Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Overview of dietary trace minerals

Sassan Pazirandeh, MD
David L Burns, MD
Ian J Griffin, MB ChB
Section Editor
Timothy O Lipman, MD
Deputy Editor
Alison G Hoppin, MD


Minerals form only 5 percent of the typical human diet but are essential for normal health and function. Macrominerals are defined as minerals that are required by adults in amounts greater than 100 mg/day or make up less than 1 percent of total body weight. Trace elements (or trace minerals) are usually defined as minerals that are required in amounts between 1 to 100 mg/day by adults or make up less than 0.01 percent of total body weight. Ultra-trace minerals generally are defined as minerals that are required in amounts less than 1 mg/day. Although the classification of mineral may be controversial and somewhat arbitrary, one outline is given in Table 1 (table 1).

This topic review will discuss the physiological and biochemical functions, dietary requirements, and signs and symptoms of excess and deficiency for the essential trace minerals, including iron, zinc, copper, manganese, fluoride, and selenium. Iodine (an ultra-trace mineral) will also be discussed because of its global importance in iodine deficiency. Several of these minerals are considered in more depth elsewhere. (See "Iodine deficiency disorders" and "Zinc deficiency and supplementation in children and adolescents".)


Several systems have been used to describe nutritional requirements of a population. Dietary Reference Intakes (DRIs) were developed by the Food and Nutrition Board of the Institute of Medicine to guide nutrient intake in a variety of settings. Under this system, requirements can be expressed as a Recommended Dietary Allowance (RDA), which is defined as the dietary intake that is sufficient to meet the daily nutrient requirements of 97 percent of the individuals in a specific life stage group. If there is insufficient data to determine an RDA for a given nutrient, requirements can be expressed as an Adequate Intake (AI), which is an estimation of the nutrient intake necessary to maintain a healthy state. The upper limit (UL) is the maximum daily intake of a nutrient that is likely to pose no risk of adverse effects. Intake of nutrients far in excess of the RDA is considered to be "pharmacologic" dosing. Dietary guidelines, which incorporate the RDAs, are periodically updated as new information arises.

The United States Department of Agriculture uses different nomenclature and age groupings, setting "Daily Values" to describe recommended intake for adults and children older than four years of age. What appears on food labels is the estimation of the amount of a nutrient provided based upon a 2000 calorie diet. Updated information can be found at the website of the Food and Nutrition Information Center of the United States Department of Agriculture (www.nal.usda.gov/fnic/index.html).

These terms are described in greater detail in a separate topic review. (See "Dietary history and recommended dietary intake in children".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Aug 28, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. SCHWARZ K, MERTZ W. A glucose tolerance factor and its differentiation from factor 3. Arch Biochem Biophys 1957; 72:515.
  2. Mertz W. Chromium in human nutrition: a review. J Nutr 1993; 123:626.
  3. Hardwick LL, Jones MR, Brautbar N, Lee DB. Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate. J Nutr 1991; 121:13.
  4. Offenbacher EG, Pi-Sunyer FX, Stoecker BJ. Chromium. In: Handbook of nutritionally essential mineral elements, O'Dell BL, Sunde RA (Eds), Marcel Dekker, New York 1997. p.389.
  5. Offenbacher EG, Spencer H, Dowling HJ, Pi-Sunyer FX. Metabolic chromium balances in men. Am J Clin Nutr 1986; 44:77.
  6. Kamath SM, Stoecker BJ, Davis-Whitenack ML, et al. Absorption, retention and urinary excretion of chromium-51 in rats pretreated with indomethacin and dosed with dimethylprostaglandin E2, misoprostol or prostacyclin. J Nutr 1997; 127:478.
  7. Mertz W. Chromium occurrence and function in biological systems. Physiol Rev 1969; 49:163.
  8. Jeejeebhoy KN, Chu RC, Marliss EB, et al. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr 1977; 30:531.
  9. Nielsen FH. Nutritional significance of the ultratrace elements. Nutr Rev 1988; 46:337.
  10. Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care 2004; 27:2741.
