
Vitamin D, part 3 – The Evidence - usefulcat
https://www.devaboone.com/post/vitamin-d-part-3-the-evidence?postId=5f4e8bf673d853002ded6cd3
======
staticassertion
It seems interesting that Vitamin D may be so much more prone to false
correlations due to the fact that it's tied to going out in the sun, and going
out in the sun is what healthy people do. Since so many illnesses and
conditions, from psychological to physical, can keep you indoors, one could
conclude that vitamin D is really a miracle pill.

I take 1k iu a day, since I barely go outside anymore, but I'd probably cut
that in half if life were normal again. I think of _most_ vitamins as a "cover
my bases in cases I eat like shit today", not as a "this is going to keep me
from getting cancer".

I also found the commentary on metanalyses interesting - they're touted as
being very high quality, but of course there's always the garbage in garbage
out.

~~~
bad_user
RCTs are high quality, because they are done in a controlled setting, testing
against a control group, testing the null hypothesis. RCTs are able to show
causality. The problem with RCTs is that they are very expensive, since it
involves keeping people in a clinic, so usually RCTs are short term and can
only afford to look at surrogate markers.

However most often than not, surrogate markers are enough. Also RCTs tend to
coroborate the findings from observational studies in about 70% of the cases.
Also for really hot topics, like diabetes management, we do have year-long
RCTs too.

And drawing conclusions from systematic reviews and meta analyses of RCTs,
well, that's basically the best we can do.

For assessing the strength of available evidence, I recommend reading the
following: [https://examine.news/how-to-read-a-
study](https://examine.news/how-to-read-a-study)

~~~
waterhouse
> The problem with RCTs is that they are very expensive, since it involves
> keeping people in a clinic

This may be a noob question, but why? For something like a vitamin supplement,
can't you just give the study participants a box of their 50 possibly-placebo
pills and require them to take one per day? If you're worried about
compliance, can't you require them to write down the time each day when they
take the pill—or even have the pills in a one-pill-per-box calendar
arrangement and require them to take a photo with their phone each day?
(Doesn't stop malicious noncompliance, but it should cover
laziness/forgetting.)

~~~
gojomo
They're not all done in a completely-controlled clinic - indeed the 25,000
person study highlighted here, with followup after around 5 years, of course
had the subjects going about their daily lives except during original
enrollment & occasional check-ins.

But when outcomes are finer-grained than "did the subject die or get diagnosed
with a major new disease", or short-term, or need high compliance & regular
monitoring, RCTs can become a lot more intense & expensive.

------
TacticalCoder
What about the study in Spain from a few days ago (I'm in Spain atm and it's
kinda big news over here), at the Reina Sofia University Hospital in Córdoba,
where they just announced the results of the randomized blind controlled trial
and the results are incredible: 1 person out of 50 who got huge doses of
vitamin D for a few days after arriving at the hospital with Covid-19 symptoms
ended up in the ICU, where 13 out of 26 who didn't get any vitamin D ended up
in the ICU? It's "only" 76 people but it's 2% vs 50%.

It was a blind study (AFAICT): patients had no idea whether they got vit D or
not and patients got randomly selected.

Here's a doctor's analysis of that study:

[https://youtu.be/V8Ks9fUh2k8](https://youtu.be/V8Ks9fUh2k8)

~~~
devaboone
There is a lot of excitement about this study, but the details in it matter.
It was randomized - but when you look at the two groups (treatment vs.
control), they had some key differences. The control group (who didn't receive
Vitamin D) had more men (69% vs 54%), more people with hypertension (57% vs
24%) and diabetes (19% vs 6%). So the groups were not the same. If you just
compare the numbers of those who went into the ICU vs. not, then the results
look amazing. But once you correct for hypertension and diabetes, it was not
so impressive - it was not statistically significant in the study. (It is in
the study but most people breeze right over that.)

~~~
ellyagg
Interesting! Can you quote the part of the study where they say the results
are not statistically signifcant when you control for diabetes and
hypertension?

~~~
devaboone
Here is what the article states: "Therefore, a multivariate logistic
regression analysis was performed to adjust the model by possible confounding
variables such as hypertension and type 2 diabetes mellitus for the
probability of the admission to the Intensive Care Unit in patients with
Calcifediol treatment vs Without Calcifediol treatment (odds ratio: 0.03
(95%CI: 0.003-0.25) (Table 3). The dependent variable considered was the need
to be treated or not in ICU (dichotomous variable).) CI:-0.30 - 0.03 p:0.08."
The statement is worded in a confusing way, but that is a non-significant p
value. Of course we should not put too much into "statistical significance"
but it is interesting to note.

~~~
harterrt
Unless I'm reading your comment wrong, this p-value (0.03) _is_ actually
significant for a 95% confidence test.

~~~
Jeriko
0.03 is the odds ratio (a measure of effect size, an odds ratio of 1 would
mean the treatment and control arms had the same rate of ICU admittance). The
p value is 0.08 from here "CI:-0.30 - 0.03 p:0.08." which captures the
likelihood the treatment had an effect.

That said, just looking at p values and applying a cutoff at 0.05 is pretty
bad practice that is getting a lot of heat thanks to the replication crisis
(does it make sense to behave as though p=0.08 is not true and something at
p=0.049 is true? almost certainly not). If you get a value in this range and a
huge effect size then it's a really good idea to repeat the experiment with
way more data. It's also a common stats error to act as though p>0.05 is the
same as knowing something DOES NOT work, all you can say is this specific
study wasn't able to show that it does work with 95% confidence.

------
m12k
So Vitamin D deficiency is linked to cancer, heart disease, respiratory
infection, stroke, diabetes, and death. But taking it as a supplement helps
with none of the above. What is a reasonable hypothesis then? That having an
active lifestyle that brings you outside in the sun both causes your Vitamin D
to go up, and is correlated with better physical health in general?

~~~
scott_s
I would frame it in the opposite direction: having a serious illness is
correlated with low levels of Vitamin D. People with a serious illness may
stay inside more, and go outside less. It's possible that "low levels" of
Vitamin D are still within the healthy range, and they merely are an
indication of how much time the person has spent outside during the day.

In other words, it's possible that Vitamin D is pure symptom. It's not even
necessarily the case that going outside is _healthy_ , but that healthy people
tend to go outside more.

