-mds/#calcifediol-not-calcitriol I cite Leaf et al. 2014 who found no benefit from calcitriol for sepsis patients. Both RCTs should not have been conducted, since it is clear that calcitriol cannot help to any significant degree and that bolus D3 does. Now we know - and it should be no surprise - that calcifediol is much better. So how it is ethical to deny any patients this treatment?

There is a profound and harmful / deadly (for patients) proclivity in some physicians to keep thinking of the three vitamin D compounds purely as a hormonal system, which is the correct understanding only for the very low level of circulating 1,25-dihydroxyvitamin D. Years later, David Leaf was still thinking that the level of circulating 1,25-hydroxyvitamin D was important to the immune system, as you can see in this 2021 article: https://jamanetwork.com/journals/jama/fullarticle/2776736 ". . . the authors demonstrated that circulating levels of 25(OH)D increased in the patients who received vitamin D3, they did not measure circulating levels of 1,25-dihydroxyvitamin D, the active form of vitamin D."

If he understood autocrine signaling he would know that the circulating level of 1,25-dihydroxyvitamin D is for regulating calcium bone metabolism and doesn't affect immune cells to any significant degree.

As an extreme example of how difficult some physicians find it to extend their hormonal conception of "vitamin D" to the non-hormonal mechanisms by which immune cells use these compounds, yesterday I read this comment on the magnificent Chauss et al. article (the forerunner of which is summarised at: https://aminotheory.com/cv19/icu/#2021-Chauss ). The 2 page review of Chauss it all does not disagree with it, and the authors evidently picked up on lots of its many details:

"Role of the T cell vitamin D receptor in severe COVID-19" Jay K. Kolls and Robert F. Garry, Nature Immunology, 2021-12-20.

Chauss et al. clearly show that a good _supply_ of 25-hydroxyvitamin D is required for Th1 lymphocytes to successfully operate their vitamin D based autocrine signalling system ("Autocrine" is in the title), which needs to work in order for each individual cell to respond to its changing circumstances by switching to its anti-inflammatory shutdown program. It does this by generating 1-hydroxylase enzyme and vitamin D receptor (VDR - should be called the "calcitriol receptor") in the cytoplasm, which should convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) which binds to the VDR molecules and so alters cell behaviour.

It is evident from all that Kolls and Garry wrote that they do not understand autocrine signaling! They processed the whole text of the Chauss et al. article via their 100% hormonal conceptual framework of how vitamin D compounds work. I might write a whole article detailing their profound failure to understand what Chauss et al. so clearly elucidated.

This is not a minor storm in a scientific teacup. We can vastly improve human health and suppress the COVID-19 pandemic by raising 25-hydroxyvitamin D levels to 50ng/ml or more. But this will only happen once most physicians correctly understand how immune cells need a good supply of 25-hydroxyvitamin D. This 25-hydroxyvitamin D does not "regulate" (Kolls and Garry repeatedly use this term) anything about the immune system. Neither does 1,25-hydroxyvitamin D - though Kolls and Garry are sure that it does.

They contemplate carefully timed vitamin D supplementation at the disease stage at which Th1 lymphocytes need to switch to their anti-inflammatory shutdown program, because they mistakenly think that this will only happen with boosted circulating 1,25-dihydroxyvitamin D levels, which will only occur if they give the kidneys more 250-hydroxyvitamin D, which would occur after several days of liver activity hydroxylating newly ingested vitamin D3 (or much faster with oral calcitriol). They have no idea about autocrine signaling - they don't refer to it. They end by indicating that the "tissue levels of active vitamin D [calcitriol, 1,25-dihydroxyvitamin D]" are what matters to the Th1 lymphocytes.

We need physicians to understand that the immune system uses the vitamin D compounds in ways which are entirely different from how the kidney uses them to regulate calcium bone metabolism. One might think that clearly explaining this would be sufficient, but it seems that something extra is required for some or many physicians (and Robert F. Garry is an immunologist), to _displace_ their former conceptualisation of how vitamin D compounds always work, to make space for them understanding how the immune cells use these compounds.

Expand full comment

Oi Robin,

I was surprised to learn the efficacy of vitamin D3 is dependent on the manufacturer. Not all bottles of D3 are the same!

Which brands in AUSTRALIA do you know that people use, that you would use or recommend to your loved ones?

