Study Title:

Zinc intake and resistance to H1N1 influenza.

Study Abstract

Stevenson, et al1 summarized the needs of children at risk for H1N1 influenza and noted the poverty of 14.5 million child recipients of free school meals every day in the United States. Such children are at risk for dietary zinc deficiency, a condition likely to afflict at least 1 in 5 persons worldwide,2 in part because of low intakes of foods derived from animal flesh, especially red meat (the richest common dietary source of zinc), and high intakes of whole grain cereal products and legumes rich in phytate and other indigestible zinc-binding ligands.3

Zinc deficiency is relevant to H1N1 influenza because it decreases cell-mediated immunity.4 At the practical level, zinc treatment has been found to be efficacious for a variety of infections4; in low-income Mexican Americans aged 6 to 7 years who are not visibly ill but have mild zinc deficiency (normal plasma zinc), a randomized trial showed that the administration of zinc and other micronutrients together were significantly more efficacious for cell-mediated immunity than was administration of other micronutrients alone.5

The presence of zinc in the diet affects various aspects of cell-mediated immunity, including expression of interleukin-2 and interferon-γ.4 Interleukin-2 stimulates generation of natural killer and cytolytic T cells that kill viruses, bacteria, and tumor cells. Interferon-γ and interleukin-2 together activate macrophage monocytes that kill parasites. Zinc also suppresses ICAM-1, which serves as a receptor for viruses, and inhibits the protease from HIV type 1.6

Pertinent to bacterial pneumonia–complicating influenza, a 1-year study of 420 nursing home patients who daily were administered 50% of the United States Department of Agriculture Recommended Daily Allowance for vitamins and minerals found that participants with plasma concentrations of zinc greater than 70 μg/dL had a significantly lower risk of pneumonia requiring antibiotics than did participants with plasma zinc levels of less than 70 μg/dL.7

Zinc treatment is likely to be most efficacious when administered with a mixture of other micronutrients.8 In nature, micronutrient deficiencies seldom occur alone, and micronutrients act in concert. For example, the methionine cycle–transsulfuration pathway requires folate, riboflavin, pyridoxine, cobalamine, choline/betaine, methionine, and zinc for several reactions.9

Food fortification is an effective method for prevention of nutrient deficiencies. Groups at high risk for zinc deficiency could be specifically targeted by the introduction of inexpensive, culturally acceptable fortified foods into their diets, thus avoiding treatment of groups at low risk. We believe it would be appropriate to use such an approach to ascertain if zinc given with other micronutrients is at least as efficacious for preventing H1N1 influenza as zinc administered with oral rehydration fluids is for treatment of diarrhea.10

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We thank John Walker, MD, of the Texas Department of Health for bringing E. Stevenson's article to our attention, and asking the question “Is zinc deficiency a factor in morbidity from H1N1 influenza, especially among Mexican American children?” He also motivated H. H. Sandstead and A. S. Prasad to propose a practical intervention to answer the question.

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1. Stevenson E, Barrios L, Cordell R, et al. Pandemic influenza planning: addressing the needs of children. Am J Public Health 2009;99(suppl 2):S255–S260. [PubMed]

2. Wuehler SE, Peerson JM, Brown KH. Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates. Public Health Nutr 2005;8(7):812–819. [PubMed]

3. Sandstead HH. Causes of iron and zinc deficiencies and their effects on brain. J Nutr 2000;130(supp 2):347S–349S. [PubMed]

4. Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009;12(6):646–652. [PubMed]

5. Sandstead HH, Prasad AS, Penland JG, et al. Zinc deficiency in Mexican American children: influence of zinc and other micronutrients on T cells, cytokines, and anti-inflammatory plasma proteins. Am J Clin Nutr 2008;88(4):1067–1073. [PubMed]

6. Zhang ZY, Reardon IM, Hui JO, et al. Zinc inhibition of renin and the protease from human immunodeficiency virus type 1. Biochemistry 1991;30(36):8717–8721. [PubMed]

7. Meydani SN, Barnett JB, Dallal GE, et al. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr 2007;86(4):1167–1173. [PMC free article] [PubMed]

8. Allen LH, Peerson JM, Olney DK. Provision of multiple rather than two or fewer micronutrients more effectively improves growth and other outcomes in micronutrient-deficient children and adults. J Nutr 2009;139(5):1022–1030. [PubMed]

9. Maret W, Sandstead HH. Possible roles of zinc nutriture in the fetal origins of disease. Exp Gerontol 2008;43(5):378–381. [PubMed]

10. Fischer Walker C, Black RE. Zinc and the risk for infectious disease. Annu Rev Nutr 2004;24:255–275. [PubMed]

Study Information

Sandstead HH, Prasad AS.
Zinc intake and resistance to H1N1 influenza.
Am J Public Health.
2010 June
Division of Human Nutrition, Department of Preventive Medicine and Community Health, University of Texas.

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