  11. Balk EM, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care 2007; 30:2154.
  12. Guimarães MM, Martins Silva Carvalho AC, Silva MS. Chromium nicotinate has no effect on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes. J Am Coll Nutr 2013; 32:243.
  13. Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther 2014; 39:292.
  14. Bailey CH. Improved meta-analytic methods show no effect of chromium supplements on fasting glucose. Biol Trace Elem Res 2014; 157:1.
  15. Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996; 63:954.
  16. Hallmark MA, Reynolds TH, DeSouza CA, et al. Effects of chromium and resistive training on muscle strength and body composition. Med Sci Sports Exerc 1996; 28:139.
  17. Pittler MH, Ernst E. Dietary supplements for body-weight reduction: a systematic review. Am J Clin Nutr 2004; 79:529.
  18. Hathcock JN. Safety limits for nutrients. J Nutr 1996; 126:2386S.
  19. Gad SC. Acute and chronic systemic chromium toxicity. Sci Total Environ 1989; 86:149.
  20. United States Environmental Protection Agency. Toxicological review of hexavalent chromium, 1998 http://www.epa.gov/iris (Accessed on January 27, 2009).
  21. Stearns DM, Wetterhahn KE. Reaction of chromium(VI) with ascorbate produces chromium(V), chromium(IV), and carbon-based radicals. Chem Res Toxicol 1994; 7:219.
  22. Randall JA, Gibson RS. Serum and urine chromium as indices of chromium status in tannery workers. Proc Soc Exp Biol Med 1987; 185:16.
  23. Food and Nutrition Board of the Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press, Washington DC, 2000. www.nap.org (Accessed on May 03, 2012).
  24. Johnson MA, Kays SE. Copper: Its role in human nutrition. Nutrition Today 1990; 25:6.
  25. Turnlund JR. Copper. In: Modern nutrition in health and disease, 10th, Shils ME, Shike M, Ross AC, et al (Eds), Lippincott Williams and Wilkins, Baltimore 2006. p.286.
  26. Vuori E. Intake of copper, iron, manganese and zinc by healthy, exclusively-breast-fed infants during the first 3 months of life. Br J Nutr 1979; 42:407.
  27. Lönnerdal B. Copper nutrition during infancy and childhood. Am J Clin Nutr 1998; 67:1046S.
  28. Trace elements in human nutrition. Report of a WHO expert committee. Report No. 532, World Health Organization, Geneva, 1973.
  29. Mason KE. A conspectus of research on copper metabolism and requirements of man. J Nutr 1979; 109:1979.
  30. Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutr 1998; 67:1054S.
  31. Chan WY, Rennert OM. The role of copper in iron metabolism. Ann Clin Lab Sci 1980; 10:338.
  32. Harris ED. The iron-copper connection: the link to ceruloplasmin grows stronger. Nutr Rev 1995; 53:170.
  33. Lönnerdal B. Iron-zinc-copper interactions. In: Micronutrient interactions: impact on child health and nutrition, ILSI Press, Washington, DC 1998.
  34. Prohaska JR. Biochemical functions of copper in animals. In: Essential and toxic trace elements in human health and disease, Prasad AS (Ed), Alan R Liss, New York 1988.
  35. Danks DM. Copper deficiency in humans. Annu Rev Nutr 1988; 8:235.
  36. Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology 2004; 63:33.
  37. Kumar N. Copper deficiency myelopathy (human swayback). Mayo Clin Proc 2006; 81:1371.
  38. Hoffman HN 2nd, Phyliky RL, Fleming CR. Zinc-induced copper deficiency. Gastroenterology 1988; 94:508.
  39. Fiske DN, McCoy HE 3rd, Kitchens CS. Zinc-induced sideroblastic anemia: report of a case, review of the literature, and description of the hematologic syndrome. Am J Hematol 1994; 46:147.
  40. Huff JD, Keung YK, Thakuri M, et al. Copper deficiency causes reversible myelodysplasia. Am J Hematol 2007; 82:625.
  41. Kumar N, Elliott MA, Hoyer JD, et al. "Myelodysplasia," myeloneuropathy, and copper deficiency. Mayo Clin Proc 2005; 80:943.
