Vitamin D and the Immune System: How Much Does It Really Lower Your Risk of Getting Sick?
Table of Contents
Key Takeaways
- In a 2017 individual participant data meta-analysis of 25 trials, vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted OR 0.88).[1]
- The largest benefit in that analysis was seen in people with baseline 25-hydroxyvitamin D below 25 nmol/L who received daily or weekly doses (adjusted OR 0.30), although this subgroup included only 234 participants.[1]
- A 2021 update with data from 43 trials found a small risk reduction in its primary comparison (OR 0.92); protective effects were seen in subgroup analyses of daily dosing regimens and daily doses of 400–1000 IU, although these findings did not establish either regimen as superior.[2]
- The 2025 update found an OR of 0.94 whose 95% CI now includes 1.00, indicating no statistically significant protection.[3]
- In the CORONAVIT trial, a population-level test-and-treat approach was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.[4]
- The Endocrine Society suggests empiric vitamin D for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections, but suggests against vitamin D above the current DRI for healthy adults younger than 75 years.[5]
- In endurance athletes, low vitamin D status could be an important determinant of URTI risk.[6]
- In my clinical experience, vitamin D deficiency is the deficiency I most often see in my Finnish patients’ laboratory tests, especially in autumn and winter, when the low vitamin D season usually coincides with the infection season.
- In my practice, the basic investigations, including asthma testing, rarely reveal a clear cause for recurrent infections, and in my view, unfortunately, unusual illness is often just bad luck.
Introduction: Vitamin D Immune System
Most people have heard that vitamin D “boosts immunity.” The real question is how much it actually changes your chances of catching a cold or another respiratory infection. Observational data show a clear association: in a US population sample, recent upper respiratory tract infection was reported by 24% of participants with 25(OH)D levels less than 10 ng/mL, compared with 17% at 30 ng/mL or higher.[7] But an association is not proof that taking a supplement will keep you healthier.
As a physician who runs infection clinics and a former world champion in Taekwon-Do, I see this question from both the clinical side and the athletic side. In my clinical work as a general practitioner and occupational health physician, vitamin D deficiency is something I see fairly often. In my experience, the basic laboratory panels in our occupational health service, and often at public health centres too, include a vitamin D measurement. Because we in Finland live at a high latitude, we get little sunlight, especially in winter. I find that my own patients have vitamin D deficiency quite often, perhaps more often than other deficiencies. I do sometimes see vitamin B12 or folate deficiency, but vitamin D is the deficiency I encounter most.
This article covers how vitamin D interacts with the immune system, what the large randomised trials and meta-analyses actually found, why the answer has shifted over the last decade, and what is known for athletes and for people living at northern latitudes such as Finland.
How Vitamin D Works Inside the Immune System
Vitamin D is not only a bone vitamin. Immune cells express the vitamin D receptor, including antigen presenting cells, T cells and B cells, and these cells are all capable of synthesizing the biologically active vitamin D metabolite.[8]
One of the best-described mechanisms involves innate immunity. In a laboratory study published in Science, TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1–hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis.[9] The authors concluded that these data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.[9]
The same pattern appears in athletes: the plasma cathelicidin concentration positively correlated with the plasma 25(OH)D concentration, and low vitamin D status was associated with lower pro-inflammatory cytokine production by monocytes and lymphocytes.[6]
Mechanisms explain why vitamin D could matter. Whether a supplement actually reduces how often people get sick has to be answered by clinical trials.
Low Vitamin D and Infection Risk: What Observational Studies Show
The association between low vitamin D levels and respiratory infections has been seen in several populations.
In the US NHANES III data, compared with levels of 30 ng/mL or higher, the adjusted odds ratio for recent URTI was 1.36 at levels below 10 ng/mL and 1.24 at levels of 10 to under 30 ng/mL.[7] The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease.[7]
Finnish data point the same way. In 756 young Finnish men on a military base, the mean serum 25(OH)D was 80.2 ± 29.3 nmol/L, and those with concentrations below 40 nmol/L had significantly more days of absence from duty due to respiratory infection (median 4) than control subjects (median 2).[10]
In my practice, I see vitamin D deficiency especially in autumn and winter. In summer I see it less, as people are outdoors and get sunlight. Many of these patients come to my clinic because of fatigue, and they typically suspect iron deficiency first. I check haemoglobin and iron values, and I am used to checking other vitamins at the same time, together with thyroid hormones. Many patients do turn out to have low iron, but I also find low vitamin D quite often. In my experience, the low vitamin D season usually coincides with the infection season.
