[mindviews]

Here's a link to the paper: https://www.medrxiv.org/content/10.1101/2020.05.06.20092999v...

This is interesting data. I want to see Vitamin D status included in a large population study like this because I've been following two smaller studies covering about a thousand cases total that shows Vitamin D deficiency has a risk ratio of 10 to 20 (more even than being age 80+ in the above study). The studies:

[1] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561

[2] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3571484

Table 1 in each of those papers show Vitamin D status vs Outcomes. The correlation between Vitamin D status, where Normal is >30 ng/ml (or 75 nmol/L), and death rates is stark.

From [1] (which had n=780 cases) here is the punchline: "98.9% of Vitamin D deficient cases died while only 1.1% of them were active cases. 87.8% of Vitamin D insufficient cases died while only 12.2% of them were active cases. Only 4.1% of cases with normal Vitamin D levels died while 95.9% of them were active cases."

From [2] (which had n=212 cases) here is the punchline: "Of the 212 (100.0%) cases of Covid-2019, 49 (23.1%) were identified mild, 59 (27.8%) were ordinary, 56 (26.4%) were severe, and 48 (22.6%) were critical (Table 1). Mean serum 25(OH)D level was 23.8 ng/ml. Serum 25(OH)D level of cases with mild outcome was 31.2 ng/ml, 27.4 ng/ml for ordinary, 21.2 ng/ml for severe, and 17.1 ng/ml for critical."

Note: the classification for outcomes was "(1) mild – mild clinical features without pneumonia diagnosis, (2) ordinary – confirmed pneumonia in chest computer tomography with fever and other respiratory symptoms, (3) severe – hypoxia (at most 93% oxygen saturation) and respiratory distress or abnormal blood gas analysis results (PaCO2 >50 mm Hg or PaO2 < 0 mm Hg), and (4) critical – respiratory failure requiring intensive case monitoring."

I want to see a dozen more studies like [1] and [2] to see if this holds up to replication with larger populations.

[martingoodson]

In case you weren't aware, controlled trials have shown that vitamin d supplementation protects against respiratory disease [1]. This is evidence that the association you highlight is more than a spurious correlation.

It's likely to be causal.

[1] https://www.bmj.com/content/356/bmj.i6583

[lrpublic]

Updated NHS advice on vitamin D from [1]

“ Coronavirus update Consider taking 10 micrograms of vitamin D a day to keep your bones and muscles healthy.

This is because you may not be getting enough vitamin D from sunlight if you’re indoors most of the day.

There have been some news reports about vitamin D reducing the risk of coronavirus. However, there is no evidence that this is the case.”

[1] https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-...

[roenxi]

NHS may say 'no evidence' - but it seems likely what they mean is that nobody has done a vitamin D-coronavirus trial. So it isn't that there is no evidence but rather the evidence is not overwhelming.

"No evidence" makes it sound like there is actually no evidence. There is evidence - it just got linked in the two comments that make up the root of this thread.

[mistermann]

A good example of why trust the science (among other things) with no knowledge of epistemology is dangerous.

[DanBC]

See also this: https://www.sciencedirect.com/science/article/pii/S187140212...

> COVID-19 appears to disproportionately affects black and minority ethnic individuals. The underlying mechanism is unknown.

> One potential mediator could be their higher prevalence of apparent vitamin D deficiency.

> We explored whether blood 25 hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk.

> We found no evidence that (25(OH)D) explains susceptibility to COVID-19 infection, either overall or between ethnic groups.

[martingoodson]

It's worth noting that this study only looked at risk of infection, not the severity of infection. The grandparent comment was about severity/death.

[drak0n1c]

If it's true that Vitamin D is such a large factor in reducing the lethality of respiratory disease -- perhaps it's better to loosen lockdown rules to ensure the wider population can get more sun before they inevitably catch the virus.

It may explain why heavily indoors NYC had so many lethal cases, even as most infected were already keeping themselves indoors.