  42. Halfdanarson TR, Kumar N, Li CY, et al. Hematological manifestations of copper deficiency: a retrospective review. Eur J Haematol 2008; 80:523.
  43. Barclay SM, Aggett PJ, Lloyd DJ, Duffty P. Reduced erythrocyte superoxide dismutase activity in low birth weight infants given iron supplements. Pediatr Res 1991; 29:297.
  44. Williams DM. Copper deficiency in humans. Semin Hematol 1983; 20:118.
  45. Kumar N, Ahlskog JE, Gross JB Jr. Acquired hypocupremia after gastric surgery. Clin Gastroenterol Hepatol 2004; 2:1074.
  46. Tan JC, Burns DL, Jones HR. Severe ataxia, myelopathy, and peripheral neuropathy due to acquired copper deficiency in a patient with history of gastrectomy. JPEN J Parenter Enteral Nutr 2006; 30:446.
  47. Griffith DP, Liff DA, Ziegler TR, et al. Acquired copper deficiency: a potentially serious and preventable complication following gastric bypass surgery. Obesity (Silver Spring) 2009; 17:827.
  48. Juhasz-Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology 2007; 68:1843.
  49. Shaw JC. Copper deficiency in term and preterm infants. In: Nutritional anemias, Fomon SJ, Zlotkin S (Eds), Vevey/Raven Press, New York 1992. p.105.
  50. Sutton AM, Harvie A, Cockburn F, et al. Copper deficiency in the preterm infant of very low birthweight. Four cases and a reference range for plasma copper. Arch Dis Child 1985; 60:644.
  51. Halfdanarson TR, Kumar N, Hogan WJ, Murray JA. Copper deficiency in celiac disease. J Clin Gastroenterol 2009; 43:162.
  52. Goodman BP, Mistry DH, Pasha SF, Bosch PE. Copper deficiency myeloneuropathy due to occult celiac disease. Neurologist 2009; 15:355.
  53. Yaldizli O, Johansson U, Gizewski ER, Maschke M. Copper deficiency myelopathy induced by repetitive parenteral zinc supplementation during chronic hemodialysis. J Neurol 2006; 253:1507.
  54. Willis MS, Monaghan SA, Miller ML, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005; 123:125.
  55. Nations SP, Boyer PJ, Love LA, et al. Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease. Neurology 2008; 71:639.
  56. Hedera P, Peltier A, Fink JK, et al. Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin II. The denture cream is a primary source of excessive zinc. Neurotoxicology 2009; 30:996.
  57. Pawa S, Khalifa AJ, Ehrinpreis MN, et al. Zinc toxicity from massive and prolonged coin ingestion in an adult. Am J Med Sci 2008; 336:430.
  58. van den Hamer CJ, Hoogenraad TU. Copper deficiency in Wilson's disease. Lancet 1989; 2:442.
  59. Foubert-Samier A, Kazadi A, Rouanet M, et al. Axonal sensory motor neuropathy in copper-deficient Wilson's disease. Muscle Nerve 2009; 40:294.
  60. Konagaya M, Matsumoto A, Takase S, et al. Clinical analysis of longstanding subacute myelo-optico-neuropathy: sequelae of clioquinol at 32 years after its ban. J Neurol Sci 2004; 218:85.
  61. Kumar N, Knopman D. SMON, clioquinol, and copper. Postgrad Med J 2005; 81:227.
  62. Schaumburg H, Herskovitz S. Copper deficiency myeloneuropathy: a clue to clioquinol-induced subacute myelo-optic neuropathy? Neurology 2008; 71:622.
  63. Lang TF, Glynne-Jones R, Blake S, et al. Iatrogenic copper deficiency following information and drugs obtained over the Internet. Ann Clin Biochem 2004; 41:417.
  64. Fleming CR. Trace element metabolism in adult patients requiring total parenteral nutrition. Am J Clin Nutr 1989; 49:573.
