Vit D supplementation to prevent acute resp infections: review and meta-analysis(thelancet.com)
thelancet.com
Vit D supplementation to prevent acute resp infections: review and meta-analysis
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00348-6/fulltext
48 comments
The more interesting finding is that people with low baseline Vitamin D levels (<25 nmol/L) did not show any improvement. Odds ratio of 0.98 (0.80–1.20).
A lot of previous Vitamin D research was dismissed with the claim that Vitamin D would be more effective if you only looked at people with low baseline Vitamin D status. This paper does not show that to be true.
A lot of previous Vitamin D research was dismissed with the claim that Vitamin D would be more effective if you only looked at people with low baseline Vitamin D status. This paper does not show that to be true.
The proper claim is that raising people from deficient (<20ng/ml) to a sufficient level (>30ng/ml ideally) should improve outcomes. Sometimes looking at a subset of those who started deficient is good enough to find such an effect, but sometimes it isn't, such as if the dose used was not high enough to raise people up enough, particularly common if the subjects weights were high which requires higher intakes to move the needle a lot, so other subset analysis look at norm-weight subjects. Proper study guidelines were published in the mid 2010s and meta-analyses like this one that aggregate many studies that don't conform to these guidelines are just as invalid as individual studies that don't.
For detailed treatment of this see this thread on X: https://x.com/KarlPfleger/status/1732514710715514883
For detailed treatment of this see this thread on X: https://x.com/KarlPfleger/status/1732514710715514883
if we're teetering on significance seems like a subgroup analysis is worth considering
Related
High-dose Vitamin D reduces disease activity in early multiple sclerosis onset (91 points, 15 days ago, 52 comments) https://news.ycombinator.com/item?id=43469661
Over 80% of Covid-19 patients in a hospital study have Vitamin D deficiency (654 points, 4 years ago, 363 comments) https://news.ycombinator.com/item?id=24912172
Adequate Vitamin D Levels Cuts Risk of Dying from Covid-19 in Half, Study Finds (372 points, 5 years ago, 211 comments) https://news.ycombinator.com/item?id=24607645
High-dose Vitamin D reduces disease activity in early multiple sclerosis onset (91 points, 15 days ago, 52 comments) https://news.ycombinator.com/item?id=43469661
Over 80% of Covid-19 patients in a hospital study have Vitamin D deficiency (654 points, 4 years ago, 363 comments) https://news.ycombinator.com/item?id=24912172
Adequate Vitamin D Levels Cuts Risk of Dying from Covid-19 in Half, Study Finds (372 points, 5 years ago, 211 comments) https://news.ycombinator.com/item?id=24607645
Those last two are not actually related.
This review was about testing supplementation of vitamin D, what you posted is mostly about correlation between serum levels and health outcomes, and those levels are largely about non-supplemented “natural” vitamin d.
The distinction is important because science has been trying to figure out whether vitamin d itself has the benefits, or if it is a marker for a larger salubrious process.
This review was about testing supplementation of vitamin D, what you posted is mostly about correlation between serum levels and health outcomes, and those levels are largely about non-supplemented “natural” vitamin d.
The distinction is important because science has been trying to figure out whether vitamin d itself has the benefits, or if it is a marker for a larger salubrious process.
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The title is wrong. The study concluded that Vitamin D supplementation doesn't help prevent acute respiratory infections.
The title doesn't contain any conclusion.
Right, my bad. Misleading would be the correct word.
Full title as published in Lancet:
>Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data
What with HN's 80 character limit something had to go!
I apologize for making it "misleading" but what would you have done?
>Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data
What with HN's 80 character limit something had to go!
I apologize for making it "misleading" but what would you have done?
The title should be something like "Could Vitamin D supplementation help prevent acute respiratory infection? Systematic review and meta-analysis".
When I read the "Vitamin D supplementation to prevent" part, I got excited because I thought the research implied that supplementation does help. So I had to read it.
With the first title, I wouldn't read the study because I've read dozens of other studies showing how Vitamin D supplementation doesn't improve health outcomes.
When I read the "Vitamin D supplementation to prevent" part, I got excited because I thought the research implied that supplementation does help. So I had to read it.
