> I’m not sure why they flip-flop between “lower doses are better” and “lower doses are the same”,
I am not a scientist and I don't read many studies, but it's weird to me how many times I read people like Scott talking about studies and see these sorts of incongruities in the text of the study.
My understanding regarding covid was more that there was a correlation between higher vitamin D levels and faring better with the virus, including long covid. Which leads to some experimentation with giving vitamin D as treatment, but really levels need to be up before then. Also, just anecdotally, my friends and I who have thyroid issues all have had lower vitamin D levels less than 30 ng/mL (which is what one study mentioned as a threshold back in 2020) and have all been advised by our doctors to take D3 w/K to supplement daily.
> If you want to go higher in that range, you can trade off a tiny mostly-theoretical risk of a very mild insufficiency for a tiny and mostly-theoretical risk of a very mild toxicity.
Is there any research about what that risk of toxicity could be? I assume that Hoffman is currently taking huge doses of vitamin D to match his assumptions about ancestral populations. Is there a specific reason to believe that he is in danger here (as opposed to generic "too much of anything can be dangerous" reasons)?
I was at 16 ng/ML 2 weeks ago. Started to supplement at 50K IU a week for 3 months, will check my blood again when done. Out of curiosity, if readers here were to make me a market for my Vit D level at the end of this period (even odds buy/sell levels), what would it be?
There is folklore that Vitamin D provides some benefit against the winter blues (SAD). A quick Google search has some sites which say the evidence is 'mixed' for this purpose but also that some studies claim Vitamin D increases levels of serotonin in the brain which something something helps with depression.
How credible should I find this theory? I've been taking Vitamin D supplements for years and anecdotally they seem to be helpful (weeks I don't take my supplements I generally feel worse - of course, this could be correlation not causation...), but it also seems quite likely I'm just a master placebomancer.
"because they confused correlation and causation (sicker people have less vitamin D)."
I think it's weird how little this kind of context is discussed in regards to Vitamin D. Shouldn't all Vit D studies be controlling for CRP or some other marker for inflammation? Also, what about the risk of arterial calcification if Vit K2 levels are too low? I think we could even give Vit K2 a lot of the credit for increasing bone strength currently given to vit D. As some have remarked, a piece of chalk will appear bright white if you're just looking at bone mineralization. But it's easy to break.
I admit to not having checked in on this topic in about a decade, but the calculations still just seem a little... acontextual.
Also, I've sometimes wondered, given that statin drugs reduce cholesterol and vitamin D is produced from cholesterol, what portion of the benefit of statin drugs is related to its reduction in vitamin D levels in individuals with chronic inflammation. Perhaps that's an errant thought, I admit, but I wonder.
> The nationwide average is about 27 mg/nl, but black people (whose dark skin blocks sunlight) are almost all insufficient and bring down the average; for whites, it’s about 30 ng/ml.
Are American blacks almost all at insufficient levels of vitamin D, or do they just require less of it?
> a typical model of “deficiency” (technically insufficiency, you’re not supposed to use the word “deficient” unless there are observable health consequences)
Wait, so we're *stipulating* that there are no negative effects, but we're calling them "insufficient" anyway, just for fun?
My memory is that the first time I thought vitamin D might be useful for covid was when I read articles pretty early on in the pandemic that claimed that African-Americans and South-Asian-Americans had the worst results in America, but Africans and South Asians were actually doing pretty well. There are other things that could explain this (mostly that countries near the equator are not logging all the data on deaths), but dark-skinned people in higher latitudes having the worst outcomes seems to fit the vitamin D story pretty well, and makes my prior higher than yours that vitamin D does something for Covid.
> Some people originally thought Vitamin D did all those things. They mostly thought this on the basis of studies, done at low doses, which found that it did. Those studies mostly found that it did because they confused correlation and causation (sicker people have less vitamin D). Then we did better studies (still at low doses) which found that none of those things were true after all, at least at the low doses which the studies investigated.
> If we then say “Yeah, but it could still be true at higher doses”, we’re missing the point. Now that our original reason for thinking it’s true is no longer valid, we should be back to our prior for any given random chemical, like hydroxymethylbilane.
Among other things, Andrew Gelman occasionally writes about the problem in science publishing of chronological non-independence. He points out that in reality, the truth is not affected by whether you do study A first and follow it up with study B, or whether you begin with study B and follow it up with study A.
The problem is that the norm in publishing is that someone does a low-quality, low-information study that is so bad that it can produce a spurious finding of statistical significance. (This is easier for bad studies to accomplish than it is for good ones. Incentives!) That study has a surprising, interesting, and "statistically significant" result, so it gets published. It is now Official Science, because it's published.
Someone else will then do a better study finding no significant effect. This is also easy to do, because the effect the first study found was an artifact of chance and low quality. And because the first study was published, the second one can be too. But nobody is willing to admit that the second study removes every reason to give any credence at all to the first study. The effect in the first study is real, by definition, because it's published. So the second study is always taken as refining the result, not as rejecting it. You can't reject an effect that is really there. Perhaps the effect is only present when the researcher's last name starts with P.
Gelman writes that this is ridiculous because -- among several other reasons -- if the studies had been done in reverse order, everyone would come to the opposite conclusion, rejecting the idea that the effect was real under any circumstances.
The attitude was that is an obvious thing to try, that it was easily and safely testable, and that it could help people. It looks like a civilizational failure that no one has tried it yet.
I think that the solution to the riddle is that most of the people trying to treat SAD are doctors and that doctors have justifiably strong priors against dramatically increasing the dosage of anything. "What if we tried more power?" is a refrain for scientists & engineers, not for doctors. Even the safest drug might do nasty things if used in high enough doses. Even water has an LD50.
The particular example of treating SAD with more light is distinct enough from the things that doctors build their intuitions on, that we shouldn't be surprised when they miss something.
> yes, this is the second scientist in this essay studying sun exposure with “Lux” in their name
Unrelated to Vitamin D, but related to light: One ought to do RCT on nominative determinism in general and light-related names in particular. During my Masters I read a seminal paper on light coming from black holes, by Jean-Pierre Luminet (https://en.wikipedia.org/wiki/Jean-Pierre_Luminet).
So, I might be overly emphasizing individual experiences, but I am trying to figure out how a modern urban/suburban office working human is getting anywhere enough sunlight to approximate ancestor sun exposure, even assuming damp little northern island ancestors who wore hats and bonnets a lot.
(I am also remembering time in Korea and other Asian countries, where middle class office working gals walked outside with a purse on their shoulder to keep their faces shaded, at least until they were married, as tans were seen as quite low class and not pretty. So maybe my perception of ancestor exposure is not entirely accurate.)
To me, assuming that diet replacement is sufficient is...assuming a lot? Even reading Scott I am not convinced otherwise.
Sitting in the morning sun on my east-facing balcony is my favorite source of vitamin D. It's best applied with dark coffee and a sativa/Indica blend. As I haven't got covid-36 yet, that makes the process postmodern-clinical proof the process cures cancer.
The reason for the persistent association of ill health and low vitamin D is most likely confounding. Deficient animal meat intake and low sunlight exposure are independently associated with unfavourable outcomes, and vitamin D mostly serves as a marker for both.
But since there is an anti-meat campaign (supported by all kinds of special interests) on the way, and an anti-sunlight campaign (supported by mostly the same special interests) as well, none of that will get rectified in the near future, so we can enjoy tedious debates such as this one, whether a boring bone hormone somehow will prevent you from dying.
The vitamin D supplementation bandwagon has been going on long enough, can we please put it to sleep?
I’d be interested in your views on this Medcram video. The argument it puts is that people with high vitamin D do better against Covid but that vitamin D doesn’t protect against Covid. That’s because the the thing that actually does protect against Covid is produced by the thing that produces vitamin D. That thing being sunlight. I think his hypothesis is melatonin but the take away for me was to make sure to get outside as often as you can which I already do! https://youtu.be/9eEyWlbToI4
I think a better way of expressing this idea is "circular locating the hypotheses".
There are countless chemicals and microelements that could, in theory, be supplemented with good results. The difficulty is primarily in focusing on the right ones - the actual checking is less bits of information than the focusing.
For various reasons we focused on Vitamin D. Probably because it really helps in a minority of cases, and also because we had a plausible story - less light exposure due to staying indoors and dressed. But once we focused on it, the checking is done and we didn't find anything.
What we're doing now is looking at the vast amount of possible chemicals and saying "hmm, that Vitamin D looks interesting, look at all that fuss around it. I wonder if it's good? Let's check". That's a feedback loop - more you check, more "interesting" it looks, regardless of actual results. The only way to break the loop is to look at the evidence, accept (or not, as the case may be) that it's been studied enough, and move on.
