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

Adrian F Gombart, Adeline Pierre, Silvia Maggini, Adrian F Gombart, Adeline Pierre, Silvia Maggini

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.

Keywords: immune system; infection; micronutrients; minerals; vitamins.

Conflict of interest statement

S.M. and A.P. are employed by Bayer Consumer Care Ltd., a manufacturer of multivitamins. A.F.G. has received funding for conducting research on a product from Bayer Consumer Care Ltd.

Figures

Figure 1
Figure 1
Basic components of the immune system, including key micronutrients that contribute to immune function. The schematic highlights the areas of immunity and the micronutrients that affect these functions that are covered in this review. Abbreviations: Ig, immunoglobulins; MHC, major histocompatibility complex.
Figure 2
Figure 2
Micronutrients have key roles at every stage of the immune response [2,7,8,9]. This schematic summarizes important components and processes that are involved in different aspects of the innate and adaptive immune responses. The circles highlight those micronutrients that are known to affect these responses. The significant overlap between micronutrients and processes indicates the importance of multiple micronutrients in supporting proper function of the immune system. Abbreviations: APCs, antigen-presenting cells; C3, complement component 3; CRP, C-reactive protein; Cu, copper; Fe, iron; IFNs, interferons; Igs, immunoglobulins; ILs, interleukins; GI, gastrointestinal; GM-CSF, granulocyte-macrophage colony stimulating factor; MAC, membrane attack complex; MCP-1, monocyte chemoattractant protein-1; Mg, magnesium; MHCs, major histocompatibility complexes; NK, natural killer; NO, nitric oxide; ROS, reactive oxygen species; Se, selenium; TLRs, toll-like receptors; TNF, tumor-necrosis factors; Zn, zinc.
Figure 3
Figure 3
For optimal immune protection and resistance to infection, daily intakes may need to be much higher than the RDAs [24,27]. Abbreviations: RDA, recommended dietary allowance [143]; UL = tolerable upper intake level, the maximum daily intake unlikely to cause adverse health effects.

References

    1. McFall-Ngai M., Hadfield M.G., Bosch T.C., Carey H.V., Domazet-Loso T., Douglas A.E., Dubilier N., Eberl G., Fukami T., Gilbert S.F., et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl. Acad. Sci. USA. 2013;110:3229–3236. doi: 10.1073/pnas.1218525110.
    1. Maggini S., Pierre A., Calder P.C. Immune function and micronutrient requirements change over the life course. Nutrients. 2018;10:1531. doi: 10.3390/nu10101531.
    1. Haryanto B., Suksmasari T., Wintergerst E., Maggini S. Multivitamin supplementation supports immune function and ameliorates conditions triggered by reduced air quality. Vitam. Miner. 2015;4:1–15.
    1. Dolan L.C., Matulka R.A., Burdock G.A. Naturally occurring food toxins. Toxins. 2010;2:2289–2332. doi: 10.3390/toxins2092289.
    1. Julier Z., Park A.J., Briquez P.S., Martino M.M. Promoting tissue regeneration by modulating the immune system. Acta Biomater. 2017;53:13–28. doi: 10.1016/j.actbio.2017.01.056.
    1. Bartholomew M. James Lind’s Treatise of the Scurvy (1753) Postgrad. Med. J. 2002;78:695–696. doi: 10.1136/pmj.78.925.695.
    1. Micronutrient Information Center Immunity in Depth. [(accessed on 10 May 2019)];2016 Linus Pauling Institute. Available online: .
    1. Maggini S., Beveridge S., Sorbara J.P., Senatore G. Feeding the immune system: The role of micronutrients in restoring resistance to infections. CAB Rev. 2008;3:1–21. doi: 10.1079/PAVSNNR20083098.
    1. Maggini S., Wintergerst E., Beveridge S., Hornig D. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br. J. Nutr. 2007;98:S29–S35. doi: 10.1017/S0007114507832971.
    1. Biesalski H.K. Nutrition meets the microbiome: Micronutrients and the microbiota. Ann. N. Y. Acad. Sci. 2016;1372:53–64. doi: 10.1111/nyas.13145.
    1. Levy M., Thaiss C.A., Elinav E. Metabolites: Messengers between the microbiota and the immune system. Genes Dev. 2016;30:1589–1597. doi: 10.1101/gad.284091.116.
    1. Sirisinha S. The pleiotropic role of vitamin A in regulating mucosal immunity. Asian Pac. J. Allergy Immunol. 2015;33:71–89.
    1. Chew B.P., Park J.S. Carotenoid action on the immune response. J. Nutr. 2004;134:257S–261S. doi: 10.1093/jn/134.1.257S.
    1. Clark A., Mach N. Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response. Front. Immunol. 2016;7:627. doi: 10.3389/fimmu.2016.00627.
    1. Gombart A.F. The vitamin D–antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009;4:1151. doi: 10.2217/fmb.09.87.
    1. Clairmont A., Tessman D., Stock A., Nicolai S., Stahl W., Sies H. Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear vitamin D receptor. Carcinogenesis. 1996;17:1389–1391.
    1. Gniadecki R., Gajkowska B., Hansen M. 1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in keratinocytes: Involvement of protein kinase C. Endocrinology. 1997;138:2241–2248. doi: 10.1210/endo.138.6.5156.
    1. Palmer H.G., Gonzalez-Sancho J.M., Espada J., Berciano M.T., Puig I., Baulida J., Quintanilla M., Cano A., de Herreros A.G., Lafarga M., et al. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J. Cell Biol. 2001;154:369–387. doi: 10.1083/jcb.200102028.
    1. Mihajlovic M., Fedecostante M., Oost M.J., Steenhuis S.K.P., Lentjes E., Maitimu-Smeele I., Janssen M.J., Hilbrands L.B., Masereeuw R. Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. Int. J. Mol. Sci. 2017;18:2531. doi: 10.3390/ijms18122531.
    1. Yin Z., Pintea V., Lin Y., Hammock B.D., Watsky M.A. Vitamin D enhances corneal epithelial barrier function. Investig. Ophthalmol. Vis. Sci. 2011;52:7359–7364. doi: 10.1167/iovs.11-7605.
    1. Carr A., Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. doi: 10.3390/nu9111211.
    1. Yoshii K., Hosomi K., Sawane K., Kunisawa J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front. Nutr. 2019;6:48. doi: 10.3389/fnut.2019.00048.
    1. Lin P.H., Sermersheim M., Li H., Lee P.H.U., Steinberg S.M., Ma J. Zinc in Wound Healing Modulation. Nutrients. 2017;10:16. doi: 10.3390/nu10010016.
    1. Wishart K. Increased micronutrient requirements during physiologically demanding situations: Review of the current evidence. Vitamin. Miner. 2017;6:1–16. doi: 10.4172/2376-1318.1000166.