With the first title, I wouldn't read the study because I've read dozens of other studies showing how Vitamin D supplementation doesn't improve health outcomes.
I put your title into the HN title box for submission: "29 too long"
No need to apologise. It's not misleading at all.
It's lacking. A good title should save a click for those who are not interested in details but just the conclusion.
It's a scientific study. It's conclusion is the study results which is a bunch of confidence intervals and statistics.
Someone else quoted this as the results from the study:
> For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88–1·00], p=0·057; 40 studies; 61 589 participants; I2=26·4%).
Are you suggesting that should be in the title? Would it even fit?
Someone else quoted this as the results from the study:
> For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88–1·00], p=0·057; 40 studies; 61 589 participants; I2=26·4%).
Are you suggesting that should be in the title? Would it even fit?
Then the title could be "Meta analysis finds Vitamin D supplementation doesn't improve Acute Respiratory Illness" or some variation of that, which is something I've known about Vitamin D for a while.
"7 too long"
I ask again: what do you believe the title should be?
For what it's worth, it is good to know:
- Low Vitamin D Status despite Abundant Sun Exposure (https://academic.oup.com/jcem/article/92/6/2130/2597445)
- Vitamin D deficiency can still occur despite supplementation (https://emedicine.medscape.com/article/128762-overview?form=..., https://www.ccjm.org/content/89/3/154, https://www.health.harvard.edu/healthbeat/9-things-that-can-...)
Thus, you can be deficient despite sun exposure and/or supplementation.
You should probably get tests done to be sure.
I have MS, I take daily 10k IU. I should probably get some tests done myself.
- Low Vitamin D Status despite Abundant Sun Exposure (https://academic.oup.com/jcem/article/92/6/2130/2597445)
- Vitamin D deficiency can still occur despite supplementation (https://emedicine.medscape.com/article/128762-overview?form=..., https://www.ccjm.org/content/89/3/154, https://www.health.harvard.edu/healthbeat/9-things-that-can-...)
Thus, you can be deficient despite sun exposure and/or supplementation.
You should probably get tests done to be sure.
I have MS, I take daily 10k IU. I should probably get some tests done myself.
For anyone who is familiar with the Security Now podcast there is an excellent write-up from Steve Gibson on the topic for nerds as we all work in man made caves and don't get sun. Highly recommended.
I would also recommend Dr. John Campbell's videos on the topic as he is quite thorough when reviewing the medical research.
One interesting point John makes is that if you are already sick Vit D is to slow as it needs to metabolize and calcifediol (25-hydroxyvitamin D3, the active form) is what patents need after infection.
Links:
https://www.grc.com/health/vitamin-d.htm
https://www.youtube.com/@Campbellteaching/search?query=vitam...
I would also recommend Dr. John Campbell's videos on the topic as he is quite thorough when reviewing the medical research.
One interesting point John makes is that if you are already sick Vit D is to slow as it needs to metabolize and calcifediol (25-hydroxyvitamin D3, the active form) is what patents need after infection.
Links:
https://www.grc.com/health/vitamin-d.htm
https://www.youtube.com/@Campbellteaching/search?query=vitam...
Just curious, other than taking Vitamin D pills - what are some natural diets that are rich in Vitamin D?
Mushrooms. You need to leave them gill side up in the sun for a day (behind a window is fine).
There are a lot of every day foods with a good supply of vitamin D.
https://www.dietaryguidelines.gov/resources/2020-2025-dietar...
I recommend saving a copy of .gov website sources in case the regime decides it is unacceptable speech.
https://www.dietaryguidelines.gov/resources/2020-2025-dietar...
I recommend saving a copy of .gov website sources in case the regime decides it is unacceptable speech.
Sources: Fish (generally fatty: trout, salmon, tuna, herring, sardines, tilapia, flounder), Mushrooms (some, large variety in quantity).
Note the article is "food sources" so it includes fortified (dairy, juice) which do not contain vitamin D naturally.
Note the article is "food sources" so it includes fortified (dairy, juice) which do not contain vitamin D naturally.
The substance in mushrooms (ergocalciferol) has a structure similar to the true vitamin D (cholecalciferol a.k.a. vitamin D3).
Nevertheless, it seems that it is not able to substitute vitamin D in all its functions. Therefore it is not advisable to count on it as a source of vitamin D.