Having lived in the US and Europe, one thing that I noticed was how much less sunlight you get in Europe, at least seemingly. A huge fraction of the US population have ancestors who lived much further north. My ancestors came from the British Isles, Germany, and Scandinavia (AFAIK). Scotland is much further north than Indianapolis, where I group up. Indianapolis is level with Rome. It's quite plausible that, even while being inside for more hours, a person whose ancestors lived in northern europe would be exposed to roughly as much sunlight in a place like Indianapolis. When I moved from California to Moscow, Russia. So, when there, I supplemented with vitamin D for six months in winter. As an academic, at some point I went searching for high-quality RCTs which showed vitamin D supplements boosted immunity. I probably overlooked a bunch of studies, but at the time I couldn't really find anything too impressive. Nevertheless, b/c of the online hype, and total lack of sunlight in the northern European winter, I'd supplement with vitamin D daily. In summer I try to get outside for at least 30 minutes a day and be active.
I can see the attraction of vitamin D pills. Who doesn't want to believe in a magic pill that makes you healthier at almost no cost? To my reading, that "pill" is to get exercise, eat a balanced diet with vegetables, fruits, seafood and meat, and don't do things that interfere with your sleep schedule. Go light on alcohol and don't smoke. Do some kind of resistance training.
Maybe I'm wrong here though, and I should be supplementing with something.
Another question I had: is it obvious that taking a supplement pill would be the same as getting more sunlight? I don't understand the physiology at all. But it seems plausible to me that getting vitamin d from natural sunlight might do more than taking a vitamin d pill.
A related, but slightly different point is that it's healthier to be outside than in a tight, confined space, potentially inhaling viruses from other people. And it's also healthier to be active. Vitamin D can be a proxy for both of these things.
The other thing to talk about here is skin cancer. In Australia, which has a huge population of people whose ancestors lived in Britain, skin cancer is a huge problem.
In 1972 my physical anthropology prof flatly stated that darker skin selected against skin cancer and lighter against rickets—and that explains the relationship between skin color and distance from the equator—particularly in cloudy Europe. I don’t see rickets mentioned.
Maybe I'm a dopey layman, but didn't hunter-gatherers in temperate climates wear shirts? I'll go so far as to suggest that they didn't wear Abercrombie & Fitch [citation needed], but the things that live out in the sun, like flies, brambles, and pole cats, all can mess up your skin and introduce disease. That's not a modern realization.
"Surprisingly, average American levels seem about as high. The nationwide average is about 27 mg/nl, but black people (whose dark skin blocks sunlight) are almost all insufficient and bring down the average; for whites, it’s about 30 ng/ml. Why are these levels as high as some of the farmer-specific studies elsewhere? Maybe it’s Americans’ better nutrition - or maybe it’s that lots of Americans already take Vitamin D supplements. Canadians are close behind at 26 ng/ml; they fail to break this down by season but I’m guessing it was in the summer."
Because all of our milk is Vitamin D fortified, I strongly suspect it's the milk keeping most americans relatively high. On top of the reduced effect of sun, blacks are much more likely to be lactose intolerant. It would be interesting to see numbers separated by latitude and milk consumption.
I do wonder if the effects of vitamin D are secondary effects. If you have issues caused by D deficiency, fixing that allows your body to repurpose other resources towards other issues. Kind of like the anti-parasite drug that seemed to help against covid... in areas which had a higher prevalence of parasites.
Personally I take 10,000 IUs, and it seems to help both me, and everybody I have recommended it to.
However - I, and everybody I have recommended it to, also happen to be lactose intolerant office workers who get very little sunlight. Social bubbles, I guess? Dunno why lactose intolerance is so insanely common in my social bubbles, though.
Additionally, the observation pattern is not "This helps me", it's "It's not the vitamin D, I'm just having a better week than normal. Oh. It happened again. Oh god. Oh god I'm a bag of chemicals."
My guess would be that 10,000 IUs is too low to be directly harmful, while also being sufficiently high to quickly resolve long-term severe deficiencies in a timeframe short enough to be personally observable.
Given social bubbles, I don't think "General population who is at normal or slightly insufficient levels" is the correct reference class. Nor should vitamin D be considered a "normal" vitamin when considering deficiencies; the cluster of people who benefit from it are going to benefit from a significantly higher dosage than you'd expect looking at the average population.
Glad Scott mentioned obesity, because a lot of the discussion of Vitamin D I've seen omits what seems to be important differences in vitamin absorption in obese people. It's a harder topic to talk about due to PC, but IMO should be noted whenever statistics about what percentage of Americans are Vitamin D deficient are thrown around. People who at a healthy weight are at a lower risk of deficiency than the general population and should supplement less. (Although de facto, just as vaccinated people are more likely to wear masks, I expect that non-obese people are more likely to take Vitamin D.)
(Also—if you're supplementing D because you get outside very rarely, consider changing that?)
Having seen crippling adult asthma mostly cured through high dose Vitamin D, I will persist in believing that there is something besides calcium regulation going on.
As for what constitutes Paleo Vitamin D levels, look at some National Geographic magazines from a century ago. Many warm weather people wear considerably more clothes these days. Conversely, Americans wear considerably less than they did a century ago.
wow: as Biologist (me) instead of focusing on evolutionary "theory" and Vitamin D dosing it would be more appropriate to look up modern data which is available on our (humans) ability to metabolize and use Vitamin D on a daily basis. Vitamin K is in its own category because of its relationship to blood coagulation, so that should be medically evaluated. Vitamin C has many studies, along with Zinc which show that it does boost immune responses. People think that Vitamin dosing is a benign response but I have personally known people who had some bipolar issues and other symptoms who overdosed on Vitamins giving them diarrhea, cramps, etc. A lot of clinical data on modern daily doses of all Vitamins is available. Still a good article. :) lots of work too. more than what I would do :) have a great day! '-
Chemicals on the giant chart of metabolic pathways are kind of like religions. For any chemical with a large enough biological role, there is going to be some group of people exhibiting cult-like behavior, who are absolutely convinced that it is the One True Chemical that is the ultimate solution to all disease.
Frustratingly, some of these groups are probably correct, in the same way that on the day the world goes up in flames in a nuclear apocalypse, there is bound to be some conspiracy theorist somewhere in the world who predicted it correctly.
I do think that I'm sure I spend less time outside than my father (who grew up on a farm) and he was outside less than his father (lived on farm his entire life) and him less than every other ancestor before him (worked on farms using only horse power). In times before sunblock or sunglasses were invented.
Does this mean my vitamin D levels are lower than any ancestor? Is this why I'm so near-sighted?
"Hunter-gatherers in the environment where most of our evolution happened might have been outside all day shirtless. On average the sun's halfway from peak, so that might be equivalent to 8 hours of peak sunlight at the equator."
Okay, from the start I am going to dispute this. We've been told hunter-gatherers had this idyllic ancestral lifestyle where they got all their needs met in a few hours and had the rest of the day for leisure time. They weren't forced to be out toiling in the fields under the blazing sun for hours every day.
If they're walking around shirtless under the equatorial sun for eight hours a day, then they are stupider than lions:
"Lions are most active during dawn, dusk and periodically throughout the night. During daylight hours they can be found lounging or sleeping in the shade."
If our shirtless hunter-gatherer can't figure out "get under a bush, stay in the shade, don't move around too much, and drink water", then he has more problems going on than "boy, I must be generating *so* much Vitamin D right now!" can solve.
After all it's just mad dogs and Englishmen who go out in the mid-day sun:
me and everyone in my family is vitamin D deficient in the winter (dark skin + live in UK), and the main complaint we had that got fixed by taking vitamin D was extreme fatigue. We went to the doctor about tiredness, got blood tests and then got given the 20,000 IU or 50,000IU pills. At no point did anything about bones come up when discussing it with the doctor for me (can't speak about everyone else).
So many paragraphs on D without hitting the most important points. You hold up the IOM (now renamed the NAM) as more prestigious than the Endocrine Society despite their statistical mistake and the fact that the Endocrine society has 18,000 members (in "medicine, molecular and cellular biology, biochemistry, physiology, genetics, immunology, education, industry, and allied health" according to Wikipedia). Okay. The IOM's own minimum serum level recommendation for 25(OH)D is 20ng/ml. This is also the target min set by the European Food Safety Authority, Germany, Austria, Switzerland, Nordic Countries, Australia, & New Zealand. It was also the consensus rec of 11 international orgs (see https://academic.oup.com/jcem/article/101/2/394/2810292?login=false). Despite this consensus roughly 50% of humans globally do not achieve this level. Calculations & citations for the 3-4 papers involved can be found at: https://twitter.com/KarlPfleger/status/1390775110257102848 (I welcome corrections). Why don't you see this as a big problem? Even if only for global bone health. For the Endocrine Society's recommended 30ng/ml minimum, roughly 3/4 of people globally are too low. Note also that this higher 30ng/ml is the level at which typical blood tests from Quest or LabCorp in the US are flagged as low. What governments are making concerted efforts to drive down these deficiency rates? 25(OH)D tests are inexpensive & widely available. The normal standard is that RDAs are set so that 2.5% or fewer people are deficient. The US estimates typically come in at 25-35% or sometimes 40% at the 20ng/ml level. That's 10x the deficiency prevalence max target. What US government agency is responsible for reducing these deficiency numbers?
You both downplay the importance of the observational studies too much. Much of science and many important clinical medical decisions are & should be based on observed correlations together with understanding of the basic underlying science (physics/chemistry/biology). Astronomy and other scientific fields make progress without the use of any RCTs. Seatbelts, parachutes, and smoking warnings on cigarettes are all justified without recourse to RCTs.