  65. Fuhrman MP, Herrmann V, Masidonski P, Eby C. Pancytopenia after removal of copper from total parenteral nutrition. JPEN J Parenter Enteral Nutr 2000; 24:361.
  66. Mercer JF. The molecular basis of copper-transport diseases. Trends Mol Med 2001; 7:64.
  67. Danks D. Hereditary disorders of copper metabolism in Wilson's disease and Menkes' disease. In: The metabolic basis of inherited disease, 5th, Stanbury JB, Wyngaarden JB, Fredrickson DS, et al (Eds), MacGraw-Hill, New York 1983.
  68. Verrotti A, Carelli A, Coppola G. Epilepsy in children with Menkes disease: a systematic review of literature. J Child Neurol 2014; 29:1757.
  69. de Bie P, Muller P, Wijmenga C, Klomp LW. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2007; 44:673.
  70. Turnland JR. Copper. In: Modern nutrition in health and disease, Shils ME, Olson JA, Shike M, Ross AC (Eds), Williams and Wilkins, Baltimore 1999. p.241.
  71. Turnlund JR. Copper. In: Modern nutrition in health and disease, Shils ME, Olson JA, Shike M (Eds), Lippincott, Philadelphia 2000. p.241.
  72. Davis GK, Mertz W. Copper. In: Trace elements in human and animal nutrition, 5th, Mertz W (Ed), Academic Press, San Diego 1987. Vol 1, p.301.
  73. Harris ED. Cellular copper transport and metabolism. Annu Rev Nutr 2000; 20:291.
  74. Linder MC. Copper. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), ILSI Press, Washington, DC 1996. p.307.
  75. Stamp TC. Fluoride. In: Encyclopedia of food science, food technology, and nutrition, Macrae R, Robinson RK, Sadler MJ (Eds), Academic Press, London 1993. p.1932.
  76. Subcommittee on the Tenth Edition of the RDAs. Fluoride. In: Recommended dietary allowances, 10th, National Academy Press, Washington, DC 1989. p.235.
  77. Phipps KR. Flouoride. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), ILSI Press, Washington, DC 1996. p.329.
  78. Position of the American Dietetic Association: the impact of fluoride on health. J Am Diet Assoc 2000; 100:1208.
  79. Kleerekoper M. The role of fluoride in the prevention of osteoporosis. Endocrinol Metab Clin North Am 1998; 27:441.
  80. Haguenauer D, Welch V, Shea B, et al. Fluoride for treating postmenopausal osteoporosis. Cochrane Database Syst Rev 2000; :CD002825.
  81. Merialdi M, Caulfield LE, Zavaleta N, et al. Randomized controlled trial of prenatal zinc supplementation and fetal bone growth. Am J Clin Nutr 2004; 79:826.
  82. Jenkins GN. Review of fluoride research since 1959. Arch Oral Biol 1999; 44:985.
  83. Burt BA. The case for eliminating the use of dietary fluoride supplements for young children. J Public Health Dent 1999; 59:269.
  84. Augenstein WL, Spoerke DG, Kulig KW, et al. Fluoride ingestion in children: a review of 87 cases. Pediatrics 1991; 88:907.
  85. Rackoff P. Skeletal fluorosis--a tricky diagnosis. Arthritis Rheumatol 2015; 67:2701.
  86. Hetzel BS, Potter BJ, Dulberg EM. The iodine deficiency disorders: nature, pathogenesis and epidemiology. World Rev Nutr Diet 1990; 62:59.
  87. Hetzel BS. The story of diodide3 deficiency- an international challenge in nutrition, Oxford University Press, Oxford 1989.
  88. Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet 2008; 372:1251.
  89. Stanbury JB. Iodine deficiency and the iodine deficiency disorders. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), ILSI Press, Washington, DC 1996. p.378.
  90. Kavishe FP. Iodine. In: Encyclopedia of food science, food technology, and nutrition, Macrae R, Robinson RK, Sadler MJ (Eds), Academic Press, London 1993. p.2558.