~~~
black_puppydog
> It's not even necessarily the case that going outside is healthy, but that
> healthy people tend to go outside more.

This is a departure from the discussion of _supplementing_ vitamin D though,
isn't it?

I guess the treatment "go out and do sports" is a very different one compared
to "X amount of vitamin D per day as a supplement" and the former may indeed
be _healthy_ , while the latter may not be, even though they both result in
higher levels of vitamin D.

~~~
scott_s
> This is a departure from the discussion of supplementing vitamin D though,
> isn't it?

I don't think so, no. If my hypothesis is correct, the problem is not that
they _didn 't_ go outside and play sports. The problem is that they _are sick_
, and sick people don't go outside as much.

Forget Vitamin D for a moment. Imagine that every time you were outside for an
hour, the Outside Fairy granted you one Outside Token. Over the course of a
month, it's reasonable to assume that healthy people would have more Outside
Tokens than sick people. But these Outside Tokens obviously would have no
causal effect on whether or not people are sick. Giving sick people Outside
Tokens would obviously not help them - their problem is that they are sick.
They have less Outside Tokens because being sick makes it more difficult to be
outside for an hour.

In other words, the arrow of causation is _being sick_ -> _less Outside
Tokens_ , and _not being sick_ -> _more Outside Tokens_. If that's the case,
then Outside Tokens are irrelevant to treating the sick people. If, say, they
have cancer, you should ignore the Outside Tokens and treat the cancer with
all of the standard means we have of treating cancer.

They hypothesis is that "low levels of Vitamin D" are just those Outside
Tokens.

(Yes, when Vitamin D levels are low enough, that can cause other kinds of
health problems. But this hypothesis is that what we're measuring as "low" is
still within the healthy range. How do we know when it's not in the healthy
range? When it tends to cause the kinds of problems we are more confident are
directly linked to low levels of Vitamin D.)

~~~
dnh44
That’s very true, but Outside Tokens are really cheap and are low risk so
encouraging people to buy them seems like a reasonable hedge to make until the
hypothesis can be proven.

~~~
cortic
So long as it doesn't supplant other real treatments, which it inevitably will
within the framework of a recommendation to potentially very ill/desperate
people.

------
dcx
This seems like it might be a little selective.

What about these [1] [2] randomised controlled trials that show vitamin D
supplementation has an effect on IBS symptoms?

Or this [3] double-blinded trial showing supplementation improved sleep
quality in people with sleep disorders?

Or this [4] one showing improvements in depressive symptoms in overweight and
obese subjects? The study cited in TFA is large but only uses participants
aged 50 and above, with a relatively low dose of vitamin D.

Also, is it just me or is the line of argument used a little bit weak? You
could use the same kind of argument to dismiss the need for dietary vitamin C,
as follows: (a) vitamin C deficiency is associated with a bunch of other
health conditions (as it's a marker of poor nutrition or socioeconomic
status), so (b) let's look at the effects of supplementing vitamin C, which
(c) naturally finds that supplementation does nothing for said conditions, and
therefore (d) conclude that it is a pretty useless vitamin, while placing
minimal focus on the things that it actually does fix, such as scurvy?

I am not an academic, so perhaps I am missing some context though.

[1]
[https://pubmed.ncbi.nlm.nih.gov/27154424/](https://pubmed.ncbi.nlm.nih.gov/27154424/)

[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900470/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900470/)

[3]
[https://tumj.tums.ac.ir/article-1-8272-en.html](https://tumj.tums.ac.ir/article-1-8272-en.html)

[4]
[https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796...](https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2008.02008.x)

~~~
ljhsiung
Did you read the article?

> It is an essential hormone, definitely, but not a magical pill that will
> ward off disease. There are conditions that benefit from Vitamin D
> supplementation - for hypoparathyroidism, a condition that can cause
> dangerously low calcium levels, Vitamin D is lifesaving. For otherwise
> healthy adults, the benefit is less clear.

Takeaways: it's not clear what preventative benefits it has.

Even to use your vitamin C example, it's also widely touted to take vitamin C
for general well being, such as helping colds. But its preventative benefits
aren't clear [1]. Nobody has _ever_ said vitamin C is useless, but it's just
not a panacea (much like the article claims about vitamin D).

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160577/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160577/)

~~~
dcx
Yes. See response to author's comment below.

On vitamin C - I stated _dietary_ vitamin C to make it clear I was not
referring to supplemental vitamin C. I was hoping to avoid this exact rabbit
hole; that example was just to highlight an issue with the argumentation.

------
0-_-0
Vitamin D study showing a positive effect on treating Covid-19:

[https://news.ycombinator.com/item?id=24366006](https://news.ycombinator.com/item?id=24366006)

------
gambler
This picture in the article is misleading:

[https://static.wixstatic.com/media/3e0600_a25ba8bbf26b47a096...](https://static.wixstatic.com/media/3e0600_a25ba8bbf26b47a096d2dc2ee7e41fcd~mv2.png/v1/fill/w_644,h_469,al_c,q_90,usm_0.66_1.00_0.01/3e0600_a25ba8bbf26b47a096d2dc2ee7e41fcd~mv2.webp)

At the very leat, vitamin D _does_ seem to prevent respiratory infections. The
article even admits as much later on. There are several RCTs that verify this.
So why put a red cross next to "prevention of respiratory infections"?

Also, worth reading:

"Why randomized controlled trials of calcium and vitamin D sometimes fail"

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427206/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427206/)

~~~
devaboone
The chart is only regarding RCTs. In the best individual trials that we have,
it does not show a benefit for respiratory infections. But we do see some
suggestion of benefit in meta-analyses. In general, if the meta-analysis shows
something that is not seen in RCTs, then we probably need more evidence. But
it does seem to be a real effect.

------
mixmastamyk
May be an unpopular take, but this one felt a bit too academic to me. It also,
perhaps inadvertently, argues against several strawmen too.

