The placebo discussions which precede my comment are interesting and a valuable lesson. Since COVID I have difficulty reading pack inserts without wondering if I can trust the data citations. Only a dive into the raw data by fresh eyes will give me a better feeling.
And, by the way, I had been in practice for almost 40 years mostly with a large organization and had never heard of VAERS until it was publicized in 2021.
Gladwell is after clicks so it’s not surprising that he’s only presenting part of the truth. It’s disappointing that the HHS secretary is not holding himself to a higher standard than your generic podcaster. But such is the MAGA/MAHA way it seems. (I’m very happy about the appointments of Drs. B, M, and P….but the nonsense-to-signal ratio is pretty high overall).
I think Dr. JMM has made this point eloquently in the past: we need RCT to define efficacy; but we need to rely on registry data to really parse out safety signals, since they tend to be rare.
Why vaccinate children to protect them from severe symptoms of rotavirus infection, when proper vitamin D3 supplementation, to attain the 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D the immune system needs to function properly, will greatly reduce the incidence of severe diarrhea? *
"Seventy patients with rotaviral diarrhea and 67 healthy patients were enrolled in this study. . . .
"There were no differences between the groups with regard to gender and age, but 25(OH)D3 was significantly different: 14.6 ± 8.7 ng/mL in the rotaviral diarrhea patients versus 29.06 ± 6.51 ng/mL in the health controls (P < 0.001), and serum 25(OH)D3 <20 ng/mL (OR, 6.3; 95%CI: 3.638–10.909; P < 0.001) was associated with rotaviral diarrhea."
25-hydroxyvitamin D levels rise and fall over weeks and months. There's no reason to believe that such stark differences in 25-hydroxyvitamin D are explained to any significant extent, by the infection lowering these levels (reverse causality). Therefore, unless there is some other significant factor which is linked to 25-hydroxyvitamin D levels and which affecting severity, the low 25-hydroxyvitamin D level is a very significant *cause* of the severe symptoms.
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
These recommendations are included in a recent article with another professor of medicine Scott T. Weiss and professor of pediatrics Bruce W. Hollis: https://www.mdpi.com/2072-6643/16/22/3969. All three have been researching vitamin D for decades.
There's very little vitamin D in food, whether it is fortified with vitamin D3 or the the less effective D2. While UV-B exposure of ideally white skin can produce plenty of vitamin D3, this is not available all year round far from the equator - and it always damages DNA and so raises the risk of skin cancer.
Vitamin D3 and 25-hydroxyvitamin D (made primarily in the liver, over several days, from vitamin D3) are not hormones. They are not signaling molecules. Multiple types of immune cell require a good supply of 25(OH)D to run their 25(OH)D -> calcitriol (1,25-dihydroxyvitamin D) intracrine signaling signaling systems. Each such system operates entirely within a single cell, and is crucial to the ability of the cell to adapt its behavior in response to its changing circumstances.
Calcitriol has one well-known hormonal function - when the kidneys maintain a very low level (0.05 to 0.1 ng/mL) in the bloodstream, where it acts as a long-distance endocrine signaling molecule (hormone) which affects the behavior of several cell types which are involved in calcium-phosphorus-bone metabolism.
Unfortunately, the great majority of doctors and immunologists have never heard of 25-hydroxyvitamin D -> calcitriol intracrine signaling. (See https://vitamindstopscovid.info/00-evi/#02-compounds for a tutorial.) Likewise many people who write vitamin D research articles. They falsely believe that increased 25(OH)D increases the level of circulating calcitriol (which it does to small degree) and that this somehow "boosts" the immune system. However, the immune system does not use hormonal signaling and is not significantly affected by the 0.05 or 0.1 ng.mL level of calcitriol circulating in the bloodstream.
Fortifying food with vitamin D3 or the less effective vitamin D2 can marginally improve extremely low 25-hydroxyvitamin D levels, but it cannot attain the 50 ng/mL 125 nmol/L level of circulating 25-hydroxyvitamin D the immune system needs to work properly. Such fortification would give false assurances to many people. I argue that all effort which could go into fortifying food with vitamin D3/2 would be better directed to supporting proper vitamin D3 supplementation: https://vitamindstopscovid.info/00-evi/#07-fortif.
* The answer of course is that there is millions or billions of dollars to be made from vaccines, that the medical profession and much of the public is overly focused on vaccines and that many medical professionals take far too little interest in nutrition.
Do you have RCT data to support your claims for the purported benefits of Vit D supplementation (esp for individuals who are not “deficient”)?
And if you’re going to implicate money-trails, it would be remiss to leave out the billions of $ that go into the “supplements” industry, which itself is largely unregulated and are not constrained against making claims without substantiation.
With a proper definition of 25-hydroxyvitamin D levels, an RCT involving vitamin D3 supplementation for people who are "not deficient" would produce no improvement in health.