  91. Subcommittee on the Tenth Edition of the RDAs. Iodine. In: Recommended dietary allowances, 10th, National Academy Press, Washington, DC 1989. p.213.
  92. Yip R, Dallman PR.. Iron. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), International Life Sciences Institute, Washington, DC 1996. p.277.
  93. Subar AF, Krebs-Smith SM, Cook A, Kahle LL. Dietary sources of nutrients among US children, 1989-1991. Pediatrics 1998; 102:913.
  94. Rolfs A, Hediger MA. Intestinal metal ion absorption: an update. Curr Opin Gastroenterol 2001; 17:177.
  95. Fairbanks VF. Iron in medicine and nutrition. In: Modern nutrition in health and disease, 9th, Shils ME, Olson JA, Shike M, Ross AC (Eds), Williams and Wilkins, Baltimore 1999. p.193.
  96. Kime RA, Gibson AT, Powers HJ. The quantification of non-transferrin-bound iron in plasma from neonates, using high performance liquid chromatography. Proc Nutr Soc 1996; 55:95A.
  97. Weinberg ED. Iron withholding: a defense against infection and neoplasia. Physiol Rev 1984; 64:65.
  98. Winterbourn CC. Toxicity of iron and hydrogen peroxide: the Fenton reaction. Toxicol Lett 1995; 82-83:969.
  99. Yehuda S. Neurochemical basis of behavioural effects of brain iron deficiency in animals. In: Brain, behaviour, and iron in the infant diet, Dobbings J (Ed), Springer Verlag, London 1990. p.63.
  100. Dallman PR. Iron. In: Present knowledge in nutrition, 6th, Brown ML (Ed), International Life Sciences Institute/Nutritional Foundation, Washington, DC 1990. p.241.
  101. Aggett PJ. Neonatal trace element metabolism. In: Principles of perinatal-neonatal metabolism, Cowett RM (Ed), Springer-Verlag, New York 19991. p.500.
  102. Cook JD, Lynch SR. The liabilities of iron deficiency. Blood 1986; 68:803.
  103. Lozoff B, Klein NK, Nelson EC, et al. Behavior of infants with iron-deficiency anemia. Child Dev 1998; 69:24.
  104. Walter T. Effect of iron-deficiency anaemia on cognitive skills in infancy and childhood. Baillieres Clin Haematol 1994; 7:815.
  105. Lozoff B, Jimenez E, Hagen J, et al. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000; 105:E51.
  106. Scholl TO, Hediger ML, Fischer RL, Shearer JW. Anemia vs iron deficiency: increased risk of preterm delivery in a prospective study. Am J Clin Nutr 1992; 55:985.
  107. Keen CL, Zidenburg-Cherr S.. Manganese. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), International Life Sciences Institute, Washington, DC 1996. p.334.
  108. Nielsen FH. Ultratrace minerals. In: Modern nutrition in health and disease, 9th, Shils ME, Olson JA, Shike M, Ross AC (Eds), Williams and Wilkins, Baltimore 1999. p.283.
  109. Keen CL, Zidenburg-Cherr S. Manganese. In: Encyclopedia of food science, food technology, and nutrition, Macrae R, Robinson RK, Sadler MJ (Eds), Academic Press, London 1993. p.2863.
  110. American Academy of Pediatrics. Trace elements. In: Pediatric Nutrition, 7th ed, Kleinman RE, Greer FR (Eds), American Academy of Pediatrics, Elk Grove Village 2011. p.467.
  111. Wedler FC. Biochemical and nutritional role of manganese: An overview. In: Manganese in health and disease, Klimis-Tavantzis DJ (Ed), CRC Press, Boca Raton 1994. p.1.
  112. Soldin OP, Aschner M. Effects of manganese on thyroid hormone homeostasis: potential links. Neurotoxicology 2007; 28:951.
  113. Finley JW, Johnson PE. Manganese deficiency and excess in rodents. In: Manganese in health and disease, Klimis-Tavantzis DJ (Ed), CRC Press, Boca Raton 1994. p.85.