We've long known D is an essential component of bone-health and the immune
system, since it was noticed a century ago that tuberculosis patients that
went outside in the sun had better outcomes. Known to prevents rickets too.

The fact that some have tried to apply it to heart disease or asthma, or
random unrelated ailments and failed is immaterial, no?

The fact that the benefit of supplementation is strongest for those with the
weakest levels is not particularly surprising either.

We also know that the body can make adjustments when nutrients are low in the
short term, and that can mitigate some issues and pose unintuitive outcomes in
such a time frame.

Bottom line, do we want to face Covid/Flu with an immune system at full
strength, or one with one arm tied behind its back due to a deficiency?

Finally, given that a large majority of folks are D-deficient, and few can or
will overdose, this push back (on HN and this piece) to warn folks that it is
useless/dangerous (on the whole) does more harm than those recommending it, in
my opinion.

Moderation continues to be the best path, and a number of studies linked here
support benefits of supplementation for bone-health and immune system, but
those things only. Don't overthink it.

------
dorenarode
I read Dr. Boone's article and looked over each intervention in the study's
she listed. I noticed that many researchers were dosing once a month (one was
only once a year!) at levels I would not consider therapeutic. Yes, at non-
therapeutic levels, I would expect vitamin D to not show much difference from
Placebo. I am not a vitamin D expert, but am wondering why she selected to
discuss research that didn't even match current vitamin D recommnedations. Her
favorite research was VITAL which I was thrilled to learn was daily for 5
years. Unfortunately, it was at a level (2000IUs) that could leave many people
at subnormal levels of vitamin D. 1000 IU will bring up blood levels 5 ng/mL.
30 ng/Ml is considered okay. Many people believe that levels between 60-100
ng/mL is better. I have a genetic defect that keeps me below 30ng/ml
regardless of sun exposure. I supplement at 15000 IU per day. Which brings my
levels up around 70-90ng/mL

------
ComputerGuru
I don’t want to be the contrarian that persists in the face of scientific
evidences, but I will point out that none of the RCTs listed combined Vitamin
D with supplementation of Vitamin K, which several studies suggest plays a
synergistic role when it comes to the health benefits. This OSU link covers a
number of such studies:
[https://lpi.oregonstate.edu/mic/vitamins/vitamin-K](https://lpi.oregonstate.edu/mic/vitamins/vitamin-K)

------
amai
It's the magnesium, stupid!

Dai (2018): Magnesium status and supplementation influence vitamin D status
and metabolism: results from a randomized trial
[https://pubmed.ncbi.nlm.nih.gov/30541089/](https://pubmed.ncbi.nlm.nih.gov/30541089/)
"Our findings suggest that optimal magnesium status may be important for
optimizing 25(OH)D status. "

Coincidence?

"Vitamin D is currently the only Essential Vitamin or Mineral which appears to
have deficiency rates at a similar level to Magnesium"

[https://examine.com/supplements/magnesium/research/#nutrient...](https://examine.com/supplements/magnesium/research/#nutrient-
nutrient-interactions\\_vitamin-d)

------
LinuxBender
Perhaps I missed it, but I did not see the study including K2 MK-7 and
magnesium with D3. The 3 work together and can not support all of the
metabolic functions on their own in a silo. There are also enzymes and co-
enzymes that are part of the picture and I did not see any mention of them. Is
there a more detailed version of the study? Again, could be me, I may have
overlooked a link.

~~~
grok22
The doc said "don't think of vit-d as something magical" and you are saying
"what if it was with k2 and magnesium; that might be more potent and magical"
\-- I think the doctor's general conclusion still holds that it is not proven
that vitamin-d helps with certain diseases. And the fact that doing RCTs is
time-consuming and expensive still holds. And without these RCTs, at present,
we can't conclusively tell if the combination you suggest will help for those
diseases that she mentioned.

------
api
The most obvious evidence to me has always been that Europeans are not black.
A change like the loss of melanin requires selective pressure, which in this
case was likely furnished by less vitamin D as we migrated away from the
equator. The pressure must have been significant since being white carries a
big downside: higher vulnerability to sunburn and skin cancer. When I lived in
Cali I always envied my darker skinned friends who did not have to smear goo
on themselves at the beach.

I gotta say though... the world would have far less race problems had that odd
little quirk of photosynthesis of a key nutrient not existed.

~~~
tchaffee
> A change like the loss of melanin requires selective pressure

It does? What about genetic drift, random mutations, and artificial selection,
where humans select based on qualities not necessarily conducive to survival?

There is also some evidence that this change in skin color was only widespread
as recently as 8,000 years ago [1].

> which in this case was likely furnished by less vitamin D

How likely?

> The pressure must have been significant since being white carries a big
> downside: : higher vulnerability to sunburn and skin cancer.

Unless you are trying to hide from predators or your prey in snow? As far as
skin cancer, as long as it doesn't kill you before you breed, it's not going
to have a big impact on natural selection, right?

[1] [https://www.smithsonianmag.com/smart-news/heres-how-
european...](https://www.smithsonianmag.com/smart-news/heres-how-europeans-
quickly-evolved-lighter-skin-180954874/)

~~~
neetdeth
One aspect of sexual selection is that a disadvantageous trait needn't kill to
cause differential outcomes in reproduction. If a deficiency results lower
hunting success, diminished fighting prowess, loss of mental acuity etc. the
individual will be disfavored in mate selection. Iterated over generations,
this eventually extinguishes some genes.

There's also the aesthetic aspect, where some traits seem to be favored simply
because they are attractive to the opposite sex, which can be justified
because offspring will have more favorable opportunities for reproduction, but
only because the trait is well liked. A strange attractor in the genetic code,
if you will. This happens across species, so I wouldn't call it artificial
selection - artificial selection applied to humans is also known as eugenics.

~~~
tchaffee
> One aspect of sexual selection is that a disadvantageous trait needn't kill
> to cause differential outcomes in reproduction. If a deficiency results
> lower hunting success, diminished fighting prowess, loss of mental acuity
> etc. the individual will be disfavored in mate selection.

