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What's the Big Deal About Zinc? Ian J. Griffin, M.D. Dr. Griffin is Assistant Professor of Pediatrics, Baylor College of Medicine, Houston TX. This work is a publication of the U.S. Department of Agriculture (USDA)/Agricultural Research Service (ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, Texas. This project has been funded in part with federal funds from the USDA/ARS under Cooperative Agreement number 58-6250-6-001, the NIH, NCRR General Clinical Research for Children Grant number RR00188. Contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. Zinc is incredibly common in our bodies. It is a component of over 250 enzymes essential for human health and development.1,2,3 It is required for DNA and RNA replication, gene transcription and apoptosis (programmed cell death).4 It is necessary for a healthy immune system, aids in healing and plays a key role in our senses of taste and smell. Zinc is also required for normal growth during pregnancy, childhood and adolescence. Given the importance of zinc to so many biochemical functions, it may seem surprising it took us so long to recognize it as vital to human health.5 But zinc is an undercover operator. It hides in plain sight. There is no single test that adequately measures whether or not we have enough zinc. Certain risk factors, such as low caloric intake, alcoholism, digestive and other diseases, and impaired growth in infants and children often cause doctors to suspect zinc deficiency. Vegetarians may need more zinc than non-vegetarians because zinc from plant foods is harder for the body to absorb. Zinc Deficiency Our bodies' need for zinc becomes clear when we look at what happens to people who are deficient in it. In 1961 a landmark study examined a group of 11 Iranian men with a wide variety of symptoms: iron deficiency; dwarfism; geophagia (the practice of eating clay, chalk or other forms of earth, usually because of a mineral-deficient diet); and hypogonadism, a defect of the reproductive system that results in a lack of function of the ovaries or testes and can cause defective sexual development and infertility.6 At first, iron deficiency was suspected. The men responded well to an improved, iron-rich diet but researchers were left scratching their heads, as iron deficiency alone could not explain every symptom. A few years later, a similar set of symptoms was seen in a group of Egyptian men.7 As with the Iranian subjects, their diet was lacking in variety, particularly in animal protein, and they practiced geophagia. The Egyptians were found to have abnormally low zinc concentra- tions in their plasma and red blood cells, an indication of zinc deficiency. Their physical growth increased dramatically after they were given zinc supplements. We are now certain that both groups had zinc deficiency in addition to other nutrient deficiencies. Zinc deficiency doesn't just cause diseases and problems like those in the studies above. It can also be caused by other diseases. An example is acrodermatitis enteropathica, a congenital disorder that prevents the digestive system from absorbing enough zinc into the body.8,9,10 Foods Rich in Zinc Zinc is absorbed from food throughout the gut but mostly in the small intestine.11,12 It is found in many foods. Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good sources of zinc include beans, nuts, seafood, whole grains, fortified breakfast cereals and dairy products. Unneeded or excess zinc is excreted in feces and urine.13,14,15,16,17,18 The amount of zinc in our bodies is regulated by so-called zinc transporters, which maintain proper levels of zinc in a complex and overlapping process.19,20,21,22,23,24,25,26,27,28,29,30,31 What Diseases Cause Zinc Deficiency? Two diseases are caused by mutations in these transporters: acrodermatitis enteropathica and breast-feeding associated zinc deficiency. Acrodermatitis enteropathica (AE) is the best-known cause of zinc deficiency in humans.32 It is caused by an inherited inability to absorb zinc through the digestive system. Early symptoms echo those in the studies described earlier. They include diarrhea, dermatitis (eczema or skin rash) and alopecia (loss of hair).33 The skin rash is most commonly found around the mouth and on the limbs. Other features include eye problems, irritability, apathy, depression, tremors, a loss of coordination and increased sensitivity to light. Cold sore-like lesions may appear at the corners of the mouth as may skin infections near the cuticles. Other signs of zinc deficiency are the sudden development of lactose intolerance, failure