Expand full comment
author

I don't know which brands are more reliable. Small differences in content are unimportant. The Australian limit of 0.025mg 1000 IU makes no sense when the average weight person needs 5000 IU / day.

I take a 1.25mg 50,000 IU dry powder vitamin D3 capsule every week = 7143 IU/day (69kg). The manufacturer of these capsules does not want their name mentioned in a COVID-19 context due to US regulations. You can find bottles of 100 50,000 IU capsules from Australian eBay sellers by searching for:

vitamin d3-50

and selecting Item location > Australia only. Searching for:

vitamin d3 10000iu

turns up a bottle of 360 10,000 IU tablets for AUD$29.99 including postage. This could be used every 2 days, or X times a week, depending on the amount needed by bodyweight using the ratios of Afshar et al. https://vitamindstopscovid.info/01-supp/#2020-Afshar . So for a 40kg child x 70 IU/kg = 2800 IU.day = 19,600 IU/week = 2 of these tablets a week.

Please read https://vitamindstopscovid.info/04-calcifediol/#01-rapid to see the research articles I cite. You should make your own decisions on nutrition and health, rather than relying on my opinions. I provide a guide to the pertinent research so you can see how I arrived at my views.

Expand full comment

Why do you say to take calcifediol when you first get covid? Why not take the big dose you recommend before, as soon as possible. That is what I did. My level was 38 before not sure what it is now.

Expand full comment
author

The primary topic of this article is what to do for people who contract COVID-19, or have sepsis or the other conditions mentioned - or really any acute medical problem for which their immune system is important, which would be all of them - when that person is reasonably suspected of having 25-hydroxyvitamin D levels well below the 50ng/ml which is needed for the immune system to have a chance of working properly.

What you did is the best approach - get your 25-hydroxyvitamin D levels up ASAP by taking more than the long-term healthy daily quantity of vitamin D3 to start with, such as by following the bolus arrangement I suggested. This is a suggestion, but it fits with existing research and it is broadly in line with what I am discussing with researchers and medical professionals, such as mentioned in my reply to your other question here.

Now, if and when you develop an illness, or have a challenge such as being badly burned (which leads to infections unless the immune system is in top form) at least you know you have done all you can in terms of the crucial 25-hydroxyvitamin D supply to all your immune cells. There are no-doubt other nutrients such as boron, zinc, magnesium, vitamin C etc. which are important, but vitamin D deficiency is so serious and so common, that you just improved your chance of suppressing infections, and avoiding hyper-inflammatory immune responses, by a great deal with this one simple action.

Some people are keen to have their 25-hydroxyvitamin D levels tested. I wouldn't argue against this, but I don't think it is necessary if the long-term vitamin D intake matches the bodyweight ratio guidelines I referred to above by Afshar et al. or the Grassroots Health calculator, or the ratios I derived - all linked to at: https://vitamindstopscovid.info/01-supp/ . However, the Grassroots Health calculator will not calculate a quantity higher than 10,000 IU a day, when this clearly is required for people with high bodyweights and who are suffering from obesity.

I haven't had my 25-hydroxyvitamin D level tested. I guess it is most likely normally in the 70 to 90ng/ml range, which I am happy about. I just ingested 1mg of calcifediol - as part of https://vitamindstopscovid.info/04-calcifediol/#liquid . If my level was 80ng/ml I guess it went up to ~~120ng/ml (I use tlldes to denote approximation), so I could return to my normal level after a few weeks without taking 1.25mg 50,000 IU a week.

I took the calcifediol to test the suspension I made was drinkable - not to boost my 25-hydroxyvitamin D levels. As far as I know there's nothing to be gained in terms of immune system function by going above whatever my previous level was. If I suffered from auto-immune problems, such higher levels may well be useful: https://vitamindstopscovid.info/06-adv/ .

Expand full comment

Hi Robin thanks for this information. I have a question. My weight is 150 lb at 6ft and my vitamin d level is 38 and I took 500 micrograms of d.velop calcifediol. Do you have an estimate of what level that would bring me to? I want

50-70. And do you have any suggestions as to how much of the daily or weekly cholecalciferol I would need to take to maintain levels of 50 to 70?

Expand full comment
author

Hi Dj, 150 lb / 2.2 = 68kg. Afshar et al. 2020 https://vitamindstopscovid.info/01-supp/#2020-Afshar found that 70 to 100 IU D3 a day attained 40 to 79ng/ml 25-hydroxyvitamin D in the long term. This would have included some people suffering from obesity, who need more per kg.