That makes sense, and it also supports my claim that skin cancer would likely
not be a trait selected against, right? It's something that usually happens
later in life and that would not be involved during mate selection.

> so I wouldn't call it artificial selection - artificial selection applied to
> humans is also known as eugenics.

Thanks for that distinction. If this attraction is happening naturally and
unspoken, it's fair to include it as a part of natural selection. However, I
do think some of it is cultural, is spoken, and goes beyond natural
attraction. A common example might be the preference for lighter skin in mates
that we unfortunately find in several cultures. Maybe we should start calling
it eugenics instead of softening it to artificial selection.

~~~
neetdeth
For skin cancer narrowly, sure. I don't know what it's like to live with white
skin near the equator with primitive or no clothing and no access to
sunscreen, though. Losing melanin every winter, getting scorched every
summer... It seems like you'd have an individual who is pretty useless for
persistence hunting across the savannah. On the other side, a darker skinned
individual may experience lethargy and malaise in winter at higher latitude.
So we should broaden the considerations to include chronic, nonlethal
conditions, and competitive sexual selection amplifies their effects. This was
my only point.

> A common example might be the preference for lighter skin in mates that we
> unfortunately find in several cultures. Maybe we should start calling it
> eugenics instead of softening it to artificial selection.

You can do that if you want. People really like their mate preferences and
this seems more likely to soften their perception of eugenics as a concept
than the other way around.

------
mola
This is wonderful scientific writing; approachable without being condescending
or over simplifying, without a trace of sensationalism. Really beautiful.

~~~
ajhurliman
I thought the opposite: It campaigns against vitamin D as if it were a wolf in
sheep's clothes. I've seen the author (and her partner) post and link about
the dangers of vitamin D for a while now and it seems very unscientific to
come at a subject with your mind already made up.

The author has clearly made up their mind about vitamin D and now they've made
it duty to lobby on behalf of that belief, but I don't think they're capable
of honest, unbiased science regarding this subject anymore.

~~~
mola
huh? They did the research, reached conclusions, and inform the public. That's
what scientists should do. Why do you think they first decided they don't like
vitamin D, and only then cherry picked research to prove it?

Anyway, If you are an informed enough, you don't have to believe them, you can
just read all the research they provided, and see for yourself.

Otherwise, all you can do is trust them. Or not.

~~~
conorh
I think the idea of these articles was to help make people more informed
consumers. As Deva says:

> Finally, no one needs to blindly believe what I say - or what anyone else
> says - about Vitamin D. You can and should critically evaluate the evidence
> for yourself. Below I have listed out some of the most important RCTs and
> meta-analyses of RCTs, with summaries and links. When looking at meta-
> analyses, Cochrane always provides top quality reviews, and I often look to
> them first for quality analyses and thoughtful interpretations.

------
oa335
I would have loved to see some of her advice and information dis-aggregated by
race.

Low Vitamin D levels of are not evenly distributed among different ethic
groups. e.g. "53%–76% of non-Hispanic blacks [ had low vitamin D levels, in
the Southern U.S.] compared with 8%–33% of non-Hispanic whites [0]".

Thus the risk-reward considerations of taking vitamin D are likely different
for dark-skinned individuals than for light skinned individuals.

I have to assume her advice at the end is targeted at light-skinned people. As
a dark-skinned person myself, I'm irritated that she couldn't bother to at
least mention the above issues.

[0]
[https://academic.oup.com/jn/article/136/4/1126/4664238](https://academic.oup.com/jn/article/136/4/1126/4664238)

~~~
devaboone
I wrote the article. It was very hard to write a concise article about all of
Vitamin D research, and so I didn't have space to address it, though I really
appreciate the feedback. Race and Vitamin D is an interesting area. The VITAL
trial, which is the largest study on Vitamin D that we have, with 25,000
participants, tried to enroll more Blacks, and in the end 20% of the
participants were Black. They showed the same results, but interestingly it
did seem like there might be a trend toward fewer cancers for Blacks who
received Vitamin D, but this was not definitive. More research on this is
needed.

The other reason I didn't get into race and Vitamin D is that we then start
getting into the blood levels, and what really constitutes deficiency. I think
we are a little too liberal with our diagnosis of deficiency right now.

------
jeffreyrogers
Shouldn't they be looking at getting vitamin D via sun exposure, rather than
supplementation? If the real benefit is sun exposure, which also increases
vitamin D, then just supplementing vitamin D won't show any benefits.

~~~
CyanLite2
Very hard to quantify sun exposure and do this in a controlled way.

~~~
coldtea
Very hard? Sounds one of the easiest things to measure and control for...

Tack a sensor (e.g. watch like) to people working outside, vs people working
inside, inmates, etc for example...

Check people in long norther nights vs the carribean (you can find lots of
people of either place in the other).

~~~
CyanLite2
I'll clarify: it's harder than giving everybody the same 5,000 ICU tablet of
vitamin D. Can it be solved? Yes.

------
lprd
I have a couple questions for any doctors out there.

How many times a year should one check his vitamin levels?

I live in Paris, and during the winter months we don't get that much sunlight.
My doctor gave me a prescription for vitamin D3 (100,000 IU vial, once a
month, for three months). Is this a good dose for the year (provided you get
adequate sunlight during the summer months)? How long does vitamin D3 stay in
the body until it uses/flushes excess out? Are you better off taking a high
dose like this for 3 months, or adopting a more slow and steady method (i.e.
supplementing daily).

~~~
baccheion
Can you get D3 from a store? Prescriptions are usually vitamin D2.

20,000 IU or 50,000 IU D3 1x/week is a great amount. Or you could try taking a
lesser/proportional amount each day.

You could also get one of those sun/S.A.D. lamps or red light devices to
increase topically.

~~~
lprd
Just checked the box again and it says "cholecalciferol (vitamin D3) 100,000
IU". I believe the prescription is required due to the dosage (100,000 IUs is
pretty high).

