“Normal” ranges for blood chemistries are determined by the central 95% of distribution among a “healthy” population, or in some cases by 99th percentile upper reference limit. I don’t know what applies for vit D.
In any event, if your contention is that the currently accepted “normal” for vitamin D is in fact still physiologically defici…
“Normal” ranges for blood chemistries are determined by the central 95% of distribution among a “healthy” population, or in some cases by 99th percentile upper reference limit. I don’t know what applies for vit D.
In any event, if your contention is that the currently accepted “normal” for vitamin D is in fact still physiologically deficient, then it should make it EASIER for you to prove a benefit of supplementation. Yet despite your data dump, I see no such proof on offer.
Much of what you quoted are associations. On their best day, they can only be hypothesis-generating.
The post op infections paper was only association.
The “peer reviewed” paper by Dr. Sunil W. wasn’t even a study of any sort….just a navel gazing exercise by someone who has drank the koolaid….and perhaps made the koolaid himself.
The 2020 Spanish Covid paper does seem to have been a proper study….although even the authors acknowledge the need for much larger confirmatory trials. You can’t draw too firm a conclusion based on 76 patients. Also, I’m curious about word-choice as they seem to use “allocate” and “randomize” interchangeably. Perhaps it is a language issue. But in their conclusion they note a need for “larger trials with groups properly matched”….and “proper matching” is not a concern for an actual RCT.
So despite all the verbiage and the enormous links, I see absolutely bupkis proving vit D to be causally of benefit in an adequately sized and powered RCT. Where’s all this hot air coming from, bud?
The 25-hydroxyvitamin D levels of most people who do not supplement vitamin D properly and who have not had recent extensive UV-B exposure of ideally white skin are indeed normal, but they are not healthy.
The Massachusetts General Hospital study shows very clearly that immune responses against bacterial pathogens which cause post-operative infections decline the further the preoperative 25-hydroxyvitamin D level was below 50 ng/mL. Even if half or 3/4 of this is due to confounding - and even 1/4 is difficult to imagine - this is still a very strong association with the causality flowing from pre-operative 25-hydroxyvitamin D to post-operative 25-hydroxyvitamin D which many types of immune cell need to run their intracrine signaling systems, which are a crucial part of how each cell responds to its changing circumstances.
You can read about 25-hydroxyvitamin D to calcitriol intracrine signaling at: https://vitamindstopscovid.info/00-evi/#02-compounds. Most doctors and immunologists are not aware of this at all. My web page is full of research which shows how important it is to attain at least 50 ng/mL circulating 25-hydroxyvitamin D.
Thanks for looking at Castillo et al. 2020. As I wrote at: https://vitamindstopscovid.info/00-evi/#castillo, Jungreis and Kellis at MIT wrote a preprint https://www.medrxiv.org/content/10.1101/2020.11.08.20222638v2 in which they argue that even accounting for the fact that the randomization happened to put patients with more comorbidities into the control group, the results of this RCT are still a very powerful argument for this intervention, which raised 25-hydroxyvitamin D levels generally over 50 ng/mL in a few hours. The researchers - and Jungreis and Kellis - did not seem to know how fast this was. Bolus oral (or injected) vitamin D3, such as 10 mg 400,000 IU, takes several days. I found a patent https://patents.google.com/patent/WO2016124724A1/ which graphs the 25-hydroxyvitamin D level curve after the exact same 0.532 mg calcifediol oral dose, using the exact same 0.266 mg capsules.
By all means wait for an RCT which raises all participants' 25-hydroxyvitamin D levels over 50 ng/mL for a few years and surveys all cause mortality, every disease and health condition etc. I wish we had such a study.
Your desire to wait - and to encourage others to wait - probably for a decade or two, might make more sense if the intervention was some new drug, vaccine, mRNA etc. gene therapy, monoclonal antibody, surgery or implanted device. However, the intervention is to attain at least 50 ng/mL circulating 25-hydroxyvitamin D, rather than 5 to 25 (with somewhat higher levels in summer for white-skinned people) in the context of our immune systems having evolved in African Ancestors with much higher 25 hydroxyvitamin D levels than the great majority of the population of temperate countries today. The only research along these lines is Luxwolda et al. 2012 "Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/L (46 ng/mL)" https://doi.org/10.1017/S0007114511007161.
"We measured the sum of serum 25-hydroxyvitamin D2 and D3 (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (sd 10) years, 43 % male) and twenty-five Hadzabe hunter–gatherers (35 (sd 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible."
The average 25-hydroxyvitamin D level was 115 nmol/L 46 ng/mL.
You apparently did not find much of value in the research I cite and discuss at: https://vitamindstopscovid.info/00-evi/ . Most people who are concerned about their health, the health of their loved ones and of the public in general are not so avoidant. Most such people are not as keen as you seem to be to defend the current, clueless, position of mainstream medicine regarding 25-hydroxyvitamin D and the immune system.
Causation does NOT flow from association. We can have a separate discussion about Bradford Hill criteria regarding when an exception to that rule may be in order (eg. Smoking). But let’s just say the case for vitamin D is nowhere on par with that.
As I said, that Spanish RCT seems legit and its authors are to be commended for being appropriately conservative in their conclusions (rather than making wild claims not supported by the evidence). So the answer is not to excessively navel gaze at a 76 patient study; the answer is to take the hypothesis it generated, and to test it properly and prospectively in an adequately powered study.