    1. Sly L.M., Lopez M., Nauseef W.M., Reiner N.E. 1alpha,25-Dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase. J. Biol. Chem. 2001;276:35482–35493. doi: 10.1074/jbc.M102876200.
    1. Tanaka H., Hruska K.A., Seino Y., Malone J.D., Nishii Y., Teitelbaum S.L. Disassociation of the macrophage-maturational effects of vitamin D from respiratory burst priming. J. Biol. Chem. 1991;266:10888–10892.
    1. Wu D., Lewis E.D., Pae M., Meydani S.N. Nutritional modulation of immune function: Analysis of evidence, mechanisms, and clinical relevance. Front. Immunol. 2019;9:3160. doi: 10.3389/fimmu.2018.03160.
    1. Bozonet S.M., Carr A.C. The Role of Physiological Vitamin C Concentrations on Key Functions of Neutrophils Isolated from Healthy Individuals. Nutrients. 2019;11:1363. doi: 10.3390/nu11061363.
    1. Wu D., Meydani S.N. Age-associated changes in immune function: Impact of vitamin E intervention and the underlying mechanisms. Endocr. Metab. Immune. Disord. Drug Targets. 2014;14:283–289. doi: 10.2174/1871530314666140922143950.
    1. World Health Organization. Food and Agricultural Organization of the United Nations . Guidelines on Food Fortification with Micronutrients. WHO; Geneva, Switzerland: 2006. Part 2. Evaluating the public health significance of micronutrient malnutrition.
    1. Gao H., Dai W., Zhao L., Min J., Wang F. The Role of Zinc and Zinc Homeostasis in Macrophage Function. J. Immunol. Res. 2018;2018:6872621. doi: 10.1155/2018/6872621.
    1. Sheikh A., Shamsuzzaman S., Ahmad S.M., Nasrin D., Nahar S., Alam M.M., Al Tarique A., Begum Y.A., Qadri S.S., Chowdhury M.I., et al. Zinc influences innate immune responses in children with enterotoxigenic Escherichia coli-induced diarrhea. J. Nutr. 2010;140:1049–1056. doi: 10.3945/jn.109.111492.
    1. Agoro R., Taleb M., Quesniaux V.F.J., Mura C. Cell iron status influences macrophage polarization. PLoS ONE. 2018;13:e0196921. doi: 10.1371/journal.pone.0196921.
    1. Besold A.N., Culbertson E.M., Culotta V.C. The Yin and Yang of copper during infection. J. Biol. Inorg. Chem. 2016;21:137–144. doi: 10.1007/s00775-016-1335-1.
    1. Saeed F., Nadeem M., Ahmed R., Nadeem M., Arshad M., Ullah A. Studying the impact of nutritional immunology underlying the modulation of immune responses by nutritional compounds—A review. Food Agric. Immunol. 2016;27:205–229. doi: 10.1080/09540105.2015.1079600.
    1. Beck M.A. Military Strategies for Sustainment of Nutrition and Immune Function in the Field. National Academy Press; Washington, DC, USA: 1999. Trace minerals, immune function, and viral evolution; p. 339.
    1. Petrovic J., Stanic D., Dmitrasinovic G., Plecas-Solarovic B., Ignjatovic S., Batinic B., Popovic D., Pesic V. Magnesium Supplementation Diminishes Peripheral Blood Lymphocyte DNA Oxidative Damage in Athletes and Sedentary Young Man. Oxidat. Med. Cell. Longev. 2016;2016:2019643. doi: 10.1155/2016/2019643.
    1. Laires M.J., Monteiro C. Exercise, magnesium and immune function. Magnes. Res. 2008;21:92–96.
    1. Wang T.T., Nestel F.P., Bourdeau V., Nagai Y., Wang Q., Liao J., Tavera-Mendoza L., Lin R., Hanrahan J.W., Mader S., et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 2004;173:2909–2912. doi: 10.4049/jimmunol.173.5.2909.
    1. Gombart A.F., Borregaard N., Koeffler H.P. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005;19:1067–1077. doi: 10.1096/fj.04-3284com.
    1. Weber G., Heilborn J.D., Chamorro Jimenez C.I., Hammarsjö A., Törmä H., Ståhle M. Vitamin D induces the antimicrobial protein hCAP18 in human skin. J. Investig. Dermatol. 2005;124:1080–1082. doi: 10.1111/j.0022-202X.2005.23687.x.
    1. Matsui T., Takahashi R., Nakao Y., Koizumi T., Katakami Y., Mihara K., Sugiyama T., Fujita T. 1,25-Dihydroxyvitamin D3-regulated expression of genes involved in human T-lymphocyte proliferation and differentiation. Cancer Res. 1986;46:5827–5831.
    1. Reichel H., Koeffler H.P., Tobler A., Norman A.W. 1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc. Natl. Acad. Sci. USA. 1987;84:3385–3389. doi: 10.1073/pnas.84.10.3385.
    1. Rigby W.F., Denome S., Fanger M.W. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J. Clin. Investig. 1987;79:1659–1664. doi: 10.1172/JCI113004.
    1. Inoue M., Matsui T., Nishibu A., Nihei Y., Iwatsuki K., Kaneko F. Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in psoriasis. Eur. J. Dermatol. 1998;8:16–20.
    1. Lin Z., Li W. The Roles of Vitamin D and Its Analogs in Inflammatory Diseases. Curr. Top. Med. Chem. 2016;16:1242–1261. doi: 10.2174/1568026615666150915111557.
    1. Zhang Y., Leung D.Y.M., Richers B.N., Liu Y., Remigio L.K., Riches D.W., Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol. 2012;188:2127–2135. doi: 10.4049/jimmunol.1102412.
    1. Topilski I., Flaishon L., Naveh Y., Harmelin A., Levo Y., Shachar I. The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur. J. Immunol. 2004;34:1068–1076. doi: 10.1002/eji.200324532.
    1. Wintergerst E., Maggini S., Hornig D. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann. Nutr. Metab. 2006;50:85–94. doi: 10.1159/000090495.
    1. Lee G.Y., Han S.N. The Role of Vitamin E in Immunity. Nutrients. 2018;10:1614. doi: 10.3390/nu10111614.
    1. Sakakeeny L., Roubenoff R., Obin M., Fontes J.D., Benjamin E.J., Bujanover Y., Jacques P.F., Selhub J. Plasma Pyridoxal-5-Phosphate Is Inversely Associated with Systemic Markers of Inflammation in a Population of U.S. Adults. J. Nutr. 2012;142:1280–1285. doi: 10.3945/jn.111.153056.
    1. Ueland P.M., McCann A., Midttun O., Ulvik A. Inflammation, vitamin B6 and related pathways. Mol. Asp. Med. 2017;53:10–27. doi: 10.1016/j.mam.2016.08.001.
