The NIH Office of Dietary Supplements published a fact sheet in March 2025 reviewing the evidence behind vitamins C, D, and A, along with zinc, selenium, and probiotics for immune function and infectious diseases. The review lands at a time when supplement sales continue to climb and respiratory virus season pushes millions of Americans toward the vitamin aisle. But the science behind these products is more selective than most labels suggest, and the benefits depend heavily on who is taking them and why.
Vitamin D: The Strongest Case, With Caveats
Of all the micronutrients linked to immune defense, vitamin D has the deepest pool of clinical trial data. The CDC notes that vitamin D supports immune defenses against bacteria and viruses, a claim backed by multiple randomized trials. A landmark individual participant data meta-analysis published in the BMJ, drawing on 25 randomized controlled trials and approximately 11,321 participants, found that vitamin D supplementation reduced the risk of acute respiratory infections overall. The benefit was strongest in people with very low baseline blood levels of 25-hydroxyvitamin D and in those who took daily or weekly doses rather than large, infrequent bolus doses, suggesting that steady intake matters more than sporadic megadoses.
An updated meta-analysis published in The Lancet Diabetes and Endocrinology built on that earlier work by adding six newer eligible randomized controlled trials, including one large trial with approximately 15,804 participants. That update reported an odds ratio of 0.92 from the prior 2021 analysis, and the newer data continued to show a modest protective effect of vitamin D against acute respiratory infections. For clinicians and patients, the practical takeaway is clear: people who are already deficient in vitamin D stand to gain the most from supplementation, while those with adequate levels see little additional protection. Daily intake appears to outperform the occasional mega-dose, which means the once-a-month pill some people favor may not deliver the same results, and routine blood testing can help determine who truly needs extra vitamin D.
Vitamin C: Popular but Overpromised
Vitamin C has been treated as a go-to immune supplement for decades, and it remains the single most recognized name in the category. Harvard Health describes it as an essential micronutrient important to many functions in the body, including antioxidant protection and collagen synthesis. Research dating back to the mid-20th century has explored its effects on infections, with 148 animal studies alone investigating the relationship between vitamin C and diverse infectious agents. Yet despite this long history and the ubiquity of high-dose products, the clinical picture in humans is less dramatic than supplement marketing implies.
A research summary last updated in December 2023 by the German Institute for Quality and Efficiency in Health Care, hosted on NCBI, found that regular vitamin C supplementation did not prevent colds in the general population, though it modestly reduced their duration and severity compared to placebo. That distinction matters: taking vitamin C every day may shave roughly a day off a cold, but starting it after symptoms appear does little. People under extreme physical stress, such as marathon runners or soldiers in subarctic conditions, appear to benefit more than sedentary adults, likely because their baseline needs and oxidative stress levels are higher. For most people, a diet rich in citrus, peppers, and leafy greens already provides sufficient vitamin C without the need for high-dose pills, and exceeding the body’s saturation point mainly results in expensive urine and, at very high intakes, digestive upset.
Zinc and Vitamin A: Targeted Benefits, Real Risks
Zinc affects multiple aspects of the immune system, from the normal development and function of neutrophils and natural killer cells to the signaling pathways that coordinate the body’s inflammatory response. Laboratory research has shown that zinc ions can inhibit rhinovirus replication in experimental systems, which is the biological rationale behind zinc lozenges for colds. A review of 82 eligible studies examining self-care remedies for the common cold found that zinc and certain vitamins showed evidence-based effects on immune barriers, though the authors emphasized that more rigorous research is needed. Zinc lozenges taken within 24 hours of symptom onset have shortened cold duration in several trials, but the NIH’s zinc guidance also warns that chronic high intake can cause copper deficiency and neurological problems, side effects that rarely appear on product labels.
Vitamin A plays a different role. Rather than preventing everyday colds, it becomes critical during specific infectious disease outbreaks and in populations with frank deficiency. During the Central Ohio measles outbreak from November 2022 to February 2023, clinicians treated 85 pediatric cases, 42% of whom required hospitalization, and the majority of those children received vitamin A as part of their treatment following World Health Organization guidelines. That outbreak illustrated how vitamin A deficiency can worsen outcomes in vaccine-preventable diseases, but it also highlighted real-world barriers to implementing guideline-recommended dosing consistently. For the average adult eating a balanced diet, vitamin A deficiency is uncommon in the United States, meaning routine supplementation offers limited benefit and carries its own toxicity risks at high doses, including liver damage and birth defects when taken to excess during pregnancy.
Why “More” Does Not Mean “Better”
The most common misconception about immune-supporting vitamins is that higher doses produce stronger protection. The NIH’s technical review on dietary supplements and immune health stresses that many claims outpace the underlying evidence and that benefits often plateau once basic nutritional needs are met. Its accompanying consumer fact sheet explains that key vitamins and minerals such as A, C, D, E, B6, B12, folate, iron, copper, magnesium, selenium, and zinc all contribute to normal immune function, but taking them in amounts above recommended levels has not been shown to supercharge immunity. In some cases, like fat-soluble vitamins and certain minerals, excess intake can actually impair immune responses or damage organs over time.
The same consumer guidance makes another crucial point: getting enough vitamins and minerals from food or supplements helps the immune system work properly, but there is no convincing evidence that extra amounts prevent infections entirely or help people recover faster once sick. This nuance often gets lost in advertising that blurs the line between correcting deficiency and promising disease prevention. In practice, that means people with documented shortfalls (such as low vitamin D levels, iron deficiency, or limited dietary zinc) may benefit from targeted supplementation, while those already meeting their needs gain little by adding multivitamins, “immune gummies,” or high-dose single-nutrient products on top of a reasonably balanced diet.
Food First, Supplements When Needed
Nutrition researchers and clinicians increasingly emphasize a “food first” approach to immune support. A registered dietitian from Florida International University highlighted that vitamins C and D and the mineral zinc can support immune defenses, but underscored that they are most reliably obtained from foods and fortified products rather than relying solely on pills. Citrus fruits, berries, and bell peppers provide vitamin C; fatty fish, fortified milk, and egg yolks contribute vitamin D; and meat, beans, nuts, and seeds are rich in zinc. Building meals around these foods also delivers fiber and phytonutrients that supplements cannot replicate, supporting the gut microbiome and metabolic health in ways that indirectly bolster immune resilience.
Major health systems echo this message. Mayo Clinic advises people to support immune defenses with overall good nutrition, including plenty of fruits, vegetables, whole grains, lean protein, and healthy fats, rather than chasing single “magic” nutrients. This broader pattern aligns with the NIH’s immune function fact sheets, which frame supplements as tools to fill specific gaps (such as vitamin D in people with limited sun exposure or vitamin B12 in strict vegans), rather than universal necessities. For consumers, the most evidence-based strategy is to prioritize a varied diet, stay up to date on vaccinations, get adequate sleep and physical activity, and then, in consultation with a clinician, use targeted supplements when lab data, medical conditions, or dietary restrictions show a clear need.
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*This article was researched with the help of AI, with human editors creating the final content.
