The 2025 National Institutes of Health (NIH) Dietary Supplements for Immune Function and Infectious Diseases fact sheet describes that adequate intake of vitamins and minerals is required for normal immune function, and deficiencies in nutrients such as vitamins A, B6, B12, C, D, and E, as well as minerals including zinc and selenium, are associated with impaired immune responses and increased susceptibility to infection. Supplementation can restore immune function in deficient individuals, but routine supplementation in individuals without deficiency has limited effect on preventing or treating infections. [1]
Clinical evidence for specific micronutrients is mixed and population-dependent. Vitamin A supplementation reduces diarrhea incidence and mortality in children in low- and middle-income countries but shows inconsistent or no benefit for respiratory infections and does not improve most HIV-related outcomes. Vitamin C supplementation does not reduce incidence of the common cold in the general population but modestly reduces duration and severity of symptoms, with greater effects in individuals under physical stress or with low baseline levels. Vitamin D supplementation shows mixed results across trials, with some meta-analyses demonstrating small reductions in respiratory infection risk, particularly in individuals with low baseline vitamin D status, while other trials show no effect. Vitamin E supplementation has inconsistent effects and does not reduce respiratory infection incidence, with some evidence suggesting increased symptom severity in certain populations. Selenium supplementation shows limited or no consistent effects on immune outcomes in humans despite mechanistic roles. Zinc has demonstrated relatively consistent effects across clinical trials, particularly in reducing duration of common cold symptoms and decreasing incidence of pneumonia and diarrhea in children in low-resource settings, though effects are less pronounced in well-nourished populations. [1]
Evidence for botanicals is heterogeneous and generally limited. Andrographis may reduce symptom severity and duration of respiratory infections, though studies are variable in quality. Echinacea may slightly reduce the risk of upper respiratory infections but does not consistently affect duration or severity. Elderberry may reduce duration and severity of symptoms when taken early, but does not prevent infection and findings are inconsistent. Garlic and ginseng have limited and inconclusive evidence, with some trials suggesting reduced incidence of infections but inconsistent effects on symptom outcomes. [1]
Other supplements show context-specific and variable evidence. Probiotics demonstrate modest reductions in risk and duration of respiratory tract infections in some trials and meta-analyses, though results are strain-specific and heterogeneous, with more consistent evidence in pediatric infectious diarrhea historically but conflicting recent data. Omega-3 fatty acids, glutamine, and N-acetylcysteine have been studied primarily in critically ill or specialized populations, with mixed and inconclusive effects on immune or infection-related outcomes. [1]
Overall, these data suggest that while multiple supplements have been studied for immune function and infectious disease outcomes, evidence is inconsistent, effects are generally modest, and benefits are most evident in populations with nutrient deficiencies or specific clinical conditions rather than in otherwise healthy individuals. [1]
A 2021 meta-analysis evaluated 80 randomized controlled trials (RCTs) assessing micronutrient supplementation for prevention and treatment of acute respiratory tract infections (ARIs) in adults. The authors reported that prior evidence has shown vitamin C and vitamin D reduce the risk of ARIs, while vitamin C and zinc shorten symptom duration, and sought to evaluate the impact of micronutrient supplementation on ARI occurrence and duration. Vitamin D reduced ARI risk (risk ratio [RR] 0.97; 95% confidence interval [CI] 0.94 to 1.00; p= 0.028) and shortened symptom duration by 6% (95% CI −9% to −2%; p= 0.003), and vitamin C reduced ARI risk (RR 0.96; 95% CI 0.93 to 0.99; p= 0.01) and shortened symptom duration by 9% (95% CI −16% to −2%; p= 0.014). Zinc did not reduce ARI risk (RR 1.06; 95% CI 0.95 to 1.18; p= 0.31) but shortened symptom duration by 47% (95% CI −73% to −21%; p= 0.0004). The preventive effect of vitamin D was greater with clinically or laboratory confirmed ARIs and with daily doses ≥2,000 IU and loading doses <60,000 IU, while vitamin C preventive effects were greater among men and in middle-income countries. Evidence for multiple micronutrient supplementation was heterogeneous and not pooled. Overall, the authors concluded that micronutrient supplementation including vitamin D, vitamin C, zinc, and multiple micronutrients may be modestly effective in preventing ARIs and improving their clinical course, although further research is warranted to better understand whether the magnitude of these effects is clinically meaningful. [2]
A 2022 systematic review evaluated 39 RCTs of dietary supplements for immune health in otherwise healthy individuals. The review identified eight ingredients: echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Some studies reported reductions in incidence, severity, or duration of acute respiratory infections with echinacea, garlic, vitamin C, vitamin D, and zinc; however, findings were inconsistent, frequently not statistically significant, and varied by population, dosing, and formulation. Vitamin E showed no benefit and was associated with worse illness outcomes in one study, while evidence for elderberry and vitamin A was limited. No pooled analyses were conducted due to heterogeneity across studies. Overall, the authors concluded that the available evidence is insufficient to determine which supplement provides the most reliable benefit for immune function. [3]
A 2020 review evaluated the role of micronutrients in immune function and infection. The authors reported that vitamins A, D, C, E, B6, and B12, folate, and minerals such as zinc, iron, copper, and selenium are required at multiple stages of the immune response, supporting physical barriers, innate immunity, and adaptive immunity. Evidence indicated that deficiencies, including marginal deficiencies, are associated with impaired immune function and increased susceptibility to infection, and that certain populations, such as those with inadequate dietary intake or increased physiological demands, typically have insufficient micronutrient status. The authors stated that although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection, with the strongest evidence for vitamins C and D and zinc. Rigorously designed clinical studies are required to substantiate the benefits of micronutrient supplementation against infection. Refer to Table 1 for detailed descriptions of the impact of micronutrient deficiencies and supplementation on immune functions. [4]
A 2018 review examined 82 eligible studies evaluating vitamin C, vitamin D, zinc, and Echinacea in relation to immune defenses and prevention or treatment of the common cold. The review reported that these agents have evidence-based activity across physical barriers and innate and adaptive immunity. Regular vitamin C supplementation at 1 to 2 g/day has demonstrated a reduction in common cold duration by 8% in adults and 14% in children and also reduced symptom severity. Zinc supplementation was reported to shorten cold duration by approximately 33%, particularly when started within 24 hours of symptom onset. Vitamin D supplementation was reported to protect against common cold overall, with greater benefit in individuals with deficiency and in those not receiving bolus doses. Prophylactic Echinacea extract at 2,400 mg/day over 4 months appeared beneficial for prevention and treatment of common colds. The authors concluded that, based on these findings, patients may be encouraged to try these supplements for prevention or treatment of the common cold, although further high-quality evidence is needed. [5]