If you adjust for a confounder using a thing which is only partly correlated with the confounder, some of the confounder slips through. This is bad enough when it's something like using income to represent socioeconomic status, but it's really bad when it's something like using ZIP code for race. At high enough n, any amount of confounder slipping through will make a result appear significant.
If they had based it on proportion black, though, presumably this wouldn't be AS bad. Instead, it looks like they made binary indicators for majority black, etc. I'm guessing this is because they wanted simple odds ratios, but if so, this is a case of blindly following "literature standards" exacerbating empirical problems. Did they run it using the proportion itself somewhere else that I'm missing?
I just wanted to say that I'm really grateful that you're still posting Scott :). I check my email multiples times a day to see if there's a new post, and seeing a notification from ACX makes the day that much better
Another great example showing why science is actually pretty hard to do well, even when we are trying to answer questions that appear simple at first glance.
If it's so difficult to answer whether a major vitamin helps with one of the most significant diseases we've seen in decades a full year in, one should consider to what extent they should place strong confidence in their convictions in similar areas with similar scientific processes, for example nutrition and diet (these are also very hard, like most areas, and you should exercise extreme epistemic humility and adaptability, imo)
"Another great example showing why science is actually pretty hard to do well, even when we are trying to answer questions that appear simple at first glance."
And why yelling "trust the science" at people isn't the simple solution some make it out to be.
Of course! But a slogan "Trust that we get there, in the end, using different methods and looking at the probabilities...hopefully" isn't a great rallying cry ;)
AIUI, scientific method = accept the fact that you can only ever have an approximate model of the "real world" and all you can ever do is refine that model so it produces ever more accurate results *in the areas where you're applying that model*.
Hoping for the absolute truth invariably makes you disappointed and likely to utter nonsense like "there is no scientific method".
The problem with that model is that it ignores the issue of systemic errors (which is a giant blind spot in science). Currently very many scientists and other people who matter (like financiers and journalists) think that there is a holy grail methodology. They think that you asymptotically approach the truth, the larger the N and/or the more studies you do, with that same methodology. So at a certain point you can be confident that the interpretation of the results is scientifically very certain.
However, you merely eliminate random error in this manner, not systemic errors in the methodology. It also doesn't solve the problem of interpretations of the results that are not true to to the data or biased publication of the results, for example by tossing out negative findings. Both the interpretation and publication step are actually part of the methodology and thus subject to error, but are commonly treated as being distinct, which often results in them being treated as sacrosanct.
Truly good science requires getting fairly consistent results when using multiple different, sufficiently strong methodologies (or at least validating a methodology by using other methodologies). Only then can you have real confidence that your scientific process has done better than common sense.
My newspaper recently wrote an article advocating having lay people suggest what sociology papers should be replicated based on applying common sense to the findings. They didn't seem to recognize how damning their suggestion was, when common sense is needed as a check on what people in that field call science.
One more point: a significant proportion of readers will have been staying inside (so away from sunlight) much more than they did before in the past 11 months; just think about not commuting to work everyday.
This will have reduced their (already on average pretty bad, for UK and some US states) level of Vitamin D... in which case a supplement would hurt them even less than the very little theoretical hurt it did in those pre-2020 studies.
I also side with "take Vitamin D supplements". My parents have also been taking one since November because they trust me (and their doctors are fine with them taking it).
I started taking a Vitamin D supplement the instant lockdown started because I realised that it was going to reduce my sunlight exposure by a lot and it seemed like an obviously good idea.
Could seasonal, latitude, and minority trends not be linked directly toward indoors exposure and multigenerational households?
Individuals are much more likely to congregate outdoors during the summer than the winter. This corroborates with the known facts that outdoors exposure poses a much lesser risk to corona than indoors exposure. In addition, we know that cold air carries the virus droplets much better than warm air. It seems to me that these facts would almost entirely explain the seasonal and latitude trends.
To explain the "vitamin d" trend in skin color, asian and african american households are much more likely to be intergenerational and/or involved in service jobs.
Same :) Anecdotally, in my immediate community, there was a massive shift from outdoor gatherings to indoor gatherings around the start of the winter wave. And we know outdoor gatherings lead to substantially reduced transmission, and for the people that do get infected, they likely lead to lower viral loads.
To exacerbate confounding with vitamin D even further, sunlight probably has some direct effect on transmission. Bad source, but lets you play with some sketchy model: https://www.dhs.gov/science-and-technology/sars-calculator. (I haven't seen a follow-up on this since last summer.)
This would probably only matter in a scenario where most transmission was _already_ happening outside, which I think is... never? But in such a world, you'd see that people who hung out in the sun (who have more vit D) did better than those in the shade, I guess.
"To explain the "vitamin d" trend in skin color, asian and african american households are much more likely to be intergenerational and/or involved in service jobs." But wouldn't this primarily affect infection rates not severity? That's not what's showing up in the Asian data (lower infection rates, but worse outcomes)
Well... if studies did not control for age, the worse outcomes could be linked to older asian individuals getting the virus than their white cohorts. This would mirror asian american populations having more multigenerational households.
However, I am not sure we can extrapolate "lower infection rates" from past data as testing was much more widespread in higher income, white areas. Immigrant and poorer communities likely had much higher caseloads of the virus in the August - December months than was reported in the data. But because of the lack of fine-toothed data on the subject, these higher caseloads reported as "worse results per case".
The whole corona experiment has been a case study in poor data extrapolation and terrible logistics. And often the simplest, most logical answers are the best ones.
None of this is to say I dismiss vitamin D. I take a vitamin D supplement during the winter months for mental health (and regardless of the science, the placebo is worth it in my case). But I am concerned by people trying to make large conclusions off much-polluted data as well as the wider trend of people trying to invent the wheel when often the wheel is already on our doorstep...
Think deeply about simple things. Not simply about deep ones.
Watch out here for the difference in the meaning of the word Asian in the American context and in the British context - in which it typically means South Asian (i.e. people from India, Pakistan, or Bangladesh). So if you're looking at data from both countries, it's something you need to be aware of.
Regarding vitamin D pharmacokinetics: the actual active form is calcitriol, which has three hydroxy groups. This is produced by a series of enzymatic hydroxylations starting with cholecalciferol (1 hydroxy), and then calcifediol (2 hydroxy groups). So giving people calcifediol is going to act more quickly than cholecalciferol.
Still, I'm not sure why they didn't just dose them with calcitriol. (One reason may be that it's easier to overdose on calcitriol, since the calcifediol -> calcitriol enzymes normally regulate how much calcitriol gets produced.) Even with giving calcifediol, it takes a few days for calcitriol to accumulate. See: https://www.sciencedirect.com/science/article/abs/pii/S8756328213003967
Ok (how much?). Ok (how much? when?). Wrong, e.g. "I'm feeling a cold coming on" zinc lozenges (of the right kind) do nothing after 2 days and reduce duration to roughly half if started in the first day of symptoms.
(assuming looking up 'usual active form' for the acknowledge function of vit D re: calcium means we can presume that this is the primary active form for speculative antiviral effect - definitely not a 100% certain implication)
It would be interesting to know what were the criteria for ICU admission in the Indian study, as well as the baseline O2 saturation in both groups. 50% of the patients needing ICU care is a little unexpected
Doesn't vitamin D have a build-up time and decay time, in the body. If so, this filter effect would rule out instant-on attempts to use it (e.g. hospital data)
Here are the findings (curious Scott didn't cite this most recent study, while citing previous study with n=76):
"A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379).
Findings: ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%; p<0.0001). "
I would guess he didn't cite it either because it is a preprint, or because of the study's flawed methodology. I think it would have been worth mentioning, however, to better evaluate the dependability of the initial Spanish study he cites.
The criticism of the study, referenced in here via a link to a Twitter stream, is that the randomization was flawed. I don't have the time to follow all the details in the link, but I tend to trust the study authors as to having valid reasons for conducting the study the way they did -- using separate wards for the subject v control groups.
So often during the past year, we nitpick studies for not being perfect rather than considering probabilities that the authors were politically biased or incompetent.
. . . Or maybe even very well trained doctors trying to save lives - do we not have a case of the SEMMELWEIS effect here? - a Doctor has found a protocol that; appears to significantly reduce mortality; BUT does not fit current paradigms, is embarrassingly simple, and makes nobody a lot of money - did the medical research community go - WOW - now that is big-time interesting!!! - we MUST check out ASAP with urgent studies just in case he is right - NO! - to save embarrassment and stepping out of the comfort zone, they claimed the Doctor was a loon; their patients continued to die in large numbers of puerperal fever; and it took maybe 30 years, for it to be accepted handwashing between autopsies and childbirth delivery saves lives by reducing infection spread - somewhat ironically hand disinfection is now a central COVID-19 control strategy . . . https://www.npr.org/sections/health-shots/2015/01/12/375663920/the-doctor-who-championed-hand-washing-and-saved-women-s-lives
Absolutely right. I see Wilson and Haber as just preening here. There are lots of good administrative reasons why they may have had to run the case / control split by ward and did the best they could in real-world conditions.
There's at least one thing you get from sunlight that isn't vitamin D-- people have subcutaneous nitric oxide precursors. The really fun part is that you won't find this out by studying mice. Mice are not only covered with fur, they prefer going out at dusk and pre-dawn, so they don't have that body system.
Nitric oxide and sunlight for people was discovered as a result of studying why there were more heart attacks in the UK than in Australia.
If that's true, then shouldn't people who use poppers (alkyl nitrites) be significantly less likely to have health problems associated with lack of sunlight? I don't know how you'd do a study to show that, though. The group of people who do poppers is not exactly representative of the overall population. :)
I think if you're using poppers regularly, you're also engaging in other risky behaviours likely to garner you a bunch of exciting infections never mind Covid-19.
Would it? I understand that the sociologists of race talk a lot about "colorism" where darker black people face more obstacles than lighter black people. If we found darker black people got more coronavirus we wouldn't be able to distinguish between sunlight effects and colorism effects.
South Indians often have darker skin color, but very different SES from African-Americans. I've heard South Asian doctors got hit quite hard in the UK by COVID.
South Indian =/= South Asian, which includes North Indian. Most Brits from South Asia are from North India or Pakistan or Bangladesh, not from South India or Sri Lanka.
If you want to see the difference, google for team photos of the Pakistani (north) and Sri Lankan (south) national cricket teams. It's not a very big difference, but it's enough to notice.
I was going to share this map of reported covid cases by state in India, but then realized that we have a confound of darker skin correlating with lower latitude. It's hard to tell what the actual pattern is on the map though:
It would give us approximate information about how much vitamin D people get from sunlight, but then it would be necessary to think about confounding factors.
From what I've read, colorism isn't just about black people, it's also in play among Asians.
And I'm not sure what's covered by "face more obstacles"-- it can happen that which children in a family are favored or disfavored depends on their skin color.
By the way, the CDC's report of the excess deaths by race/ethnicity shows that while blacks died far more than whites did of covid during the first wave and somewhat more of covid during the second wave, by the third wave, the rate of excess deaths was very close to equal between whites and blacks.
In contrast, Hispanics died at high rates in all three waves.
To see the CDC data, click on "Change in Number of Deaths by Race/Ethnicity" at:
Does that take into account the fact that the third wave was most pronounced in the least black region of the country? (It spread strongly to the Hispanic parts of Colorado, New Mexico, and Texas, but never got as big in the Southeastern states or northeastern cities where the largest black populations are.)
No doubt there is some kind of connection between ethnic death rates, regionality, and perhaps seasonality, any of which could be of relevance to the Vitamin D discussion. I bring this fact up because almost nobody knows that black and white death rates were about equal during the Third Wave, because that's not the kind of thing that gets publicized these days.
I'm still not finding that data. Does it show that black people in North Dakota were equally likely as white people in North Dakota to die in the third wave, and that black people in Alabama were equally likely as white people in Alabama to die in the third wave? Or does it show that within each state, black people were more likely to die, but because North Dakotans were more likely to die in the third wave than Alabamans, black people in North-Dakota-or-Alabama (who are mostly in Alabama) were equally as likely to die as white people in North-Dakota-or-Alabama (who are more evenly spread).
Seems like an interesting question, no? But now that equality between whites and blacks in excess deaths occurred during the Third Wave, nobody in the press seems terribly interested anymore in talking about covid and race, whereas previously it was a topic of obsessive interest.
I read a bit about this when I had a patient with GFAP encephalomyelitis who had a dramatic recovery after getting sunburned. I was really pissed off with the staff who let a very cognitively impaired man sit in the sunshine and get sunburned. But then he recovered, from literal psychosis and profound memory and executive impairment, to seeming fairly normal, and Neuropsych testing confirmed this. I wasn’t sure if it was vitamin D or not.
So I read about MS, because GFAP encephalomyelitis is incredibly rare, and found that some researchers were arguing that the latitude effect is due to UV rather than Vitamin D itself, and had a mouse model of multiple sclerosis showing mice under UV did better than either controls or vitamin D mice. I can try to find the reference again if you like.
Obviously my sample was n=1 of an extremely rare disease, but it got me thinking.
If it was UV, could that explain the latitude effect but also why vitamin D supplementation studies with good designs had mixed results.
Also, in the UK, NICE, which is our equivalent of the FDA to some extent, says that most Northern Europeans are Vitamin D deficient in the winter, and recommends that *everyone* supplement with Vitamin D between September and March. It’s just buried there in one of the NICE guidelines that almost no one ever reads. So that’s a good enough reason for me.
Thanks, I was just coming here to say the same thing. I believe they at one point also recommended that those with darker skin tones take it all year round.
But then the UK is at a much higher latitude than the US. I do wonder if the 75% probability Scott assigned to Vit D supplementation being useful should state which latitude/race he’s estimating that for.
This wasn’t the paper I found the first time around because it’s a different experimental design, but this is the same mouse model of MS. The UV seems to work independently of Vitamin D by good study design, but the mechanism is unknown. Presumably it prevents the immune system from attacking myelin in some way, which makes me wonder to what proportion of people with COVID are dying from an overactive immune response, the cytokine storm findings from early on.
This is another anecdote -- a friend of mine with an MS diagnosis went from quite symptomatic to completely not symptomatic after high Vitamin D dosing. I'm foggy on the details because it's been awhile, but it seems like she was in touch with a number of other people who'd had the same experience. Is this something other people have heard about?
If UV is an important factor, this could explain Australia and New Zealand's success in dealing with the coronavirus (for those who don't know, both countries are close enough to the ozone hole to have far higher rates of UV exposure than the rest of the planet. You can get sunburned in less than half an hour without taking precautions).
Hard disagree. Aus and NZ either explicitly or effectively pursued a strategy of elimination. Robust public health response, and in the case of Victoria, a 3 month+ lockdown that banned socialising outside your household.
That probably had a bit more to do with it than UV.
"Do the benefits of taking a Vitamin D supplement at a normal dose equal or outweigh the costs for most people?"
I'd say the percentage is closer to 100%.
There have been numerous studies showing that low vit D levels are correlated with increased risk of depression, diabetes, cancer and influenza (though I haven't looked at all of these studies with the rigor or Mr Alexander so who knows after you disect all of these studies). Anyway, I tell my patients to take it.
EDIT: this is based on the cost of the vitamin D (aprox £10 for a years supply of 5000 iu/capsule) and the potential side effects (I read of a study finding that the main side effect of vit D overdose, renal stones, was not statistically significant compared to the placebo group) vs the likely many benefits.
Yeah, seems to me the greatest cost associated with Vit D supplementation is literally the fiscal cost. I think if you're someone who can afford to throw $50/mo or whatever at supplements, it's probably worth it.
Another potential cost, which I wish this post addressed, is giving people a false sense of security with the Vitamin D thing. If someone is overweight, has hypertension, and maybe another comorbidity, but thinks they're safe from corona just because they've been taking Vitamin D supplements for a few months, then that's a problem. Anything that reduces vigilance sans justification should be perceived as a pretty serious cost.
I hate the 'false sense of security' argument (even tho I also think it's sometimes true) – it's an almost perfect general counter-argument to doing _anything_ for anyone.
If anything, the largest source of a 'false sense of security' is probably 'if I follow official advice I'll be fine'.
Unless you are actually deficient in Vitamin D, I don't think you could say it's 100%. There are risks associated with taking supplements from a largely unregulated industry (USA at least). Taking Vitamin D doesn't necessarily reduce the risk for getting your list of diseases. Some good summaries of the research on sciencebasedmedicine.org:
Of course, indeed. I read some of the back-and-forth and did some basic fact-checking and as expected the truth appears to be somewhere between "sunscreen is poison foolishly pushed on us by evil Big Pharma" and "you'll get skin cancer if you merely *say* the word 'sunshine.'"
Even those rebuttals you linked are more nuanced. From the first:
"But such advice is not one-size-fits-all: it’s most likely not true for people of African descent. “Your risk of skin cancer is directly related to how much melanin you have in your skin … I don’t recommend sunscreen for darker patients for skin cancer prevention,” Adamson said."
"Most people can make enough vitamin D from being out in the sun daily for short periods with their forearms, hands or lower legs uncovered and without sunscreen from late March or early April to the end of September, especially from 11am to 3pm."
So, indeed, it's not universally the case that dermatologists recommend against (cautious, limited) sun exposure. And it seems like perhaps those in the US may be overly risk-averse or conservative with respect to updating guidelines, when compared with their international counterparts.
Yes, dermatologists, who should have put me on Isotretinoin way earlier. Or mentioned that a permanent solution to acne actually exists. Instead of me finding this out years later. A very conservative bunch.
I consider "sunshine is bad for you, if it doesn't involve sunburn" an extraordinary claim. That would imply to me that "skin cancer" was a leading cause of mortality among white hunter-gatherers.
Somehow I have trouble imagining that.
I also have heard a similar claim in that vein, that you should always use sunscreen, which as far as I know is some kind of chemical goop including titanium oxide and zinc oxide. I follow the precautionary principle wrt to smearing random metal cream on my skin, though. [on the first couple of beach days in Egypt sure, but every day I have sun exposure in cloudy Europe?!] I also know from experience that on a German summer day, I can stay outside for hours and not get a sunburn.
An apothecary was surprised to hear that, apparently believing that sunburn is inevitable then. But then she still insisted that the skin cancer risk made this irrational.
But what the hell did she know about skin? She didn't even know that sunburn wasn't a given. Would it be rational to take her word for it?
US doctors are people who subjected themselves thru yearlong sleep deprivation torture for status reasons during med school.
This makes everything they say, a priori suspect.
Is that an ad-hominem or the sensible heuristic of "Don't listen to masochistic, intense, crazy people who faced extreme sleep deprivation continue defending the practice as necessary for health advice"? Perhaps both.
I also am worried, that the claim "sun is bad for you" is too appealing for a nerd like me, who's prone to staying indoors in front of a computer for long periods.
Like isn't it awfully convenient that that's also the best way to live?
When I look at people who have a tan, well they do look healthy and happily smug about it. On beach vacation, I was the same way and it feels excellent.
The mood boost is NOT FUCKING SUBTLE!
Smoking is bad for you. And the EAE did not have tanning beds so they probably aren't good either. [I never wanted to tan like that, so I don't care to be certain of it]<br>There is extraordinary evidence for those claims.
But from what I could gather about this question, the evidence is conflicted.
If there is an increased skin cancer risk, that would be more than outweighed by the reduced cardiovascular risks, mood benefits, exercise and fresh air, I totally would expect the medical establishment to zero in on the "increased skin cancer risk", because of the precautionary principle. I suspect that this is from the same impulse that makes "them" want to ban vaping in California.
My judgment might be wrong, this might be sloppy reasoning and I will die for it.
And that I am coming up with a story that confirms what I want to believe.
But that's always true and I'm okay with that.
It's not like I can trust someone else's judgment for my decision-making, in the end.
If Scott ever wants to make an effort-post on the topic, well then I'm willing to entertain the notion of "sunlight is bad for you", again.
If he comes to that conclusion and I can follow and agree with his reasoning, that would indeed be extraordinary evidence.
"sunshine is bad for you, if it doesn't involve sunburn".
"That would imply to me that "skin cancer" was a leading cause of mortality among white hunter-gatherers"
Never mind hunter-gatherers, it would imply it among European subsistence farmers before mechanisation, a group for which we have vastly better records.
However, it is worth asking how much ozone depletion affects this - if the evidence gathering was in the mid 1990s at the peak of ozone depletion, then that would go a long way to explaining why they get results that suggest that sun exposure is much worse than the historical record.
IOW, we may have an excessive concern for the sun because we happen to live during a short period in earth's history when it was much more dangerous than it was before 1975 or after 2075.
This. I am told "the lifetime risk of getting melanoma is about 2.6% (1 in 38) for whites" and "The average age of people when it is diagnosed is 65."
Hundreds of years ago, life expectancy was typically below 40, and people faced major health threats every single year.
People worried about things like Smallpox (which reportedly had an "overall fatality rate of about 30%" - I can't find a "chance a random person would be killed by smallpox", but it was endemic, so it's probably quite a substantial probability), Cholera, Malaria, and for awhile there, the Black Plague.
Relatively uncommon deadly threats, like skin cancer, just wouldn't have been very noteworthy back then. Also, white skin responds to sunlight by generating melanin, so while the extra time they spent in the sun might have raised their risk, the risk probably wasn't raised by a large amount, thanks to the melanin. The risk would then be reduced simply by not living long enough to reach an age associated with a substantial risk of skin cancer.
I wonder if that formulation was combined with other minerals, such as magnesium (that can cause diarrhoea)? Best sources are from food but since Vitamin D comes from animal-derived products and you're trying for vegetarian/vegan, a supplement is probably your best bet (unless you eat fish?):
" Choose fortified dairy products (which have the nutrient added to the food), fatty fish, and sun-dried mushrooms, which are all high in vitamin D."
Holland & Barrett (a UK health store chain who are a bit chi-chi: "Holland & Barrett was formed in 1870 by Alfred Slapps Barrett and Major William Holland, who bought a grocery store in Bishop's Stortford, selling groceries and clothing. ...The brand has become synonymous with the sale of vitamins, supplements and homeopathy, to the point that pro-homeopathy former MP David Tredinnick has been dubbed "The Hon. Member for Holland and Barrett") do have some reasonable advice on where to get dietary Vitamin D:
While there are few Vitamin D sources in food, the good news is, some of these sources are vegan. For instance, 1 cup of almond milk will give you 100mg of Vitamin D, orange juice, 100mg and 1 cup of portobello mushrooms, 634mg. Other vegan sources of Vitamin D in food, include Maitake mushrooms, soy milk, soy yoghurt and ready-to-eat cereal.
Mushrooms
Mushrooms are the only plant source of Vitamin D (apart from fortified foods). They can synthesise Vitamin D when they are exposed to UV light, just like we can. Choose wild mushrooms or mushrooms grown in UV light.
Top tip: Slice up some mushrooms and leave them exposed to the sun outside from 10 am – 4pm on a sunny day on 2 separate occasions, e.g. Monday is bright, Tuesday is dull and Wednesday is sunny again, so you’d put the mushrooms out in the sun on Monday and Wednesday. Cook and enjoy!
Or, you can dry them thoroughly (e.g. using a food dehydrator) add to a jar with 1 tablespoon of uncooked rice, and store for a later day. Just rehydrate them in water 1 hour before you want to cook with them.
Tofu
Tofu is not just for vegetarians and vegans! It is a highly versatile source of dietary Vitamin D which you can use for snacks, lunches, and main meals.
There are a few different types you will come across, so here is our advice about how to best use them:
Silken / Japanese-style tofu: Silky and creamy, this can be used as a thick cream, to make a vegan cheesecake, put in smoothies or even make creamy dips with.
Regular tofu: It is soft like silken, but a little more compact. This type of tofu soaks up flavours of stocks and sauces – it is usually used in noodle soups. Try making vegan scrambled eggs with it, just sprinkle in some turmeric and black Himalayan salt.
Firm tofu: Perhaps the most common tofu, firm tofu usually comes soaked in liquid. The texture will be like feta cheese.
Before use, dry it before using it by pressing it (placing it on a plate in the sink and putting something heavy on it works too! Then let it soak in a marinade for at least an hour. Finally, pan-fry, stir-fry, deep-fry or bake it in a yummy sauce in the oven.10
Plant-based dairy alternatives
Soya Milk: Most dietary Vitamin D is found in animal products. So fortified food sources of vitamin D are particularly useful for vegans and vegetarians. Soya milk contains around 100-120 IU in one cup and lots of protein. Try using it in your morning smoothie or cereal to start your day off right.