Observational studies cannot rule out reverse causation or confounding.
Does Vitamin D Prevent Colds? What the Vitamin D Immune System Trials Found
The strongest evidence comes from randomised controlled trials pooled in meta-analyses. The answer has shifted as more trials were added.
2017: A modest overall benefit, larger in deficient people
An individual participant data meta-analysis of 25 randomised trials (11,321 participants aged 0 to 95 years, with individual participant data obtained for 10,933) found that vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted OR 0.88, 95% CI 0.81 to 0.96).[1] Protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted OR 0.81), but not in those receiving one or more bolus doses (adjusted OR 0.97).[1]
The effect was strongest in people who were very deficient. Among those receiving daily or weekly vitamin D, the adjusted OR was 0.30 in those with baseline 25-hydroxyvitamin D levels below 25 nmol/L (a subgroup of 234 participants), compared with 0.75 in those at 25 nmol/L or above.[1]
2021: A smaller effect, best with daily dosing
The 2021 update obtained data for 48,488 participants in 43 studies.[2] In the primary comparison, at least one acute respiratory infection occurred in 61.3% of participants in the vitamin D group versus 62.3% in the placebo group (OR 0.92, 95% CI 0.86–0.99).[2] In subgroup analyses, protective effects were observed with daily dosing (OR 0.78), at daily dose equivalents of 400–1000 IU (OR 0.70), for interventions lasting 12 months or less (OR 0.82), and at age 1.00–15.99 years at enrolment (OR 0.71).[2] The authors concluded that vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small.[2]
2025: No longer statistically significant
In the primary comparison of the most recent update, data from 61,589 participants in 40 studies were analysed.[3] The overall effect was OR 0.94 (95% CI 0.88–1.00), and the 95% CI for this effect estimate now includes 1.00, indicating no statistically significant protection.[3] Prespecified subgroup analyses found no evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size.[3]
In a Finnish randomised trial in 164 young conscripts, 400 IU of vitamin D3 daily did not significantly reduce days absent from duty due to respiratory infection, but 51.3% of the vitamin D group remained healthy throughout the 6 months, compared with 35.7% of the placebo group.[11]
The CORONAVIT trial
In the UK CORONAVIT trial, people with 25(OH)D below 75 nmol/L were offered 800 IU/day or 3200 IU/day for six months, and this test-and-treat approach was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.[4]
In my practice, many patients with recurrent infections ask whether there is anything they could do. When vitamin D deficiency has been confirmed in these situations, I have sometimes suggested vitamin D supplementation to these individual patients. On a personal level, my subjective experience is that I and my family have been ill less often since we started taking vitamin D supplements. It is hard to say what is due to what, so this is only my own subjective experience.
Vitamin D, the Immune System and Athletes
Vitamin D status and respiratory illness have also been studied specifically in athletes.
In a study of 225 endurance athletes over 16 weeks of winter training, 38% at the start and 55% at the end had inadequate (25(OH)D 30–50 nmol/L) or deficient (below 30 nmol/L) vitamin D status.[6] There was a significantly higher proportion of subjects with URTI symptoms in the vitamin D deficient group than in the optimal vitamin D group, and the total number of URTI symptom days and the median symptom-severity score in the deficient group were significantly higher.[6]
A review on athletes and military personnel reports vitamin D insufficiency (circulating 25(OH)D below 50 nmol/L) in more than half of all athletes and military personnel tested during the winter, when skin sunlight UVB is negligible.[8] The authors provide practical recommendations for how vitamin D sufficiency can be achieved in most individuals by safe sunlight exposure in the summer and daily 1,000 IU vitamin D3 supplementation in the winter.[8]
In a military training study combining an observational cohort and a randomised trial, only 21% of recruits in the cohort were vitamin D sufficient during winter, and the authors concluded that vitamin D sufficiency reduced the URTI burden during military training.[12]
In my practice, many patients are troubled by repeated illnesses during the autumn and winter season. Many of my patients who play sports are understandably worried about what happens if they train while sick (I have covered this in more detail in Exercise When Sick). Some athletes do not mind a mild cold and train anyway, while others are especially careful. Either way, in my experience recurrent illness does make it harder for athletes to perform and can affect their careers, and they often come to my clinic to ask whether there is anything they could do to prevent it.