I couldn’t tell Prof W from a hole in the ground. And appeals to authority are meaningless, intellectually weak, and of zero persuasive use on me. If he had the evidence of vitamin D benefit, he should bring it. He hasn’t. Someone who relies on his authority to make claims without evidence is a scheister until proven otherwise. In my field, someone like Eugene Braunwald enjoys much deference. But even for him, I’d only listen when he speaks from a position backed by evidence, and not otherwise.
The research you cited without exception is fine for generating hypotheses, but is woefully inadequate for changing practice. As an apparently enthusiastic proponent, the burden is on you to generate proper evidence to substantiate your claims. You may well be proven correct in the future. But I am only persuaded by evidence, and not enthusiasm. Your reliance on people wanting to be healthy is EXACTLY the formula used by scheisters who sell snake oil.
Your rejection of perfectly good evidence strikes me as clueless and overly trusting of current mainstream medical opinion. This is about correcting a deficiency, not introducing a new drug or vaccine.
Post operative infections do not cause low pre-operative 25-hydroxyvitamin D. So unless there is significant confounding - and you haven't suggested how this might be the case - low pre-operative 25-hydroxyvitamin D causes a greatly increased risk of post-operative infections.
I was not suggesting an appeal to authority - just that Prof. Wimalawansa's contributions to science and health are greater than yours. You doubled down on your insulting statements about him - someone you don't even know. Yet you couldn't be bothered stating what you think is wrong with his vitamin D3 supplemental intake guidelines or anything else he wrote. I looked at your profile to see if you had written anything constructive or told us anything about yourself, but you hadn't. You apparently read 27 Substacks, but have never Liked an article (post) or comment. You have never written an article or a note.
Btw, you should know that your fundamental assertion makes no sense in terms of evolutionary biology.
If humans actually needed the “higher” levels of vitamin D than is seen among current population normals, then selection pressure would have resulted in a genetic advantage for those with such higher vitamin D levels. The result of this selection is that current “normals” would reflect what you contend to be the “real” required amount of vitamin D.
So not only does your assertion lack proper scientific support, but it also runs counter to Darwin.
Low 25-hydroxyvitamin D levels have been a problem for an increasingly large proportion of humanity since the migrations out of Africa into northern Europe, Siberia and other locations far from the equator. The evolutionary response in these populations was to evolve genes which reduced melanin pigmentation, except to a small extent when exposed to extensive ultraviolet light. However, the lack of UV-B light ca. 297 nanometres (at the extreme short-wavelength, high frequency, high energy per excited electron) range of the solar radiation which reaches the Earth's surface) far from the equator, most especially in winter, means that no-one can produce enough vitamin D3 cholecalciferol to sustain 50 ng/mL circulating 25-hydroxyvitamin D.
The only way known in nature or industry https://sci-hub.se/10.1016/B978-0-12-381978-9.10006-X of producing vitamin D3, or any similar molecules, is by breaking one of the bonds in one of the carbon rings of 7-dehydrocholesterol or a similar molecule. No-one knows a chemical approach to this. The only way is the photochemical approach which requires this short wavelength, high energy per excited electron, UV-B light. These wavelengths always damage DNA and so kill cells and raise the risk of cancer.
In the past tens of thousands of years, as today, populations survived far from the equator, but they do not thrive - as can be seen by the prevalence of disease in countries like the UK today. The seasonality of influenza should be your first clue as to how this works - low 25-hydroxyvitamin D in winter and spring enables the virus to infect cells more easily, since the immune cells do not have as much 25-hydroxyvitamin D as they need to run their intracrine and paracrine signaling systems properly.
There isn't a way the immune cells can work properly with less than this, unless perhaps they all evolved an active transport system for 25-hydroxyvitamin D across their cell walls, as is the case with the kidney cells which produce calcitriol to go into circulation as a hormone. The immune and other cells which use 25-hydroxyvitamin D to produce 1,25-dihydroxyvitamin D calcitriol as an intracrine signaling agent only do so when a particular cell-type specific condition is detected. (https://vitamindstopscovid.info/00-evi/#02-compounds). They need to produce an internal level of calcitriol which clearly exceeds the hormonal background level, which diffuses into the cells as well. That level is pretty low, ca. 0.05 to 0.1 ng/mL in the bloodstream. I am not aware of any research which measures the calcitriol levels inside cells when the intracrine signaling system runs properly. I suspect there is no reliable way of measuring this at present.
Maybe one day, after hundreds of thousands or millions of years, immune cells might evolve to work well with lower levels of 25-hydroxyvitamin D. However, at present, we need 50 ng/mL to be healthy.
As I wrote earlier, I am not aware of any RCT which raises the intervention group's 25-hydroxyvitamin D level over 50 ng/mL and has a suitably long time, such as a few years, to collect all manner of health data. I wish there was one. Maybe there will be one in the next ten years - that would be great.
You want to wait for the golden RCT on a silver platter before you might contemplate vitamin D3 supplementation. Good luck with your risks of dementia in the decades to come: https://vitamindstopscovid.info/00-evi/#3.3.