[simonh]

If the extra time out from loosening was all spent out in the sunshine, maybe it might just balance out the increase in cases, but there’s no way that’s what would happen. To make a significant difference requires an extra several hours a day out in sunshine. Better to just advise people to take supplements.

[elorant]

But what about Spain? A Mediterranean country with lots and lots of sunshine.

[AQuantized]

Sunnier countries can still have large vitamin D deficient populations. I read a study regarding the correlation between mental illness and vitamin D deficiency a few years ago, and Italian patients were still often very deficient. If people don't go out in the sun enough, or wear too much sun cream, it doesn't matter how sunny it is.

[whiddershins]

Also worth noting that Europe in general is really far north compared to the US. Spain is on the same latitude more or less as NYC.

[spiralx]

That's misleading because Europe is on the western edge of the Eurasian landmass, meaning it gets the benefit of warm air heated up over the ocean. By the time the air gets to the eastern edge of a landmass it's a lot colder, which is why London has a milder average temperature than NY and Vladivostok, despite being almost 10° further north than both.

[ejanus]

But it has slower transmission in Africa and low mortality.. This is getting hard to factor...

[joemazerino]

Vitamin D deficiency can still occur in sunny countries. To get the adequate amount of Sun from Vitamin D takes a day out in the sun entirely as opposed to basic supplementation.

[jansan]

It may also explain why every year Corona Virus related infections appear in November and end in May.[1]

Also, SARS 1 ended at the beginning of June 2002. There is clearly a correlation that needs to be looked into.[2]

[1] https://www.medscape.com/answers/302460-86798/what-are-the-s...

[2] https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndr...

[m463]

A friend of mine had cancer and they had him taking D3 immediately.

also I was out shopping recently and they seemed to sell many varieties of D3, but I didn't see any other D vitamins offered for sale. Is D deficiency really D3 deficiency? or have the other D vitamins sold out?

[leto_ii]

The way I understood it, D3 is the easiest one to absorb. Both D2 and D3 do the same thing, but their efficiency is different.

[vixen99]

https://vitamindwiki.com/ is a useful aggregate site for papers (peer-reviewed and others) on vitamin D. The latter is cholecalciferol (https://en.wikipedia.org/wiki/Cholecalciferol).

https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessiona... (excellent series for all vitamins)

Different manufacturers = varieties? It's the same stuff or should be.

[odrekf]

As a vegan, I learned that there's D2 (comes from plants) and D3 (comes from animals), and they are the same as far as I know. Not sure about using them for treatments.

[irishcoffee]

As a carnivore I’ve learned the same.

[oarsinsync]

As an omnivore I didn’t know either of these things before now, so I thank my learned extreme-dieted colleagues for sharing.

[Throwawayaerlei]

> A friend of mine had cancer and they had him taking D3 immediately.

The last thing in the world a cancer patient needs is well nourished cancer cells, most grow and reproduce quickly.

[Zach_the_Lizard]

There is some evidence that vitamin D deficiency is associated with prostate cancer: https://clincancerres.aacrjournals.org/content/20/9/2289.abs...

There are a number of other studies on this. From what little I've read, if the effect is real,it seems the it is relatively weak, but still worth doing.

[ashtonkem]

Two takeaways.

[2] is pretty scary. As a 30 year old I know that my chance of death is low, but I’d like to avoid a “severe” or “critical” case. There are a large number of unpleasant states between “fine” and “dead” that I’d like to not experience. A 50/50 chance of it being no big deal are worse odds than I’d prefer.

[1] is sending me back out onto the patio this weekend for tanning.

[Filligree]

Unless you spend literally hours outside every day, it's not likely to be enough.

Get some cod liver oil, drink a tablespoon every day. Does wonders.

[hanoz]

I heard British prof Steve Jones on the radio recently say that 15 minutes in the middle of the day was enough at this time of year.

[xkapastel]

Posts like this really need to specify what type of person they are talking about. 15 minutes is very clearly not enough for someone with dark skin.

[ip26]

The critical question remains though- is vitamin D the causal factor, or instead an indicator of something else?

