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

Evolutionary theory predicts that mothers of different condition should adjust the birth sex ratio of their offspring in relation to future reproductive benefits. Published studies addressing variation in mammalian sex ratios have produced surprisingly contradictory results. Explaining the source of such variation has been a challenge for sex-ratio theory, not least because no mechanism for sex-ratio adjustment is known. I conducted a meta-analysis of previous mammalian sex-ratio studies to determine if there are any overall patterns in sex-ratio variation. The contradictory nature of previous results was confirmed. However, studies that investigated indices of condition around conception show almost unanimous support for the prediction that mothers in good condition bias their litters towards sons. Recent research on the role of glucose in reproductive functioning have shown that excess glucose favours the development of male blastocysts, providing a potential mechanism for sex-ratio variation in relation to maternal condition around conception. Furthermore, many of the conflicting results from studies on sex-ratio adjustment would be explained if glucose levels in utero during early cell division contributed to the determination of offspring sex ratios.

Facultative adjustment of mammalian sex ratios in support of the Trivers-Willard hypothesis: evidence for a mechanism.

Zinc and small babies.

The discrepancy between the number of boys and girls born has been interpreted as a natural selection response to differential survival prospects. There also exists a discrepancy in birth weight, length, head circumference at birth of boys and girls; on the other hand, placental weights were not so strongly biased by the sex of the fetus. Metabolic differences between the sexes are clearly recognized in adults. It is therefore argued that the anthropometric differences at birth, examples of which are presented in this paper, can only be achieved if the products of conception are also expressing a sexual bias in metabolism and physiology. It would then be this bias which would determine the efficiency of the implantation and growth processes and lead to rates of survival to birth. The speculation arising from this and the experimental manipulation of the sex ratio is that the physiological component most likely to be involved would be the lipid compartment with its strong sex difference.

Gender differences at birth and differences in fetal growth

The oral bioavailability of zinc was studied in nonpregnant adults before and 24 hours after two weeks of oral supplementation with iron and folic acid. Bioavailability was greatly reduced, and the shape of the plasma curves suggested that this was due to impairment of the intestinal absorption of zinc. The findings suggest that the reduced bioavailability of zinc occurs because of interelement competition in the bowel wall. This might induce zinc depletion.

https://www.bmj.com/content/bmj/287/6398/1013.full.pdf

Oral iron and the bioavailability of zinc.

The zinc content of peripheral blood leucocytes from the cord blood of 63 normal and 20 preterm babies, and of 27 babies with evidence of idiopathic intrauterine growth retardation (IUGR) was measured. Leucocyte zinc depletion was present in babies with acute IUGR (IUGR babies compared with controls, mean 47.8 v 51.5 ng zinc/mg dry weight), but was especially severe in those with prolonged IUGR (mean 43.2 ng zinc/mg dry weight), while preterm babies were normal (mean 51.9 ng zinc/mg dry weight). We suggest that this fetal tissue zinc depletion is caused by maternal zinc depletion, and may reflect a reduction of whole body zinc status.

https://adc.bmj.com/content/archdischild/58/10/807.full.pdf

Peripheral blood leucocyte zinc depletion in babies with intrauterine growth retardation.

1. Cats fed for 4 months with a diet with less than 7 p.p.m. zinc developed tissue zinc depletion, as judged by reduced muscle zinc content. 2. Dark adapted electroretinogram (ERG) thresholds became elevated in zinc depleted cats. Electroretinograms and muscle zinc levels were reversed by zinc supplementation. 3. Rod ERG to suprathreshold stimuli became reduced in b-wave amplitude in cats with zinc depletion, but suprathreshold cone ERG were unchanged. 4. The ERG changes in zinc depleted cats were unlike those in cats fed on a taurine depleted diet.

N. J. Meadows

Papers

Zinc and small babies.

Gender differences at birth and differences in fetal growth

Oral iron and the bioavailability of zinc.

Peripheral blood leucocyte zinc depletion in babies with intrauterine growth retardation.

Rod mediated retinal dysfunction in cats with zinc depletion: Comparison with taurine depletion