
Study of the effect of Vitamin D, Magnesium and Vitamin B12 on Covid-19 patients - ageitgey
https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v1
======
mikece
I wonder, when I see stories about studies about treating patients with basic
nutrients and vitamins, if a root-cause to consider is that our standard diets
are so deprived of essential vitamins and minerals that "treating" someone
with what they have been missing causes the body to simply function the way
it's supposed to. I haven't read the full study but if it takes into account
what someone's diet was prior to this treatment as well as their vitamin and
mineral levels (however that is measured) I think it would be more interesting
to see how such a vitamin boost affects those who are vitamin starved versus
those who were taking a "decent amount" of vitamins but where given a boost
because of an illness. It just seems the more we learn in this field the more
it shows us what we don't know.

~~~
Traubenfuchs
You are right and it is no secret:

\- 40% of US Americans are B12 deficient
[https://www.livekindly.co/b12-deficiency-genetic-
makeup/#:~:...](https://www.livekindly.co/b12-deficiency-genetic-
makeup/#:~:text=B12%20deficiency%20is%20often%20perceived,are%20deficient%20in%20this%20nutrient).

\- 42% are Vitamin D deficient:
[https://www.cantonmercy.org/healthchat/42-percent-of-
america...](https://www.cantonmercy.org/healthchat/42-percent-of-americans-
are-vitamin-d-
deficient/#:~:text=42%25%20Percent%20of%20Americans%20Are%20Vitamin%20D%20Deficient).

\- up to 50% are Magnesium deficient:
[https://www.sciencedaily.com/releases/2018/02/180226122548.h...](https://www.sciencedaily.com/releases/2018/02/180226122548.htm)

\- 10 - 20% of women are iron deficient:
[https://www.aafp.org/afp/2007/0301/p671.html#:~:text=The%20p...](https://www.aafp.org/afp/2007/0301/p671.html#:~:text=The%20prevalence%20of%20iron%20deficiency,a%20gastrointestinal%20cancer%20when%20evaluated).

My unscientific conclusion is that the vast majority of people world-wide
probably suffer from at least one and probably more significant nutrient
deficiency. With that we are wasting our "performance potential" and, less
capitalistic, our "well-being potential". The lack of any of just those
nutrients I looked up can cause anything from debilitating brain fog, over
physical and mental deterioration to numerous physical ailments...

Yet for most of them, taking them in excess causes the exact same problem. If
I was filthy rich I would get nutrient levels measured once a week. (-;

~~~
pbhjpbhj
Presumably it's relatively easy for a lab to run a panel of tests on me and
say "you're deficient in X, Y, Z; try eating more A B C; spend 30mins extra a
week outside; drink less alcohol".

How easy is it too get such tests (in UK), I'm surprised we don't seem to have
anything like this as part of our health system. I've had blood pressure and
height/weight taken a couple of times (I'm middle aged). But that's about all
wrt biological metrics, seems lackadaisical?

~~~
Traubenfuchs
Just measuring those 4 costs 83€ in a laboratory in Vienna. And there are more
measurements one should probably take! And you need to test them more than
once to see if supplementation works and you are not getting too much.

That's not cheap...

~~~
krageon
We're talking an expense of somewhere around 1k total over a period of a few
months. While not within everyone's reach (and if a single check is performed
say yearly after initial alteration of your diet also an ongoing expense),
it's far from an insurmountable cost. Especially considering this directly
impacts your day-to-day well-being.

~~~
danaris
If shouldered by the individual, an extra $1k over a few months, plus however
much it costs to keep re-testing, and the cost of supplements or better food
to correct the deficiency, is a staggeringly insurmountable cost for the
people who need it most—the poor.

As you say, this directly impacts day-to-day wellbeing. It's exactly the kind
of thing that should, if it's even moderately effective, be provided free of
charge for every human being.

~~~
krageon
I agree with you, but I must also admit it's not much of a concern if you live
in a country with solid health insurance.

------
barbegal
The methodology mentions nothing about randomization so its unclear if there
was any selection bias here.

If you look a table 2, the control group was on average 6 years older and had
more co-morbidities. This suggests that there was some selection bias and that
other undocumented factors could have greatly affected this experiment.

Doing multi-variate analysis with such a small sample size gives rise to huge
uncertainties. In all, this study is only very weak evidence.

~~~
arghzzz
However, taking 3 vitamins is almost entirely harmless.