But now let's talk about Covid risk factors. Age, obesity/overweight, and comorbidities like diabetes are established Covid risk factors that no one questions. All of these are based exclusively on observational data. No RCTs are part of establishing these as legitimate risk factors. Vitamin D status, ie 25(OH)D, is also unquestionably at this point a statistically significant risk factor for Covid. 75+ studies with aggregate ~2M subjects. Multiple meta-analyses. Narrow confidence intervals. And effect size of 1.5-2x different risk, mostly based on the 30ng/ml threshold or the 20ng/ml threshold. (See https://twitter.com/KarlPfleger/status/1486565564671692804 for citations.) This is not just important for hypothesis generation for therapeutic potential, it's also important for stratifying the absolute risk level for groups or individuals which is how one clinical computes Number Needed to Treat (NNT) for helping to decide on relative benefit vs risk of potential interventions, such as vaccination or use of anti-viral drugs.
Meantime, no evidence suggests that being vitamin D deficient is protective for Covid. And known immune biology suggests multiple clear mechanisms of action by which D should be protective. (See eg https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbm4.10405 but more mechanism papers in the previously linked Twitter thread). So, that leaves a pretty clear-cut benefit vs risk analysis:
If governments / public health officials emphasize reducing deficiency for pandemic control & end up being wrong about D helping Covid, the biggest side-effect would be reduction in the huge prevalence of deficiency (see other comment I just made here), w/ consequent improvements in population wide bone health, and probably autoimmune health, & resistance to other ARIs.
Or conversely, if officials recommend a concerted effort to reduce deficiency for the non-Covid benefits, reduced Covid transmission, hospital burden, & deaths are all plausible side effects even if not guaranteed. But a worse pandemic is not. I find your overall stance puzzling given the apparent imbalance when viewing things this way.
Lastly, (this is the 3rd of 3 top level comments I'm making here) let's talk about scientific hypotheses and the proper ways to test them. The massive observational data showing correlation between 25(OH)D and increased Covid risk suggests more than anything else a specific form of clinical intervention: Give deficient people vitamin D until they have enough (eg for example those starting at <20ng/ml until they have >= 30ng/ml). This is in fact exactly the form of intervention long advocated by vitamin D researchers such as Heaney: https://academic.oup.com/nutritionreviews/article/72/1/48/1933554 and Grant et al: https://www.sciencedirect.com/science/article/abs/pii/S0960076017302236?via%3Dihub
The intervention give a fixed amount of D to people for whom one hasn't tested baseline D levels, or the intervention to give a fixed amount to people after testing their levels but without testing to see that they have achieved sufficient levels before beginning to record adverse event differences vs control are not correct forms of study design to properly test the main hypothesis. And in fact these problems are the main reasons why many vitamin D RCTs fail. See for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487184/
Given the massive observational data, the many clear mechanisms of action, and the fact that no pharma company will fund a study of an inexpensive supplement, it is puzzling that governments have not adequately funded a properly designed study to test the hypothesis properly. To this day there is no RCT testing the use of the intervention raise 25(OH)D from 20 to 30ng/ml powered to adequately rule of the hypothesis that it would reduce severe Covid outcomes like death & ICU, yet people (including this piece) keep (inappropriately in my opinion) casting doubt on that hypothesis despite compelling biology.
The observational data is solid. It doesn't prove causality, but it's suggestive of such a strong potential benefit, that it should be someone's responsibility to disprove the causality by finding the confounding shared causal variable that fully explains the causation. Until then it's reasonable to apply precautionary principle and try to ensure people are not deficient.
I remember reading an article back in the 1990s or early 2000s in Natural History (AMNH's member magazine) about vitamin D and folic acid. It pointed out that increased sunlight raises vitamin D levels but lowers folic acid levels, so there is a tradeoff between getting enough of each. This suggests that there is probably a limit on how much D a person can acquire from sun exposure without running into a folic acid shortage.
(The authors also argued that this accounts for women having slightly lighter skin than men as a result of their having a different balance point for the two chemicals. Is this even true? I have no idea. I can think of dozens of confounding factors, but that's a discussion for another time and place.)
Is it that hard to believe that Vitamin D is a boring bone and immune system chemical, as opposed to just a boring bone chemical?
The idea that it can "treat COVID, prevent cancer, prevent cardiovascular disease, and lower all-cause mortality" sounds ridiculous when described like that, largely because it implies that those are all separate things that Vitamin D just happens to fix. But really, it's all one simple (and thus not especially unlikely) effect: It improves the immune system's functioning, and anything that improves the immune system's functioning is going to make the body more capable of dealing with illnesses in general, including COVID, cancer, and probably some forms of heart disease (specifically, whichever types are caused by pathogens). Obviously it's not a miracle cure for any of those things - it's not guaranteed to prevent you from getting them, nor to make them go away once you have them. But it can make your body a little better at dealing with them.
> Our priors on a random chemical doing that have to be less than 1%, or we get caught in weird logical traps.
Maybe not all of those at once, but what are the chances that a chemical does any one of those? If it's less than 5%, then that means that, given some random chemical passes a well-done controlled randomized trial, it probably doesn't work.
On the importance of vitamin D: we dropped our skin pigmentation on our way out of Afrika in evolutionary record time, whatever the reason was it apparently changed either mortality or reproduction success dramatically. And it's not unreasonable to assume that this is vitamin D, or that vitamin D plays an important role in it. Not sure how this can be proven though, its just a hypothesis.
Regarding the minimal/optimal levels: i know the Hadza studies, but there are much more .. I remember a few from India and Italy that look at people working outside, with less or little clothing like farmers, construction workers, and they all come out at levels between 40 and 60ng/ml as the "normal/optimal" range. But of course there are plenty of studies pointing in the other direction considering 40ng/ml as way to high, the official recommendation here in germany was for ages "nobody needs any supplements, including vitamin d, you get all you need from a balanced diet!". Exception of the rule: babies in their first year get 400IU here because this dramatically lowers chances of rickets.
And this is the point which made me overthink my position a few years ago: the body of a pregnant or nursing mother makes sure the embryo/baby gets everything it needs, all the stores of the female body are depleted, if necessary even more. Except for vitamin D, which is often minimal in human milk. Unless, and this has been tested clinically, the vitamin d in the mother reaches around 40ng/ml 25(OH)D or above, then the milk contains enough vitamin, no supplementation necessary.
There were several studies looking at this, small/medium RCTs if i remember correctly, with supplementation in the range of 4000-6500IU daily, and beside the milk issue they found effects like 20% lower probability of birth complications and other things improving. I really should dig out these studies again .. I haven't bookmarked them.
The only one that made it into my "google keep" is this one: "New insights into the vitamin D requirements during pregnancy" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573964 which is an overview of the state of things during pregnancy, with over 140 references
PS: bear with me, english is not my first language ;-)
Adding more anecdotal evidence to the pile: I have fibromyalgia and have been dealing with flareups for approximately my whole life, without knowing what they were (I wasn't certain I was chronically ill until 2020). My worst episode was in mid-2019, where for nearly three months I was so fatigued that there was a noticeable drop in my work quality, and I had to start working from home because I couldn't make the ten minute walk to the train station. I was essentially bed-ridden for part of the time, and I had at least one day where I couldn't reliably speak or focus my eyes.
Doctors did a full blood panel, and the only unusual thing they found was that my vitamin D was at 24.8 ng/mL, considered insufficient but not deficient. I started taking 10,000 IU daily, and the months-long episode cleared up within a week or two. I've been taking 5,000 IU daily for the past two years and my rate of flareups — which previously happened every couple months, unpredictably — has dropped to basically zero. I also talked to a fibromyalgia specialist (who was maybe a bit of a quack, but ¯\_(ツ)_/¯) who said she recommends all her patients take 5,000-10,000 IU daily — not that I trust much of anything she said, but it did feel like it backed up the idea that I was not totally crazy to think that supplementing vitamin D was helping.
My current hypothesis or story of Vitamin D is this in short: Vitamin D helps controlling and adapting our metabolismisms to summer / winter cycles. Nearly every cell in our bodies has receptors for Vitamin D.
The farer a region is from the equator the less sun and energy reaches the ground during the winter and the less food is available for animals in the end. Therefore the evolution invented hybernation. This is a special 'low activity low power consumption mode which helps to survive hard, long Winters without food. In autumn many animals prepare for the coming winter by eating es much as they can and store a lot of additional energy as fat in their bodies. This fat is then slowly converted into energy during winter while many of these animals just sleep most of the time. Research about hybernation seems pretty new. Only recently researchers found hybernation mechanisms in animals which were not known for that. Mongolian wild horses which move way less and reduce their body temperature for example.
If I look at all the random facts I learned the past 20 years I see a pattern: I have more apatite in dark times, I get fat in autumn and winter, I eat less in Summer, I'm depressed when it's darker, I'm happy when it's light, in winter I move way less compared to summer, Vitamin D, SSRI, Serotonine, Melatonine, sleep, and mood/motivation/missing motivation are related to each other asf
Not sure , where I heard first about the Hybernation-Hypothesis first but I cannot un-learn it anymore.
