Vitamin D, part 3 – The Evidence
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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.
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
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.)
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.
I have a personal interest in Amyotrophic Lateral Sclerosis, so I am reading patients' Internet forums since two years.
Several patients report participating in trials but they also tell that they take other drugs without telling doctors (they do not want to be expelled from the trial). Those drugs could be whatever they fancy, and they change often: A week seems too long for them, if there is no improvement.
I expect the situation being the same in every life challenging condition, so I doubt that RCTs are of high quality.
Moreover even the pharmaceutical industry seems to be not sure: Sometimes they are repetitively testing the same drug (for example Memantine in ALS):
https://clinicaltrials.gov/ct2/results?term=Memantine&cond=A...
The results of one study could be an anomaly, which is why replication is important in science. But when those results get replicated in tens or hundreds of such studies, we can start trusting those findings (although when surrogate markers are involved, their interpretation can be up for debate).
Also when people say "high quality", it's important to understand what it refers to. It means the authors can show that the study was designed for the declared primary outcomes. It means that adherence was ensured, versus an observational study relying on questionnaires. And it means a control group was used for comparison, which was randomized, thus the study preferably showing a dose dependent response.
Having a control group BTW minimizes the impact of the subjects not adhering to the program in the way that you describe, since you'd have rebels in both camps.
https://bcmj.org/news/vitamin-d-effective-reducing-flu-and-c...
Harvard Gazette: Study confirms vitamin D protects against colds and flu
https://news.harvard.edu/gazette/story/2017/02/study-confirm...
WebMD: Vitamin D May Cut Risk of Flu
https://www.webmd.com/cold-and-flu/news/20100616/vitamin-d-m...
Vitamin D protects against colds and flu, finds major global study https://www.sciencedaily.com/releases/2017/02/170216110002.h...
Such an approach as you mention may work well enough if growth is finished (ie, plates fused) and there's a movement away from calcium to magnesium. That is, get more magnesium than phosphorus and then 1/3rd-1/2 as much calcium. For example, 1.5g phosphorus + 1.5g magnesium + 500-750 mg calcium.
As much calcium isn't needed after growth and I am assuming all RDAs are being met (with just a variety of whole quality foods before adding supplements). Especially enough potassium to ensure a negative PRAL score to further lessen stress reactions.
At such a low amount, you could try the sun/S.A.D. or red lamp therapy.
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:
> Randomization generated groups with comparable percentage of unfavorable risk factors as there was no significant difference in subjects with at least one risk factor, except for high blood pressure and diabetes mellitus, known risk factors for unfavorable disease progression, which were more frequent in patients not treated with calcifediol.
> However, even considering these factors, calcifediol significantly decreased the need for ICU admission in COVID-19 patients in a way not previously reported in this process until now.
That said, I don't think it's fair to characterize the COVID study as low-quality. It's worth mentioning contrary results, even if it's an exception that proves the rule.
But even with those variables controlled, the 95% confidence interval is 0.003-0.25, which at worst is a 4-fold reduction in ICU risk.
We should also note that the Calcifediol treatment group had 14 patients ≥ 60 years old, and the non-Calcifediol group had 5. So the study looks even better with that in mind...
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.
The null hypothesis is that it's highly unlikely VitD has an effect, and we should expect to see that substantiated often in tests. How often? 95% of the time. 5% of the time we can expect to see spurious results from our simplistic model of random processes. Upshot, it's a small change to move those numbers to 92% vs. 8%. In this context, it's fine to say "this was a small pilot that directionally shows we should do a much bigger test", which is what they're now doing.
It's unlikely that the strongly significant result we're seeing in the study is due to sampling error.
It's unfortunate that exposure to UV is so harmful, I'm left wondering if trials using UV lightboxes to stimulate vitamin D production would change the kinds of outcomes (cancer, heart disease, depression...) we're expecting it to .
What is harmful is being indoors all the time, and getting out so rarely that you get sunburned in short amount of time. Far more damage is done by being indoors too much than being outdoors too much.
The white skin has evolved because the body needs sun and UV light to function, one would die otherwise.
This is an extremely popular simplification. The scientific jury is still out on this one, as it seems that paradoxically people with constant exposure to sunlight are less likely to get skin cancer as compared to those that get sporadic exposure.
Also MS is extremely prevalent at high latitudes compared to the tropics. Why? We know vitamin D has a role in protecting the insulation of the nerves, so maybe that's the mechanism. Anecdotal, but the one person I know with MS is white as the snow and avoids the sun like it's the devil.
e.g. our bodies need sunlight and cholesterol in order to synthesize vitamin D; This process also apparently has some other outputs like NO which are much harder to measure since they get used quickly. It is possible that vitamin D is merely (mostly) a measure of the prevalence of this process, and it is the other (harder to measure) outputs are much more important; Or that it's the consumption of cholesterol that's more important than the production of vitamin D; Or that sunlight has other functions we don't measure that are the important ones. Or that it's all just a correlation to some other process we're not even aware of.
That said, my own experience and anecdotally other people I know (and gwern has some blind n=1 experiments on his site to back this up) is that taking vitamin D early in the morning improves sleep at night, and taking vitamin D in the afternoon/evening reduces sleep quality. For that reason alone, I take vitamin D in the morning, and anecdotally, I burn less when I'm in the sun without sunscreen as well.
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.
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.
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.)
Right, that's why I used the word correlated - while it's not unreasonable to think that having an active lifestyle could cause you to be more healthy, it's pretty much a statistical necessity that the two are correlated, because being very sick precludes you from having a lifestyle like that.
I can sort of tolerate a UV index of 1, usually.
So I walk a lot in evenings and early mornings.
During summer I’m basically trapped in house or gym. This past summer it was just the house.
We are more than just a pile of various materials.
And don't forget: It can be multiple causes combined. (I.e. it may be a mix of a confounder like being outside and reverse causality.)
> How can we reconcile promising early observational studies linking Vitamin D to most major causes of death with our current results? One thing that seems increasingly clear is that in most cases low Vitamin D (truly low Vitamin D) is a marker of poor health rather than a cause. Vitamin D is made in the skin after exposure to sunlight. A chronically ill, frail individual may leave the house less often, leading to lower Vitamin D levels. Fixing the Vitamin D will not fix the chronic illness.
"TFA" is indeed a back-formation from "RTFA", which is the online-forum equivalent of the aggressive and obnoxious acronym "RTFM". But it contains no verb; and in online discussions there's a sort of a hole in our language for an efficient way to say for "the article currently under discussion". So it quickly lost the aggressive and obnoxious connotations that RFTA has.
As such, I think "The Fine Article" is an expansion more fitting with its evolved usage.
The logical conclusion is that vitamin D, as we measure it, is proxying for another factor that we haven't yet detected. This X-factor is heavily influenced by sun exposure, but at most weakly influenced by vitamin D supplementation in its current form.
Analogously imagine that we had no concept of the health benefits of exercise. We detected that people with gym memberships were much healthier than those without. So, we try giving a bunch of people a free gym membership. Yet few of the recipients end up using it to do any exercise. In this case the supplement group would show nowhere near the health gains of the baseline gym members. The key issue is that gym membership is only proxying for the underlying X-factor of physical activity.
Michael Pollan makes a great critique of a type of thinking called "nutrionism". Basically that the determinants of health can be broken down into their isolated sub-components. "You need X amount of protein, Y amount of this vitamin, and Z amount of this mineral." The problem is that unless our understanding of biology is perfect, there's almost certainly going to be flaws in the decomposition. When we try to replicate a healthy diet with a synthetic mixture of vitamins and macronutrients, we still fall well short of natural food. A very famous example of this is when people on total parenteral nutrition kept dying, because the original formulations lacked chromium. Humans only need a microscopic amount, yet die without it. Nobody realized this because almost all natural foods have trace amounts that satisfy the requirement.
As for vitamin D specifically, I think there's three pretty good candidates for what the missing X-factor is. In order from least to most controversial:
1) Our current understanding of the sub-types of Vitamin D is not complete. It wasn't too long ago that we began to learn that Vitamin D3 is much more essential than Vitamin D2. It's possible that there are sub-types of Vitamin D3 that are made in the correct proportion in the skin, but aren't represented in supplements.
2) There are other micronutrients, not yet discovered, that are synthesized in the skin. This goes back to the chromium example. Sun-exposed people may have high levels of Vitamin D + Vitamin X. Yet we can only measure the former, so we over-attribute the importance of Vitamin D.
3) Sun exposure induces the same physiological adaptations as physical exercise. Consider what we know about the mechanism of how exercise induces its health benefits. Micro-traumas to the muscle fibers and metabolic stress leads to an acute stress response. That peak leads to a down regulation of the HPA axis with accompanying metabolic benefits. The muscles recover, with an adaptation against the stress.
Is it not possible that something similar happens when we sunbathe? Without a doubt UV exposure induces micro-traumas in the skin cells, that looks very similar to what's found in the muscle cells. There's also emerging evidence that sun exposure triggers the HPA stress response[1], in the same way that exercise does.
If this is the case, then trying to replicate the benefits of sun exposure with supplements is a fool's errand. It's the sun exposure itself, specifically the sun damage, that is directly responsible for the health benefits.
One, even careful attempts to control confounders, still shows a substantial health benefit associated with higher sun exposure.[1] In other words, even among people with no discernible health conditions, the most sun exposed are healthier.
Two, randomized control trials show improvements in biomarkers like blood pressure[2] and lipid profile[3]. In animal experiments, intense UV exposure is directly linked to a reduction in obesity and metabolic disease.[4]
[1] https://pubmed.ncbi.nlm.nih.gov/24697969/ [2] https://www.sciencedaily.com/releases/2014/01/140117090139.h... [3] https://pubmed.ncbi.nlm.nih.gov/28553593/ [4] https://diabetes.diabetesjournals.org/content/63/11/3759
> As a measure of comorbid illness at the start of the study, we created a dummy variable ‘comorbidity’ identifying women who have been treated with antidiabetic [Anatomical Therapeutic Chemical Classification System (ATC) A:10] or anticoagulant (ATC B:01) drugs or medications for cardiovascular disease (ATC C:01–C:10) for more than 1 month.
This is extremely simple, hardly careful controlling. If anything it's a good example of bad science. Grabbed whatever was easily available in the database and claims they've adequately controlled for comorbidity while doing no such thing.
If you look at the difference in exercise, income, education and BMI there's a LOT going on between the two groups. You'd wish scientists would include the raw data and source code to easily calculate the adjustments yourself.
Just like they discovered using cannabinoids to treat seizures required the "full spectrum" of the plant to be the most effective, we are finding out the hard way that trying to isolate compounds to treat anything in a biological system is often the wrong approach.
It's been 20 years since "the only thing more effective is regular exercise" was a punchline on the Simpsons. It's disappointing that we are still prioritizing R&D for magic pills rather than getting fresh food and physical activity reintegrated into our lives.
"Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort" https://pubmed.ncbi.nlm.nih.gov/24697969/
I think there's some confounding factors in 'outdoorsy' people having other healthy lifestyle habits, but it also seems likely that there is some other mechanism, beneficial to human health, triggered by uv exposure.
Being in the sun (not excessively) feels incredible, at a very deep level. The same way eating a really healthy diet and exercising every day feels.
I frequently wonder: if I'm correct, what other things are like this? Fats are good for you, not carbs as they've said. That's one example that comes trivially to mind. But I'm convinced there is a ton of stuff we do because it's "good" when in really, the positives far outweigh the negatives.
/s #APillForEveryIll
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“For every complex problem there is an answer that is clear, simple, and wrong.” H. L. Mencken
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/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900470/
[3] https://tumj.tums.ac.ir/article-1-8272-en.html
[4] https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796...
As for my argument, I would never claim that Vitamin D is "a pretty useless vitamin". It is extremely useful, and is lifesaving for people with hypoparathyroidism. But that doesn't mean we should all be taking it. Note that the studies you mention are looking at treating something, not preventing something. Many of the people supplementing are doing it because they believe it will keep them healthy - and this does not appear to be the case. That is more the point of my article. The articles you cite are interesting and hopefully will produce larger trials.
I agree with much of your thinking - just not this particular conclusion.
1. As you mention, we know that low-to-moderate levels of vitamin D supplementation is safe.
2. We also know that a solid chunk of the population does not get enough sunlight / is vitamin D insufficient.
3. There are no large-scale trials yet for some items where vitamin D is suspected to have good effects. But there are a few nevertheless, which you share within the article itself - cancer, mortality, respiratory disease particularly stand out.
4. There are also a pile of smaller but promising, statistically significant, double-blinded, randomised controlled trials in a bunch of useful areas.
5. So this seems to be a Pascal's Wager type of situation, where supplementation is all upside and no downside, as long as people don't get crazy with it.
