Seven nutrients have EFSA-approved claims for contributing to normal immune function: vitamins C, D, B6, B12, folate, zinc, and selenium. Each plays a distinct and complementary role across innate and adaptive immunity. A multi-nutrient approach addressing both immune pillars has the strongest evidence base for immune support through supplementation, particularly in populations with suboptimal nutritional status.
Key Takeaways
- Seven nutrients carry EFSA-approved claims specifically for contributing to normal immune function: vitamins C, D, B6, B12, folate, zinc, and selenium.
- The immune system comprises two interconnected branches -- innate (rapid, non-specific) and adaptive (targeted, memory-forming) -- and adequate micronutrient status is required for both.2
- Age-related decline in immune function (immunosenescence) is well-documented in humans and is associated with increased vulnerability to infections and reduced vaccine responsiveness.4
- Vitamin C supports multiple immune cell functions, including neutrophil activity and lymphocyte proliferation, and is rapidly depleted during infection.1
- Vitamin D modulates both innate and adaptive immune responses through widespread vitamin D receptor (VDR) expression on immune cells.3
- Zinc is essential for the development and function of T lymphocytes, natural killer cells, and macrophages; even marginal deficiency impairs immune competence.5
- A combined multi-nutrient approach covering all seven EFSA immune nutrients may be more effective than supplementing individual micronutrients in isolation, given their synergistic roles in immune signalling pathways.2
How the Immune System Works: A Brief Overview
The human immune system is a sophisticated, layered network that distinguishes the body's own tissues from foreign threats. It comprises two principal arms that work in continuous coordination.
The innate immune system provides the first line of defence. It responds within minutes to hours of encountering a pathogen through physical barriers (such as the skin and mucous membranes), phagocytic cells (neutrophils and macrophages), and inflammatory signalling. This arm is non-specific -- it does not remember previous encounters.
The adaptive immune system responds more slowly but with precision. B lymphocytes produce antibodies tailored to specific pathogens. T lymphocytes coordinate cellular responses and form immunological memory, enabling faster and stronger reactions upon re-exposure. It typically takes several days to weeks to mount a full adaptive response.2
Immunosenescence: Immune Ageing
With advancing age, both arms of the immune system undergo progressive functional decline -- a process called immunosenescence. Key features include reduced thymic output of naive T cells, impaired natural killer (NK) cell activity, chronic low-grade systemic inflammation (sometimes called "inflammageing"), and diminished vaccine responsiveness in older adults.4
Nutritional status plays an important supporting role in immune competence across the life course. Deficiencies in specific micronutrients are associated with impaired immune function in human populations, and correcting suboptimal status has been shown to support immune parameters in multiple well-designed trials. The research focus in this area has shifted from single-nutrient deficiency correction toward understanding how multi-nutrient combinations support immune resilience, particularly in older adults and those with inadequate dietary intake.2,4
The Seven EFSA-Approved Immune Nutrients
The European Food Safety Authority (EFSA) has reviewed and approved specific health claims for seven micronutrients in relation to normal immune function. These are the only nutrients for which such claims are permitted in the European Union. Each nutrient is reviewed individually below, covering its immune mechanisms, the EFSA-approved claim, and evidence from human studies.
1. Vitamin C
EFSA-approved claim: Vitamin C contributes to the normal function of the immune system.
Vitamin C is an essential water-soluble micronutrient with a well-established role across multiple layers of immune defence. It supports epithelial barrier integrity -- the physical first line of defence against pathogens. Within the innate immune system, vitamin C accumulates in high concentrations in neutrophils and enhances their antimicrobial activities, including chemotaxis (directional movement toward pathogens), phagocytosis, and oxidative killing of bacteria. In the adaptive arm, vitamin C plays a role in lymphocyte proliferation and antibody production.1
An important feature of vitamin C in the context of infection is its rapid depletion. Plasma and leukocyte vitamin C concentrations fall substantially during infections and periods of physiological stress, suggesting increased utilisation. Supplementation in deficient or depleted individuals has been shown to restore immune cell function parameters in human studies.1
Vitamin C is also a potent antioxidant that contributes to protection of cells from oxidative stress -- a function particularly relevant during the inflammatory phase of immune activation, when reactive oxygen species are generated in large quantities.
Dietary sources: Citrus fruits, kiwifruit, bell peppers, strawberries, broccoli, and tomatoes. The adult reference nutrient intake in the EU is 80 mg/day; studies examining immune parameters have used doses ranging from 200 mg to 1,000 mg per day.
2. Vitamin D
EFSA-approved claim: Vitamin D contributes to the normal function of the immune system.