Other folks take an interest in and come to understand the mechanisms, such as by reading what Chauss et al. found about permanently inflammatory Th1 regulatory lymphocytes in the lungs of hospitalised COVID-19 patients: "Autocrine vitamin D signaling switches off pro-inflammatory programs of Th1 cells" Nature Immunology 2021-11-11 https://www.nature.com/articles/s41590-021-01080-3. (They are actually studying intracrine signalling - autocrine is with the receptors on the outside of the cell, but here they are in the cytosol. I made the same mistake at first). My summary of this dense cell biology article, or at least of its preprint, is at: https://aminotheory.com/cv19/icu/#2021-Chauss. These cells, unlike the cells from healthy controls, failed to transition from their pro-inflammatory startup program to their anti-inflammatory shutdown program, despite detecting the condition to do so. The researchers concluded (in the final article) that this failure was due largely or entirely to inadequate supplies of 25-hydroxyvitamin D. The circulating 25-hydroxyvitamin D levels of the patients was not available, but it is well known that even lower 25-hydroxyvitamin D levels than the poor levels in the general population (compared to 50 ng/mL) are most likely to develop severe COVID-19 symptoms.
Once such folks understand the mechanisms which explain the observational evidence for immune system failure in proportion to how much below 50 ng/mL the circulating level of 25-hydroxyvitamin D level is, and recognise that absent high levels of UV-B skin exposure all year round, they can only attain this by vitamin D3 supplementation, they get very interested since the risks are so low and the benefits so important and pervasive.
They don't feel they need to wait for the golden RCT before taking supplements which will, very likely, improve their health in many respects. You do, which is your choice.
Your writing here seems to be intended to scare off other people from taking action to boost their 25-hydroxyvitamin D level before any such RCT proves, beyond reasonable doubt, that significant benefits would accrue from such supplementation. You haven't detailed any risks. Your evident concern about such risks and the need for this ideal RCT would probably be more persuasive if they knew you were a highly experienced researcher and/or clinician who had demonstrated great judgement and insight over multiple decades AND/OR if you substantiated your complaints properly. I don't know about other people reading these comments, but I know nothing about you beyond your comments to this article, in which you argue for an RCT for effectiveness of a rotavirus vaccine (which I agree with) with the (ideally, who knows??) rare adverse reactions being studied after the vaccine is widely deployed.
I argue that any vaccine needs to be studied for years with one or more RCTs precisely to detect such adverse reactions, which can be permanently debilitating or deadly.
If you will permit me an appeal to a (prior, not now) authority, none less than Dr Fauci, here goes: He wrote an article attesting to a fundamental effectiveness limitation of the COVID-19 injections in January 2023: Morens, Taubenberger and Fauci "Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses" Cell Host & Microbe 2023-01-11: https:// www.cell.com/cell-host-microbe/fulltext/ S1931-3128(22)00572-8:
". . . it is not surprising that none of the predominantly mucosal respiratory viruses have ever been effectively controlled by vaccines. This observation raises a question of fundamental importance: if natural mucosal respiratory virus infections do not elicit complete and long-term protective immunity against reinfection, how can we expect vaccines, especially systemically administered non-replicating vaccines, to do so? This is a major challenge for future vaccine development, and overcoming it is critical as we work to develop 'next-generation' vaccines."
That was concerning effectiveness, which you and I agree should be established robustly via one or more RCTs before clinical deployment.
I am with Dr Fauci's former self in supporting RCTs to discover adverse affects, which you think needn't be done. The dangers of widely deploying vaccines without a decade or more research are well known. Dr Fauci attested to this in 1999: https:// rumble.com/v20t87i-1999-fauci-said-it-could-take-up-to-12- years-for-everyone-to-realize-the-da.html. This video also includes him stating, in 2020, that a great deal of research is needed to ensure that the vaccine does not cause ADE (antibody dependent enhancement), in which the vaccine - he cites an example of an RSV vaccine - "paradoxically made the children worse" and an experimental HIV vaccine which made people more likely to become infected.
Aaron Siri and team have a list of the vaccines currently on the US childhood vaccine schedule: https://icandecide.org/article/childhood-vaccine-trials-summary-chart/. They claim "None of the vaccine doses the CDC recommends for routine injection into children were licensed by the FDA based on a long-term placebo-controlled trial."
Can you check their several dozen references before lunch?* I am kinda busy.
Assuming their claim is correct, do you think all these vaccines should be withdrawn from use until such RCTs are done, which would take a decade or so?
Alternatively, do you think that the limited testing they have done on these is good enough to prove their effectiveness, with the ill-effects left to be investigated as they harm and kill ordinary people who are enticed or forced to accept these vaccines on the premise that they are proven to be safe and effective?
“I don't know about other people reading these comments, but I know nothing about you beyond your comments to this article”
—forgot about this bit.
I do not claim to be an authority (at least on this forum).
Yet my arguments here do not require any authority.
One does not need to be a bigwig to demand proper evidence of efficacy prior to adoption of a therapeutic regimen.
The position I take here is sufficiently straightforward and fundamental to the scientific method (and logic in general) that it could be made by just about anybody.
“I am not aware of any RCT which raises the intervention group's 25-hydroxyvitamin D level over 50 ng/mL and has a suitably long time, such as a few years, to collect all manner of health data”
—- y’know, you really shoulda led with that. And maybe display that short phrase prominently somewhere on that extremely verbose site you like to link to (maybe you have….I certainly did not bother scrolling through all of it).
Now, are you aware of all the RCT of vitamin D that have shown NO benefit? (To be fair, I’d never heard of the assertion of a need for “supra-normal” levels of vitamin D, so this magical 50ng/mL business has probably not been specifically tested in RCT…which is a fact you now admit).
VITAL- null on CV events and cancer
D2D- null on prevention of diabetes
ViDA- null for CV events
WHI- null on fracture reduction
So, let’s check the tape, shall we?
