Do vitamin D supplements protect against respiratory infections?

Vitamin D capsules protect against respiratory infection

This question has actually been pretty thoroughly researched, so it should be possible to come up with a conclusive answer. A systematic review and meta-analysis of the collected data was published in the British Journal of Medicine in 2017. The review was funded by the National Institutes of Health (NIH). No companies standing to benefit from the sale of vitamin D supplements were involved in funding the study and none of the authors had financial ties to any such companies. That makes me quite prone to trust the data.

The review included data from 25 randomized double-blind placebo controlled trials of vitamin D as a means to prevent respiratory infections. Individual patient data was collected from 10,933 individuals, out of a total of 11,321 who took part in the trials. These two facts make it more likely that the data can be trusted – only randomized double-blind placebo controlled trials (the highest quality type of study) were included in the review, and individual patient data were collected from 97% of all participants across the 25 studies, allowing the investigators to do their own independent analysis of the complete data set.

The studies were conducted between 2009 and 2016. The duration ranged from eight weeks to 1.5 years and the number of study participants ranged from 40 to 3,000. The ages of the participants varied from newborn to 95 years old. Roughly 2,000 participants were healthy adults and 4,000 were healthy children. A further 2,000 were adults with some type of health problem, and the remaining 2,500 or so were children with some health problem.

Some of the studies gave vitamin D as a bolus, while others gave it daily. The daily doses ranged from 7.5 µg (300 IU) to 100 µg (4,000 IU). The bolus dosing intervals varied from weekly to monthly to quarterly, and there was a big variation in dose size in the bolus groups too. This does make the review messy, and makes it harder to get good statistics, because each group getting a certain dose size and dose interval actually ends up quite small, even though the total number of participants is over 10,000.

Ok, let’s get to the results. In the groups getting a vitamin D supplement, 40% had a respiratory infection, while in the groups getting a placebo, 42% had a respiratory infection. This difference was small, but statistically significant, but still small enough that, if that was all there was too it, most people probably wouldn’t think it was worth taking vitamin D to avoid respiratory infections.

However, luckily, there is actually a lot more to it than that. There was a lot of variation in results between the individual studies, so the authors did a sub-group analysis to see if the variation between the studies could be explained. What they found was that among people with a vitamin D deficiency at the start of the studies, the percentage getting a respiratory infection during the study periods dropped from 55% to 41% with a vitamin D supplement. That is a big effect (14% absolute reduction) and it was statistically significant. Any medication that achieved an effect size that big would be a blockbuster and make billions of dollars for the company that invented it. However, among individuals with normal vitamin D levels to begin with, no benefit was found to taking a supplement. So the entire 2% overall benefit seems at this point to be due entirely to a big benefit among those who are deficient.

But wait, there’s more. Another finding was that daily and weekly dosing was protective against infection, but that more infrequent bolus dosing (monthly or quarterly) was not protective. What this means is that there is a clear advantage to taking smaller doses of vitamin D frequently rather than large doses occasionally. When the ineffectiveness of bolus-dosing was accounted for, it was found that the decreased risk of infection was significantly bigger than it had initially appeared. Among people with a vitamin D deficiency who took vitamin D daily or weekly, the proportion that got an infection dropped from 60% to 32% . That is an absolute risk reduction of 28 percent! Among people without deficiency, the absolute risk reduction was 6% .

When looking at treatments, it’s always important to look not just at primary effect, but also side effects and safety. The review found that vitamin D supplementation at the doses used in the studies was safe, with no difference in adverse events between the vitamin D groups and the placebo groups.

Conclusions: Vitamin D isn’t going to magically make you immune to respiratory infections, but it will likely decrease the frequency with which you get them by a bit if you are not deficient, and by a lot if you are deficient. People who are likely to be deficient are those who don’t get a lot of sun (the elderly frequently fall in to this category), those with darker skin living in northern latitudes, those covering large amounts of skin whenever they are outside (a lot of muslim females fall in to this category). If you belong to any of these categories, you should definitely be taking a vitamin D supplement. If you don’t, it’s unlikely to hurt, and it might help.

The fact that infrequent bolus dosing doesn’t work suggests that it’s not enough to just get lots of sun during the summer and then no sun during the winter. So even if you have light skin but live in northern latitudes, you may well benefit from taking a daily or weekly vitamin D supplement during the winter months.