Vitamin D functions as an immunomodulatory hormone. The active form, 1,25-dihydroxyvitamin D (calcitriol), acts on vitamin D receptors (VDRs) expressed on virtually all immune cell types -- including monocytes, macrophages, dendritic cells, T cells, and B cells. Through VDR signalling, calcitriol influences the production of antimicrobial peptides (such as cathelicidin and defensins), regulates inflammatory cytokine production, promotes T-regulatory cell differentiation, and modulates the balance between pro-inflammatory and tolerogenic immune states.3
Vitamin D deficiency is highly prevalent globally, particularly in northern latitudes, among older adults (who have reduced skin synthesis), and in individuals with limited sun exposure. Low serum 25-hydroxyvitamin D (25(OH)D) status has been consistently associated with impaired immune parameters in observational studies. Multiple randomised controlled trials have examined the effects of vitamin D supplementation on immune-related outcomes, with results that are informative but mixed.3
A large, updated systematic review and meta-analysis pooling data from 46 RCTs examined the relationship between vitamin D supplementation and acute respiratory infection (ARI) incidence. Effects were variable across populations and dosing strategies, with benefit appearing most consistent in individuals with lower baseline vitamin D status and with daily or weekly (rather than bolus) dosing regimens.8
Dietary sources: Fatty fish, fortified dairy products, egg yolks. The primary source for most individuals is cutaneous synthesis via UV-B radiation. Supplementation is frequently required to maintain adequate status, particularly in higher-latitude populations.
3. Vitamin B6
EFSA-approved claim: Vitamin B6 contributes to the normal function of the immune system.
Vitamin B6 (pyridoxine) serves as a coenzyme in over 100 enzymatic reactions. In the context of immune function, B6 is involved in the synthesis of cytokines, the proliferation of lymphocytes, the production of interleukin-2 (IL-2), and the regulation of T-cell function. B6 deficiency in humans is associated with reduced lymphocyte proliferation and impaired antibody responses.2
Vitamin B6 status tends to decline with age. Older adults are more likely to have suboptimal B6 status, and population surveys have documented inadequate intakes in significant proportions of adults in multiple countries. Vitamin B6 also contributes to normal homocysteine metabolism and plays a role in psychological function -- both EFSA-approved claims relevant to overall wellbeing.
Dietary sources: Poultry, fish, potatoes, starchy vegetables, and non-citrus fruits. The EU reference intake is 1.4 mg/day for adults.
4. Vitamin B12
EFSA-approved claim: Vitamin B12 contributes to the normal function of the immune system.
Vitamin B12 (cobalamin) is required for DNA synthesis, one-carbon metabolism, and the maintenance of the myelin sheath around nerve fibres. In immune function, B12 is necessary for the proliferation and differentiation of immune cells. Adequate B12 status supports lymphocyte formation and influences the balance of cytokine production. B12 deficiency leads to impaired natural killer (NK) cell activity and reduced CD8+ T cell counts in human subjects.2
B12 deficiency is particularly common in older adults due to reduced gastric acid and intrinsic factor secretion, which are required for absorption of the dietary form of B12. Vegans and vegetarians are also at risk, as B12 is found almost exclusively in animal-derived foods. The consequences of deficiency are wide-ranging, affecting both neurological and immune competence.
Dietary sources: Meat, fish, dairy products, eggs, and fortified plant-based foods. Adults following plant-based diets should consider supplementation or fortified food sources. The EU reference intake is 2.5 mcg/day.
5. Folate
EFSA-approved claim: Folate contributes to the normal function of the immune system.
Folate (vitamin B9) works in close partnership with vitamin B12 in one-carbon metabolism, supporting DNA synthesis and methylation. Adequate folate is required for the rapid proliferation of immune cells during an immune response. Deficiency impairs lymphocyte development, reduces the functional maturity of T and B cells, and has been shown in human studies to alter cytokine production profiles toward a more inflammatory pattern.2
Folate deficiency is among the most common nutritional deficiencies globally, particularly in older adults and those with high alcohol intake. Suboptimal folate status also elevates homocysteine -- a metabolic marker associated with cardiovascular risk and with inflammatory signalling in immune tissues.
Dietary sources: Dark leafy vegetables, legumes, whole grains, and fortified foods. The EU reference intake is 200 mcg/day; higher intakes are recommended during pregnancy to support neural tube development.
6. Zinc
EFSA-approved claim: Zinc contributes to the normal function of the immune system.