I could definitely get some D3 from the store, but I am curious if taking a
prescription dosage once a month yields the same result as a lower daily dose.

~~~
baccheion
Once a month is too infrequent, but it'll work fine. 1x/week is better. 1x/day
is best. Some benefits are missing versus daily dosing, but the main things
are still in play.

------
burgerquizz
I've seen a well explained video about a study[1] saying vitamin D3 helps in
reducing severity of COVID19. What's your argument(s) against it?

[1][https://www.youtube.com/watch?v=V8Ks9fUh2k8](https://www.youtube.com/watch?v=V8Ks9fUh2k8)

~~~
jahlove
OP's article does not address Vitamin D's effects on COVID.

~~~
aidenn0
It indirectly implies that it may be efficacious though as it mentions
respiratory infections as one place where meta-analysis has shown benefits.

------
zzzeek
correct me if I'm wrong (like that ever happens on HN...) but even mainstream
SSRIs like Lexapro (which I am taking, I'm a lifelong depressive, thanks)
probably get a big red X in "prevention of depression". trying to "prevent
depression" is like trying to grab Jell-O.

~~~
pmiller2
I don't know that there is any drug or intervention that _prevents_ depression
in otherwise healthy people, besides eating a balanced diet, maintaining a
healthy weight, and getting sufficient exercise.

Preventing relapse in people whose depression is in remission may be a
different story (and, one which I'm not terribly familiar with). Part of the
problem is that the placebo effect in trials for depression is very strong.
See, for instance
[https://pubmed.ncbi.nlm.nih.gov/24172161/](https://pubmed.ncbi.nlm.nih.gov/24172161/)

BTW, I am also a lifelong sufferer of depression. SSRIs have never really done
anything for me, but bupropion has been a lifesafer.

------
DoreenMichele
A few thoughts:

Expecting vitamin D supplementation to be some cure-all is silly on the face
of it. It's like saying "Your building has a brick deficiency" after some
disaster does egregious harm to it and then ordering a bunch of bricks or
starting a charity to give away free bricks to the entire community after a
hurricane levels things.

Yes, bricks may well be a critical ingredient necessary to rebuild, but
getting a giant pile of bricks dropped at your front door is the _start_ of
the rebuilding process, not the end of it. And then you will find that you may
not able to do anything with your pile of bricks because there's no mortar to
hold them together or there are no skilled brick layers available.

The body is a very complex machine. It really shouldn't surprise anyone that a
simple solution -- like "needs more vitamin D" \-- isn't going to miraculously
get it working better across all categories of things that can go wrong,
either due to a deficiency or in a way that will cause a deficiency.

------
gojomo
The story is clearly more complicated than, "supplement Vitamin D, improve
everything that low-Vitamin-D is correlated with". Getting real sun, & doing
the whole stack of things associated with that – being active, seeing nature,
joint activities with friends outside the home, etc – is more likely to help
with the correlated conditions.

But I can also think of reasons why these RCTs don't quite close-the-book on
Vitamin-D as much as this author suggests. Looking more-closely at the 'VALID'
25,000-subject RCT that's highlighted:

* the dose of 2000IU is still small compared to the recommendation of other groups, such as the UCSD/Creighton group that highlighted a massive calculation error in the original RDA determination, that suggests the RDA should be _7000IU_ ([https://www.sciencedaily.com/releases/2015/03/150317122458.h...](https://www.sciencedaily.com/releases/2015/03/150317122458.htm))

* by only enrolling people over 50yo/55yo, the possibility that Vitamin D levels earlier-in-life are important isn't tested

* by eliminating people with any history of cancer/cardiovascular disease, the potential that Vitamin D helps specifically among people whose risk is so high these diseases turn up by their 40s can't be detected. (I'm assuming the 'history' screened for was just the patient themself; if they also screened out _family history_ , that'd be an even bigger limitation.)

* a ~5y followup can't detect effects at 10y or beyond

* Vitamin D's effects are somewhat like, & linked-to, hormones - and indeed there's some indication it should be taken in the AM, rather than before bed, to avoid mild sleep disruption. I don't see any indication as to when the VITAL study participants were coached to take their calendar-packs. Similarly, natural Vitamin D levels vary seasonally. What if unnatural timing (within the day or the year) changes the mix of effects that more natural pulsing would achieve?

Also, the VITAL study did observe "a possible vitamin D–associated benefit
with regard to the incidence of cancer among black participants".

So: a great study, in many respects, but still leaves untested lots of
plausible ways Vitamin-D supplementation could theoretically help - in higher
doses, the younger, the already-sick, during a respiratory pandemic, etc.

------
RL_Quine
For other reasons I get tested for vitamin D every few months and managed to
get my levels just above the normally recommended amount as per doctors
advice. When people are saying they’re taking 25-100k UI a day I’m just
stumped why they’d be doing that without medical advice, the amount to change
my levels was nothing in comparison.

~~~
baccheion
RDA is 400 IU. It's actually the food RDA, with 20% expected from food.
Overall RDA (sun + food) is 2000 IU. Therapeutic vitamin doses are 10x the
RDA. 6x is elevated while doing "nothing" and 20x is full saturation ("but
why").

2x and 4x for minerals.

For vitamin D, that would then be 20,000 IU or roughly 300 IU/kg/day.

No need to take that much or be outside the 40-60 ng/mL range for no reason.
On the other hand, many benefits may be had in the higher range with advancing
age. Especially when combined with vitamin K2 (1 mg MK-4 and 100 mcg MK-7 per
5,000-10,000 IU) and getting more magnesium than phosphorus (with 1/3rd-1/2
that amount as calcium; for example, 1.5g phosphorus, 1.5g magnesium, and
500-750 mg calcium).

Some magnesium as ZMA is good for males, as it improves sleep quality.

By the way, ancestral eating patterns led to ~1.5g magnesium per day.

At least after development has ceased (ie, plates fused), shifting from
calcium to magnesium is a solid step.

The main issues with higher vitamin D3 are addressed by adjusting vitamin K2,
calcium, and magnesium.

