To be clear, he recommends for getting normal levels of vitamin D and A, but against supplementing. For someone likely to be deficient, I guess that might mean supplementing small amounts, or larger amounts every few days.
I’ve skimmed it; he sounds very convincing,[1] and he previously turned me on to zinc. I’m not capable of following the science directly. I wonder if it’s worth trying to convince him to release it freely (possibly with a lump sum of money), but first I’d want someone more knowledgable than me to evaluate it. When I raised the possibility on the EA coronavirus facebook group, I mostly got the reaction that he seems sketchy (which, yeah, looking at his website he absolutely does); and that nutritionists in general are unreliable even when they seem to have good science. I’m not sure how much weight to assign to those.
Copying from what I wrote on facebook:
So the argument against vitamin D supplementation is that it increases the amount of ACE2 on our cells. ACE2′s normal role is in blood pressure and keeping the lungs and heart healthy. (There’s a lot more detail on that in the “detailed scientific analysis” section.) But SARS-Cov-2 gets into cells by hijacking ACE2. It has this in common with regular SARS and only one other known human coronavirus (NL63). Specifically the claim seems to be that ACE2 currently docked on cell surfaces would allow viral entry, and ACE2 that’s been shed from cell surfaces (“serum ACE2″) “is likely to be protective or irrelevant”, though that bit doesn’t have a citation.
The evidence that vitamin D increases ACE2 seems to be mostly based on rat studies. There were three supporting this, three contracticting (of which one was on humans). But two of the contradicting studies (including the one on humans) looked at serum ACE2 which may not correlate with docked ACE2. The other one had a thing going on with kidney injury that could have caused the effect. He concludes that “On the balance, vitamin D is likely to increase ACE2 expression” and recommends against supplementing it.
(I think the argument against vitamin A supplementation is also that it increases ACE2, but I haven’t looked closely at that.)
So I guess concrete(ish) questions that I have:
Does SARS-CoV-2 indeed get into cells by taking advantage of ACE2, and specifically ACE2 docked on the cell surface? Wikipedia on ACE2 says “ACE2 receptors have been shown to be the entry point...”, and points out that receptors are different from ACE2 itself.
Are there experimental/observational studies on the effects of Vitamin D supplementation on SARS?
Two of the rat studies showed that “calcitriol, the active metabolite of vitamin D … synergizes with diabetes to increase ACE2 protein” in different parts of rats. Does that mean they only tested on diabetic rats, and would that make the studies not generalize very well?
Does this kind of argument have a history of predicting experimental/observational results? I’m reminded of Scott’s recent post on the fat diet, which I think roughly concluded “yah that seems like a solid theoretical argument, but all the empirical evidence seems to contradict it so???”
The second one apparently is free, but behind a login screen.
Also, citations for vitamin D raising ACE2:
Xu, J. et al. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol. Med. Rep. 16, 7432–7438 (2017).
Lin, M. et al. Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease. Mol. Biol. Rep. 43, 397–406 (2016).
Cui, C. et al. Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system. Redox Biol 26, 101295 (2019).
Andersen, L. B. et al. Vitamin D depletion aggravates hypertension and target-organ damage. J. Am. Heart Assoc. 4, (2015).
Ali, R. M., Al-Shorbagy, M. Y., Helmy, M. W. & El-Abhar, H. S. Role of Wnt4/β-catenin, Ang II/TGFβ, ACE2, NF-κB, and IL-18 in attenuating renal ischemia/reperfusion-induced injury in rats treated with Vit D and pioglitazone. Eur. J. Pharmacol. 831, 68–76 (2018).
Anguiano, L. et al. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease. Nephrol. Dial. Transplant 30, 1176–1185 (2015).
The first three are pro, the others are con.
[1] By which I mean, he sounds like he’s done lots of research, weighed it up, and followed where it took him. He includes disclaimers like “as a hedge” and “here are some studies disagreeing, which I think is because...”
Note that my only mention of zinc in that comment was relating to zinc lozenges and the common cold. It seems like you’re talking about dietary zinc and Covid-19.
To be clear, he recommends for getting normal levels of vitamin D and A, but against supplementing. For someone likely to be deficient, I guess that might mean supplementing small amounts, or larger amounts every few days.
I’ve skimmed it; he sounds very convincing,[1] and he previously turned me on to zinc. I’m not capable of following the science directly. I wonder if it’s worth trying to convince him to release it freely (possibly with a lump sum of money), but first I’d want someone more knowledgable than me to evaluate it. When I raised the possibility on the EA coronavirus facebook group, I mostly got the reaction that he seems sketchy (which, yeah, looking at his website he absolutely does); and that nutritionists in general are unreliable even when they seem to have good science. I’m not sure how much weight to assign to those.
Copying from what I wrote on facebook:
Also, citations for vitamin D raising ACE2:
The first three are pro, the others are con.
[1] By which I mean, he sounds like he’s done lots of research, weighed it up, and followed where it took him. He includes disclaimers like “as a hedge” and “here are some studies disagreeing, which I think is because...”
And since I had to look it up: the RDA is only 600 IU, assuming no sun exposure. (600 IU = 15μg)
selenium may be more important than zinc:
https://docs.google.com/document/d/1q5IH2hGjjdPi-vcs4zOBlArgFJ9iSDdZVoceevUPI9c/
Note that my only mention of zinc in that comment was relating to zinc lozenges and the common cold. It seems like you’re talking about dietary zinc and Covid-19.