[slg]

I agree, we need better evidence on all the vitamin D claims. Comparing rich white people in the suburbs who have lots of open land to get sun and use for exercise versus poorer darker skinned people in dense inner city apartments who spend most of their time inside introduces numerous confound factors that will be highly correlated with vitamin D.

[gridlockd]

> I agree, we need better evidence on all the vitamin D claims.

Not really. We should be blasting "get your Vitamin D supplements" from the rooftops, because maybe that's a significant factor in COVID-19 and it's safe and people should get them anyway. There's no downside.

If in a few years it then turns out that Vitamin D had nothing to do with it, it doesn't matter. If it turns out that Vitamin D really was a big factor, we'll be sorry for being hesitant with a safe and cheap intervention.

[slg]

You are right that vitamin D is relatively safe compared to other potential treatments that were bandied about like hydroxychloroquine. But while there are fewer health risks from taking it, there are still the same behavioral issues that were present with hydroxychloroquine. The first is causing a run on vitamin D that prevents other people from acquiring if for their proven treatments. However the main issue that I think we want to prevent is luring people into a false sense of security that causes them to decrease the proven preventive measures. We don't need large groups of people gathering on beaches because they think the sun will be a miracle cure and they don't have to worry about getting sick. So if you want to personally start taking it without changing your behavior, be my guest. But any advice to take it needs to be clear that the evidence it helps is still very suspect at this point.

[gridlockd]

> The first is causing a run on vitamin D that prevents other people from acquiring if for their proven treatments.

Vitamin D is an easily manufactured supplement, it's not medicine that some people absolutely have to take every day.

Also, we're heading into summer and the sun is still rising every day.

> However the main issue that I think we want to prevent is luring people into a false sense of security that causes them to decrease the proven preventive measures.

We've had the same discussion about masks, so I think that one's settled.

> We don't need large groups of people gathering on beaches because they think the sun will be a miracle cure and they don't have to worry about getting sick.

If you don't want people gathering on the beaches, prohibit it. Having said that, the risk of infection outdoors is generally considered to be quite low.

> So if you want to personally start taking it without changing your behavior, be my guest. But any advice to take it needs to be clear that the evidence it helps is still very suspect at this point.

The evidence that Vitamin D supplementation works is there and it has already been recommended for everyone with low serum levels, well before COVID-19.

The problem is that people often aren't even aware that their serum levels are low, so that is highly prevalent - especially in the elderly and people with darker skin.

[slg]

Hand sanitizer is also easy to manufacture and I haven't seen it in a local store for over 10 weeks. The ease to manufacture is just one of the steps to getting it on the shelves. Also getting vitamin D from the sun isn't an option for some people, especially those with darker skin.

The difference between masks and vitamin D is that one is proven to work and one might work. If vitamin D doesn't help as much as people here are claiming, there is a real downside if people are behaving as if it works. That applies to my arbitrary example of beach gatherings as well as other behavior the government has no hope of preventing.

Once again, this doesn't necessarily mean that vitamin D doesn't help. We just need better data. The early indication was that hydroxychloroquine helped too and we all know how that turned out.

[MrBuddyCasino]

This. People need to take convexity of risk into account. Taleb has elaborated on this over and over again, its really straightforward.

[z3t4]

Overdosing D can be dangerous as it takes a long time to leave your body.

[gridlockd]

We shouldn't be telling people to overdose on Vitamin D, obviously. I dread the day that Donald Trump mentions "Vitamin D", but then again even a massive overdose of Vitamin D isn't going to be life-threatening.

The generally safe amount is 4000 IU daily, which should get almost everybody to healthy levels. However, if your doctor finds that you have low levels, he may prescribe far higher amounts for a while.

[jansan]

Then do not overdose. Tell people to take 1000IE per day, not more. This will have no negative impact on the health or economy, but if we are lucky, it will help reduce the impact of COVID-19. Shutting down the economy is clearly dangerous, yet enough people do not seem to have a problem with that.

[z3t4]

Vitamin D pills is just a quick fix. Moderate exercise and fresh air would probably save more lives. Healthy vitamin levels are good, but its many little things which affects health.