Several RCT of vitamin D that have shown no benefit (that I’m aware of; I imagine there are more, but this is not an area that I follow outside of my field). I certainly haven’t heard of any positive RCT for vitamin D in any field that is sufficient to be practice- changing.
Just as a logic lesson, you can’t PROVE a NEGATIVE. So I do NOT assert that vitamin D supplementation is of NO benefit. But since you assert that vitamin D supplementation IS OF benefit, the burden of proof is on you to provide evidence which sustains your assertion…which you don’t have.
So do I want to wait before taking vitamin D? Yeah. Cuz I need to see some evidence of benefit first. The real question is why you don’t have such a need.
Dementia you say? Absolutely terrible. And is this where you start the scheister routine? “Avoid dementia, take Vit D”? lol. Is this the new marketing strategy?
“They don't feel they need to wait for the golden RCT before taking supplements which will, very likely, improve their health in many respects.”
—-😂 that’s cuz “they” are suckers who will do things without evidence. Like I’ve said before, as long as there are suckers in the world, there will be scheisters who will happily rip them off…and there will always be scheisters. Your latest post is the blueprint for snake oil salesmen. Step 1- find scary ailment; step 2- concoct fancy theory of why your product will magically fix said ailment, which is just plausible enough to be believable (by suckers); step 3-take said suckers to cleaners.
Your routine is indeed tried and true, bud. No doubt you fleece many suckers with this. I’m just not one of them.
Your “perfectly good evidence” is mostly (Spanish 2020 study being a noted exception) observational data which counts as low quality evidence to me. Perhaps I’m simply a more discerning consumer of evidence than you are.
I’ve stipulated that “correcting a deficiency” is a reasonable indication for supplementation. But you’ve asserted that population “normals” still in fact denote physiologic deficiency. That’s an assertion which accrues the burden of evidence on you. This is how logic and science work. The fact that I need to explain this to you makes me wonder how much you actually know about the scientific method (my guess is “not very much”). All you need to do is produce evidence which supports your claims. You seem very confident in your claims. So presumably it won’t be hard to conduct proper studies to sustain those claims. One wonders what you’re waiting for.
“Unless there is significant confounding” - and how do you prove causation and eliminate concerns about confounding? You guessed it, a proper RCT. These truths are cold, and hard. Best get used to them (or perhaps learn them for the very first time).
I don’t need to know “Dr. W” to know he’s shovelling manure based on what I’ve read here. Again, all he needs to do is to bring proper evidence rather than unsubstantiated opinion. Any proper self-respecting scientist would know that. Which makes me really wonder whether he actually is one. Maybe that’s why you’re so enamored with him…birds of a feather, as they say.
What’s wrong with his “guidelines”? Everything. Cuz they’re not based on high quality evidence. This should not be a difficult concept (and one you seem to desperately need to learn).
I don’t purport to be a writer. I also know my limitations. That seems already to exceed the level attained by you, this Dr W dude, and scheisters of similar ilk.
Hi Steve, If you want to help people like me avoid hypothesizing that your comments here regarding the vitamin D compounds are indistinguishable from the rantings of some rando on the Internet, you might want to go easy on the personal invective and flesh out your profile with links to constructive statements, dialogue, debate etc. and some description of yourself.
I have already presented evidence that less than 50 ng/mL causes, in large part, a greatly increased risk of post-operative infections. The only research we have regarding long-term African ancestral 25-hydroxyvitamin D levels is a mean of 46 ng/mL. So what is normal for the unsupplemented or under-supplemented populations of temperate countries is not normal in long-term human evolutionary history. More importantly, it is not healthy.
It is better that readers here review the most pertinent research via links at: https://vitamindstopscovid.info/00-evi/ than me try to cite and discuss it in this comments thread, especially since I can't post graphs here.
I’m not going to read through the entire data dump.
But i did find this section comical:
“While this is not provably the case with current variants, the transmission and severity of all COVID-19 variants can best be reduced by ensuring that as many people as possible have at least 50 ng/mL (125 nmol/L) 25-hydroxyvitamin D levels AND that they are provided with multiple early treatments,…”
—-so you can’t “prove” it, but you still advocate for as many people as possible to follow your advice anyway.
Ummm…based on what, exactly?
I review more literature before lunch than most people read in a year. If you feel a call for high quality (or even decent quality) evidence is the ranting of a rando, that’s fine by me. I certainly consider your blind, ignorant, and shameless shilling for Vit D supplementation to be highly pathetic.
To be clear, you have NOT “already provided evidence that less than 50ng/mL causes” the square root of sweet jack all. What you have provided are associations (which are very much NOT the same as proof of causation). And in conflating the two repeatedly, what you have also NOT shown is any grasp of the scientific method.
My challenge is simple: provide proof of causation via properly powered prospective RCT showing that supplementation with vitamin D (in whatever formulation you prefer, to a level that exceeds whatever concentration that floats your boat) produces clinical benefit using whatever endpoint you feel like. I’m intentionally keeping your options as diverse as possible so that the bar is very low….since at this point you haven’t provided causative proof of anything (and if there is something in your data dump that fits the bill, please link to it so I don’t have to wade through all that nonsense).
What you seem to like to provide is biologic plausibility. That’s fine for a hypothesis. But what you lack is any evidence that sustains your hypothesis (and I’ve acknowledged the one Spanish 2020 study which was decent but whose limitations even the authors themselves recognize).
“Normal” ranges for blood chemistries are determined by the central 95% of distribution among a “healthy” population, or in some cases by 99th percentile upper reference limit. I don’t know what applies for vit D.