Almond Milk: 200ml of almond milk contains around 90 IU of Vitamin D. Check the label of your favourite brand to see how much Vitamin D you will get per serving.
Fortified vegan yoghurt: Similar to plant-based milks, vegan yoghurts also know their target market may be lacking in vitamin D in the winter, so a lot of them fortify their products with vitamin D. Try topping it with granola and honey or agave nectar.
Did you know? In the UK, cows’ milk is generally not a good source of vitamin D as it is not fortified like it is in other countries. Stick to the plant milks if you want to increase your dietary vitamin D.
Orange juice
Get some Vitamin D from fortified orange juice, which can contain up to 140 IU of Vitamin D per glass.
Fortified breakfast cereal
Some healthy breakfast cereals and instant oats are fortified with Vitamin D. Check the label for the amount per serving.
Meat substitutes
There are tons of meat substitutes on the market – and some are pretty realistic – adding to their authenticity is the fact they are usually fortified with vitamin D.
Real meat can be a bit hit and miss when it comes to vitamin D, with red meat, liver and other offal being the best sources. At least with fortified faux-meat, you know it contains the vitamin D you need.
Try going meat-free for a few of your meals and swap it for fortified plant-based mince, burgers, nuggets, goujons, chunks or even steak! Check the nutritional label to see if has been fortified and tuck in."
25mcg is actually much less than recommended, but is a common dose in the USA. Try finding 250mcg and take daily. There's a whole ordeal about how low vitamin D prescription is a typo and you can't really overdose or anything (you should Google it!). If you're going to take some, you might as well take the right dose!
Yes, getting too much vitamin D can be harmful. Very high levels of vitamin D in your blood (greater than 375 nmol/L or 150 ng/mL) can cause nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones. Extremely high levels of vitamin D can cause kidney failure, irregular heartbeat, and even death. High levels of vitamin D are almost always caused by consuming excessive amounts of vitamin D from dietary supplements. You cannot get too much vitamin D from sunshine because your skin limits the amount of vitamin D it makes.
The daily upper limits for vitamin D are listed below in micrograms (mcg) and international units (IU):
Ages Upper Limit
Birth to 6 months 25 mcg (1,000 IU)
Infants 7–12 months 38 mcg (1,500 IU)
Children 1–3 years 63 mcg (2,500 IU)
Children 4–8 years 75 mcg (3,000 IU)
Children 9–18 years 100 mcg (4,000 IU)
Adults 19 years and older 100 mcg (4,000 IU)
Pregnant and breastfeeding teens and women 100 mcg (4,000 IU)
Since I have gotten vacinated for Covid, I am reducing to 2,000 IU since too much Vitamin D is thought to interact with heart disease. Too little and too much can both be a problem, I think turning to the Goldielocks test is statistically correct. I will get the Vitamin D level tested the next time I have a blood test....
Okay, fish oil supplement I am taking (for my creaky joints) has a vitamin D level of 10 μg which is 400 IU, so I think I'll stick with that dosage. 25 μg/1,000 IU is a bit on the high side but seems to be the upper limit recommended. I think going any higher is not really beneficial unless you're extremely deficient and not getting any from your diet and you get prescribed high dosage to bring you up to normal level.
If you're eating dietary sources of vitamin D (animal-derived foods mostly) then additional supplementation up to a lower level probably won't hurt, but I think if you're eating a reasonable diet *and* slamming down 250 μg/10,000 IU in supplements you are asking for trouble:
"Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart."
"The IOM Report in 2011 not only discussed the upper limits (ULs) for vitamin D intake on the basis of the acute, short-term administration of high-dose vitamin D preparations for limited periods but also emphasized chronic administration of vitamin D over years of supplementation. Acute toxicity would be caused by doses of vitamin D probably in excess of 10,000 IU/day, which result in serum 25(OH)D concentrations >150 ng/ml (>375 nmol/l). That level is clearly more than the IOM-recommended UL of 4,000 IU/day. Potential chronic toxicity would result from administration of doses above 4,000 IU/day for extended periods, possibly for years, that cause serum 25(OH)D concentrations in the 50–150 ng/ml (125–375 nmol/l) range "
So safe upper limit is 100 μg/4,000 IU per day, NOT 250 μg/10,000 IU. My totally amateur advice is: eat a good diet, stay out in the sunshine when you can get it (with caveats about being careful around sunburn etc.) and in the winter months supplement your diet with NO MORE THAN 4,000 IU PER DAY (and if you're sticking to a reasonable diet, go lower on the supplements to maybe 1,000 IU per day).
"Sometimes the amount of vitamin D is expressed as International Units (IU). 1 microgram of vitamin D is equal to 40 IU. So 10 micrograms of vitamin D is equal to 400 IU.
What happens if I take too much vitamin D?
Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart.
If you choose to take vitamin D supplements, 10 micrograms a day will be enough for most people.
Do not take more than 100 micrograms (4,000 IU) of vitamin D a day as it could be harmful. This applies to adults, including pregnant and breastfeeding women and the elderly, and children aged 11 to 17 years.
Children aged 1 to 10 years should not have more than 50 micrograms (2,000 IU) a day. Infants under 12 months should not have more than 25 micrograms (1,000 IU) a day."
"For example, the Spanish study used a version of Vitamin D called calcifediol; the Brazilian one used a slightly different version called cholecalciferol. Calcifediol becomes active more quickly than cholecalciferol, enough so that if I were in the business of defending the Spanish study I might argue that it takes a few weeks for cholecalciferol to work, so giving it to someone who will already be dead or recovered by then is meaningless."
Biology is perversely complicated enough that this could indeed matter. When I was looking up magnesium supplements to take, there are ten different types https://www.mindbodygreen.com/articles/magnesium-supplement-types and depending what you want to achieve (ease sore muscles? help blood pressure? treat constipation?) then the type you should be taking differs.
And looking up about vitamin D types, the differences between the two types seem to be:
"The recommended form of vitamin D is vitamin D3 or cholecalciferol. This is the natural form of vitamin D that your body makes from sunlight. Supplements are made from the fat of lambs' wool.
However, a clinical study reported in 2008 suggested that vitamin D2 works as well as vitamin D3.
Many supplements contain vitamin D as vitamin D2 or calciferol. It's derived from irradiated fungus."
Irradiated fungus? Funky, if we want to turn into Godzilla I suppose?
"Vitamin D2 and D3 are not equal when it comes to raising your vitamin D status.
Both are effectively absorbed into the bloodstream. However, the liver metabolizes them differently.
The liver metabolizes vitamin D2 into 25-hydroxyvitamin D2 and vitamin D3 into 25-hydroxyvitamin D3. These two compounds are collectively known as calcifediol.
Calcifediol is the main circulating form of vitamin D, and its blood levels reflect your body’s stores of this nutrient.
For this reason, your health care provider can estimate your vitamin D status by measuring your levels of calcifediol.
However, vitamin D2 seems to yield less calcifediol than an equal amount of vitamin D3.
Most studies show that vitamin D3 is more effective than vitamin D2 at raising blood levels of calcifediol.
For example, one study in 32 older women found that a single dose of vitamin D3 was nearly twice as effective as vitamin D2 at raising calcifediol levels.
If you are taking vitamin D supplements, consider choosing vitamin D3."
So the Spanish study was using the inferior (?) D2 yet got good results, while the Brazilians were using the superior (?) D3 and found no difference.
Yeah, I'm puzzled too. It *may* be that the Spanish patients, who were already hospitalised when they received the supplementation, were *so* badly off for Vitamin D that anything was beneficial. The only difference I could come up with was that the Spanish study seems to demonstrate that it "drastically reduced" admissions to ICU, while the Brazilian one says it didn't reduce length of stay:
"A small randomized controlled trial in Córdoba, Spain, of calcifediol (25-hydroxyvitamin D3, or 25(OH)D3) for hospitalized COVID-19 patients (henceforth, “the Córdoba study”) found dramatic reduction in the need for ICU admission. This study has been viewed as a small preliminary study, suggesting at most that further study might be warranted. It has gotten relatively little attention, though its strengths and weaknesses were discussed in this article, and a Bayesian cost/benefit analysis found the expected benefits, in terms of lives saved and severe illness avoided, of immediately adopting the treatment protocol were considerably higher than the expected costs. Two other randomized trials of vitamin D formulations for COVID-19 had mixed results: a small trial in India found a high dose of vitamin D3 shortened time to viral clearance in asymptomatic or mildly symptomatic SARS-CoV-2 individuals, and a larger study in Sao Paulo, Brazil did not find a statistically significant benefit of a high dose of vitamin D3 in hospitalized COVID-19 patients."
"Conclusions and Relevance Among hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19."
So *maybe* it's "Vitamin D supplementation if you're hospitalised with Covid-19 means you're less likely to be admitted to ICU, but you won't get out of hospital any sooner than someone with Covid-19 that did not have to be admitted to ICU and wasn't getting Vitamin D supplementation". That is, "if you're run-down/deficient in Vitamin D, that makes it worse if you get Covid-19 and have to be hospitalised, but taking Vitamin D won't stop you getting Covid-19 although it will make it less likely you'll be so badly off you need to go to ICU".
"So the Spanish study was using the inferior (?) D2 yet got good results, while the Brazilians were using the superior (?) D3 and found no difference."
No, the Brazilian study used D3 (cholecalciferol), and the Spanish study used its metabolite 25-hydroxyvitamin D3 (calcifediol). Neither of them used D2 (calciferol).
Ah, thank you for clearing that up, I was confused about which was which. So they both used the same form of Vitamin D, just the metabolite in one case. That makes the results even odder - either the Spanish really messed up and there isn't any effect, or it is something like "if you are deficient in Vitamin D and you get Covid-19, you are more likely to have a bad outcome necessitating admission to ICU, but supplementation with Vitamin D will only mitigate the worst effects, it won't prevent you contracting Covid-19 or let you recover any faster than normal". So probably better to take a supplement just in case, but it's not a miracle cure.
I think it still leaves open the possibility that calcifediol is effective when administered to people after Covid diagnosis, but cholecalciferol is not because it takes several days for the liver to metabolize it into calcifediol, and by the time you've produced enough to matter the course of the disease is mostly decided. A bigger replication of the Spanish study would clear things up.
That seems like an EXTREMELY overoptimistic estimate, especially considering that the "positivity" of the study is questionable. When they pool all of the clinical scores, they get significance, but it was not significant for shortness of breath, not significant for hospitalization, not significant for mechanical ventilation, not significant for mortality. The authors even comment in the discussion that the difference might have been due to different baseline characteristics in oxygen saturation
Could there be something like an undershoot effect involved, where people who would ordinarily have lots of vitamin D because they spend a lot of time outside and live close to the equator actually have much less because they're locked down and stay inside instead, which does... something... to their immune systems?
One of the challenges with using serum vitamin D levels as an input variable is that we don't really know whether those levels are a cause or an effect; possibly they are a confounding factor when included with other inputs. Example: although patients with higher vitamin D levels may have fewer M.I.s, we can't produce that result by supplementing vitamin D in the diets of low-vitamin-D patients. See, e.g., https://jamanetwork.com/journals/jamacardiology/fullarticle/2735646.
Well sunlight seems way more promising, so why bother studying Vitamin D?
So here's my experimental design for testing the "something something sunlight"-hypothesis:
Set up a hospital wing with a bunch of UV lights, and another with UV lights and infrared and another with just infrared and treat only people with a specific shade of dark skin in them for Corona. [uhm.... also a control group would be nice]
If there's no difference from any of the light setups, we..... are very confused.
Maybe not enough light.
If we see improvements from all rooms except UV-lights only, we know it's not vitamin D.
If we see.... ugh, lighting is hard, make that guy design the experiment:
"Despite their superficially lighter skin, they have Vitamin D deficiencies almost as bad as blacks." Unless I'm missing something, the linked study included a total of 60 Asians all from the greater Boston area. Obviously not very representative of ~4.7 billion Asians in the world or even the Asian population in the U.S. I would point to larger studies in Japan (e.g https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755751/) that appear to point to significantly lower vitamin d deficiency than the US population and much lower than the US black population.
Vitamin D deficencies are a combined function of skin color and sunlight amount. A skin color that works for Asians in Guangzhou might not work for Asians in Boston.
Another very significant source of Vitamin D is food: salmon, tuna, mackerel, mussels, oysters, liver and egg yolks. A 2.5oz can of wild salmon drained w/ skin & bones is about 750IU of vitamin D (the D3 variety). If you want to go vegan, portabella and maitaki mushrooms grown in the sun give you ~20ug (about the daily recommended amount of about 0.5IU). The better the animal ate, the better the Vitamin D content. Chicken egg yolks from chickens eating bugs, etc. from the ground (oranger yolk) are much higher in Vitamin D than CAFO chicken eggs. Wild salmon more than farmed salmon. The oranger, the better. Traditional Japanese diet in Japan include fish pretty much every day. Vitamin D deficiency can also come from a vitamin deficient diet especially a low fat, high over-processed food diet.
Asian == South Asian, Southeast Asian, North Asian? Quite a wide range of latitudes. The hyper-focus on racial data and what it explains isn't insightful, it leads to a desire to adjust expectations based on a small set of lumped data for whatever non-white categorization we're habituated to. If a light skinned 3rd gen Japanese person or a wealthy black person scores low on Vitamin D, do we think, well they fall under the Asian / Black category...
My understanding is that hydroxychloroquine is ineffective on its own but helpful when combined with other antiviral medication, thus possibly explaining some significant variation in study results (since many studies actually did combine it with other things):
Interesting review. I only suggest that you consider British epidemiologist, Edgar Hope-Simpson's search for a parsimonious explanation in his study: The transmission of epidemic influenza (1992). There is a clear connection between these seasonal phenomena. Here's a very interesting follow up on EHS's comprehensive work in the BioMed Cenral Virology Journal. Flu is still a surprisingly mysterious phenomenon in many ways. There are probably some read across matters to SARS-CoV-2. The intriguing relationship with VitD and even it's centrality is also well covered. Worth checking out the early C20th methods for transmission research if nothing else. There are some very interesting questions and conclusions that challenge some givens about these phenomena.
Good article but the Brazil and Spain studies were carried out solely among hospitalised COVID-19 patients. The India study is very interesting because it indicates that Vitamin D helps mild cases recover faster.
The next step should be to find out whether Vitamin D can help potentially moderate-to-severe cases remain mild and therefore whether it can prevent hospitalisations in the first place. Perhaps it can be given to a sample group of people of all ages who have never had COVID-19 and who haven't been vaccinated and this group can be compared to a control group.
So anything wrong with just taking L-arginine and L-citrulline as supplements to get nitric-oxide levels up? Like, if I'm going to take a bunch of random stuff sunlight-associated stuff like Vitamin D, I might as well be a completionist about it.
Perhaps at least a portion of the seasonal and latitudinal variation is due to that COVID (and many viruses) are rather vulnerable to ultraviolet.
Thus, the seasonal variation in daily insolation would be the true causal driver, with Vitamin D correlating for the obvious reason.
If this holds water, I would expect the degree of seasonal variation to be weaker closer to the equator, although this would probably be weakened because the directly-caused variation will generate more cases that will spread to the equatorial regions anyway...
Also, I would expect the degree of the effect to vary based on the amount of UV reaching the ground - so if the data exists, plotting the health of ozone layer against the degree of seasonal variation might be informative....
"If this holds water, I would expect the degree of seasonal variation to be weaker closer to the equator"
Sub-Saharan African countries don't seem to have fared as badly as most countries so there could be something there, assuming the data from those countries is reliable of course.
Just because there's more sunlight in the summer doesn't mean that people are getting enough of it to make a difference. Most of us are pretty well clothed or inside much of the time.
For me to get my blood level up from 15 to 40 (my target) took 4000 IU per day. I'm pretty sure that not many people who are told to take more Vitamin D3 take anywhere near that much. So I think that studies like the ones Scott has reported on need to say what the actual measured blood levels are, or they will be hard for me to take seriously.
On Zvi's advice, I took 4000 IU of Vitamin D per day for about 2 months.
Then I got kidney stones, and one of the doctors I chatted with said it could likely be from the Vitamin D, and I reasoned that I'd stored up enough Vitamin D (I think it gets stored in fats?) that I should stop taking it. Because kidney stones was no fun.
I have been in the hospital twice for kidney stones. I have found that the best way to avoid more is to drink a lot of water, and more when you start feeling symptoms of stones again. I've been taking 4000 IU of D3 daily for a decade without any more stones.
Maybe it will be helpful if I say a little more here. After I had those two hospitalizations, several years apart, I realized that both times, I had experienced the same progression of symptoms. I remember seven. At various times since then, I have noticed that I got two, then three, then four of them. By that time, I would be feeling pretty uncomfortable, but not really very sick or needing a hospital. I assumed that a new stone was building up, and that's when I would start pushing very large amounts of water. Within a few days, these symptoms would abate, every time.
Also, a few times I have had an ultrasound that showed "gravel" in my kidneys, but a later one would show none. This convinced me that I really could grow new stones, and flush them out again, so I keep drinking a lot of water.
So I can't be completely sure that drinking all that water flushed out nascent kidney stones, but I'm going to go on acting as if that's the case. And with all the Vitamin D3 I've been taking, I haven't gotten another full blown attack of stones.
Laboratory tests should be designed so that around 5% of tests are reported as abnormal. I worked for almost 30 years as a hospital pathologist, and, without doing a formal study, we were reporting way more than 5% of our vitamin D levels as abnormal. Before going off and making any recommendations, I would want to work on the test and make sure that there are no issues with it. Working in a community hospital, I never had the resources to do that sort of large study, but I still have the nagging feeling that something is amiss here, and I am not sure what it is.
As for outcomes in people of East Asian descent, I know through friends in the Chinese community that many people of Chinese descent remembered the original SARS epidemic and changed their behavior way before the government was willing to admit that there was a problem. That confounder will somehow have to be corrected for before drawing any conclusions about outcomes in those patients.
I have been taking the maximum recommend daily dose of 4,000 units Vitamin D3 since Feb 2020 on recommendation from Doctors at the Harvard Medical School. Presumably Vitamin D interacts with ACE2 which was identified as the viral binding site. So presumably not having a Vitamin D deficiency can be beneficial with respect to possibly reducing the risk of becoming infected.
There are a lot of people who definitely do need more Vitamin D because they're deficient, and there are a lot of other people who don't take Vitamin D when they should (or take less than they should) because they're incorrectly worried about taking too much. If you might be in either group, you can ask your doctor for a Vitamin D test, or just buy one for $50 here:
So let’s pretend that I’m a rube who don’t hold with all that high falutin’ college talk about n=stuff and chemistry and randomized study sessions and such.
What is wrong with blurring the conclusion enough for common sense to assert itself? “Vitamin D makes you healthier, and healthy people handle the ‘Rona better.”
If somebody did the exact same studies testing Vitamin C instead of D, do you reckon there would be a similar spread along the effective-ineffective spectrum?
> What is wrong with blurring the conclusion enough for common sense to assert itself? “Vitamin D makes you healthier, and healthy people handle the ‘Rona better.”
I think the Vitamin D skeptic case is to just leave off the first clause and say "healthy people handle the ‘Rona better." Who has more Vitamin D? People who are healthy enough to be active outdoors, getting sunlight.
My guess is that this is the whole effect, but that Scott's conclusion "supplementing might help and it probably won't hurt" is correct.
Most online retailers in the UK seem to sell tablets with 4000IU each, and 6000 seems common in the US. Then the Brazilian trial you mentioned used a single megadose 200,000IU (!)
I find it hard to square the NHS's cautious position with what seems like a wide range of dose choices in practice. Any idea what gives?
My understanding is Vitamin D takes a while to accumulate in your system. Large doses are okay as a one-off, but not something you should take daily. I've seen 20K IU used as a weekly dose, for example. 200K IU sounds a bit huge though?
I suspect the NHS (and FDA) need to be cautious about supplementation recommendations because it depends on the amount of sunlight you get. 4000IU is probably fine for someone indoors all day, but might be too much for someone who's outdoors a lot. I looked into this at one point, and had trouble finding any good studies or recommendations that accounted for sunlight exposure, so would also be curious if anyone else has better info.
I have read (sorry, don't have a reference) that 10,000 IU is the do-not-exceed number. Vitamin D takes a long time to build up or discharge from the body (like around a month), so short-term dosing isn't likely to cause trouble.
I would also look at the enthusiasm for Vitamin D in a broader context. Over the past 75 years there has been sequential excitement and enthusiasm for different vitamins/minerals as panacea for many human diseases. Cycles of Vitamin C (the great Pauling first one), various B vitamins, Selenium, Zinc, Vitamin E (for a long time). Medical specialities in diverse fields (immunology, oncology, ID) all simultaneously become excited by the new trendy vitamin/supplement. Initial small studies often show dramatic benefit in whatever metric is being assessed. Sadly, almost universally when large, controlled studies are done, there is great disappointment (and sometimes even negative benefit). Vitamin D is the latest of these cure-all supplements. You could probably look at a graph of medical literature/reports on each of these magic answers, and Vitamin D is certainly trending. But skepticism is in order. But hey, it probably can't hurt...
My general physical health got a lot worse when I first started staying at home all the time (I've literally left my house/yard only twice since last March, and I think it's been a month or so since I've been in sunlight). I had back pain, wrist pain, joint cracking, and fatigue at various points (I'm in my mid 20s). Since I started taking vitamin D or other multivitamins, I have basically not had any such issues. I expect that my COVID avoidance is way more dramatic than most people's, but I think most people have been getting less sunlight than they used to, and if so, Vitamin D seems great for improving their general physical health.
One of the instances of me leaving the house was a few months in, where I thought that perhaps I should get exercise and go for a walk. However, I was unhappy about not being able to stay 6+ feet away from other people, so I aborted that and have not gone on a walk around the block since. I have a VR headset now though, which helps with exercise if not sunlight.
My roommates and I have all of our groceries delivered. My roommates are a bit less paranoid than I am and have done various things (dental appointments, trip to visit mostly-isolated family members, emergency CVS trips, etc). I planned ahead and got a haircut / dentist appointment right before our state had its first case of community transmission, so I haven't needed to do such things myself (I've been actually flossing daily to compensate for increased dental risk).
I also have a friend who visits every week or so, but he doesn't go to any public places and gets COVID-tested in his lab every week before visiting. My roommates also both have SOs who visit, but they also live in houses where everyone works from home and never goes to public places (those house might allow grocery store visits too, I'm not sure).
One of my instances of leaving was a two-week trip where I walked to a friend's apartment and stayed there (I was isolating from my roommate when he got back from a plane trip). The friend and their roommates also got delivery and never left their house (except for medical appointments). We did have to leave the apartment building once when there was a fire alarm, but that was it.
Please correct: >>we can be pretty sure that their COVID is caused by Vitamin D.<< ==> >>we can be pretty sure that their COVID is caused by lack of Vitamin D.<<[and delete this commentary]
My strong, strong prior here is that Vitamin D may be a decent biomarker, but it's a lousy therapy. It's been thrown at nearly every indication under the sun in RCTs, and almost always returns null results. To me, the most plausible explanation is that low Vitamin D levels are correlated with biological states (malnutrition, sedentary living, inflammation) that predispose to poor outcomes, but short-term Vitamin D supplementation does not address the underlying predisposition.
*grumbles about how "vitamin" is not a meaningful category, and, in the case of cholecalciferol derivates, we're actually talking about hormonal replacement instead of vitamin supplementation*
Great summary. A common "bad take" submission I've never run is along the lines of "the race disparity is explained due to vitamin D." Probably not, but maybe a little. It just strikes some people as a completely bonkers suggestion, so I get sent it regularly.
Also gets tarred by association because same people pitching also hock zinc and HCQ. (And now ivermectin, another "bad take" I can't pull the trigger on.)
1) Mendellian randomization and the Biobank studies are both invalid because people supplement in response to genetically low vitamin D, which violates one of the assumptions underlying MR. This is especially true since government guidance in the UK changed pretty dramatically on vitamin D supplementation
2) If you're looking at a racial case for vitamin D, you should really look at immigrant pairs like African immigrants to Sweden, or Indian immigrants to the UK. In all cases you see low Covid rates in poor sunny countries and high covid rates among immigrants from those countries to rich northern countries. This is the Ricketts pattern and strongly indicates vitamin D's involvement. https://shotwell.ca/posts/africa-covid/
3) The problem with the Brazillian study is that vitamin D was given way to late. If it's active against Covid it's because it works basically as an anti-viral, in that Brazillian study they gave vitamin D on average 10 days after symptom onset by which time the virus had cleared. All the supplementation studies where vitamin D has been given in or before the viral replication phase have been positive.