[jansan]

Another critical question: Why hasn't this been properly researched, yet? There were indications before, that Vitamin D insufficiency increases risk of respiratory diseases.

[trekrich]

because big pharma wont get rich.... err richer from vitamin d.

[zo1]

Is that why we have all that "government" research money going to fund supposedly unbiased researchers at Universities?

[excalibur]

Sun exposure is far more likely to be the causal factor.

[ip26]

That, or perhaps a lack of sun exposure is linked to having preexisting conditions. Diabetics, COPD, asthmatics, etc as a group probably tend to spend less time outside.

[m463]

and/or a diet deficient in D (or whatever gets converted to D with sunlight exposure)

[gridlockd]

There's nothing particular that is required in the diet to synthesize Vitamin D3 from the sun.

Without sun exposure, you'd have to be eating several pounds of fatty fish every day to get to "healthy" levels from diet alone. You need a supplement.

Keep in mind, non-severe Vitamin D deficiency doesn't cause any significant evolutionary pressure, so migrating humans just rolled with it - to this day.

[0-_-0]

> I want to see Vitamin D status included in a large population study like this

Although vitamin D is not mentioned in this study, it does show that black people have a hazard ratio of about 2 compared to whites. In the UK black people would be more vitamin D deficient than white people.

Now that I think about it, isn't the potential for vitamin D deficiency the reason there are white people in the first place?

[wongarsu]

> Now that I think about it, isn't the potential for vitamin D deficiency the reason there are white people in the first place?

Yes. Pale skin has better vitamin D production in low light, while black skin avoids skin damage even in extreme sunlight. Skin color is just evolution finding the right trade-off for the local climate.

[lrpublic]

From NHS advice on vitamin D referenced in my previous comment

“Some people will not get enough vitamin D from sunlight because they have very little or no sunshine exposure.” .. “ If you have dark skin – for example you have an African, African-Caribbean or south Asian background – you may also not get enough vitamin D from sunlight.”

[Zach_the_Lizard]

Sickle cell disease is also more common in people of African origin, so that could be another reason for a higher hazard ratio.

[pbowyer]

The Centre for Evidence-Based Medicine at Oxford did a rapid review of the literature on Vitamin D:

https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-th...

Unsurprisingly there's no direct clinical evidence.

[gridlockd]

> Unsurprisingly there's no direct clinical evidence.

"We searched for trials and didn't find any"

Unsurprisingly, there haven't been any (completed) trials on this particular combination of novel disease and possible prevention/treatment yet.

I'm concerned that people conflate "no evidence for efficacy" with "it doesn't work" instead of "we don't know if it works". You always start out with "no evidence".

There are studies that put serum Vitamin D levels against COVID-19 outcomes and they show a highly significant correlation. That's not "causal evidence", but it should put you on alert, you shouldn't be waiting for 2021 for possible Vitamin-D trials to complete.

As the authors of that review are saying, you should be supplementing anyway, whether there is a causal relationship or not.

[jansan]

You would see tons of research going on if there was more money to be made with Vitamin D.

[0-_-0]

I don't see why, since vitamin D is not patentable. If you spend the money on research others can make money from it making you lose out. Same reason why herbs are not researched even though they've been used for medicinal purposes for thousands of years: you can't patent a plant.

[emmelaich]

Not so sure. Vitamin D is cheap to make.

[trekrich]

very true.

[DanBC]

> There are studies that put serum Vitamin D levels against COVID-19 outcomes and they show a highly significant correlation

Until they correct for socio-economic factors it's a potentially misleading bit of data.

[tinus_hn]

This review found nothing, so they found ‘no clinical evidence on vitamin D in COVID-19.’ No evidence for and no evidence against.

‘We found no trials of vitamin D in COVID-19 that have reported results.’

‘As our searches returned no relevant results, [...]’

But keep on posting the paper though.