Zinc is a trace element that is indispensable for virtually every aspect of immune function. It is required for the development of innate immune cells (neutrophils, NK cells, monocytes) and for the maturation and function of adaptive immune cells (T and B lymphocytes). Zinc also acts as a co-factor for thymulin -- a thymic hormone essential for T cell differentiation -- and regulates cytokine signalling through its effects on NF-kappaB pathways.5
Even mild zinc deficiency significantly impairs immune function in humans. A systematic review and meta-analysis of 35 RCTs comprising nearly 2,000 participants found that zinc supplementation significantly reduced circulating CRP (a key inflammatory marker) and hs-CRP, and increased CD4+ T lymphocyte counts in human populations.6
Older adults are particularly prone to zinc insufficiency due to reduced dietary intake, altered absorption, and increased physiological requirements. The resulting immune impairment in older populations is a recognised contributor to immunosenescence.
Zinc also carries additional EFSA-approved claims relevant to healthy ageing, including contributions to normal cognitive function, DNA synthesis, protection of cells from oxidative stress, and maintenance of normal bones, hair, and skin.
Dietary sources: Red meat, shellfish (especially oysters), legumes, nuts, seeds, and whole grains. Absorption is lower from plant sources due to phytate content. The EU reference intake is 9.4 mg/day for men and 7.5 mg/day for women.
7. Selenium
EFSA-approved claim: Selenium contributes to the normal function of the immune system.
Selenium exerts its biological effects primarily through selenoproteins -- a family of approximately 25 proteins in which selenium is incorporated as the amino acid selenocysteine. Several glutathione peroxidase enzymes (GPx1-4) are selenoproteins with critical antioxidant functions in immune cells. Thioredoxin reductases (TrxR), also selenoproteins, regulate cellular redox balance and inflammatory signalling.
In immune cells, selenium availability is linked to lymphocyte proliferation, NK cell activity, and antibody responses. Selenium also contributes to protection of cells from oxidative stress -- relevant because immune activation generates substantial oxidative burden that can damage the very cells mounting the defence.7
A systematic review and meta-analysis of experimental human studies (nine RCTs) found that selenium supplementation in selenium-deficient populations influenced T cell counts and NK cell activity in a dose-dependent manner. Effects were most consistent in individuals with baseline selenium levels below adequate status, and the evidence indicated that raising plasma selenium above approximately 100 mcg/L did not produce additional immune benefit -- suggesting selenium's immune role is primarily linked to correcting insufficiency rather than megadosing.7
Selenium intake is notably geography-dependent: soils in parts of Europe (particularly northern and central regions) and the UK are selenium-poor, meaning that food-based selenium intake in these populations tends to be lower than in North America.
Selenium also contributes to maintenance of normal hair and nails and to normal thyroid function -- additional EFSA-approved claims relevant to overall health maintenance.
Dietary sources: Brazil nuts (a particularly concentrated source), seafood, meat, eggs, and cereals. Selenium content of plant foods varies significantly with soil content. The EU reference intake is 70 mcg/day.
Longevity Complete: Immune Nutrients in Context
All seven EFSA-approved immune nutrients -- vitamins C, D, B6, B12, folate, zinc, and selenium -- are included in Longevity Complete. This reflects a formulation philosophy built around nutritional completeness rather than single-ingredient focus.
In practice, achieving optimal status across all seven of these nutrients through diet alone can be challenging, particularly for older adults (who face absorption challenges with B12, reduced vitamin D synthesis, and frequently marginal zinc intakes), individuals with plant-based diets (who need to consider B12 and selenium sourcing), and those living in regions with selenium-poor soils or limited UV exposure.4
Products that provide a comprehensive micronutrient foundation -- rather than isolated high-dose single nutrients -- align with the current scientific understanding that immune function is a multi-nutrient process. Longevity Complete is independently tested through Eurofins laboratories and holds NZVT doping-free certification, providing independent verification of ingredient content and purity.
To be precise about approved claims: Vitamin C, D, B6, B12, folate, zinc and selenium contribute to the normal function of the immune system. No disease treatment or prevention claims are made or implied.
Beyond the Basics: Emerging Immune Research
Vitamin D Dose-Response Considerations
The relationship between vitamin D status and immune outcomes is dose-dependent and threshold-based rather than linear. Evidence from human trials suggests that achieving a serum 25(OH)D of at least 50 nmol/L (20 ng/mL) may be more important for immune support than the absolute supplemental dose taken. Daily or weekly dosing appears more consistently beneficial than high-dose bolus supplementation for immune endpoints.8 Individuals should consult a healthcare provider to assess their vitamin D status before supplementing at high doses.