As you say it's not a panacea, and to cite an old comment, I am aware [1] that there are other benefits you get from sunlight. But even if it doesn't do as much as people think, I don't see why it is bad advice for most people to supplement vitamin D to keep themselves healthy!
Speaking solely as a layman, that study seems like it might be extremely relevant to the discussion here. But at the same time I don't have the background necessary to critique or dissect it.
HN Post on the study: https://news.ycombinator.com/item?id=24366006
TFA isn't saying that you don't need vitamin D, or that it can't be used to treat Ricketts or osteomalacia (which, like scurvy, are relatively rare conditions). It's simply saying that widespread supplementation on people who have normal levels or minor deficiencies isn't supported by the evidence.
> 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).
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.
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.
https://static.wixstatic.com/media/3e0600_a25ba8bbf26b47a096...
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"
Dai (2018): Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial 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...
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.
Humans being humans, I’m sure nose shape, eye color (just ask Bran Sanderson), hair color/texture, or something else would readily suffice in the absence of a perceptible difference in skin tone.
It's not so much about the race, but about the exploitation. Blacks and whites co-lived without racism for millenia, back when anybody could become a slave.
When around the 16th century the Europeans started to exploit latin americans, indians and blacks as slaves, they spread the various theories of racism to justify the practice (both the advance of christianity and englightenment meant that such a thing should now be justified, whereas in the ancient/pagan world just being more powerful was enough to justify making slaves of the less powerful, you didn't need an excuse).
So, if Europens where also blacks, the exploitation would just have found some other justification than skin color (kind of how Hitler didn't have much issue to discriminate against the also-white Jews).
Not really, Europeans alone are capable of the same level of mess, before and after slavery.
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...
It seems unlikely to be due to these factors since there's a gradient from black to white as you move away from the equator.
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.
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.
> 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.
They do work much better when all are taken together.
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.
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.
> 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.
It is a lot less effective when taken orally. This study doesn't mention this important distinction.
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.
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.
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).
Links:
https://play.google.com/store/apps/details?id=com.ontometric...
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).
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.
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.
(I'm not sure those are the vials I'm thinking about, I remember ones that were Vit E maybe of a very oily liquid that I had to take once - not bad, but definitely weird)
https://www.sciencedirect.com/science/article/pii/S096007602...
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/
BTW, I am also a lifelong sufferer of depression. SSRIs have never really done anything for me, but bupropion has been a lifesafer.
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.
Anyhow, I've googled and googled but still can't figure out why it's called a vitamin at all. The best I can come up with is that there IS an actual vitamin D that comes from the sun, but it helps the kidneys produces the good "hormone D" which is the what people are deficient in.
Can anyone shed some light on this? My description above could be a million miles off.
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.
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...
On the other hand, I already mentioned what happens with age.
I’m taking 400mg - 800mg magnesium daily, recently added K2 (100 mcg MK-4) together with 2000 or 3000 IU D3.
What would you change? Get my blood levels first and then increase D3?
Increase my magnesium supplementation? Don’t take calcium at all?
How did you find your own doses and what else are you supplementing?
Higher amounts of D3 aren't necessary, but there are therapeutic effects. The idea is to somewhat mimic hGH/IGF-1, DHEA, and melatonin of youth while lowering stress hormones.
As a male, ZMA is a good way to improve sleep and move closer toward meeting the magnesium requirements.
Maintain a lower/normal amount of D3, clear all nutrient/sleep deficiencies, and then start increasing 25(OH)D if necessary. D3 sometimes isn't even needed until older, unless trying for the therapeutic effects I mentioned.
Such a combo works even better with resistance training to stimulate bone.
I stated minimums for MK-4 and MK-7. I like the effects of higher amounts of MK-4. 5-10 mg.
I'm currently taking: 60,000 IU D3, 15 mg MK-4, 1.35g magnesium, and 2 Naturelo One Daily capsules (provides 240 mcg MK-7).
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...)
* 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.
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.
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.
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...
Do you have any additional information or findings about this?
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.
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.
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.
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.
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?
The article states several times that very low levels of vitamin D are not good.
Apparently, current levels of deficiency are not enough to lead to large problems.
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...
"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.
"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.
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.
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.
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
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.
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.
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.
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
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.
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.
https://peterattiamd.com/randomized-controlled-trials-when-t...
tl;dr Due to the study's flawed design, you can't claim there's no connection between depression and oral vitamin D3 supplementation.
ETA: This is probably sarcasm isn't it?