There has been a company that has claimed that they have discovered a species of lichen that contains true vitamin D. Nevertheless, their advertising has seemed highly suspicious and it looked more like a scheme to separate naive vegans from their money.
Even if it were true, exploiting wild lichen would be much more unethical than eating the normal vitamin D3 supplements made from sheep wool. The reason is that wild lichens grow very slowly and exploiting a species for a food supplement would cause a very high risk of extinction for that species.
In any vertebrate animal, the liver is the part with the greatest content of vitamin D.
Nevertheless, it seems that it is not able to substitute vitamin D in all its functions. Therefore it is not advisable to count on it as a source of vitamin D.
There has been a company that has claimed that they have discovered a species of lichen that contains true vitamin D. Nevertheless, their advertising has seemed highly suspicious and it looked more like a scheme to separate naive vegans from their money.
Even if it were true, exploiting wild lichen would be much more unethical than eating the normal vitamin D3 supplements made from sheep wool. The reason is that wild lichens grow very slowly and exploiting a species for a food supplement would cause a very high risk of extinction for that species.
In any vertebrate animal, the liver is the part with the greatest content of vitamin D.
Uh. Okay buddy, thanks for that.
P.S. most milk sold in the US is Vitamin D fortified.
P.S. most milk sold in the US is Vitamin D fortified.
According to my doctor, raising vit D through diet is not reasonable. It’s sunlight or pills/shots if sunlight won’t do it (genetics or climate).
In peak summer with being outdoors 2+ hours every day my Vit D was 30 (<30 is inadequate) and drank fortified almond milk daily. In winter it drops to 20 with similar outdoor time. Been on a 50,000 pill once a week since.
Maybe someone will share a well informed diet that contradicts my doctor.
I get the sense that you have to eat a lot of fish, which introduces heavy metal concerns because of modern fishing, which is why my doctor went the route he did. And how do you know the one type of mushroom actually gets the right light to have natural Vit D—-raw ingredients like mushrooms don’t usually have nutrition labels.
In peak summer with being outdoors 2+ hours every day my Vit D was 30 (<30 is inadequate) and drank fortified almond milk daily. In winter it drops to 20 with similar outdoor time. Been on a 50,000 pill once a week since.
Maybe someone will share a well informed diet that contradicts my doctor.
I get the sense that you have to eat a lot of fish, which introduces heavy metal concerns because of modern fishing, which is why my doctor went the route he did. And how do you know the one type of mushroom actually gets the right light to have natural Vit D—-raw ingredients like mushrooms don’t usually have nutrition labels.
> Been on a 50,000 pill once a week since.
FYI, spiking Vitamin D levels in the blood weekly might not be the best idea, though it's not exactly proven. There's a theory that spiking Vitamin D like that can promote blood vessel calcification. There's some more theory that Vitamin K administered at the same time might help.
It could be safer to do 5,000 IU seven days a week than spikes of 50K once a week.
Watch out, though. I was on a similar daily dose and ended up with Vitamin D levels touching the upper limit. Too much Vitamin D is not good for you.
> and drank fortified almond milk daily.
Can't say without seeing the labels, but I wouldn't expect a cup of almond milk to have more than 10-20% of your daily value.
FYI, spiking Vitamin D levels in the blood weekly might not be the best idea, though it's not exactly proven. There's a theory that spiking Vitamin D like that can promote blood vessel calcification. There's some more theory that Vitamin K administered at the same time might help.
It could be safer to do 5,000 IU seven days a week than spikes of 50K once a week.
Watch out, though. I was on a similar daily dose and ended up with Vitamin D levels touching the upper limit. Too much Vitamin D is not good for you.
> and drank fortified almond milk daily.
Can't say without seeing the labels, but I wouldn't expect a cup of almond milk to have more than 10-20% of your daily value.
IIRC supplementing K with D also helps D to be absorbed and/or utilized better.
Are you getting enough Magnesium (and also Vitamin B6)? Magnesium is a required cofactor of Vitamin D in many bodily processes.
see https://www.qeios.com/read/479KRZ
see https://www.qeios.com/read/479KRZ
Cod liver oil is probably the best choice, as it also includes DHA, EPA and vitamin A, providing most things that would not be provided by vegetable oil (the only essential fatty substance that is neither in vegetable oil nor in cod liver oil is vitamin K2).