With these patients, I am used to checking the basic investigations, such as routine laboratory tests, and we often do asthma testing as well, since asthma may develop. However, these rarely reveal anything clearly increasing susceptibility to infection. I seldom suspect an immunodeficiency either, as in many of these patients no particular susceptibility to infection was evident in childhood. Some have had recurrent ear infections when they were young, but once past that age, many have had no exceptional illness. This does not rule out an immunodeficiency, but as I see it, it speaks somewhat against it. In my experience, these illnesses often fall in the cold and flu season, when patients also often have lower vitamin D levels, and one can always wonder whether this plays a role. For an individual patient, it is difficult to say what affects what, and in my view, unfortunately, unusual illness is often just bad luck.
Some of my patients have chronic sinusitis, which keeps the illness going: it may improve for a while, but then it can recur again. Some have nasal polyps or long-standing pansinusitis or chronic rhinosinusitis that keep flaring up. On the other hand, I also regularly see patients at my clinic with clear symptoms suggestive of indoor air problems. In my experience, investigating these is usually very difficult, as cause and effect are hard to demonstrate, especially if the patient does not have asthma. If spirometry does not reveal asthma, I have found that the possibilities to intervene are very limited.
What the Guidelines Say About Vitamin D and Infections
The 2024 Endocrine Society guideline focuses on vitamin D to lower the risk of disease in people without established indications for treatment.[5]
- The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections.[5]
- The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years.[5]
- No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, and the panel suggests against routine 25(OH)D testing in all populations considered.[5]
Many of my patients already take a vitamin D supplement. For many people it is a familiar supplement, and it is available straight off the shelf even in grocery stores. When a deficiency has been found, I have suggested vitamin D supplementation to these individual patients. I have also discussed with patients that a light, modest daily supplement is something many people take without testing, which is different from taking large amounts; the Endocrine Society suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years.[5] Patients also ask how much vitamin D they can take and whether extra is worthwhile. In those conversations, I have told them that vitamin D probably helps mainly in correcting a deficiency, and I have not usually suggested routine extra vitamin D on top of that.
What the Research Doesn’t Tell Us
Several questions remain open. The 2025 update found no evidence of effect modification by baseline vitamin D status,[3] even though the 2017 analysis had found the strongest protection in people below 25 nmol/L.[1] For athletes, the review authors note that studies are required to determine the impact of these recommendations on immunity and URI, and to demonstrate the purported benefit of achieving 25(OH)D above 75 nmol/L.[8]
On safety, the authors of the 2021 meta-analysis concluded that vitamin D supplementation was safe.[2]
Conclusion
Vitamin D clearly interacts with the immune system, and low levels are associated with more respiratory infections in observational data.[7][10] The trial evidence, however, points to a small effect at most. The 2017 meta-analysis found an adjusted OR of 0.88,[1] the 2021 update an OR of 0.92,[2] and the 2025 update an OR of 0.94 with no statistically significant protection.[3] The Endocrine Society suggests empiric vitamin D for children and adolescents aged 1 to 18 years, but suggests against doses above the current DRI for healthy adults younger than 75 years.[5]
This matches what I see in practice: I see low vitamin D most often in autumn and winter, the same season when patients come in with recurrent infections. For an individual patient, it is difficult to say what affects what, and in my view, unfortunately, unusual illness is often just bad luck.
Vitamin D is not a shield against every winter infection, but understanding what the evidence does and does not show helps you have a better-informed conversation with your own doctor.
References
- https://doi.org/10.1136/bmj.i6583
- https://doi.org/10.1016/S2213-8587(21)00051-6
- https://doi.org/10.1016/S2213-8587(24)00348-6
- https://doi.org/10.1136/bmj-2022-071230
- https://doi.org/10.1210/clinem/dgae290
- https://pubmed.ncbi.nlm.nih.gov/23977722/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3447082/
- https://pubmed.ncbi.nlm.nih.gov/26853300/
- https://doi.org/10.1126/science.1123933
- https://doi.org/10.1093/ajcn/86.3.714
- https://doi.org/10.1086/654881
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8208091/