IDK about Africans in Sweden but the British South Asian population is much more urbanised than the total British population and probably moreso than South Asia in general.
Not really, the population density of Nairobi or Dehli is many times higher than Stockholm or London. Also South Asian people in London are have a Covid jeopardy that's several times higher than white people in england after accounting for income, preexisting conditions, and neighborhood. https://www.medrxiv.org/content/10.1101/2020.09.22.20198754v1
This means that Indians in the UK have a covid jeopardy that's several hundred times higher than those in India despite having more money and better medical care.
As an aside, I think one of the biggest unanswered questions about COVID-19 is why so few people in equatorial Africa have died. Equatorial South America has done pretty terribly (Manaus = 3.1190°S), and outcomes from the first world indicate that African ancestry does not confer a survival advantage.
Seems for individuals, the first question is whether one might be borderline vitamin-D deficient to begin with (little sunlight, milk-free diet for some reason, etc.). It might help more for Covid in such folks (and only in such folks?). And all sorts of below-the-radar effects of low-D may well get solved besides.
This article seems to miss discussion on the most important claim I've heard around Vitamin D supplementation: that daily Vitamin D supplementation substantially reduces your risk of contracting severe cases of covid.
This is quite different from a) vitamin D reduces your risk of getting covid (why would it) or b) taking vitamin D when you get covid improves outcomes.
My understanding is that *it takes a long time to increase serum vitamin D levels through supplementation.* See this article from the NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820059/ . In short: infrequent, low doses (1-2k IU) of vitamin D do not raise serum vitamin D. Dose and frequency (per week) mattered more than duration, but duration was at least a month, not 7 days! And duration effects were increasing - the longer you took vitamin D, the bigger the effect!
Scott dismisses this entire argument by saying "people who can do anything consistently for a year will do better" without actually analyzing it in more depth. No, you actually have to take vitamin D supplements frequently over time (at least one month, with effects increasing up to 6 months), at higher dosage for them to have an effect. Dismissing the underlying mechanism as being a selection effect, means that Scott misses the best argument in favor of long-term vitamin D supplementation.
This hypothesis may be wrong - maybe that research paper is incorrect, maybe there's more evidence behind Scott's handwave - but right now it seems to me that Scott is ignoring the crux of the debate: can long-term vitamin D supplementation reduce your odds of a severe covid case, conditional on you getting covid? Scott unfortunately does not address this question, which is the most important one, IMO.
Given that long-term vitamin D supplementation does increase serum vitamin D levels significantly more than short-term vitamin D supplementation (at least according to the research), I am inclined to believe the research does suggest that vitamin D supplementation can reduce the odds of contracting *severe* covid cases much more than Scott does.
Long-term supplementation works independent of Vitamin D levels, which makes me think confounder rather than real effect. Also, the correlational studies ought to capture the same effect that long-term supplementing should have, and they show nothing.
That's quite different, no? The study you linked (https://pubmed.ncbi.nlm.nih.gov/33515005/) says that taking vitamin D consistently is associated with a lower risk of getting infected with covid, but that is different from the conditional risk of getting a severe covid case once you have covid. Vitamin D can "work" not just by preventing you from getting covid, but by helping you fight it off once you get it.
I can understand how conscientiousness may be a confounder for the risk of getting covid at all (e.g., related to how often you wear a mask), but I can't understand the causal mechanism between conscientiousness and how bad covid is *once you have it.*
Once someone has covid, it seems to me that it comes down to biological processes, not personality traits. Given the evidence that a) it takes high duration, frequency, and dosage to raise vitamin D levels b) lower levels of vitamin D are associated with worse cases of covid *once you have it,* the mechanism seems like it is there, but nothing that has been cited actually investigates that specific mechanism.
I'm with AB but on the specific point of how germ avoidance would reduce the severity of covid conditional on testing positive for it, 1. false positives and more importantly 2. initial viral load determines severity
As far as mechanisms, there is circa 30 years of research illustrating Vitamin D’s involvement in activating/modulating the diverse weapons of the innate immune system, the “dumb” first line of defense that doesn’t require antibodies or the subtleties of active immunity. The cells of the innate immune system, as I understand it, express the VDR, Vitamin D Receptor, for signaling purposes related to active Vitamin D. More specifically, one component of the innate immune is a range of antimicrobial peptides that are produced, something akin to rather indiscriminate artillery. One such peptide that’s gotten a fair number of mentions already in relation to COVID is known as LL-37. This pre-print claims to have found that the peptide LL-37, which is induced by Vitamin D, directly inhibits the binding of SARS-CoV-2’s Spike protein to the ACE2 receptor, which is the receptor on the cells of various organ systems that this coronavirus uses to infect. (https://www.biorxiv.org/content/10.1101/2020.12.02.408153v2)
I think the prior here should be other respiratory infections, where long term vitamin D supplementation was shown to be effective while high dose bolus supplementation (like that used in the Brazilian trial was not.
To what degree can it be that people with low vitamin D are more conscientious (indoor workers) and therefore have a lower risk of getting infected?
Seems like the studies shouldn’t control just for race, but also for behavior.
I’d say low vit D white people will be more likely to get infected due to low vit D, but less likely to get infected due to behavior. Which could easily mask the relation between vit D and covid incidence completely.
It would be better to look at severity for this reason, since it’s presumably affected less by conscientiousness than incidence — but it still *is* affected. Conscientious people can do other things that decrease the severity.
One the one hand, you're right that a 50:50 bet is pretty nice if you have 75% confidence. On the other hand, a $100,000 wager is substantial enough even plenty of upper-middle-class people aren't likely to be willing to tolerate the risk. This is part of my irritation with regards to these rootclaim challenges... are they showing that people are being irrational, or are they just showing that most of their readership doesn't have sufficient risk tolerance to throw large sums at their shenanigans for claims with middling confidence?
I don't know about you, but I'm happier putting my disposable income in a well-diversified portfolio.
"We are open to discussing lower or higher amounts, and the funds can be pooled from multiple sources."
I'm not familiar with them enough to know how much lower they'd go, but seems like pooling from multiple sources would mostly solve the problem you mention? Agreed that most people reading this, myself included, wouldn't plunk down $100k, but it doesn't seem crazy that n people would be willing to bet $100k / n.
I think this qualifies as an enema recommendation, though perhaps there's enough evidence in favor that it doesn't. An old joke:
An actor collapses on stage, and a doctor is found in the audience. As he tends to the actor, an old lady calls from the cheaper seats: "Give him an enema!" She is ignored. She cries again, "Give him an enema!", and again, nobody pays attention. After a third "Give him an enema" is heard, the doctor turns, and says, "Ma'am, I assure you, giving this man an enema would do him no earthly good whatsoever." The lady replies, "Well, it couldn't hurt."
I think you took the wrong side regarding the Spanish Vs Brazilian trials. The Spanish one was peer reviewed. It was better conducted with more activated form of vitamin D. It is totally not wise to give D3 to already hospitalised person. It takes precious time to be converted to the active form. The Spanish trial also was small achieved remarkable p value. This is the unbiased estimator which means that no matter it was small study, the results proves causality. Patients were divided for the true treatment or placebo randomly by a computer. How can one argue against this method ...
But if we were living in a world where the Spanish study is true, I can't explain the Biobank and the Montreal genetic study would give negative results.
I can think of lots of good reasons why a seemingly-decent study would wrongly yield a positive result (we missed a confounder, conflicts of interest, ...) but it's much harder to believe a strong-looking study would *miss* a phenomenon with such a huge effect size.
Agreed except you have to account for the possibility of scientific fraud (or its accidental equivalent) especially in the first study that popularizes a sexy new hypothesis. Also, people are presuming that the form of D which is 'active' for calcium absorption and bone hormonal signaling is the one that's useful for respiratory/antiviral effect. We really need to be agnostic about which step in the sunlight->D chain is useful for fighting colds. Many things have more than one use in our body.
The latitude thing might be exterior UV killing COVID on surfaces. In Asia, there's been a buying spree for indoor UV lamps to provide some viral load reduction indoors, complete with timers and motion sensors and shut off whenever a person walks into a room.
I have a very strong prior on surface and contact transmission, so I don't really buy the "unimportant surfaces" idea. A mask will protect you from droplets, but it won't protect you from your hand wiping your nose or touching your face.
Many chunks of East Asia have 99% mask compliance rates and still have transmission chains.
But a mask at best protects you partially from aerosols, unless you're wearing a very tightly fitted N95 or better. I don't think you have 99% compliance on that.
My current guess is that surfaces are really important for the kinds of bacterial infections that cause major problems in medical settings, so the medical system over-learned the Semmelweis story, especially when they were trying to kills the miasma theory in favor of the germ theory. But the other part of my guess is that surfaces are much less significant for respiratory infections than we've been told.
It would be amazing if someone were actually able to do a thorough examination of a representative set of cases in an ordinary flu season, to figure out where everyone picked up the virus. But unfortunately I don't think we'll be able to get that, to properly confirm or deny my conjecture.
In East Asia, it was common knowledge that masks worked and all the professors, to the man, were screaming for masks from January 2020 onwards. It is also common knowledge that you should "wash your hands after taking public transport and avoid touching your eyes, nose, and mouth". Hand hygiene, hand hygiene, more hand hygiene!
Granted, that does not mean surfaces are necessarily important, but it's been drilled heavily into the population.
What are the risks of those UV lamps generating UV-resistant germs for us in 10 years? Is there a way for this to happen, or is it just too much to overcome at once?
It would be useful to check the methodologies utilized for measuring vitamin D levels in these studies, since it seems that the measured value for 25-hydroxyvitamin D (predominant in testing) largely depends on differences in vitamin D binding protein (VDBP) between individuals. Ginsburg & coworkers identified a vitamin D metabolite ratio (VMR) which is dependent on concentration and not on the amount of VDBP that is present in an individual.
> The VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status.
"The Vitamin D Metabolite Ratio Is Independent of Vitamin D Binding Protein Concentration", Clinical Chemistry, 2020, doi: 10.1093/clinchem/hvaa238 , https://pubmed.ncbi.nlm.nih.gov/33188595/
I can help with the seasonal pattern. The smallish bump in the summer was in the hotter, southern states primarily. The much larger bump in the winter was in the cooler, northern states primarily. Common theme? People spending lots of time indoors in climate controlled environments.
So in order to test this one could run zip code latitude vs month of infection, or average zip code temp that month. I'd predict that temps outside of 55-85 or so cause a bump in COVID.
There is a metric used in the energy industry that tracks this called cooling degree days and heating degree days. You can even trade financial instruments on that number. It seems to me that the pattern in the US has been outbreaks when HDD's or CDD's start increasing in a location.
It looks like there's another randomized controlled trial in the works for Vitamin D supplementation being planned, from Wang et al. (N = 2700): https://doi.org/10.1016/j.cct.2020.106176
That's a pretty substantial sample size. Can someone take a look at the trial design plan and see if it's reasonable? That isn't my skillset.
A veritable cacophony of Vitamin D studies. I'm frankly surprised you implicitly lend credence to the results. Given the file drawer problem, replication issues and paradoxes within your speculations, there's really no basis for your last 3 paragraphs except intuition/ guessing/ idiosyncratic heuristics. You certainly know that mechanistic thinking just doesn't go very far in medicine; and that case-control and other observational studies are sometimes useful but overall weak. To argue seasonal variation may occur related to sunlight/ vit D while later noting levels are usually stable over long periods is not consistent.
Those criticisms aside, your collection of studies just shows once again how poorly medicine and the lay public have been served by academia in a time of great need. Large well-designed studies capable of definitive answers are sorely lacking among the utter cacophony.
> And maybe some day, after countless false leads and stupid red herrings, one of the claims people make about this substance will actually pan out. Who knows?
One thing that always struck me as weird about vit D is how ubiquitous it is among health-conscious people
I wonder if th lis is a case of memes spreading with no reason, or of the studies missing an important factor.
It's been years since I looked at it but the kidney stone risk should be lowered by simultaneously supplementing vitamin K (which is another one of these quite likely positive supplements).
Regarding summer: sars2 is highly unstable when it comes to light, heathings dries the air which makes your mucous membrane dry and live inside has no wind. Source: christian drosten's podcasts.
My thoughts are that possibly low vitamin d could also simply be a marker of poor diet and lifestyle.
A possible downside of supplementation could be that it makes more postive change less likely.
I.e. more outdoor physical activity, combined with nutrient rich diet will likely* sort vitamin d levels, plus have a host of other benefits that would be missed by supps alone.
Supplements in general have a very poor track record, possibly as many people end up taking them as "substitutes" to a nutrient rich diet rather than supplements? (Purely speculative).
Given the choice between go outside, exercise and eat well, vs take a pill, many will opt for the pill. Which is fair enough providing we know the true efficacy of the pill and can make the trade-off. But I don't think this is the case (for vit d and covid or any other supp and health outcome).
* Possibly for darker skinned individuals, living at northern latitudes, working indoors all day it might be impossible to achieve optimum vitamin d levels through sun exposure and diet?
n all of this you haven't mentioned to what level of Vitamin D you are testing against. The level described as "deficient" for bone health isn't the one described as "deficient" for respiratory health (if that is indeed a thing).
If you want a null hypothesis to aim at, here's one
"The bottom line is that there is no downside to increasing our intake of vitamin D to maintain serum 25(OH)D at at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve optimal overall health benefits of vitamin D."
Reassess against that much higher than standard level and everybody can avoid talking past each other.
In this instance the obsession with the precautionary principle is to avoid hypercalcemia at all costs - even if that means people succumbing to respiratory illnesses. Something they didn't do, for some reason, with masks.
"The bottom line is that there is no downside to increasing our intake of vitamin D to maintain serum 25(OH)D at at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve optimal overall health benefits of vitamin D".
The recommendation buried in that study is 4,000-6,000 IU per day, which falls in line with the maximum recommended limit of 4,000 IU/100 μg. But this does not mean that someone should then decide "if that much is good, then 10,000 IU would be even better!" because NO, IT REALLY WOULD NOT BE. And again, get it from your diet and exposure to sunlight, not from dosing on supplements (unless during winter months when no sunlight and/or your diet is really crappy).
We know that getting covid is correlated with breathing it in. We can be fairly confident that better ventilation reduces the risk of covid. What do people do in warm sunny weather? Open windows, and go outside. We should expect the latitude and seasonal effects, even if vitamin D was nothing to do with it.
My intuitive take is that vitamin D has some effect on immunity but compared to bone health, it is much less pronounced. The bone mass is comparatively large and we need a lot of calcium therefore vitamin D deficit can quickly cause problems. Whereas the immune system can adapt with lower vitamin D levels.
Very low vitamin D levels in people could make the immunity much worse too but in practice we notice problems with the bones first and treat them accordingly. Supplementing subclinical vitamin D deficit provides only marginal benefits.
In conclusion, it is good to maintain vitamin D levels in the recommended range, and take supplements if you need to, mainly, to help your bones. Maybe it will have a secondary benefit by slightly improving your immunity too but don't rely on that too much.
Given that almost all of us get way less sunlight than our ancestors, I would advocate supplements anyway, to bring us up to the levels that our bodies are adapted to.
Vitamin D has low toxicity, so it's very unlikely that you err on the side of having too much.
The best explanation I've seen for the seasonal and latitude nature of the virus so far is indoor humidity. If the temperature is below 15 degrees C, the air indoors is heated and becomes dry. This causes droplets expelled from the mouth that would settle in more humid conditions to evaporate and become smaller and float around for longer providing a more effective transmission in confined spaces.
A leimilar but lesser effect can occur from airconditioning in summer.
In places with really sealed up indoor spaces the humidity is lowish in winter but not as low as some not as cold places because the less sealed up spaces have more cool outdoor air comes in to be heated. Places with winter daily maximums in the 5 to 15 degree range tend to have the dryest indoor air in winter.
Seasonality/latitude dependence could be completely explained by people gathering indoors vs. outdoors. Very hard to get aerosol transmission in a windy park.
People still spend a lot of time indoors in all seasons. Virus transmission changes by a factor of 3 in most temperate climates throughout the year but people's time in offices, homes and shops does not vary by anything like that much.
Regarding the Mendelian randomization study: When you buy a 1/4" drill bit (or perhaps a 6.5 mm drill bit if you're into that sort of thing), it's not because you want to own a drill bit, but because you want to own some 1/4" holes. In the same way, we don't want vitamin D in our systems because the vitamin D molecules strut around the body punching corona viruses in their little faces, ripping apart cancer cells, and blocking the depression rays emitted from the dirty laundry pile. We want it in our system because it does something else. Perhaps the people with hereditary vitamin D deficiency have some other source for this, uh, "something else". Maybe they make their 1/4" holes with punches, lasers, or well-disciplined termites.
You should really clarify your definition of "Asian". That term covers a much, much broader range of latitudes than white or black does. Probably difficult to suss out small lineage differences in the entire subpopulation, but you could just focus in on two groups with different historical ranges, like Koreans and Indonesians. Or Native Siberians, if you can find data.
> The loose ends that bother me the most are the seasonal pattern, the latitude data, plus the increased risk of hospitalization and death in Asians. I don't have a great explanation for those.
Couldn't the first two be explained simply by the fact that during the winter in northern countries, people tend to meet indoors rather than outdoors? This facilitates the spread more.
"For example, infection rate from coronavirus seems latitude dependent; in general, the further north an area, the worse it's been hit."
This isn't obvious; the statistics from the southerly countries aren't as reliable as those from the northern ones, and it is known many southerly countries (Mexico, Peru, Bolivia, Ecuador, Indonesia) have been very hard hit. It was true during the first wave in the U.S. and at the beginning of the third, but Mississippi, Louisiana, Alabama, and Arizona have been some of the hardest-hit states. In the E.U., Spain has been hit rather badly. It is true that Russia, the Dakotas, and the U.S. Northeast have been very hard-hit, though, but the U.S. Northeast pandemic seems to have been due to its better connectedness, while the harsh pandemic in the Dakotas and Russia was likely due to lack of social distancing.
Does anyone have a quantitative idea, which proportion of the skin should be exposed to the sun for how long for normal cholecalciferol production, let's say for a maximally light-skinned bloke? Where I live, from october to april, the only exposed body part is face, and we get to see the sun every 3rd day or so. Is there any chance that we're still producing adequate amounts of cholecalciferol if we spend, say, 1 hour a day outdoors?
Get the free dminder app. It was developed by a top Vitamin D researcher, and it will show you exactly how much Vitamin D your skin is producing in real-time, based on your location, the angle of the sun, your skin type, the % of skin you are exposing, etc.
You're probably not making any vitamin D from Oct-April if you live above the 37th parallel. I posted a 4 question Vit D calculator on my site https://vatsalthakkar.com/vitamin-d-calculator.html (based on treating >1000 patients with Vit D deficiency, myself included, and from published studies incl one based on > 20,000 patients who supplemented).
Lastly, I'm not sure where the idea came from that levels are stable over time. There are studies showing the 10-15yr old UK Biobank levels don't correlate well with recent levels. IIRC one correlation coefficient was around 0.4, which makes more intuitive sense in the first place. The idea of stability over time is reasonable in the face of no measurement or intervention/change, but the UK Biobank participants didn't have their levels hidden from them. It's pretty reasonable to assume those people who discovered they were deficient as a result of the UK biobank participation took steps to correct their deficiency. Their doctors certainly should have encouraged them to do so.
So trust Kaufman et al, Merzon et al, Meltzer et al more.
Dismissing the Indian RCT is inappropriate. This was small n but a well designed trial registered in advance and regardless of the importance of seroconversion clinically in terms of severity to individual patients, this data clearly shows a causal link whereby vitamin D affects SARS-CoV-2 infection.
Favoring the Brazil trial over Cordoba, Spain is also picking the wrong one. The Brazil trial didn't start giving patients D3 until they already needed supplemental oxygen (90% of them at baseline) because they were already 10 days post symptom onset and they were only average 7 days from discharge from hospital in terms of recovery. D3 doesn't ramp up fast enough to make a difference that late in infection is the only conclusion that can be drawn. See the comments of the medRxiv page of that Brazil study for many comments along these lines and other issues: https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1#disqus_thread
The Cordoba study used calcifediol which skips liver conversion and restores D levels within hours and thus had a much better effect. If they had used it in Brazil maybe the results would have been better. What's more, there's now a new preprint which has statistical issues but nonetheless adds to the positive data. It also used calcifediol and had 10x the patients (though the randomization was by hospital ward not patient, but it still makes the D helps conclusion more likely despite its flaws):
I'm not sure why the Brazil hospital in that study got the patients so late in the infection. Worse healthcare infrastructure in that country?
But the trend is clear: 3 of 3 randomized controlled intervention studies started at hospital admission in countries in which that hospital admission came before patients were so far along that they mostly needed supplemental oxygen all showed positive results. And 2 of 2 calcifediol studies showed extremely positive results.
You said, "in the past I have learned to side with negative RCTs rather than astoundingly massively positive ones when the two conflict." That's a reasonable default for clinical trials of still-on-patent pharmaceutical agents because those tend to be sponsored by the pharma company that has strong financial incentives. For trials of natural agents especially those run by non-industry groups, the opposite should probably be the default. Eg see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487184/
You said, "I am going to assume that whichever doctors ran these studies did not completely bungle them and use forms of Vitamin D that could not possibly have worked in the time period involved." Completely bungled in the Brazil study is a reasonable conclusion. It's not completely absurd that it could have worked in the time involved, and the study organizers may not have known how far from recovery the patients would be when they started, so we don't have to fault them for running it. But the late stage of initial administration compared with the time it takes for that version of D to ramp up means its negative result cannot be applied to initiating the same treatment earlier in infection, nor does it cast doubt on D for prophylaxis, nor is it negative for calcifediol which is much faster acting.
Thanks for posting this. Any opinions on N-Acetyl Cysteine (NAC) supplements? I have read/heard claims of reduced covid symptoms associated with it’s regular use.
How many scientists & doctors work on the NICE committee?
Here's a list of hundreds of scientists & doctors who say the evidence is convincing enough that it should be default to use vitamin D for covid as a precaution: https://vitamindforall.org/rollcall.html
It terms of credentials, these groups include many of the top vitamin D researchers in the world (based on citations), a former surgeon general, and many notable names.
Based on the prior 2 corrections I just posted in earlier comments (on Hastie & on the clear pattern from the RCTs) and this appeal to experts, you might want to update your % guesses on D's relevance. My personal guesses are 80% chance that D affects infection risk & 80% that it can help as treatment if given early enough in infection or as calcifediol. And 99% chance that benefits outweigh costs.
Correct reading of the evidence together with understanding the underlying biology makes the situation very clear. It just isn't quite clear at the level of approving a new pharmaceutical drug, and the big problem is that that is the evidentiary bar that NICE and other officials at 3-4 letter acronym bodies are applying. That's not the way to handle public health especially in an acute crisis. It's *astoundingly* clear that the balance of risks is such that increasing vitamin D intakes and reducing deficiency rates is a clear public health win net-net, especially now.
Good piece. Not mainly for the conclusion, which doesn't hinge on the analysis, but for an example of what a careful examination of evidence looks like.
"We assume that people with the genes for low Vitamin D in fact have low Vitamin D. And this isn't confounded by anything; we know their low Vitamin D is genetic. So if these people get COVID more, we can be pretty sure that their COVID is caused by Vitamin D."
Probably the assumption in the first sentence there is at least somewhat false, no? Since people can change their vitamin D levels by taking vitamin D.
Also, it could be that a genetic predisposition to low vitamin D is associated with some *other* genetic thing that has an effect on severity of covid infections (in either direction - so you could get an illusory effect if it's associated with something that makes covid worse, or an illusory absence of effect if it's associated with something that makes covid less bad). (I don't have any specific knowledge that this is the case, but it seems like a gap in the logic as presented here.)
Scott, I suspect it was delayed by the Blog closure but I've definitely been waiting for your thoughts on 'no evidence' and the other scientific messaging in this pandemic. The language used to scientific uncertainty to the general public needs a rethink and I suspect is the source of much public disinformation.
I don't blame Joe Public for thinking 'no evidence' for a *thing* means definitively that the *thing* doesn't work.