TL;DR
If I look at all those strange things happening with my body though the 'Evolution-Hybernation-Lens' it seems to make a lot more sense for me.
Our son has celiac disease and has blood tests every 6 months. Just for fun, the gastro doctor said to throw in some extra tests last time around including Vitamin D. It came out very low. We were mortified, and pledged to start supplementing straight away. She told us we could supplement if we wanted, because it's practically free after all, but that every single child she had ever tested came out low, often even lower, and it was nothing to really worry about (incidentally, while our son's symptoms are pretty out there, she has seen it all, including paralysis, fits, and psychosis as a result of celiac).
Anyway, our son has a whole suite of symptoms that occur every time he has a a 'glutening' caused by putting his fingers in his mouth after touching a crumb on the bus, or the like. You can set your watch to it. This happens roughly every three weeks and while they are not life-threatening they are sufficiently serious - both physically and mentally - that we have organised our life for years around minimising them.
Two weeks after we started supplementing, a glutening occurred. All the same symptoms, but much milder. A month later, even milder. A month later, even milder. So mild that, if we weren't so attuned to them, we wouldn't even notice them as part of a pattern. After years of fending off doctors and teachers telling us he needed Ritalin - and making faces at each other when we said his mood swings and hyperactivity were a side-effect of exposure to gluten - we found the cure. Our family doctor - who by the standards of the profession is actually pretty good - made a vague effort to feign interest before telling us not to rule out Ritalin.
A general programme of promoting vitamin D supplementation would, at the bare minimum, save tens of thousands of children from dangerous medication and essentially abusive treatment regimens for hyperactivity. All for perhaps 0.00000000000000001% of the costs of Covid policy. Whatever the actual mechanisms involved (and I lean to a Eugyppius-Yarvin type model rather than the Alex Jones version), the medical industry is functionally a criminal entity. Analyses like this one that don't rest on an understanding of the fundamentally criminal nature of the medical industry in selecting and interpreting data are literally worse than useless.
Scott writes of his priors. Mine—however anecdotal—are as follows:
About a decade ago, having moved about a decade previous to that from southern Ontario to southern England, I had a very bad winter health-wise: instead of a handful of colds and perhaps one illness bad enough to raise a fever, I had four or five bouts of illness with fever and in between I would never fully recover, remaining congested with a persistent cough.
In the decade preceding that winter I had tried taking vitamin C supplements for immune health but had stopped because they did not have any discernible effect, but around this time I read a popular press article written by a prison doctor (probably here, though URL is defunct not archived by archive.org: https://www.medicalnewstoday.com/articles/51913) who had noted that vitamin D supplementation had dramatically improved the health of the prisoners in his care, so, living in northern Europe and spending most of my time indoors (and despite being quite fair-skinned) I figured it was worth a try.
For the next two winters I took around 2000 IU of vitamin D3 every day, and had nary a sniffle. Unfortunately, however it was difficult at the time to get even modestly-high-dose vitamin D tablets in the UK (the RDI here at the time was something laughable like 40 IU/day) and eventually my imported supply ran out, so the folowing winter I took none and was terribly sickly again—perhaps not as bad as that first terrible winter, but much worse than I had been the two intervening years.
Since then I have managed to keep myself supplied and have resumed enjoying generally good winter health. Perhaps it's just the placebo effect—though a placebo which proved highly effective against COVID too, as it happens—but good enough to be in the "definitely worth it" category for me.
As the Luxwolda 2012 paper shows, the semi-nomadic pastoral Maasai tribe have a mean average level of 48 ng/ml, with the largest subset of the group (40%) having a level between 48 and 60 ng/ml, and the third largest subset (~12%) having even higher levels between 60 and 70 ng/ml. Even including the hunter-gatherer Hadzabe tribe, the largest subset is still the 48-60 ng/ml group at 33.3%. So the median (which is a more representative value of the norm than the average) will be in this range, higher than the 44 ng/ml mean level stated in this blog post, and so higher vitamin D intake will be required to reach the median value.
Vitamin d seems to have some immunomodulatory effect that is beneficial for some autoimmune conditions like the ulcerative colitis I've lived with for the past 15 years. Plus some meta-analysis said it reduced colorectal cancer risk by half and calcium absorption in the colon is plausibly related to that. If it were just "sick people go outside less" there wouldn't be a big signal for colon cancer in particular. On the downside, chronically high but non-toxic levels of vitamin D might accelerate the calcification of the pineal gland, causing melatonin deficiency, causing poor sleep, causing a variety of other health problems. I basically can't sleep well without completely blacking out all sources of light -- streetlights through blinds are way too much light for me.
If the etiology of death by covid is mostly the immune system overreacting and attacking the lungs, and we have other evidence of vitamin D being helpful in autoimmune conditions, our prior for vitamin D benefitting covid patients should not be that low. Dexamethasone reduced covid mortality by half just by blunting the immune system's overreaction against the lungs. Vitamin D is probably not as potent as dexamethasone but more study is warranted. My prior on any sort of antinflammatory or immunomodulatory benefitting covid is at least an OOM higher than my prior on dart-chemicals benefitting covid.
Some studies have supported much higher Vitamin D blood concentrations:
83.4 nmol/L : Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium, by Gaksch, et al., PLOS ONE | DOI:10.1371/journal.pone.0170791 February 16, 2017
> 50 nmol/L: Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study, by Gao et al. Clinical Epigenetics (2018) 10:84 https://doi.org/10.1186/s13148-018-0515-y
~35 nmol/L: Evidence for a U-Shaped Relationship Between Prehospital Vitamin D Status and Mortality: A Cohort Study, by Sadeq et al., J Clin Endocrinol Metab, April 2014, 99(4):1461–1469, doi: 10.1210/jc.2013-3481
77.5 nmol/L: Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies, by Zittermann, et al., Am J Clin Nutr 2012;95:91–100 doi: 10.3945/ajcn.111.014779
75 nmol/L: Commentary: Additional strong evidence that optimal serum 25- hydroxyvitamin D levels are at least 75 nmol/l, by WB Grant, International Journal of Epidemiology 2011;40:1005–1007
and finally the big kahuna of them all:
110 nmol/L: An estimate of the global reduction in mortality rates through doubling
vitamin D levels, by WB Grant, et al., European Journal of Clinical Nutrition (2011) 65, 1016–1026
But wait! There's more! Namely, magnesium!
Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III, by Deng et al., BMC Medicine 2013 11:187. doi:10.1186/1741-7015-11-187
Finally, rather than being a boring bone chemical, there have been some studies on the relationship between Vitamin D levels and Depression:
Vitamin D deficiency and depression in adults: systematic review and meta-analysis, by Anglin et al., The British Journal of Psychiatry (2013) 202, 100–107. doi: 10.1192/bjp.bp.111.106666
"One case–control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23–0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0–1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40–3.49)."
Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial, by Sepehrmanesh et al., The Journal of Nutrition November 25, 2015; doi:10.3945/jn.115.218883.
" Baseline concentrations of mean serum 25-hydroxyvitamin D were significantly different between the 2 groups (9.2 6 6.0 and 13.6 6 7.9 mg/L in the placebo and control groups, respectively, P = 0.02). After 8 wk of intervention, changes in serum 25-hydroxyvitamin D concentrations were significantly greater in the vitamin D group (+20.4 mg/L) than in the placebo group (20.9 mg/L, P < 0.001). A trend toward a greater decrease in the BDI was observed in the vitamin D group than in the placebo group (28.0 and 23.3, respectively, P = 0.06). Changes in serum insulin (23.6 compared with +2.9 mIU/mL, P = 0.02), estimated homeostasis model assessment of insulin resistance (21.0 compared with +0.6, P = 0.01), estimated homeostasis model assessment of b cell function (213.9 compared with +10.3, P = 0.03), plasma total antioxidant capacity (+63.1 compared with 223.4 mmol/L, P = 0.04), and glutathione (+170 compared with 2213 mmol/L, P = 0.04) in the vitamin D group were significantly different from those in the placebo group"
If I recall correctly, there were pretty robust metanalyses showing that Vitamin D supplementation helped recovery from respiratory infections long before COVID. Not cure-all good, but still meaningfully good.
> I’m not sure why they flip-flop between “lower doses are better” and “lower doses are the same”,
I am not a scientist and I don't read many studies, but it's weird to me how many times I read people like Scott talking about studies and see these sorts of incongruities in the text of the study.
My understanding regarding covid was more that there was a correlation between higher vitamin D levels and faring better with the virus, including long covid. Which leads to some experimentation with giving vitamin D as treatment, but really levels need to be up before then. Also, just anecdotally, my friends and I who have thyroid issues all have had lower vitamin D levels less than 30 ng/mL (which is what one study mentioned as a threshold back in 2020) and have all been advised by our doctors to take D3 w/K to supplement daily.
> If you want to go higher in that range, you can trade off a tiny mostly-theoretical risk of a very mild insufficiency for a tiny and mostly-theoretical risk of a very mild toxicity.