~~~
zwaps
This is a thread about an article citing many studies of RCTs showing no such
benefit. For that reason, where is your recommendation coming from?

~~~
baccheion
I said no need to take so much.. for no reason.

With advancing age, higher amounts (+ magnesium and K2) mimic/amplify the
actions of hGH/IGF-1 pushing back toward youth. More D3 is often needed with
age for the same effect.

The combo is also protecting bone and the higher amount of magnesium does
countless things: released when the body is ready to unroll inflammation,
opposes excess lipid peroxidation, opposes lipofuscin, lengthens telomeres,
shifts the calcium:magnesium balance such that less calcium is absorbed into
stressed cells, keeps calcium dissolved, decalcifies, vasodilation at skin
(improves nutrient flow, slowing aging effects), binds and clears heavy metals
as excreted, sensitizes to LH, increases testosterone/progesterone and IGF-1
(directly and indirectly), aids in clearance of estrogens, opposes stress,
lowers cortisol and aldosterone, shifting to DHEA and potentially anabolism,
improves sleep if taken at night (ZMA for males), etc...

~~~
zwaps
You are repeating yourself, so I will as well. The article claims that these
health benefits do not exist for normal people. The article has studies with
high quality RCTs that would trump other, observational studies.

~~~
baccheion
I said higher doses wouldn't be needed for no reason.

On the other hand, I already mentioned what happens with age.

------
solinent
I think it's related to diet, a deficiency in Vitamin D probably indicates a
certain type of diet that leads to obesity. I wonder if metabolic syndrome and
vitamin D deficiency are also comorbid.

You need fat to absorb vitamin D and perhaps this fat has additional benefits
(satiety, less feeding periods, the integral of insulin over time is smaller).
Ketosis probably has some role to play, I should check if they're controlling
for this factor. Until they can control for the entire diet it's hard to
really tell based purely on vitamin D, the metabolic processes can be so
complicated in a human.

Disclaimer: mindless speculation above--I'm no expert, just a mathematician.

------
mekoka
My main dissatisfaction with Vitamin D studies is the fact that they usually
try to isolate it as a self-contained factor that you can simply raise or
lower and observe effects, while neglecting the complex system it is normally
a part of.

How about instead treating it as a simple block of that complex system? What I
mean is that Vitamin D typically correlates with sun exposure and a healthy
outdoorsy lifestyle (i.e. the system). I would think that if you want to
understand how its presence affects an individual, you would try
raising/lowering it specifically on subjects whose lifestyle guarantees the
presence of that system.

------
KerryJones
Thank you for this deep-dive, I definitely agree it's not a panacea, though I
do supplement and recommend most people supplement.

The question I have -- you did a deep dive into many of the "larger" claims,
but the claim that I have found most substantiated and most relevant is
preventative to various viruses (such as influenza):
[https://www.sciencedaily.com/releases/2017/02/170216110002.h...](https://www.sciencedaily.com/releases/2017/02/170216110002.htm)

Do you have any additional information or findings about this?

------
goda90
It seems like its easy to identify the harms of extremes. Too little of X
causes Y and too much of W causes Z. But with so many variables affecting the
human body(nutritional, genetic, environmental, microbial, mental, etc) how
can we even approach being certain about optimal levels in the middle? I don't
see how we could control for enough variables for long enough to know how much
vitamin D is best for the body, and exactly how it interacts with other
variables in regards to various diseases.

~~~
Nursie
But we can see how supplementation affects outcomes, and it turns out that so
far the results on that are pretty 'meh', unless you're supplementing
specifically for severe vit D deficiency.

~~~
goda90
I guess my point is, if outcomes are affected by a couple dozen variables,
unless we can control for all those variables, then we might not see any
affect from this one variable. And there is a limit to how many variables we
can reasonably control for.

~~~
zwaps
Controling for variables is important to establish causality in observational
studies. Many fields in social sciences are developing increasingly
sophisticated methods to tease out causal relationships (see Pearl,
Angrist&Pischke etc.).

However, many of these methods try to obtain the conditions similar to the
gold standard: Randomized Control Trials.

In an RCT, if you assign treatment randomly to balanced subgroups of a
population you care about (or one that is even representative), then you do
not require to controls.

To see that, imagine the treatment being independent of the confounding
factors and the distributions across group being the same. It then follows
that you can estimate the average treatment effect without bias.

------
lizzard
Serious question, whenever I read something about a Vitamin D deficiency, or a
huge number of people getting tests back as lacking Vitamin D, I wonder --
what determined what the baseline of not-deficient is, and for which
population? How were the baseline expectations set?

------
refresher
>3\. Act in moderation. Low to moderate doses of Vitamin D (e.g. 400 to 2000
IUs daily) have proven to be safe in trials. If you think there is a benefit
and we just don't have enough data to prove it yet, you may be right. We do
know the harms of taking too much, though, so supplement in moderation. And if
you are taking Vitamin D, ask your doctor to check your blood levels.

I'll probably carry on with this then. I was taking a single 4000 IU pill
every four days (which was the suggested dosage) but once a week for around
570 IUs a day should be fine. Frankly I hate blood tests and don't believe I'm
D deficient, so I'd rather take a lower, even if useless, amount.

------
chmod600
Don't over-think (unless you're a researcher, in which case that's your job).
It's pretty simple:

Low levels are bad. If your levels are low, supplement.

Err on the high side because the risks are low, but don't go crazy for long
periods of time without testing.

~~~
beervirus
A little more thinking may be in order, since the whole point of TFA is that
supplementing doesn't seem to do much good.

~~~
chmod600
It has a green check next to "treatment for Vitamin D deficiency". What part
of the article says that you should just ignore low vitamin D levels?

~~~
scott_s
"Deficient" is not the same as "lower end of the normal range." If you suspect
you are deficient, go to a doctor.

