Zinc requirements and the risks and benefits of zinc supplementation

This review critically summarizes the literature on the spectrum of health effects of zinc status, ranging from symptoms of zinc deficiency to excess exposure. Studies on zinc intake are reviewed in relation to optimum requirements as a function of age and sex. Current knowledge on the biochemical properties of zinc which are critical to the essential role of this metal in biological systems is summarized. Dietary and physiological factors influencing the bioavailability and utilization of zinc are considered with special attention to interactions with iron and copper status. The effects of zinc deficiency and toxicity are reviewed with respect to specific organs, immunological and reproductive function, and genotoxicity and carcinogenicity. Finally, key questions are identified where research is needed, such as the risks to human health of altered environmental distribution of zinc, assessment of zinc status in humans, effects of zinc status in relation to other essential metals on immune function, reproduction, neurological function, and the cardiovascular system, and mechanistic studies to further elucidate the biological effects of zinc at the molecular level.

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Zinc: health effects and research priorities for the 1990s.

1. Physiology of Zinc: General Aspects.- 2. An Introduction to the Biochemistry of Zinc.- 3. Intestinal Absorption of Zinc.- 4. Promoters and Antagonists of Zinc Absorption.- 5. Systemic Transport of Zinc.- 6. Systemic Interactions of Zinc.- 7. Biochemistry of Zinc in Cell Division and Tissue Growth.- 8. Zinc in Cell Division and Tissue Growth: Physiological Aspects.- 9. Biochemical Pathologies of Zinc Deficiency.- 10. Zinc and Iron in Free Radical Pathology and Cellular Control.- 11. Zinc Status and Food Intake.- 12. Zinc and Reproduction: Effects of Deficiency on Foetal and Postnatal Development.- 13. A Note on Zinc and Immunocompetence.- 14. Zinc and Behaviour.- 15. Neurobiology of Zinc.- 16. Zinc in Endocrine Function.- 17. Severe Zinc Deficiency.- 18. Mild Zinc Deficiency in Human Subjects.- 19. Putative Therapeutic Roles for Zinc.- 20. The Diagnosis of Zinc Deficiency.- 21. Human Zinc Requirements.- 22. Dietary Pattern and Zinc Supply.- 23. Zinc Excess.- 24. The Biological Significance of Zinc for Man: Problems and Prospects.

Zinc in Human Biology

Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion-of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, still-births, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake dereases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.

Zinc, copper and selenium in reproduction

Objective. —To evaluate whether zinc supplementation during pregnancy is associated with an increase in birth weight. Design. —A randomized double-blind placebo-controlled trial. Setting. —Outpatient clinic and delivery service at the University of Alabama at Birmingham. Patients. —Five hundred eighty medically indigent but otherwise healthy African-American pregnant women with plasma zinc levels below the median at enrollment in prenatal care, randomized at 19 weeks' gestational age. Women were subdivided by the population median body mass index of 26 kg/m 2 into two groups for additional analyses. Intervention. —Women who were taking a non—zinc-containing prenatal multivitamin/mineral tablet were randomized to receive either a daily dose of 25 mg of zinc or a placebo until delivery. Main Outcome Measures. —Birth weight, gestational age at birth, and head circumference at birth. Results. —In all women, infants in the zinc supplement group had a significantly greater birth weight (126 g, P =.03) and head circumference (0.4 cm, P =.02) than infants in the placebo group. In women with a body mass index less than 26 kg/m 2 , zinc supplementation was associated with a 248-g higher infant birth weight ( P =.005) and a 0.7-cm larger infant head circumference ( P =.007). Plasma zinc concentrations were significantly higher in the zinc supplement group. Conclusions. —Daily zinc supplementation in women with relatively low plasma zinc concentrations in early pregnancy is associated with greater infant birth weights and head circumferences, with the effect occurring predominantly in women with a body mass index less than 26 kg/m 2 . ( JAMA . 1995;274:463-468)

J. Day

Papers

Zinc and small babies.