Is there any research about what that risk of toxicity could be? I assume that Hoffman is currently taking huge doses of vitamin D to match his assumptions about ancestral populations. Is there a specific reason to believe that he is in danger here (as opposed to generic "too much of anything can be dangerous" reasons)?
I think the statement that vitamin D is "a boring bone-related chemical" can be easily dismissed.
A recent high quality study on 25000 people found it is effective for autoimmune disease: https://www.bmj.com/content/376/bmj-2021-066452
As for COVID, we already discussed it enough, but worth mentioning there's a new study showing strong results (RR 0.23): https://www.sciencedirect.com/science/article/pii/S0188440922000455?via%3Dihub
This article inspired me to take a Vitamin D pill (1000 IU).
I was at 16 ng/ML 2 weeks ago. Started to supplement at 50K IU a week for 3 months, will check my blood again when done. Out of curiosity, if readers here were to make me a market for my Vit D level at the end of this period (even odds buy/sell levels), what would it be?
This changed my mind -- I had agreed with Ben for the last year, and I now I agree with you instead.
There is folklore that Vitamin D provides some benefit against the winter blues (SAD). A quick Google search has some sites which say the evidence is 'mixed' for this purpose but also that some studies claim Vitamin D increases levels of serotonin in the brain which something something helps with depression.
How credible should I find this theory? I've been taking Vitamin D supplements for years and anecdotally they seem to be helpful (weeks I don't take my supplements I generally feel worse - of course, this could be correlation not causation...), but it also seems quite likely I'm just a master placebomancer.
Characterizing vitamin D as a boring bone related vitamin is a little weird to me. I'd considered it more of a testosterone precursor; this RCT
https://pubmed.ncbi.nlm.nih.gov/21154195/
Found substantial increases in t levels after a year of supplementation.
In any case it's cheap and not likely to be toxic. Gonna keep taking my Pascal's wager in the form of my 4000 IU/d.
Everyone needs to learn more about hepatic metabolism
"because they confused correlation and causation (sicker people have less vitamin D)."
I think it's weird how little this kind of context is discussed in regards to Vitamin D. Shouldn't all Vit D studies be controlling for CRP or some other marker for inflammation? Also, what about the risk of arterial calcification if Vit K2 levels are too low? I think we could even give Vit K2 a lot of the credit for increasing bone strength currently given to vit D. As some have remarked, a piece of chalk will appear bright white if you're just looking at bone mineralization. But it's easy to break.
I admit to not having checked in on this topic in about a decade, but the calculations still just seem a little... acontextual.
Also, I've sometimes wondered, given that statin drugs reduce cholesterol and vitamin D is produced from cholesterol, what portion of the benefit of statin drugs is related to its reduction in vitamin D levels in individuals with chronic inflammation. Perhaps that's an errant thought, I admit, but I wonder.
> The nationwide average is about 27 mg/nl, but black people (whose dark skin blocks sunlight) are almost all insufficient and bring down the average; for whites, it’s about 30 ng/ml.
Are American blacks almost all at insufficient levels of vitamin D, or do they just require less of it?
> a typical model of “deficiency” (technically insufficiency, you’re not supposed to use the word “deficient” unless there are observable health consequences)
Wait, so we're *stipulating* that there are no negative effects, but we're calling them "insufficient" anyway, just for fun?
If you'd like to know way more, and probably too much, about vitamin D, this series is good: https://www.devaboone.com/post/vitamin-d-part-1-back-to-basics
My memory is that the first time I thought vitamin D might be useful for covid was when I read articles pretty early on in the pandemic that claimed that African-Americans and South-Asian-Americans had the worst results in America, but Africans and South Asians were actually doing pretty well. There are other things that could explain this (mostly that countries near the equator are not logging all the data on deaths), but dark-skinned people in higher latitudes having the worst outcomes seems to fit the vitamin D story pretty well, and makes my prior higher than yours that vitamin D does something for Covid.
> Some people originally thought Vitamin D did all those things. They mostly thought this on the basis of studies, done at low doses, which found that it did. Those studies mostly found that it did because they confused correlation and causation (sicker people have less vitamin D). Then we did better studies (still at low doses) which found that none of those things were true after all, at least at the low doses which the studies investigated.
> If we then say “Yeah, but it could still be true at higher doses”, we’re missing the point. Now that our original reason for thinking it’s true is no longer valid, we should be back to our prior for any given random chemical, like hydroxymethylbilane.
Among other things, Andrew Gelman occasionally writes about the problem in science publishing of chronological non-independence. He points out that in reality, the truth is not affected by whether you do study A first and follow it up with study B, or whether you begin with study B and follow it up with study A.
The problem is that the norm in publishing is that someone does a low-quality, low-information study that is so bad that it can produce a spurious finding of statistical significance. (This is easier for bad studies to accomplish than it is for good ones. Incentives!) That study has a surprising, interesting, and "statistically significant" result, so it gets published. It is now Official Science, because it's published.
Someone else will then do a better study finding no significant effect. This is also easy to do, because the effect the first study found was an artifact of chance and low quality. And because the first study was published, the second one can be too. But nobody is willing to admit that the second study removes every reason to give any credence at all to the first study. The effect in the first study is real, by definition, because it's published. So the second study is always taken as refining the result, not as rejecting it. You can't reject an effect that is really there. Perhaps the effect is only present when the researcher's last name starts with P.
Gelman writes that this is ridiculous because -- among several other reasons -- if the studies had been done in reverse order, everyone would come to the opposite conclusion, rejecting the idea that the effect was real under any circumstances.
I'm reminded of one of the early rationalist efforts involving using more light to treat seasonal affective disorder (SAD): https://www.medrxiv.org/content/10.1101/2021.10.29.21265530v1
The attitude was that is an obvious thing to try, that it was easily and safely testable, and that it could help people. It looks like a civilizational failure that no one has tried it yet.
I think that the solution to the riddle is that most of the people trying to treat SAD are doctors and that doctors have justifiably strong priors against dramatically increasing the dosage of anything. "What if we tried more power?" is a refrain for scientists & engineers, not for doctors. Even the safest drug might do nasty things if used in high enough doses. Even water has an LD50.
The particular example of treating SAD with more light is distinct enough from the things that doctors build their intuitions on, that we shouldn't be surprised when they miss something.
> yes, this is the second scientist in this essay studying sun exposure with “Lux” in their name
Unrelated to Vitamin D, but related to light: One ought to do RCT on nominative determinism in general and light-related names in particular. During my Masters I read a seminal paper on light coming from black holes, by Jean-Pierre Luminet (https://en.wikipedia.org/wiki/Jean-Pierre_Luminet).
So, I might be overly emphasizing individual experiences, but I am trying to figure out how a modern urban/suburban office working human is getting anywhere enough sunlight to approximate ancestor sun exposure, even assuming damp little northern island ancestors who wore hats and bonnets a lot.
(I am also remembering time in Korea and other Asian countries, where middle class office working gals walked outside with a purse on their shoulder to keep their faces shaded, at least until they were married, as tans were seen as quite low class and not pretty. So maybe my perception of ancestor exposure is not entirely accurate.)
To me, assuming that diet replacement is sufficient is...assuming a lot? Even reading Scott I am not convinced otherwise.
Sitting in the morning sun on my east-facing balcony is my favorite source of vitamin D. It's best applied with dark coffee and a sativa/Indica blend. As I haven't got covid-36 yet, that makes the process postmodern-clinical proof the process cures cancer.
The reason for the persistent association of ill health and low vitamin D is most likely confounding. Deficient animal meat intake and low sunlight exposure are independently associated with unfavourable outcomes, and vitamin D mostly serves as a marker for both.
But since there is an anti-meat campaign (supported by all kinds of special interests) on the way, and an anti-sunlight campaign (supported by mostly the same special interests) as well, none of that will get rectified in the near future, so we can enjoy tedious debates such as this one, whether a boring bone hormone somehow will prevent you from dying.
The vitamin D supplementation bandwagon has been going on long enough, can we please put it to sleep?
I’d be interested in your views on this Medcram video. The argument it puts is that people with high vitamin D do better against Covid but that vitamin D doesn’t protect against Covid. That’s because the the thing that actually does protect against Covid is produced by the thing that produces vitamin D. That thing being sunlight. I think his hypothesis is melatonin but the take away for me was to make sure to get outside as often as you can which I already do! https://youtu.be/9eEyWlbToI4
Whenever I read anything like this, I just come away thinking it's a miracle we know anything. Apparently medicine is real hard.
There’s a bracket that shouldn’t be there at the end of the unit conversion paragraph I think
I think a better way of expressing this idea is "circular locating the hypotheses".
There are countless chemicals and microelements that could, in theory, be supplemented with good results. The difficulty is primarily in focusing on the right ones - the actual checking is less bits of information than the focusing.
For various reasons we focused on Vitamin D. Probably because it really helps in a minority of cases, and also because we had a plausible story - less light exposure due to staying indoors and dressed. But once we focused on it, the checking is done and we didn't find anything.
What we're doing now is looking at the vast amount of possible chemicals and saying "hmm, that Vitamin D looks interesting, look at all that fuss around it. I wonder if it's good? Let's check". That's a feedback loop - more you check, more "interesting" it looks, regardless of actual results. The only way to break the loop is to look at the evidence, accept (or not, as the case may be) that it's been studied enough, and move on.