Vitamin D for patients admitted to hospital could cut Covid deaths by 60 per cent University of Barcelona preprint for the lancet not peerreviewed yet... I had low Vit D (22ng/ml) when last measured 4 yrs ago (after spending 45min everyday in the midday sun in June...... I started taking 2,000 iu but after reading a few articles associating low vit D levels with the worst outcomes in covid I started taking 10,000 iu (250mcg?) but will be getting tested after my 2nd vaccine shot (1 week) I am aiming for a blood level of 60-80.... Depending on your age and genetics it can take a lot to boost your levels up.... any blood level up to 150 is most likely safe
When the limit of 100 was decided on the actual research showed a level above 300 was toxic....but to err on the safe side an upper limit of 100 was recommended....
Yeah. I took 5000 IU daily for years (upped it to 10,000 in 2020 on more or less the same logic/spec as this post describes), and that dosage was barely keeping my level in the 30s, ie, in the very low end of normal range. Not everyone absorbs vit D equally efficiently.
The issue was already analyzed probabilistically by Rootclaim. They are also offering a $100,000 bet on it. If you're at 25% it's easy money for you (but don't, you'll lose - your analysis is wrong on many points).
25% isn't "easy money". It might be "strongly positive expectation", but that is quite different from "easy money" in the absence of easy ways to diversify.
Somebody on facebook argued, that Hydroxychloroquine is still in the game. Because the trial, which said it didn't help was made by Surgisphere, which gave fraudulent data. (I a lazy to look it up on my own).
There were many, many trials, not just a few. It's true that a couple of the ones that said it didn't help were fraudulent, but there were many others that weren't.
1) Vitamin D correlates with activity/exercise levels pretty strongly. Consider this as a serious confounder in any observational study.
2) The Mendelian Randomization study I have strong reservations about. To run MR, you need to make strong assumptions about the genetic variants that you are using. So MR makes sense in cases where you know a lot about the variants. But here they are doing a GWAS to get the variants, i.e. taking anything that associates with Vitamin D levels. There's no theoretical reason to assume a priori that these variants have the properties needed to run this MR. Instead, you do some statistical tests and hope you can catch it if it's a problem. But those statistical tests make their own assumptions that I don't find very plausible.
The authors know this and address it and do a reasonable job at that. They try restricting just to variants that lie near genes that are known to directly impact Vitamin D and see the same thing, and they toss out variants that are also known to impact other phenotypes and so could confound. But it's just the reality of the problem: MR is a bit questionable if you haven't study your variants carefully. The fact that they find a null result makes this all less concerning, though it is plausible that confounders could cancel out the true effect.
I always felt, right after reading the original speculation, that Vit. D is a prophylactic rather than a cure. Firstly, you should have been taking this as a supplement already. So, if you have a decent amount of Vit. D taken as supplements cruising in your bloodstream; it is not going to prevent you from getting infected; but do two things: 1) maybe increase the viral load required for infection, 2) when infected the symptoms won't be as severe.
All these studies that you referenced don't seem to contradict this, or am I reading you wrong?
I would note that in general, anyone taking Vitamin D3 regularly in amounts of say 4000 IU a day, would be well served to take Vitamin K2 (probably MK-4) and Magnesium as well. And look into a source of Vitamin A (cod liver oil).
I'm 75 years old, and decrepit enough to be unable to what I used to. Vitamin D pills at Sam's cost pennies per day, hence I have been taking megadoses of it since June, 2020. No downside, possible benefits.
What is the explanation for 80%+ of Covid positive patients in Spain being vitamin D deficient? I would also like to see a regional analysis of Vitamin D deficiency rates in Brazil. Also, what about the 50 other studies? Overall this analysis seems a little weak, although the lack of enthusiasm from authoritative institutions is surprising.
The post-symptom/post-positive RCTs that find a (gigantic!) effect use calcifediol - the form that oral cholecalciferol slowly turns into, over a ~week. The RCTs showing no effect use cholecalciferol, whose conversion into calcifediol won't outrace an infection. I don't blame some researchers for trying plain cholecalciferol - it's a cheap OTC supplement, and maybe megadoses would help! Meanwhile calcifediol is a prescription-drug, & expensive in the US. But assuming "assume that whichever doctors ran these [cholecalciferol] studies did not completely bungle them" is picking one set of researchers arbitrarily to respect, & ignoring the contrast signal between the two choices. Why not assume, conversely, that the researchers who tested calcifediol did not completely bungle their inclination to test something with distinct effects from cholecalciferol? (The effect sizes in the calcifediol studies are gigantic!)
D3 needs to be taken with K2 (prevents kidney stones and other calcium mismanagement effects), magnesium (increases resorbtion) and A (reduces side effects from K2 related enzymes). It also needs to be taken with oil. And in small doses (5-20k IU/day) over a long time, megadoses like 200k IU will have way less resorbtion. I've read dozens of studies, even very recent ones, that showed side effects like kidney stones or artery calcification because K2 was ignored. Never ever assume the people doing these studies are aware of these problems, assume the opposite unless its expressly mentioned in the study. Keep that in mind when facing supposedly simple questions like "did they give an oil-soluble form/gelcap or the much cheaper dry form and if its the latter, did they give it with oil or fatty food". "Surely they couldn't have fucked up this badly"- yes they could lol.
I became a paid subscriber just to post this comment. Here is a hypothesis, which explains the seasonal variance and the latitude data without vitamin D.
Red light.
A very specific wavelength of red light penetrates the skin very deeply and is absorbed by the respiratory enzyme cytochrome c oxidase, which is involved in the electron transport chain in mitochondria, causing an increase in intracellular ATP.
Red light therapy aka low-level laser therapy cures a lot of weird problems. This specific wavelength of red light is also component of sunlight. We get more of it during summer and near the equator.
Vitamin D could be a red herring. Sunlight can do lots of other things too.
Here's a longer version of the above. I posted this on my Facebook yesterday.
This post might solve the pandemic. Or it might not. I need someone smarter to check my work, so I’m posting it in public in the hopes that it will reach someone, who can check it.
The data shows that COVID-19 has seasonal and latitudinal variance, so we know that sunlight has something to do with it. Everyone knows that when sunlight hits your skin, you get Vitamin-D, so doctors started doing clinical trials on COVID patients involving Vitamin-D.
Preliminary results are in and it seems like there is no signal in the noise. Vitamin-D does not seem to be the important factor here. But sunlight clearly is.
That seemed like an interesting problem to work on (instead of actual work) so I started looking into it.
I think I can explain the seasonal and latitudinal variance of COVID-19 without Vitamin-D. My hypothesis can be tested for cheap and with zero risk to human health. And I can explain the full biochemical pathway of this effect.
Vitamin-D is not the only molecule produced by sunlight acting on the skin.
There is another one, much more important, but very few people know about it, because it was discovered by Russian scientists in the 1990s and not widely studied outside Russia. (Based on the name of the chief scientist, who discovered this effect, she’s probably Estonian.)
If you put your hand in front of a bright white light, what do you see? You see that only red light penetrates through the thinner parts of your hand. This implies that red light goes very deep in your body. A centimeter at least.
Red light with a wavelength of about 810 nanometers is absorbed by an enzyme called "cytochrome c oxidase", which is part of the electron transport chain inside the mitochondria of every cell. The result of this is a photochemical reaction, which boosts intracellular ATP production. ATP is the "fuel" that cells use for most internal processes. When a muscle cell contracts, for example, it spends ATP.
With more ATP available, the cell can do more. Including repair. So your body recovers better and faster.
This effect is used by a "new" field of medicine, which has many names: "red light therapy", "photobiomodulation therapy", "low-level laser therapy", and even "cold laser therapy". The content is the same: intense red light is used to boost body's own healing mechanisms.
I put "new" in quotes, because red light therapy was a pseudoscience for 50 years until Russians figured out that it works by stimulating ATP production via the absorbtion of red light by cytochrome c oxidase.
It's not magic and it's not a super powerful effect unless you haven't gotten enough natural light. Based on the seasonal and latitudinal variance of COVID, however, it looks like red light therapy might be the key to solving this pandemic.
There might be a third light-based biochemical pathway besides Vitamin-D and cytochrome c oxidase that could instead be the key factor in explaining COVID’s seasonal and latitudinal variance, but I haven’t found one.
Here is a scientific overview of the history of red light therapy. How it went from pseudoscience to acceptable medical practice:
Quote from that article: “The work of Tiina Karu in Russia was instrumental in putting the mechanism on a sound footing by identifying cytochrome c oxidase in the mitochondrial respiratory chain as a primary chromophore, and it introduced the concept of “retrograde mitochondrial signalling” to explain how a single relatively brief exposure to light could have effects on the organism that lasted for hours, days or even weeks”
I searched on pubmed if any doctor has tried red light therapy on COVID patients and found two case studies, both showing remarkable improvement:
I also found a paper recommending that doctors try red light therapy for COVID: "Based on the clinical experience, peer-reviewed studies, and solid laboratory data in experimental animal models, LLLT attenuates cytokine storm at multiple levels and reduces the major inflammatory metabolites."
If I'm right and COVID's seasonal variance and latitudinal variance is mediated not via Vitamin-D, but via cytochrome c oxidase, then all you need to test this hypothesis is to get some suitable red light therapy LED panels and hang them above COVID patients.
I'm pretty sure you don't need to get an ethics board approval to change the lighting in a hospital room from white to red.
A statistically significant randomized trial could be done in any hospital for about $10k spent on lamps, with zero health risk and zero ethical considerations. Just keep doing what you're already doing, but randomly put half the patients under red lamps.
If it works, then soon we're all gonna have red lamps in our homes and we're gonna be so much healthier than before!
P.S: If I'm correct and this idea ends up solving this pandemic, then please send some ETH to my wallet at 0x4aD7690c3cCe53De570738dDE90B8D01027a0f84 It would be funny to say I got a car for solving the COVID pandemic 🙂
Seasonality is an independent variable via temp and humidity, and one study neatly combined them in enthalpy, which you may remember from school! (How do I do hyperlinks?**)
You may find a bigger effect with selenium.
Vitamin D itself has no effect: it's levels in the blood of 25(OH)D3 and its metabolites that count.
The reason it doesn't work if vitamin D given after admission is that it takes 2 weeks for serum levels to rise, so that's way too late to do any good, so the Brazil study was pointless, and was anyway a preprint, and your "use in hospital" figure should maybe be lower than the other one. The Spanish study has the same problem and also didn't check serum levels at all (but did at least use calcifediol/25(OH)D3 ) and still found benefit! An even more metabolised form has been trialed in ICUs and that did indeed work better. Sorry can't find the trial now.
Many prevention trials don't test for D deficiency and have too few participants for significance. Also it takes about 2 years to do a population level prevention RCT, and it's really expensive and hard to get drug companies interested, so that's a tough ask. Prof Adrian Martineau got funding to do one.
Review on seasonality of coronaviruses in general, table 2 very useful as divides studies up by country or continent, may give us warning of likely timing of next waves eg June in India, November in USA/UK (assuming no nasty or resistant new variant before then):
I've been going back and forth on these Vitamin D studies. However, unlike HCQ vitamin D has no toxic side effects in moderate doses (<50,000 IU). It's cheap to manufacture. It seems like a no-brainer to use it as a prophylactic. Just don't confuse it with a cure. I'm taking 2,000 IU/day, which is above the generally recommended dose of 600 IU/day, but well within the safe limits.
Vitamin D is needed for lots more than dealing with Covid and like a great many nutrient requirements, more and more past a min. level is a waste. Good ex is Vitamin C where no good data for taking lots of supplemental C, but overwhelming data for what happens if deficient. I did not see the Author of the post say what levels of D3 25 OhD were deemed too low nor did i see what targeted level of D supplementation range was tried for.
D absorption with age decreases and diet for many insufficient to reach appropriate minimal levels needed for overall health and even with supplementation one size not fit all as different people will absorb differently with some needing more D to reach the same level of Blood 25Ohd than others. Add age being an issue to absorbing from the sun and hence it likely that most will need some level of supplementation whether it helps with Covid or not
This is somewhat unrelated, but I've noticed that if my wife takes a vitamin D supplement for an extended period of time, or a larger dose, her anxiety increases. Her vitamin D tends to drop in January/February, but we have to be very careful about trying to increase it. Any ideas why, or if there is a way to raise vitamin D levels without raising anxiety?
I'm absolutely convinced that vitamin D works. It's all about the way how you take it: you have to take it every day over long periods of time, BUT only in the short time span between your cardio exercise and your yoga exercise. Or if you have no time span between these two exercises, then you can take it right before your regular meditation practice. Studies also show that vit. D works better against covid if you unpack a clean face mask anytime you unpack a vitamin D pill. ;-)
If the supplementation studies used accepted recommended doses and levels of vitamin D, these might have been simply too low to produce a therapeutic effect, compared with sunlight exposure. This would account for the discrepancy between those studies and latitude/season effects. To quote a review of vitamin D medicine from 2007 (www.nejm.org/doi/full/10.1056/NEJMra070553):
--
Much evidence suggests that the recommended adequate intakes are actually inadequate and need to be increased to at least 800 IU of vitamin D3 per day. Unless a person eats oily fish frequently, it is very difficult to obtain that much vitamin D3 on a daily basis from dietary sources. Excessive exposure to sunlight, especially sunlight that causes sunburn, will increase the risk of skin cancer.125,126 Thus, sensible sun exposure (or ultraviolet B irradiation) and the use of supplements are needed to fulfill the body's vitamin D requirement.
--
Note also that the relationship between dietary vitamin D intake (including supplements) and serum levels is not linear but logarithmic. This makes it difficult to raise serum concentrations of vitamin D to useful levels with supplements. P.D. Mangan links to more publications here https://roguehealthandfitness.com/how-much-vitamin-d-do-we-need/.
PS: what sort of formatting does Substack support in comments? Not being able to blockquote is very annoying.
Has there been any research on whether sunlight-based vitamin D is good because of the increase of vitamin D vs. the reduction of cholesterol (which is what sunlight converts to vitamin D)? If it's the reduction of cholesterol, then vitamin D pills might not help.
"...if I were in the business of defending the Spanish study I might argue that it takes a few weeks for cholecalciferol to work, so giving it to someone who will already be dead or recovered by then is meaningless.
It would make me more comfortable if someone who did understand Vitamin D biochemistry would confirm this, but I'm not going to hang the whole argument on it."
Not wanting to hang the whole argument on the fact that it takes cholecalciferol 10 days to become available in the patient's body, and that it wasn't even adminstered until 11 days after onset of Covid, is utterly ridiculous. Those are the crucial flaws in the entire study, so it should not only be set aside, but thrown aside with great force. The author is nothing but a flak.
I would just add that there is likely also an age factor - average population age decreasing as you approach the equator because of the old people in the US and Europe.
I am reading this blog for the first time via the Naked Capitalism blog. As a chemist, I tend to focus on perspectives that include a biochemical view. Last fall, there were reports about AI studies that examined the broad array of Covid symptoms, and pointed to a bradykinin storm instead of a cytokine storm as a potential cause of the symptoms. Here is one magazine link that describes some of the biochemical cascades in the bradykinin system:
The article includes a list of potential treatments based on the bradykinin system, including the following quote:
“Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19”.
Also, I saw that one commenter here wrote about red light treatment. While I agree that low intensity laser light can be used to treat inflammation and respiratory problems, I think it’s possible that Vitamin D may be helping through a different mechanism. I and my friends and family have had good results with red light therapy for a range of indications. If you are curious, here is Dr. Fred Kahn’s blog post on light therapy and Covid:
He can’t promote the light therapy as a treatment for covid, but offers his opinion. (Spoiler alert: Dr. Kahn is a former vascular surgeon. I have been to him myself and he has very strong opinions about the medical system.) In a nutshell, when properly done using appropriate wavelengths, the light therapy triggers an increase in ATP formation, angiogenesis, and other knock effects including changes in the rate of DNA transcription in some cases.
> "Whenever you see a disease that's better in summer and worse in winter, Vitamin D is one of the possible culprits."
Um, then why haven't I been told to take vitamin D to prevent the flu during winter flu season? What I mean is, isn't there some other explanation you ought to have mentioned, like "people staying longer indoors makes viral spread easier" or "viruses can survive longer outside a host when temperatures are colder and there is less sunlight"?
Later in the article you mention reasons to be skeptical, but in general, I recommend against front-loading all evidence for X (and saving evidence against X for the bottom) unless readers are informed up front that you're structuring the article that way.
You should factor in the absolute huge mess of a country that Brazil is before you put any faith at all in a Brazilian study.
This is not xenophobia. I'm Brazilian. You have to either be here or have lived here for a while to get a grasp of what I'm talking about.
If the study showed no Vitamin D effects, odds are extremely high that the vitamin D used in the trial is simply counterfeit. Brazil has absolutely no QA in its genes. Bribery, on the other hand...
This was good. The CDC and FDA's inability to do simple cost-benefit analysis was shocking and lead to tens if not hundreds of thousands of excess deaths when it came to masks. Sometimes, knowing something won't hurt is enough and the efficacy can be hazy. You need to look at the risk and reward and if something like wearing a mask or taking vitamin d is cheap, easy, and safe you just do it.
If you adjust for a confounder using a thing which is only partly correlated with the confounder, some of the confounder slips through. This is bad enough when it's something like using income to represent socioeconomic status, but it's really bad when it's something like using ZIP code for race. At high enough n, any amount of confounder slipping through will make a result appear significant.
If they had based it on proportion black, though, presumably this wouldn't be AS bad. Instead, it looks like they made binary indicators for majority black, etc. I'm guessing this is because they wanted simple odds ratios, but if so, this is a case of blindly following "literature standards" exacerbating empirical problems. Did they run it using the proportion itself somewhere else that I'm missing?
I just wanted to say that I'm really grateful that you're still posting Scott :). I check my email multiples times a day to see if there's a new post, and seeing a notification from ACX makes the day that much better
I am glad we are settling on "ACX" as the abbreviation instead of "ACT" which has far too many collisions.
AC10?
Too many would understand AC 2.
If you have kids nearing college age, you'd think ACT and SAT.
>ask me about schizophrenia rates sometime!
Consider yourself asked! I'd love to hear more about this.
Another great example showing why science is actually pretty hard to do well, even when we are trying to answer questions that appear simple at first glance.
If it's so difficult to answer whether a major vitamin helps with one of the most significant diseases we've seen in decades a full year in, one should consider to what extent they should place strong confidence in their convictions in similar areas with similar scientific processes, for example nutrition and diet (these are also very hard, like most areas, and you should exercise extreme epistemic humility and adaptability, imo)
"Another great example showing why science is actually pretty hard to do well, even when we are trying to answer questions that appear simple at first glance."
And why yelling "trust the science" at people isn't the simple solution some make it out to be.
my belief is the phrase should have been "Trust the scientific method" followed by a campaign teaching what that means
There is no scientific method. There are scientific methodologies, with greater and smaller weaknesses, none of which are perfect.
I wish that they teach this instead, not in the least to scientists.
Of course! But a slogan "Trust that we get there, in the end, using different methods and looking at the probabilities...hopefully" isn't a great rallying cry ;)
They should have to constantly prove that they are worth that trust, though (just like anyone who wants to be trusted).
AIUI, scientific method = accept the fact that you can only ever have an approximate model of the "real world" and all you can ever do is refine that model so it produces ever more accurate results *in the areas where you're applying that model*.
Hoping for the absolute truth invariably makes you disappointed and likely to utter nonsense like "there is no scientific method".
The problem with that model is that it ignores the issue of systemic errors (which is a giant blind spot in science). Currently very many scientists and other people who matter (like financiers and journalists) think that there is a holy grail methodology. They think that you asymptotically approach the truth, the larger the N and/or the more studies you do, with that same methodology. So at a certain point you can be confident that the interpretation of the results is scientifically very certain.
However, you merely eliminate random error in this manner, not systemic errors in the methodology. It also doesn't solve the problem of interpretations of the results that are not true to to the data or biased publication of the results, for example by tossing out negative findings. Both the interpretation and publication step are actually part of the methodology and thus subject to error, but are commonly treated as being distinct, which often results in them being treated as sacrosanct.
Truly good science requires getting fairly consistent results when using multiple different, sufficiently strong methodologies (or at least validating a methodology by using other methodologies). Only then can you have real confidence that your scientific process has done better than common sense.
My newspaper recently wrote an article advocating having lay people suggest what sociology papers should be replicated based on applying common sense to the findings. They didn't seem to recognize how damning their suggestion was, when common sense is needed as a check on what people in that field call science.
Indeed, "...science is actually pretty hard to do well...". So bad, weak science is a great deal of what is published. Incentives need to change.
Seasonality is a whole thing. I love this review, and it does say quite a bit about Vitamin D. There are also a host of other factors that are in general responsibility for coronaviruses doing better during the winter. https://www.annualreviews.org/doi/pdf/10.1146/annurev-virology-012420-022445
One more point: a significant proportion of readers will have been staying inside (so away from sunlight) much more than they did before in the past 11 months; just think about not commuting to work everyday.
This will have reduced their (already on average pretty bad, for UK and some US states) level of Vitamin D... in which case a supplement would hurt them even less than the very little theoretical hurt it did in those pre-2020 studies.
I also side with "take Vitamin D supplements". My parents have also been taking one since November because they trust me (and their doctors are fine with them taking it).
I started taking a Vitamin D supplement the instant lockdown started because I realised that it was going to reduce my sunlight exposure by a lot and it seemed like an obviously good idea.
Could seasonal, latitude, and minority trends not be linked directly toward indoors exposure and multigenerational households?
Individuals are much more likely to congregate outdoors during the summer than the winter. This corroborates with the known facts that outdoors exposure poses a much lesser risk to corona than indoors exposure. In addition, we know that cold air carries the virus droplets much better than warm air. It seems to me that these facts would almost entirely explain the seasonal and latitude trends.
To explain the "vitamin d" trend in skin color, asian and african american households are much more likely to be intergenerational and/or involved in service jobs.
You saved me from having to write a similar post about seasonality and congregating indoors in the winter :)
I also came here to make this point!
Same :) Anecdotally, in my immediate community, there was a massive shift from outdoor gatherings to indoor gatherings around the start of the winter wave. And we know outdoor gatherings lead to substantially reduced transmission, and for the people that do get infected, they likely lead to lower viral loads.
Yes, me too :D
To exacerbate confounding with vitamin D even further, sunlight probably has some direct effect on transmission. Bad source, but lets you play with some sketchy model: https://www.dhs.gov/science-and-technology/sars-calculator. (I haven't seen a follow-up on this since last summer.)
This would probably only matter in a scenario where most transmission was _already_ happening outside, which I think is... never? But in such a world, you'd see that people who hung out in the sun (who have more vit D) did better than those in the shade, I guess.
+1
"To explain the "vitamin d" trend in skin color, asian and african american households are much more likely to be intergenerational and/or involved in service jobs." But wouldn't this primarily affect infection rates not severity? That's not what's showing up in the Asian data (lower infection rates, but worse outcomes)
Well... if studies did not control for age, the worse outcomes could be linked to older asian individuals getting the virus than their white cohorts. This would mirror asian american populations having more multigenerational households.
However, I am not sure we can extrapolate "lower infection rates" from past data as testing was much more widespread in higher income, white areas. Immigrant and poorer communities likely had much higher caseloads of the virus in the August - December months than was reported in the data. But because of the lack of fine-toothed data on the subject, these higher caseloads reported as "worse results per case".
The whole corona experiment has been a case study in poor data extrapolation and terrible logistics. And often the simplest, most logical answers are the best ones.
None of this is to say I dismiss vitamin D. I take a vitamin D supplement during the winter months for mental health (and regardless of the science, the placebo is worth it in my case). But I am concerned by people trying to make large conclusions off much-polluted data as well as the wider trend of people trying to invent the wheel when often the wheel is already on our doorstep...
Think deeply about simple things. Not simply about deep ones.
Watch out here for the difference in the meaning of the word Asian in the American context and in the British context - in which it typically means South Asian (i.e. people from India, Pakistan, or Bangladesh). So if you're looking at data from both countries, it's something you need to be aware of.
Regarding vitamin D pharmacokinetics: the actual active form is calcitriol, which has three hydroxy groups. This is produced by a series of enzymatic hydroxylations starting with cholecalciferol (1 hydroxy), and then calcifediol (2 hydroxy groups). So giving people calcifediol is going to act more quickly than cholecalciferol.
Wikipedia states that, "At a typical daily intake of vitamin D3, its full conversion to calcifediol takes approximately 7 days." And for high doses it's probably slower if the enzymes are saturated. (Source: https://en.wikipedia.org/wiki/Calcifediol which cites https://academic.oup.com/ajcn/article/87/6/1738/4633505)
So I think giving emergency doses of cholecalciferol is a dumb move by doctors.