~~~
RL_Quine
Many are toxic (vitamin D included) in unsuitable amounts, that’s probably too
strong of a statement.

~~~
cj
The study mentions 1,000 IU D3 dosage. A quick google turns up a rough figure
of 60,000 IU "daily for multiple months" can become toxic.

You're probably right, most things taken at 100x the normal dose for long
period of time are toxic. (Water included)

~~~
caseysoftware
The largest dosage of D3 I can find on Amazon is 5000 IU in a 240 capsule
bottle. To take 60000 IU, you'd have to take a dozen capsules daily, getting a
new bottle every 20 days, probably multiple times.

While possible, it does seem unlikely.

~~~
valarauko
I'm currently taking 60K IU D3. The dosage is 1 capsule a week, for 8 weeks,
and the capsules come 4 to a pack. This is followed by a maintenance dosage of
1 60k capsule once a month.

~~~
cj
Is this to treat a medical condition?

I'm curious why an acute high dose would be preferable over a lower dose taken
daily.

~~~
valarauko
No obvious medical condition, other than a vit D serum level of 15 ng/mL.
Depending on who you ask, that's a deficiency. I'm personally less convinced.

It's not quite an acute high dose. The body produces the equivalent of 10,000
IU per day in high sun exposure, so 60K per week tries to achieve that level.
I believe the high dosage is simply convenience. The 2K IU daily dose is
pretty common as well.

------
ageitgey
N=43 (17 given vitamins vs 26 not)

Highlights:

"Significantly fewer DMB patients than controls required initiation of oxygen
therapy subsequently throughout their hospitalization (17.6% vs 61.5%,
P=0.006)."

"DMB combination in older COVID-19 patients was associated with a significant
reduction in proportion of patients with clinical deterioration requiring
oxygen support and/or intensive care support. This study supports further
larger randomized control trials to ascertain the full benefit of DMB in
ameliorating COVID-19 severity."

So while this is too small of a study to do anything but call for bigger
studies, its additional evidence that vitamin deficiency may play a role in
COVID-19 severity. Since taking a basic multi-vitamin is good anyway, it seems
wise to do that.

~~~
Foivos
> Since taking a basic multi-vitamin is good anyway....

Could you elaborate on that? I thought that taking vitamin supplements without
a recommendation from a doctor is just a way to have very expensive piss. Most
of the things that get in, are removed from the body without being absorbed.

~~~
ses1984
If you're deficient in something, your body probably up-regulates absorption.

You can get higher quality vitamins with forms that are more easily absorbed,
for example chelated magnesium instead of magnesium oxide.

That said, I thought the evidence actually pointed to higher all cause
mortality in people who take vitamins.

~~~
partyboat1586
If you have a study that shows higher all cause mortality please link it.

My hypothesis would be that healthy people don't take vitamins because they
never saw the need, putting already sick people in the second category. I
doubt that taking vitamins can actually do much harm in low doses.

~~~
ses1984
I just Googled "vitamins lead to higher all cause mortality."

First result:
[https://www.sciencedaily.com/releases/2011/10/111010173019.h...](https://www.sciencedaily.com/releases/2011/10/111010173019.htm)

>After adjustment, use of multivitamins, vitamin B6, folic acid, iron,
magnesium, zinc and copper, were all associated with increased risk of death
in the study population.

The top three links showed association between beta carotene supplementation
and risk of death.

A little further down, a study showing "higher plasma concentrations of
vitamin B12 were associated with a 25% increased adjusted risk of all-cause
mortality per 1-SD increase"
[https://jamanetwork.com/journals/jamanetworkopen/fullarticle...](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758742)

>The use of multivitamins overall was associated with 2.4% increased absolute
risk for death (hazard ratio [HR], 1.06; 95% confidence interval, 1.02 -
1.10).

[https://www.medscape.org/viewarticle/751462#:~:text=The%20us...](https://www.medscape.org/viewarticle/751462#:~:text=The%20use%20of%20multivitamins%20overall,substantially%20between%201986%20and%202004).

The conclusion I personally draw from all this is: don't take a multi vitamin.
Don't take any vitamins unless I have a good reason like a tested deficiency.
If I think I could benefit from a supplement then I try to increase it in my
diet instead.