    1. Jarosz M., Olbert M., Wyszogrodzka G., Młyniec K., Librowski T. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology. 2017;25:11–24. doi: 10.1007/s10787-017-0309-4.
    1. Kitabayashi C., Fukada T., Kanamoto M., Ohashi W., Hojyo S., Atsumi T., Ueda N., Azuma I., Hirota H., Murakami M., et al. Zinc suppresses Th17 development via inhibition of STAT3 activation. Int Immunol. 2010;22:375–386. doi: 10.1093/intimm/dxq017.
    1. Maywald M., Wang F., Rink L. Zinc supplementation plays a crucial role in T helper 9 differentiation in allogeneic immune reactions and non-activated T cells. J. Trace Elem. Med. Biol. 2018;50:482–488. doi: 10.1016/j.jtemb.2018.02.004.
    1. Foster M., Samman S. Zinc and regulation of inflammatory cytokines: Implications for cardiometabolic disease. Nutrients. 2012;4:676–694. doi: 10.3390/nu4070676.
    1. Wessels I., Rink L. Micronutrients in autoimmune diseases: Possible therapeutic benefits of zinc and vitamin D. J. Nutr. Biochem. 2019;77:108240. doi: 10.1016/j.jnutbio.2019.108240.
    1. Alpert P. The role of vitamins and minerals on the immune system. Home Health Care Manag. Pract. 2017;29:199–202. doi: 10.1177/1084822317713300.
    1. Bussiere F.I., Mazur A., Fauquert J.L., Labbe A., Rayssiguier Y., Tridon A. High magnesium concentration in vitro decreases human leukocyte activation. Magnes. Res. 2002;15:43–48.
    1. Ross A.C. Vitamin A and retinoic acid in T cell-related immunity. Am. J. Clin. Nutr. 2012;96:1166s–1172s. doi: 10.3945/ajcn.112.034637.
    1. Sigmundsdottir H., Pan J., Debes G.F., Alt C., Habtezion A., Soler D., Butcher E.C. DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat. Immunol. 2007;8:285–293. doi: 10.1038/ni1433.
    1. Sassi F., Tamone C., D’Amelio P. Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients. 2018;10:1656. doi: 10.3390/nu10111656.
    1. Cantorna M.T., Snyder L., Lin Y.D., Yang L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015;7:3011–3021. doi: 10.3390/nu7043011.
    1. Penna G., Adorini L. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 2000;164:2405–2411. doi: 10.4049/jimmunol.164.5.2405.
    1. Piemonti L., Monti P., Sironi M., Fraticelli P., Leone B.E., Dal Cin E., Allavena P., Di Carlo V. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J. Immunol. 2000;164:4443–4451. doi: 10.4049/jimmunol.164.9.4443.
    1. Bscheider M., Butcher E.C. Vitamin D immunoregulation through dendritic cells. Immunology. 2016;148:227–236. doi: 10.1111/imm.12610.
    1. Wintergerst E., Maggini S., Hornig D. Contribution of selected vitamins and trace elements to immune function. Nutr. Metab. 2007;51:301–323. doi: 10.1159/000107673.
    1. Hurwitz B.E., Klaus J.R., Llabre M.M., Gonzalez A., Lawrence P.J., Maher K.J., Greeson J.M., Baum M.K., Shor-Posner G., Skyler J.S., et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: A randomized controlled trial. Arch. Intern. Med. 2007;167:148–154. doi: 10.1001/archinte.167.2.148.
    1. Shankar A.H., Prasad A.S. Zinc and immune function: The biological basis of altered resistance to infection. Am. J. Clin. Nutr. 1998;68:447s–463s. doi: 10.1093/ajcn/68.2.447S.
    1. Ibs K.-H., Rink L. Zinc-Altered Immune function. J. Nutr. 2003;133:1452S–1456S. doi: 10.1093/jn/133.5.1452S.
    1. Han S.N., Adolfsson O., Lee C.K., Prolla T.A., Ordovas J., Meydani S.N. Vitamin E and gene expression in immune cells. Ann. N. Y. Acad. Sci. 2004;1031:96–101. doi: 10.1196/annals.1331.010.
    1. Ooi J.H., Li Y., Rogers C.J., Cantorna M.T. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. J. Nutr. 2013;143:1679–1686. doi: 10.3945/jn.113.180794.
    1. Cantorna M.T., McDaniel K., Bora S., Chen J., James J. Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease. Exp. Biol. Med. 2014;239:1524–1530. doi: 10.1177/1535370214523890.
    1. Cantorna M.T., Snyder L., Arora J. Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit. Rev. Biochem. Mol. Biol. 2019;54:184–192. doi: 10.1080/10409238.2019.1611734.
    1. Lee H., Ko G. Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome. Sci. Rep. 2016;6:25835. doi: 10.1038/srep25835.
    1. Pullar J.M., Carr A.C., Vissers M.C.M. The Roles of Vitamin C in Skin Health. Nutrients. 2017;9:866. doi: 10.3390/nu9080866.
    1. Forman H.J., Torres M., Fukuto J. Redox signaling. Mol. Cell Biochem. 2002;234–235:49–62. doi: 10.1023/A:1015913229650.
    1. Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin. Interv. Aging. 2007;2:219–236.
    1. Delfino R.J., Staimer N., Vaziri N.D. Air pollution and circulating biomarkers of oxidative stress. Air Qual. Atmos. Health. 2011;4:37–52. doi: 10.1007/s11869-010-0095-2.
    1. Halliwell B. Antioxidants in human health and disease. Annu. Rev. Nutr. 1996;16:33–50. doi: 10.1146/annurev.nu.16.070196.000341.
    1. Takiishi T., Fenero C.I.M., Câmara N.O.S. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers. 2017;5:e1373208. doi: 10.1080/21688370.2017.1373208.
    1. Broome C.S., McArdle F., Kyle J.A., Andrews F., Lowe N.M., Hart C.A., Arthur J.R., Jackson M.J. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am. J. Clin. Nutr. 2004;80:154–162. doi: 10.1093/ajcn/80.1.154.
    1. Nan R., Tetchner S., Rodriguez E., Pao P.J., Gor J., Lengyel I., Perkins S.J. Zinc-induced self-association of complement C3b and Factor H: Implications for inflammation and age-related macular degeneration. J. Biol. Chem. 2013;288:19197–19210. doi: 10.1074/jbc.M113.476143.
    1. Yang D., de la Rosa G., Tewary P., Oppenheim J.J. Alarmins link neutrophils and dendritic cells. Trends Immunol. 2009;30:531–537. doi: 10.1016/j.it.2009.07.004.
    1. Davies L.C., Jenkins S.J., Allen J.E., Taylor P.R. Tissue-resident macrophages. Nat. Immunol. 2013;14:986–995. doi: 10.1038/ni.2705.