Still, I'm not sure why they didn't just dose them with calcitriol. (One reason may be that it's easier to overdose on calcitriol, since the calcifediol -> calcitriol enzymes normally regulate how much calcitriol gets produced.) Even with giving calcifediol, it takes a few days for calcitriol to accumulate. See: https://www.sciencedirect.com/science/article/abs/pii/S8756328213003967
Seven days into the disease it would still be helpful. And some would be converted before then. Only expecting an immediate action would be dumb.
Ok (how much?). Ok (how much? when?). Wrong, e.g. "I'm feeling a cold coming on" zinc lozenges (of the right kind) do nothing after 2 days and reduce duration to roughly half if started in the first day of symptoms.
This means the Brazil RCT should not be allowed to wave off the encouraging initial studies (which are smaller and likely overoptimistic, still)
(assuming looking up 'usual active form' for the acknowledge function of vit D re: calcium means we can presume that this is the primary active form for speculative antiviral effect - definitely not a 100% certain implication)
It would be interesting to know what were the criteria for ICU admission in the Indian study, as well as the baseline O2 saturation in both groups. 50% of the patients needing ICU care is a little unexpected
Doesn't vitamin D have a build-up time and decay time, in the body. If so, this filter effect would rule out instant-on attempts to use it (e.g. hospital data)
There appears to be a more recent calcifediol study from Spain, with some of the same authors: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3771318 Apparently has some significant flaws, which makes me question the earlier study: https://twitter.com/fperrywilson/status/1360944814271979523?s=20
Here are the findings (curious Scott didn't cite this most recent study, while citing previous study with n=76):
"A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379).
Findings: ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%; p<0.0001). "
I would guess he didn't cite it either because it is a preprint, or because of the study's flawed methodology. I think it would have been worth mentioning, however, to better evaluate the dependability of the initial Spanish study he cites.
The criticism of the study, referenced in here via a link to a Twitter stream, is that the randomization was flawed. I don't have the time to follow all the details in the link, but I tend to trust the study authors as to having valid reasons for conducting the study the way they did -- using separate wards for the subject v control groups.
So often during the past year, we nitpick studies for not being perfect rather than considering probabilities that the authors were politically biased or incompetent.
. . . Or maybe even very well trained doctors trying to save lives - do we not have a case of the SEMMELWEIS effect here? - a Doctor has found a protocol that; appears to significantly reduce mortality; BUT does not fit current paradigms, is embarrassingly simple, and makes nobody a lot of money - did the medical research community go - WOW - now that is big-time interesting!!! - we MUST check out ASAP with urgent studies just in case he is right - NO! - to save embarrassment and stepping out of the comfort zone, they claimed the Doctor was a loon; their patients continued to die in large numbers of puerperal fever; and it took maybe 30 years, for it to be accepted handwashing between autopsies and childbirth delivery saves lives by reducing infection spread - somewhat ironically hand disinfection is now a central COVID-19 control strategy . . . https://www.npr.org/sections/health-shots/2015/01/12/375663920/the-doctor-who-championed-hand-washing-and-saved-women-s-lives
Absolutely right. I see Wilson and Haber as just preening here. There are lots of good administrative reasons why they may have had to run the case / control split by ward and did the best they could in real-world conditions.
There's at least one thing you get from sunlight that isn't vitamin D-- people have subcutaneous nitric oxide precursors. The really fun part is that you won't find this out by studying mice. Mice are not only covered with fur, they prefer going out at dusk and pre-dawn, so they don't have that body system.
Nitric oxide and sunlight for people was discovered as a result of studying why there were more heart attacks in the UK than in Australia.
If that's true, then shouldn't people who use poppers (alkyl nitrites) be significantly less likely to have health problems associated with lack of sunlight? I don't know how you'd do a study to show that, though. The group of people who do poppers is not exactly representative of the overall population. :)
Getting nitric oxide through the lungs might not be the same as getting it from the skin, aside from any other issues.
I think if you're using poppers regularly, you're also engaging in other risky behaviours likely to garner you a bunch of exciting infections never mind Covid-19.
From five minutes of googling, it looks like alkyl nitrite NO action may not last as long as endothelial NO synthase.
Is there a study which includes people's actual skin color? This would be more informative than knowing their race.
Would it? I understand that the sociologists of race talk a lot about "colorism" where darker black people face more obstacles than lighter black people. If we found darker black people got more coronavirus we wouldn't be able to distinguish between sunlight effects and colorism effects.
South Indians often have darker skin color, but very different SES from African-Americans. I've heard South Asian doctors got hit quite hard in the UK by COVID.
South Indian =/= South Asian, which includes North Indian. Most Brits from South Asia are from North India or Pakistan or Bangladesh, not from South India or Sri Lanka.
If you want to see the difference, google for team photos of the Pakistani (north) and Sri Lankan (south) national cricket teams. It's not a very big difference, but it's enough to notice.
Yeah, I'd be interested in hearing if anybody studied whether there was a north/south difference in south asian susceptibility to COVID.
I was going to share this map of reported covid cases by state in India, but then realized that we have a confound of darker skin correlating with lower latitude. It's hard to tell what the actual pattern is on the map though:
https://www.nytimes.com/interactive/2020/world/asia/india-coronavirus-cases.html
Yeah, so looking at people of South Asian descent in other countries could help reduce that confound.
It would give us approximate information about how much vitamin D people get from sunlight, but then it would be necessary to think about confounding factors.
From what I've read, colorism isn't just about black people, it's also in play among Asians.
And I'm not sure what's covered by "face more obstacles"-- it can happen that which children in a family are favored or disfavored depends on their skin color.
By the way, the CDC's report of the excess deaths by race/ethnicity shows that while blacks died far more than whites did of covid during the first wave and somewhat more of covid during the second wave, by the third wave, the rate of excess deaths was very close to equal between whites and blacks.
In contrast, Hispanics died at high rates in all three waves.
To see the CDC data, click on "Change in Number of Deaths by Race/Ethnicity" at:
https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm
Does that take into account the fact that the third wave was most pronounced in the least black region of the country? (It spread strongly to the Hispanic parts of Colorado, New Mexico, and Texas, but never got as big in the Southeastern states or northeastern cities where the largest black populations are.)
No doubt there is some kind of connection between ethnic death rates, regionality, and perhaps seasonality, any of which could be of relevance to the Vitamin D discussion. I bring this fact up because almost nobody knows that black and white death rates were about equal during the Third Wave, because that's not the kind of thing that gets publicized these days.
I'm still not finding that data. Does it show that black people in North Dakota were equally likely as white people in North Dakota to die in the third wave, and that black people in Alabama were equally likely as white people in Alabama to die in the third wave? Or does it show that within each state, black people were more likely to die, but because North Dakotans were more likely to die in the third wave than Alabamans, black people in North-Dakota-or-Alabama (who are mostly in Alabama) were equally as likely to die as white people in North-Dakota-or-Alabama (who are more evenly spread).
Seems like an interesting question, no? But now that equality between whites and blacks in excess deaths occurred during the Third Wave, nobody in the press seems terribly interested anymore in talking about covid and race, whereas previously it was a topic of obsessive interest.
I read a bit about this when I had a patient with GFAP encephalomyelitis who had a dramatic recovery after getting sunburned. I was really pissed off with the staff who let a very cognitively impaired man sit in the sunshine and get sunburned. But then he recovered, from literal psychosis and profound memory and executive impairment, to seeming fairly normal, and Neuropsych testing confirmed this. I wasn’t sure if it was vitamin D or not.
So I read about MS, because GFAP encephalomyelitis is incredibly rare, and found that some researchers were arguing that the latitude effect is due to UV rather than Vitamin D itself, and had a mouse model of multiple sclerosis showing mice under UV did better than either controls or vitamin D mice. I can try to find the reference again if you like.
Obviously my sample was n=1 of an extremely rare disease, but it got me thinking.
If it was UV, could that explain the latitude effect but also why vitamin D supplementation studies with good designs had mixed results.
I still take vitamin D 😁
Also, in the UK, NICE, which is our equivalent of the FDA to some extent, says that most Northern Europeans are Vitamin D deficient in the winter, and recommends that *everyone* supplement with Vitamin D between September and March. It’s just buried there in one of the NICE guidelines that almost no one ever reads. So that’s a good enough reason for me.
Thanks, I was just coming here to say the same thing. I believe they at one point also recommended that those with darker skin tones take it all year round.
But then the UK is at a much higher latitude than the US. I do wonder if the 75% probability Scott assigned to Vit D supplementation being useful should state which latitude/race he’s estimating that for.
Thanks, I suspect a lot of things like this but it's good to hear from someone who's done more research.
https://doi.org/10.1073/pnas.1913294116
This wasn’t the paper I found the first time around because it’s a different experimental design, but this is the same mouse model of MS. The UV seems to work independently of Vitamin D by good study design, but the mechanism is unknown. Presumably it prevents the immune system from attacking myelin in some way, which makes me wonder to what proportion of people with COVID are dying from an overactive immune response, the cytokine storm findings from early on.
This is another anecdote -- a friend of mine with an MS diagnosis went from quite symptomatic to completely not symptomatic after high Vitamin D dosing. I'm foggy on the details because it's been awhile, but it seems like she was in touch with a number of other people who'd had the same experience. Is this something other people have heard about?
If UV is an important factor, this could explain Australia and New Zealand's success in dealing with the coronavirus (for those who don't know, both countries are close enough to the ozone hole to have far higher rates of UV exposure than the rest of the planet. You can get sunburned in less than half an hour without taking precautions).
Hard disagree. Aus and NZ either explicitly or effectively pursued a strategy of elimination. Robust public health response, and in the case of Victoria, a 3 month+ lockdown that banned socialising outside your household.
That probably had a bit more to do with it than UV.
"Do the benefits of taking a Vitamin D supplement at a normal dose equal or outweigh the costs for most people?"
I'd say the percentage is closer to 100%.
There have been numerous studies showing that low vit D levels are correlated with increased risk of depression, diabetes, cancer and influenza (though I haven't looked at all of these studies with the rigor or Mr Alexander so who knows after you disect all of these studies). Anyway, I tell my patients to take it.
Here's a recent one on influenza
https://pubmed.ncbi.nlm.nih.gov/32252338/
EDIT: this is based on the cost of the vitamin D (aprox £10 for a years supply of 5000 iu/capsule) and the potential side effects (I read of a study finding that the main side effect of vit D overdose, renal stones, was not statistically significant compared to the placebo group) vs the likely many benefits.
https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/vitamin-d-fact-sheet#what-is-the-evidence-that-vitamin-d-can-help-reduce-the-risk-of-cancer-in-people
Yeah, seems to me the greatest cost associated with Vit D supplementation is literally the fiscal cost. I think if you're someone who can afford to throw $50/mo or whatever at supplements, it's probably worth it.
Another potential cost, which I wish this post addressed, is giving people a false sense of security with the Vitamin D thing. If someone is overweight, has hypertension, and maybe another comorbidity, but thinks they're safe from corona just because they've been taking Vitamin D supplements for a few months, then that's a problem. Anything that reduces vigilance sans justification should be perceived as a pretty serious cost.
The point is the cost of vitamin D is extremely low. £10 is $13.86, and that's per year.
I hate the 'false sense of security' argument (even tho I also think it's sometimes true) – it's an almost perfect general counter-argument to doing _anything_ for anyone.
If anything, the largest source of a 'false sense of security' is probably 'if I follow official advice I'll be fine'.
Unless you are actually deficient in Vitamin D, I don't think you could say it's 100%. There are risks associated with taking supplements from a largely unregulated industry (USA at least). Taking Vitamin D doesn't necessarily reduce the risk for getting your list of diseases. Some good summaries of the research on sciencebasedmedicine.org:
https://sciencebasedmedicine.org/vitamin-d-supplements-do-not-reduce-the-risk-of-depression/
https://sciencebasedmedicine.org/vitamin-d-and-diabetes-another-case-where-supplementation-sounded-like-a-good-idea-but-wasnt/
https://sciencebasedmedicine.org/vitamin-d-supplements-do-not-reduce-the-risk-of-cancer-or-cardiovascular-disease/
https://sciencebasedmedicine.org/are-guidelines-for-calcium-and-vitamin-d-rooted-in-evidence-or-vested-interests/
https://sciencebasedmedicine.org/the-rise-and-inevitable-fall-of-vitamin-d/
The world would be a better place if Vitamin D supplementation, especially at higher latitudes, becomes routine for most people.
Hmmm.... I'd be more confident that the world would be a better place if getting some sun every day becomes routine for most people.
Well said!
Have you spoken to a dermatologist ... ever? They seem to be convinced that you'll get skin cancer if you merely *say* the word "sunshine".
From what I've read this isn't the case universally, and dermatologists outside the US are more likely to give moderate advice and encourage some healthy sun exposure. See for example https://www.outsideonline.com/2380751/sunscreen-sun-exposure-skin-cancer-science#close
Of course this popular article was widely criticized by dermatologists after it came out, possibly also because it has a somewhat 'conspirational' undertone. For example I remember reading: https://theoutline.com/post/6988/for-the-love-of-all-that-is-holy-please-wear-sunscreen https://www.skintour.com/q-and-a/rebuttal-to-outside-magazines-piece-is-sunscreen-the-new-margarine/ I never tried to fact-check the claims, but I would love to read more informed opinions than mine on this matter!
Of course, indeed. I read some of the back-and-forth and did some basic fact-checking and as expected the truth appears to be somewhere between "sunscreen is poison foolishly pushed on us by evil Big Pharma" and "you'll get skin cancer if you merely *say* the word 'sunshine.'"
Even those rebuttals you linked are more nuanced. From the first:
"But such advice is not one-size-fits-all: it’s most likely not true for people of African descent. “Your risk of skin cancer is directly related to how much melanin you have in your skin … I don’t recommend sunscreen for darker patients for skin cancer prevention,” Adamson said."
The NHS (UK) does actually recommend spending time in the sun without sunscreen - see here: https://www.nhs.uk/live-well/healthy-body/how-to-get-vitamin-d-from-sunlight/
"Most people can make enough vitamin D from being out in the sun daily for short periods with their forearms, hands or lower legs uncovered and without sunscreen from late March or early April to the end of September, especially from 11am to 3pm."
So, indeed, it's not universally the case that dermatologists recommend against (cautious, limited) sun exposure. And it seems like perhaps those in the US may be overly risk-averse or conservative with respect to updating guidelines, when compared with their international counterparts.
Exactly. My doctor gave me a pamphlet with the words skin cancer on it and I got skin cancer.
Yes, dermatologists, who should have put me on Isotretinoin way earlier. Or mentioned that a permanent solution to acne actually exists. Instead of me finding this out years later. A very conservative bunch.
I consider "sunshine is bad for you, if it doesn't involve sunburn" an extraordinary claim. That would imply to me that "skin cancer" was a leading cause of mortality among white hunter-gatherers.
Somehow I have trouble imagining that.
I also have heard a similar claim in that vein, that you should always use sunscreen, which as far as I know is some kind of chemical goop including titanium oxide and zinc oxide. I follow the precautionary principle wrt to smearing random metal cream on my skin, though. [on the first couple of beach days in Egypt sure, but every day I have sun exposure in cloudy Europe?!] I also know from experience that on a German summer day, I can stay outside for hours and not get a sunburn.
An apothecary was surprised to hear that, apparently believing that sunburn is inevitable then. But then she still insisted that the skin cancer risk made this irrational.
But what the hell did she know about skin? She didn't even know that sunburn wasn't a given. Would it be rational to take her word for it?
US doctors are people who subjected themselves thru yearlong sleep deprivation torture for status reasons during med school.
This makes everything they say, a priori suspect.
Is that an ad-hominem or the sensible heuristic of "Don't listen to masochistic, intense, crazy people who faced extreme sleep deprivation continue defending the practice as necessary for health advice"? Perhaps both.
I also am worried, that the claim "sun is bad for you" is too appealing for a nerd like me, who's prone to staying indoors in front of a computer for long periods.
Like isn't it awfully convenient that that's also the best way to live?
When I look at people who have a tan, well they do look healthy and happily smug about it. On beach vacation, I was the same way and it feels excellent.
The mood boost is NOT FUCKING SUBTLE!
Smoking is bad for you. And the EAE did not have tanning beds so they probably aren't good either. [I never wanted to tan like that, so I don't care to be certain of it]<br>There is extraordinary evidence for those claims.
But from what I could gather about this question, the evidence is conflicted.
If there is an increased skin cancer risk, that would be more than outweighed by the reduced cardiovascular risks, mood benefits, exercise and fresh air, I totally would expect the medical establishment to zero in on the "increased skin cancer risk", because of the precautionary principle. I suspect that this is from the same impulse that makes "them" want to ban vaping in California.
My judgment might be wrong, this might be sloppy reasoning and I will die for it.
And that I am coming up with a story that confirms what I want to believe.
But that's always true and I'm okay with that.
It's not like I can trust someone else's judgment for my decision-making, in the end.
If Scott ever wants to make an effort-post on the topic, well then I'm willing to entertain the notion of "sunlight is bad for you", again.
If he comes to that conclusion and I can follow and agree with his reasoning, that would indeed be extraordinary evidence.
"sunshine is bad for you, if it doesn't involve sunburn".
"That would imply to me that "skin cancer" was a leading cause of mortality among white hunter-gatherers"
Never mind hunter-gatherers, it would imply it among European subsistence farmers before mechanisation, a group for which we have vastly better records.
However, it is worth asking how much ozone depletion affects this - if the evidence gathering was in the mid 1990s at the peak of ozone depletion, then that would go a long way to explaining why they get results that suggest that sun exposure is much worse than the historical record.
IOW, we may have an excessive concern for the sun because we happen to live during a short period in earth's history when it was much more dangerous than it was before 1975 or after 2075.
Mankind didn't care much about cancer until we got wealthy enough to get rid of the other causes of death.
This. I am told "the lifetime risk of getting melanoma is about 2.6% (1 in 38) for whites" and "The average age of people when it is diagnosed is 65."
Hundreds of years ago, life expectancy was typically below 40, and people faced major health threats every single year.
People worried about things like Smallpox (which reportedly had an "overall fatality rate of about 30%" - I can't find a "chance a random person would be killed by smallpox", but it was endemic, so it's probably quite a substantial probability), Cholera, Malaria, and for awhile there, the Black Plague.
Relatively uncommon deadly threats, like skin cancer, just wouldn't have been very noteworthy back then. Also, white skin responds to sunlight by generating melanin, so while the extra time they spent in the sun might have raised their risk, the risk probably wasn't raised by a large amount, thanks to the melanin. The risk would then be reduced simply by not living long enough to reach an age associated with a substantial risk of skin cancer.
"getting some sun every day becomes routine for most people"
We have just had four solid days of rain (and winds from Siberia) all day and all night here so... well, maybe June will be sunny? 😁
So, are you taking a daily dose of vitamin D?
Disclosure: I am taking 25mcg of D3 just because
No, I tried it once, the specific formulation gave me diarrhea, and I haven't bothered finding a formulation that doesn't.
Statistically, don't you think you should have done more trials? Perhaps to n=3?
On brief reading, diarrhea with Vitamin D can occur if a person has taken to much, ie at a toxic level, but is not likely at recommended dosages
Yet another reason to clone Scott.
I wonder if that formulation was combined with other minerals, such as magnesium (that can cause diarrhoea)? Best sources are from food but since Vitamin D comes from animal-derived products and you're trying for vegetarian/vegan, a supplement is probably your best bet (unless you eat fish?):
" Choose fortified dairy products (which have the nutrient added to the food), fatty fish, and sun-dried mushrooms, which are all high in vitamin D."
Holland & Barrett (a UK health store chain who are a bit chi-chi: "Holland & Barrett was formed in 1870 by Alfred Slapps Barrett and Major William Holland, who bought a grocery store in Bishop's Stortford, selling groceries and clothing. ...The brand has become synonymous with the sale of vitamins, supplements and homeopathy, to the point that pro-homeopathy former MP David Tredinnick has been dubbed "The Hon. Member for Holland and Barrett") do have some reasonable advice on where to get dietary Vitamin D:
https://www.hollandandbarrett.com/the-health-hub/vitamins-and-supplements/vitamins/vitamin-d/sources-of-vitamin-d/?icmp=Menu_HH
Vegan sources of Vitamin D
While there are few Vitamin D sources in food, the good news is, some of these sources are vegan. For instance, 1 cup of almond milk will give you 100mg of Vitamin D, orange juice, 100mg and 1 cup of portobello mushrooms, 634mg. Other vegan sources of Vitamin D in food, include Maitake mushrooms, soy milk, soy yoghurt and ready-to-eat cereal.
Mushrooms
Mushrooms are the only plant source of Vitamin D (apart from fortified foods). They can synthesise Vitamin D when they are exposed to UV light, just like we can. Choose wild mushrooms or mushrooms grown in UV light.
Top tip: Slice up some mushrooms and leave them exposed to the sun outside from 10 am – 4pm on a sunny day on 2 separate occasions, e.g. Monday is bright, Tuesday is dull and Wednesday is sunny again, so you’d put the mushrooms out in the sun on Monday and Wednesday. Cook and enjoy!
Or, you can dry them thoroughly (e.g. using a food dehydrator) add to a jar with 1 tablespoon of uncooked rice, and store for a later day. Just rehydrate them in water 1 hour before you want to cook with them.
Tofu
Tofu is not just for vegetarians and vegans! It is a highly versatile source of dietary Vitamin D which you can use for snacks, lunches, and main meals.
There are a few different types you will come across, so here is our advice about how to best use them:
Silken / Japanese-style tofu: Silky and creamy, this can be used as a thick cream, to make a vegan cheesecake, put in smoothies or even make creamy dips with.
Regular tofu: It is soft like silken, but a little more compact. This type of tofu soaks up flavours of stocks and sauces – it is usually used in noodle soups. Try making vegan scrambled eggs with it, just sprinkle in some turmeric and black Himalayan salt.
Firm tofu: Perhaps the most common tofu, firm tofu usually comes soaked in liquid. The texture will be like feta cheese.
Before use, dry it before using it by pressing it (placing it on a plate in the sink and putting something heavy on it works too! Then let it soak in a marinade for at least an hour. Finally, pan-fry, stir-fry, deep-fry or bake it in a yummy sauce in the oven.10
Plant-based dairy alternatives
Soya Milk: Most dietary Vitamin D is found in animal products. So fortified food sources of vitamin D are particularly useful for vegans and vegetarians. Soya milk contains around 100-120 IU in one cup and lots of protein. Try using it in your morning smoothie or cereal to start your day off right.
Almond Milk: 200ml of almond milk contains around 90 IU of Vitamin D. Check the label of your favourite brand to see how much Vitamin D you will get per serving.
Fortified vegan yoghurt: Similar to plant-based milks, vegan yoghurts also know their target market may be lacking in vitamin D in the winter, so a lot of them fortify their products with vitamin D. Try topping it with granola and honey or agave nectar.
Did you know? In the UK, cows’ milk is generally not a good source of vitamin D as it is not fortified like it is in other countries. Stick to the plant milks if you want to increase your dietary vitamin D.
Orange juice
Get some Vitamin D from fortified orange juice, which can contain up to 140 IU of Vitamin D per glass.
Fortified breakfast cereal
Some healthy breakfast cereals and instant oats are fortified with Vitamin D. Check the label for the amount per serving.
Meat substitutes
There are tons of meat substitutes on the market – and some are pretty realistic – adding to their authenticity is the fact they are usually fortified with vitamin D.
Real meat can be a bit hit and miss when it comes to vitamin D, with red meat, liver and other offal being the best sources. At least with fortified faux-meat, you know it contains the vitamin D you need.
Try going meat-free for a few of your meals and swap it for fortified plant-based mince, burgers, nuggets, goujons, chunks or even steak! Check the nutritional label to see if has been fortified and tuck in."
25mcg is actually much less than recommended, but is a common dose in the USA. Try finding 250mcg and take daily. There's a whole ordeal about how low vitamin D prescription is a typo and you can't really overdose or anything (you should Google it!). If you're going to take some, you might as well take the right dose!
4000 IU (100 mcg) per day increases vitamin D blood levels 40 ng/ml (100 nmol/L). Best to stay at or below 100mcg
Here's the article i read. The safe limit is 10,000 IU.
https://www.newswise.com/articles/scientists-confirm-institute-of-medicine-recommendation-for-vitamin-d-intake-was-miscalculated-and-is-far-too-low
NIH Vitamin D Fact sheet
https://ods.od.nih.gov/factsheets/VitaminD-Consumer/
Can vitamin D be harmful?
