Key Takeaways
- Zinc contributes to normal immune function, cognitive function, DNA synthesis, and protection of cells from oxidative stress (EFSA-approved claims).
- Selenium contributes to normal immune function, normal thyroid function, protection of cells from oxidative stress, and maintenance of normal hair and nails (EFSA-approved claims).
- A meta-analysis of 35 RCTs (1,995 participants) found that zinc supplementation significantly reduced inflammatory markers (CRP, TNF-alpha, IL-6) and increased CD4+ T-cell counts in adults.1
- Zinc deficiency is common in older adults. A review estimated that up to 40% of elderly populations in developed countries may have inadequate zinc intake, with parallels between zinc deficiency and age-related immune decline.2
- Selenium status varies significantly by geographic region, with parts of Europe having notably low soil selenium levels. Adequate selenium is required for the function of selenoproteins including glutathione peroxidase.3
- Both minerals have a narrow optimal range: deficiency impairs immune function, while excessive intake can also cause harm. The tolerable upper intake level is 25 mg/day for zinc and 300 micrograms/day for selenium in the EU.
Zinc: The Immune Mineral
Zinc is an essential trace element involved in over 300 enzymatic reactions and more than 1,000 transcription factors. It plays a central role in both innate and adaptive immunity, from the function of natural killer cells and neutrophils to T-cell maturation and antibody production.
Zinc contributes to normal immune function (EFSA-approved claim). This claim reflects the well-established biochemical roles of zinc in immune cell signalling, proliferation, and differentiation. Zinc also contributes to normal cognitive function, normal DNA synthesis, and protection of cells from oxidative stress (EFSA-approved claims).
A systematic review and meta-analysis of 35 randomised controlled trials (1,995 participants) evaluated the effects of zinc supplementation on immune factors in adults. The analysis found significant reductions in C-reactive protein (CRP), high-sensitivity CRP, TNF-alpha, and IL-6 following zinc supplementation. CD4+ T-cell counts also increased significantly. However, no significant effects were observed on total white blood cell count, lymphocyte count, or monocyte levels.1
A separate meta-analysis confirmed that zinc supplementation is associated with reductions in serum markers of both inflammation (CRP, TNF-alpha) and oxidative stress (malondialdehyde) in adults.4
Zinc Deficiency in Ageing Populations
Zinc deficiency becomes more common with age due to several factors: reduced dietary intake, decreased absorption efficiency, medication interactions (particularly diuretics and proton pump inhibitors), and altered metabolic requirements. A comprehensive review noted that up to 40% of elderly populations in developed countries may have inadequate zinc intake, and that marginal zinc deprivation, even without overt clinical deficiency, can impair immune function.2
The parallels between zinc deficiency and immunosenescence (age-related immune decline) are well documented. Both are characterised by thymic involution, a shift from Th1 to Th2 immune responses, decreased vaccination response, and increased inflammatory signalling. A 2025 review described zinc deficiency as a possible link between immunosenescence and age-related conditions, noting that zinc supplementation in older adults has demonstrated potential to improve immune responses and reduce chronic low-grade inflammation (sometimes termed "inflammaging").5
Selenium: Antioxidant and Thyroid Support
Selenium is an essential trace element incorporated into selenoproteins, a family of at least 25 proteins that play critical roles in antioxidant defence, thyroid hormone metabolism, and immune regulation. The most well-studied selenoproteins include glutathione peroxidase (which neutralises hydrogen peroxide and lipid hydroperoxides), thioredoxin reductase (which regenerates thioredoxin for antioxidant defence), and iodothyronine deiodinases (which convert thyroid hormones between their active and inactive forms).
Selenium contributes to normal immune function, normal thyroid function, protection of cells from oxidative stress, and maintenance of normal hair and nails (EFSA-approved claims).
Geographic Variation in Selenium Status
Selenium status varies substantially by region, because soil selenium content directly affects the selenium concentration in locally grown crops and, consequently, in the food supply. Parts of Northern Europe, including areas of the United Kingdom, Scandinavia, and Eastern Europe, have relatively low soil selenium levels. In contrast, regions such as parts of North America tend to have higher soil selenium. This geographic variation means that selenium deficiency is more prevalent in certain European populations than in others.
A 2024 systematic review and meta-analysis of randomised controlled trials (35 studies) examined selenium supplementation in the context of thyroid autoimmunity. The analysis found that selenium supplementation was associated with reductions in thyroid peroxidase antibody levels in certain populations, though the clinical significance of this finding and its relevance to healthy individuals remains debated.3 Selenium's role in thyroid function is well established at the biochemical level: the thyroid gland contains the highest selenium concentration per gram of tissue in the body.
Zinc and Selenium in Longevity Research
Both zinc and selenium have been studied for their roles in ageing-related pathways, though it is important to note that this research is largely observational and does not establish causation.
An umbrella review of 43 meta-analyses examined the totality of evidence for zinc intake and health outcomes. The review found associations between adequate zinc status and various aspects of health, but also noted that higher-dose supplementation (above 40 mg/day) did not show clear additional benefits for all-cause mortality.6
A review in the journal Immunity and Ageing described the relationship between zinc status and immunosenescence, noting that zinc is required for the function of key immune cells including neutrophils, macrophages, natural killer cells, and lymphocytes. The authors suggested that addressing zinc deficiency in ageing populations could help support immune resilience, though they emphasised that more high-quality interventional studies are needed.5
For selenium, a Swedish cohort study of 403 elderly individuals with low baseline selenium levels (mean 67 micrograms/L) found that supplementation with selenium yeast (200 micrograms/day) combined with coenzyme Q10 (200 mg/day) for four years was associated with lower levels of the inflammatory marker CRP and with longer leukocyte telomere length compared to placebo. However, this was a single study with combined supplementation, and the individual contributions of selenium and CoQ10 cannot be separated.7
Forms, Dosing, Safety, and Food Sources
Zinc Forms and Dosing
Zinc is available in several supplemental forms, each with different levels of elemental zinc and bioavailability. Common forms include zinc picolinate, zinc citrate, zinc gluconate, and zinc bisglycinate. Zinc picolinate and bisglycinate are generally considered to have good bioavailability, though comparative human studies are limited. The recommended daily intake varies by region: the EU reference intake is 10 mg/day for men and 8 mg/day for women, though higher amounts may be appropriate for individuals with documented deficiency.
The tolerable upper intake level for zinc in the EU is 25 mg/day for adults. Long-term intake above this level may interfere with copper absorption, potentially leading to copper deficiency and associated complications including anaemia and neutropenia. For this reason, when supplementing zinc at doses above 15 mg/day, concurrent copper intake should be considered.
Zinc-rich foods: oysters (exceptionally high), red meat, poultry, beans, chickpeas, lentils, nuts, seeds, whole grains, and dairy products.
Selenium Forms and Dosing
The two most common supplemental forms of selenium are selenomethionine (an organic form found naturally in foods) and sodium selenite (an inorganic form). Selenomethionine is generally better absorbed and retained in the body, while sodium selenite is converted to selenide before incorporation into selenoproteins.
The EU recommended daily intake for selenium is 55 micrograms/day for adults. The tolerable upper intake level is 300 micrograms/day. Chronic intake above 400 micrograms/day may lead to selenosis, characterised by garlic breath, hair loss, nail brittleness, and gastrointestinal symptoms.
Selenium-rich foods: Brazil nuts (exceptionally high; 1-2 nuts may provide the full daily requirement, though content varies widely), seafood, organ meats, eggs, sunflower seeds, mushrooms, and whole grains. Brazil nut selenium content is highly variable depending on soil conditions, so consistent supplemental forms may be preferred when precise dosing is needed.
Safety Considerations
Both zinc and selenium have a U-shaped relationship with health: both deficiency and excess are associated with adverse outcomes. This makes appropriate dosing important. Zinc supplementation should not exceed 25 mg/day long-term without healthcare supervision, and selenium supplementation should not exceed 200 micrograms/day for general health purposes.
Questions and Answers
How do zinc and selenium support immune function?
Zinc and selenium both contribute to normal immune function (EFSA-approved claims). Zinc is required for the development and activation of T-cells, natural killer cells, and macrophages. Selenium is incorporated into selenoproteins that regulate immune cell activity and antioxidant defence. A meta-analysis of 35 RCTs found that zinc supplementation significantly reduced inflammatory markers and increased CD4+ T-cell counts.1
Who is at risk of zinc deficiency?
Groups at higher risk include older adults (due to reduced intake and absorption), vegetarians and vegans (plant-based zinc is less bioavailable due to phytates), individuals taking certain medications (diuretics, proton pump inhibitors), and those with gastrointestinal conditions affecting absorption. A review estimated that up to 40% of elderly populations in developed countries may have inadequate zinc status.2
Why does selenium status vary by region?
Soil selenium content differs greatly between geographic areas, directly affecting food supply levels. Parts of Northern Europe have relatively low soil selenium, while areas of North America tend to be higher. This means dietary selenium intake varies by location even when overall diet quality is similar.
What is the connection between selenium and thyroid function?
Selenium contributes to normal thyroid function (EFSA-approved claim). The thyroid gland has the highest selenium concentration per gram of tissue in the body. Selenoproteins, particularly the iodothyronine deiodinases, are essential for converting thyroid hormones between their active and inactive forms. A meta-analysis of 35 RCTs examined selenium supplementation in thyroid autoimmunity contexts.3
Can I get enough zinc and selenium from food alone?
A varied diet including seafood, meat, nuts, seeds, legumes, and whole grains generally provides adequate zinc and selenium. However, certain populations, particularly older adults, those on restricted diets, and those in low-selenium regions, may benefit from supplementation. Just 1-2 Brazil nuts per day can provide the full daily selenium requirement, though content varies considerably.
What happens if I take too much zinc?
Long-term zinc supplementation above 25 mg/day (the EU tolerable upper limit) can interfere with copper absorption, potentially leading to copper deficiency, anaemia, and neutropenia. High-dose zinc can also suppress immune function rather than support it. This U-shaped relationship makes appropriate dosing essential.
What are the signs of selenium excess?
Chronic selenium intake above 400 micrograms/day may lead to selenosis, with symptoms including garlic-like breath odour, hair loss, brittle nails, and gastrointestinal distress. The EU tolerable upper intake level is 300 micrograms/day. Supplementation above 200 micrograms/day is generally not recommended without professional guidance.
Do zinc and selenium work together?
Zinc and selenium have complementary roles in immune function and antioxidant defence. Both contribute to protection of cells from oxidative stress (EFSA-approved claims). However, they operate through different mechanisms: zinc primarily through enzyme cofactor roles and immune cell signalling, and selenium through incorporation into selenoproteins. Adequate status of both minerals supports a well-functioning immune system.
Frequently Asked Questions
What is the best form of zinc supplement?
Zinc picolinate, zinc bisglycinate, and zinc citrate are generally considered to have good bioavailability, though head-to-head human comparisons are limited. Zinc oxide is less bioavailable and typically not recommended for supplementation. The most important factor is consistent intake at an appropriate dose (typically 10-25 mg elemental zinc per day for adults).
How many Brazil nuts should I eat for selenium?
Just 1-2 Brazil nuts per day can provide the full recommended daily selenium intake (55 micrograms). However, selenium content in Brazil nuts is highly variable depending on the soil where they were grown. Eating more than 3-4 daily on a regular basis is generally not recommended due to the risk of exceeding safe intake levels.
Should I take zinc and selenium at the same time?
Zinc and selenium can be taken together without significant interaction concerns. Some multi-nutrient formulations include both minerals. If taking zinc at higher doses (above 15 mg/day), consider including copper (1-2 mg/day) to prevent copper depletion. Taking mineral supplements with food can improve absorption and reduce potential gastrointestinal discomfort.
Can zinc help with the common cold?
An umbrella review of meta-analyses found some evidence that zinc lozenges may be associated with reduced duration of cold symptoms when taken within 24 hours of symptom onset.6 However, the evidence is inconsistent across studies, and the effect appears specific to certain zinc formulations (lozenges, not tablets). Zinc contributes to normal immune function (EFSA-approved claim), but no disease prevention claims can be made.
Is selenium supplementation safe for everyone?
Selenium supplementation within recommended ranges (55-200 micrograms/day) is generally well tolerated. However, individuals in selenium-replete regions may not benefit from additional supplementation, and excessive intake carries risks. Those with thyroid conditions or those taking thyroid medications should consult a healthcare professional before supplementing selenium, given its role in thyroid hormone metabolism.
How do I know if I am deficient in zinc or selenium?
Zinc and selenium status can be assessed through blood tests, though interpretation can be complex. Serum zinc levels below 70 micrograms/dL may indicate deficiency. For selenium, serum levels below 85 micrograms/L suggest suboptimal status. Individuals with risk factors for deficiency (restricted diets, older age, malabsorption conditions, low-selenium geographic regions) should consider testing and should consult a healthcare professional.
References
- 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. View on PubMed ↗
- Haase H, Rink L. The immune system and the impact of zinc during aging. Immun Ageing. 2009;6:9. View on PubMed ↗
- Huwiler VV, Maissen-Abgottspon S, Stanga Z, et al. Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Thyroid. 2024;34(3):295-313. View on PubMed ↗
- Hosseini R, Ferns GA, Sahebkar A, Mirshekar MA, Jalali M. Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials. Cytokine. 2021;138:155396. View on PubMed ↗
- Wessels I, Pupke JT, Troschke-Meurer S, Rink L. Zinc deficiency as possible link between immunosenescence and age-related diseases. Immun Ageing. 2025;22:24. View on PubMed ↗
- Li J, Cao D, Huang Y, et al. Zinc Intakes and Health Outcomes: An Umbrella Review. Front Nutr. 2022;9:798078. View on PubMed ↗
- Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018;13(4):e0193120. View on PubMed ↗
- Prasad AS. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85(3):837-844. View on PubMed ↗
Disclaimer: Educational content only. Not medical advice. Supplements are not intended to diagnose, treat, cure, or prevent any disease. Consult a qualified healthcare professional if you have a medical condition or take medication.
