What does zinc do? ================== * Abi Berger Adequate zinc intake is critical for health. Zinc deficiency affects cells of the immune system. It causes a reduction in the number B lymphocytes and T lymphocytes (CD4 lymphocytes in particular) through increased apoptosis and also reduces their functional capacity. The functions of the macrophage, another key immunological cell that engulfs and destroys bacteria, are also compromised. The production and potency of several cytokines, the central messengers of the immune system, are also perturbed by zinc deficiency. Many of these changes occur even in the early stages of deficiency. Zinc plays a part in the maintenance of epithelial and tissue integrity through promoting cell growth and suppressing apoptosis and through its underappreciated role as an antioxidant, protecting against free radical damage during inflammatory responses. Thus, in the case of diarrhoea, multiple functions of zinc may help to maintain the integrity of the gut mucosa to reduce or prevent fluid loss. Notably, these responses can occur within 48 hours, much more rapidly than the direct effects of zinc on cellular development. The recommended daily allowance is only 10 mg elemental zinc, but many people in both developing and industrialised countries do not have this in their diet.1 Zinc deficiency is biochemically defined as a serum concentration of less than 9 μmol/l. However, serum zinc concentrations may not fully reflect the physiological zinc status in an individual, and individuals with apparently normal serum concentrations may benefit from daily zinc supplements.2 ## Benefits of supplementation This is clearly illustrated in several randomised controlled trials of zinc supplementation. A meta-analysis indicated that daily zinc supplementation can reduce the incidence of pneumonia by 41% and diarrhoea by 18%.3 A meta-analysis of trials of adjunctive zinc supplementation in children with diarrhoea reduced the duration of the illness by 24%.4 A trial of daily zinc supplementation in otherwise healthy children from New Guinea reduced the number of cases of malaria seen at a health clinic by 38%.5 There is also evidence that zinc supplementation could offer benefit to pregnant women and their babies.6 One study showed that prenatal zinc supplementation can increase birth weight,7 and another indicated reduced incidence of diarrhoea and other morbidities in the infants.8 Babies who are small for gestational age also seem to benefit from taking daily zinc supplementation. A trial in India found that babies who received zinc from 1 month onwards were 60% less likely to die during infancy.9 Lastly, several studies indicate a potential role for zinc and supplements that contain zinc in improving immune status10 and health in elderly people.11 Zinc supplementation, therefore, seems be particularly critical during periods of immune development or degeneration: early childhood, pregnancy, and later life. ## Problems caused by too much zinc Taking too much daily zinc could also be a problem because, although it is not toxic, high doses can impair copper absorption. This can lead to copper deficiency with immunosuppression and other subtle and apparent adverse effects, especially for the mother and fetus during pregnancy.12 For this reason, doses more than twice the recommended daily allowance are not recommended and prenatal zinc supplements should contain copper,13 especially in populations with low mineral intakes. ## References 1. Gibson RS, Vanderkooy PD, MacDonald AC, Goldman A, Ryan BA, Berry M. A growth-limiting, mild zinc-deficiency syndrome in some southern Ontario boys with low height percentiles. Am J Clin Nutr 1989; 49: 1266–1275. [Abstract/FREE Full Text](http://www.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpjbiI7czo1OiJyZXNpZCI7czo5OiI0OS82LzEyNjYiO3M6NDoiYXRvbSI7czoyMzoiL2Jtai8zMjUvNzM3Mi8xMDYyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 2. Black RE, Sazawal S. Zinc and childhood infectious disease morbidity and mortality. Br J Nutr 2001; 85(suppl 2): S125–S129. 3. Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr 1999; 135: 689–697. [CrossRef](http://www.bmj.com/lookup/external-ref?access_num=10.1016/S0022-3476(99)70086-7&link_type=DOI) [PubMed](http://www.bmj.com/lookup/external-ref?access_num=10586170&link_type=MED&atom=%2Fbmj%2F325%2F7372%2F1062.atom) [Web of Science](http://www.bmj.com/lookup/external-ref?access_num=000084263700013&link_type=ISI) 4. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000; 72: 1516–1522. [Abstract/FREE Full Text](http://www.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpjbiI7czo1OiJyZXNpZCI7czo5OiI3Mi82LzE1MTYiO3M6NDoiYXRvbSI7czoyMzoiL2Jtai8zMjUvNzM3Mi8xMDYyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 5. Shankar AH, Genton B, Baisor M, Paino J, Tamja S, Adiguma T, et al. The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. Am J Trop Med Hyg 2000; 62: 663–669. [Abstract](http://www.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NzoidHJvcG1lZCI7czo1OiJyZXNpZCI7czo4OiI2Mi82LzY2MyI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzMyNS83MzcyLzEwNjIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 6. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr 1998; 68(2 suppl): S499–S508. 7. Goldenberg RL, Tamura T, Neggers Y, Copper RL, Johnston KE, DuBard MB, et al. The effect of zinc supplementation on pregnancy outcome. JAMA 1995; 274: 463–468. [CrossRef](http://www.bmj.com/lookup/external-ref?access_num=10.1001/jama.1995.03530060037030&link_type=DOI) [PubMed](http://www.bmj.com/lookup/external-ref?access_num=7629954&link_type=MED&atom=%2Fbmj%2F325%2F7372%2F1062.atom) [Web of Science](http://www.bmj.com/lookup/external-ref?access_num=A1995RM69900025&link_type=ISI) 8. Osendarp SJ, van Raaij JM, Darmstadt GL, Baqui AH, Hautvast JG, Fuchs GJ. Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomised placebo controlled trial. Lancet 2001; 357: 1080–1085. [CrossRef](http://www.bmj.com/lookup/external-ref?access_num=10.1016/S0140-6736(00)04260-4&link_type=DOI) [PubMed](http://www.bmj.com/lookup/external-ref?access_num=11297959&link_type=MED&atom=%2Fbmj%2F325%2F7372%2F1062.atom) [Web of Science](http://www.bmj.com/lookup/external-ref?access_num=000167996200010&link_type=ISI) 9. Sazawal S, Black RE, Menon VP, Dinghra P, Caulfield LE, Dhingra U, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. Pediatrics 2001; 108: 1280–1286. [Abstract/FREE Full Text](http://www.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTA6InBlZGlhdHJpY3MiO3M6NToicmVzaWQiO3M6MTA6IjEwOC82LzEyODAiO3M6NDoiYXRvbSI7czoyMzoiL2Jtai8zMjUvNzM3Mi8xMDYyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 10. Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F, et al. The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc 1998; 46: 19–26. [PubMed](http://www.bmj.com/lookup/external-ref?access_num=9434661&link_type=MED&atom=%2Fbmj%2F325%2F7372%2F1062.atom) [Web of Science](http://www.bmj.com/lookup/external-ref?access_num=000071342100004&link_type=ISI) 11. Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med 1999; 159: 748–754. [CrossRef](http://www.bmj.com/lookup/external-ref?access_num=10.1001/archinte.159.7.748&link_type=DOI) [PubMed](http://www.bmj.com/lookup/external-ref?access_num=10218756&link_type=MED&atom=%2Fbmj%2F325%2F7372%2F1062.atom) [Web of Science](http://www.bmj.com/lookup/external-ref?access_num=000079670600016&link_type=ISI) 12. Keen CL, Uriu-Hare JY, Hawk SN, Jankowski MA, Daston GP, Kwik-Uribe CL, et al. Effect of copper deficiency on prenatal development and pregnancy outcome. Am J Clin Nutr 1998;7(suppl 5): S1003–S1011. 13. Institute of Medicine, Subcommittee on Nutritional Status and Weight Gain During Pregnancy. Nutrition during pregnancy. Part 1: weight gain. Part 11: nutrition supplements. Washington, DC: National Academy Press, 1990.