
Effect of High-Dose Vitamin D on Volumetric Bone Density and Bone Strength - bookofjoe
https://jamanetwork.com/journals/jama/article-abstract/2748796
======
01100011
I thought you needed both vitamin D and vitamin K2 - D to mobilize the calcium
and K2 to put it into the right place.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613455/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613455/)

~~~
mrfusion
In my mind that’s what makes this kind of a garbage study.

~~~
AstralStorm
Alongside focus on just osteoporosis, lack of control for calcium levels
(other than blind supplementing with low dietary intake), phosphate levels.

Some people may be responding poorly to the supplement, especially at high
doses and low calcium. Direct blood test for status would help.

~~~
LinuxBender
CAC tests are a good indication if D3+K2+mag is mobilizing calcium. That is of
course if your current CAC score is above 0 which it should not be.

------
ForTheTimeBeing
To preface here, what I'm to share goes beyond what's in the article. That
said, I worked for years in a clinical "bone lab" (and at a notable university
hospital with respect to this area of research) investigating bone wasting
diseases; namely, idiopathic hypercalciuria, and osteopenia & osteoporosis.

Not say that lends me too much authority on the matter, but many of the
biological effects of D3 are pretty poorly understood, still. Simplifying a
bit, this can be chalked up to the fact that it's roles in molecular networks
across the systems are myriad, and of these, many of its (downstream) effects
seem -- and, if not, are -- contradictory. (To the initial point, in it's
bioactive form, it's classified as a hormone.)

At high dosages, typically what's found it many OTC supplements (5-10K IUs vs
500 IU daily allowance), there is evidence that it facilitates significant
bone resorption.

So not only does it not strengthen bones, D3 actively makes it more brittle.
Typically, this is linked to inadequate calcium & phosphate minerals to match
the excess D3 (and these minerals in excess introduce additional problems of
their own).

I didn't cite literature here but it is readily available & abundant (But I
can pull some if anyone would like). And, within it, there is a glaring lack
of consensus. And hence, why my language is couched in so many conditionals.

~~~
mntmoss
One of the big asterisks with most D3 bone density studies(and is applicable
to this one) is that they are studying older adults specifically, vs, say,
athletes. There are bodybuilders, for example, who swear by high-dose D3.

------
ChrisSD
In other words, a lack of Vitamin D reduces bone strength but getting more
than necessary doesn't increase bone strength any further.

Makes sense. This is often how the body works. You should get enough of
<nutrient> but having more than needed doesn't turn you into a superhero (but
it can be poisonous).

------
AlexanderNull
Why are there so many studies looking at vitamin D and bone health? Vitamin D
levels affect expression of over 400 genes in the human body, make a
difference in cancer survival and are strongly inversely correlated with all
cause mortality
([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103214/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103214/)
[https://www.mdedge.com/psychiatry/article/66349/depression/v...](https://www.mdedge.com/psychiatry/article/66349/depression/vitamin-
d-deficiency-and-psychiatric-illness)
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201256/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201256/)).
Does the lay person really only associate vitamin D with bones?

~~~
Tryptaminded
Time to start taking vitamin D

~~~
nradov
You would probably benefit more from being out in the sun than from taking
vitamin D supplements.

~~~
nikolay
Yeah, and possibly die of malignant melanoma. At the same time, no sun
exposure is also a risk of melanoma - not sure if due to vitamin D or more
possibly - due to the hormetic effect of mild skin DNA damage.

~~~
nradov
A little daily sun exposure won't significantly increase your risk of melanoma
(unless you have a rare genetic disorder).

~~~
nikolay
True, but you get enough vitamin D - especially not during the winter.

------
pkaye
Being a dialysis patient, I have to deal with a lot of the issues of my
kidneys not functioning. There is a complex interplay of vitamin D, PTH (from
parathroid), phosphorus, calcium levels and bone loss. So I have to take
vitamin D, calcitriol and phosphrous binder and dietary restrictions to
balance it all. Going too far one way or the other is not good. Every month I
get blood tests for all these things and my doses adjusted. Vitamin D is the
least of my concern in this process.