Yes, getting too much vitamin D can be harmful. Very high levels of vitamin D in your blood (greater than 375 nmol/L or 150 ng/mL) can cause nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones. Extremely high levels of vitamin D can cause kidney failure, irregular heartbeat, and even death. High levels of vitamin D are almost always caused by consuming excessive amounts of vitamin D from dietary supplements. You cannot get too much vitamin D from sunshine because your skin limits the amount of vitamin D it makes.
The daily upper limits for vitamin D are listed below in micrograms (mcg) and international units (IU):
Ages Upper Limit
Birth to 6 months 25 mcg (1,000 IU)
Infants 7–12 months 38 mcg (1,500 IU)
Children 1–3 years 63 mcg (2,500 IU)
Children 4–8 years 75 mcg (3,000 IU)
Children 9–18 years 100 mcg (4,000 IU)
Adults 19 years and older 100 mcg (4,000 IU)
Pregnant and breastfeeding teens and women 100 mcg (4,000 IU)
You just made me reduce my dosage.
I now remember I had upped it when the really bad wave hit in the winter, 3k deaths/day, and hadn't intended to keep it at 6000-7000 IU for long.
Since I have gotten vacinated for Covid, I am reducing to 2,000 IU since too much Vitamin D is thought to interact with heart disease. Too little and too much can both be a problem, I think turning to the Goldielocks test is statistically correct. I will get the Vitamin D level tested the next time I have a blood test....
Interesting - my doctor always told me to get 5,000 IU (she also told my very white boyfriend to).
Further reading indicates 10,000IU as the onset of toxicity lower limit.
Okay, fish oil supplement I am taking (for my creaky joints) has a vitamin D level of 10 μg which is 400 IU, so I think I'll stick with that dosage. 25 μg/1,000 IU is a bit on the high side but seems to be the upper limit recommended. I think going any higher is not really beneficial unless you're extremely deficient and not getting any from your diet and you get prescribed high dosage to bring you up to normal level.
If you're eating dietary sources of vitamin D (animal-derived foods mostly) then additional supplementation up to a lower level probably won't hurt, but I think if you're eating a reasonable diet *and* slamming down 250 μg/10,000 IU in supplements you are asking for trouble:
"Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart."
See this study on vitamin D toxicity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158375/
"The IOM Report in 2011 not only discussed the upper limits (ULs) for vitamin D intake on the basis of the acute, short-term administration of high-dose vitamin D preparations for limited periods but also emphasized chronic administration of vitamin D over years of supplementation. Acute toxicity would be caused by doses of vitamin D probably in excess of 10,000 IU/day, which result in serum 25(OH)D concentrations >150 ng/ml (>375 nmol/l). That level is clearly more than the IOM-recommended UL of 4,000 IU/day. Potential chronic toxicity would result from administration of doses above 4,000 IU/day for extended periods, possibly for years, that cause serum 25(OH)D concentrations in the 50–150 ng/ml (125–375 nmol/l) range "
So safe upper limit is 100 μg/4,000 IU per day, NOT 250 μg/10,000 IU. My totally amateur advice is: eat a good diet, stay out in the sunshine when you can get it (with caveats about being careful around sunburn etc.) and in the winter months supplement your diet with NO MORE THAN 4,000 IU PER DAY (and if you're sticking to a reasonable diet, go lower on the supplements to maybe 1,000 IU per day).
That sounds like too much, NHS advice is rather similar to this post - no evidence that it prevents Covid-19 but probably beneficial for other reasons: https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-d/
And you can certainly take too much Vitamin D:
"Sometimes the amount of vitamin D is expressed as International Units (IU). 1 microgram of vitamin D is equal to 40 IU. So 10 micrograms of vitamin D is equal to 400 IU.
What happens if I take too much vitamin D?
Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart.
If you choose to take vitamin D supplements, 10 micrograms a day will be enough for most people.
Do not take more than 100 micrograms (4,000 IU) of vitamin D a day as it could be harmful. This applies to adults, including pregnant and breastfeeding women and the elderly, and children aged 11 to 17 years.
Children aged 1 to 10 years should not have more than 50 micrograms (2,000 IU) a day. Infants under 12 months should not have more than 25 micrograms (1,000 IU) a day."
via negativa
"For example, the Spanish study used a version of Vitamin D called calcifediol; the Brazilian one used a slightly different version called cholecalciferol. Calcifediol becomes active more quickly than cholecalciferol, enough so that if I were in the business of defending the Spanish study I might argue that it takes a few weeks for cholecalciferol to work, so giving it to someone who will already be dead or recovered by then is meaningless."
Biology is perversely complicated enough that this could indeed matter. When I was looking up magnesium supplements to take, there are ten different types https://www.mindbodygreen.com/articles/magnesium-supplement-types and depending what you want to achieve (ease sore muscles? help blood pressure? treat constipation?) then the type you should be taking differs.
And looking up about vitamin D types, the differences between the two types seem to be:
"The recommended form of vitamin D is vitamin D3 or cholecalciferol. This is the natural form of vitamin D that your body makes from sunlight. Supplements are made from the fat of lambs' wool.
However, a clinical study reported in 2008 suggested that vitamin D2 works as well as vitamin D3.
Many supplements contain vitamin D as vitamin D2 or calciferol. It's derived from irradiated fungus."
Irradiated fungus? Funky, if we want to turn into Godzilla I suppose?
D3 being the form that is made when sunlight hits our skin, another site advises that there is a difference in bioavailability: https://www.healthline.com/nutrition/vitamin-d2-vs-d3
"Vitamin D2 and D3 are not equal when it comes to raising your vitamin D status.
Both are effectively absorbed into the bloodstream. However, the liver metabolizes them differently.
The liver metabolizes vitamin D2 into 25-hydroxyvitamin D2 and vitamin D3 into 25-hydroxyvitamin D3. These two compounds are collectively known as calcifediol.
Calcifediol is the main circulating form of vitamin D, and its blood levels reflect your body’s stores of this nutrient.
For this reason, your health care provider can estimate your vitamin D status by measuring your levels of calcifediol.
However, vitamin D2 seems to yield less calcifediol than an equal amount of vitamin D3.
Most studies show that vitamin D3 is more effective than vitamin D2 at raising blood levels of calcifediol.
For example, one study in 32 older women found that a single dose of vitamin D3 was nearly twice as effective as vitamin D2 at raising calcifediol levels.
If you are taking vitamin D supplements, consider choosing vitamin D3."
So the Spanish study was using the inferior (?) D2 yet got good results, while the Brazilians were using the superior (?) D3 and found no difference.
Yeah, I'm puzzled too. It *may* be that the Spanish patients, who were already hospitalised when they received the supplementation, were *so* badly off for Vitamin D that anything was beneficial. The only difference I could come up with was that the Spanish study seems to demonstrate that it "drastically reduced" admissions to ICU, while the Brazilian one says it didn't reduce length of stay:
"A small randomized controlled trial in Córdoba, Spain, of calcifediol (25-hydroxyvitamin D3, or 25(OH)D3) for hospitalized COVID-19 patients (henceforth, “the Córdoba study”) found dramatic reduction in the need for ICU admission. This study has been viewed as a small preliminary study, suggesting at most that further study might be warranted. It has gotten relatively little attention, though its strengths and weaknesses were discussed in this article, and a Bayesian cost/benefit analysis found the expected benefits, in terms of lives saved and severe illness avoided, of immediately adopting the treatment protocol were considerably higher than the expected costs. Two other randomized trials of vitamin D formulations for COVID-19 had mixed results: a small trial in India found a high dose of vitamin D3 shortened time to viral clearance in asymptomatic or mildly symptomatic SARS-CoV-2 individuals, and a larger study in Sao Paulo, Brazil did not find a statistically significant benefit of a high dose of vitamin D3 in hospitalized COVID-19 patients."
"Conclusions and Relevance Among hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19."
So *maybe* it's "Vitamin D supplementation if you're hospitalised with Covid-19 means you're less likely to be admitted to ICU, but you won't get out of hospital any sooner than someone with Covid-19 that did not have to be admitted to ICU and wasn't getting Vitamin D supplementation". That is, "if you're run-down/deficient in Vitamin D, that makes it worse if you get Covid-19 and have to be hospitalised, but taking Vitamin D won't stop you getting Covid-19 although it will make it less likely you'll be so badly off you need to go to ICU".
"So the Spanish study was using the inferior (?) D2 yet got good results, while the Brazilians were using the superior (?) D3 and found no difference."
No, the Brazilian study used D3 (cholecalciferol), and the Spanish study used its metabolite 25-hydroxyvitamin D3 (calcifediol). Neither of them used D2 (calciferol).
Ah, thank you for clearing that up, I was confused about which was which. So they both used the same form of Vitamin D, just the metabolite in one case. That makes the results even odder - either the Spanish really messed up and there isn't any effect, or it is something like "if you are deficient in Vitamin D and you get Covid-19, you are more likely to have a bad outcome necessitating admission to ICU, but supplementation with Vitamin D will only mitigate the worst effects, it won't prevent you contracting Covid-19 or let you recover any faster than normal". So probably better to take a supplement just in case, but it's not a miracle cure.
I think it still leaves open the possibility that calcifediol is effective when administered to people after Covid diagnosis, but cholecalciferol is not because it takes several days for the liver to metabolize it into calcifediol, and by the time you've produced enough to matter the course of the disease is mostly decided. A bigger replication of the Spanish study would clear things up.
Can you look at Fluvoxamine? People have been saying "there is a 95% chance that it will reduce hospitalization/death rates by 75% or more" here: https://www.quora.com/What-is-the-current-treatment-for-Covid-19/answer/Steve-Kirsch
That seems like an EXTREMELY overoptimistic estimate, especially considering that the "positivity" of the study is questionable. When they pool all of the clinical scores, they get significance, but it was not significant for shortness of breath, not significant for hospitalization, not significant for mechanical ventilation, not significant for mortality. The authors even comment in the discussion that the difference might have been due to different baseline characteristics in oxygen saturation
Could there be something like an undershoot effect involved, where people who would ordinarily have lots of vitamin D because they spend a lot of time outside and live close to the equator actually have much less because they're locked down and stay inside instead, which does... something... to their immune systems?
No, I don't think so... because in many countries close to the equator, COVID rates are less than we would expect.
One of the challenges with using serum vitamin D levels as an input variable is that we don't really know whether those levels are a cause or an effect; possibly they are a confounding factor when included with other inputs. Example: although patients with higher vitamin D levels may have fewer M.I.s, we can't produce that result by supplementing vitamin D in the diets of low-vitamin-D patients. See, e.g., https://jamanetwork.com/journals/jamacardiology/fullarticle/2735646.
Well sunlight seems way more promising, so why bother studying Vitamin D?
So here's my experimental design for testing the "something something sunlight"-hypothesis:
Set up a hospital wing with a bunch of UV lights, and another with UV lights and infrared and another with just infrared and treat only people with a specific shade of dark skin in them for Corona. [uhm.... also a control group would be nice]
If there's no difference from any of the light setups, we..... are very confused.
Maybe not enough light.
If we see improvements from all rooms except UV-lights only, we know it's not vitamin D.
If we see.... ugh, lighting is hard, make that guy design the experiment:
https://www.lesswrong.com/posts/7izSBpNJSEXSAbaFh/why-indoor-lighting-is-hard-to-get-right-and-how-to-fix-it
And someone who understands Vitamin D and Nitric Oxide biochem to write the interpretation.
Preregister the paper, get a hospital to run this and just fill in the numbers they report.
https://www.lesswrong.com/posts/7izSBpNJSEXSAbaFh/why-indoor-lighting-is-hard-to-get-right-and-how-to-fix-it
And make the Thiel foundation, Kickstarter or whatever fund it. And if you're reading this, you can organize it :)
"Despite their superficially lighter skin, they have Vitamin D deficiencies almost as bad as blacks." Unless I'm missing something, the linked study included a total of 60 Asians all from the greater Boston area. Obviously not very representative of ~4.7 billion Asians in the world or even the Asian population in the U.S. I would point to larger studies in Japan (e.g https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755751/) that appear to point to significantly lower vitamin d deficiency than the US population and much lower than the US black population.
That surprised me: I thought that East Asians evolved lighter skin for the same vitamin D related reasons as Europeans.
Vitamin D deficencies are a combined function of skin color and sunlight amount. A skin color that works for Asians in Guangzhou might not work for Asians in Boston.
Another very significant source of Vitamin D is food: salmon, tuna, mackerel, mussels, oysters, liver and egg yolks. A 2.5oz can of wild salmon drained w/ skin & bones is about 750IU of vitamin D (the D3 variety). If you want to go vegan, portabella and maitaki mushrooms grown in the sun give you ~20ug (about the daily recommended amount of about 0.5IU). The better the animal ate, the better the Vitamin D content. Chicken egg yolks from chickens eating bugs, etc. from the ground (oranger yolk) are much higher in Vitamin D than CAFO chicken eggs. Wild salmon more than farmed salmon. The oranger, the better. Traditional Japanese diet in Japan include fish pretty much every day. Vitamin D deficiency can also come from a vitamin deficient diet especially a low fat, high over-processed food diet.
> The oranger, the better.
Check for added/fed carotene, though.
Asian == South Asian, Southeast Asian, North Asian? Quite a wide range of latitudes. The hyper-focus on racial data and what it explains isn't insightful, it leads to a desire to adjust expectations based on a small set of lumped data for whatever non-white categorization we're habituated to. If a light skinned 3rd gen Japanese person or a wealthy black person scores low on Vitamin D, do we think, well they fall under the Asian / Black category...
My understanding is that hydroxychloroquine is ineffective on its own but helpful when combined with other antiviral medication, thus possibly explaining some significant variation in study results (since many studies actually did combine it with other things):
https://twitter.com/__ice9/status/1336164630851428357
Hmm, not sure about this. Arizona, the sunniest state in the US, also has the sixth highest covid infection rate per capita of the 50 states.
I've heard a theory this is due to people staying indoors with AC on. (Same story für Brazil.
As an aside, ACs in the US are way too cold way too often.
Interesting review. I only suggest that you consider British epidemiologist, Edgar Hope-Simpson's search for a parsimonious explanation in his study: The transmission of epidemic influenza (1992). There is a clear connection between these seasonal phenomena. Here's a very interesting follow up on EHS's comprehensive work in the BioMed Cenral Virology Journal. Flu is still a surprisingly mysterious phenomenon in many ways. There are probably some read across matters to SARS-CoV-2. The intriguing relationship with VitD and even it's centrality is also well covered. Worth checking out the early C20th methods for transmission research if nothing else. There are some very interesting questions and conclusions that challenge some givens about these phenomena.
https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-5-29
Good article but the Brazil and Spain studies were carried out solely among hospitalised COVID-19 patients. The India study is very interesting because it indicates that Vitamin D helps mild cases recover faster.
The next step should be to find out whether Vitamin D can help potentially moderate-to-severe cases remain mild and therefore whether it can prevent hospitalisations in the first place. Perhaps it can be given to a sample group of people of all ages who have never had COVID-19 and who haven't been vaccinated and this group can be compared to a control group.
A Mass general study is underway giving 3-10k IU to cases and close contacts to investigate this https://clinicaltrials.gov/ct2/show/NCT04536298
Dr. Atlas is at it again. Pied Piper much?
Can you unpack or decode that, please?
It's a troll calling our host by the name of our former President's quack doctor.
Do not feed.
So anything wrong with just taking L-arginine and L-citrulline as supplements to get nitric-oxide levels up? Like, if I'm going to take a bunch of random stuff sunlight-associated stuff like Vitamin D, I might as well be a completionist about it.
There's all sorts of factors that go into the seasonal pattern. At least when it comes to influenza, high humidity seems to be the most important (see eg https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000316 and https://www.pnas.org/content/106/9/3243 and https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057485). But there's also temperature, UV radiation, and of course behavioral changes.
Perhaps at least a portion of the seasonal and latitudinal variation is due to that COVID (and many viruses) are rather vulnerable to ultraviolet.
Thus, the seasonal variation in daily insolation would be the true causal driver, with Vitamin D correlating for the obvious reason.
If this holds water, I would expect the degree of seasonal variation to be weaker closer to the equator, although this would probably be weakened because the directly-caused variation will generate more cases that will spread to the equatorial regions anyway...
Also, I would expect the degree of the effect to vary based on the amount of UV reaching the ground - so if the data exists, plotting the health of ozone layer against the degree of seasonal variation might be informative....
"If this holds water, I would expect the degree of seasonal variation to be weaker closer to the equator"
Sub-Saharan African countries don't seem to have fared as badly as most countries so there could be something there, assuming the data from those countries is reliable of course.
Just because there's more sunlight in the summer doesn't mean that people are getting enough of it to make a difference. Most of us are pretty well clothed or inside much of the time.
For me to get my blood level up from 15 to 40 (my target) took 4000 IU per day. I'm pretty sure that not many people who are told to take more Vitamin D3 take anywhere near that much. So I think that studies like the ones Scott has reported on need to say what the actual measured blood levels are, or they will be hard for me to take seriously.
On Zvi's advice, I took 4000 IU of Vitamin D per day for about 2 months.
Then I got kidney stones, and one of the doctors I chatted with said it could likely be from the Vitamin D, and I reasoned that I'd stored up enough Vitamin D (I think it gets stored in fats?) that I should stop taking it. Because kidney stones was no fun.
Heck. I didn't know about this.
I have been in the hospital twice for kidney stones. I have found that the best way to avoid more is to drink a lot of water, and more when you start feeling symptoms of stones again. I've been taking 4000 IU of D3 daily for a decade without any more stones.
Thx, that's somewhat reassuring. Yes, water is key.
I did have a kidney stone 2 years ago, so it's plausible that getting it again is independent. (Or that it exacerbated it.)
Maybe it will be helpful if I say a little more here. After I had those two hospitalizations, several years apart, I realized that both times, I had experienced the same progression of symptoms. I remember seven. At various times since then, I have noticed that I got two, then three, then four of them. By that time, I would be feeling pretty uncomfortable, but not really very sick or needing a hospital. I assumed that a new stone was building up, and that's when I would start pushing very large amounts of water. Within a few days, these symptoms would abate, every time.
Also, a few times I have had an ultrasound that showed "gravel" in my kidneys, but a later one would show none. This convinced me that I really could grow new stones, and flush them out again, so I keep drinking a lot of water.
So I can't be completely sure that drinking all that water flushed out nascent kidney stones, but I'm going to go on acting as if that's the case. And with all the Vitamin D3 I've been taking, I haven't gotten another full blown attack of stones.
Laboratory tests should be designed so that around 5% of tests are reported as abnormal. I worked for almost 30 years as a hospital pathologist, and, without doing a formal study, we were reporting way more than 5% of our vitamin D levels as abnormal. Before going off and making any recommendations, I would want to work on the test and make sure that there are no issues with it. Working in a community hospital, I never had the resources to do that sort of large study, but I still have the nagging feeling that something is amiss here, and I am not sure what it is.
As for outcomes in people of East Asian descent, I know through friends in the Chinese community that many people of Chinese descent remembered the original SARS epidemic and changed their behavior way before the government was willing to admit that there was a problem. That confounder will somehow have to be corrected for before drawing any conclusions about outcomes in those patients.
I have been taking the maximum recommend daily dose of 4,000 units Vitamin D3 since Feb 2020 on recommendation from Doctors at the Harvard Medical School. Presumably Vitamin D interacts with ACE2 which was identified as the viral binding site. So presumably not having a Vitamin D deficiency can be beneficial with respect to possibly reducing the risk of becoming infected.
https://elemental.medium.com/what-science-says-about-vitamins-and-supplements-for-covid-19-b5feaedbb9f1
There are a lot of people who definitely do need more Vitamin D because they're deficient, and there are a lot of other people who don't take Vitamin D when they should (or take less than they should) because they're incorrectly worried about taking too much. If you might be in either group, you can ask your doctor for a Vitamin D test, or just buy one for $50 here:
https://www.everlywell.com/products/vitamin-d-test/
So let’s pretend that I’m a rube who don’t hold with all that high falutin’ college talk about n=stuff and chemistry and randomized study sessions and such.
What is wrong with blurring the conclusion enough for common sense to assert itself? “Vitamin D makes you healthier, and healthy people handle the ‘Rona better.”
If somebody did the exact same studies testing Vitamin C instead of D, do you reckon there would be a similar spread along the effective-ineffective spectrum?
https://elemental.medium.com/what-science-says-about-vitamins-and-supplements-for-covid-19-b5feaedbb9f1
> What is wrong with blurring the conclusion enough for common sense to assert itself? “Vitamin D makes you healthier, and healthy people handle the ‘Rona better.”
I think the Vitamin D skeptic case is to just leave off the first clause and say "healthy people handle the ‘Rona better." Who has more Vitamin D? People who are healthy enough to be active outdoors, getting sunlight.
My guess is that this is the whole effect, but that Scott's conclusion "supplementing might help and it probably won't hurt" is correct.
Thanks Scott - super interesting as ever.
Any thoughts on safe dosing? The NHS recommends 400 IU/day and cautions against taking over 4000 and warns that more can be harmful (https://www.gov.uk/government/publications/vitamin-d-supplements-how-to-take-them-safely/vitamin-d-supplements-how-to-take-them-safely).
Most online retailers in the UK seem to sell tablets with 4000IU each, and 6000 seems common in the US. Then the Brazilian trial you mentioned used a single megadose 200,000IU (!)
I find it hard to square the NHS's cautious position with what seems like a wide range of dose choices in practice. Any idea what gives?
My understanding is Vitamin D takes a while to accumulate in your system. Large doses are okay as a one-off, but not something you should take daily. I've seen 20K IU used as a weekly dose, for example. 200K IU sounds a bit huge though?
I suspect the NHS (and FDA) need to be cautious about supplementation recommendations because it depends on the amount of sunlight you get. 4000IU is probably fine for someone indoors all day, but might be too much for someone who's outdoors a lot. I looked into this at one point, and had trouble finding any good studies or recommendations that accounted for sunlight exposure, so would also be curious if anyone else has better info.
I have read (sorry, don't have a reference) that 10,000 IU is the do-not-exceed number. Vitamin D takes a long time to build up or discharge from the body (like around a month), so short-term dosing isn't likely to cause trouble.
I would also look at the enthusiasm for Vitamin D in a broader context. Over the past 75 years there has been sequential excitement and enthusiasm for different vitamins/minerals as panacea for many human diseases. Cycles of Vitamin C (the great Pauling first one), various B vitamins, Selenium, Zinc, Vitamin E (for a long time). Medical specialities in diverse fields (immunology, oncology, ID) all simultaneously become excited by the new trendy vitamin/supplement. Initial small studies often show dramatic benefit in whatever metric is being assessed. Sadly, almost universally when large, controlled studies are done, there is great disappointment (and sometimes even negative benefit). Vitamin D is the latest of these cure-all supplements. You could probably look at a graph of medical literature/reports on each of these magic answers, and Vitamin D is certainly trending. But skepticism is in order. But hey, it probably can't hurt...
My general physical health got a lot worse when I first started staying at home all the time (I've literally left my house/yard only twice since last March, and I think it's been a month or so since I've been in sunlight). I had back pain, wrist pain, joint cracking, and fatigue at various points (I'm in my mid 20s). Since I started taking vitamin D or other multivitamins, I have basically not had any such issues. I expect that my COVID avoidance is way more dramatic than most people's, but I think most people have been getting less sunlight than they used to, and if so, Vitamin D seems great for improving their general physical health.
This sounds very dangerous... Do you not even leave to visit the store and such ?
Or at least go for a walk around the block!
One of the instances of me leaving the house was a few months in, where I thought that perhaps I should get exercise and go for a walk. However, I was unhappy about not being able to stay 6+ feet away from other people, so I aborted that and have not gone on a walk around the block since. I have a VR headset now though, which helps with exercise if not sunlight.
My roommates and I have all of our groceries delivered. My roommates are a bit less paranoid than I am and have done various things (dental appointments, trip to visit mostly-isolated family members, emergency CVS trips, etc). I planned ahead and got a haircut / dentist appointment right before our state had its first case of community transmission, so I haven't needed to do such things myself (I've been actually flossing daily to compensate for increased dental risk).
I also have a friend who visits every week or so, but he doesn't go to any public places and gets COVID-tested in his lab every week before visiting. My roommates also both have SOs who visit, but they also live in houses where everyone works from home and never goes to public places (those house might allow grocery store visits too, I'm not sure).