I think that if they had set a higher range of ratios for those suffering from obesity, the people most likely to have low 25-hydroxyvitamin D levels would have had higher levels, so their range would be something like 50 to 79ng/ml.

For you, this means 68 * 70 = 4760 IU/day to 68 * 100 = 6800 IU / day. There is a great deal of individual variation so the ideal intake is not something narrow and precise.

From the second graph at the top, I guess, that on average, people with your bodyweight who, who like you are not suffering from obesity, and who started with an average of 38ng/ml would probably average around 65 to 70ng/ml a day or two after ingesting 0.5mg calcifediol. This is a good level to aim for, so I suggest you take 5000 to 7000 IU a day from now on. You could do this with 10,000 IU capsules every 2 days, or for instance, Monday, Wednesday, Friday and Sunday (5714 IU/day) or 50,000 IU / week = 7143 IU / day, which is what I take.

Please remember I am an electronic technician. This is my response to what you told me. You should make your own decisions. My purpose in writing these articles and in working out the above calculations is to show you how I came to these conclusions, so you can refer to the research articles yourself and figure out how you want to interpret their observations and hypotheses when deciding how to look after your own health.

Regarding the Grassroots Health article, I will wait till I hear back from the proponents of the D3 conversion in cells to 25OHD hypothesis before mentioning it to the Grassroots Health researcher I know.

Expand full comment

Thank you, I was thinking of continuing to take 6000 IU per day.

I thought I shared this with you but maybe not. I think you will find it interesting.

One year ago I had my vitamin d level tested as part of an overall blood test at a local lab. I had been taking supplemental vitamin d for a while.

That test showed

Vitamin D, 25-Hydroxy, Total78 ng/mL>=30

I continued to take vitamin d over the last year at about 4 to 6k IU per day but my test from Grassroots last month showed it at 38.

I was kind of shocked. Do you have any ideas how that could happen?

I am getting another blood test at the local lab soon and I have asked them to include vitamin d, but because I recently took 500 mcg of calcifediol, so I guess that might not tell me much but I will let you know.

Expand full comment

Grass roots says need to take it daily. Am I misunderstanding something?

Vitamin D3 has a half-life in the autocrine system of roughly 24 hours, so in order for it to have a meaningful impact on cellular functions, you need a new supply of it every day. This understanding means that frequency of dosing matters when testing for disease reduction and immune control – which can help explain why large monthly or quarterly doses that may be effective for bone health are not likely to show positive results for disease reduction. For disease prevention and treatment, daily dosing (food, sun, and supplement) is very important.

Expand full comment
author

Hi Dj, Thanks for your question.

Grassroots Health has a page https://www.grassrootshealth.net/blog/take-vitamin-d-daily/ which I had not seem before.

This is correct regarding the long half-life of 25-hydroxyvitamin D calcifediol meaning that daily vitamin D3 cholecalciferol is not required to maintain good circulating 25-hydroxyvitamin D levels. They cite a 3 week half-life for 25-hydroxyvitamin D and this is probably about right for healthy levels such as 50ng/ml. The half life is shorter for higher levels, due to the level dependent (broadly speaking, the mechanisms are complex and I am not sure that anyone completely understands them) self-limiting enzymatic conversion to 24,25-dihydroxyvitamin D, which is irreversible, with that compound being broken down and its parts excreted. The half life of 25-hydroxyvitamin D at lower levels would be longer.

Autocrine and paracrine signaling relies on the cells (such as immune cells, although some other cell types use vitamin D based autocrine and paracrine signaling) having 25-hydroxyvitamin D in the cytosol ready to be hydroxylated to 1,25-dihydroxyvitamin D when the autocrine signaling system is activated in that particular cell. The conditions which activate it vary from one cell type to the next. https://vitamindstopscovid.info/02-autocrine/

As it is hydroxylated, it needs to be replaced. This, broadly - and perhaps exactly - occurs via 25-hydroxyvitamin D diffusing from the bloodstream, into the tissues and across the cell's plasma membrane. (There are no active transporters - as far as I know it diffused across the plasma membrane lipid bilayer so the concentration inside he cell adjusts to match the concentration outside the cell, except to the extent that 25-hydroxyvitamin D is being consumed inside the cell and the diffusion processes does not keep up. The 25-hydroxyvitamin D in the blood's plasma (the fluid, not the red or other blood cells) is largely bound to the vitamin D binding protein and less strongly bound to albumin proteins. I think there is not complete agreement about the processes at work by which the presumably unbound (small - ~~1% or less) fraction of total 25-hydroxyvitamin D diffuses into cells, or the concentrations in those cells. As far as I know, it is impossible to measure the concentration of 25-hydroxyvitamin D in individual cells, since they are so tiny and even 50ng/ml is only 1 part in 20,000,000 by mass.