~~~
tomcam
Dialysis sucks. It takes away so many of life’s little pleasures. My best to
you, brave person.

~~~
pkaye
The kind of treatment I'm having isn't so bad. Its just the time it sucks up
plus the inconvenience of travel. I haven't gone on an out of town vacation is
ages because of all the equipment I have to drag along. The best I can pull of
is weekend trips and stay-cations.

------
JohnJamesRambo
[https://www.outsideonline.com/2380751/sunscreen-sun-
exposure...](https://www.outsideonline.com/2380751/sunscreen-sun-exposure-
skin-cancer-science)

One of my favorite articles. Vitamin D supplementation has a very poor track
record of doing anything positive. It’s very likely that most of the studies
attributing benefits to vitamin D and correlations between serum vitamin D and
health are because it is a surrogate marker for getting sunlight, which may be
the real health improver. When we supplement with D in properly controlled
studies, the health benefits disappear.

------
heavymark
To those who only read the HackerNews title and not the title of the actual
article, it does not say that Vitamin D does not strengthen bones, but rather
higher does don't seem to strengthen more than lower doses, not compared to
not taking any at all as one would probably interpret from the HackerNews
title.

~~~
matthewdgreen
I don't think "compared to not taking any at all" is an accurate summary here.
Even if you never touch a Vitamin D supplement, many people are already
getting an amount comparable to the baseline used in this study from a typical
diet, or from sun exposure.

~~~
airstrike
Except, say, for 6-9 months every year if you're vegan and living in cold
climates...

~~~
matthewdgreen
2/3 of Americans get the RDA of Vitamin D. Picking a specific outlier case for
your control group wouldn't make a lot of sense for a scientific study (not to
mention, as others have pointed out in this thread, would be difficult or
unethical.) If you are a vegan living in a low-sunlight location, look into
supplementation.

~~~
airstrike
So you're saying 1/3 of Americans don't get the RDA of Vitamin D, yet calling
33% of cases "an outlier"

I'm not vegan and I actually take Vitamin D3 supplements, but wanted to point
out the flaw in assuming that everyone is in the same bucket as me.

~~~
matthewdgreen
I'm saying that probably a very tiny percentage of Americans get 0 IU. Which
makes 0 IU a very poor choice of a baseline. Since you need some concrete
amount to use for your control group, what would you propose using?

------
maerF0x0
> hree-year, double-blind, randomized clinical trial conducted in a single
> center in Calgary, Canada, from August 2013 to December 2017 ...

Generally speaking, interesting to consider that Calgary is a fairly northern
city and they say more northern people get less natural VitaminD from sun
exposure... So even in a generally vitaminD short populace the results are
showing no stronger of bones. I say all this iirc, not from specific
scientific sources...

------
dogmatism
D3 is converted to 1,25(OH)2-D3 which is the active form. The transformation
is limited by 1α(OH)-ase which in turn is regulated by levels of calcium and
PTH and degraded by renal 24-OH-ase, which previous work has shown is
upregulated by high 1,25(OH)2-D3, _and_ 25(OH)D (formed in the liver from the
oral cholecalciferol), thereby providing a brake on the system. It has also
been shown that the upregulation of 24(OH)ase can be enough to actually
decrease 1,25(OH)2-D3 levels, thereby resulting in osteoclastic activity. PTH
is also suppressed by high 1.25(OH)2-D3.

tl;dr there are homeostatic mechanisms in place in calcium metabolism that
result in a "counterintuitive" reduction in the active metabolite with
supraphysiologic supplementation. Also, this is actually in line with prior
work, though the authors don't mention any of it until the discussion at the
end, and then only two papers. In about 5 minutes of searching, I found papers
going back to 1995 suggesting the same thing.

~~~
PavlikPaja
It isn't counterintuitive. Too much calcium (especially in the absence of
mangesium) hurts your bones (and many other things)

------
pcvarmint
I have osteomalacia, and I have suffered 4 bone fractures in the last 4 years,
two spontaneously: one during my sleep, and one while twisting in my car to
pick up something from the passenger seat.

I take Vitamin D, Calcium, and alendronate (Fosamax), and when the sun is out,
I go out for a while without sunscreen.

My last DXA (2.8 years ago) had a Z-score of -2. I'm only in my 40's, so I
don't have a T-score.

I don't really care about the validity of this study. I just know I have to
take Vitamin D and Calcium supplements regularly, and Magnesium less often,
but regularly.

------
mrfusion
Folks on reddit we’re saying this isn’t a useful study because they’re not
considering the roles of vit K and magnesium.

I mean no one really expects vitamin d by itself to improve bone density. It’s
but one step in the process.

------
PhasmaFelis
The results confuse me. Taking 4000 or 10,000 IU results in _lower_ bone
mineral density than 400. Is lower BMD better? Otherwise it sounds like
vitamin D is actually bad for you.