~~~
raverbashing
The risk of excessive iron is known and not new

If you read that link you'll see the findings for iron and calcium were
replicated. (Not to mention this article is basically referencing a different
article which is somewhere else, so we're missing the context)

The B12 issue, as the own article mentions, is not necessarily connected to a
dietary excess consumption

> Participants within the highest quartile of vitamin B12 plasma
> concentrations (>455.41 pg/mL) were more likely to be older and have higher
> BMI and blood pressure.

~~~
ses1984
>The risk of excessive iron is known and not new

OK so that's one mineral they called out from a long list that includes multi
vitamins, B6, and magnesium, very common recommendations. What about the rest?

Point taken about the B12 study.

What about
[https://www.medscape.org/viewarticle/751462#:~:text=The%20us...](https://www.medscape.org/viewarticle/751462#:~:text=The%20use%20of%20multivitamins%20overall,substantially%20between%201986%20and%202004)

------
rmelhem
just a personal note, I had many many respiratory tract problems -
tonsillitis, flu, cold, at least 3 times a year. I always thought it was
something natural, given the seasonality of these diseases, especially in
winter. but after a routine blood test, my doctor prescribed vitamin D because
mine was way below recommended. since 2017, when i started taking vitamin D
supplementation, only a mild flu is what I had in 3 years, so to me that
article is no surprise, of course in a personal experience level.

~~~
ageitgey
There were big studies in 2016/2017 that demonstrated the connection between
Vitamin D and lowering the incidence of colds and other respiratory
infections. This led to some governments (like the UK) recommending universal
daily supplements for all citizens during the winter months.

See
[https://www.sciencedaily.com/releases/2017/02/170216110002.h...](https://www.sciencedaily.com/releases/2017/02/170216110002.htm)

~~~
rmelhem
cool, that's great. will check it, thanks!

------
_0ffh
PSA: Before supplementing Vitamin D, do some research on calcification and
Vitamin K2.

Or you can trust a random person from the internet and supplement 40mcg K2 mk7
all-trans per every 1000IU of Vitamin D. That seems to be around the usual
amount used in studies [1].

I'm not sure if this is the appropriate factor for high Vitamin D dosages of
multiple tenths of thousands IU. Personally, I'd be wary of such dosages
anyway.

[1] [https://www.heise.de/tp/features/Schuetzt-Vitamin-D-vor-
Covi...](https://www.heise.de/tp/features/Schuetzt-Vitamin-D-vor-
Covid-19-4704193.html?seite=2)

~~~
neuronic
Why would you be wary? 15min of full body sunexposure will net you ~20,000 IU.
Supplementing 8-10,000 IU will not bring you into danger territory by a LONG
shot.

~~~
James_Henry
Getting vitamin D from the sun is different than from supplements.
[https://en.wikipedia.org/wiki/Hypervitaminosis_D#Long-
term_e...](https://en.wikipedia.org/wiki/Hypervitaminosis_D#Long-
term_effects_of_supplementary_oral_intake)

------
PudgePacket
> Patients were administered oral vitamin D3 1000 IU OD

I've seen multiple sources say that 1000 IU of vit D is usually insufficient
to boost levels, with suggestions of up to 5000 a day. My mothers doctor put
her up to 2000 a day because 1000 did nothing to her levels, which were
already low.

~~~
carlosfvp
How did the doctor know her vitamin levels were low? I once asked a doctor if
the vitamins in our body can be measured, and he said it can't be done, is not
something you can measure.

~~~
scarlac
It can be measured with a blood test:

> The most accurate way to measure how much vitamin D is in your body is the
> 25-hydroxy vitamin D blood test.

[https://www.webmd.com/diet/guide/vitamin-d-
deficiency](https://www.webmd.com/diet/guide/vitamin-d-deficiency)

------
kaycebasques
FYI this site provides helpful "top 10" lists of foods that naturally contain
a lot of vitamins and minerals (or are fortified). E.g. here's the Vitamin D
list: [https://www.myfooddata.com/articles/high-vitamin-D-
foods.php](https://www.myfooddata.com/articles/high-vitamin-D-foods.php)

P.S. I learned a fascinating factoid from that Vitamin D list. You might be
aware that standing out in the sun for 20 minutes is a good way to generate
Vitamin D. Supposedly the same process happens by leaving crimini mushrooms
out in the sun for 20 minutes before eating them.

------
Spooky23
Was this known early on about COVID?

Early on in the lockdown I noticed that these vitamins were among the kind of
weird items completely cleared out of stores.

People were very selective... initially all FHD laptops and Chromebooks were
gone, along with power strips, ibuprofen, hair clippers, etc.

