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?
I read (maybe here on HN comments) that Vitamin D could only be the indicator. People who live a certain lifestyle have low risk of the mentioned diseases AND have good Vitamin D levels. But you have to live that lifestyle, not just take supplements.
It might just be that the production of vitamin D via sunlight has other effects on the body, perhaps vitamin D has been a proxy for those effects but for obvious reasons taking it as a supplement doesn't trigger the same outcome.
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.
> It's unfortunate that exposure to UV is so harmful,
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.
There was an interesting study (sorry I don't like to lookup citations on my mobile) showing that the prognosis for skin cancer patients is better in the summer than the winter, presumably because they get more sunlight. Not causative, but interesting nonetheless.
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.
Nobody knows yet, but sunlight exposure causes the body to produce other things than Vitamin D, like nitric oxide (or similar correct me if I'm wrong here). It also affects circadian rhythms, so maybe people who get out more sleep better, maybe they are in better health from being more active, etc etc.
There are thousands of reasonable hypothesis, and it is extremely costly (and in some cases, nearly impossible) to test.
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.
The NO production might explain most of this through it's anti-inflammatory properties. The instant reduction in blood pressure is likely just the tip of the iceberg for UV's effects on the body.
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.
> 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.
The point is, you can’t just supplement everything and just eat starch and sit before the computer all day.
It’s a healthy balanced lifestyle that matters.
> 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.)
Perhaps sick people should be going outside more? There doesn't appear to be any reliable clinical evidence of better outcomes for respiratory disease patients who stay inside. Someone ought to run a clinical trial on that.
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.
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.
"It's not even necessarily the case that going outside is healthy, but that healthy people tend to go outside more."
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 guess you could frame being unwilling to go outside and/or exercise as a chronic illnesses in and of themselves, but otherwise I don't see how anyone would consider this plausible.
There is a fundamental difference between vitamin D generated in your skin versus vitamin D placed in your gut. The mechanisms by which it acts and the effects it has on you are probably radically different.
We are more than just a pile of various materials.
That is a reasonable hypothesis. Also, people who are very ill are less likely to get outside and get enough sun, so they will develop low Vitamin D. Vitamin D is likely a marker of poor health. (Once the Vitamin D gets low enough, we do see direct harmful effects from it (think rickets in children), and this may contribute to poor health at that point.)
I’m healthy, fit and relatively active (3-4 hours exercise / week, 30-1h walk everyday), and I just tested relatively low in Vitamin D (before winter even started). What should I do?
I’m not sure my doctor has access to better studies than what is in the TFA. My question is weirdly formulated, what I ask is is supplementation useless given what we know? Or is it safer to stay in the (arbitrary?) recommended range? What I get from the parent post is that given low vitamin D is a symptom of poor health, supplementation is useless if someone is in good health.
The thing with vitamin D supplementation is that, as TFA mentions, low to moderate doses (under 4000 IU per day) are generally very safe. And, being deficient in such a crucial nutrient certainly isn't a good thing. So, if you are deficient, supplementing in that range is probably something you could feel comfortable doing on your own. If it were me, I'd go out and buy a bottle of D3 and get my levels tested at my next checkup.
You must have some great doctors to ask questions like these to. In my experience there's nothing cutting edge about any answers I ever got from a doctor, and more often than not it's a predictable, nothing-to-see-here attitude. And I learned long ago to be cautious when I say something like, "I was reading about a study that suggested..." as you risk getting pinned with the loons at worst, and mostly ignored at best.
> 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.
Although that's what I originally learned it to mean -- from a horribly toxic online space -- some people use TFA to mean "The Featured Article" aka "the article under discussion."
And nice means "mean or small-minded", and silly means "saintly", and terrible means "inspiring terror". Or at least they used to -- but usage evolves over time past etymological roots.
"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.
You're still assuming that Vitamin D is involved in some interaction that itself is the cause of people being sick. Your reasoning is not allowing for the simpler possibility: sick people have less Vitamin D because sick people are too sick to go outside.
That's certainly a possibility, but we have two reasons to believe it's not true.
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]
The first study you linked looked at 29518 people and that's how they controlled for comorbid illnesses:
> 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.
Perhaps it's just more complicated than the prevailing paradigm of "have problem -> take drug -> problem go away." It could be that Vitamin D deficiency is itself a symptom of an array of underlying problems, or that it is one factor among many leading to a pathology, or that various levels of Vitamin D have various effects among different patients, or all of the above.
I think it's also that health has become a product, which is skewing all the solutions into things that are easy to market, package, and distribute. You probably need sunlight in addition to foods with other nutrients to optimize systems that regulate Vitamin D levels, whether it's just a marker or not.
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.
Sun exposure (and even tanning beds) produces vitamin D, but it also causes other changes in the human body. It appears sun exposure OR tanning bed use (!!!) reduces all cause mortality.
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.
It's a classic case of correlation does not imply causation. As implied in the article, people who are sick, stay indoors. So naturally, when they don't get enough sun from staying indoors, they also get lower levels of Vitamin D. And so that is the correlation. It doesn't mean that a lack of Vitamin D causes illness, or that taking Vitamin D supplements will magically cure those illnesses.
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.
> 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.
You would actually have to compare (dark skinned people in equatorial regions, light skinned people in places with less sunlight) to (light skinned people in equatorial regions) and optionally against (dark skinned people in places with less sunlight), with group A being the control, group B being expected to fare better, and group C expected to date worse.
With some exceptions, in general we're much likely to be indoors nowadays than say... 300 years ago, regardless of how much sunlight is available. But it is hypothesized that people of color see higher frequencies of epithelial related diseases (high blood pressure, heart disease) because we're mostly indoors nowadays and the shorter stints outside aren't long enough to absorb enough sunlight through darker skin. Epidemiologists have typically assumed this is due to socio-economic reasons, but even in affluent black communities, we're still seeing outsized incidences of these disease than in "lighter shade" communities.