My account of this is more authoritative than that of the average electronic technician because I discuss these matters with a number of vitamin D researchers, some of whom are MDs and professors.

There is a hypothesis that circulating vitamin D3 cholecalciferol is not only hydroxylated in the liver to circulating 25-hydroxyvitamin D, but to a significant degree is hydroxylated to 25-hydroxyvitamin D inside cells such as those of the immune system which at times (autocrine signalling only occurs in a cell when it senses particular conditions) consume 25-hydroxyvitamin D to produce 1,25-hydroxyvitamin D.

I recently partly read this 2013 article which suggests significant intracellular vitamin D3 conversion in cells to 25-hydroxyvitamin D. I guess this or similar research is what prompted the statements in the 2019 Grassroots Health page.

The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes

Bruce W. Hollis and Carol L. Wagner

The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 12, 1 December 2013, Pages 4619–4628

https://academic.oup.com/jcem/article/98/12/4619/2833974

I wrote to one of the authors last month about the current status of this hypothesis. These are two long-time and highly respected researchers who devote a lot of their professional lives to vitamin D.

I looked at the titles of the 254 articles which Google links to as citing this one, but I didn't see any which seemed to concern the role of vitamin D3 cholecalciferol being hydroxylated in extra renal (outside the kidney) cells where the resultant 25-hydroxyvitamin D might be used.

I haven't heard back regarding this. To the best of my knowledge it is not regarded as a crucial process, though perhaps it plays a minor and probably incidental role in the provision of 25-hydroxyvitamin D to cells which use this. It is also possible that if enough D3 does diffuse into cells immediately after being ingested or produced in the skin, when 25-hydroxyvitamin D levels were very low, that even moderate levels of conversion there to 25-hydroxyvitamin D may be significant to that cell for a few days in the time it takes the liver (primarily - such non-liver cells could do some of the work) to convert the newly supplied vitamin D3 to circulating 25-hydroxyvitamin D which will diffuse into the cell.

So I regard the statement, from Grassroots Health (which likewise is very highly respected) as incorrect:

>>> Vitamin D3 has a half-life in the autocrine system of roughly 24 hours, so in order for it to have a meaningful impact on cellular functions, you need a new supply of it every day. This understanding means that frequency of dosing matters when testing for disease reduction and immune control – large monthly or quarterly doses that are effective for bone health are not likely to show positive results for disease reduction. For disease prevention and treatment, daily dosing (food, sun, and supplement) is very important! <<<

I have just co-written a journal letter with (retired, but very active) Professor of Medicine Sunil Wimalawansa and we agree that daily to weekly vitamin D3 intake intervals are fine and that monthly intervals are too long. The letter is being considered for publication.

It is not really true to state that D3 has a half-life in the autocrine system of roughly 24 hours, or of any period, since "the autocrine system" is a system for each individual cell. There is no body-wide "autocrine" system. It is an internal mechanism for each individual cells of multiple cell types, which requires 25-hydroxyvitamin D. Maybe a little of this comes from vitamin D3 which has diffused into the cell, but I believe this cannot be crucial to its operation. Mammals evolved to cope with periods of no significant UV-B skin exposure. A week or a few weeks is OK. None of us are properly adapted to going 10 months without lots of UV-B exposure - but this is not a problem for our African ancestors. It is a problem for Africans today who spend most of their time indoors or in vehicles - and of course for all those who live far from the equator.

The multi-week stability of 25-hydoxyvitamin D in the bloodstream, with some exchange to tissues which at least to some degree can return it to circulation as circulating levels drop, is a fundamental part of the supply arrangements for each cell's vitamin D based autocrine signaling system. So I think that weekly intervals between vitamin D3 supplemental intake are fine.

Expand full comment

Hi Robin, thanks for the thorough explanation. Might be good to send to Grassroots.

Expand full comment