Ok, so you’ve decided to take a vitamin D supplement based on this review. What dose should you be taking? Unfortunately, the review does not mention anything about dosing, or the relationship between dose size and effect. But the main benefit seems to come from going from being deficient to having a normal level in the blood stream. The Recommended Dietary Allowance (RDA) of vitamin D for an adult under 70 is 600 IU (15 µg), and for an adult over 70 it’s 800 IU (20 µg). If you’re taking a supplement that gives you that amount, it’s probably enough. If you want to be on the safe side and be absolutely certain that you’re getting enough to decrease your risk of infection, you could take a bit more than that. According to the FDA, doses up to 4,000 IU (100 µg) are completely safe for adults. The daily dose I would recommend would thus be somewhere in the interval 1,000-4,000 IU per day. Personally I take a supplement containing 3,000 IU per day.

You might also be interested in my article about whether vitamin D supplements can be used to prevent depression or my article about whether you should take fever lowering drugs when you have an infection.

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13 thoughts on “Do vitamin D supplements protect against respiratory infections?”

  1. You write well, but a simpler way to put the conclusion is that Vitamin D deficiency makes a person more suspectible to colds.
    Is there a theoretical reason to expect that, something to do with the functions of vitamin D in the body?
    One thing to worry about with this kind of study is that sometimes they start out to analyze one question (e.g., does vitamin D help reduce colds?) and then discover something else (e.g., vitamin D seems to reduce colds in left-handed people with asthma) and think they can apply the standard t-values for statistical significance. Doesn’t look like that’s the case here, but do watch out for it.

    Your speculations on covid19 in Sweden article is very good. Write more!

  2. There has been some suggestion that the protective value (if there is one) for Vitamin D against Covid (or other respiratory illnesses) requires concentrations in excess of 30ng/ml (75 nmol/l). All the meta studies I’ve seen (including the one UK NICE rely on) are starting from the low 20ng/ml (50 nmol/l) base – and therefore will conclude it has little or no effect.

    Have you seen anything looking at people in the 75-100 nmol/l range?

  3. Epidemiological studies indicate association but not causation. Causation requires defining a biological mechanism that can explain the epidemiological finding. In Vitamin D we have both. The associations noted in this study and the mechanism.
    It is not clear that the mechanism whereby vitamin D protects against death from COVID-19 is the same mechanism that protects against upper respiratory tract infections.

    The mechanism for COVID-19: COVID-19 is clinically 2 diseases: the much more common asymptomatic/mildly symptomatic viral like syndrome and the life-threatening immune dysfunction called the “cytokine storm”. The cytokine storm is to a autoimmune response what a CAT5 hurricane is to a thunderstorm. The mechanism of vitamin D for the life threatening immune system is understood tot the extent that vitamin D is necessary to blunt an autoimmune reaction. Lung epithelial cells express high basal levels of CYP27B1 and low levels of CYP24A1, favoring conversion of vitamin D to its active form. When treated with vitamin D, these cells increase the levels of the TLR co-receptor CD-14 and cathelicidin (LL-37). In airway epithelial cells, treatment with vitamin D induces IkBα, an NF-kB inhibitor resulting in a decrease of viral induction of inflammatory genes. Vitamin D keeps the dendritic reticulum cell in an immature/immune tolerant state, alters the M1 pro-inflammatory macrophage to a M2 anti-inflammatory macrophage, and alters the TH1 response to a TH2 response, decreasing the autoreactivity of T cells. These help and blunt the immune response and the development of the cytokine storm.

    The anti-viral effect of vitamin D is not fully understood. Cathelicidin (LL-37) is able to disrupt the envelop of enveloped viruses. Vitamin D blocks the ability of viruses that bind to the carbohydrate moieties on cell surfaces. Many viruses, include the coronavirus, use this moiety to clin to the cell and thereby allow the virus to interact with the AEC2 receptor.

    The peculiar susceptibility of type 2 diabetics may be partially explained by vitamin D and cathelicidin. Cathelicidin is stored in neutrophils (and macrophages). In DMT2, the neutrophilic response is blunted (with resulting increase susceptibility to infections of all types.

    1. Another reason T2 diabetics are worse affected…. is T2D damages the (Blood vessel) endothelium in general, and glycocalyx in particular which exposes it to passing pathogens…
      Adequate vitamin D keeps the immune system humming along nicely. Direct measurement is a better idea than relying on a notional ‘dose’. – we are all very differant! – Don’t forget to accompany the D3 with K2, to keep calcium where it belongs.
      I’ve seen 100 to 200 mcg of K2 suggested for every 1,000IU of D3.

      1. I know calcium and vitamin D are commonly taken together. Does that look, in theory or practice, like it would be relevant for the beneficial effects of vitamin D on covid? Suppose it is true that too little vitamin D is bad for covid, but it’s a threshold effect, so once you have a certain level of vitamin D, getting more is useless against covid. For covid– ignoring other vitamin D deficiency problems– should the person take calcium along with vitamin D pills? Or is the good effect of calcium only relevant to vitamin D’s everyday, non-epidemic, usefulness?

    1. Vitamin D enhances calcium absorption, but calcium is a magnesium antagonist in the sense that it depletes magnesium levels in the body. I would avoid calcium supplements if your diet is already high in calcium (the typical American diet sure is). From what I have read, magnesium is a critical cofactor in hundreds of enzymatic processes, so magnesium supplementation should be prioritized over calcium.

  4. Good article. I was surprised that it missed any discussion of the primary differentiator between studies showing a very significant positive effect from vitamin D and those showing little to no positive effect: whether the study measured blood levels via a serum 25-hydroxy test. Blood levels tell a far better and more accurate story than trying to look at the effects of differing supplementation amounts. How much of an effect Vitamin D supplementation has on blood levels is affected by a number of other factors beyond frequency of supplementation, including: sun exposure, skin melanin, magnesium intake, etc. Measuring supplementation tells you nothing about current blood levels, including whether someone is deficient or not. (which seems to be a hotly debated threshold by itself) Studies that rely only on measuring vitamin D supplementation could be likened to trying to determine where various people currently are on a cross country trip by relying only how much gasoline they purchased and knowing nothing of the starting point, vehicle fuel efficiency, or route.

  5. Dr Rushworth, a very nice post — because of the rich knowledge make simple . With very good work added by readers.

    A little story of mine:
    I live in Portugal and my skin is type IV (Fitzpatrick). I thought that I would have enough vitamin D because all the year long I have sun and my friends always asked to what beach I used to go.
    Three years ago I had Clamydia pnemophila interstitial pneumonia. For 2 years I didn’t went to a beach… My vitamin D level were very, very, low. Since then I take 20000 IU of Cholecalciferol 3 times a month.

    Thank for your work.

  6. Vitamin D dosage is important and generally misunderstood
    (I’m just copying and pasting something here; I have the refs/links if anybody wants them)

    Recent studies have suggested in discussion that more than 4000 IU per day of vitamin D3 may carry a risk of harm, citing the UK Scientific Advisory Committee on Nutrition report of 2016 which set the recommended Upper Level (UL) intakes of 50mcg/2000IU per day.[10] That report says;
    “Excessive vitamin D intakes have, however, been shown to have toxic effects (Vieth, 2006)”.[10]
    However this is misleading, as the Vieth paper [11] states: “Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L.” This leaves a wide margin of safety.

    The 3 papers mentioned above [3-5] show that a vitamin D3 blood level of at least 75 nmol/L (30 ng/ml) is needed for protection against COVID-19. Government recommendations for vitamin D intake – 400 IU/day for the UK and 600 IU/day for the USA (800 IU for >70 years) and the EU – are based primarily on bone health. This is woefully inadequate in the pandemic context. An adult will need to take 4000 IU/day of vitamin D3 for 3 months to reliably achieve a 75 nmol/L level [12]. Persons of color may need twice as much [13]. These doses can reduce the risk of infection, but are not for treatment of an acute viral infection. And since vitamin D is fat-soluble and its level in the body rises slowly, for those with a deficiency, taking a initial dose of 5-fold the normal dose (20,000 IU/day) for 2 weeks can help to raise the level up to an adequate level to lower infection risk.

  7. “Another finding was that daily and weekly dosing was protective against infection, but that more infrequent bolus dosing (monthly or quarterly) was not protective. ”

    Pharmacokinetics ought not be ignored. Cholecalciferol (D3) serum half-life looks to be around a day or so.

    Calcifediol (25OHD) deficiency is below 20 ng/ml (50 nM/dl) and calcifediol insufficiency is between 20-29 ng/ml (50-74 nM/dl).

    Here’s a 2015 Mayo Clinic article about vitamin D toxicology:

    “Vitamin D is not as toxic as was once thought: A Historical and Up-To-Date Perspective”

    From the paper, 25OHD levels begin to be mildly toxic beginning at 150 ng/ml (375 nM/dl).

    The paper says that toxicity only occurs if between 60-100,000 units of D3 are taken for months or years in most people. (Of course, there are a few people who are sensitive to D3 who cannot supplement it.)

    Putting D3 levels in perspective–most adults can produce between 14,000 and 20,000 units of D3 from one sun exposure and safely do this all summer long multiple times a week. So getting excited about possible toxic effects from dosing with 9,000 units of D3 is silly.

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