    1. Wang J., Pantopoulos K. Regulation of cellular iron metabolism. Biochem. J. 2011;434:365–381. doi: 10.1042/BJ20101825.
    1. Hewison M. Vitamin D and the intracrinology of innate immunity. Mol. Cell. Endocrinol. 2010;321:103–111. doi: 10.1016/j.mce.2010.02.013.
    1. Wu D., Meydani S.N. Age-associated changes in immune and inflammatory responses: Impact of vitamin E intervention. J. Leukoc. Biol. 2008;84:900–914. doi: 10.1189/jlb.0108023.
    1. Nguyen G.T., Green E.R., Mecsas J. Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance. Front. Cell. Infect. Microbiol. 2017;7:373. doi: 10.3389/fcimb.2017.00373.
    1. Dupont C.L., Grass G., Rensing C. Copper toxicity and the origin of bacterial resistance—New insights and applications. Metallomics. 2011;3:1109–1118. doi: 10.1039/c1mt00107h.
    1. Abu-Amer Y., Bar-Shavit Z. Regulation of TNF-alpha release from bone marrow-derived macrophages by vitamin D. J. Cell. Biochem. 1994;55:435–444. doi: 10.1002/jcb.240550404.
    1. Cañedo-Dorantes L., Cañedo-Ayala M. Skin Acute Wound Healing: A Comprehensive Review. Int. J. Inflamm. 2019;2019:3706315. doi: 10.1155/2019/3706315.
    1. Romano M., Fanelli G., Albany C.J., Giganti G., Lombardi G. Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity. Front. Immunol. 2019;10 doi: 10.3389/fimmu.2019.00043.
    1. Lemire J.M. Immunomodulatory actions of 1,25-dihydroxyvitamin D3. J. Steroid Biochem. Mol. Biol. 1995;53:599–602. doi: 10.1016/0960-0760(95)00106-A.
    1. Jeffery L.E., Burke F., Mura M., Zheng Y., Qureshi O.S., Hewison M., Walker L.S., Lammas D.A., Raza K., Sansom D.M. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol. 2009;183:5458–5467. doi: 10.4049/jimmunol.0803217.
    1. McCully M.L., Ladell K., Hakobyan S., Mansel R.E., Price D.A., Moser B. Epidermis instructs skin homing receptor expression in human T cells. Blood. 2012;120:4591–4598. doi: 10.1182/blood-2012-05-433037.
    1. Rosenkranz E., Maywald M., Hilgers R.-D., Brieger A., Clarner T., Kipp M., Plümäkers B., Meyer S., Schwerdtle T., Rink L. Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration. J. Nutr. Biochem. 2016;29:116–123. doi: 10.1016/j.jnutbio.2015.11.010.
    1. Rosenkranz E., Metz C.H.D., Maywald M., Hilgers R.-D., Weßels I., Senff T., Haase H., Jäger M., Ott M., Aspinall R., et al. Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures. Mol. Nutr. Food Res. 2016;60:661–671. doi: 10.1002/mnfr.201500524.
    1. Rigby W.F., Stacy T., Fanger M.W. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol) J. Clin. Investig. 1984;74:1451–1455. doi: 10.1172/JCI111557.
    1. Tsoukas C.D., Provvedini D.M., Manolagas S.C. 1,25-dihydroxyvitamin D3: A novel immunoregulatory hormone. Science. 1984;224:1438–1440. doi: 10.1126/science.6427926.
    1. Saggese G., Federico G., Balestri M., Toniolo A. Calcitriol inhibits the PHA-induced production of IL-2 and IFN-gamma and the proliferation of human peripheral blood leukocytes while enhancing the surface expression of HLA class II molecules. J. Endocrinol. Investig. 1989;12:329–335. doi: 10.1007/BF03349999.
    1. Li T.X., Li Y. Synergistic effect of zinc and vitamin A on T cell functions. Biomed. Environ. Sci. 2007;20:131–134.
    1. Tamura J., Kubota K., Murakami H., Sawamura M., Matsushima T., Tamura T., Saitoh T., Kurabayshi H., Naruse T. Immunomodulation by vitamin B12: Augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin. Exp. Immunol. 1999;116:28–32. doi: 10.1046/j.1365-2249.1999.00870.x.
    1. Manicassamy S., Pulendran B. Retinoic acid-dependent regulation of immune responses by dendritic cells and macrophages. Semin. Immunol. 2009;21:22–27. doi: 10.1016/j.smim.2008.07.007.
    1. Moore J.B., Blanchard R.K., McCormack W.T., Cousins R.J. cDNA array analysis identifies thymic LCK as upregulated in moderate murine zinc deficiency before T-lymphocyte population changes. J. Nutr. 2001;131:3189–3196. doi: 10.1093/jn/131.12.3189.
    1. Calder P. Conference on ‘Transforming the nutrition landscape in Africa’. Plenary Session 1: Feeding the immune system. Proc. Nutr. Soc. 2013;72:299–309. doi: 10.1017/S0029665113001286.
    1. Bhaskaram P. Micronutrient malnutrition, infection, and immunity: An overview. Nutr. Rev. 2002;60:S40–S45. doi: 10.1301/00296640260130722.
    1. Milner J., Beck M. Micronutrients, immunology and inflammation. The impact of obesity on the immune response to infection. Proc. Nutr. Soc. 2012;71:298–306. doi: 10.1017/S0029665112000158.
    1. Calder P., Prescott S., Caplan M. Scientific Review: The Role of Nutrients in Immune Function of Infants and Young Children Emerging Evidence for Long-Chain Polyunsaturated Fatty Acids. Mead Johnson & Company; Glenview, IL, USA: 2007.
    1. Prentice S. They are what you eat: Can nutritional factors during gestation and early infancy modulate the neonatal immune response? Front. Immunol. 2017;8:1641. doi: 10.3389/fimmu.2017.01641.
    1. Hemilä H. Vitamin C and infections. Nutrients. 2017;9:339. doi: 10.3390/nu9040339.
    1. GBD 2017 Causes of Death Collaborators Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736–1788. doi: 10.1016/S0140-6736(18)32203-7.
    1. Semba R.D. The historical evolution of thought regarding multiple micronutrient nutrition. J. Nutr. 2012;142:143s–156s. doi: 10.3945/jn.110.137745.
    1. Elmadfa I., Meyer A., Nowak V., Hasenegger V., Putz P., Verstraeten R., Remaut-DeWinter A.M. European Nutrition and Health Report. Forum. Nutr. 2009;62:1–405.
    1. Anderson R., Oosthuizen R., Maritz R., Theron A., Van Rensburg A. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am. J. Clin. Nutr. 1980;33:71–76. doi: 10.1093/ajcn/33.1.71.
