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Association between Vitamin D supplementation and Covid infection and mortality (nature.com)
86 points by qclibre22 12 days ago | hide | past | favorite | 61 comments

I'm fascinated by Vitamin D and it's effect on the immune system. Particularly the association between deficiency and increased risk of cancer and cardiovascular disease. We put together a tool that scrapes semantic scholar, summarizes and key word extracts and then maps keywords in relation to each other. We chose that topic as one of our sample dashboards.


One weird thing I noticed was that Vitamin D supplementation, while it improves outcomes in terms of cancer, does not seem to improve risk of cardiovascular disease. Maybe it's just that people who get sufficient Vitamin D from sunlight are more likely to get outdoors and exercise ;-) But it made me wonder if there's some additional benefit of sun exposure, some vitamin we haven't discovered yet.

It's not too weird if you think about it. Vitamin D boosts calcium serum levels in the blood. There are other factors, like adequate vitamin K, that prevent that calcium from precipitating on artery walls as plaque. So if someone's calcium metabolism is leading to calcification, vitamin D alone could accelerate that.

But incidentally, that's one of several reasons vitamin D is thought to protect from bad covid outcomes: in studies, people with higher blood calcium levels were also shown to do better. Other electrolytes were also positively correlated with better covid outcomes as well.

Aside from raising calcium serum levels vitamin D also directly modulates genes involved in the regulating angiotensin-renin system, including ACE-2.

The third thing, vitamin D is involved in circadian rhythm signaling. Good sleep is important for overall well-being! Especially if you're sick.

There are lots of papers and books about this stuff yet for some reason people still doubt that adequate vitamin D is important.

The real atrocity of it is that some people with more melanin in their skin store less vitamin D, since more melanin means their skin can make it quicker in the presence of sunlight. But in regions where there's less sunlight, these people aren't keeping around as much vitamin D. I'm convinced this is one reason for disparity in COVID outcomes and it really bothers me that the early studies and theory papers about the vitamin D / calcium / COVID connection got so ignored in the face of blatant racial disparities in COVID outcomes.

Vitamin D3 + K2 had huge potential to save lives, and people who knew what they were talking about advocated for this early on. I'm still frustrated that it took so long to catch on.

Vitamin D also requires magnesium to metabolize. Magnesium is very important for heart health so that might also contribute to the lack of positive effect of Vitamin D on heart disease

It's not that surprising when you consider the major effects are usually co-dependent on another variable (i.e. K2), or small over shorter time periods. I just take my 5k iu of d3 and what would be considered a megadose of k complex and keep my head down and my arteries relatively clear.

I realized I forgot to mention one more thing, vitamin D modulates certain relevant cytokine levels too, if I'm remembering right!

I don’t have the source, but on a podcast I listened to recently I recall the guest discussing that vitamin D is just one byproduct of sun exposure, and that the correlation between endogenous D levels and cancer/CV health is a function of the other related molecules produced due to sun exposure.

Nitric oxide being another big one.

This researcher does think sunlight exposure does more than manufacture vitamin D:


Vitamin D is incredible, from time to time my mind starts the day with negative thoughts and if I take a Vitamin D suplement they go away, I feel happier, act happier and have more energy to start my day.

For people who are just reading comments, it might be worth highlighting the magnitude of their findings, they suggest that a third of covid deaths could be avoided with a cheap and plentiful vitamin: "Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D3 and 25% lower with D2 (D3 HR = 0.67, [95% CI 0.59, 0.75]; D2 HR = 0.75, [95% CI 0.55, 1.04])."

This finding was very clear to me early in the pandemic when people said racism was "the real virus." It's clear that the heavy death toll on dark-skinned minorities probably had a physiological reason.

Ninja Nerds Medicine did an informative video* on the biochemistry & immunology of vitamin D in the context of SARS-CoV2 infection.

Vitamin D3 can be toxic at high doses. I live in Seattle and was at one point (years ago) tested and found deficient. My doc said many of his patients are. I was on 50k IU weekly for a few months to get back into range, and now I take 2k IU daily, with vitamin K2.

Anecdotally, I had something nasty with COVID-like symptoms in late 2019 and have had 1 minor cold since. I take other vitamin/mineral supplements, but passed on the experimental shots.

*COVID-19 and Vitamin D | Association Between Vitamin D Deficiency and COVID-19 https://www.youtube.com/watch?v=cT1CaTv5-e4

This is broadly consistent with what most other studies have found. See this link for an index of other studies.


The trouble with most of these studies is that they don't actually measure blood vitamin D levels. The amount of supplementation necessary to reach a target level can vary by an order of magnitude between individuals based on sun exposure, skin color, diet, genetics, and other pathologies. So ideally researchers should periodically run blood tests on the study patients, then titrate supplements to hit the study's target vitamin D blood level for each one. If course, this is more expensive.