Having lived in the US and Europe, one thing that I noticed was how much less sunlight you get in Europe, at least seemingly. A huge fraction of the US population have ancestors who lived much further north. My ancestors came from the British Isles, Germany, and Scandinavia (AFAIK). Scotland is much further north than Indianapolis, where I group up. Indianapolis is level with Rome. It's quite plausible that, even while being inside for more hours, a person whose ancestors lived in northern europe would be exposed to roughly as much sunlight in a place like Indianapolis. When I moved from California to Moscow, Russia. So, when there, I supplemented with vitamin D for six months in winter. As an academic, at some point I went searching for high-quality RCTs which showed vitamin D supplements boosted immunity. I probably overlooked a bunch of studies, but at the time I couldn't really find anything too impressive. Nevertheless, b/c of the online hype, and total lack of sunlight in the northern European winter, I'd supplement with vitamin D daily. In summer I try to get outside for at least 30 minutes a day and be active.
I can see the attraction of vitamin D pills. Who doesn't want to believe in a magic pill that makes you healthier at almost no cost? To my reading, that "pill" is to get exercise, eat a balanced diet with vegetables, fruits, seafood and meat, and don't do things that interfere with your sleep schedule. Go light on alcohol and don't smoke. Do some kind of resistance training.
Maybe I'm wrong here though, and I should be supplementing with something.
Another question I had: is it obvious that taking a supplement pill would be the same as getting more sunlight? I don't understand the physiology at all. But it seems plausible to me that getting vitamin d from natural sunlight might do more than taking a vitamin d pill.
A related, but slightly different point is that it's healthier to be outside than in a tight, confined space, potentially inhaling viruses from other people. And it's also healthier to be active. Vitamin D can be a proxy for both of these things.
The other thing to talk about here is skin cancer. In Australia, which has a huge population of people whose ancestors lived in Britain, skin cancer is a huge problem.
In 1972 my physical anthropology prof flatly stated that darker skin selected against skin cancer and lighter against rickets—and that explains the relationship between skin color and distance from the equator—particularly in cloudy Europe. I don’t see rickets mentioned.
Maybe I'm a dopey layman, but didn't hunter-gatherers in temperate climates wear shirts? I'll go so far as to suggest that they didn't wear Abercrombie & Fitch [citation needed], but the things that live out in the sun, like flies, brambles, and pole cats, all can mess up your skin and introduce disease. That's not a modern realization.
100k IU/d for a week completely resolves my colitis episodes, from 30 stools with nothing but blood to no symptoms, so make of that what you will.
You say:
"Surprisingly, average American levels seem about as high. The nationwide average is about 27 mg/nl, but black people (whose dark skin blocks sunlight) are almost all insufficient and bring down the average; for whites, it’s about 30 ng/ml. Why are these levels as high as some of the farmer-specific studies elsewhere? Maybe it’s Americans’ better nutrition - or maybe it’s that lots of Americans already take Vitamin D supplements. Canadians are close behind at 26 ng/ml; they fail to break this down by season but I’m guessing it was in the summer."
Because all of our milk is Vitamin D fortified, I strongly suspect it's the milk keeping most americans relatively high. On top of the reduced effect of sun, blacks are much more likely to be lactose intolerant. It would be interesting to see numbers separated by latitude and milk consumption.
I do wonder if the effects of vitamin D are secondary effects. If you have issues caused by D deficiency, fixing that allows your body to repurpose other resources towards other issues. Kind of like the anti-parasite drug that seemed to help against covid... in areas which had a higher prevalence of parasites.
Personally I take 10,000 IUs, and it seems to help both me, and everybody I have recommended it to.
However - I, and everybody I have recommended it to, also happen to be lactose intolerant office workers who get very little sunlight. Social bubbles, I guess? Dunno why lactose intolerance is so insanely common in my social bubbles, though.
Additionally, the observation pattern is not "This helps me", it's "It's not the vitamin D, I'm just having a better week than normal. Oh. It happened again. Oh god. Oh god I'm a bag of chemicals."
My guess would be that 10,000 IUs is too low to be directly harmful, while also being sufficiently high to quickly resolve long-term severe deficiencies in a timeframe short enough to be personally observable.
Given social bubbles, I don't think "General population who is at normal or slightly insufficient levels" is the correct reference class. Nor should vitamin D be considered a "normal" vitamin when considering deficiencies; the cluster of people who benefit from it are going to benefit from a significantly higher dosage than you'd expect looking at the average population.
Glad Scott mentioned obesity, because a lot of the discussion of Vitamin D I've seen omits what seems to be important differences in vitamin absorption in obese people. It's a harder topic to talk about due to PC, but IMO should be noted whenever statistics about what percentage of Americans are Vitamin D deficient are thrown around. People who at a healthy weight are at a lower risk of deficiency than the general population and should supplement less. (Although de facto, just as vaccinated people are more likely to wear masks, I expect that non-obese people are more likely to take Vitamin D.)
(Also—if you're supplementing D because you get outside very rarely, consider changing that?)
Having seen crippling adult asthma mostly cured through high dose Vitamin D, I will persist in believing that there is something besides calcium regulation going on.
As for what constitutes Paleo Vitamin D levels, look at some National Geographic magazines from a century ago. Many warm weather people wear considerably more clothes these days. Conversely, Americans wear considerably less than they did a century ago.
wow: as Biologist (me) instead of focusing on evolutionary "theory" and Vitamin D dosing it would be more appropriate to look up modern data which is available on our (humans) ability to metabolize and use Vitamin D on a daily basis. Vitamin K is in its own category because of its relationship to blood coagulation, so that should be medically evaluated. Vitamin C has many studies, along with Zinc which show that it does boost immune responses. People think that Vitamin dosing is a benign response but I have personally known people who had some bipolar issues and other symptoms who overdosed on Vitamins giving them diarrhea, cramps, etc. A lot of clinical data on modern daily doses of all Vitamins is available. Still a good article. :) lots of work too. more than what I would do :) have a great day! '-
Charts like that make me despair for medical science.
Chemicals on the giant chart of metabolic pathways are kind of like religions. For any chemical with a large enough biological role, there is going to be some group of people exhibiting cult-like behavior, who are absolutely convinced that it is the One True Chemical that is the ultimate solution to all disease.
Frustratingly, some of these groups are probably correct, in the same way that on the day the world goes up in flames in a nuclear apocalypse, there is bound to be some conspiracy theorist somewhere in the world who predicted it correctly.
I do think that I'm sure I spend less time outside than my father (who grew up on a farm) and he was outside less than his father (lived on farm his entire life) and him less than every other ancestor before him (worked on farms using only horse power). In times before sunblock or sunglasses were invented.
Does this mean my vitamin D levels are lower than any ancestor? Is this why I'm so near-sighted?
"Hunter-gatherers in the environment where most of our evolution happened might have been outside all day shirtless. On average the sun's halfway from peak, so that might be equivalent to 8 hours of peak sunlight at the equator."
Okay, from the start I am going to dispute this. We've been told hunter-gatherers had this idyllic ancestral lifestyle where they got all their needs met in a few hours and had the rest of the day for leisure time. They weren't forced to be out toiling in the fields under the blazing sun for hours every day.
If they're walking around shirtless under the equatorial sun for eight hours a day, then they are stupider than lions:
"Lions are most active during dawn, dusk and periodically throughout the night. During daylight hours they can be found lounging or sleeping in the shade."
If our shirtless hunter-gatherer can't figure out "get under a bush, stay in the shade, don't move around too much, and drink water", then he has more problems going on than "boy, I must be generating *so* much Vitamin D right now!" can solve.
After all it's just mad dogs and Englishmen who go out in the mid-day sun:
https://www.youtube.com/watch?v=BifLPGi4X6A
me and everyone in my family is vitamin D deficient in the winter (dark skin + live in UK), and the main complaint we had that got fixed by taking vitamin D was extreme fatigue. We went to the doctor about tiredness, got blood tests and then got given the 20,000 IU or 50,000IU pills. At no point did anything about bones come up when discussing it with the doctor for me (can't speak about everyone else).
So i'm surprised that you didn't even MENTION it.
So many paragraphs on D without hitting the most important points. You hold up the IOM (now renamed the NAM) as more prestigious than the Endocrine Society despite their statistical mistake and the fact that the Endocrine society has 18,000 members (in "medicine, molecular and cellular biology, biochemistry, physiology, genetics, immunology, education, industry, and allied health" according to Wikipedia). Okay. The IOM's own minimum serum level recommendation for 25(OH)D is 20ng/ml. This is also the target min set by the European Food Safety Authority, Germany, Austria, Switzerland, Nordic Countries, Australia, & New Zealand. It was also the consensus rec of 11 international orgs (see https://academic.oup.com/jcem/article/101/2/394/2810292?login=false). Despite this consensus roughly 50% of humans globally do not achieve this level. Calculations & citations for the 3-4 papers involved can be found at: https://twitter.com/KarlPfleger/status/1390775110257102848 (I welcome corrections). Why don't you see this as a big problem? Even if only for global bone health. For the Endocrine Society's recommended 30ng/ml minimum, roughly 3/4 of people globally are too low. Note also that this higher 30ng/ml is the level at which typical blood tests from Quest or LabCorp in the US are flagged as low. What governments are making concerted efforts to drive down these deficiency rates? 25(OH)D tests are inexpensive & widely available. The normal standard is that RDAs are set so that 2.5% or fewer people are deficient. The US estimates typically come in at 25-35% or sometimes 40% at the 20ng/ml level. That's 10x the deficiency prevalence max target. What US government agency is responsible for reducing these deficiency numbers?