[conistonwater]

I think that's a poor summary of the paper, here's the rest of the abstract:

"There is some evidence that daily vitamin D3 supplementation over weeks to months may prevent other acute respiratory infections, particularly in people with low or very low vitamin D status. This evidence has limitations, including heterogeneity in study populations, interventions, and definitions of respiratory infections that include upper and lower respiratory tract involvement."

"The current advice is that the whole population of the UK should take vitamin D supplements to prevent vitamin D deficiency. This advice applies irrespective of any possible link with respiratory infection."

[tinus_hn]

That doesn’t quite help the argument that there’s no connection, right?

[leto_ii]

The old adage applies here: absence of evidence is not evidence of absence.

[hhw]

However, evidence of absence is unlikely to be found as the vast majority of researchers tend not to bother publishing papers with negative results. So if an idea seems like it should have been researched already, but no research papers are to be found, it may very well be because the evidence of absence simply hasn't been shared.

[russfink]

I wonder how many papers give a negative result because p was found to be .049 or so. I'm recalling that thread here a while back debating whether the statistical critical value is too high.

[9wzYQbTYsAIc]

.049 is a positive result with a threshold of .05 - lower numbers mean smaller chance of no relationship.

[AshamedCaptain]

However, it is also the best predictor of "absence" the scientific method has to offer.

[leto_ii]

There are absences and then there are absences :D

Absence of evidence because you haven't tried much/ there's no data yet is not the meaningful kind.

[melvinroest]

"98.9% of Vitamin D deficient cases died while only 1.1% of them were active cases. 87.8% of Vitamin D insufficient cases died while only 12.2% of them were active cases. Only 4.1% of cases with normal Vitamin D levels died while 95.9% of them were active cases."

Wait, only 13.3% (1.1 + 12.2) of all the active cases in total were vitamin D insufficient or worse? I thought the majority of people had insufficient vitamin D.

This data doesn't fully make sense to me. How come that so few people with a vitamin D insufficiency were active cases? I get that most of them died. But I don't get that so few, less than 15 percent, got to become an active case.

Edit: ah, it's an Indonesian study. Nevermind, I wouldn't know the numbers from there.

[user4682]

That's not right. 87.8 + 12.2% = 100% of insufficient etc. Active case = not dead

[yosito]

Thank you, I was confused by the term "active cases".

[iddiid]

Since aging reduces vitamin D production in skin, we have that vitamin D level is correlated with age that is correlated with worse response to COVID-19.

Aging reduces vitamin D production in skin. There is a decrease in the concentration of 7-dehydrocholesterol in the epidermis in old compared with young individuals and a reduced response to UV light, resulting in a 50% decrease in the formation of previtamin D3

[russfink]

Is there any data showing which patients took D supplements (or daily multivitamin) vs having naturally normal/high levels? Medical people, does the answer matter?

[dassafina]

I am curious, what does it take to innovate in vitamin level testing space? Being able to know vitamin level in your body at any given day just like you can measure your heart rate. Not via mailing in blood sample, but something simpler. is it too far fetched to think that we can have something like a watch to be able to measure our vitamin levels regularly?

[myself248]

I'd picture something like a finger-prick blood sampler akin to a glucose meter.

Might not be something I'd do every day forever, but I could see doing daily samples for a week to get a feel for aboroption, then occasionally to check how my supplements and sun exposure are working.

If you could build a thing that can measure several different parameters depending on which test strips you load into it, I'd buy a pack of vitamin D strips, a pack of vitamin B, a pack of testosterone, and pack that looks for markers of inflammation. Heck yeah. My doctor would eat that data right up.

[dominotw]

I've been thinking about vitamin D all last week after listening to Dr. Rhona patrick on joe rogan podcast( dont' hate).

I haven't found and answer to this, if Vitamin D is such big factor then why aren't vitamin D deficient populations in the subcontinent ( india/pakistan ..) being hit hard.

[wolfi1]

I'm a little bit hesitant about vitamin deficiency. this sounds like orthomolecular medicine and I wouldn't trust that. I'm especially hesitant if that vitamin is fat-soluble because it can accumulate in your body fat and eventually be poisonous.