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.
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.
The vitamin "misnomer" really confuses me. I don't think if it was called "hormone D" that people would be snaffling it up trying to self-medicate.
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.
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.
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...
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.
Use CRON-o-meter. Meet all RDAs with just a variety of whole quality foods, get more magnesium than phosphorus (and 1/3rd-1/2 as much as calcium), ensure alkaline PRAL score, and ensure sufficient quality sleep.
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).
For reference I take 5,000 IU daily, recommended by my doctor. We worked up to that amount over time, testing my Vit D levels until they made into the "normal" range. I live in a very sunny state and am outside in the sun at least an hour a day during peak daylight hours, sometimes much more. Many other members of my immediate family also have amazingly low Vit D levels despite plenty of outside time.
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."
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.
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?
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.
I installed an app a few months back called dminder that attempts to do exactly that. You pick your skin tone, it figures out your location, time of day, cloud cover and uses that to estimate the amount of vitamin D you can get based on the amount of time you're outside.
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.
> 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.
What's interesting is how strong the selection pressure seems to be to have melanin content adjusted to match the local conditions for sunlight. In the western hemisphere, where humans have only lived for ~20,000 years, there was already notable variations in pigmentation developing prior to 1500AD. That would make sense if vitamin D production is very important to health.
>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.
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).
I agree with the general conclusion about exploitation, but racist theories and justifications existed in different cultures long before the 16th century.
> 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?
> It does? What about genetic drift, random mutations, and artificial selection, where humans select based on qualities not necessarily conducive to survival?
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.
You could have responded to my post but instead you did this. Why?
There are more than two skin tone phenotypes. It's a gradient that gets lighter as you move away from areas of higher UV radiation to areas of lower UV radiation.
> You could have responded to my post but instead you did this. Why?
I responded to the part of your post that was the most important to me: that discussions like this head towards more scientific rigor the longer they go on.
> There are more than two skin tone phenotypes. It's a gradient that gets lighter as you move away from areas of higher UV radiation to areas of lower UV radiation.
Sure. And I'm not much interested in what "seems likely" in terms of what caused that. Lots of things that seem likely turn out to be wrong when it comes to causation.
If you want to look for scientific papers about the obvious correlation between melanin content and UV radiation then use google.
You should read Hume. He didn't think that casuation had anything to do with reason, but rather was a habit of the mind. You're not going to find any causal smoking gun here and you're really just blithely dismissing ideas that don't fit whatever vague, unacknowledged biases you have.
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.
> 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.
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.
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.
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/
BTW, I am also a lifelong sufferer of depression. SSRIs have never really done anything for me, but bupropion has been a lifesafer.
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.
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.
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.
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.
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.
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.
I didn't watch the whole video but I read the study. 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%). These are all areas that increase the risk of severe disease. 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.
This does not mean that I think Vitamin D has no effect. There is some evidence for Vitamin D in respiratory illnesses. But the effect is not as dramatic as some of the headlines for this study would imply.
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.
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
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?
Isn't a large fraction of the US an UK populations deficient in vitamin D? Doesn't deficiency mean that there's a benefit to supplementation? I thought that at least the correction of deficiency should have showed up in some study.
> 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?
"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.
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.
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.
> 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.
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"
> 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.
> 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.
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.
>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.
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.
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.
> 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.)
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.
> RCTs are high quality, because they are done in a controlled setting
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):
Those are anecdotes, the question is how often does it happen? Sure, it's possible, which is why we have reviews aggregating the findings of multiple studies.
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.
People who boost their vitamin D levels with supplements reduce their risk of respiratory tract infections, such as the flu, by up to 12%, according to a new systematic review and meta-analysis study of 25 randomized controlled trial (RCT) studies published in The BMJ.
400 IU is the RDA. On the other hand, the RDA assumes 20% will come from food and the other 80% from sunlight. That is, 2000 IU/day is actually what's expected from all sources. Enough to get 25(OH)D in range is the more generalizable rule.
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.
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.
217 comments
[ 3.7 ms ] story [ 181 ms ] threadIt'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.
[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398592/
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
--
“For every complex problem there is an answer that is clear, simple, and wrong.” H. L. Mencken
ETA: This is probably sarcasm isn't it?
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://news.ycombinator.com/item?id=24366006
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).
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.
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...
https://apps.apple.com/us/app/d-minder-pro/id547102495
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.
That's fairly far from any scientific method I would have confidence in.
There are more than two skin tone phenotypes. It's a gradient that gets lighter as you move away from areas of higher UV radiation to areas of lower UV radiation.
I responded to the part of your post that was the most important to me: that discussions like this head towards more scientific rigor the longer they go on.
> There are more than two skin tone phenotypes. It's a gradient that gets lighter as you move away from areas of higher UV radiation to areas of lower UV radiation.
Sure. And I'm not much interested in what "seems likely" in terms of what caused that. Lots of things that seem likely turn out to be wrong when it comes to causation.
You should read Hume. He didn't think that casuation had anything to do with reason, but rather was a habit of the mind. You're not going to find any causal smoking gun here and you're really just blithely dismissing ideas that don't fit whatever vague, unacknowledged biases you have.
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.
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.
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.
[1]https://www.youtube.com/watch?v=V8Ks9fUh2k8
https://www.sciencedirect.com/science/article/pii/S096007602...
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.
https://www.sciencedirect.com/science/article/pii/S096007602...
A larger trial would be even more conclusive.
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.
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.
[1] https://en.wikipedia.org/wiki/Light_skin#Evolution
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'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.
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.