to thrive, delayed puberty, hypogonadism and recurrent infections of all kinds.34,35,36,37 Improvement occurs rapidly once zinc supplementation is started because AE is caused by an inherited inability to absorb zinc through the digestive system.40,41,42,43,44 Zinc Deficiency in Breast-Fed Infants Occasionally, breast-fed babies will develop a disease similar to acrodermatitis enteropathica. This condition is quite rare and is caused by deficient levels of zinc in the mother's breast milk.45,46,47,48,49 The condition differs from AE in that zinc absorption is normal and zinc levels return to normal if the baby is weaned or provided with foods containing zinc.50,51,52 Breast-feeding associated zinc deficiency is extremely rare and few doctors are likely ever to see a case. However, breast-fed infants grow more slowly than formula-fed infants -- even in the U.S. -- and it has been speculated that this may in part be explained by differences in zinc intake.53 Research studies have failed to show that giving breast fed babies zinc supplements makes a significant difference in their health or development. On the other hand, studies in developing countries have shown that giving zinc supplements to high-risk infants has significant health benefits, including improved growth.54,55 The Health Benefits of Zinc Supplementation in Developing Countries Although most breast-fed U.S. infants may not need supplementary zinc, the same is not true in developing countries. Many56,57 but not all58 studies have suggested that supplementing the diets of at-risk populations with zinc during the first year of life helps growth. Those most likely to benefit from zinc supplements are older children with low zinc levels and those whose growth is stunted. Zinc has also received much attention for its possible ability to reduce childhood mortality in developing countries59,60,61,62,63
What about the claims that zinc can help cure the common cold? The jury is still out. Early studies suggested that zinc gluconate lozenges could significantly reduce the duration of colds.66,67 Some studies of zinc gluconate lozenges and zinc nasal sprays suggested that they could reduce symptom duration from 7.6 days to 4.4 days68 and that zinc acetate lozenges reduced the duration of some symptoms by 25 to 50%.69,70 However, other studies have failed to replicate these findings.71,72,73,74,75,76,77 So far, studies indicate that zinc nasal sprays are best avoided and the usefulness of zinc lozenges is questionable; neither is recommended by the American Academy of Family Physicians. A possible role for zinc as a treatment for the common cold remains to be proved.78,79 The Bottom Line Zinc's health value is indisputable. People with zinc deficiencies can achieve remarkable improvement when given zinc supplementally. In addition, zinc supplementation is playing an increasingly important role in preventing disease and improving mortality rates in high-risk populations of children in developing countries. If properly applied, the therapeutic use of zinc in acute diarrhea and other illnesses has the potential to save the lives of millions of children annually. In healthy subjects in developed countries, the role of, and need for, zinc supplementation is far less clear. There have been considerable recent advances in understanding the molecular physiology which underlies the role of zinc in our bodily metabolism and functions. Much has been learned about zinc transport proteins and two inherited human diseases known to be caused by mutations in these proteins.
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Springfield, IL: Charles G Thomas, 1966:250-303. return 6. Prasad AS, Halsted JA, Nadimi M. Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Amer J Med 1961;31:532-46. return 7. Prasad AS, Miale A, Farid Z, Sandsted HH, Darby WJ. Biochemical studies on dwarfism, hypogonadism and anemia. Arch Intern Med 1963;11:407-28. return 8. Aggett PJ. Acrodermatitis enteropathica. J Inherit Metab Dis 1983;6 Suppl 1:39-43. return 9. Brandt T. Dermatitis in children with disturbancies of the general condition and the absorption of food elements. Acta Derm Venerol 1936;17:513-46. return 10. Moynahan EJ, Johnson FR, Mc MR. Acrodermatitis enteropathica: demonstration of possible intestinal enzyme defect. Proc R Soc Med 1963;56:300-1. return 11. Lee HH, Prasad AS, Brewer GJ, Owyang C. Zinc absorption in human small intestine. Am J Physiol 1989;256:G87-91. return 12. Matseshe JW, Phillips SF, Malagelada JR, McCall JT. Recovery of dietary iron and zinc from the proximal intestine of healthy man: studies of different