One of my instances of leaving was a two-week trip where I walked to a friend's apartment and stayed there (I was isolating from my roommate when he got back from a plane trip). The friend and their roommates also got delivery and never left their house (except for medical appointments). We did have to leave the apartment building once when there was a fire alarm, but that was it.
Please correct: >>we can be pretty sure that their COVID is caused by Vitamin D.<< ==> >>we can be pretty sure that their COVID is caused by lack of Vitamin D.<<[and delete this commentary]
My strong, strong prior here is that Vitamin D may be a decent biomarker, but it's a lousy therapy. It's been thrown at nearly every indication under the sun in RCTs, and almost always returns null results. To me, the most plausible explanation is that low Vitamin D levels are correlated with biological states (malnutrition, sedentary living, inflammation) that predispose to poor outcomes, but short-term Vitamin D supplementation does not address the underlying predisposition.
"every indication under the sun"
I see what you did there
I'd also like to add that, if it wasn't called "vitamin", people would care way less about it
*grumbles about how "vitamin" is not a meaningful category, and, in the case of cholecalciferol derivates, we're actually talking about hormonal replacement instead of vitamin supplementation*
Great summary. A common "bad take" submission I've never run is along the lines of "the race disparity is explained due to vitamin D." Probably not, but maybe a little. It just strikes some people as a completely bonkers suggestion, so I get sent it regularly.
Also gets tarred by association because same people pitching also hock zinc and HCQ. (And now ivermectin, another "bad take" I can't pull the trigger on.)
Three things to consider:
1) Mendellian randomization and the Biobank studies are both invalid because people supplement in response to genetically low vitamin D, which violates one of the assumptions underlying MR. This is especially true since government guidance in the UK changed pretty dramatically on vitamin D supplementation
2) If you're looking at a racial case for vitamin D, you should really look at immigrant pairs like African immigrants to Sweden, or Indian immigrants to the UK. In all cases you see low Covid rates in poor sunny countries and high covid rates among immigrants from those countries to rich northern countries. This is the Ricketts pattern and strongly indicates vitamin D's involvement. https://shotwell.ca/posts/africa-covid/
3) The problem with the Brazillian study is that vitamin D was given way to late. If it's active against Covid it's because it works basically as an anti-viral, in that Brazillian study they gave vitamin D on average 10 days after symptom onset by which time the virus had cleared. All the supplementation studies where vitamin D has been given in or before the viral replication phase have been positive.
IDK about Africans in Sweden but the British South Asian population is much more urbanised than the total British population and probably moreso than South Asia in general.
Not really, the population density of Nairobi or Dehli is many times higher than Stockholm or London. Also South Asian people in London are have a Covid jeopardy that's several times higher than white people in england after accounting for income, preexisting conditions, and neighborhood. https://www.medrxiv.org/content/10.1101/2020.09.22.20198754v1
This means that Indians in the UK have a covid jeopardy that's several hundred times higher than those in India despite having more money and better medical care.
https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&time=2019-12-31..latest&country=IND~GBR®ion=World&deathsMetric=true&interval=smoothed&hideControls=true&perCapita=true&smoothing=7&pickerMetric=location&pickerSort=asc
Re: Asians
Older population?
As an aside, I think one of the biggest unanswered questions about COVID-19 is why so few people in equatorial Africa have died. Equatorial South America has done pretty terribly (Manaus = 3.1190°S), and outcomes from the first world indicate that African ancestry does not confer a survival advantage.
Many fewer elderly people in Africa than in South America, I guess.
you don't mention this study here. https://nypost.com/2021/02/15/covid-19-study-revives-heavily-disputed-vitamin-d-theory/
This study seems to have severe limitations, as explained here. ( https://mobile.twitter.com/fperrywilson/status/1360944830600400896 ). The way it's written is very questionable, and raises my scepticism on the quality of the research by the same group
Seems for individuals, the first question is whether one might be borderline vitamin-D deficient to begin with (little sunlight, milk-free diet for some reason, etc.). It might help more for Covid in such folks (and only in such folks?). And all sorts of below-the-radar effects of low-D may well get solved besides.
This article seems to miss discussion on the most important claim I've heard around Vitamin D supplementation: that daily Vitamin D supplementation substantially reduces your risk of contracting severe cases of covid.
This is quite different from a) vitamin D reduces your risk of getting covid (why would it) or b) taking vitamin D when you get covid improves outcomes.
My understanding is that *it takes a long time to increase serum vitamin D levels through supplementation.* See this article from the NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820059/ . In short: infrequent, low doses (1-2k IU) of vitamin D do not raise serum vitamin D. Dose and frequency (per week) mattered more than duration, but duration was at least a month, not 7 days! And duration effects were increasing - the longer you took vitamin D, the bigger the effect!
Scott dismisses this entire argument by saying "people who can do anything consistently for a year will do better" without actually analyzing it in more depth. No, you actually have to take vitamin D supplements frequently over time (at least one month, with effects increasing up to 6 months), at higher dosage for them to have an effect. Dismissing the underlying mechanism as being a selection effect, means that Scott misses the best argument in favor of long-term vitamin D supplementation.
This hypothesis may be wrong - maybe that research paper is incorrect, maybe there's more evidence behind Scott's handwave - but right now it seems to me that Scott is ignoring the crux of the debate: can long-term vitamin D supplementation reduce your odds of a severe covid case, conditional on you getting covid? Scott unfortunately does not address this question, which is the most important one, IMO.
Given that long-term vitamin D supplementation does increase serum vitamin D levels significantly more than short-term vitamin D supplementation (at least according to the research), I am inclined to believe the research does suggest that vitamin D supplementation can reduce the odds of contracting *severe* covid cases much more than Scott does.
Long-term supplementation works independent of Vitamin D levels, which makes me think confounder rather than real effect. Also, the correlational studies ought to capture the same effect that long-term supplementing should have, and they show nothing.
That's quite different, no? The study you linked (https://pubmed.ncbi.nlm.nih.gov/33515005/) says that taking vitamin D consistently is associated with a lower risk of getting infected with covid, but that is different from the conditional risk of getting a severe covid case once you have covid. Vitamin D can "work" not just by preventing you from getting covid, but by helping you fight it off once you get it.
I can understand how conscientiousness may be a confounder for the risk of getting covid at all (e.g., related to how often you wear a mask), but I can't understand the causal mechanism between conscientiousness and how bad covid is *once you have it.*
Once someone has covid, it seems to me that it comes down to biological processes, not personality traits. Given the evidence that a) it takes high duration, frequency, and dosage to raise vitamin D levels b) lower levels of vitamin D are associated with worse cases of covid *once you have it,* the mechanism seems like it is there, but nothing that has been cited actually investigates that specific mechanism.
I'm with AB but on the specific point of how germ avoidance would reduce the severity of covid conditional on testing positive for it, 1. false positives and more importantly 2. initial viral load determines severity
As far as mechanisms, there is circa 30 years of research illustrating Vitamin D’s involvement in activating/modulating the diverse weapons of the innate immune system, the “dumb” first line of defense that doesn’t require antibodies or the subtleties of active immunity. The cells of the innate immune system, as I understand it, express the VDR, Vitamin D Receptor, for signaling purposes related to active Vitamin D. More specifically, one component of the innate immune is a range of antimicrobial peptides that are produced, something akin to rather indiscriminate artillery. One such peptide that’s gotten a fair number of mentions already in relation to COVID is known as LL-37. This pre-print claims to have found that the peptide LL-37, which is induced by Vitamin D, directly inhibits the binding of SARS-CoV-2’s Spike protein to the ACE2 receptor, which is the receptor on the cells of various organ systems that this coronavirus uses to infect. (https://www.biorxiv.org/content/10.1101/2020.12.02.408153v2)
I think the prior here should be other respiratory infections, where long term vitamin D supplementation was shown to be effective while high dose bolus supplementation (like that used in the Brazilian trial was not.
https://www.bmj.com/content/356/bmj.i6583
To what degree can it be that people with low vitamin D are more conscientious (indoor workers) and therefore have a lower risk of getting infected?
Seems like the studies shouldn’t control just for race, but also for behavior.
I’d say low vit D white people will be more likely to get infected due to low vit D, but less likely to get infected due to behavior. Which could easily mask the relation between vit D and covid incidence completely.
It would be better to look at severity for this reason, since it’s presumably affected less by conscientiousness than incidence — but it still *is* affected. Conscientious people can do other things that decrease the severity.
Seems like taking the other side of the rootclaim challenge would be very positive EV if those estimates are correct?
https://blog.rootclaim.com/treating-covid-19-with-vitamin-d-100000-challenge/
One the one hand, you're right that a 50:50 bet is pretty nice if you have 75% confidence. On the other hand, a $100,000 wager is substantial enough even plenty of upper-middle-class people aren't likely to be willing to tolerate the risk. This is part of my irritation with regards to these rootclaim challenges... are they showing that people are being irrational, or are they just showing that most of their readership doesn't have sufficient risk tolerance to throw large sums at their shenanigans for claims with middling confidence?
I don't know about you, but I'm happier putting my disposable income in a well-diversified portfolio.
"We are open to discussing lower or higher amounts, and the funds can be pooled from multiple sources."
I'm not familiar with them enough to know how much lower they'd go, but seems like pooling from multiple sources would mostly solve the problem you mention? Agreed that most people reading this, myself included, wouldn't plunk down $100k, but it doesn't seem crazy that n people would be willing to bet $100k / n.
Yes, for large bets, the downside of going broke often outweighs positive expected value.
See Kelly Criterion (https://en.wikipedia.org/wiki/Kelly_criterion) for the mathematics of how much you should bet once you account for bankruptcy.
I should add that if you also account for the bet taking 1 year to resolve--that's a pretty huge opportunity cost--it becomes even more unattractive.
This article reminded me to take my daily Vitamin D supplement! Thanks Scott for the help.
I think this qualifies as an enema recommendation, though perhaps there's enough evidence in favor that it doesn't. An old joke:
An actor collapses on stage, and a doctor is found in the audience. As he tends to the actor, an old lady calls from the cheaper seats: "Give him an enema!" She is ignored. She cries again, "Give him an enema!", and again, nobody pays attention. After a third "Give him an enema" is heard, the doctor turns, and says, "Ma'am, I assure you, giving this man an enema would do him no earthly good whatsoever." The lady replies, "Well, it couldn't hurt."
I think you took the wrong side regarding the Spanish Vs Brazilian trials. The Spanish one was peer reviewed. It was better conducted with more activated form of vitamin D. It is totally not wise to give D3 to already hospitalised person. It takes precious time to be converted to the active form. The Spanish trial also was small achieved remarkable p value. This is the unbiased estimator which means that no matter it was small study, the results proves causality. Patients were divided for the true treatment or placebo randomly by a computer. How can one argue against this method ...
In isolation, I don't think you can.
But if we were living in a world where the Spanish study is true, I can't explain the Biobank and the Montreal genetic study would give negative results.
I can think of lots of good reasons why a seemingly-decent study would wrongly yield a positive result (we missed a confounder, conflicts of interest, ...) but it's much harder to believe a strong-looking study would *miss* a phenomenon with such a huge effect size.
Edit: I can't explain *why* the.
(I miss comment editing)
Agreed except you have to account for the possibility of scientific fraud (or its accidental equivalent) especially in the first study that popularizes a sexy new hypothesis. Also, people are presuming that the form of D which is 'active' for calcium absorption and bone hormonal signaling is the one that's useful for respiratory/antiviral effect. We really need to be agnostic about which step in the sunlight->D chain is useful for fighting colds. Many things have more than one use in our body.
The latitude thing might be exterior UV killing COVID on surfaces. In Asia, there's been a buying spree for indoor UV lamps to provide some viral load reduction indoors, complete with timers and motion sensors and shut off whenever a person walks into a room.
I think most people now think that surfaces are relatively unimportant as a vector, except in hospitals.
I have a very strong prior on surface and contact transmission, so I don't really buy the "unimportant surfaces" idea. A mask will protect you from droplets, but it won't protect you from your hand wiping your nose or touching your face.
Many chunks of East Asia have 99% mask compliance rates and still have transmission chains.
But a mask at best protects you partially from aerosols, unless you're wearing a very tightly fitted N95 or better. I don't think you have 99% compliance on that.
My current guess is that surfaces are really important for the kinds of bacterial infections that cause major problems in medical settings, so the medical system over-learned the Semmelweis story, especially when they were trying to kills the miasma theory in favor of the germ theory. But the other part of my guess is that surfaces are much less significant for respiratory infections than we've been told.
It would be amazing if someone were actually able to do a thorough examination of a representative set of cases in an ordinary flu season, to figure out where everyone picked up the virus. But unfortunately I don't think we'll be able to get that, to properly confirm or deny my conjecture.
In East Asia, it was common knowledge that masks worked and all the professors, to the man, were screaming for masks from January 2020 onwards. It is also common knowledge that you should "wash your hands after taking public transport and avoid touching your eyes, nose, and mouth". Hand hygiene, hand hygiene, more hand hygiene!
Granted, that does not mean surfaces are necessarily important, but it's been drilled heavily into the population.
i'd not trust one with a motion sensor to cut off as soon as you enter. Those germicidal lamps can generate ozone
What are the risks of those UV lamps generating UV-resistant germs for us in 10 years? Is there a way for this to happen, or is it just too much to overcome at once?
It would be useful to check the methodologies utilized for measuring vitamin D levels in these studies, since it seems that the measured value for 25-hydroxyvitamin D (predominant in testing) largely depends on differences in vitamin D binding protein (VDBP) between individuals. Ginsburg & coworkers identified a vitamin D metabolite ratio (VMR) which is dependent on concentration and not on the amount of VDBP that is present in an individual.
> The VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status.
"The Vitamin D Metabolite Ratio Is Independent of Vitamin D Binding Protein Concentration", Clinical Chemistry, 2020, doi: 10.1093/clinchem/hvaa238 , https://pubmed.ncbi.nlm.nih.gov/33188595/
The lead author also, Dr. Charles Ginsburg, a nephrologist & prof discussed the research in a 10-minute interview for the Clinical Chemistry Podcast: https://directory.libsyn.com/episode/index/show/clinchem/id/17760140
>There were some early astoundingly massively positive RCTs for hydroxychloroquine
I don't remember any, just a lot of extremely sketchy-looking stuff showing some mild effect. Which RCTs are you thinking of?
I can help with the seasonal pattern. The smallish bump in the summer was in the hotter, southern states primarily. The much larger bump in the winter was in the cooler, northern states primarily. Common theme? People spending lots of time indoors in climate controlled environments.
So in order to test this one could run zip code latitude vs month of infection, or average zip code temp that month. I'd predict that temps outside of 55-85 or so cause a bump in COVID.
There is a metric used in the energy industry that tracks this called cooling degree days and heating degree days. You can even trade financial instruments on that number. It seems to me that the pattern in the US has been outbreaks when HDD's or CDD's start increasing in a location.
It looks like there's another randomized controlled trial in the works for Vitamin D supplementation being planned, from Wang et al. (N = 2700): https://doi.org/10.1016/j.cct.2020.106176
That's a pretty substantial sample size. Can someone take a look at the trial design plan and see if it's reasonable? That isn't my skillset.
A veritable cacophony of Vitamin D studies. I'm frankly surprised you implicitly lend credence to the results. Given the file drawer problem, replication issues and paradoxes within your speculations, there's really no basis for your last 3 paragraphs except intuition/ guessing/ idiosyncratic heuristics. You certainly know that mechanistic thinking just doesn't go very far in medicine; and that case-control and other observational studies are sometimes useful but overall weak. To argue seasonal variation may occur related to sunlight/ vit D while later noting levels are usually stable over long periods is not consistent.
Those criticisms aside, your collection of studies just shows once again how poorly medicine and the lay public have been served by academia in a time of great need. Large well-designed studies capable of definitive answers are sorely lacking among the utter cacophony.
> And maybe some day, after countless false leads and stupid red herrings, one of the claims people make about this substance will actually pan out. Who knows?
One thing that always struck me as weird about vit D is how ubiquitous it is among health-conscious people
I wonder if th lis is a case of memes spreading with no reason, or of the studies missing an important factor.
It's been years since I looked at it but the kidney stone risk should be lowered by simultaneously supplementing vitamin K (which is another one of these quite likely positive supplements).
Regarding summer: sars2 is highly unstable when it comes to light, heathings dries the air which makes your mucous membrane dry and live inside has no wind. Source: christian drosten's podcasts.
My thoughts are that possibly low vitamin d could also simply be a marker of poor diet and lifestyle.
A possible downside of supplementation could be that it makes more postive change less likely.
I.e. more outdoor physical activity, combined with nutrient rich diet will likely* sort vitamin d levels, plus have a host of other benefits that would be missed by supps alone.
Supplements in general have a very poor track record, possibly as many people end up taking them as "substitutes" to a nutrient rich diet rather than supplements? (Purely speculative).
Given the choice between go outside, exercise and eat well, vs take a pill, many will opt for the pill. Which is fair enough providing we know the true efficacy of the pill and can make the trade-off. But I don't think this is the case (for vit d and covid or any other supp and health outcome).
* Possibly for darker skinned individuals, living at northern latitudes, working indoors all day it might be impossible to achieve optimum vitamin d levels through sun exposure and diet?
> and die of it 3x more often
Is that number correct?
n all of this you haven't mentioned to what level of Vitamin D you are testing against. The level described as "deficient" for bone health isn't the one described as "deficient" for respiratory health (if that is indeed a thing).
If you want a null hypothesis to aim at, here's one
"The bottom line is that there is no downside to increasing our intake of vitamin D to maintain serum 25(OH)D at at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve optimal overall health benefits of vitamin D."
https://www.mdpi.com/2072-6643/12/7/2097/htm
Reassess against that much higher than standard level and everybody can avoid talking past each other.
In this instance the obsession with the precautionary principle is to avoid hypercalcemia at all costs - even if that means people succumbing to respiratory illnesses. Something they didn't do, for some reason, with masks.
"The bottom line is that there is no downside to increasing our intake of vitamin D to maintain serum 25(OH)D at at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve optimal overall health benefits of vitamin D".
The recommendation buried in that study is 4,000-6,000 IU per day, which falls in line with the maximum recommended limit of 4,000 IU/100 μg. But this does not mean that someone should then decide "if that much is good, then 10,000 IU would be even better!" because NO, IT REALLY WOULD NOT BE. And again, get it from your diet and exposure to sunlight, not from dosing on supplements (unless during winter months when no sunlight and/or your diet is really crappy).
We know that getting covid is correlated with breathing it in. We can be fairly confident that better ventilation reduces the risk of covid. What do people do in warm sunny weather? Open windows, and go outside. We should expect the latitude and seasonal effects, even if vitamin D was nothing to do with it.
My intuitive take is that vitamin D has some effect on immunity but compared to bone health, it is much less pronounced. The bone mass is comparatively large and we need a lot of calcium therefore vitamin D deficit can quickly cause problems. Whereas the immune system can adapt with lower vitamin D levels.
Very low vitamin D levels in people could make the immunity much worse too but in practice we notice problems with the bones first and treat them accordingly. Supplementing subclinical vitamin D deficit provides only marginal benefits.
In conclusion, it is good to maintain vitamin D levels in the recommended range, and take supplements if you need to, mainly, to help your bones. Maybe it will have a secondary benefit by slightly improving your immunity too but don't rely on that too much.
Given that almost all of us get way less sunlight than our ancestors, I would advocate supplements anyway, to bring us up to the levels that our bodies are adapted to.
Vitamin D has low toxicity, so it's very unlikely that you err on the side of having too much.
The best explanation I've seen for the seasonal and latitude nature of the virus so far is indoor humidity. If the temperature is below 15 degrees C, the air indoors is heated and becomes dry. This causes droplets expelled from the mouth that would settle in more humid conditions to evaporate and become smaller and float around for longer providing a more effective transmission in confined spaces.
A leimilar but lesser effect can occur from airconditioning in summer.
In places with really sealed up indoor spaces the humidity is lowish in winter but not as low as some not as cold places because the less sealed up spaces have more cool outdoor air comes in to be heated. Places with winter daily maximums in the 5 to 15 degree range tend to have the dryest indoor air in winter.
"In the US, more blacks than whites have gotten coronavirus."
In some alternate reality version of the US, perhaps. But not in this US.
I assume the sotto voce proviso is "relative to their base rate in the population."
Seasonality/latitude dependence could be completely explained by people gathering indoors vs. outdoors. Very hard to get aerosol transmission in a windy park.
People still spend a lot of time indoors in all seasons. Virus transmission changes by a factor of 3 in most temperate climates throughout the year but people's time in offices, homes and shops does not vary by anything like that much.
Regarding the Mendelian randomization study: When you buy a 1/4" drill bit (or perhaps a 6.5 mm drill bit if you're into that sort of thing), it's not because you want to own a drill bit, but because you want to own some 1/4" holes. In the same way, we don't want vitamin D in our systems because the vitamin D molecules strut around the body punching corona viruses in their little faces, ripping apart cancer cells, and blocking the depression rays emitted from the dirty laundry pile. We want it in our system because it does something else. Perhaps the people with hereditary vitamin D deficiency have some other source for this, uh, "something else". Maybe they make their 1/4" holes with punches, lasers, or well-disciplined termites.
in all earnest: please start a blog
You should really clarify your definition of "Asian". That term covers a much, much broader range of latitudes than white or black does. Probably difficult to suss out small lineage differences in the entire subpopulation, but you could just focus in on two groups with different historical ranges, like Koreans and Indonesians. Or Native Siberians, if you can find data.
> The loose ends that bother me the most are the seasonal pattern, the latitude data, plus the increased risk of hospitalization and death in Asians. I don't have a great explanation for those.
Couldn't the first two be explained simply by the fact that during the winter in northern countries, people tend to meet indoors rather than outdoors? This facilitates the spread more.
"For example, infection rate from coronavirus seems latitude dependent; in general, the further north an area, the worse it's been hit."
This isn't obvious; the statistics from the southerly countries aren't as reliable as those from the northern ones, and it is known many southerly countries (Mexico, Peru, Bolivia, Ecuador, Indonesia) have been very hard hit. It was true during the first wave in the U.S. and at the beginning of the third, but Mississippi, Louisiana, Alabama, and Arizona have been some of the hardest-hit states. In the E.U., Spain has been hit rather badly. It is true that Russia, the Dakotas, and the U.S. Northeast have been very hard-hit, though, but the U.S. Northeast pandemic seems to have been due to its better connectedness, while the harsh pandemic in the Dakotas and Russia was likely due to lack of social distancing.
Have you considered posting these as questions on Metaculus?
Does anyone have a quantitative idea, which proportion of the skin should be exposed to the sun for how long for normal cholecalciferol production, let's say for a maximally light-skinned bloke? Where I live, from october to april, the only exposed body part is face, and we get to see the sun every 3rd day or so. Is there any chance that we're still producing adequate amounts of cholecalciferol if we spend, say, 1 hour a day outdoors?
Probably best to just take a test and see your levels
Get the free dminder app. It was developed by a top Vitamin D researcher, and it will show you exactly how much Vitamin D your skin is producing in real-time, based on your location, the angle of the sun, your skin type, the % of skin you are exposing, etc.
You're probably not making any vitamin D from Oct-April if you live above the 37th parallel. I posted a 4 question Vit D calculator on my site https://vatsalthakkar.com/vitamin-d-calculator.html (based on treating >1000 patients with Vit D deficiency, myself included, and from published studies incl one based on > 20,000 patients who supplemented).
The UK Biobank studies are flawed, especially Hastie.
See: https://www.sciencedirect.com/science/article/pii/S1871402121000394 (peer reviewed & published)
and https://www.researchgate.net/publication/346922274_Serious_Statistical_Flaws_in_Biobank_Analyses (preprint with more details)
Lastly, I'm not sure where the idea came from that levels are stable over time. There are studies showing the 10-15yr old UK Biobank levels don't correlate well with recent levels. IIRC one correlation coefficient was around 0.4, which makes more intuitive sense in the first place. The idea of stability over time is reasonable in the face of no measurement or intervention/change, but the UK Biobank participants didn't have their levels hidden from them. It's pretty reasonable to assume those people who discovered they were deficient as a result of the UK biobank participation took steps to correct their deficiency. Their doctors certainly should have encouraged them to do so.
So trust Kaufman et al, Merzon et al, Meltzer et al more.
On the RCTs:
Dismissing the Indian RCT is inappropriate. This was small n but a well designed trial registered in advance and regardless of the importance of seroconversion clinically in terms of severity to individual patients, this data clearly shows a causal link whereby vitamin D affects SARS-CoV-2 infection.