Well made cod liver oil is tasty and you can add it to food together with whatever else kind of oil you prefer (after food is cooked, not before, as it is heat sensitive). No more than 10 mL/day is necessary.
At least at the analysis reports that I have seen in the EU, fish oil has never been found with high content of mercury, even if the fish from which it has been extracted are likely to have been contaminated with mercury. Moreover, cod liver oil is sold in the EU as recommended for children and pregnant women. I doubt that any company would have the guts to sell such products here without taking care to make frequent chemical analyses to ensure that the product is never contaminated.
Chicken liver is also rich in vitamin D, but it is not advisable to eat great quantities, because it may contain too much vitamin A (which is toxic in excessive amounts). The amount of vitamin A in chicken liver or turkey liver is pretty much unpredictable, because it may vary by more than an order of magnitude between various producers, depending on how they feed the birds.
Most vitamin D3 pills contain vitamin D3 that is produced from sheep wool (i.e. from lanolin).
Well made cod liver oil is tasty and you can add it to food together with whatever else kind of oil you prefer (after food is cooked, not before, as it is heat sensitive). No more than 10 mL/day is necessary.
At least at the analysis reports that I have seen in the EU, fish oil has never been found with high content of mercury, even if the fish from which it has been extracted are likely to have been contaminated with mercury. Moreover, cod liver oil is sold in the EU as recommended for children and pregnant women. I doubt that any company would have the guts to sell such products here without taking care to make frequent chemical analyses to ensure that the product is never contaminated.
Chicken liver is also rich in vitamin D, but it is not advisable to eat great quantities, because it may contain too much vitamin A (which is toxic in excessive amounts). The amount of vitamin A in chicken liver or turkey liver is pretty much unpredictable, because it may vary by more than an order of magnitude between various producers, depending on how they feed the birds.
Most vitamin D3 pills contain vitamin D3 that is produced from sheep wool (i.e. from lanolin).
Not possible with diet alone.
So what now? If we know that low vit D levels correlate with flu, but vit D intake doesn't help, then we should assume that it's not vit D but something else instead?
Having looked pretty deeply into Vit D studies a while back, my takeaway was (in broad strokes):
* Adding more Vit D doesn't appear to meaningfully prevent upper respiratory infections.
* However, being deficient in Vit D appears to be correlated with a meaningful number of D deficient people who do happen to get an upper respiratory infection having a more serious impact. Basically, a higher percentage of deficient people (but certainly far from all) appear to have worse symptoms for longer and have more trouble fighting the infection off. Whether that just means an extra day of feeling under the weather or that you join the very small percentage of those hospitalized for upper respiratory infection depends on the other factors you already know (age, overall health, etc) much more than on Vit D deficiency. But Vit D deficiency is very probably in the top 5 somewhere behind the two statistical Godzillas at the top, age and overall health (which are overwhelmingly correlated).
This is only worth talking about because a fairly significant number of people are Vit D deficient at least some of the time (probably more than 20% but less than half). Who and how much depends on where they live, lifestyle, age, diet, time of year and there is also a genetic propensity for deficiency that's primarily based on race.
Bottom line: If you're Vit D deficient then it may be a good idea to supplement a little Vit D which is cheap, easy and extremely low risk (Note: nothing is ever zero risk across a large enough population but supplementing a small amount of Vit D is about as safe as these things ever get). It may be especially worth considering if you're in a statistically higher risk group, location and/or season. So, if you're at elevated risk and can't be younger or healthier, at least don't be Vit D deficient too. Once you're not deficient, taking even more Vit D won't help more (and can be harmful). Mega-dosing can definitely be harmful, so please don't. Starting oral supplements once you have symptoms is also too late to matter.