~~~
chmod600
I said "low" not "lower end of normal". What part of my suggestion is refuted
by the article?

~~~
scott_s
"Low" is ambiguous. We are clarifying it.

------
rossdavidh
It seems like the nth example of cases where isolating a vitamin as a pill, is
not a substitute for acquiring it in the normal way for our species. We are
not descended from nocturnal species, as our vision system and other
characteristics show. We are evolved to spend a lot of time outdoors. The fact
that we have been told for 30+ years to avoid the sun, is an awkward example
of experts being incorrect. It happens, even in fields where experts are
normally correct, and nutrition is not one of those fields. Keeping a non-
nocturnal animal out of the sun all the time, is likely bad for us, in ways
that are measured (but not necessarily caused) by vitamin D levels.

------
tim333
The July Radiolab episode it good on vitamin D and sunshine and its effect on
covid and also on the 1918 flu. In both cases getting out in the sun seemed to
have a dramatic reduction in deaths.
[https://pca.st/dwgcmlx1](https://pca.st/dwgcmlx1)

I guess it must have quite an effect on things to evolutionarily justify the
difference in appearance between fair skinned and dark skinned people - the
fair skin is mostly to allow sun in to produce vit D in northern climes.

------
remote_phone
Which part of the body needs to be exposed to UV light in order to produce
Vitamin D?

If I wear a baseball cap and jeans and expose only my arms, is that good
enough? Or do I need to expose my face?

------
0-_-0
So what's the purpose of vitamin D then? It must be important if it was worth
evolving white skin over, so why are studies failing to find that important
reason?

~~~
tchaffee
> It must be important if it was worth evolving white skin over

Where is the evidence that we evolved white skin to produce more vitamin D?
Light skin in Europe may have evolved as a widespread thing as recently as
8,000 years ago [1], which doesn't support the idea that it was essential for
survival in northern less sunny areas. Are there any studies giving strong
evidence as to the causation for evolving white skin?

[1] [https://www.smithsonianmag.com/smart-news/heres-how-
european...](https://www.smithsonianmag.com/smart-news/heres-how-europeans-
quickly-evolved-lighter-skin-180954874/)

~~~
0-_-0
From the article you linked:

"A sun lower in the sky and shorter day lengths would have favored skin that
more easily synthesized vitamin D."

The article also points out a correlation between latitude and light skin, so
the evidence is pretty strong (based only what you linked) for why light skin
evolved.

~~~
tchaffee
If you look at the full quote, the purpose is not to confirm your theory but
to inject healthy doubt in your theory:

"A sun lower in the sky and shorter day lengths would have favored skin that
more easily synthesized vitamin D. But researchers are now learning that other
factors must have been at play."

> The article also points out a correlation between latitude and light skin

Well yes, exactly. Correlation. I asked for causation, which it seems you are
still lacking.

~~~
0-_-0
I read the article but failed to see what doubt it sheds on the idea that
light skin evolved to increase vitamin D production. Could you help me find it
please?

You asked for evidence of causation, which I provided. Correlation of latitude
with skin colour is evidence of causation. Light skin colour providing vitamin
D while increasing skin cancer risk is evidence of causation. No other known
advantage of light skin colour existing is an evidence of causation. Taken
together, there is strong evidence of a causative link between the evolution
of white skin and vitamin D production.

~~~
tchaffee
> Correlation of latitude with skin colour is evidence of causation.

Correlation is not causation. I'm sorry but I don't think you have any
evidence at all that lighter skin was caused by a need for more vitamin D.
It's just an educated guess on your part. Lighter skin could have just as
easily been an adaptation related to less visibility to predators and prey in
snow. Like the article I cited said "researchers are now learning that other
factors must have been at play."

And with the article that started this thread we now have quite a few studies
telling us that vitamin D supplementation doesn't do anything helpful. So why
would humans undergo an adaptation that provides no benefit? Perhaps exposure
to the sun provides health benefits? Or is it that healthy people get outside
more and therefor have higher vitamin D levels? I'm happy saying "I don't
know" and asking more questions. I encourage you to do the same instead of
claiming causation when all you have is correlation.

~~~
0-_-0
Correlation is not causation, but you didn't ask for proof, you asked for
evidence, and correlation is evidence. For example, do you know whether
smoking causes cancer? Because all the evidence we have that it does is based
on correlation. Or you're happy saying "I don't know" and asking more
questions? How would you show a causal link between vitamin D deficiency
causing the evolution of light skin colour without being able to conduct a
double blind study? It's fundamentally impossible to prove, all we have is
evidence, which is this case is sufficient to say as the first sentence in
Wikipedia [1]: "An abundance of clinical and epidemiological evidence supports
that light skin pigmentation developed due to the importance of maintaining
vitamin D3 production in the skin"

[1]
[https://en.wikipedia.org/wiki/Light_skin#Evolution](https://en.wikipedia.org/wiki/Light_skin#Evolution)

~~~
tchaffee
> you didn't ask for proof, you asked for evidence

I didn't ask for evidence from you. I asked more specifically "Are there any
_studies_ giving strong evidence as to the causation for evolving white skin?

> do you know whether smoking causes cancer? Because all the evidence we have
> that it does is based on correlation.

That's wrong. We understand why smoking causes cancer. Just for example one of
chemicals produced by tobacco smoke is benzoapyrene which is a DNA disruptor,
producing mutations that can lead to cancer. [1]

> It's fundamentally impossible to prove, all we have is evidence.

That's progress. We've gone from "It must be important if it was worth
evolving white skin over" to "we can't prove that's why we have white skin".

The Wikipedia sentence claims an "abundance" of evidence and then only gives
one source, which is behind a paywall. So I'm going to recommend an edit to
that article to either give more sources or change the "abundance" claim.
Furthermore just a few sentences later it contradicts itself with this:

"This accounts for the development of dark skin pigmentation of people living
near the equator but does not account for the increasingly lighter-skinned
people living outside the tropics."

Yet more doubt as to why we have white skin. From your source.

Finally, the article that started this discussion provides strong evidence
that our need for vitamin D is less important than we previously thought. For
sure very low levels of vitamin D are dangerous. But the link between vitamin
D and health could be reverse causation: sick people stay inside and therefor
have less vitamin D. It could also be that exposure to sun provides something
more important to health than vitamin D that we are not aware of yet. So the
claim that we evolved white skin just for vitamin D is increasingly on less
stable ground.