    1. Hemila H., Chalker E. Vitamin C can shorten the length of stay in the ICU: A meta-analysis. Nutrients. 2019;11:708. doi: 10.3390/nu11040708.
    1. Meghil M.M., Hutchens L., Raed A., Multani N.A., Rajendran M., Zhu H., Looney S., Elashiry M., Arce R.M., Peacock M.E., et al. The influence of vitamin D supplementation on local and systemic inflammatory markers in periodontitis patients: A pilot study. Oral Dis. 2019;25:1403–1413. doi: 10.1111/odi.13097.
    1. Cannell J., Vieth R., Umhau J., Holick M., Grant W., Madronich S., Garland C., Giovannucci E. Epidemic influenza and vitamin D. Epidemiol. Infect. 2006;134:1129–1140. doi: 10.1017/S0950268806007175.
    1. Jat K.R. Vitamin D deficiency and lower respiratory tract infections in children: A systematic review and meta-analysis of observational studies. Trop. Dr. 2017;47:77–84. doi: 10.1177/0049475516644141.
    1. Autier P., Mullie P., Macacu A., Dragomir M., Boniol M., Coppens K., Pizot C., Boniol M. Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5:986–1004. doi: 10.1016/S2213-8587(17)30357-1.
    1. Villamor E., Fawzi W.W. Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. Clin. Microbiol. Rev. 2005;18:446–464. doi: 10.1128/CMR.18.3.446-464.2005.
    1. Ross A.C., Caballero B., Cousins R.J., Tucker K.L., Ziegler T.R. Modern Nutrition in Health and Disease. 11th ed. Wolters Kluwer Health Adis (ESP); Philadelphia, PA, USA: 2012.
    1. Traber M.G. Vitamin E inadequacy in humans: Causes and consequences. Adv. Nutr. 2014;5:503–514. doi: 10.3945/an.114.006254.
    1. De la Fuente M., Hernanz A., Guayerbas N., Victor V., Arnalich F. Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic. Res. 2008;42:272–280. doi: 10.1080/10715760801898838.
    1. Qian B., Shen S., Zhang J., Jing P. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations. J. Immunol. Res. 2017;2017:12. doi: 10.1155/2017/2197975.
    1. Cheng C.H., Chang S.J., Lee B.J., Lin K.L., Huang Y.C. Vitamin B6 supplementation increases immune responses in critically ill patients. Eur. J. Clin. Nutr. 2006;60:1207–1213. doi: 10.1038/sj.ejcn.1602439.
    1. Rowley C.A., Kendall M.M. To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions. PLoS Pathog. 2019;15:e1007479. doi: 10.1371/journal.ppat.1007479.
    1. Troen A.M., Mitchell B., Sorensen B., Wener M.H., Johnston A., Wood B., Selhub J., McTiernan A., Yasui Y., Oral E., et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J. Nutr. 2006;136:189–194. doi: 10.1093/jn/136.1.189.
    1. Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J. Nutr. Health Aging. 2002;6:39–42.
    1. Bunout D., Barrera G., Hirsch S., Gattas V., de la Maza M.P., Haschke F., Steenhout P., Klassen P., Hager C., Avendano M., et al. Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. J. Parenter. Enteral Nutr. 2004;28:348–354. doi: 10.1177/0148607104028005348.
    1. Maywald M., Wessels I., Rink L. Zinc Signals and Immunity. Int. J. Mol. Sci. 2017;18:2222. doi: 10.3390/ijms18102222.
    1. Sandström B., Cederblad A., Lindblad B.S., Lönnerdal B. Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function. Arch. Pediatr. Adolesc. Med. 1994;148:980–985. doi: 10.1001/archpedi.1994.02170090094017.
    1. Bonaventura P., Benedetti G., Albarede F., Miossec P. Zinc and its role in immunity and inflammation. Autoimmun. Rev. 2015;14:277–285. doi: 10.1016/j.autrev.2014.11.008.
    1. Savino W., Dardenne M. Nutritional imbalances and infections affect the thymus: Consequences on T-cell-mediated immune responses. Proc. Nutr. Soc. 2010;69:636–643. doi: 10.1017/S0029665110002545.
    1. Maxfield L., Crane J.S. StatPearls. StatPearls Publishing LLC; Treasure Island, FL, USA: 2019. Zinc Deficiency.
    1. Kumar V., Choudhry V. Iron deficiency and infection. Indian J. Pediatr. 2010;77:789–793. doi: 10.1007/s12098-010-0120-3.
    1. Chen K., Chen X.-R., Zhang L., Luo H.-Y., Gao N., Wang J., Fu G.-Y., Mao M. Effect of simultaneous supplementation of vitamin A and iron on diarrheal and respiratory tract infection in preschool children in Chengdu City, China. Nutrition. 2013;29:1197–1203. doi: 10.1016/j.nut.2013.03.025.
    1. Percival S.S. Copper and immunity. Am. J. Clin. Nutr. 1998;67:1064s–1068s. doi: 10.1093/ajcn/67.5.1064S.
    1. Bonham M., O’Connor J.M., Hannigan B.M., Strain J.J. The immune system as a physiological indicator of marginal copper status? Br. J. Nutr. 2002;87:393–403. doi: 10.1079/BJN2002558.
    1. Nielsen F.H., Lukaski H.C. Update on the relationship between magnesium and exercise. Magnes. Res. 2006;19:180–189.
    1. Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med. Hypotheses. 2001;56:163–170. doi: 10.1054/mehy.2000.1133.
    1. Mooren F.C., Golf S.W., Volker K. Effect of magnesium on granulocyte function and on the exercise induced inflammatory response. Magnes. Res. 2003;16:49–58.
    1. IOM (Institute of Medicine) Dietary Reference Intakes for Calcium and Vitamin D. The National Academies Press; Washington, DC, USA: 2011.
    1. Padayatty S.J., Levine M. Vitamin C: The known and the unknown and Goldilocks. Oral Dis. 2016;22:463–493. doi: 10.1111/odi.12446.
    1. Elste V., Troesch B., Eggersdorfer M., Weber P. Emerging Evidence on Neutrophil Motility Supporting Its Usefulness to Define Vitamin C Intake Requirements. Nutrients. 2017;9:503. doi: 10.3390/nu9050503.
    1. Hume R., Weyers E. Changes in leucocyte ascorbic acid during the common cold. Scott. Med. J. 1973;18:3–7. doi: 10.1177/003693307301800102.
    1. Pallast E.G., Schouten E.G., de Waart F.G., Fonk H.C., Doekes G., von Blomberg B.M., Kok F.J. Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons. Am. J. Clin. Nutr. 1999;69:1273–1281. doi: 10.1093/ajcn/69.6.1273.
    1. Meydani S.N., Meydani M., Blumberg J.B., Leka L.S., Siber G., Loszewski R., Thompson C., Pedrosa M.C., Diamond R.D., Stollar B.D. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277:1380–1386. doi: 10.1001/jama.1997.03540410058031.