You both downplay the importance of the observational studies too much. Much of science and many important clinical medical decisions are & should be based on observed correlations together with understanding of the basic underlying science (physics/chemistry/biology). Astronomy and other scientific fields make progress without the use of any RCTs. Seatbelts, parachutes, and smoking warnings on cigarettes are all justified without recourse to RCTs.
But now let's talk about Covid risk factors. Age, obesity/overweight, and comorbidities like diabetes are established Covid risk factors that no one questions. All of these are based exclusively on observational data. No RCTs are part of establishing these as legitimate risk factors. Vitamin D status, ie 25(OH)D, is also unquestionably at this point a statistically significant risk factor for Covid. 75+ studies with aggregate ~2M subjects. Multiple meta-analyses. Narrow confidence intervals. And effect size of 1.5-2x different risk, mostly based on the 30ng/ml threshold or the 20ng/ml threshold. (See https://twitter.com/KarlPfleger/status/1486565564671692804 for citations.) This is not just important for hypothesis generation for therapeutic potential, it's also important for stratifying the absolute risk level for groups or individuals which is how one clinical computes Number Needed to Treat (NNT) for helping to decide on relative benefit vs risk of potential interventions, such as vaccination or use of anti-viral drugs.
Meantime, no evidence suggests that being vitamin D deficient is protective for Covid. And known immune biology suggests multiple clear mechanisms of action by which D should be protective. (See eg https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbm4.10405 but more mechanism papers in the previously linked Twitter thread). So, that leaves a pretty clear-cut benefit vs risk analysis:
If governments / public health officials emphasize reducing deficiency for pandemic control & end up being wrong about D helping Covid, the biggest side-effect would be reduction in the huge prevalence of deficiency (see other comment I just made here), w/ consequent improvements in population wide bone health, and probably autoimmune health, & resistance to other ARIs.
Or conversely, if officials recommend a concerted effort to reduce deficiency for the non-Covid benefits, reduced Covid transmission, hospital burden, & deaths are all plausible side effects even if not guaranteed. But a worse pandemic is not. I find your overall stance puzzling given the apparent imbalance when viewing things this way.
Lastly, (this is the 3rd of 3 top level comments I'm making here) let's talk about scientific hypotheses and the proper ways to test them. The massive observational data showing correlation between 25(OH)D and increased Covid risk suggests more than anything else a specific form of clinical intervention: Give deficient people vitamin D until they have enough (eg for example those starting at <20ng/ml until they have >= 30ng/ml). This is in fact exactly the form of intervention long advocated by vitamin D researchers such as Heaney: https://academic.oup.com/nutritionreviews/article/72/1/48/1933554 and Grant et al: https://www.sciencedirect.com/science/article/abs/pii/S0960076017302236?via%3Dihub
The intervention give a fixed amount of D to people for whom one hasn't tested baseline D levels, or the intervention to give a fixed amount to people after testing their levels but without testing to see that they have achieved sufficient levels before beginning to record adverse event differences vs control are not correct forms of study design to properly test the main hypothesis. And in fact these problems are the main reasons why many vitamin D RCTs fail. See for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487184/
Given the massive observational data, the many clear mechanisms of action, and the fact that no pharma company will fund a study of an inexpensive supplement, it is puzzling that governments have not adequately funded a properly designed study to test the hypothesis properly. To this day there is no RCT testing the use of the intervention raise 25(OH)D from 20 to 30ng/ml powered to adequately rule of the hypothesis that it would reduce severe Covid outcomes like death & ICU, yet people (including this piece) keep (inappropriately in my opinion) casting doubt on that hypothesis despite compelling biology.
The observational data is solid. It doesn't prove causality, but it's suggestive of such a strong potential benefit, that it should be someone's responsibility to disprove the causality by finding the confounding shared causal variable that fully explains the causation. Until then it's reasonable to apply precautionary principle and try to ensure people are not deficient.
I remember reading an article back in the 1990s or early 2000s in Natural History (AMNH's member magazine) about vitamin D and folic acid. It pointed out that increased sunlight raises vitamin D levels but lowers folic acid levels, so there is a tradeoff between getting enough of each. This suggests that there is probably a limit on how much D a person can acquire from sun exposure without running into a folic acid shortage.
(The authors also argued that this accounts for women having slightly lighter skin than men as a result of their having a different balance point for the two chemicals. Is this even true? I have no idea. I can think of dozens of confounding factors, but that's a discussion for another time and place.)
Is it that hard to believe that Vitamin D is a boring bone and immune system chemical, as opposed to just a boring bone chemical?
The idea that it can "treat COVID, prevent cancer, prevent cardiovascular disease, and lower all-cause mortality" sounds ridiculous when described like that, largely because it implies that those are all separate things that Vitamin D just happens to fix. But really, it's all one simple (and thus not especially unlikely) effect: It improves the immune system's functioning, and anything that improves the immune system's functioning is going to make the body more capable of dealing with illnesses in general, including COVID, cancer, and probably some forms of heart disease (specifically, whichever types are caused by pathogens). Obviously it's not a miracle cure for any of those things - it's not guaranteed to prevent you from getting them, nor to make them go away once you have them. But it can make your body a little better at dealing with them.
> Our priors on a random chemical doing that have to be less than 1%, or we get caught in weird logical traps.
Maybe not all of those at once, but what are the chances that a chemical does any one of those? If it's less than 5%, then that means that, given some random chemical passes a well-done controlled randomized trial, it probably doesn't work.
On the importance of vitamin D: we dropped our skin pigmentation on our way out of Afrika in evolutionary record time, whatever the reason was it apparently changed either mortality or reproduction success dramatically. And it's not unreasonable to assume that this is vitamin D, or that vitamin D plays an important role in it. Not sure how this can be proven though, its just a hypothesis.
Regarding the minimal/optimal levels: i know the Hadza studies, but there are much more .. I remember a few from India and Italy that look at people working outside, with less or little clothing like farmers, construction workers, and they all come out at levels between 40 and 60ng/ml as the "normal/optimal" range. But of course there are plenty of studies pointing in the other direction considering 40ng/ml as way to high, the official recommendation here in germany was for ages "nobody needs any supplements, including vitamin d, you get all you need from a balanced diet!". Exception of the rule: babies in their first year get 400IU here because this dramatically lowers chances of rickets.
And this is the point which made me overthink my position a few years ago: the body of a pregnant or nursing mother makes sure the embryo/baby gets everything it needs, all the stores of the female body are depleted, if necessary even more. Except for vitamin D, which is often minimal in human milk. Unless, and this has been tested clinically, the vitamin d in the mother reaches around 40ng/ml 25(OH)D or above, then the milk contains enough vitamin, no supplementation necessary.
There were several studies looking at this, small/medium RCTs if i remember correctly, with supplementation in the range of 4000-6500IU daily, and beside the milk issue they found effects like 20% lower probability of birth complications and other things improving. I really should dig out these studies again .. I haven't bookmarked them.
The only one that made it into my "google keep" is this one: "New insights into the vitamin D requirements during pregnancy" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573964 which is an overview of the state of things during pregnancy, with over 140 references
PS: bear with me, english is not my first language ;-)
Adding more anecdotal evidence to the pile: I have fibromyalgia and have been dealing with flareups for approximately my whole life, without knowing what they were (I wasn't certain I was chronically ill until 2020). My worst episode was in mid-2019, where for nearly three months I was so fatigued that there was a noticeable drop in my work quality, and I had to start working from home because I couldn't make the ten minute walk to the train station. I was essentially bed-ridden for part of the time, and I had at least one day where I couldn't reliably speak or focus my eyes.
Doctors did a full blood panel, and the only unusual thing they found was that my vitamin D was at 24.8 ng/mL, considered insufficient but not deficient. I started taking 10,000 IU daily, and the months-long episode cleared up within a week or two. I've been taking 5,000 IU daily for the past two years and my rate of flareups — which previously happened every couple months, unpredictably — has dropped to basically zero. I also talked to a fibromyalgia specialist (who was maybe a bit of a quack, but ¯\_(ツ)_/¯) who said she recommends all her patients take 5,000-10,000 IU daily — not that I trust much of anything she said, but it did feel like it backed up the idea that I was not totally crazy to think that supplementing vitamin D was helping.
My current hypothesis or story of Vitamin D is this in short: Vitamin D helps controlling and adapting our metabolismisms to summer / winter cycles. Nearly every cell in our bodies has receptors for Vitamin D.