I'll stop here because I'm happy that you've gone from what seemed like a
factual claim to you claiming that it's something we cannot prove. Who knows,
maybe someone clever can prove it. But it sure does seem like the evidence
itself (about both vitamin D _and_ skin color) is fairly rapidly changing.

[1] [https://www.mskcc.org/news/how-do-cigarettes-cause-
cancer](https://www.mskcc.org/news/how-do-cigarettes-cause-cancer)

~~~
0-_-0
> I didn't ask for evidence from you. I asked more specifically "Are there any
> studies giving strong evidence as to the causation for evolving white skin?

Correlation is evidence of causation, and the correlation between skin colour
and latitude comes from studies. Therefore I provided that evidence.

> We've gone from "It must be important if it was worth evolving white skin
> over" to "we can't prove that's why we have white skin".

We did evolve white skin to produce vitamin D, the evidence is overwhelming.
Just like evidence was overwhelming about smoking causing cancer, even before
the 2018 article you linked came out. You seem to be misunderstanding the
Wikipedia article. It's not contradicting itself. The correct interpretation
is that the need for dark skin at the equators doesn't explain white skin
nearer the poles, therefore there must be a different reason for it (vitamin
D). That article wikipedia links to can be found on SciHub.

Overall, your approach reminds me of creationists that claim that evolution is
"just a theory" because noone has ever proven it in a lab, and correlation is
not causation. And tobacco companies who have denied that smoking causes
cancer because correlation does not equal causation.

------
throwawaybutwhy
Unfortunately, Vitamin D submissions are now in the same systematic group on
HN as posts from NY Times, Zettelcasteln, Rust, Haskell,'Greenland is
melting', 'Tesla is bound to fail', etc.

I understand that dang cannot stem the tide with the resources at his
disposal, and the coming November looms over everything else. Still, one can
hope for higher SNR here.

------
stubish
Is this about Vitamin D or Vitamin D supplements? We already know taking
supplements does not equate to the body actually being able to make use of the
vitamin. I'd be interested if this study also discounts Vitamin D produced by
the body, or if some extra ingredient is needed to allow the body to benefit
from the vitamin.

------
pmiller2
Thank you again for this, Dr. Boone. This particular article has made me feel
a little bit better about taking my moderate dose of D3 every day: I have
asthma, have had a flare up or two of eczema, don’t want to die of cancer, and
don’t want to break any bones at an advanced age.

------
nw05678
I'm still on the fence about this. Until someone from my health care system
comes out and states that the research looks good I am not going to eulogise
it. Do I take vitamin supplements yes, would I say it produces the affect on
covid patents to other people, no.

------
raverbashing
TL;DR: skip to the part "The areas in which meta-analyses have identified
benefits from Vitamin D"

Also "Vitamin D failed to prevent cancer, stroke, heart attack, or
cardiovascular death. "

Which is fair enough. But at least for the cardiovascular diseases mentioned,
I don't think it was expected.

And of course, this _does not mean anything against the role of Vitamin D in
Covid prevention_

Basically: don't dismiss X for disease D1 if you tested it with disease D2

~~~
scott_s
I find it odd to encourage people to skip what I consider the most important
conclusion for most people: "Vitamin D does not appear to prevent disease in
healthy adults."

~~~
raverbashing
2nd line of my post

Describing it as "prevent disease in healthy adults" means pretty much
nothing. Which diseases? Does being Vit D deficient count as healthy? It's an
empty statement.

~~~
qmmmur
Diseases americans are concerned with. You definitely don't even hear about
vitamin d in Australia but soon cancer research would easily eclipse it. Can
you imagine why?

------
Scarbutt
Is there a study that has measure how much vitamin D a person can get from
sunlight within some timeframe/hour of the day/place on earth?

------
xwdv
If deficiency is linked to all these maladies then why aren’t we seeing them
occur with less frequency in areas that get full sun year round?

~~~
0-_-0
Do areas that get full sun year round have people with more vitamin D? Those
places have people with darker skin which blocks vitamin D production.
Actually, the only reason white people exist in the first place is because of
vitamin D, so you would expect vitamin D to have strong positive effects based
on this fact alone.

~~~
tchaffee
> the only reason white people exist in the first place is because of vitamin
> D

Is there a study to back up that claim? I haven't seen anything claiming to
prove that lighter skin was a definite cause of a need for higher vitamin D
levels. In fact, the article would seem to prove this theory wrong. Vitamin D
supplementation does not help with much of anything as far as we can tell so
far.

------
laplacesdemon48
There was also an ancillary study to VITAL that focused on looking at
depression & vitamin D3. Here's some good commentary on that study:

[https://peterattiamd.com/randomized-controlled-trials-
when-t...](https://peterattiamd.com/randomized-controlled-trials-when-the-
gold-standard-leaves-you-with-fools-gold/)

tl;dr Due to the study's flawed design, you can't claim there's no connection
between depression and oral vitamin D3 supplementation.

------
pcvarmint
I don't really care what RCT trials show.

I have suffered from bone fractures 3 times, 2 spontaneously, and I was
eventually diagnosed with osteomalacia at age 46.

I therefore take Vitamin D and Calcium supplements regularly.

My Z score was -5.0 four years ago, but after taking supplementation and
Fosamax for several years, it was raised to -2.0.

------
graeme
Have there been any studies on vitamin d from the sun or lamps and health
outcomes?

------
jccalhoun
A couple years ago my blood tests showed low Vit D and so I've been taking it
twice a week since. I don't know about health but on the two days I take it I
seem to have a lot more motivation to get things done and instead of thinking
"I should go do X" I find myself just doing it.

------
afrojack123
Every year they issue a winter influenza vaccine instead of making vitamin D
pills and artificial sunlight available. Young people never take the winter
flu vaccine and are fine.

------
mike_ivanov
Don't you love it when somebody says "there is no evidence" and never shows
you confidence/credible intervals?

------
privacy-matters
But the lady on Joe Rogan disagrees. I now take 25,000 IUs each day so I won’t
get coronavirus.

~~~
sauwan
Good grief. Please be careful and work with your doctor...

ETA: This is probably sarcasm isn't it?

~~~
LandR
Clearly....