~~~
chrisco255
The study is saying that too much MIGHT be bad for you. 400IUs was the control
(not 0). Some vitamins have adverse effects in high doses. Vitamin D might be
one of them, but the study just posed the question, it didn't conclude that
that was the case. It would take more studies to confirm that.

------
Ensorceled
A larger, longitudinal study would be awesome for establishing other Vitamin D
claims (in particular, reduced MS incidence and reduced cancer incidences)

------
bsanr2
As with all Vitamin D studies, this one should discuss or acknowledge the
differences in intake requirements for people of different ethnic groups. It
doesn't, which means that for some of us, the findings balance somewhere
between useless and dangerous.

------
macawfish
Magnesium is also a part of this!

------
ebg13
So high doses reduce mineral density but have no effect on strength? How is
that possible? Is strength not a function of density?

~~~
spikels
Here are two possibilities:

1) It probably easier to measure density than strength. Additional measurement
noise could mean the strength difference is not statistically significant
while the density difference is.

2) The relationship between density and strength is probably not a simple 1:1
linear function. For example a 10% bone mass reduction may only result in a 1%
strength reduction. Therefore one many be statistically significant while the
other is.

Likely is is a combination of factors like this. Things are rarely simple in
the lab.

------
fractal618
Isn't that a pretty narrow age group?

"mean [SD] age, 62.2 [4.2] years"

~~~
epmaybe
It's actually good for the purposes of the study, as the highest risk
populations for decreased bone mineral density are elderly populations. We
know from multiple studies that women are at highest risk due to decreasing
estrogen levels post-menopause, and around peak risk around age 65 (hence why
it's recommended to get osteoporosis screening done at age 65). Men aren't
quite as susceptible as our testosterone levels are relatively stable, and
maybe including them isn't the best of ideas. However, proportion of gender is
nearly equal in all treatment arms of the study, so it shouldn't skew the
results.

------
chrisco255
I thought calcium had a bigger impact on bone density than Vitamin D?

~~~
DiffEq
Generally the greatest way to increase bone density is to lift "heavy"
weights. Compared to that any other solution pales in comparison but doctors
never seem to prescribe that.

~~~
maerF0x0
Many things in the weight lifting world revolve around 3 things:

1\. Stimulus: ie lifting heavy, nutrients to support hormonal response

2\. Materials: ie Calcium / minerals

3\. Rest: ie Sleep, recovery time etc.

I would expect any isolated intervention to find lackluster results despite
considerable results in conjunction.

------
aladoc99
Headline is imprecise. The study is saying that higher doses of vit D do not
strengthen bone more than lower doses, not that they don't strengthen bone at
all, which is suggested by this headline.

~~~
phnofive
As usual, the headline ought to be taken from the publication. Bone strength
was virtually unchanged for every group in the study; no participant had
osteoporosis. Mean BMD went down a hair for all groups, but estimated failure
load was considered statistically the same:

> At trial end[...]

> mean percent change in [radial] volumetric BMD of −1.2% (400 IU group),
> −2.4% (4000 IU group), and −3.5% (10 000 IU group).

> mean percent change [...in tibial volumetric BMD] of −0.4% (400 IU), −1.0%
> (4000 IU), and −1.7% (10 000 IU).

> There were no significant differences for changes in failure load (radius, P
> = .06; tibia, P = .12).

~~~
hanklazard
Agreed the differences look small but find a copy of the full article (I would
link but I saw a hard copy). The time curve will convince you this effect is
real. All participants start at the same place and you see the dose curves
move apart over time and very consistently. What definitely isn’t clear is
whether vitamin D supplementation is benefiting the participants at all,
thanks to their lack of a proper control.

The bone density decreases may look minor on paper but look at it this way:
it’s quite possible that a very large cohort of elderly and middle aged people
concerned about their bone health (potentially because they were told they
have reason to be concerned) have been paying a lot of money annually to
actually worsen their situation. That sucks.