In terms of confidence levels, my sense was there's pretty clearly a meaningful correlation here but causation and relative effect are fuzzy. The correlation mostly comes from looking retrospectively at the Vit D levels of those who have infections serious enough to get hospitalized. However, the Vit D correlation is far less than age or overall health (which are overwhelmingly large). The challenge is looking at it the other way, from the front end, where it gets pretty fuzzy trying to tease out high confidence causal data, narrow other factor's contributions or derive a degree of impact specific to Vit D. There are a lot of potentially confounding factors and Vit D is not usually checked in many blood work panels unless there's a reason to. Worse, long-term diary studies of diet are notoriously inexact. So much so that as an armchair amateur scientist just trying to objectively assess data, I have to attach error bars to longitudinal diary diet studies so large they usually swamp any signal. For example, the question: "Does being Vit D deficient meaningfully increase susceptibility to infection?" I don't think there's sufficiently clear data to make any judgement.
* Adding more Vit D doesn't appear to meaningfully prevent upper respiratory infections.
* However, being deficient in Vit D appears to be correlated with a meaningful number of D deficient people who do happen to get an upper respiratory infection having a more serious impact. Basically, a higher percentage of deficient people (but certainly far from all) appear to have worse symptoms for longer and have more trouble fighting the infection off. Whether that just means an extra day of feeling under the weather or that you join the very small percentage of those hospitalized for upper respiratory infection depends on the other factors you already know (age, overall health, etc) much more than on Vit D deficiency. But Vit D deficiency is very probably in the top 5 somewhere behind the two statistical Godzillas at the top, age and overall health (which are overwhelmingly correlated).
This is only worth talking about because a fairly significant number of people are Vit D deficient at least some of the time (probably more than 20% but less than half). Who and how much depends on where they live, lifestyle, age, diet, time of year and there is also a genetic propensity for deficiency that's primarily based on race.
Bottom line: If you're Vit D deficient then it may be a good idea to supplement a little Vit D which is cheap, easy and extremely low risk (Note: nothing is ever zero risk across a large enough population but supplementing a small amount of Vit D is about as safe as these things ever get). It may be especially worth considering if you're in a statistically higher risk group, location and/or season. So, if you're at elevated risk and can't be younger or healthier, at least don't be Vit D deficient too. Once you're not deficient, taking even more Vit D won't help more (and can be harmful). Mega-dosing can definitely be harmful, so please don't. Starting oral supplements once you have symptoms is also too late to matter.
In terms of confidence levels, my sense was there's pretty clearly a meaningful correlation here but causation and relative effect are fuzzy. The correlation mostly comes from looking retrospectively at the Vit D levels of those who have infections serious enough to get hospitalized. However, the Vit D correlation is far less than age or overall health (which are overwhelmingly large). The challenge is looking at it the other way, from the front end, where it gets pretty fuzzy trying to tease out high confidence causal data, narrow other factor's contributions or derive a degree of impact specific to Vit D. There are a lot of potentially confounding factors and Vit D is not usually checked in many blood work panels unless there's a reason to. Worse, long-term diary studies of diet are notoriously inexact. So much so that as an armchair amateur scientist just trying to objectively assess data, I have to attach error bars to longitudinal diary diet studies so large they usually swamp any signal. For example, the question: "Does being Vit D deficient meaningfully increase susceptibility to infection?" I don't think there's sufficiently clear data to make any judgement.
> you'll just pee out the extra Vit D.
It’s fat soluble, rather than water soluble
It’s fat soluble, rather than water soluble
True.
I have not checked this, but I assume that most excess vitamin D, which is stored in the liver, is excreted by the liver together with cholesterol and other cholesterol derivatives, in the biliary secretion, reaching thus the intestine, and not by the kidneys in urine.
I have not checked this, but I assume that most excess vitamin D, which is stored in the liver, is excreted by the liver together with cholesterol and other cholesterol derivatives, in the biliary secretion, reaching thus the intestine, and not by the kidneys in urine.
Thanks! I removed that line.
> Bottom line: If you're Vit D deficient then it may be a good idea to supplement a little Vit D which is cheap, easy and extremely low risk (Note: nothing is ever zero risk across a large enough population but supplementing a small amount of Vit D is about as safe as these things ever get).
Too much vitamin D can cause pretty serious symptoms, including neurological symptoms. This condition has been getting more common since so many people are supplementing.
Too much vitamin D can cause pretty serious symptoms, including neurological symptoms. This condition has been getting more common since so many people are supplementing.