In any event, if your contention is that the currently accepted “normal” for vitamin D is in fact still physiologically deficient, then it should make it EASIER for you to prove a benefit of supplementation. Yet despite your data dump, I see no such proof on offer.
Much of what you quoted are associations. On their best day, they can only be hypothesis-generating.
The post op infections paper was only association.
The “peer reviewed” paper by Dr. Sunil W. wasn’t even a study of any sort….just a navel gazing exercise by someone who has drank the koolaid….and perhaps made the koolaid himself.
The 2020 Spanish Covid paper does seem to have been a proper study….although even the authors acknowledge the need for much larger confirmatory trials. You can’t draw too firm a conclusion based on 76 patients. Also, I’m curious about word-choice as they seem to use “allocate” and “randomize” interchangeably. Perhaps it is a language issue. But in their conclusion they note a need for “larger trials with groups properly matched”….and “proper matching” is not a concern for an actual RCT.
So despite all the verbiage and the enormous links, I see absolutely bupkis proving vit D to be causally of benefit in an adequately sized and powered RCT. Where’s all this hot air coming from, bud?
The 25-hydroxyvitamin D levels of most people who do not supplement vitamin D properly and who have not had recent extensive UV-B exposure of ideally white skin are indeed normal, but they are not healthy.
The Massachusetts General Hospital study shows very clearly that immune responses against bacterial pathogens which cause post-operative infections decline the further the preoperative 25-hydroxyvitamin D level was below 50 ng/mL. Even if half or 3/4 of this is due to confounding - and even 1/4 is difficult to imagine - this is still a very strong association with the causality flowing from pre-operative 25-hydroxyvitamin D to post-operative 25-hydroxyvitamin D which many types of immune cell need to run their intracrine signaling systems, which are a crucial part of how each cell responds to its changing circumstances.
You can read about 25-hydroxyvitamin D to calcitriol intracrine signaling at: https://vitamindstopscovid.info/00-evi/#02-compounds. Most doctors and immunologists are not aware of this at all. My web page is full of research which shows how important it is to attain at least 50 ng/mL circulating 25-hydroxyvitamin D.
Thanks for looking at Castillo et al. 2020. As I wrote at: https://vitamindstopscovid.info/00-evi/#castillo, Jungreis and Kellis at MIT wrote a preprint https://www.medrxiv.org/content/10.1101/2020.11.08.20222638v2 in which they argue that even accounting for the fact that the randomization happened to put patients with more comorbidities into the control group, the results of this RCT are still a very powerful argument for this intervention, which raised 25-hydroxyvitamin D levels generally over 50 ng/mL in a few hours. The researchers - and Jungreis and Kellis - did not seem to know how fast this was. Bolus oral (or injected) vitamin D3, such as 10 mg 400,000 IU, takes several days. I found a patent https://patents.google.com/patent/WO2016124724A1/ which graphs the 25-hydroxyvitamin D level curve after the exact same 0.532 mg calcifediol oral dose, using the exact same 0.266 mg capsules.
Who are you to insult Prof Wimalawansa or expect anyone to take seriously your broad-brush condemnation of his peer-reviewed article and vitamin D3 supplementary intake recommendations? Your contributions to science and health? His CV: https://www.ama-assn.org/system/files/2019-03/bio-sketch-sunil-wimalawansa_0.pdf.
By all means wait for an RCT which raises all participants' 25-hydroxyvitamin D levels over 50 ng/mL for a few years and surveys all cause mortality, every disease and health condition etc. I wish we had such a study.
Your desire to wait - and to encourage others to wait - probably for a decade or two, might make more sense if the intervention was some new drug, vaccine, mRNA etc. gene therapy, monoclonal antibody, surgery or implanted device. However, the intervention is to attain at least 50 ng/mL circulating 25-hydroxyvitamin D, rather than 5 to 25 (with somewhat higher levels in summer for white-skinned people) in the context of our immune systems having evolved in African Ancestors with much higher 25 hydroxyvitamin D levels than the great majority of the population of temperate countries today. The only research along these lines is Luxwolda et al. 2012 "Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/L (46 ng/mL)" https://doi.org/10.1017/S0007114511007161.
"We measured the sum of serum 25-hydroxyvitamin D2 and D3 (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (sd 10) years, 43 % male) and twenty-five Hadzabe hunter–gatherers (35 (sd 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible."
The average 25-hydroxyvitamin D level was 115 nmol/L 46 ng/mL.
You apparently did not find much of value in the research I cite and discuss at: https://vitamindstopscovid.info/00-evi/ . Most people who are concerned about their health, the health of their loved ones and of the public in general are not so avoidant. Most such people are not as keen as you seem to be to defend the current, clueless, position of mainstream medicine regarding 25-hydroxyvitamin D and the immune system.
Causation does NOT flow from association. We can have a separate discussion about Bradford Hill criteria regarding when an exception to that rule may be in order (eg. Smoking). But let’s just say the case for vitamin D is nowhere on par with that.
As I said, that Spanish RCT seems legit and its authors are to be commended for being appropriately conservative in their conclusions (rather than making wild claims not supported by the evidence). So the answer is not to excessively navel gaze at a 76 patient study; the answer is to take the hypothesis it generated, and to test it properly and prospectively in an adequately powered study.
I couldn’t tell Prof W from a hole in the ground. And appeals to authority are meaningless, intellectually weak, and of zero persuasive use on me. If he had the evidence of vitamin D benefit, he should bring it. He hasn’t. Someone who relies on his authority to make claims without evidence is a scheister until proven otherwise. In my field, someone like Eugene Braunwald enjoys much deference. But even for him, I’d only listen when he speaks from a position backed by evidence, and not otherwise.