Testing the actual intervention seems arguably more useful than testing blood concentrations.

You're missing the point. The amount of the intervention should vary. There is a huge variation in response to varying levels of variation. This is just common knowledge in medicine.

Sorry I meant varying levels of supplementation (too late to edit).

50k IUs per day. That seems like a lot. I have been taking 5k twice a day with zinc and quercetin since my last bout of illness. Maybe I should consider more.

Get blood tests and use those to determine how much you take, don't guesstimate or take large amounts like that without doing so, because you can overdose on it and it can do damage as a result.

Huh. I'm on 50k once a week and was under the impression that that was a lot.

My prescription is 50k 3x a week.

I maintain stable levels long term with 5K every other day, which roughly matches most dosage recommendations for people without acute deficiency. But as a sibling comment says, you should check your levels and adjust accordingly. 10K per day is already a lot if you don’t have an acute high deficiency.

That was probably the cumulative. But they were also monitoring the blood levels.

Absolutely should not do anything like 50k per day. I found that 5k could help but if I did that every day it felt like maybe too much.

> Absolutely should not do anything like 50k per day.

I had never heard of IU. It's a very weird unit that is different for different substances.[1] One IU of Vitamin D is 0.025µg, so 50K IU of Vitamin D is 0.00125g. Someone could probably get 50K IU of Vitamin D stuck in their eye by accident and not even realize it.

[1] https://en.wikipedia.org/wiki/International_unit

you should test your serum levels and go from there. 50k IUs a day is a lot if your blood level of d3 is already 50 nmol/l or higher, it's probably the right dose if your level is 19 nmol/l and you are being supervised by a doctor to recheck on regular intervals to back the dosage off once you get the serum level close to where you want it to be. Me personally any more than 5000 IUs a day I would be checking my levels at least once a year just to make sure I'm not slowly poisoning myself (I'm an obese guy who has tested low before that lives in the northern hemisphere and likes to use computers all day and not go outside much. If I was smaller/lived closer to equator/spent more time outside I would want to test at least yearly over 4000 IUs a day, but this is just my personal opinion none of this is medical advice).

yeah that's a crazy amount. the absolute max I've seen for "long term" varies from 1000 to 10000. I take 2000 (d3 in oil) myself as I don't get a lot of sun. That's as a result of having "pretty low" vit D after not having had a physical/labs for several years. Over that time I went from being outdoors a lot to being indoors and programming a lot :) . My numbers were up in the normal range (middling value) after doing that for a couple of months and going back for new blood work. I refused the 50k or so superdose they want to give me for a few goes if I recall correctly. Didn't seem like a good idea to me, and I wasn't feeling "bad" per se. I honestly didn't notice any difference other than my blood work came back normal. I continue to take 2k per day and my GP has no issue with that

I was taking 5k once a day but not even every day and tested almost above the high limit.

10k a day is a lot, one would be strongly advised to regularly check blood levels if you want to keep that up.

There seem to be studies with similar results for standalone zinc, vitamin B1 and B3.

e.g. zinc twice a day: https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

Also check out https://www.c19early.com - they have a subpage: https://c19early.org/dmeta.html

Lately I’m seeing information indicating that actual sunlight or perhaps near infrared light is more important than just vitamin D.

that wouldn't surprise me, maybe the body uses the sunlight for not yet documented uses other than making D. I was suffering from very low levels of vitamin d evidently but taking it didn't really change anything, and I felt just fine before and after. currently take 2k a day and my blood work stays "normal" range for the past few years. I still don't get much sunlight. I do a 10k walk but do it pretty early or pretty late as I live in Texas and 3/4 of the years it's just too hot and sweaty :)

Sunlight exposure also stimulates nitric oxide production. This is well documented. It acts as a vasodilator, lowering blood pressure.

There are likely other benefits as well.

John Campbell did a video today on a D2/D3 study. I think this is the same study.

The guy that promoted Ivermectin. He is a proven crank at this stage

Never promoted just showed data. Is that promotion. Here is data: https://www.ivmmeta.com

It's probably more of a neutral signal; there's a "anything that isn't a vaccine" crowd that latches on to any treatment proposed that isn't a vaccine (although now they're down on Paxlovid?).

Doesn't say whether it works or not, just whether or not it is a vaccine.

It's almost as if people, knowing options, want options. But, surely there must be only One True Way, and those pesky outliers who would rather select their choice of risk management product from a free market are wrong and must be injected with instructions to manufacture a lot of one just specific bilogical defense.

Somehow your ad hominem argument via a strawman fallacy projected on a medical professional who provided valid data when orthodoxy opposed this data on emotionally biased political grounds is not super compelling.

if this were true wouldn’t we see different levels of infection in southern latitudes bvs northern latitudes during winter? that’s what i’ve never understood about vitamin d and infection. covid or the flu hit florida just as bad as minnesota

"Panarese and Shahini ranked the 108 countries with at least 100 COVID-19 cases on 2 April 2020 by latitude, demonstrating visually that, overall, deaths per million were higher in the northern-most countries, whose citizens would be the most likely to be vitamin D deficient from the dark winter (198). Following up on Panarese and Shahini's work, Rhodes et al., compared the 120 countries with more than 150 COVID-19 cases by 15 April 2020, finding that COVID-19 mortality rates were significantly correlated with latitude (r = 0.53, p < 0.0001) (26). Rhodes et al., used a simple scatter-graph to illustrate that the COVID-19 mortality rates per million population were dramatically lower in countries with capitals south of 35°N, where sunshine in the time immediately preceding the pandemic made maintaining vitamin D levels possible (26)." https://www.frontiersin.org/articles/10.3389/fpubh.2020.0051...

The "folk wisdom" that colds cause the Common Cold has the correlation correct, but not the causation.

During winter people get less Vitamin D and stay indoors in close proximity.

The low temperatures do not make you sick. The secondary effects of the season-that-is-cold does.

Temperature and humidity can have a marked effect on the stability of enveloped viruses themselves. e.g. coronaviruses & RSV, which comprise a subset of the viruses responsible for common colds. Another common cold virus, Rhinoviruses, are non-enveloped.

Which is true, but studies have shown that it is the increased time spent in the heated indoors that causes disease, not the time spent in the cold outdoors.

Sure but there are a lot of people that barely go outside these days. Suppose they are wearing a hat and long sleeves and walk 60 seconds to their car.

Even if you have nice big windows the UV doesn't pass through so inside regardless of where you are does next to nothing for you.

Windows block most of the UV light that causes Vit D synthesis.

There've been a lot of articles in the mainstream press lately warning against supplementation. I take this as advice to supplement, personally.


what you conveniently leave out, of course, is all the other quack science that did, in fact, turn out to be harmful. this wasn’t "don’t tell them about the vitamin d!", this was "don’t make unsubstantiated claims". the claim is substantiated now.

In 2020 virtually everything was someone’s secret solution to covid that the man was suppressing.

There was enough pre-existing theory to suggest that vitamin D could be beneficial, and enough preliminary data suggesting that it was beneficial, that several government bodies and public health officials did strongly recommend mass vitamin D supplementation as a low risk intervention. Aside from that, some places already supplement milk with vitamin D because the effects of insufficiency have been known for many decades.

The language of uninformed skepticism really bothers me. Using terms like "quack science" and "crank". What does that do? It just heaps stigma into an already complex and messy conversation that really needs nuance, thoughtfulness and care.

For what? To distinguish yourself as smart? To me that kind of language just comes off as reductionist.

Indeed, there was a great deal of evidence to support usage of vitamin D from the get-go, including the actually-settled science that lower levels of vitamin D are associated with worse outcomes in tons of other respiratory illnesses.

Despite this fact, it was "The Science" that vitamin D was not to he taken and "COVID Disinformation" to suggest otherwise.

"basically a crime"? Huh?

just eat good food. plan your meals to have daily intake filled. overdosing vit D can be really really bad.

Some people, especially those with darker skin living outside the tropics during winter months, find it impossible to maintain the recommended blood levels just by eating good food. While overdosing can be dangerous, that would take a pretty extreme amount of supplementation for most people.

If you want to go the "natural" route then you need to have significant direct sunlight exposure.

Doesn't have to mean tanning for half an hour. But more than walking to your car.

Greatly depends on your longitude and time of year as well. I still supplement vitamin d, but get regular blood work.

That's right. Just being out in the sun for several hours per day will do wonders for you.

Naturally, you'll want to start engaging in activities that increase your heart rate to the level necessary to remain healthy over the many decades of your life.

My understanding is that _several_ hours per day can mean a very significant chance of skin cancer down the road especially for lighter skinned people in subtropical or tropical regions.

Fair point. I'm an extremely light skinned person. That's the main reason I don't live outside of the climate zone in which my direct ancestors lived.

weaingr suncream is pretty much a given that should be pushed way more. and I am not talking about tropical countries only

Active ingredients in most sunscreens are carcinogenic upon exposure to sunlight. Careful about studies which say the sun causes cancer in light-skinned people without accounting for their increased use of (non-mineral-based) sunscreen. Consider which industry profits from and funds such studies.

I was tested recently and my doctor said I had dangerously low Vitamin D. It was so low they were going to proscribe high dose supplements. I eat very healthy, mostly salads and a bit of dairy and fish here and there. I bet a lot of people didn't get enough sunlight during covid. Also people with darker skin need more sun exposure to get enough. (Among Black people in snowy climates something like 70% of the population have a Vitamin D deficiency)

If you take over-the counter supplements and follow the instructions you're unlikely to overdose.

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