Very true. That said, I've been taking 5000IU daily for the last couple years after a blood test showed my levels were a bit low. As of last week, my 25-Hydroxy D level is 76, near the middle of the 30-100 normal range.
Everyone's different: what's right for me isn't right for you. I just mean that to demonstrate that it's possible for some healthy adults to take a pretty significant amount every single day and have perfectly reasonable blood levels.
Everyone's different: what's right for me isn't right for you. I just mean that to demonstrate that it's possible for some healthy adults to take a pretty significant amount every single day and have perfectly reasonable blood levels.
Vitamin D has a very long half-life in the body once stored. On the order of a month or two.
This leads a lot of people into slowly overdosing over several years. They start with low levels, get up to mid-range on their next blood test, and think they're on the right track. Continuing the same dose for years can easily put you over the top if you're not careful.
This leads a lot of people into slowly overdosing over several years. They start with low levels, get up to mid-range on their next blood test, and think they're on the right track. Continuing the same dose for years can easily put you over the top if you're not careful.
I read somewhere that additionally supplied vitamin K decreases these side effects. However I'd like to see a scientific paper instead of an article
https://www.health.com/vitamin-d-and-k-8427006
https://www.health.com/vitamin-d-and-k-8427006
If we’re deficient then it may well mean that our bodies aren’t being accorded the usual natural opportunities to manufacture it!
Therefore a deficiency here is an indicator of sedentary, indoor, face-in-a-screen lifestyles that risk all sorts of poor health conditions.
The solution to D deficiency is to manufacture it by touching grass, enjoying sunlight (unprotected!!!) and exercising—not in a gym—but in that extremely large room, lit by a bright, warm lamp that’s 93 million miles away.
Therefore a deficiency here is an indicator of sedentary, indoor, face-in-a-screen lifestyles that risk all sorts of poor health conditions.
The solution to D deficiency is to manufacture it by touching grass, enjoying sunlight (unprotected!!!) and exercising—not in a gym—but in that extremely large room, lit by a bright, warm lamp that’s 93 million miles away.
We don't need to hypothesize about our bodies not getting the natural opportunities to manufacture it. We know we don't. Plenty of people live in places where the sunlight is insufficient for significant portions of the year to generate any vitamin D. Many others live in places where they may nominally be getting enough ultraviolet to make enough vitamin D, but have too much melanin in their skin for the ultraviolet conditions where they live.
This isn't all about "oooh sooo much indoors too much screen time stop sitting so much lol lol lol". You can go outside all day in the middle of winter at the 45 degree latitude, where a lot of people live, and you will generate zero vitamin D, no matter what you do, because it isn't the visible spectrum you need. You need something that isn't in the winter sunlight at all. AIUI, it's technically not the same part of the UV spectrum that causes sun burns, but you're at least on the right track if you think of it as if you can't burn (modulo melanin), you can't generate vitamin D at all.
This isn't all about "oooh sooo much indoors too much screen time stop sitting so much lol lol lol". You can go outside all day in the middle of winter at the 45 degree latitude, where a lot of people live, and you will generate zero vitamin D, no matter what you do, because it isn't the visible spectrum you need. You need something that isn't in the winter sunlight at all. AIUI, it's technically not the same part of the UV spectrum that causes sun burns, but you're at least on the right track if you think of it as if you can't burn (modulo melanin), you can't generate vitamin D at all.
Just taper into the sunlight exposure so you don't get burnt. Skin cancer is not really a price you want to pay for adequate Vitamin D levels.
Skin cancer is not something I anticipate, since I scrupulously avoid slathering carcinogens onto it. I protect with clothing, umbrellas, and old-fashioned hanging out in the shade [my skin tone is porcelain, minimal freckling, 100% Celtic edition]. 26 years in Phoenix metro with literally no burns and no cancer: homelessness and public transit benches notwithstanding.
To much words for truth:
More does not help by to little will harm.
I live where the sun does not shine, so I take some.
More does not help by to little will harm.
I live where the sun does not shine, so I take some.
Recommend dminder app for an illuminated way to count D intake from both sun and supps.
Okay, so the 95% confidence interval is reduction from 0% to 12%, but since this barely is on the other side of p=0.05 the conclusion is fully that the claim is not supported.