The research you cited without exception is fine for generating hypotheses, but is woefully inadequate for changing practice. As an apparently enthusiastic proponent, the burden is on you to generate proper evidence to substantiate your claims. You may well be proven correct in the future. But I am only persuaded by evidence, and not enthusiasm. Your reliance on people wanting to be healthy is EXACTLY the formula used by scheisters who sell snake oil.
Your rejection of perfectly good evidence strikes me as clueless and overly trusting of current mainstream medical opinion. This is about correcting a deficiency, not introducing a new drug or vaccine.
Post operative infections do not cause low pre-operative 25-hydroxyvitamin D. So unless there is significant confounding - and you haven't suggested how this might be the case - low pre-operative 25-hydroxyvitamin D causes a greatly increased risk of post-operative infections.
I was not suggesting an appeal to authority - just that Prof. Wimalawansa's contributions to science and health are greater than yours. You doubled down on your insulting statements about him - someone you don't even know. Yet you couldn't be bothered stating what you think is wrong with his vitamin D3 supplemental intake guidelines or anything else he wrote. I looked at your profile to see if you had written anything constructive or told us anything about yourself, but you hadn't. You apparently read 27 Substacks, but have never Liked an article (post) or comment. You have never written an article or a note.
Btw, you should know that your fundamental assertion makes no sense in terms of evolutionary biology.
If humans actually needed the “higher” levels of vitamin D than is seen among current population normals, then selection pressure would have resulted in a genetic advantage for those with such higher vitamin D levels. The result of this selection is that current “normals” would reflect what you contend to be the “real” required amount of vitamin D.
So not only does your assertion lack proper scientific support, but it also runs counter to Darwin.
Low 25-hydroxyvitamin D levels have been a problem for an increasingly large proportion of humanity since the migrations out of Africa into northern Europe, Siberia and other locations far from the equator. The evolutionary response in these populations was to evolve genes which reduced melanin pigmentation, except to a small extent when exposed to extensive ultraviolet light. However, the lack of UV-B light ca. 297 nanometres (at the extreme short-wavelength, high frequency, high energy per excited electron) range of the solar radiation which reaches the Earth's surface) far from the equator, most especially in winter, means that no-one can produce enough vitamin D3 cholecalciferol to sustain 50 ng/mL circulating 25-hydroxyvitamin D.
The only way known in nature or industry https://sci-hub.se/10.1016/B978-0-12-381978-9.10006-X of producing vitamin D3, or any similar molecules, is by breaking one of the bonds in one of the carbon rings of 7-dehydrocholesterol or a similar molecule. No-one knows a chemical approach to this. The only way is the photochemical approach which requires this short wavelength, high energy per excited electron, UV-B light. These wavelengths always damage DNA and so kill cells and raise the risk of cancer.
In the past tens of thousands of years, as today, populations survived far from the equator, but they do not thrive - as can be seen by the prevalence of disease in countries like the UK today. The seasonality of influenza should be your first clue as to how this works - low 25-hydroxyvitamin D in winter and spring enables the virus to infect cells more easily, since the immune cells do not have as much 25-hydroxyvitamin D as they need to run their intracrine and paracrine signaling systems properly.
There isn't a way the immune cells can work properly with less than this, unless perhaps they all evolved an active transport system for 25-hydroxyvitamin D across their cell walls, as is the case with the kidney cells which produce calcitriol to go into circulation as a hormone. The immune and other cells which use 25-hydroxyvitamin D to produce 1,25-dihydroxyvitamin D calcitriol as an intracrine signaling agent only do so when a particular cell-type specific condition is detected. (https://vitamindstopscovid.info/00-evi/#02-compounds). They need to produce an internal level of calcitriol which clearly exceeds the hormonal background level, which diffuses into the cells as well. That level is pretty low, ca. 0.05 to 0.1 ng/mL in the bloodstream. I am not aware of any research which measures the calcitriol levels inside cells when the intracrine signaling system runs properly. I suspect there is no reliable way of measuring this at present.
Maybe one day, after hundreds of thousands or millions of years, immune cells might evolve to work well with lower levels of 25-hydroxyvitamin D. However, at present, we need 50 ng/mL to be healthy.
So once again, an impressive exercise in biologic plausibility. That seems like a fantastic and testable hypothesis.
Where is the RCT that proves supplementation of vit D to more than 50 ng/mL “improves health”?
As I wrote earlier, I am not aware of any RCT which raises the intervention group's 25-hydroxyvitamin D level over 50 ng/mL and has a suitably long time, such as a few years, to collect all manner of health data. I wish there was one. Maybe there will be one in the next ten years - that would be great.
You want to wait for the golden RCT on a silver platter before you might contemplate vitamin D3 supplementation. Good luck with your risks of dementia in the decades to come: https://vitamindstopscovid.info/00-evi/#3.3.