Zinc Lozenges and Acute Situations
Some clinical research has examined zinc lozenges (delivering ionic zinc to the upper respiratory mucosa) in the context of common colds. The evidence base is separate from that of supplemental zinc for general immune support, and results have been mixed. High-dose zinc supplementation is not recommended without medical supervision, as excessive zinc intake can interfere with copper absorption and, paradoxically, impair immune function.
Beta-Glucans and Immune Priming
Beta-1,3/1,6-glucans, derived from yeast or oats, have been studied in human RCTs for their effects on immune cell activity. Several trials have reported effects on natural killer cell function and upper respiratory infection outcomes. Beta-glucans are not among the seven EFSA-approved immune nutrients but represent an area of active human research. Results are promising but evidence is still accumulating, and no EFSA health claims are currently approved for beta-glucans and immune function.
The Gut-Immune Axis
Approximately 70% of the body's immune tissue is located in the gut-associated lymphoid tissue (GALT). Micronutrient status influences gut barrier integrity, and several of the EFSA immune nutrients (particularly vitamin D, zinc, and vitamin A) play roles in maintaining the physical and immunological integrity of the intestinal lining. Probiotic and prebiotic research in the context of immune function is ongoing; this topic is addressed in more detail in the gut health article (see internal links).
Q&A: Immune System Nutrients
Which nutrients have EFSA-approved claims for immune function?
Seven nutrients carry EFSA-approved claims for contributing to normal immune function: vitamins C, D, B6, B12, folate (vitamin B9), zinc, and selenium. These are the only nutrients for which the European Food Safety Authority has reviewed and approved immune-function claims based on available scientific evidence. Each plays a distinct, mechanistically characterised role in immune competence.2
Does vitamin D really affect immunity?
Yes. Vitamin D receptor (VDR) expression has been identified on virtually all immune cells, including T cells, B cells, monocytes, and dendritic cells. The active form of vitamin D modulates both innate and adaptive immune responses, including the production of antimicrobial peptides and the regulation of inflammatory signalling.3 Human RCT evidence on supplementation outcomes is variable but strongest in those with deficient baseline vitamin D status.
What does zinc deficiency do to the immune system?
Zinc deficiency -- even at a marginal level -- impairs multiple aspects of immune function in humans. These include reduced thymulin activity (impairing T cell maturation), decreased NK cell cytotoxicity, impaired neutrophil function, and dysregulated cytokine production.5 Older adults are particularly vulnerable to marginal zinc insufficiency due to reduced intake and altered absorption.
Why does vitamin C deplete during illness?
Vitamin C is rapidly consumed during immune activation. Neutrophils -- which are mobilised in large numbers during infection -- accumulate vitamin C at concentrations up to 100 times higher than plasma levels to support their oxidative killing mechanisms. Additionally, physiological stress and systemic inflammation increase utilisation of vitamin C as an antioxidant, depleting body stores.1
Are B vitamins important for the immune system?
Yes, three B vitamins -- B6, B12, and folate -- contribute to normal immune function (EFSA-approved). Their shared involvement in one-carbon metabolism supports DNA synthesis, which is essential for the rapid cell division required during an immune response. B12 and folate are especially important for lymphocyte production and function. B6 is required for cytokine synthesis and T-cell proliferation.2
What is immunosenescence?
Immunosenescence refers to the age-related decline in immune system function. It encompasses thymic involution (reducing the supply of naive T cells), reduced innate immune responsiveness, chronic low-grade inflammation, impaired vaccine responses, and greater vulnerability to infections. Multiple micronutrient deficiencies -- common in older adults -- contribute to immunosenescence and can be partially addressed by adequate nutritional status.4
Is it better to take individual immune nutrients or a multi-nutrient formula?
The current scientific understanding favours a multi-nutrient approach. The seven EFSA immune nutrients act synergistically -- for example, vitamin C, zinc, and selenium all support antioxidant protection of immune cells, while B6, B12, and folate contribute to the DNA synthesis required for lymphocyte proliferation. Deficiencies often coexist, and supplementing a broad micronutrient foundation may be more practical and physiologically appropriate than addressing single-nutrient gaps in isolation.2,4
Does selenium improve immune function in humans?
Human RCT evidence shows that selenium supplementation can influence T cell counts and NK cell activity in selenium-deficient individuals.7 Importantly, these effects appear to be most pronounced in those correcting insufficiency rather than in already-replete individuals. Selenium's role in antioxidant protection of immune cells via glutathione peroxidase enzymes is well-established mechanistically.
Can I get all seven immune nutrients from food alone?