    1. Meydani S., Leka L., Fine B., Dallal G., Keusch G., Singh M., Hamer D. Vitamin E and respiratory tract infections in elderly nursing home residents: A randomized controlled trial. JAMA. 2004;292:828–836. doi: 10.1001/jama.292.7.828.
    1. Kwak H.-K., Hansen C.M., Leklem J.E., Hardin K., Shultz T.D. Improved vitamin B-6 status is positively related to lymphocyte proliferation in young women consuming a controlled diet. J. Nutr. 2002;132:3308–3313. doi: 10.1093/jn/132.11.3308.
    1. Steinbrenner H., Al-Quraishy S., Dkhil M.A., Wunderlich F., Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv. Nutr. 2015;6:73–82. doi: 10.3945/an.114.007575.
    1. Hewison M. An update on vitamin D and human immunity. Clin. Endocrinol. 2012;76:315–325. doi: 10.1111/j.1365-2265.2011.04261.x.
    1. Wimalawansa S.J. Vitamin D in the new millennium. Curr. Osteoporos. Rep. 2012;10:4–15. doi: 10.1007/s11914-011-0094-8.
    1. World Health Organization . Nations, Nations, Food and Agricultural Organization of the United Nations. In: Allen L., de Benoist B., Dary O., Hurrell R., editors. Guidelines on Food Fortification with Micronutrients. World Health Organization; Geneva, Switzerland: 2006.
    1. World Health Organization . Nutritional Rickets: A Review of Disease Burden, Causes, Diagnosis, Prevention and Treatment. World Health Organization; Geneva, Switzerland: 2019.
    1. WHO . Guideline: Potassium Intake for Adults and Children. World Health Organization (WHO); Geneva, Switzerland: 2012.
    1. Troesch B., Hoeft B., McBurney M., Eggersdorfer M., Weber P. Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries. Br. J. Nutr. 2012;108:692–698. doi: 10.1017/S0007114512001808.
    1. United States Department of Agriculture What We Eat in America, NHANES 2013–2016. Usual Nutrient Intake from Food and Beverages, by Gender and Age. [(accessed on 28 May 2019)];2019 Available online: .
    1. WHO . Guideline: Use of Multiple Micronutrient Powders for Point-of-Use Fortification of Foods Consumed by Infants and Young Children Aged 6–23 Months and Children Aged 2–12 Years. World Health Organization; Geneva, Switzerland: 2016. [(accessed on 15 January 2020)]. Available online:
    1. Bailey R., West K.J., Black R. The epidemiology of global micronutrient deficiencies. Ann. Nutr. Metab. 2015;66:22–33. doi: 10.1159/000371618.
    1. Platel K., Srinivasan K. Bioavailability of Micronutrients from Plant Foods: An Update. Crit. Rev. Food Sci. Nutr. 2016;56:1608–1619. doi: 10.1080/10408398.2013.781011.
    1. Bohn T., Davidsson L., Walczyk T., Hurrell R.F. Fractional magnesium absorption is significantly lower in human subjects from a meal served with an oxalate-rich vegetable, spinach, as compared with a meal served with kale, a vegetable with a low oxalate content. Br. J. Nutr. 2007;91:601–606. doi: 10.1079/BJN20031081.
    1. Gibson R.S., Raboy V., King J.C. Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies. Nutr. Rev. 2018;76:793–804. doi: 10.1093/nutrit/nuy028.
    1. Schwartz R., Spencer H., Welsh J.J. Magnesium absorption in human subjects from leafy vegetables, intrinsically labeled with stable 26 Mg. Am. J. Clin. Nutr. 1984;39:571–576. doi: 10.1093/ajcn/39.4.571.
    1. Suliburska J., Krejpcio Z. Evaluation of the content and bioaccessibility of iron, zinc, calcium and magnesium from groats, rice, leguminous grains and nuts. J. Food Sci. Technol. 2014;51:589–594. doi: 10.1007/s13197-011-0535-5.
    1. Hurrell R., Egli I. Iron bioavailability and dietary reference values. Am. J. Clin. Nutr. 2010;91:1461S–1467S. doi: 10.3945/ajcn.2010.28674F.
    1. Kaur B., Henry J. Micronutrient status in type 2 diabetes: A review. Adv. Food Nutr. Res. 2014;71:55–100.
    1. Thomas-Valdes S., Tostes M., Anunciacao P.C., da Silva B.P., Sant’Ana H.M.P. Association between vitamin deficiency and metabolic disorders related to obesity. Crit. Rev. Food Sci. Nutr. 2017;57:3332–3343. doi: 10.1080/10408398.2015.1117413.
    1. Desmarchelier C., Borel P., Goncalves A., Kopec R., Nowicki M., Morange S., Lesavre N., Portugal H., Reboul E. A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men. J. Nutr. 2016;146:2421–2428. doi: 10.3945/jn.116.237115.
    1. Borel P., Desmarchelier C. Bioavailability of Fat-Soluble Vitamins and Phytochemicals in Humans: Effects of Genetic Variation. Ann. Rev. Nutr. 2018;38:69–96. doi: 10.1146/annurev-nutr-082117-051628.
    1. Péter S., Holguin F., Wood L.G., Clougherty J.E., Raederstorff D., Antal M., Weber P., Eggersdorfer M. Nutritional solutions to reduce risks of negative health impacts of air pollution. Nutrients. 2015;7:10398–10416. doi: 10.3390/nu7125539.
    1. Agarwal K.S., Mughal M.Z., Upadhyay P., Berry J.L., Mawer E.B., Puliyel J.M. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch. Dis. Child. 2002;87:111–113. doi: 10.1136/adc.87.2.111.
    1. European Food Safety Authority (EFSA) Scientific Opinion on Dietary Reference Values for vitamin C. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) EFSA J. 2013;11:3418.
    1. Carr A.C., Shaw G.M., Fowler A.A., Natarajan R. Ascorbate-dependent vasopressor synthesis: A rationale for vitamin C administration in severe sepsis and septic shock? Crit. Care. 2015;19:418. doi: 10.1186/s13054-015-1131-2.
    1. Schmoranzer F., Fuchs N., Markolin G., Carlin E., Sakr L., Sommeregger U. Influence of a complex micronutrient supplement on the immune status of elderly individuals. Int. J. Vitam. Nutr. Res. 2009;79:308–318. doi: 10.1024/0300-9831.79.56.308.
    1. Scrimgeour A.G., Condlin M.L. Zinc and micronutrient combinations to combat gastrointestinal inflammation. Curr. Opin. Clin. Nutr. Metab. Care. 2009;12:653–660. doi: 10.1097/MCO.0b013e3283308dd6.