The farer a region is from the equator the less sun and energy reaches the ground during the winter and the less food is available for animals in the end. Therefore the evolution invented hybernation. This is a special 'low activity low power consumption mode which helps to survive hard, long Winters without food. In autumn many animals prepare for the coming winter by eating es much as they can and store a lot of additional energy as fat in their bodies. This fat is then slowly converted into energy during winter while many of these animals just sleep most of the time. Research about hybernation seems pretty new. Only recently researchers found hybernation mechanisms in animals which were not known for that. Mongolian wild horses which move way less and reduce their body temperature for example.
If I look at all the random facts I learned the past 20 years I see a pattern: I have more apatite in dark times, I get fat in autumn and winter, I eat less in Summer, I'm depressed when it's darker, I'm happy when it's light, in winter I move way less compared to summer, Vitamin D, SSRI, Serotonine, Melatonine, sleep, and mood/motivation/missing motivation are related to each other asf
Not sure , where I heard first about the Hybernation-Hypothesis first but I cannot un-learn it anymore.
TL;DR
If I look at all those strange things happening with my body though the 'Evolution-Hybernation-Lens' it seems to make a lot more sense for me.
Our son has celiac disease and has blood tests every 6 months. Just for fun, the gastro doctor said to throw in some extra tests last time around including Vitamin D. It came out very low. We were mortified, and pledged to start supplementing straight away. She told us we could supplement if we wanted, because it's practically free after all, but that every single child she had ever tested came out low, often even lower, and it was nothing to really worry about (incidentally, while our son's symptoms are pretty out there, she has seen it all, including paralysis, fits, and psychosis as a result of celiac).
Anyway, our son has a whole suite of symptoms that occur every time he has a a 'glutening' caused by putting his fingers in his mouth after touching a crumb on the bus, or the like. You can set your watch to it. This happens roughly every three weeks and while they are not life-threatening they are sufficiently serious - both physically and mentally - that we have organised our life for years around minimising them.
Two weeks after we started supplementing, a glutening occurred. All the same symptoms, but much milder. A month later, even milder. A month later, even milder. So mild that, if we weren't so attuned to them, we wouldn't even notice them as part of a pattern. After years of fending off doctors and teachers telling us he needed Ritalin - and making faces at each other when we said his mood swings and hyperactivity were a side-effect of exposure to gluten - we found the cure. Our family doctor - who by the standards of the profession is actually pretty good - made a vague effort to feign interest before telling us not to rule out Ritalin.
A general programme of promoting vitamin D supplementation would, at the bare minimum, save tens of thousands of children from dangerous medication and essentially abusive treatment regimens for hyperactivity. All for perhaps 0.00000000000000001% of the costs of Covid policy. Whatever the actual mechanisms involved (and I lean to a Eugyppius-Yarvin type model rather than the Alex Jones version), the medical industry is functionally a criminal entity. Analyses like this one that don't rest on an understanding of the fundamentally criminal nature of the medical industry in selecting and interpreting data are literally worse than useless.
Scott writes of his priors. Mine—however anecdotal—are as follows:
About a decade ago, having moved about a decade previous to that from southern Ontario to southern England, I had a very bad winter health-wise: instead of a handful of colds and perhaps one illness bad enough to raise a fever, I had four or five bouts of illness with fever and in between I would never fully recover, remaining congested with a persistent cough.
In the decade preceding that winter I had tried taking vitamin C supplements for immune health but had stopped because they did not have any discernible effect, but around this time I read a popular press article written by a prison doctor (probably here, though URL is defunct not archived by archive.org: https://www.medicalnewstoday.com/articles/51913) who had noted that vitamin D supplementation had dramatically improved the health of the prisoners in his care, so, living in northern Europe and spending most of my time indoors (and despite being quite fair-skinned) I figured it was worth a try.
For the next two winters I took around 2000 IU of vitamin D3 every day, and had nary a sniffle. Unfortunately, however it was difficult at the time to get even modestly-high-dose vitamin D tablets in the UK (the RDI here at the time was something laughable like 40 IU/day) and eventually my imported supply ran out, so the folowing winter I took none and was terribly sickly again—perhaps not as bad as that first terrible winter, but much worse than I had been the two intervening years.
Since then I have managed to keep myself supplied and have resumed enjoying generally good winter health. Perhaps it's just the placebo effect—though a placebo which proved highly effective against COVID too, as it happens—but good enough to be in the "definitely worth it" category for me.
If hydroxymethylbilane supplementation cures anything, it'll be vampirism.
As the Luxwolda 2012 paper shows, the semi-nomadic pastoral Maasai tribe have a mean average level of 48 ng/ml, with the largest subset of the group (40%) having a level between 48 and 60 ng/ml, and the third largest subset (~12%) having even higher levels between 60 and 70 ng/ml. Even including the hunter-gatherer Hadzabe tribe, the largest subset is still the 48-60 ng/ml group at 33.3%. So the median (which is a more representative value of the norm than the average) will be in this range, higher than the 44 ng/ml mean level stated in this blog post, and so higher vitamin D intake will be required to reach the median value.
Vitamin d seems to have some immunomodulatory effect that is beneficial for some autoimmune conditions like the ulcerative colitis I've lived with for the past 15 years. Plus some meta-analysis said it reduced colorectal cancer risk by half and calcium absorption in the colon is plausibly related to that. If it were just "sick people go outside less" there wouldn't be a big signal for colon cancer in particular. On the downside, chronically high but non-toxic levels of vitamin D might accelerate the calcification of the pineal gland, causing melatonin deficiency, causing poor sleep, causing a variety of other health problems. I basically can't sleep well without completely blacking out all sources of light -- streetlights through blinds are way too much light for me.
If the etiology of death by covid is mostly the immune system overreacting and attacking the lungs, and we have other evidence of vitamin D being helpful in autoimmune conditions, our prior for vitamin D benefitting covid patients should not be that low. Dexamethasone reduced covid mortality by half just by blunting the immune system's overreaction against the lungs. Vitamin D is probably not as potent as dexamethasone but more study is warranted. My prior on any sort of antinflammatory or immunomodulatory benefitting covid is at least an OOM higher than my prior on dart-chemicals benefitting covid.
Some studies have supported much higher Vitamin D blood concentrations:
83.4 nmol/L : Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium, by Gaksch, et al., PLOS ONE | DOI:10.1371/journal.pone.0170791 February 16, 2017
> 50 nmol/L: Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study, by Gao et al. Clinical Epigenetics (2018) 10:84 https://doi.org/10.1186/s13148-018-0515-y
~35 nmol/L: Evidence for a U-Shaped Relationship Between Prehospital Vitamin D Status and Mortality: A Cohort Study, by Sadeq et al., J Clin Endocrinol Metab, April 2014, 99(4):1461–1469, doi: 10.1210/jc.2013-3481
77.5 nmol/L: Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies, by Zittermann, et al., Am J Clin Nutr 2012;95:91–100 doi: 10.3945/ajcn.111.014779
75 nmol/L: Commentary: Additional strong evidence that optimal serum 25- hydroxyvitamin D levels are at least 75 nmol/l, by WB Grant, International Journal of Epidemiology 2011;40:1005–1007
and finally the big kahuna of them all:
110 nmol/L: An estimate of the global reduction in mortality rates through doubling
vitamin D levels, by WB Grant, et al., European Journal of Clinical Nutrition (2011) 65, 1016–1026
But wait! There's more! Namely, magnesium!
Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III, by Deng et al., BMC Medicine 2013 11:187. doi:10.1186/1741-7015-11-187
Finally, rather than being a boring bone chemical, there have been some studies on the relationship between Vitamin D levels and Depression:
Vitamin D deficiency and depression in adults: systematic review and meta-analysis, by Anglin et al., The British Journal of Psychiatry (2013) 202, 100–107. doi: 10.1192/bjp.bp.111.106666
"One case–control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23–0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0–1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40–3.49)."
Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial, by Sepehrmanesh et al., The Journal of Nutrition November 25, 2015; doi:10.3945/jn.115.218883.
" Baseline concentrations of mean serum 25-hydroxyvitamin D were significantly different between the 2 groups (9.2 6 6.0 and 13.6 6 7.9 mg/L in the placebo and control groups, respectively, P = 0.02). After 8 wk of intervention, changes in serum 25-hydroxyvitamin D concentrations were significantly greater in the vitamin D group (+20.4 mg/L) than in the placebo group (20.9 mg/L, P < 0.001). A trend toward a greater decrease in the BDI was observed in the vitamin D group than in the placebo group (28.0 and 23.3, respectively, P = 0.06). Changes in serum insulin (23.6 compared with +2.9 mIU/mL, P = 0.02), estimated homeostasis model assessment of insulin resistance (21.0 compared with +0.6, P = 0.01), estimated homeostasis model assessment of b cell function (213.9 compared with +10.3, P = 0.03), plasma total antioxidant capacity (+63.1 compared with 223.4 mmol/L, P = 0.04), and glutathione (+170 compared with 2213 mmol/L, P = 0.04) in the vitamin D group were significantly different from those in the placebo group"
If I recall correctly, there were pretty robust metanalyses showing that Vitamin D supplementation helped recovery from respiratory infections long before COVID. Not cure-all good, but still meaningfully good.