Other folks take an interest in and come to understand the mechanisms, such as by reading what Chauss et al. found about permanently inflammatory Th1 regulatory lymphocytes in the lungs of hospitalised COVID-19 patients: "Autocrine vitamin D signaling switches off pro-inflammatory programs of Th1 cells" Nature Immunology 2021-11-11 https://www.nature.com/articles/s41590-021-01080-3. (They are actually studying intracrine signalling - autocrine is with the receptors on the outside of the cell, but here they are in the cytosol. I made the same mistake at first). My summary of this dense cell biology article, or at least of its preprint, is at: https://aminotheory.com/cv19/icu/#2021-Chauss. These cells, unlike the cells from healthy controls, failed to transition from their pro-inflammatory startup program to their anti-inflammatory shutdown program, despite detecting the condition to do so. The researchers concluded (in the final article) that this failure was due largely or entirely to inadequate supplies of 25-hydroxyvitamin D. The circulating 25-hydroxyvitamin D levels of the patients was not available, but it is well known that even lower 25-hydroxyvitamin D levels than the poor levels in the general population (compared to 50 ng/mL) are most likely to develop severe COVID-19 symptoms.
Once such folks understand the mechanisms which explain the observational evidence for immune system failure in proportion to how much below 50 ng/mL the circulating level of 25-hydroxyvitamin D level is, and recognise that absent high levels of UV-B skin exposure all year round, they can only attain this by vitamin D3 supplementation, they get very interested since the risks are so low and the benefits so important and pervasive.
They don't feel they need to wait for the golden RCT before taking supplements which will, very likely, improve their health in many respects. You do, which is your choice.
Your writing here seems to be intended to scare off other people from taking action to boost their 25-hydroxyvitamin D level before any such RCT proves, beyond reasonable doubt, that significant benefits would accrue from such supplementation. You haven't detailed any risks. Your evident concern about such risks and the need for this ideal RCT would probably be more persuasive if they knew you were a highly experienced researcher and/or clinician who had demonstrated great judgement and insight over multiple decades AND/OR if you substantiated your complaints properly. I don't know about other people reading these comments, but I know nothing about you beyond your comments to this article, in which you argue for an RCT for effectiveness of a rotavirus vaccine (which I agree with) with the (ideally, who knows??) rare adverse reactions being studied after the vaccine is widely deployed.
I argue that any vaccine needs to be studied for years with one or more RCTs precisely to detect such adverse reactions, which can be permanently debilitating or deadly.
If you will permit me an appeal to a (prior, not now) authority, none less than Dr Fauci, here goes: He wrote an article attesting to a fundamental effectiveness limitation of the COVID-19 injections in January 2023: Morens, Taubenberger and Fauci "Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses" Cell Host & Microbe 2023-01-11: https:// www.cell.com/cell-host-microbe/fulltext/ S1931-3128(22)00572-8:
". . . it is not surprising that none of the predominantly mucosal respiratory viruses have ever been effectively controlled by vaccines. This observation raises a question of fundamental importance: if natural mucosal respiratory virus infections do not elicit complete and long-term protective immunity against reinfection, how can we expect vaccines, especially systemically administered non-replicating vaccines, to do so? This is a major challenge for future vaccine development, and overcoming it is critical as we work to develop 'next-generation' vaccines."
That was concerning effectiveness, which you and I agree should be established robustly via one or more RCTs before clinical deployment.
I am with Dr Fauci's former self in supporting RCTs to discover adverse affects, which you think needn't be done. The dangers of widely deploying vaccines without a decade or more research are well known. Dr Fauci attested to this in 1999: https:// rumble.com/v20t87i-1999-fauci-said-it-could-take-up-to-12- years-for-everyone-to-realize-the-da.html. This video also includes him stating, in 2020, that a great deal of research is needed to ensure that the vaccine does not cause ADE (antibody dependent enhancement), in which the vaccine - he cites an example of an RSV vaccine - "paradoxically made the children worse" and an experimental HIV vaccine which made people more likely to become infected.
Aaron Siri and team have a list of the vaccines currently on the US childhood vaccine schedule: https://icandecide.org/article/childhood-vaccine-trials-summary-chart/. They claim "None of the vaccine doses the CDC recommends for routine injection into children were licensed by the FDA based on a long-term placebo-controlled trial."
Can you check their several dozen references before lunch?* I am kinda busy.
Assuming their claim is correct, do you think all these vaccines should be withdrawn from use until such RCTs are done, which would take a decade or so?
Alternatively, do you think that the limited testing they have done on these is good enough to prove their effectiveness, with the ill-effects left to be investigated as they harm and kill ordinary people who are enticed or forced to accept these vaccines on the premise that they are proven to be safe and effective?
* You wrote, in another comment https://www.sensible-med.com/p/rotavirus-vaccination-deserves-nuanced/comment/123846399: "I review more literature before lunch than most people read in a year."
“I don't know about other people reading these comments, but I know nothing about you beyond your comments to this article”
—forgot about this bit.
I do not claim to be an authority (at least on this forum).
Yet my arguments here do not require any authority.
One does not need to be a bigwig to demand proper evidence of efficacy prior to adoption of a therapeutic regimen.
The position I take here is sufficiently straightforward and fundamental to the scientific method (and logic in general) that it could be made by just about anybody.
“I am not aware of any RCT which raises the intervention group's 25-hydroxyvitamin D level over 50 ng/mL and has a suitably long time, such as a few years, to collect all manner of health data”
—- y’know, you really shoulda led with that. And maybe display that short phrase prominently somewhere on that extremely verbose site you like to link to (maybe you have….I certainly did not bother scrolling through all of it).
Now, are you aware of all the RCT of vitamin D that have shown NO benefit? (To be fair, I’d never heard of the assertion of a need for “supra-normal” levels of vitamin D, so this magical 50ng/mL business has probably not been specifically tested in RCT…which is a fact you now admit).
VITAL- null on CV events and cancer
D2D- null on prevention of diabetes
ViDA- null for CV events
WHI- null on fracture reduction
So, let’s check the tape, shall we?
Several RCT of vitamin D that have shown no benefit (that I’m aware of; I imagine there are more, but this is not an area that I follow outside of my field). I certainly haven’t heard of any positive RCT for vitamin D in any field that is sufficient to be practice- changing.
Just as a logic lesson, you can’t PROVE a NEGATIVE. So I do NOT assert that vitamin D supplementation is of NO benefit. But since you assert that vitamin D supplementation IS OF benefit, the burden of proof is on you to provide evidence which sustains your assertion…which you don’t have.
So do I want to wait before taking vitamin D? Yeah. Cuz I need to see some evidence of benefit first. The real question is why you don’t have such a need.
Dementia you say? Absolutely terrible. And is this where you start the scheister routine? “Avoid dementia, take Vit D”? lol. Is this the new marketing strategy?
“They don't feel they need to wait for the golden RCT before taking supplements which will, very likely, improve their health in many respects.”
—-😂 that’s cuz “they” are suckers who will do things without evidence. Like I’ve said before, as long as there are suckers in the world, there will be scheisters who will happily rip them off…and there will always be scheisters. Your latest post is the blueprint for snake oil salesmen. Step 1- find scary ailment; step 2- concoct fancy theory of why your product will magically fix said ailment, which is just plausible enough to be believable (by suckers); step 3-take said suckers to cleaners.
Your routine is indeed tried and true, bud. No doubt you fleece many suckers with this. I’m just not one of them.
Your “perfectly good evidence” is mostly (Spanish 2020 study being a noted exception) observational data which counts as low quality evidence to me. Perhaps I’m simply a more discerning consumer of evidence than you are.
I’ve stipulated that “correcting a deficiency” is a reasonable indication for supplementation. But you’ve asserted that population “normals” still in fact denote physiologic deficiency. That’s an assertion which accrues the burden of evidence on you. This is how logic and science work. The fact that I need to explain this to you makes me wonder how much you actually know about the scientific method (my guess is “not very much”). All you need to do is produce evidence which supports your claims. You seem very confident in your claims. So presumably it won’t be hard to conduct proper studies to sustain those claims. One wonders what you’re waiting for.
“Unless there is significant confounding” - and how do you prove causation and eliminate concerns about confounding? You guessed it, a proper RCT. These truths are cold, and hard. Best get used to them (or perhaps learn them for the very first time).
I don’t need to know “Dr. W” to know he’s shovelling manure based on what I’ve read here. Again, all he needs to do is to bring proper evidence rather than unsubstantiated opinion. Any proper self-respecting scientist would know that. Which makes me really wonder whether he actually is one. Maybe that’s why you’re so enamored with him…birds of a feather, as they say.
What’s wrong with his “guidelines”? Everything. Cuz they’re not based on high quality evidence. This should not be a difficult concept (and one you seem to desperately need to learn).
I don’t purport to be a writer. I also know my limitations. That seems already to exceed the level attained by you, this Dr W dude, and scheisters of similar ilk.
Hi Steve, If you want to help people like me avoid hypothesizing that your comments here regarding the vitamin D compounds are indistinguishable from the rantings of some rando on the Internet, you might want to go easy on the personal invective and flesh out your profile with links to constructive statements, dialogue, debate etc. and some description of yourself.
I have already presented evidence that less than 50 ng/mL causes, in large part, a greatly increased risk of post-operative infections. The only research we have regarding long-term African ancestral 25-hydroxyvitamin D levels is a mean of 46 ng/mL. So what is normal for the unsupplemented or under-supplemented populations of temperate countries is not normal in long-term human evolutionary history. More importantly, it is not healthy.
It is better that readers here review the most pertinent research via links at: https://vitamindstopscovid.info/00-evi/ than me try to cite and discuss it in this comments thread, especially since I can't post graphs here.
I’m not going to read through the entire data dump.
But i did find this section comical:
“While this is not provably the case with current variants, the transmission and severity of all COVID-19 variants can best be reduced by ensuring that as many people as possible have at least 50 ng/mL (125 nmol/L) 25-hydroxyvitamin D levels AND that they are provided with multiple early treatments,…”
—-so you can’t “prove” it, but you still advocate for as many people as possible to follow your advice anyway.
Ummm…based on what, exactly?
I review more literature before lunch than most people read in a year. If you feel a call for high quality (or even decent quality) evidence is the ranting of a rando, that’s fine by me. I certainly consider your blind, ignorant, and shameless shilling for Vit D supplementation to be highly pathetic.
To be clear, you have NOT “already provided evidence that less than 50ng/mL causes” the square root of sweet jack all. What you have provided are associations (which are very much NOT the same as proof of causation). And in conflating the two repeatedly, what you have also NOT shown is any grasp of the scientific method.
My challenge is simple: provide proof of causation via properly powered prospective RCT showing that supplementation with vitamin D (in whatever formulation you prefer, to a level that exceeds whatever concentration that floats your boat) produces clinical benefit using whatever endpoint you feel like. I’m intentionally keeping your options as diverse as possible so that the bar is very low….since at this point you haven’t provided causative proof of anything (and if there is something in your data dump that fits the bill, please link to it so I don’t have to wade through all that nonsense).
What you seem to like to provide is biologic plausibility. That’s fine for a hypothesis. But what you lack is any evidence that sustains your hypothesis (and I’ve acknowledged the one Spanish 2020 study which was decent but whose limitations even the authors themselves recognize).