    1. Girodon F., Galan P., Monget A.L., Boutron-Ruault M.C., Brunet-Lecomte P., Preziosi P., Arnaud J., Manuguerra J.C., Herchberg S. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: A randomized controlled trial. Arch. Intern. Med. 1999;159:748–754. doi: 10.1001/archinte.159.7.748.
    1. Penn N.D., Purkins L., Kelleher J., Heatley R.V., Mascie-Taylor B.H., Belfield P.W. The effect of dietary supplementation with vitamins A, C, and E on cell-mediated immune function in elderly log-stay patients: A randomized controlled trial. Age Ageing. 1991;20:169–174. doi: 10.1093/ageing/20.3.169.
    1. Kieliszek M. Selenium⁻Fascinating Microelement, Properties and Sources in Food. Molecules. 2019;24:1298. doi: 10.3390/molecules24071298.
    1. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) Scientific Opinion on the re-evaluation of iron oxides and hydroxides (E 172) as food additives. EFSA J. 2015;13:4317.
    1. Martinez-Estevez N.S., Alvarez-Guevara A.N., Rodriguez-Martinez C.E. Effects of zinc supplementation in the prevention of respiratory tract infections and diarrheal disease in Colombian children: A 12-month randomised controlled trial. Allergol. Immunopathol. 2016;44:368–375. doi: 10.1016/j.aller.2015.12.006.
    1. Ginde A.A., Blatchford P., Breese K., Zarrabi L., Linnebur S.A., Wallace J.I., Schwartz R.S. High-Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long-Term Care Residents: A Randomized Clinical Trial. J. Am. Geriatr. Soc. 2017;65:496–503. doi: 10.1111/jgs.14679.
    1. Hemila H. Vitamin E administration may decrease the incidence of pneumonia in elderly males. Clin. Interv. Aging. 2016;11:1379–1385. doi: 10.2147/CIA.S114515.
    1. Yousefichaijan P., Naziri M., Taherahmadi H., Kahbazi M., Tabaei A. Zinc Supplementation in Treatment of Children with Urinary Tract Infection. Iran. J. Kidney Dis. 2016;10:213–216.
    1. Johnston C., Barkyoumb G.M., Schumacher S.S. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: A randomized controlled trial. Nutrients. 2014;6:2572–2583. doi: 10.3390/nu6072572.
    1. Constantini N.W., Dubnov-Raz G., Eyal B.B., Berry E.M., Cohen A.H., Hemila H. The effect of vitamin C on upper respiratory infections in adolescent swimmers: A randomized trial. Eur. J. Pediatr. 2011;170:59–63. doi: 10.1007/s00431-010-1270-z.
    1. Sezikli M., Cetinkaya Z.A., Sezikli H., Guzelbulut F., Tiftikci A., Ince A.T., Gokden Y., Yasar B., Atalay S., Kurdas O.O. Oxidative stress in Helicobacter pylori infection: Does supplementation with vitamins C and E increase the eradication rate? Helicobacter. 2009;14:280–285. doi: 10.1111/j.1523-5378.2009.00686.x.
    1. Meydani S.N., Barnett J.B., Dallal G.E., Fine B.C., Jacques P.F., Leka L.S., Hamer D.H. Serum zinc and pneumonia in nursing home elderly. Am. J. Clin. Nutr. 2007;86:1167–1173. doi: 10.1093/ajcn/86.4.1167.
    1. Stephen A.I., Avenell A. A systematic review of multivitamin and multimineral supplementation for infection. J. Hum. Nutr Diet. 2006;19:179–190. doi: 10.1111/j.1365-277X.2006.00694.x.
    1. Imdad A., Mayo-Wilson E., Herzer K., Bhutta Z.A. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst. Rev. 2017;3:CD008524. doi: 10.1002/14651858.CD008524.pub3.
    1. Mathew J.L. Vitamin A supplementation for prophylaxis or therapy in childhood pneumonia: A systematic review of randomized controlled trials. Indian Pediatr. 2010;47:255–261. doi: 10.1007/s13312-010-0042-1.
    1. Chen H., Zhuo Q., Yuan W., Wang J., Wu T. Vitamin A for preventing acute lower respiratory tract infections in children up to seven years of age. Cochrane Database Syst. Rev. 2008:CD006090. doi: 10.1002/14651858.CD006090.pub2.
    1. Martineau A.R., Jolliffe D.A., Hooper R.L., Greenberg L., Aloia J.F., Bergman P., Dubnov-Raz G., Esposito S., Ganmaa D., Ginde A.A., et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi: 10.1136/bmj.i6583.
    1. Rejnmark L., Bislev L.S., Cashman K.D., Eiriksdottir G., Gaksch M., Grubler M., Grimnes G., Gudnason V., Lips P., Pilz S., et al. Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data. PLoS ONE. 2017;12:e0180512. doi: 10.1371/journal.pone.0180512.
    1. Bergman P., Lindh Å., Björkhem-Bergman L., Lindh J. Vitamin D and respiratory tract infections: A systematic review and meta-analysis of randomized controlled trials. PLoS ONE. 2013;8:e65835. doi: 10.1371/journal.pone.0065835.
    1. Charan J., Goyal J., Saxena D., Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. J. Pharmacol. Pharmacother. 2012;3:300–303. doi: 10.4103/0976-500X.103685.
    1. Yamshchikov A.V., Desai N.S., Blumberg H.M., Ziegler T.R., Tangpricha V. Vitamin D for treatment and prevention of infectious diseases: A systematic review of randomized controlled trials. Endocr. Pract. 2009;15:438–449. doi: 10.4158/EP09101.ORR.
    1. Vuichard Gysin D., Dao D., Gysin C.M., Lytvyn L., Loeb M. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2016;11:e0162996. doi: 10.1371/journal.pone.0162996.
    1. Xiao L., Xing C., Yang Z., Xu S., Wang M., Du H., Liu K., Huang Z. Vitamin D supplementation for the prevention of childhood acute respiratory infections: A systematic review of randomised controlled trials. Br. J. Nutr. 2015;114:1026–1034. doi: 10.1017/S000711451500207X.
    1. Yakoob M.Y., Salam R.A., Khan F.R., Bhutta Z.A. Vitamin D supplementation for preventing infections in children under five years of age. Cochrane Database Syst. Rev. 2016;11:CD008824. doi: 10.1002/14651858.CD008824.pub2.
    1. Hemilä H., Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev. 2013;1:CD000980. doi: 10.1002/14651858.CD000980.pub4.
    1. Moreira A., Kekkonen R.A., Delgado L., Fonseca J., Korpela R., Haahtela T. Nutritional modulation of exercise-induced immunodepression in athletes: A systematic review and meta-analysis. Eur. J. Clin. Nutr. 2007;61:443–460. doi: 10.1038/sj.ejcn.1602549.
    1. Hemila H., Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst. Rev. 2013:CD005532. doi: 10.1002/14651858.CD005532.pub3.
