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Cited by 1,358Trace Elements in HealthNutrition and Health StudiesVitamin C and Antioxidants Research

A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection

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Gombart, Adrian F., Pierre, Adeline, Maggini, Silvia·2020·Nutrients
DOI 10.3390/nu12010236PMC PMC7019735
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Abstract

Immune support by micronutrients is historically based on vitamin C deficiency and supplementation in scurvy in early times. It has since been established that the complex, integrated immune system needs multiple specific micronutrients, including vitamins A, D, C, E, B6, and B12, folate, zinc, iron, copper, and selenium, which play vital, often synergistic roles at every stage of the immune response. Adequate amounts are essential to ensure the proper function of physical barriers and immune cells; however, daily micronutrient intakes necessary to support immune function may be higher than current recommended dietary allowances. Certain populations have inadequate dietary micronutrient intakes, and situations with increased requirements (e.g., infection, stress, and pollution) further decrease stores within the body. Several micronutrients may be deficient, and even marginal deficiency may impair immunity. 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. Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc. Better design of human clinical studies addressing dosage and combinations of micronutrients in different populations are required to substantiate the benefits of micronutrient supplementation against infection.

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  • Vitamin D supports bone health and immune function, while B vitamins (B6, B12, folate) contribute to homocysteine metabolism, reducing cardiovascular and cognitive risks.

    “Vitamin D supports bone health, and immune function, while B vitamins (B6, B12, folate) contribute to homocysteine metabolism, reducing cardiovascular and cognitive risks.”

    From The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento (2025) · cites this paper as [71]

    The Abstract and §2.3 (Adaptive Immunity; page not provided) support vitamin D’s role in immune function. The paper does not state that vitamin D supports bone health or that B6, B12, and folate reduce cardiovascular or cognitive risks through homocysteine metabolism. Its References list a work on those B vitamins and one-carbon metabolism, but that title does not establish the claimed risk reduction. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Magnesium is essential for energy metabolism and DNA repair, while iron and copper are critical for red blood cell production and mitochondrial function.

    “Magnesium is essential for energy metabolism and DNA repair, while iron and copper are critical for red blood cell production and mitochondrial function [70,71].”

    From The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento (2025) · cites this paper as [71]

    Section 3 (page unavailable) says magnesium helps repair DNA, and §2.2 says it protects DNA against oxidative damage. Section 3 also links magnesium status to energy expenditure, but does not establish the claimed essential role in energy metabolism. The passages on iron and copper in §2.2 discuss immune-cell responses, not red blood cell production or mitochondrial function. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The RDA values of antioxidants are based on an adjusted estimation of the average physiological requirement of a nutrient, bioavailability, and variation of their intake by the U.S. population.

    “The RDA values of antioxidants are based on an adjusted estimation of the average physiological requirement of a nutrient, bioavailability, and variation of their intake by the U.S. population; doses of antioxidants may be higher to optimize biological processes such as immune protection; however, more research is needed to determine the best dose in each scenario125–127.”

    From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [126]

    Section 3 defines the RDA as the daily intake needed to avoid deficiency in 97–98% of a healthy general population. It discusses bioavailability when assessing inadequate intakes and reports U.S. intake data, but does not say that bioavailability or variation in U.S. intake is used to calculate RDA values. Page numbers are not available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Higher intake of antioxidants than RDA may help support the immune system of populations with high stress or exposure to environmental pollution, including astronauts.

    “It is reasonable to think that a higher intake of antioxidants than those recommended by the RDA may help to support the immune system of populations with high stress or exposure to environmental pollution, and this may include astronauts.”

    From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [126]

    Section 3 (page unavailable) says stress can increase the need for antioxidant vitamins C and E, pollution can reduce their levels, and intakes above the RDA may be needed for immune protection. The paper does not address astronauts, so that population-specific extension is not supported by this source. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Antioxidants such as vitamins C and E, selenium, and zinc protect cells from oxidative damage.

    “Antioxidants such as vitamins C and E, selenium, and zinc protect cells from oxidative damage.”

    From The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento (2025) · cites this paper as [71]

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Sorted by citations

Authors
Gombart, A. F., Pierre, A., & Maggini, S.
Affiliations
  • Oregon State University (US)
  • Bayer (Switzerland) (CH)
Corresponding author
Maggini, Silvia
ORCID
Gombart, Adrian F.
Venue
Nutrients
Publisher
MDPI AG
Published
2020-01-16
Volume
12
Issue
1
Pages
236
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu12010236
PMC
PMC7019735
OpenAlex
W2999874457
Cited by
1,358
References
16
Citations by year
2026: 128 · 2025: 157 · 2024: 170 · 2023: 199 · 2022: 271 · 2021: 258 · 2020: 175
FWCI
27.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords
micronutrients, immune function, infection risk, micronutrient deficiency, vitamin C, vitamin D, zinc, vitamin E, folic acid, selenium, iron, copper, B vitamins, micronutrient supplementation, immune support, dietary intake
MeSH terms
Animals, Communicable Diseases, Humans, Immune System, Nutritional Status, Risk Factors, Infection Control, Micronutrients, Recommended Dietary Allowances, Protective Factors

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