Favoring the Brazil trial over Cordoba, Spain is also picking the wrong one. The Brazil trial didn't start giving patients D3 until they already needed supplemental oxygen (90% of them at baseline) because they were already 10 days post symptom onset and they were only average 7 days from discharge from hospital in terms of recovery. D3 doesn't ramp up fast enough to make a difference that late in infection is the only conclusion that can be drawn. See the comments of the medRxiv page of that Brazil study for many comments along these lines and other issues: https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1#disqus_thread
The Cordoba study used calcifediol which skips liver conversion and restores D levels within hours and thus had a much better effect. If they had used it in Brazil maybe the results would have been better. What's more, there's now a new preprint which has statistical issues but nonetheless adds to the positive data. It also used calcifediol and had 10x the patients (though the randomization was by hospital ward not patient, but it still makes the D helps conclusion more likely despite its flaws):
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3771318
I'm not sure why the Brazil hospital in that study got the patients so late in the infection. Worse healthcare infrastructure in that country?
But the trend is clear: 3 of 3 randomized controlled intervention studies started at hospital admission in countries in which that hospital admission came before patients were so far along that they mostly needed supplemental oxygen all showed positive results. And 2 of 2 calcifediol studies showed extremely positive results.
You said, "in the past I have learned to side with negative RCTs rather than astoundingly massively positive ones when the two conflict." That's a reasonable default for clinical trials of still-on-patent pharmaceutical agents because those tend to be sponsored by the pharma company that has strong financial incentives. For trials of natural agents especially those run by non-industry groups, the opposite should probably be the default. Eg see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487184/
You said, "I am going to assume that whichever doctors ran these studies did not completely bungle them and use forms of Vitamin D that could not possibly have worked in the time period involved." Completely bungled in the Brazil study is a reasonable conclusion. It's not completely absurd that it could have worked in the time involved, and the study organizers may not have known how far from recovery the patients would be when they started, so we don't have to fault them for running it. But the late stage of initial administration compared with the time it takes for that version of D to ramp up means its negative result cannot be applied to initiating the same treatment earlier in infection, nor does it cast doubt on D for prophylaxis, nor is it negative for calcifediol which is much faster acting.
Thanks for posting this. Any opinions on N-Acetyl Cysteine (NAC) supplements? I have read/heard claims of reduced covid symptoms associated with it’s regular use.
On appeal to authority:
How many scientists & doctors work on the NICE committee?
Here's a list of hundreds of scientists & doctors who say the evidence is convincing enough that it should be default to use vitamin D for covid as a precaution: https://vitamindforall.org/rollcall.html
It terms of credentials, these groups include many of the top vitamin D researchers in the world (based on citations), a former surgeon general, and many notable names.
Based on the prior 2 corrections I just posted in earlier comments (on Hastie & on the clear pattern from the RCTs) and this appeal to experts, you might want to update your % guesses on D's relevance. My personal guesses are 80% chance that D affects infection risk & 80% that it can help as treatment if given early enough in infection or as calcifediol. And 99% chance that benefits outweigh costs.
Correct reading of the evidence together with understanding the underlying biology makes the situation very clear. It just isn't quite clear at the level of approving a new pharmaceutical drug, and the big problem is that that is the evidentiary bar that NICE and other officials at 3-4 letter acronym bodies are applying. That's not the way to handle public health especially in an acute crisis. It's *astoundingly* clear that the balance of risks is such that increasing vitamin D intakes and reducing deficiency rates is a clear public health win net-net, especially now.
Good piece. Not mainly for the conclusion, which doesn't hinge on the analysis, but for an example of what a careful examination of evidence looks like.
This part seems unconvincing:
"We assume that people with the genes for low Vitamin D in fact have low Vitamin D. And this isn't confounded by anything; we know their low Vitamin D is genetic. So if these people get COVID more, we can be pretty sure that their COVID is caused by Vitamin D."
Probably the assumption in the first sentence there is at least somewhat false, no? Since people can change their vitamin D levels by taking vitamin D.
Also, it could be that a genetic predisposition to low vitamin D is associated with some *other* genetic thing that has an effect on severity of covid infections (in either direction - so you could get an illusory effect if it's associated with something that makes covid worse, or an illusory absence of effect if it's associated with something that makes covid less bad). (I don't have any specific knowledge that this is the case, but it seems like a gap in the logic as presented here.)
Scott, I suspect it was delayed by the Blog closure but I've definitely been waiting for your thoughts on 'no evidence' and the other scientific messaging in this pandemic. The language used to scientific uncertainty to the general public needs a rethink and I suspect is the source of much public disinformation.
I don't blame Joe Public for thinking 'no evidence' for a *thing* means definitively that the *thing* doesn't work.
Vitamin D for patients admitted to hospital could cut Covid deaths by 60 per cent University of Barcelona preprint for the lancet not peerreviewed yet... I had low Vit D (22ng/ml) when last measured 4 yrs ago (after spending 45min everyday in the midday sun in June...... I started taking 2,000 iu but after reading a few articles associating low vit D levels with the worst outcomes in covid I started taking 10,000 iu (250mcg?) but will be getting tested after my 2nd vaccine shot (1 week) I am aiming for a blood level of 60-80.... Depending on your age and genetics it can take a lot to boost your levels up.... any blood level up to 150 is most likely safe
When the limit of 100 was decided on the actual research showed a level above 300 was toxic....but to err on the safe side an upper limit of 100 was recommended....
Yeah. I took 5000 IU daily for years (upped it to 10,000 in 2020 on more or less the same logic/spec as this post describes), and that dosage was barely keeping my level in the 30s, ie, in the very low end of normal range. Not everyone absorbs vit D equally efficiently.
The issue was already analyzed probabilistically by Rootclaim. They are also offering a $100,000 bet on it. If you're at 25% it's easy money for you (but don't, you'll lose - your analysis is wrong on many points).
https://blog.rootclaim.com/vitamin-d-can-likely-end-the-covid-19-pandemic/
https://blog.rootclaim.com/treating-covid-19-with-vitamin-d-100000-challenge/
25% isn't "easy money". It might be "strongly positive expectation", but that is quite different from "easy money" in the absence of easy ways to diversify.
I view any 1:1 bet with 75% odds as 'easy money', but I agree it's more of a personal risk/reward issue.
Somebody on facebook argued, that Hydroxychloroquine is still in the game. Because the trial, which said it didn't help was made by Surgisphere, which gave fraudulent data. (I a lazy to look it up on my own).
There were many, many trials, not just a few. It's true that a couple of the ones that said it didn't help were fraudulent, but there were many others that weren't.
1) Vitamin D correlates with activity/exercise levels pretty strongly. Consider this as a serious confounder in any observational study.
2) The Mendelian Randomization study I have strong reservations about. To run MR, you need to make strong assumptions about the genetic variants that you are using. So MR makes sense in cases where you know a lot about the variants. But here they are doing a GWAS to get the variants, i.e. taking anything that associates with Vitamin D levels. There's no theoretical reason to assume a priori that these variants have the properties needed to run this MR. Instead, you do some statistical tests and hope you can catch it if it's a problem. But those statistical tests make their own assumptions that I don't find very plausible.
The authors know this and address it and do a reasonable job at that. They try restricting just to variants that lie near genes that are known to directly impact Vitamin D and see the same thing, and they toss out variants that are also known to impact other phenotypes and so could confound. But it's just the reality of the problem: MR is a bit questionable if you haven't study your variants carefully. The fact that they find a null result makes this all less concerning, though it is plausible that confounders could cancel out the true effect.
I always felt, right after reading the original speculation, that Vit. D is a prophylactic rather than a cure. Firstly, you should have been taking this as a supplement already. So, if you have a decent amount of Vit. D taken as supplements cruising in your bloodstream; it is not going to prevent you from getting infected; but do two things: 1) maybe increase the viral load required for infection, 2) when infected the symptoms won't be as severe.
All these studies that you referenced don't seem to contradict this, or am I reading you wrong?
I would note that in general, anyone taking Vitamin D3 regularly in amounts of say 4000 IU a day, would be well served to take Vitamin K2 (probably MK-4) and Magnesium as well. And look into a source of Vitamin A (cod liver oil).
I'm 75 years old, and decrepit enough to be unable to what I used to. Vitamin D pills at Sam's cost pennies per day, hence I have been taking megadoses of it since June, 2020. No downside, possible benefits.
The most obvious difference between Spain and Brazil is latitude, which we already know has an effect (for whatever reason).
What percentage of people in Spain vs. Brazil do you think have a vitamin D deficiency?
It is easy to hypothesize that vitamin D supplementation in Spain alleviated deficiencies in many patients, whereas in Brazil it was superfluous.
All your other critiques apply. But this seems relevant too.
What is the explanation for 80%+ of Covid positive patients in Spain being vitamin D deficient? I would also like to see a regional analysis of Vitamin D deficiency rates in Brazil. Also, what about the 50 other studies? Overall this analysis seems a little weak, although the lack of enthusiasm from authoritative institutions is surprising.
The post-symptom/post-positive RCTs that find a (gigantic!) effect use calcifediol - the form that oral cholecalciferol slowly turns into, over a ~week. The RCTs showing no effect use cholecalciferol, whose conversion into calcifediol won't outrace an infection. I don't blame some researchers for trying plain cholecalciferol - it's a cheap OTC supplement, and maybe megadoses would help! Meanwhile calcifediol is a prescription-drug, & expensive in the US. But assuming "assume that whichever doctors ran these [cholecalciferol] studies did not completely bungle them" is picking one set of researchers arbitrarily to respect, & ignoring the contrast signal between the two choices. Why not assume, conversely, that the researchers who tested calcifediol did not completely bungle their inclination to test something with distinct effects from cholecalciferol? (The effect sizes in the calcifediol studies are gigantic!)
D3 needs to be taken with K2 (prevents kidney stones and other calcium mismanagement effects), magnesium (increases resorbtion) and A (reduces side effects from K2 related enzymes). It also needs to be taken with oil. And in small doses (5-20k IU/day) over a long time, megadoses like 200k IU will have way less resorbtion. I've read dozens of studies, even very recent ones, that showed side effects like kidney stones or artery calcification because K2 was ignored. Never ever assume the people doing these studies are aware of these problems, assume the opposite unless its expressly mentioned in the study. Keep that in mind when facing supposedly simple questions like "did they give an oil-soluble form/gelcap or the much cheaper dry form and if its the latter, did they give it with oil or fatty food". "Surely they couldn't have fucked up this badly"- yes they could lol.
👆👆👆👆👆👆👆👆👆👆👆
I became a paid subscriber just to post this comment. Here is a hypothesis, which explains the seasonal variance and the latitude data without vitamin D.
Red light.
A very specific wavelength of red light penetrates the skin very deeply and is absorbed by the respiratory enzyme cytochrome c oxidase, which is involved in the electron transport chain in mitochondria, causing an increase in intracellular ATP.
Red light therapy aka low-level laser therapy cures a lot of weird problems. This specific wavelength of red light is also component of sunlight. We get more of it during summer and near the equator.
Vitamin D could be a red herring. Sunlight can do lots of other things too.
Here's a longer version of the above. I posted this on my Facebook yesterday.
This post might solve the pandemic. Or it might not. I need someone smarter to check my work, so I’m posting it in public in the hopes that it will reach someone, who can check it.
The data shows that COVID-19 has seasonal and latitudinal variance, so we know that sunlight has something to do with it. Everyone knows that when sunlight hits your skin, you get Vitamin-D, so doctors started doing clinical trials on COVID patients involving Vitamin-D.
Preliminary results are in and it seems like there is no signal in the noise. Vitamin-D does not seem to be the important factor here. But sunlight clearly is.
That seemed like an interesting problem to work on (instead of actual work) so I started looking into it.
I think I can explain the seasonal and latitudinal variance of COVID-19 without Vitamin-D. My hypothesis can be tested for cheap and with zero risk to human health. And I can explain the full biochemical pathway of this effect.
Vitamin-D is not the only molecule produced by sunlight acting on the skin.
There is another one, much more important, but very few people know about it, because it was discovered by Russian scientists in the 1990s and not widely studied outside Russia. (Based on the name of the chief scientist, who discovered this effect, she’s probably Estonian.)
If you put your hand in front of a bright white light, what do you see? You see that only red light penetrates through the thinner parts of your hand. This implies that red light goes very deep in your body. A centimeter at least.
Red light with a wavelength of about 810 nanometers is absorbed by an enzyme called "cytochrome c oxidase", which is part of the electron transport chain inside the mitochondria of every cell. The result of this is a photochemical reaction, which boosts intracellular ATP production. ATP is the "fuel" that cells use for most internal processes. When a muscle cell contracts, for example, it spends ATP.
With more ATP available, the cell can do more. Including repair. So your body recovers better and faster.
This effect is used by a "new" field of medicine, which has many names: "red light therapy", "photobiomodulation therapy", "low-level laser therapy", and even "cold laser therapy". The content is the same: intense red light is used to boost body's own healing mechanisms.
I put "new" in quotes, because red light therapy was a pseudoscience for 50 years until Russians figured out that it works by stimulating ATP production via the absorbtion of red light by cytochrome c oxidase.
It's not magic and it's not a super powerful effect unless you haven't gotten enough natural light. Based on the seasonal and latitudinal variance of COVID, however, it looks like red light therapy might be the key to solving this pandemic.
There might be a third light-based biochemical pathway besides Vitamin-D and cytochrome c oxidase that could instead be the key factor in explaining COVID’s seasonal and latitudinal variance, but I haven’t found one.
Here is a scientific overview of the history of red light therapy. How it went from pseudoscience to acceptable medical practice:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215795/
Quote from that article: “The work of Tiina Karu in Russia was instrumental in putting the mechanism on a sound footing by identifying cytochrome c oxidase in the mitochondrial respiratory chain as a primary chromophore, and it introduced the concept of “retrograde mitochondrial signalling” to explain how a single relatively brief exposure to light could have effects on the organism that lasted for hours, days or even weeks”
I searched on pubmed if any doctor has tried red light therapy on COVID patients and found two case studies, both showing remarkable improvement:
https://pubmed.ncbi.nlm.nih.gov/32865522/
https://pubmed.ncbi.nlm.nih.gov/33043132/
I also found a paper recommending that doctors try red light therapy for COVID: "Based on the clinical experience, peer-reviewed studies, and solid laboratory data in experimental animal models, LLLT attenuates cytokine storm at multiple levels and reduces the major inflammatory metabolites."
https://pubmed.ncbi.nlm.nih.gov/32844112/
Anyone can buy a cheap LED lamp with the right red wavelengths online. Here is one on Aliexpress:
https://www.aliexpress.com/item/32832169367.html
If I'm right and COVID's seasonal variance and latitudinal variance is mediated not via Vitamin-D, but via cytochrome c oxidase, then all you need to test this hypothesis is to get some suitable red light therapy LED panels and hang them above COVID patients.
I'm pretty sure you don't need to get an ethics board approval to change the lighting in a hospital room from white to red.
A statistically significant randomized trial could be done in any hospital for about $10k spent on lamps, with zero health risk and zero ethical considerations. Just keep doing what you're already doing, but randomly put half the patients under red lamps.
If it works, then soon we're all gonna have red lamps in our homes and we're gonna be so much healthier than before!
P.S: If I'm correct and this idea ends up solving this pandemic, then please send some ETH to my wallet at 0x4aD7690c3cCe53De570738dDE90B8D01027a0f84 It would be funny to say I got a car for solving the COVID pandemic 🙂
Seasonality is an independent variable via temp and humidity, and one study neatly combined them in enthalpy, which you may remember from school! (How do I do hyperlinks?**)
You may find a bigger effect with selenium.
Vitamin D itself has no effect: it's levels in the blood of 25(OH)D3 and its metabolites that count.
The reason it doesn't work if vitamin D given after admission is that it takes 2 weeks for serum levels to rise, so that's way too late to do any good, so the Brazil study was pointless, and was anyway a preprint, and your "use in hospital" figure should maybe be lower than the other one. The Spanish study has the same problem and also didn't check serum levels at all (but did at least use calcifediol/25(OH)D3 ) and still found benefit! An even more metabolised form has been trialed in ICUs and that did indeed work better. Sorry can't find the trial now.
Many prevention trials don't test for D deficiency and have too few participants for significance. Also it takes about 2 years to do a population level prevention RCT, and it's really expensive and hard to get drug companies interested, so that's a tough ask. Prof Adrian Martineau got funding to do one.
Studies on vitamin D, selenium etc:
https://docs.google.com/document/d/1q5IH2hGjjdPi-vcs4zOBlArgFJ9iSDdZVoceevUPI9c/edit?fbclid=IwAR1nEL2wsIWIi6XXYGs-QWHX_-pgjgg88cU7zQRrfxtCtdXChTqXMn78fyA
Humidity studies:
https://docs.google.com/document/d/1olkOb6IMxE1zYBqvv5XAI2gREbg2O-0QUq0EfUr5_tM/
Review on seasonality of coronaviruses in general, table 2 very useful as divides studies up by country or continent, may give us warning of likely timing of next waves eg June in India, November in USA/UK (assuming no nasty or resistant new variant before then):
https://academic.oup.com/ofid/article/7/11/ofaa443/5929649
I've been going back and forth on these Vitamin D studies. However, unlike HCQ vitamin D has no toxic side effects in moderate doses (<50,000 IU). It's cheap to manufacture. It seems like a no-brainer to use it as a prophylactic. Just don't confuse it with a cure. I'm taking 2,000 IU/day, which is above the generally recommended dose of 600 IU/day, but well within the safe limits.
HCQ is an incredibly safe drug. It's at least as safe as children's Tylenol.
Vitamin D is needed for lots more than dealing with Covid and like a great many nutrient requirements, more and more past a min. level is a waste. Good ex is Vitamin C where no good data for taking lots of supplemental C, but overwhelming data for what happens if deficient. I did not see the Author of the post say what levels of D3 25 OhD were deemed too low nor did i see what targeted level of D supplementation range was tried for.
D absorption with age decreases and diet for many insufficient to reach appropriate minimal levels needed for overall health and even with supplementation one size not fit all as different people will absorb differently with some needing more D to reach the same level of Blood 25Ohd than others. Add age being an issue to absorbing from the sun and hence it likely that most will need some level of supplementation whether it helps with Covid or not
This is somewhat unrelated, but I've noticed that if my wife takes a vitamin D supplement for an extended period of time, or a larger dose, her anxiety increases. Her vitamin D tends to drop in January/February, but we have to be very careful about trying to increase it. Any ideas why, or if there is a way to raise vitamin D levels without raising anxiety?
Didn't see this in the comments, so FWIW https://jamanetwork.com/journals/jama/fullarticle/2776738
I'm absolutely convinced that vitamin D works. It's all about the way how you take it: you have to take it every day over long periods of time, BUT only in the short time span between your cardio exercise and your yoga exercise. Or if you have no time span between these two exercises, then you can take it right before your regular meditation practice. Studies also show that vit. D works better against covid if you unpack a clean face mask anytime you unpack a vitamin D pill. ;-)
Noob question from somebody who knows nothing about this:
If you think that sunlight modulates immune response to Coronavirus, why would you test vitamin D, rather than, um, sunlight?
It's pretty hard to control the amount of sunlight study participants would receive, e.g. due to weather.
Did you notice that the spanish and brazilian rcts used different forms of vitamin d?
If the supplementation studies used accepted recommended doses and levels of vitamin D, these might have been simply too low to produce a therapeutic effect, compared with sunlight exposure. This would account for the discrepancy between those studies and latitude/season effects. To quote a review of vitamin D medicine from 2007 (www.nejm.org/doi/full/10.1056/NEJMra070553):
--
Much evidence suggests that the recommended adequate intakes are actually inadequate and need to be increased to at least 800 IU of vitamin D3 per day. Unless a person eats oily fish frequently, it is very difficult to obtain that much vitamin D3 on a daily basis from dietary sources. Excessive exposure to sunlight, especially sunlight that causes sunburn, will increase the risk of skin cancer.125,126 Thus, sensible sun exposure (or ultraviolet B irradiation) and the use of supplements are needed to fulfill the body's vitamin D requirement.
--
Note also that the relationship between dietary vitamin D intake (including supplements) and serum levels is not linear but logarithmic. This makes it difficult to raise serum concentrations of vitamin D to useful levels with supplements. P.D. Mangan links to more publications here https://roguehealthandfitness.com/how-much-vitamin-d-do-we-need/.
PS: what sort of formatting does Substack support in comments? Not being able to blockquote is very annoying.
Has there been any research on whether sunlight-based vitamin D is good because of the increase of vitamin D vs. the reduction of cholesterol (which is what sunlight converts to vitamin D)? If it's the reduction of cholesterol, then vitamin D pills might not help.
You should watch the medcram deep dive into Vitamin D and covid - https://www.youtube.com/watch?v=ha2mLz-Xdpg
The author says,
"...if I were in the business of defending the Spanish study I might argue that it takes a few weeks for cholecalciferol to work, so giving it to someone who will already be dead or recovered by then is meaningless.
It would make me more comfortable if someone who did understand Vitamin D biochemistry would confirm this, but I'm not going to hang the whole argument on it."
Not wanting to hang the whole argument on the fact that it takes cholecalciferol 10 days to become available in the patient's body, and that it wasn't even adminstered until 11 days after onset of Covid, is utterly ridiculous. Those are the crucial flaws in the entire study, so it should not only be set aside, but thrown aside with great force. The author is nothing but a flak.
Excellent article.
I would just add that there is likely also an age factor - average population age decreasing as you approach the equator because of the old people in the US and Europe.
Hi,
I am reading this blog for the first time via the Naked Capitalism blog. As a chemist, I tend to focus on perspectives that include a biochemical view. Last fall, there were reports about AI studies that examined the broad array of Covid symptoms, and pointed to a bradykinin storm instead of a cytokine storm as a potential cause of the symptoms. Here is one magazine link that describes some of the biochemical cascades in the bradykinin system:
https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63
The article includes a list of potential treatments based on the bradykinin system, including the following quote:
“Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19”.
Also, I saw that one commenter here wrote about red light treatment. While I agree that low intensity laser light can be used to treat inflammation and respiratory problems, I think it’s possible that Vitamin D may be helping through a different mechanism. I and my friends and family have had good results with red light therapy for a range of indications. If you are curious, here is Dr. Fred Kahn’s blog post on light therapy and Covid:
https://fredkahnmd.com/2020/04/28/bioflex-laser-therapy-in-the-treatment-of-covid-19-infection/
He can’t promote the light therapy as a treatment for covid, but offers his opinion. (Spoiler alert: Dr. Kahn is a former vascular surgeon. I have been to him myself and he has very strong opinions about the medical system.) In a nutshell, when properly done using appropriate wavelengths, the light therapy triggers an increase in ATP formation, angiogenesis, and other knock effects including changes in the rate of DNA transcription in some cases.
> "Whenever you see a disease that's better in summer and worse in winter, Vitamin D is one of the possible culprits."
Um, then why haven't I been told to take vitamin D to prevent the flu during winter flu season? What I mean is, isn't there some other explanation you ought to have mentioned, like "people staying longer indoors makes viral spread easier" or "viruses can survive longer outside a host when temperatures are colder and there is less sunlight"?
Later in the article you mention reasons to be skeptical, but in general, I recommend against front-loading all evidence for X (and saving evidence against X for the bottom) unless readers are informed up front that you're structuring the article that way.
You should factor in the absolute huge mess of a country that Brazil is before you put any faith at all in a Brazilian study.
This is not xenophobia. I'm Brazilian. You have to either be here or have lived here for a while to get a grasp of what I'm talking about.
If the study showed no Vitamin D effects, odds are extremely high that the vitamin D used in the trial is simply counterfeit. Brazil has absolutely no QA in its genes. Bribery, on the other hand...
To get a feel of what I'm talking about: an entire major city, Rio de Janeiro, has been drinking brownish water that tastes like dirt for close to two years, and nothing is being done: https://www.thetimes.co.uk/article/smelly-brown-water-is-safe-rio-residents-told-k9hbhsdvp
Don't trust the Brazilian study. Don't trust any Brazilian study. Brazil is not a normal place by any measure.
This was good. The CDC and FDA's inability to do simple cost-benefit analysis was shocking and lead to tens if not hundreds of thousands of excess deaths when it came to masks. Sometimes, knowing something won't hurt is enough and the efficacy can be hazy. You need to look at the risk and reward and if something like wearing a mask or taking vitamin d is cheap, easy, and safe you just do it.