For most adults eating a varied, balanced diet rich in fruits, vegetables, lean protein, and whole grains, it is theoretically possible to obtain adequate amounts of all seven nutrients. In practice, however, several vulnerable groups face challenges: older adults (reduced B12 absorption, vitamin D synthesis, and zinc intake), individuals on plant-based diets (B12, potentially selenium), those with limited sun exposure (vitamin D), and people living in selenium-poor regions (selenium). A targeted supplement or a well-formulated multi-nutrient product can help address these gaps.
How does the immune system change with age?
With age, the immune system undergoes structural and functional changes collectively termed immunosenescence. The thymus gland, which produces and matures T lymphocytes, progressively involutes from early adulthood. This reduces the pool of naive T cells available to respond to new pathogens. Simultaneously, chronic low-grade inflammation increases (inflammageing), and the efficiency of vaccine-induced antibody responses decreases.4 Adequate nutritional status across the seven EFSA immune nutrients is a modifiable factor that supports immune maintenance in ageing populations.
Frequently Asked Questions
What are the seven EFSA-approved nutrients for immune function?
The seven nutrients with EFSA-approved claims for contributing to normal immune function are: vitamin C, vitamin D, vitamin B6, vitamin B12, folate, zinc, and selenium. Each plays a distinct and complementary role in supporting both the innate and adaptive arms of the human immune system.2
Why is vitamin D important for immunity?
Vitamin D receptors are expressed on all major immune cell types, enabling calcitriol (the active form of vitamin D) to regulate innate and adaptive immune responses. It promotes antimicrobial peptide production, modulates inflammatory cytokine balance, and supports T-regulatory cell activity.3 Deficiency is associated with impaired immune parameters in human studies.
Which populations are most at risk of immune-relevant micronutrient deficiencies?
Older adults face the highest combined risk: reduced vitamin D synthesis from skin, impaired B12 absorption, frequently marginal zinc and folate intakes, and often limited selenium consumption depending on geography. People following strict plant-based diets are at risk for B12 deficiency in particular. Individuals in northern Europe may also have suboptimal selenium status due to low soil selenium content.4
Does zinc supplementation affect immune markers in humans?
Yes. A systematic review and meta-analysis of 35 RCTs in humans found that zinc supplementation significantly reduced circulating CRP and hs-CRP, and was associated with increased CD4+ T lymphocyte counts.6 Effects were most pronounced in populations with pre-existing zinc insufficiency. High-dose zinc supplementation should be approached cautiously and under healthcare guidance.
What does selenium do for the immune system?
Selenium is incorporated into selenoproteins, including glutathione peroxidase enzymes, which protect immune cells from oxidative damage during activation. Human RCT evidence indicates that selenium supplementation can influence T cell and NK cell activity, particularly in those correcting selenium insufficiency.7 Its EFSA-approved claim is that selenium contributes to normal immune function.
Does Longevity Complete contain all seven EFSA immune nutrients?
Yes. Longevity Complete contains all seven nutrients with EFSA-approved claims for contributing to normal immune function: vitamins C, D, B6, B12, folate, zinc, and selenium. This reflects a formulation philosophy centred on comprehensive nutritional coverage, with all ingredients independently verified through Eurofins laboratory testing. Product mention is for educational context only and no disease claims are made.
References
- Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. doi: 10.3390/nu9111211. View on PubMed ↑
- Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System -- Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020;12(1):236. doi: 10.3390/nu12010236. View on PubMed ↑
- Bikle DD. Vitamin D: Production, Metabolism, Mechanism of Action, and Clinical Requirements. In: Feingold KR, et al., eds. Endotext. 2020. PMID: 32679784. View on PubMed ↑
- Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020;12(4):1181. doi: 10.3390/nu12041181. View on PubMed ↑
- Wessels I, Fischer HJ, Rink L. Dietary and Physiological Effects of Zinc on the Immune System. Annu Rev Nutr. 2021;41:133-175. doi: 10.1146/annurev-nutr-122019-120635. View on PubMed ↑
- Jafari A, Noormohammadi Z, Askari M, Daneshzad E. Zinc supplementation and immune factors in adults: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Food Sci Nutr. 2022;62(11):3023-3041. doi: 10.1080/10408398.2020.1862048. View on PubMed ↑
- Filippini T, Fairweather-Tait S, Vinceti M. Selenium and immune function: a systematic review and meta-analysis of experimental human studies. Am J Clin Nutr. 2023;117(1):93-110. doi: 10.1016/j.ajcnut.2022.11.007. View on PubMed ↑
- Jolliffe DA, et al. Vitamin D supplementation to prevent acute respiratory infections: updated systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2025. PMID: 39993397. View on PubMed ↑