    1. Ghouri F., Hollywood A., Ryan K. A systematic review of non-antibiotic measures for the prevention of urinary tract infections in pregnancy. BMC Pregnancy Childbirth. 2018;18:99. doi: 10.1186/s12884-018-1732-2.
    1. Gulani A., Sachdev H.S. Zinc supplements for preventing otitis media. Cochrane Database Syst. Rev. 2014;4:CD006639. doi: 10.1002/14651858.CD006639.pub4.
    1. Roth D.E., Richard S.A., Black R.E. Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: Meta-analysis and meta-regression of randomized trials. Int. J. Epidemiol. 2010;39:795–808. doi: 10.1093/ije/dyp391.
    1. Aggarwal R., Sentz J., Miller M.A. Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: A meta-analysis. Pediatrics. 2007;119:1120–1130. doi: 10.1542/peds.2006-3481.
    1. Mayo-Wilson E., Imdad A., Junior J., Dean S., Bhutta Z.A. Preventive zinc supplementation for children, and the effect of additional iron: A systematic review and meta-analysis. BMJ Open. 2014;4:e004647. doi: 10.1136/bmjopen-2013-004647.
    1. Mayo-Wilson E., Junior J.A., Imdad A., Dean S., Chan X.H., Chan E.S., Jaswal A., Bhutta Z.A. Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age. Cochrane Database Syst. Rev. 2014;5:CD009384. doi: 10.1002/14651858.CD009384.pub2.
    1. Gera T., Sachdev H.P. Effect of iron supplementation on incidence of infectious illness in children: Systematic review. BMJ. 2002;325:1142. doi: 10.1136/bmj.325.7373.1142.
    1. De Gier B., Campos Ponce M., van de Bor M., Doak C.M., Polman K. Helminth infections and micronutrients in school-age children: A systematic review and meta-analysis. Am. J. Clin. Nutr. 2014;99:1499–1509. doi: 10.3945/ajcn.113.069955.
    1. El-Kadiki A., Sutton A.J. Role of multivitamins and mineral supplements in preventing infections in elderly people: Systematic review and meta-analysis of randomised controlled trials. BMJ. 2005;330:871. doi: 10.1136/bmj.38399.495648.8F.
    1. Wu T., Ni J., Wei J. Vitamin A for non-measles pneumonia in children. Cochrane Database Syst. Rev. 2005;3:CD003700. doi: 10.1002/14651858.CD003700.pub2.
    1. Glasziou P.P., Mackerras D.E. Vitamin A supplementation in infectious diseases: A meta-analysis. BMJ. 1993;306:366–370. doi: 10.1136/bmj.306.6874.366.
    1. Das R.R., Singh M., Naik S.S. Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia. Cochrane Database Syst. Rev. 2018;7:CD011597. doi: 10.1002/14651858.CD011597.pub2.
    1. Ran L., Zhao W., Wang J., Wang H., Zhao Y., Tseng Y., Bu H. Extra dose of vitamin C based on a daily supplementation shortens the common cold: A meta-analysis of 9 randomized controlled trials. BioMed Res. Int. 2018;2018:1837634. doi: 10.1155/2018/1837634.
    1. Li G., Li L., Yu C., Chen L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: A meta-analysis. Br. J. Nutr. 2011;106:1632–1637. doi: 10.1017/S0007114511003813.
    1. Caicedo Ochoa E.Y., Quintero Moreno C.O., Mendez Fandino Y.R., Sanchez Fonseca S.C., Cortes Motta H.F., Guio Guerra S.A. Assessment of the use of vitamin C and E supplements concomitantly to antibiotic treatment against Helicobacter pylori: A systematic review and meta-analysis. Med. Clin. 2018;151:45–52. doi: 10.1016/j.medcli.2017.09.014.
    1. Hemilä H. Zinc lozenges may shorten the duration of colds: A systematic review. Open Respir. Med. J. 2011;5:51–58.
    1. Tie H.T., Tan Q., Luo M.Z., Li Q., Yu J.L., Wu Q.C. Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: A meta-analysis of randomised-controlled trials. Br. J. Nutr. 2016;115:807–816.
    1. Das R.R., Singh M., Shafiq N. Short-term therapeutic role of zinc in children <5 years of age hospitalised for severe acute lower respiratory tract infection. Paediatr. Respir. Rev. 2012;13:184–191.
    1. Haider B.A., Lassi Z.S., Ahmed A., Bhutta Z.A. Zinc supplementation as an adjunct to antibiotics in the treatment of pneumonia in children 2 to 59 months of age. Cochrane Database Syst. Rev. 2011;10:CD007368. doi: 10.1002/14651858.CD007368.pub2.
    1. Grobler L., Nagpal S., Sudarsanam T.D., Sinclair D. Nutritional supplements for people being treated for active tuberculosis. Cochrane Database Syst. Rev. 2016;6:CD006086. doi: 10.1002/14651858.CD006086.pub4.
    1. Pilz S., März W., Cashman K.D., Kiely M.E., Whiting S.J., Holick M.F., Grant W.B., Pludowski P., Hiligsmann M., Trummer C., et al. Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper. Front. Endocrinol. 2018;9:373. doi: 10.3389/fendo.2018.00373.
    1. Mason J., Lotfi M., Dalmiya N., Sethuraman K., Deitchler M. The Micronutrient Report: Current Progress and Trends in the Control of Vitamin A, Iodine, and Iron Deficiencies. Micronutrient Initiative and International Development Research Centre; Ottawa, ON, Canada: 2001.
    1. Guallar E., Stranges S., Mulrow C., Appel L.J., Miller E.R. Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Ann. Intern. Med. 2013;159:850–851. doi: 10.7326/0003-4819-159-12-201312170-00011.
    1. Gombart A.F., CRONOS Study Group Effect of multimicronutrient supplementation on the function of the immune system in healthy elderly adults. in preparation.
    1. World Health Organization . Guideline: Vitamin A Supplementation in Postpartum Women. World Health Organization; Geneva, Switzerland: 2011. [(accessed on 16 December 2019)]. Available online:
    1. World Health Organization . Guideline: Vitamin A Supplementation in Pregnant Women. World Health Organization; Geneva, Switzerland: 2011. [(accessed on 16 December 2019)]. Available online:
    1. Huang H.-Y., Caballero B., Chang S., Alberg A., Semba R., Schneyer C., Wilson R.F., Cheng T.-Y., Prokopowicz G., Barnes G.J., et al. Multivitamin/mineral supplements and prevention of chronic disease. Evid Rep. Technol Assess. Full Rep. 2006;139:1–117.
    1. Slatore C.G., Littman A.J., Au D.H., Satia J.A., White E. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am. J. Respir. Crit. Care Med. 2008;177:524–530. doi: 10.1164/rccm.200709-1398OC.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner