
Role of Vitamin D in the prevention of Coronavirus 2019 infection and mortality - pseudolus
https://www.researchsquare.com/article/rs-21211/v1
======
klmadfejno
I haven't dug into this, and, for the record, I do think vitamin D is likely
an important factor here. But I find the two charts to be very worrisome.

Their claim of a very high p value and significant effect is VERY strongly
influenced by a single outlier. It's not even close. On this unlabeled graph,
I think x axis is vitamin D levels and y axis is deaths per million. They've
got ~16 data points in the range of 0-10 deaths, one point at ~20, and one at
65. If you removed the 65 point the line would get a hell of a lot less
convincing.

~~~
zebrafish
This study is not exactly rigorous. There doesn't appear to be any controls
for age or health risks or anything else. Their methods are literally to take
worldometers data and vitamin D concentration data per country from the
European Calcified Tissue Society and plug those values into a t-test
calculator.

When HN was in a tizzy over p-values a year or so ago, this is what people
were concerned about. It's below .05, so what?

Not saying there is or isn't an affect on covid by vit D, but this isn't the
study to prove it.

~~~
namdnay
Wait a sec... they're taking their data at country level? How on earth is that
supposed to mean anything for anywhere apart from Belgium and the like?

------
interestica
It's so strange to me that these studies seem to generalize findings (eg
results by country) when one of the key biological factors for how we get
vitamin D is skin colour. And at its most basic relationship, the whiter ones'
skin, the better one is at generating Vitamin D from sunlight. Perhaps it
points to another way in which this disease could disproportionately affect
persons of colour?

If anyone has any literature that explores it more I'd love some direction.

~~~
kerkeslager
> It's so strange to me that these studies seem to generalize findings (eg
> results by country) when one of the key biological factors for how we get
> vitamin D is skin colour.

They bypass skin color by just measuring levels of Vitamin D directly. This
study doesn't care how you got the Vitamin D, it just cares how much you have.

There are tons of problems with this study, but failure to look at skin color
isn't one of them.

~~~
JumpCrisscross
> _They bypass skin color by just measuring levels of Vitamin D directly_

People with darker skin will, _ceteris paribus_ , have lower vitamin D levels.
And all else is not equal.

~~~
kerkeslager
True, but irrelevant.

Even if skin color is a predictor of vitamin D levels, this study doesn't need
to predict vitamin D levels because they used measured vitamin D levels.

~~~
JumpCrisscross
> _this study doesn 't need to predict vitamin D levels because they used
> measured vitamin D levels_

If darker-skinned people have, on average, lower vitamin D levels, then
measuring vitamin D levels proxies for skin color.

So if the underlying cause is _e.g._ access to healthcare or stress or
exposure to airborne particulates, and those correlate with skin color, those
will _also_ correlate with vitamin D levels.

One could thus find vitamin D levels relate strongly to outcomes. But
increasing vitamin D has zero effect on the outcome. Because it's not the
cause. (We see this a lot with poverty correlates in education.)

~~~
kerkeslager
> If darker-skinned people have, on average, lower vitamin D levels, then
> measuring vitamin D levels proxies for skin color.

"Proxies for" doesn't have a scientific meaning that I'm aware of, so I can't
be sure that I understand what you're saying.

If what you're saying is that vitamin D levels are correlated with skin color,
true, but irrelevant to this study.

If what you're saying is that the (poorly substantiated) correlation between
Covid19 and vitamin D can be used to claim a correlation between Covid19 and
skin color: no, because it's quite possible that vitamin D levels have no
effect on Covid19 in people with darker skin, but a huge effect on Covid19 in
people with light skin. You also have to keep in mind that your errors
multiply across different correlations: the error margin of correlating Covid
19 with skin color via this method is the error margin of correlating Covid19
with vitamin D _and_ the error margi of correlating vitamin D with skin color.

If what you're saying is that the (poorly substantiated) correlation between
Covid19 and vitamin D can be used to establish a _causal relation_ between
Covid 19 and skin color, no, because in addition to the previous problems,
you're ignoring that there at least 10 confounding factors besides skin color
which also have correlation with vitamin D levels:

1\. Latitude

2\. _How much_ time you spend outside

3\. _Which_ time you spend outside

4\. Clothing

5\. Sunscreen

6\. Liver function

7\. Diet

8\. Supplementation

9\. Cloud cover over time

10\. Season

If what you're saying is that _this study_ can be used to establish a causal
relation between Covid19 and skin color: in addition to all the previous
problems, this study can't even really be used to establish a correlation
between vitamin D and Covid19, so do we really need to pile on more logical
fallacies than are already present?

~~~
JumpCrisscross
> _" Proxies for" doesn't have a scientific meaning that I'm aware of_

It's a term, roughly, for intermediate variables [1]. Vitamin D levels are a
likely proxy for a host of race-variant socioeconomic factors.

[1]
[https://en.wikipedia.org/wiki/Proxy_(statistics)](https://en.wikipedia.org/wiki/Proxy_\(statistics\))

~~~
kerkeslager
By the definition on that page, vitamin D isn't a proxy for skin color.

> In statistics, a proxy or proxy variable is a variable that is not in itself
> directly relevant, but that serves in place of an unobservable or
> immeasurable variable. In order for a variable to be a good proxy, it must
> have a close correlation, not necessarily linear, with the variable of
> interest. This correlation might be either positive or negative.

> Proxy variable must relate to unobserved variable, must correlate with
> disturbance, and must not correlate with regressors once disturbance is
> controlled for.

Skin color isn't an unobservable or immeasurable variable, and it does
correlate with regressors once disturbance is controlled for.

------
dwheeler
This is a quick study, and there are lots of flaws in it.

That said, vitamin D deficiency is a real thing, and is especially common in
as you get older. Vitamin D supplements are also pretty cheap.

It's not unusual to have to make quick decisions with little information. This
study is enough to justify making sure that you have enough vitamin D, and
probably to take reasonable dosages of supplements. You have to be careful,
you can kill yourself with overdosages of vitamin D... it is a hormone and not
technically a vitamin.

Vitamin D supplemenation is an easy and cheap thing to do, not harmful as long
as you don't overdose, and there is some evidence here that could be helpful.
So it is reasonable for the moment to take Vitamin D supplements, at least
until we've had time to do more detailed studies.

~~~
ColanR
There have been other studies into the use of Vitamin D to prevent the flu,
where it has been shown to be very effective. I think there's a decent
connection between contracting the flu and contracting Covid?

------
Hitton
The study from which they took average vitamin D levels per country is rather
flimsy source to make reliable conclusions from. If you look it up, you'll see
that the data is gathered from multiple studies with different methodologies.

And it seems they didn't control for various factors which could influence
spread and mortality of the virus either.

~~~
hocuspocus
You don't even need to look this far.

Number of Covid cases and deaths reported across Europe mean wildly different
things. Especially in early April.

Even if I look at today's numbers in my country, there's been only 30k cases
officially. We know we could be off by a factor of 6, even though Switzerland
did quite a bit of testing:

[https://www.swissinfo.ch/eng/serological-test_antibody-
test-...](https://www.swissinfo.ch/eng/serological-test_antibody-test-results-
suggest-6x-more-covid-19-infections-in-geneva/45712418)

------
dna_polymerase
I know of at least one study in COVID-19 cases that suggested a correlation
between mortality and Vitamin D levels [0], tested in patients rather than
comparing national averages. That said, I'd like to see more tests in
confirmed cases and even more than just mortality correlation, I'd like to see
if it helps with long term lung damage.

[0]:
[https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561](https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561)

~~~
atourgates
That's really interesting, and has an even stronger conclusion:

"When controlling for age, sex, and comorbidity, Vitamin D status is strongly
associated with COVID-19 mortality outcome of cases."

~~~
elliekelly
The vitamin D deficiency is particularly interesting to me with respect to
pregnant women and smokers. There have been cases of pregnant women who were
unknowingly infected with Covid-19[1] and it seems there’s some evidence the
smokers are less likely to be admitted to the hospital with a severe case.

I would expect both groups to have higher than average vitamin D regardless of
their age, background, health issues. Pregnant women consistently take
prenatal vitamins for months and (most) smokers consistently get daily sun
exposure because they go outside to smoke. And from what little we know it
seems both groups fare better when they are infected.

[1][https://www.nejm.org/doi/full/10.1056/NEJMc2009316](https://www.nejm.org/doi/full/10.1056/NEJMc2009316)

------
CyanLite2
Classic case of causation versus correlation.

Is COVID-19 more severe because of a Vitamin D deficiency or does severe
COVID-19 cause vitamin D deficiency? Or perhaps people with Vitamin D
deficiencies also not get outside for enough sunlight or eat healthy enough,
and poor diet/nutrition results in more severe symptoms of COVID-19?

~~~
hirundo
It could be that Vitamin D levels are correlated with sun exposure, which
improves health via a hormesis response to oxidative stress on the blood in
the skin and eyes.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122858/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122858/)

~~~
SketchySeaBeast
> Vitamin D levels are severely low in the aging population especially in
> Spain, Italy and Switzerland. This is also the most vulnerable group of
> population for COVID-19.

It could also be that age is the important factor here and that Vitamin D
actually isn't relevant at all - as they said Vitamin D is low in all those
populations already.

~~~
vixen99
No, it is relevant because "a cause and effect relationship has been
established between the dietary intake of vitamin D and contribution to the
normal function of the immune system" & "The (EFSA) Panel considers that the
role of vitamin D in the functioning of the immune system applies to all ages,
including children."

European Food Safety Authority:
[https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa....](https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2015.4096)

Worth noting that in general and very roughly, at least 85% on average, of old
people survive infection with Covid-19 a group which includes those in their
90s.

~~~
SketchySeaBeast
So if we assume most old people are low in vitamin d, but also most old people
survive, does it tell us nothing?

------
KerryJones
For those that missed it, this came up recently in another place that links to
many more studies relating to it:
[http://agingbiotech.info/vitamindcovid19/](http://agingbiotech.info/vitamindcovid19/)

HN Link:
[https://news.ycombinator.com/item?id=23119949](https://news.ycombinator.com/item?id=23119949)

~~~
fattire
Posted this previously when the subject came up, but John Campbell, an nurse
and educator in Northern England who's been doing daily Youtube updates on
global Covid news since January I believe, has put out a few videos from time
to time related to vitamin D:

[https://www.youtube.com/watch?v=W5yVGmfivAk](https://www.youtube.com/watch?v=W5yVGmfivAk)
\- 2 months ago

[https://www.youtube.com/watch?v=GCSXNGc7pfs](https://www.youtube.com/watch?v=GCSXNGc7pfs)
\- 4 weeks ago

[https://www.youtube.com/watch?v=K-mHCn74E5o](https://www.youtube.com/watch?v=K-mHCn74E5o)
\- 1 week ago

[https://www.youtube.com/watch?v=Bga_qG30JyY](https://www.youtube.com/watch?v=Bga_qG30JyY)
\- 4 days ago

[https://www.youtube.com/watch?v=1fxw3nTZYlA](https://www.youtube.com/watch?v=1fxw3nTZYlA)
\- today

He offers published studies as evidence to suggest vitamin D deficiency may
play a partial role in explaining higher mortality rates among people with
darker skin (other important social disparities notwithstanding).

------
econcon
Isn't it that when someone is sick or their health is detriorating, the first
thing that happens is that their body stops producing Vitamin D? And since
they are not able to go out from that point it further reduces vitamin D?

~~~
zamfi
This is looking at population-wide measures of Vitamin D deficiency from
before COVID-19, so...maybe the argument you're making is that these
populations with lower Vitamin D were already sick and thus more prone to
COVID-19?

Because they're not measuring post-COVID-exposure Vitamin D levels.

~~~
hanniabu
> maybe the argument you're making is that these populations with lower
> Vitamin D were already sick and thus more prone to COVID-19?

No, he's making an observation unrelated to covid. At any time you're sick
your vitamin D production stops so you're deficient and then on top of that
you don't feel good enough to go outside so your further deprived of vitamin
D.

------
mikece
Most of us (computer people) are Vitamin D deficient and taking a supplement
to get us up to the healthier levels is a good thing, but focusing on just one
nutrient without taking all of nutrition into account is like focusing on
fixing only one nasty anti-pattern while letting dozens of other anti-patterns
continue unchecked.

~~~
new2628
How do you know it is a good thing? Maybe vit-D is just a marker for sunlight-
exposure, and you are gaming the marker with the supplements.

------
ltbarcly3
Vitamin D supplementation is relatively harmless at reasonable levels, so
advising it makes sense.

However, taking country wide averages is begging for confounding factors,
right? I bet you could find a higher correlation with lots of things than
Vitamin D, for example amount of per capita olive oil usage (Spain and Italy
are #2 and #3), time that dinner is eaten (Spain and Italy both tend towards
9pm, vs 6:30 for Germany), etc etc etc. It doesn't prove anything and there
isn't a proposed mechanism of action, so it's just correlation bingo at this
point.

------
Eric_WVGG
There was an article here just the other week suggesting that vitamin D could
very well be not a supplement to, but rather a marker of, good health.

If it is true that Vitamin D is a marker of good health, and people with high
levels of Vitamin D do well against the virus, this study suddenly turns out
to be a lot less interesting.

[https://news.ycombinator.com/item?id=23086211](https://news.ycombinator.com/item?id=23086211)

------
zapf
Urgh...

[https://en.wikipedia.org/wiki/Correlation_does_not_imply_cau...](https://en.wikipedia.org/wiki/Correlation_does_not_imply_causation)

or

[https://www.goodreads.com/book/show/195024.A_Mathematician_R...](https://www.goodreads.com/book/show/195024.A_Mathematician_Reads_the_Newspaper)

------
m463
I think people should be aware of sunlight and vitamin D.

Lots of old people never go out in the sun, and that could be a huge
contributing factor.

From wikipedia[1]

 _Adequate amounts of vitamin D can be produced with moderate sun exposure to
the face, arms and legs, averaging 5–30 minutes twice per week, or
approximately 25% of the time for minimal sunburn._

[1]
[https://en.wikipedia.org/wiki/Vitamin_D#Synthesis_in_the_ski...](https://en.wikipedia.org/wiki/Vitamin_D#Synthesis_in_the_skin)

~~~
cameronh90
For what it’s worth, I had an extremely severe vitamin D deficiency (8 nmol/L
- not a mistake!) measured in mid summer, despite going outside 5hrs a week on
my commute by bicycle. I’m pale and Scottish.

I now take a supplement every few days and my level is up to around 150. I
feel much better now.

Point is, if anyone’s reading this and thinking they can’t be deficient
because they are outside a lot, that is not a always the case.

------
yters
If you graph covid-19 death rate by latitude, all the warmer latitudes
(tropics and southern hemisphere) have significantly lower death rate.

I'd say vitamin D is a proxy for sunnier latitudes.

~~~
hocuspocus
Trivial counter-example: Iceland.

Very few countries can give you an accurate death rate at this point.

If you look at mortality among demographics that were thoroughly tested, you
can tell that the age distribution was definitely higher on the Diamond
Princess than on the French aircraft carrier. That's about it.

~~~
yters
That's the other interesting point about graphing by latitude: the very cold
countries such as Iceland also have remarkably low death rates.

It is the temperate, winter latitudes that have extremely high death rates.

Here's the graph, you can see for yourself. A very clear trend based on
latitude.

[https://github.com/yters/covid-19-latitude/blob/master/coron...](https://github.com/yters/covid-19-latitude/blob/master/coronavirus_hemisphere.png)

I'm not sure why this trend isn't discussed more in the popular media. Seems
quite significant, and is very easy to reproduce. Just scrape Google's
covid-19 stats and join with a geographic coordinate source. A journalist
could do this by hand with an Excel spreadsheet in about half an hour.

If this trend holds up, then as the Northern hemisphere hits summer, the death
rates should plummet. On the other hand, in the Southern hemisphere as winter
approaches the death rates will go up.

------
kylehotchkiss
Can these studies lead to a recommendation for how much vitamin D supplements
for adults to take to reduce likelihood of severe infection?

~~~
open-source-ux
In the UK, the NHS (National Health Service) recommends a daily vitamin D
supplement of 10 micrograms (400 IU). In a previous discussion on Hacker News
a few days ago, some posters mentioned this was a low and outdate dosage.

However, the NHS site also warns against taking more than 100 micrograms (4000
IU) of vitamin D. In the previously mentioned HN discussion, some posters
stated they take more than this (some have been told to by their doctors).

What the NHS website says:

 _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 of vitamin D a day as it could be
harmful._

[1]
[https://news.ycombinator.com/item?id=23119949](https://news.ycombinator.com/item?id=23119949)
[2] [https://www.nhs.uk/conditions/vitamins-and-
minerals/vitamin-...](https://www.nhs.uk/conditions/vitamins-and-
minerals/vitamin-d/)

~~~
bluecalm
The calcium build up of the reason they often add vitamin K2 to vitamin D
supplements. I am not qualified to say if it works at preventing the build up
but it's often the stated rationale.

------
cameldrv
It may be that people with low Vitamin D are low because of a combination of
their skin tone and the amount of sunlight they get. This causes them to also
be low on Nitric Oxide. You see the low Vitamin D as a marker, but it might
not be the true cause.

The shelter in place is causing people to get less sunlight, so until we know
more, I'd focus on getting more sun.

------
ginko
If that were the case you'd see significantly different infection and
mortality numbers for the Nordic countries than for the rest of Europe since
many people supplement vitamin D there. Norway, Denmark and Finland seem to be
doing relatively well, but Sweden's rates are pretty similar to France's.

------
stx
Adequate sleep is very important to immune function. I should sleep more at
night but its my most productive time. I started taking some vitamin D when
all this started because a doctor recommended it. Granted I think if I just go
outside into the sun a little bit I should have enough.

------
lultimouomo
Old people lack vitamin D. Old people get symptomatic Covid-19. Thus lack of
vitamin D causes exposes to Covid-19. NOT.

~~~
rustybelt
I'm guessing wrinkles and gray hair make covid worse, too. Hair dye and
facelifts for everyone!

~~~
tinus_hn
Lol so funny! Better dismiss this out of hand and keep doing nothing!

------
cpncrunch
Pretty poor study. Look at figure 1...

~~~
cpncrunch
For a proper review, see:

[https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-
th...](https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-the-evidence-
for-treatment-or-prevention-in-
covid-19/?fbclid=IwAR2IScy7tPofyBebQVGzL5g23KxlQbJN0XWBbZJIryJzWU8N_vXDqhRjzwo)

~~~
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, [...]’

------
ColanR
Prior discussions that seem similar enough to be relevant:

[https://news.ycombinator.com/item?id=23023703](https://news.ycombinator.com/item?id=23023703)

[https://news.ycombinator.com/item?id=22463713](https://news.ycombinator.com/item?id=22463713)

[https://news.ycombinator.com/item?id=23119949](https://news.ycombinator.com/item?id=23119949)

[https://news.ycombinator.com/item?id=22582387](https://news.ycombinator.com/item?id=22582387)

[https://news.ycombinator.com/item?id=23167802](https://news.ycombinator.com/item?id=23167802)

[https://news.ycombinator.com/item?id=22600685](https://news.ycombinator.com/item?id=22600685)

[https://news.ycombinator.com/item?id=23083619](https://news.ycombinator.com/item?id=23083619)

[https://news.ycombinator.com/item?id=23069001](https://news.ycombinator.com/item?id=23069001)

[https://news.ycombinator.com/item?id=22632542](https://news.ycombinator.com/item?id=22632542)

[https://news.ycombinator.com/item?id=23118830](https://news.ycombinator.com/item?id=23118830)

[https://news.ycombinator.com/item?id=22621191](https://news.ycombinator.com/item?id=22621191)

[https://news.ycombinator.com/item?id=23040868](https://news.ycombinator.com/item?id=23040868)

[https://news.ycombinator.com/item?id=23129529](https://news.ycombinator.com/item?id=23129529)

[https://news.ycombinator.com/item?id=23137546](https://news.ycombinator.com/item?id=23137546)

[https://news.ycombinator.com/item?id=23102020](https://news.ycombinator.com/item?id=23102020)

[https://news.ycombinator.com/item?id=22594740](https://news.ycombinator.com/item?id=22594740)

[https://news.ycombinator.com/item?id=22529035](https://news.ycombinator.com/item?id=22529035)

[https://news.ycombinator.com/item?id=20014940](https://news.ycombinator.com/item?id=20014940)

[https://news.ycombinator.com/item?id=23155437](https://news.ycombinator.com/item?id=23155437)

[https://news.ycombinator.com/item?id=23123222](https://news.ycombinator.com/item?id=23123222)

[https://news.ycombinator.com/item?id=22600709](https://news.ycombinator.com/item?id=22600709)

[https://news.ycombinator.com/item?id=20776603](https://news.ycombinator.com/item?id=20776603)

[https://news.ycombinator.com/item?id=20020134](https://news.ycombinator.com/item?id=20020134)

[https://news.ycombinator.com/item?id=22675466](https://news.ycombinator.com/item?id=22675466)

[https://news.ycombinator.com/item?id=22104904](https://news.ycombinator.com/item?id=22104904)

[https://news.ycombinator.com/item?id=23150839](https://news.ycombinator.com/item?id=23150839)

------
meiraleal
Healthy people have healthy levels of Vitamin D. Sick people that ingest VitD
will still get sick, vitamin D is a signal of healthiness, not something you
can ingest to get healthier. Lose weight, eat meat, sunbath.

~~~
alexbanks
I'd prob delete this.

------
briantakita
Which is why the beaches & parks should be open to the public...

Edit: The down votes only supports what I have suspected, many on HN are
authoritarian & should not be in positions of power. This is why many in the
public don't trust you or your "Science", which are mainly buggy software
models built on a tower of assumptions, enforced ( _ahem_ peer reviewed) by a
priesthood of like-minded fools.

People do support empiricism & the humility of knowing there are unknown
unknowns in any model

~~~
kerkeslager
There are some good reasons that beaches and parks should be open to the
public. There are also good reasons that beaches and parks should not be open
to the public.

This study is not one of those reasons. The conclusion of this study is not
one of those reasons.

~~~
briantakita
The study recommends supplementation, which could come from sunlight & being
outdoors, as sunlight increases vitamin d in the body. Getting out of the
house by going to public parks or the beach is one way of getting sunlight &
vitamin d...

~~~
kerkeslager
Nobody was confused about what you've clarified.

The study is not remotely conclusive. The methods are indirect, the controls
are weak, and the correlation model is misleading. Recommendations based on
this study can and should be ignored, because _this study doesn 't prove
anything_. The _only_ thing that should be done with this data, is using it to
get funding for a better-designed study. To the credit of the scientists
involved, I think that was probably their intent.

~~~
briantakita
Yet we cite buggy & non-deterministic computer models to justify mass social &
economic disruption. Funny these double standards...

I suppose, by your standards, that a healthy immune system is not yet "proven"
to have any effect on Covid-19. Perhaps we don't have enough data to make a
determination one way or another? Yet there's enough data to determine that we
need heavy-handed government policy to lock everything down. Strange...

------
vmception
okay and now explain Italy

~~~
kasperni
Vitamin D deficiency in Northern Italy is prevalent.

