> 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.
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.
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.
"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.
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.
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.
We are more than just a pile of various materials.
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.
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.)
/s #APillForEveryIll
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“For every complex problem there is an answer that is clear, simple, and wrong.” H. L. Mencken