~~~
nkozyra
Vitamin D has been thrown around a lot from the get-go, probably because of
its value against other forms of coronavirus including SARS and viral
infection in general. My layman's understanding is that supplementation hasn't
shown to be effective, meaning D deficiency may be a co-indicator.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189189/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189189/)
[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308600/#:~:tex...](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308600/#:~:text=Newer%20evidence%20suggests%20that%20it,influenza%20and%20respiratory%20tract%20infection).

~~~
snikeris
Perhaps Vitamin D status is just an indicator of adequate sunshine on the
skin. This would explain why people with low vitamin D are more susceptible,
yet supplementation with Vitamin D is ineffective.

~~~
nkozyra
I've seen two theories floated:

1\. Vitamin D as a side effect of sun exposure is not itself the important
indicator. Instead, some other biological response increases immune response
simultaneously. Hence, D supplementation is itself copying the wrong response.

2\. Vitamin D deficiency is caused by illness, hence it actually doesn't
affect mortality and the relationship is not casual.

~~~
snikeris
My money is on 1. Vitamin D deficiency is caused by lack of sunlight. I'm
skeptical of doctors telling me to avoid the sun and take a pill instead.

~~~
Spooky23
I eye-rolled at that guidance too, until a loved one was diagnosed out of the
blue with stage-2 melanoma. It's terrifying.

Don't screw around with sun protection. Despite what the internet says, people
who work outside get it too.

~~~
snikeris
I don't doubt that skin cancer happens. I doubt that vitamin D supplementation
is delivering all the benefits that sunshine does.

~~~
ryder9
and you're basing this on....

~~~
snikeris
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593895/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593895/)

------
michaelterryio
There is a ton of correlational evidence of low vitamin D and C19. And it
would be easy to ignore that as having cause and effect weaknesses.

But we also have dozens of RCTs showing that vitamin D supplementation
suppresses respiratory infections!

Folks always act like we just take this study in isolation. That’s not how it
should work. The totality of the evidence is quite strong for vitamin D versus
C19.

------
gshotwell
Here's a github with various vitamin D covid resources, to my knowledge this
is all of the relevant preprints and publications.

[https://github.com/GShotwell/vitamin_d_covid](https://github.com/GShotwell/vitamin_d_covid)

------
kpfleger
Every time a new D & C19 item comes up, 75+% of the comments are already
addressed in my review:
[http://agingbiotech.info/vitamindcovid19/](http://agingbiotech.info/vitamindcovid19/)
This new study is already incorporated there with a couple paragraphs of good
discussion in strengths, weaknesses, importance, etc. Broadly, it's consistent
with prior evidence but significant for being the 1st controlled trial (even
if not random, which would be unethical at this point and thus should be
impossible now). It's too bad the control group had so much more comorbidity.
Hopefully their multivariate model is trustable for taking baseline
differences in the 2 arms into account. The effect size is huge (OR=0.15).

Other common comment topics here (correlation vs causation, sun exposure,
burden of proof for correcting deficiency, etc.) are all covered in the review
already. If something important isn't covered, email me.

------
robocat
It looks like the preprint was published 6 weeks after the study finished (15
April 2020).

It is a real shame we can’t get our science moving faster (maybe slow so we
don’t break things?).

~~~
vmurthy
Perhaps it's the fact that breaking things in science leads to really bad long
term effects? Think what would happen if we rushed through a medicine for
cancer and it had an effect after a few hundred thousand patients have started
taking it.

------
jungletime
One more reason to go for a walk everyday outside for at least 60 minutes.

~~~
vmurthy
From the article linked above [0], it appears that 20 minutes is good enough.
My GP mentioned something similar to me a couple of weeks ago. The interesting
point is _when_ to go out for 20 mins walk and for where I stay
(Sydney,Australia), the timing seems to be this :

Noon during winter Before 10 AM or after 3 PM during summer

[0][https://www.myfooddata.com/articles/high-vitamin-D-
foods.php](https://www.myfooddata.com/articles/high-vitamin-D-foods.php)