meals and supplements. Am J Clin Nutr 1980;33:1946-53. return 13. Tran CD, Miller LV, Krebs NF, Lei S, Hambidge KM. Zinc absorption as a function of the dose of zinc sulfate in aqueous solution. Am J Clin Nutr 2004;80:1570-3. return 14. Lee DY, Prasad AS, Hydrick-Adair C, Brewer G, Johnson PE. Homeostasis of zinc in marginal human zinc deficiency: role of absorption and endogenous excretion of zinc. J Lab Clin Med 1993;122:549-56. return 15. Wada L, Turnlund JR, King JC. Zinc utilization in young men fed adequate and low zinc intakes. J Nutr 1985;115:1345-54. return 16. Istfan NW, Janghorbani M, Young VR. Absorption of stable70 Zn in healthy young men in relation to zinc intake. Am J Clin Nutr 1983;38:187-94. return 17. Jackson MJ, Jones DA, Edwards RH, Swainbank IG, Coleman ML. Zinc homeostasis in man: studies using a new stable isotope-dilution technique. 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The possible role of diodoquin as a zinc ionophore in the treatment of acrodermatitis enteropathica. Biochem Biophys Res Commun 1979;87:513-7. return 37. Aggett PJ, Delves HT, Thorn JM, Atherton DJ, Harris JT, Bangham AD. The therapeutic effect of amphotericin in acrodermatitis enteropathica: hypothesis and implications. Eur J Pediatr 1981;137:23-5. return 38. Moynahan EJ. Acrodermatitis enteropathica: A lethal inherited human zinc-deficiency disorder. Lancet 1974;2:399-400. 39. Leupold D, Poley JR, Meigel WN. Zinc therapy in acrodermatitis enteropathica. Helv Paediatr Acta 1976;31:109-15. return 40. Weismann K, Hoe S, Knudsen L, Sorensen SS. 65-Zinc absorption in patients suffering from acrodermatitis enteropathica and in normal adults assessed by whole-body counting technique. Br J Dermatol 1979;101:573-9. return 41. Lombeck T, Schnippering HG, Ritzl F, Feinendegen LE, Bremer HJ. Letter: Absorption of zinc in acrodermatitis enteropathica. Lancet 1975;1:855. return 42. Atherton DJ, Muller DP, Aggett PJ, Harries JT. A defect in zinc uptake by jejunal biopsies in acrodermatitis enteropathica. Clin Sci 1979;56:505-7. return 43. Vazquez F, Grider A. The effect of the acrodermatitis enteropathica mutation on zinc uptake in human fibroblasts. Biol Trace Elem Res 1995;50:109-17. return 44. Grider A, Young EM. The acrodermatitis enteropathica mutation transiently affects zinc metabolism in human fibroblasts. J Nutr 1996;126:219-24. return 45. Kuramoto Y, Igarashi Y, Tagami H. Acquired zinc deficiency in breast fed infants. Semin Derm 1991;10:309-12. return 46. Glover MT, Atherton DJ. Transient zinc deficiency in two full term breast-fed siblings associated with low maternal breast milk zinc concentration. Pediatr Derm 1988;5:10-13. return 47. Piela Z, Szuber M, Mach B, Janniger CK. Zinc deficiency in exclusively breast-fed infants. Cutis 1998;61:197-200. return 48. Stevens J, Lubitz L. Symptomatic zinc deficiency in breast-fed term and premature infants. 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Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000;133:245-52. return 70. Barrett B, Harahan B, Brown D, Zhang Z, Brown R. Sufficiently important difference for common cold: severity reduction. Ann Fam Med 2007;5:216-23. return 71. Farr BM, Conner EM, Betts RF, Oleske J, Minnefor A, Gwaltney JM, Jr. Two randomized controlled trials of zinc gluconate lozenge therapy of experimentally induced rhinovirus colds. Antimicrob Agents Chemother 1987;31:1183-7. return 72. Weismann K, Jakobsen JP, Weismann JE, Hammer UM, Nyholm SM, Hansen B, Lomholt KE, Schmidt K. Zinc gluconate lozenges for common cold. A double-blind clinical trial. Dan Med Bull 1990;37:279-81. return 73. Macknin ML, Piedmonte M, Calendine C, Janosky J, Wald E. Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial. Jama 1998;279:1962-7. return 74. Simasek M, Blandino DA. Treatment of the common cold. Am Fam Physician 2007;75:515-20. return 75. Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202-8. return 76. Eby GA, Halcomb WW. Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial. Altern Ther Health Med 2006;12:34-8. return 77. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20. return 78. McElroy BH, Miller SP. Effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) against the common cold in school-aged subjects: a retrospective chart review. Am J Ther 2002;9:472-5. return 79. McElroy BH, Miller SP. An open-label, single-center, phase IV clinical study of the effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) in reducing the duration and symptoms of the common cold in school-aged subjects. Am J Ther 2003;10:324-9. return |
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