Governments and many medical professionals regard 20 ng/mL (50 nmol/L = 1 part in 50,000,000 by mass) circulating 25-hydroxyvitamin D as "sufficient". However, this is sufficient, in general, only for the best known function of 25-hydroxyvitamin D: to supply the kidneys so cells there can hydroxylate some of it into a very low (ca. 0.05 to 0.1 ng/mL) level of circulating 1,25-dihydroxyvitamin D (calcitriol). This functions as a hormone (a long distance blood borne signaling molecule) to alter the behavior of several cell types which are involved in calcium-phosphate-bone metabolism.
However a proper definition of sufficiency would be about 50 ng/mL, since below that, we see, in general worse outcome for numerous infectious diseases. Most clearly and dramatically, we see the risks of (usually bacterial) post-operative infections rising enormously the further below 50 ng/mL the pre-operative 25-hydroxyvitamin D level is. See the graphs at the end of the PDF (they are not in the web page version) of Quraishi et al. (Massachusetts General Hospital doctors) 2014: https://jamanetwork.com/journals/jamasurgery/articlepdf/1782085/soi130062.pdf. Discussion and the two graphs combined: https://vitamindstopscovid.info/00-evi/#00-50ngmL 2.5% risk of hospital acquired infections and 2.5% risk of surgical site infections at 50ng/mL both rise to about 25% at 20 ng/mL.
This has nothing to do with circulating hormonal 1,25-dihydroxyvitamin D (calcitriol), which is hardly altered by higher 25-hydroxyvitamin D levels. Multiple types of immune system need a good supply of 25-hydroxyvitamin D for their intracrine signaling systems, which are crucial to the ability of individual cells to respond to their changing circumstances.
A Substack comment is not the place to explain all this - please see a proper explanation with numerous links to peer-reviewed articles: https://vitamindstopscovid.info/00-evi/.
If the question is about RCTs for people who have 20 to 30 ng/mL circulating 25-hydroxyvitamin D, these won't show much benefit regarding calcium-phosphate-bone metabolism, but should, ideally, if they are sufficiently powered and take place over suitably long time frames, show benefits in numerous aspects of health regarding the immune system. I don't know of an RCT of sufficient length which raised all the intervention group's 25-hydroxyvitamin D levels to at least 50 ng/mL. Some doctors regard this as potentially toxic, but they are mistaken.
The patients in the Quraishi et al. retrospective study who had 25-hydroxyvitamin D levels above 20 ng/mL or so would have attained this entirely, or almost entirely, by robust vitamin D3 supplementation. They were morbidly obese and all had the same Roux-en-Y gastric bypass operation for weight loss. They cannot have received so much vitamin D3 from food, fortified or not, and it would be extremely difficult (especially in Massachusetts) to attain 50 ng/mL from sun or artificial UV-B exposure, people suffering from obesity tend to to produce little vitamin D3 in this way, relative to body mass. This is not an RCT, but it shows the benefits of raising 25-hydroxyvitamin D levels above 20 or 30 ng/mL. The need more vitamin D3 as a ratio of body mass anyway to attain a given 25-hydroxyvitamin D level. See: https://5nn.info/temp/250hd-obesity/.
A similar study Levanio et al. 2020 "Association between preoperative levels of 25-hydroxyvitamin D and hospital-acquired infections after hepatobiliary surgery A prospective study in a third-level hospital" https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230336 reports that the risk hospital acquired infections decreased by 34% for every 10.5 ng/mL increase in pre-operative 25-hydroxyvitamin D levels. The lower tertile had a range of 3.5 to 10 ng/mL preoperative circulating 25-hydroxyvitamin D and the upper tertile had a range 17.2 to 89.2 ng/mL. The upper tertile had 47.6% of the risk of hospital aquired infections with respect to the lower tertile.
Confounding, such as healthier people happening to supplement vitamin D substantially, might explain at best a small fraction of this highly significant association. As with the Quraishi study, those patients (in Spain) with more than about 30 ng/mL would have attained this mostly or entirely with substantial vitamin D3 supplementation, well above the lousy 20 micrograms (800 IU) recommended for adults by most governments and many doctors.
There's plenty of robust evidence of the importance of higher than 20 ng/mL circulating 25-hydroxyvitamin D enabling better immune responses. RCTs are not the only form of evidence from which reliable nutrition guidance can be derived A subset of these research articles are cited and discussed at: https://vitamindstopscovid.info/00-evi/.
For instance, Castillo et al. 2020 was an RCT in which hospitalised COVID-19 patients were randomized to receive 0.532 mg calcifediol, which *is* 25-hydroxyvitamin D on admission. This goes straight into circulation and raise the level of 25-hydroxyvitamin D over 50 ng/mL (average, so not every person) in 4 hours or less. (The researchers did not know it was so fast.) This drastically reduced the rate of transfer to intensive care and reduced the death rate to zero. See: https://www.sciencedirect.com/science/article/pii/S0960076020302764 and https://www.medrxiv.org/content/10.1101/2020.11.08.20222638v2. My discussion of this important RCT, which should have changed the course of the COVID-19 pandemic, but was almost entirely ignored: https://vitamindstopscovid.info/00-evi/#castillo .
“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?
Treating a child with lifelong chronic health conditions (ex: asthma, diabetes, various auto immune, cancer, etc... ) is way more lucrative (i would guess TRILLIONs of $) for pharma. The whole "supplements cost money too, so how do you know they really work either" argument is a red herring.
(R&D)Pharma products cost $ to be sure. But they have passed some measure of efficacy prior to marketing approval. We can certainly quibble about how “effective “ some approved meds actually are. But there’s no comparison with supplements.
The only thing you’re guaranteed to have, by taking supplements, is expensive urine.
The really hilarious part is when people shun the stuff that has shown some measure of efficacy, whilst embracing all the garbage that hasn’t.
I remain grateful for these nuanced discussions and also for RFK Jr for forcing these discussions to happen. I elected not to give the rotavirus vaccine to my baby. When I read the data- it didn't seem like it was supported. So I was surprised by Adam's article a little while ago that talked about how amazing the rotavirus vaccine was. But I can see it may be "amazing" in low income countries.
I think the rationale for including it never sat right with me "to reduce days away from work for parent".. no need to risk adverse events from an intervention in a healthy baby just to reduce days away from work for a parent. Anyway- that's what I remember from my research a few months ago.
1) There is an inflection towards increased death in the <12 months age group around the time of vaccine introduction in mid 2014. Figure 1 says vaccine coverage was very low in 2014, but this is misleading. ChatGPT tells me: "WHO guidelines and Kenya’s national immunization program recommend giving dose 1 of rotavirus vaccine between 6–14 weeks, with a strict upper age cutoff (typically around 24 weeks) for safety reasons (risk of intussusception)." So there is a death inflection signal exactly in time with vaccine rollout, and it is appearing in only one age group - the one that was vaccinated...
2) The drops ain all-cause mortality from rotavirus vaccine are implausible. For example, supplementary materials say 61% drop in the <12 months. This is inplausible. Only about 10% of deaths were diarrhea-related, and only a fraction of those would be from rotavirus. Massive healthy user bias, as always.
3) They say vaccination is treated as time-varying. Wouldn't this cause immportal time bias? Not the kind that favors the vaccine group, but favors the unvaccinated group? Some unvaccianted time could have come from people who were destined to not die, as they later get vaccinated. This should make the vaccine look less effective, yet it still looks implausibly effective. Healthy user bias is massive.
So what exactly is Kennedy's argument? The author does not say. Kennedy sometimes say things without elaboration. But this does not necessarily mean he doesn't have any.
Did I miss reading in your “nuanced discussion” what the comparator (placebo) was? Most of the vaccine trials compare the study drug (vaccine) against another vaccine which they call a “placebo”. A clever sleight of hand to make that 2.7% serious adverse reaction rate not look so bad. RFK has made that point and advocates for vaccine trials using a true placebo
A “vaccine” has an active ingredient + an adjuvant. Both components cause some immunogenicity. This immunogenicity may account for both efficacy/benefits and side effects/harms.
Whereas saline is inert and should contribute nothing to “effect” or “side effect”.
So if you study “vaccine”(active agent + adjuvant) vs saline, you will get a larger signal of effect AND a larger signal of side effect. Whereas a trial vs adjuvant will give a smaller signal on both counts.
Ideally, you would have a 3-arm trial of “vaccine” vs adjuvant vs saline, to be able to truly discern the effects and side effects of the active ingredient.
And the fact that virtually no vaccine approved for the childhood schedule has done a saline placebo test should speak volumes
I think Gardasil maybe had a small (~250 kids) third arm that was supposed to be saline, but i think they were later injected with the real product, thus eliminating the control group for long term study. Same thing was done to control groups in Pfizer C19 trials.
Well, live vaccines such as rotavirus, MMR, varicella, and shingles don't use adjuvants, so only inert placebos make sense. Agree in regard to inactivated vaccines.
"The study vaccine, the calcium carbonate buffer, and the placebo were developed and manufactured by GlaxoSmithKline Biologicals. The composition of the vaccine was the same as the commercial formulation, and the placebo was the same formulation without the viral antigen.11"
I can't find any evidence for your claim that the REST trial used a "saline placebo". Where are you getting this from?
The only description i could find in the linked study (or the package insert) is --- " Infants were randomly assigned, in a 1:1 ratio, to receive three 2-ml oral doses of vaccine or visibly indistinguishable placebo, 4 to 10 weeks apart."
"visibly indistinguishable placebo" does NOT mean saline. It might, but i'm willing to bet that like every other childhood vaccine, it's not. Probably the same solution as the vaccine, minus the antigen. This is a common trick to hide adverse events.
Thank you for weighing in. Looking back, I agree. It is not evident from the package insert, the NEJM publication, or elsewhere that the placebo consisted of simple saline. If the vaccine excipients were used, something like polysorbate 80 could potentially cause overlapping adverse reactions. Saline should be used in trials like this, but I realize this is not the case in many vaccine trials. This adds to the case that improved RCTs (with broad endpoints and saline placebo) are needed. Or at least better access to information like this.
I have never commented on a Substack article before and just upgraded to a paid subscription so I could do so now...
I strongly recommend the book "Turtles All the Way Down: Vaccine Science and Myth," published in English in 2022 by anonymous Israeli authors (you can imagine why they felt the need to be anonymous). I listened to it on Audible and it is unlike any vaccine book I've read before (and I've read a lot of them). It is a serious book with over 1,200 references in a separate PDF. You can read the first chapter and access the references PDF here: https:tinyurl.com/TurtlesBookChap1Eng
Chapter 1, 66-69: They go over Rotarix (withdrawn) and RotaTeq. At the time, there was no other oral vaccine used in the US that they could use as a placebo. Rotarix used the vaccine-sans-antigen for the control group. It's harder to determine what RotaTeq used "because Merck deleted its description from the licensing document submitted to FDA. It appears that the trial's placebo is a trade secret, which implies its contents were very similar to the vaccine's. Further examination of the RotaTeq documents support this hypothesis: In another RotaTeq trial, the control group received the vaccine-sans-antigen, similar to the compound control groups subjects received in the Rotarix trial" (68). Since RotaTeq is a live vaccine, it does not include an adjuvant like aluminum, but does contain polysorbate 80 and so on.
They also note that the Rotarix and RotaTeq trials had similar rates of intussusception and deaths.
Obviously it would have been cheaper and easier to use saline/sugar water for the placebo. If they did go to the expense and trouble of using the vaccine-sans-antigen, it is hard not to assume that this was done to obscure the real rate of adverse events. Also note the ethics: a true placebo has no health risks. The vaccine-sans-antigen is a useless substance with NO BENEFIT but likely the potential to do harm.
Also, the insert makes it clear that other vaccines could and were given concomitantly. While this is standard practice and would not effect the efficacy data, it certainly doesn't enhance the clarity of safety data.
I recommend the table (pages 72-75) which goes over many of the childhood vaccines and determines that none of them did safety trial RCTs with a true placebo.
This is why RFK Jr recently called for all new vaccines to be tested against inert placebos, because despite appearances, a great many are not.
I too took up a paid subscription so I could comment - on how severe symptoms and so death due to rotovirus infection are "associated with" - in this case very significantly caused by - low 25-hydroxyvitamin D levels, such as 15 ng/mL on average, which is 30% of the level the immune system needs to function properly.
It took me a minute or so to find the relevant article, from 2015, since it is the first article listed by Google Scholar when searching for rotavirus and "vitamin D".
Wouldn't you know....most of the placebo components are redacted...
Of the 29 vaccines in the ICAN table, only 2 had listed an INERT (saline) Placebo. The rest are tested against older vaccines (which themselves never underwent RCT testing against an INERT placebo), or the vaccine sans-antigen, or some EXPERIMENTAL compound (see Prevnar 7). No good reason for this except to hide harms.
Great to see a nuanced conversation about the pros and cons of specific vaccines in countries with low child mortality. If nothing else, RFK has made it possible to have these discussions. Until now childhood vaccines has been a sacred cow of medicine whose risk/benefit value could never be debated in the same way we debate the value of other therapeutic interventions. I see that as a win for evidence-based medicine.
The placebo discussions which precede my comment are interesting and a valuable lesson. Since COVID I have difficulty reading pack inserts without wondering if I can trust the data citations. Only a dive into the raw data by fresh eyes will give me a better feeling.
And, by the way, I had been in practice for almost 40 years mostly with a large organization and had never heard of VAERS until it was publicized in 2021.
Gladwell is after clicks so it’s not surprising that he’s only presenting part of the truth. It’s disappointing that the HHS secretary is not holding himself to a higher standard than your generic podcaster. But such is the MAGA/MAHA way it seems. (I’m very happy about the appointments of Drs. B, M, and P….but the nonsense-to-signal ratio is pretty high overall).
I think Dr. JMM has made this point eloquently in the past: we need RCT to define efficacy; but we need to rely on registry data to really parse out safety signals, since they tend to be rare.
It is reasonable to critique and compare the content of what is claimed by these individuals.
It is unreasonable to treat their comments as if they have equal impact.
One is the head of HHS who makes “almost certainly false” claims. The other is a journalist who writes pithy books/articles in order to make money.
To say that both “selectively report and misinterpret data” is obvious.
I would not make Malcolm Gladwell the head of HHS.
I call for RFK Jr to resign and refuse to give him credit for making it possible to have vaccine discussions.
We can and should have those discussions apart from and in spite of whatever these guys say.
Why vaccinate children to protect them from severe symptoms of rotavirus infection, when proper vitamin D3 supplementation, to attain the 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D the immune system needs to function properly, will greatly reduce the incidence of severe diarrhea? *
I searched Google Scholar for:
rotavirus "vitamin D".
This lead directly to Bucak et al. 2015 "Is there a relationship between low vitamin D and rotaviral diarrhea?" Pediatrics International https://onlinelibrary.wiley.com/doi/epdf/10.1111/ped.12809 .
"Seventy patients with rotaviral diarrhea and 67 healthy patients were enrolled in this study. . . .
"There were no differences between the groups with regard to gender and age, but 25(OH)D3 was significantly different: 14.6 ± 8.7 ng/mL in the rotaviral diarrhea patients versus 29.06 ± 6.51 ng/mL in the health controls (P < 0.001), and serum 25(OH)D3 <20 ng/mL (OR, 6.3; 95%CI: 3.638–10.909; P < 0.001) was associated with rotaviral diarrhea."
25-hydroxyvitamin D levels rise and fall over weeks and months. There's no reason to believe that such stark differences in 25-hydroxyvitamin D are explained to any significant extent, by the infection lowering these levels (reverse causality). Therefore, unless there is some other significant factor which is linked to 25-hydroxyvitamin D levels and which affecting severity, the low 25-hydroxyvitamin D level is a very significant *cause* of the severe symptoms.
Please see the research cited and discussed regarding the vitamin D compounds and the immune system at: https://vitamindstopscovid.info/00-evi/.
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
These recommendations are included in a recent article with another professor of medicine Scott T. Weiss and professor of pediatrics Bruce W. Hollis: https://www.mdpi.com/2072-6643/16/22/3969. All three have been researching vitamin D for decades.
There's very little vitamin D in food, whether it is fortified with vitamin D3 or the the less effective D2. While UV-B exposure of ideally white skin can produce plenty of vitamin D3, this is not available all year round far from the equator - and it always damages DNA and so raises the risk of skin cancer.
Vitamin D3 and 25-hydroxyvitamin D (made primarily in the liver, over several days, from vitamin D3) are not hormones. They are not signaling molecules. Multiple types of immune cell require a good supply of 25(OH)D to run their 25(OH)D -> calcitriol (1,25-dihydroxyvitamin D) intracrine signaling signaling systems. Each such system operates entirely within a single cell, and is crucial to the ability of the cell to adapt its behavior in response to its changing circumstances.
Calcitriol has one well-known hormonal function - when the kidneys maintain a very low level (0.05 to 0.1 ng/mL) in the bloodstream, where it acts as a long-distance endocrine signaling molecule (hormone) which affects the behavior of several cell types which are involved in calcium-phosphorus-bone metabolism.
Unfortunately, the great majority of doctors and immunologists have never heard of 25-hydroxyvitamin D -> calcitriol intracrine signaling. (See https://vitamindstopscovid.info/00-evi/#02-compounds for a tutorial.) Likewise many people who write vitamin D research articles. They falsely believe that increased 25(OH)D increases the level of circulating calcitriol (which it does to small degree) and that this somehow "boosts" the immune system. However, the immune system does not use hormonal signaling and is not significantly affected by the 0.05 or 0.1 ng.mL level of calcitriol circulating in the bloodstream.
Fortifying food with vitamin D3 or the less effective vitamin D2 can marginally improve extremely low 25-hydroxyvitamin D levels, but it cannot attain the 50 ng/mL 125 nmol/L level of circulating 25-hydroxyvitamin D the immune system needs to work properly. Such fortification would give false assurances to many people. I argue that all effort which could go into fortifying food with vitamin D3/2 would be better directed to supporting proper vitamin D3 supplementation: https://vitamindstopscovid.info/00-evi/#07-fortif.
* The answer of course is that there is millions or billions of dollars to be made from vaccines, that the medical profession and much of the public is overly focused on vaccines and that many medical professionals take far too little interest in nutrition.
Do you have RCT data to support your claims for the purported benefits of Vit D supplementation (esp for individuals who are not “deficient”)?
And if you’re going to implicate money-trails, it would be remiss to leave out the billions of $ that go into the “supplements” industry, which itself is largely unregulated and are not constrained against making claims without substantiation.
With a proper definition of 25-hydroxyvitamin D levels, an RCT involving vitamin D3 supplementation for people who are "not deficient" would produce no improvement in health.
Governments and many medical professionals regard 20 ng/mL (50 nmol/L = 1 part in 50,000,000 by mass) circulating 25-hydroxyvitamin D as "sufficient". However, this is sufficient, in general, only for the best known function of 25-hydroxyvitamin D: to supply the kidneys so cells there can hydroxylate some of it into a very low (ca. 0.05 to 0.1 ng/mL) level of circulating 1,25-dihydroxyvitamin D (calcitriol). This functions as a hormone (a long distance blood borne signaling molecule) to alter the behavior of several cell types which are involved in calcium-phosphate-bone metabolism.
However a proper definition of sufficiency would be about 50 ng/mL, since below that, we see, in general worse outcome for numerous infectious diseases. Most clearly and dramatically, we see the risks of (usually bacterial) post-operative infections rising enormously the further below 50 ng/mL the pre-operative 25-hydroxyvitamin D level is. See the graphs at the end of the PDF (they are not in the web page version) of Quraishi et al. (Massachusetts General Hospital doctors) 2014: https://jamanetwork.com/journals/jamasurgery/articlepdf/1782085/soi130062.pdf. Discussion and the two graphs combined: https://vitamindstopscovid.info/00-evi/#00-50ngmL 2.5% risk of hospital acquired infections and 2.5% risk of surgical site infections at 50ng/mL both rise to about 25% at 20 ng/mL.
This has nothing to do with circulating hormonal 1,25-dihydroxyvitamin D (calcitriol), which is hardly altered by higher 25-hydroxyvitamin D levels. Multiple types of immune system need a good supply of 25-hydroxyvitamin D for their intracrine signaling systems, which are crucial to the ability of individual cells to respond to their changing circumstances.
A Substack comment is not the place to explain all this - please see a proper explanation with numerous links to peer-reviewed articles: https://vitamindstopscovid.info/00-evi/.
If the question is about RCTs for people who have 20 to 30 ng/mL circulating 25-hydroxyvitamin D, these won't show much benefit regarding calcium-phosphate-bone metabolism, but should, ideally, if they are sufficiently powered and take place over suitably long time frames, show benefits in numerous aspects of health regarding the immune system. I don't know of an RCT of sufficient length which raised all the intervention group's 25-hydroxyvitamin D levels to at least 50 ng/mL. Some doctors regard this as potentially toxic, but they are mistaken.
The patients in the Quraishi et al. retrospective study who had 25-hydroxyvitamin D levels above 20 ng/mL or so would have attained this entirely, or almost entirely, by robust vitamin D3 supplementation. They were morbidly obese and all had the same Roux-en-Y gastric bypass operation for weight loss. They cannot have received so much vitamin D3 from food, fortified or not, and it would be extremely difficult (especially in Massachusetts) to attain 50 ng/mL from sun or artificial UV-B exposure, people suffering from obesity tend to to produce little vitamin D3 in this way, relative to body mass. This is not an RCT, but it shows the benefits of raising 25-hydroxyvitamin D levels above 20 or 30 ng/mL. The need more vitamin D3 as a ratio of body mass anyway to attain a given 25-hydroxyvitamin D level. See: https://5nn.info/temp/250hd-obesity/.
A similar study Levanio et al. 2020 "Association between preoperative levels of 25-hydroxyvitamin D and hospital-acquired infections after hepatobiliary surgery A prospective study in a third-level hospital" https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230336 reports that the risk hospital acquired infections decreased by 34% for every 10.5 ng/mL increase in pre-operative 25-hydroxyvitamin D levels. The lower tertile had a range of 3.5 to 10 ng/mL preoperative circulating 25-hydroxyvitamin D and the upper tertile had a range 17.2 to 89.2 ng/mL. The upper tertile had 47.6% of the risk of hospital aquired infections with respect to the lower tertile.
Confounding, such as healthier people happening to supplement vitamin D substantially, might explain at best a small fraction of this highly significant association. As with the Quraishi study, those patients (in Spain) with more than about 30 ng/mL would have attained this mostly or entirely with substantial vitamin D3 supplementation, well above the lousy 20 micrograms (800 IU) recommended for adults by most governments and many doctors.
There's plenty of robust evidence of the importance of higher than 20 ng/mL circulating 25-hydroxyvitamin D enabling better immune responses. RCTs are not the only form of evidence from which reliable nutrition guidance can be derived A subset of these research articles are cited and discussed at: https://vitamindstopscovid.info/00-evi/.
For instance, Castillo et al. 2020 was an RCT in which hospitalised COVID-19 patients were randomized to receive 0.532 mg calcifediol, which *is* 25-hydroxyvitamin D on admission. This goes straight into circulation and raise the level of 25-hydroxyvitamin D over 50 ng/mL (average, so not every person) in 4 hours or less. (The researchers did not know it was so fast.) This drastically reduced the rate of transfer to intensive care and reduced the death rate to zero. See: https://www.sciencedirect.com/science/article/pii/S0960076020302764 and https://www.medrxiv.org/content/10.1101/2020.11.08.20222638v2. My discussion of this important RCT, which should have changed the course of the COVID-19 pandemic, but was almost entirely ignored: https://vitamindstopscovid.info/00-evi/#castillo .
“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?
Treating a child with lifelong chronic health conditions (ex: asthma, diabetes, various auto immune, cancer, etc... ) is way more lucrative (i would guess TRILLIONs of $) for pharma. The whole "supplements cost money too, so how do you know they really work either" argument is a red herring.
Not sure what you mean by red herring.
(R&D)Pharma products cost $ to be sure. But they have passed some measure of efficacy prior to marketing approval. We can certainly quibble about how “effective “ some approved meds actually are. But there’s no comparison with supplements.
The only thing you’re guaranteed to have, by taking supplements, is expensive urine.
The really hilarious part is when people shun the stuff that has shown some measure of efficacy, whilst embracing all the garbage that hasn’t.
I remain grateful for these nuanced discussions and also for RFK Jr for forcing these discussions to happen. I elected not to give the rotavirus vaccine to my baby. When I read the data- it didn't seem like it was supported. So I was surprised by Adam's article a little while ago that talked about how amazing the rotavirus vaccine was. But I can see it may be "amazing" in low income countries.
I think the rationale for including it never sat right with me "to reduce days away from work for parent".. no need to risk adverse events from an intervention in a healthy baby just to reduce days away from work for a parent. Anyway- that's what I remember from my research a few months ago.
The Kenya natural experiment suggests vaccine deaths to me:
https://www.mdpi.com/2076-393X/11/8/1299
1) There is an inflection towards increased death in the <12 months age group around the time of vaccine introduction in mid 2014. Figure 1 says vaccine coverage was very low in 2014, but this is misleading. ChatGPT tells me: "WHO guidelines and Kenya’s national immunization program recommend giving dose 1 of rotavirus vaccine between 6–14 weeks, with a strict upper age cutoff (typically around 24 weeks) for safety reasons (risk of intussusception)." So there is a death inflection signal exactly in time with vaccine rollout, and it is appearing in only one age group - the one that was vaccinated...
2) The drops ain all-cause mortality from rotavirus vaccine are implausible. For example, supplementary materials say 61% drop in the <12 months. This is inplausible. Only about 10% of deaths were diarrhea-related, and only a fraction of those would be from rotavirus. Massive healthy user bias, as always.
3) They say vaccination is treated as time-varying. Wouldn't this cause immportal time bias? Not the kind that favors the vaccine group, but favors the unvaccinated group? Some unvaccianted time could have come from people who were destined to not die, as they later get vaccinated. This should make the vaccine look less effective, yet it still looks implausibly effective. Healthy user bias is massive.
So what exactly is Kennedy's argument? The author does not say. Kennedy sometimes say things without elaboration. But this does not necessarily mean he doesn't have any.
Did I miss reading in your “nuanced discussion” what the comparator (placebo) was? Most of the vaccine trials compare the study drug (vaccine) against another vaccine which they call a “placebo”. A clever sleight of hand to make that 2.7% serious adverse reaction rate not look so bad. RFK has made that point and advocates for vaccine trials using a true placebo
It’s a research choice that needs to be made.
A “vaccine” has an active ingredient + an adjuvant. Both components cause some immunogenicity. This immunogenicity may account for both efficacy/benefits and side effects/harms.
Whereas saline is inert and should contribute nothing to “effect” or “side effect”.
So if you study “vaccine”(active agent + adjuvant) vs saline, you will get a larger signal of effect AND a larger signal of side effect. Whereas a trial vs adjuvant will give a smaller signal on both counts.
Ideally, you would have a 3-arm trial of “vaccine” vs adjuvant vs saline, to be able to truly discern the effects and side effects of the active ingredient.
And the fact that virtually no vaccine approved for the childhood schedule has done a saline placebo test should speak volumes
I think Gardasil maybe had a small (~250 kids) third arm that was supposed to be saline, but i think they were later injected with the real product, thus eliminating the control group for long term study. Same thing was done to control groups in Pfizer C19 trials.
As I noted above, I wouldn’t say a saline placebo is categorically “better” than an adjuvant placebo.
But I would agree that a 3-arm trial with both saline and adjuvant controls would provide the most clarity.
Well, live vaccines such as rotavirus, MMR, varicella, and shingles don't use adjuvants, so only inert placebos make sense. Agree in regard to inactivated vaccines.
Bingo! This is from the RCT cited:
"The study vaccine, the calcium carbonate buffer, and the placebo were developed and manufactured by GlaxoSmithKline Biologicals. The composition of the vaccine was the same as the commercial formulation, and the placebo was the same formulation without the viral antigen.11"
So it seems the placebo still has the adjuvant...
Which makes it ludicrous to call a "placebo"
I can't find any evidence for your claim that the REST trial used a "saline placebo". Where are you getting this from?
The only description i could find in the linked study (or the package insert) is --- " Infants were randomly assigned, in a 1:1 ratio, to receive three 2-ml oral doses of vaccine or visibly indistinguishable placebo, 4 to 10 weeks apart."
"visibly indistinguishable placebo" does NOT mean saline. It might, but i'm willing to bet that like every other childhood vaccine, it's not. Probably the same solution as the vaccine, minus the antigen. This is a common trick to hide adverse events.
Thank you for weighing in. Looking back, I agree. It is not evident from the package insert, the NEJM publication, or elsewhere that the placebo consisted of simple saline. If the vaccine excipients were used, something like polysorbate 80 could potentially cause overlapping adverse reactions. Saline should be used in trials like this, but I realize this is not the case in many vaccine trials. This adds to the case that improved RCTs (with broad endpoints and saline placebo) are needed. Or at least better access to information like this.
I have never commented on a Substack article before and just upgraded to a paid subscription so I could do so now...
I strongly recommend the book "Turtles All the Way Down: Vaccine Science and Myth," published in English in 2022 by anonymous Israeli authors (you can imagine why they felt the need to be anonymous). I listened to it on Audible and it is unlike any vaccine book I've read before (and I've read a lot of them). It is a serious book with over 1,200 references in a separate PDF. You can read the first chapter and access the references PDF here: https:tinyurl.com/TurtlesBookChap1Eng
Chapter 1, 66-69: They go over Rotarix (withdrawn) and RotaTeq. At the time, there was no other oral vaccine used in the US that they could use as a placebo. Rotarix used the vaccine-sans-antigen for the control group. It's harder to determine what RotaTeq used "because Merck deleted its description from the licensing document submitted to FDA. It appears that the trial's placebo is a trade secret, which implies its contents were very similar to the vaccine's. Further examination of the RotaTeq documents support this hypothesis: In another RotaTeq trial, the control group received the vaccine-sans-antigen, similar to the compound control groups subjects received in the Rotarix trial" (68). Since RotaTeq is a live vaccine, it does not include an adjuvant like aluminum, but does contain polysorbate 80 and so on.
They also note that the Rotarix and RotaTeq trials had similar rates of intussusception and deaths.
Obviously it would have been cheaper and easier to use saline/sugar water for the placebo. If they did go to the expense and trouble of using the vaccine-sans-antigen, it is hard not to assume that this was done to obscure the real rate of adverse events. Also note the ethics: a true placebo has no health risks. The vaccine-sans-antigen is a useless substance with NO BENEFIT but likely the potential to do harm.
Also, the insert makes it clear that other vaccines could and were given concomitantly. While this is standard practice and would not effect the efficacy data, it certainly doesn't enhance the clarity of safety data.
I recommend the table (pages 72-75) which goes over many of the childhood vaccines and determines that none of them did safety trial RCTs with a true placebo.
This is why RFK Jr recently called for all new vaccines to be tested against inert placebos, because despite appearances, a great many are not.
Read it, and learned so much
I too took up a paid subscription so I could comment - on how severe symptoms and so death due to rotovirus infection are "associated with" - in this case very significantly caused by - low 25-hydroxyvitamin D levels, such as 15 ng/mL on average, which is 30% of the level the immune system needs to function properly.
It took me a minute or so to find the relevant article, from 2015, since it is the first article listed by Google Scholar when searching for rotavirus and "vitamin D".
The best info I can find on this is from the ICAN "No Placebo Table"
https://icandecide.org/wp-content/uploads/2024/03/no-placebo-101823.pdf
For RotaTeq, the control is: "Polysorbate-80, Tissue Culture Medium, Fetal Bovine Serum, and Sodium Phosphate"
The table also links to a clinical review, which lists the vaccine and placebo components near the top of the page: https://icandecide.org/wp-content/uploads/2023/06/rotateq_placebo.pdf
Wouldn't you know....most of the placebo components are redacted...
Of the 29 vaccines in the ICAN table, only 2 had listed an INERT (saline) Placebo. The rest are tested against older vaccines (which themselves never underwent RCT testing against an INERT placebo), or the vaccine sans-antigen, or some EXPERIMENTAL compound (see Prevnar 7). No good reason for this except to hide harms.
Great to see a nuanced conversation about the pros and cons of specific vaccines in countries with low child mortality. If nothing else, RFK has made it possible to have these discussions. Until now childhood vaccines has been a sacred cow of medicine whose risk/benefit value could never be debated in the same way we debate the value of other therapeutic interventions. I see that as a win for evidence-based medicine.