  114. Friedman BJ, Freeland-Graves JH, Bales CW, et al. Manganese balance and clinical observations in young men fed a manganese-deficient diet. J Nutr 1987; 117:133.
  115. Hall AJ, Margetts BM, Barker DJ, et al. Low blood manganese levels in Liverpool children with Perthes' disease. Paediatr Perinat Epidemiol 1989; 3:131.
  116. Perry CA, Taylor JF, Nunn A, et al. Perthes' disease and blood manganese levels. Arch Dis Child 2000; 82:428.
  117. Woolf A, Wright R, Amarasiriwardena C, Bellinger D. A child with chronic manganese exposure from drinking water. Environ Health Perspect 2002; 110:613.
  118. McMillan DE. A brief history of the neurobehavioral toxicity of manganese: some unanswered questions. Neurotoxicology 1999; 20:499.
  119. Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet 1996; 347:1218.
  120. Masumoto K, Suita S, Taguchi T, et al. Manganese intoxication during intermittent parenteral nutrition: report of two cases. JPEN J Parenter Enteral Nutr 2001; 25:95.
  121. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med 2005; 26:353.
  122. Dickerson RN. Manganese intoxication and parenteral nutrition. Nutrition 2001; 17:689.
  123. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. JPEN J Parenter Enteral Nutr 2004; 28:S39.
  124. Hardy IJ, Gillanders L, Hardy G. Is manganese an essential supplement for parenteral nutrition? Curr Opin Clin Nutr Metab Care 2008; 11:289.
  125. Howard L, Ashley C, Lyon D, Shenkin A. Autopsy tissue trace elements in 8 long-term parenteral nutrition patients who received the current U.S. Food and Drug Administration formulation. JPEN J Parenter Enteral Nutr 2007; 31:388.
  126. Schwartz K, Foltz CM. Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. J Am Chem Soc 1957; 79:3293.
  127. Rayman MP. Selenium and human health. Lancet 2012; 379:1256.
  128. Levander OA, Burk RF. Selenium. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), ILSI Press, Washington, DC 1996. p.320.
  129. Thomson C, Robinson M. Selenium. In: Encyclopedia of food science, food technology, and nutrition, Macrae R, Robinson RK, Sadler MJ (Eds), Academic Press, London 1993. p.4014.
  130. Subcommittee on the Tenth Edition of the RDAs. Selenium. In: Recommended dietary allowances, 10th, National Academy Press, Washington, DC 1989. p.217.
  131. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999; 37:279.
  132. Holben DH, Smith AM. The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc 1999; 99:836.
  133. Allan CB, Lacourciere GM, Stadtman TC. Responsiveness of selenoproteins to dietary selenium. Annu Rev Nutr 1999; 19:1.
  134. Rayman MP. The importance of selenium to human health. Lancet 2000; 356:233.
  135. Hawkes WC, Hornbostel L. Effects of dietary selenium on mood in healthy men living in a metabolic research unit. Biol Psychiatry 1996; 39:121.
  136. Finley JW, Penland JG. Adequacy or deprivation of dietary selenium in healthy men: Clinical and psychologica findings. J Trace Elem Exp Med 1998; 11:11.
  137. Sappey C, Legrand-Poels S, Best-Belpomme M, et al. Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AIDS Res Hum Retroviruses 1994; 10:1451.
  138. Taylor EW, Nadimpalli RG, Ramanathan CS. Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res 1997; 56:63.
  139. Ishida T, Himeno K, Torigoe Y, et al. Selenium deficiency in a patient with Crohn's disease receiving long-term total parenteral nutrition. Intern Med 2003; 42:154.
  140. Observations on effect of sodium selenite in prevention of Keshan disease. Chin Med J (Engl) 1979; 92:471.
  141. Beck MA, Shi Q, Morris VC, Levander OA. Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat Med 1995; 1:433.
  142. van Rij AM, Thomson CD, McKenzie JM, Robinson MF. Selenium deficiency in total parenteral nutrition. Am J Clin Nutr 1979; 32:2076.
  143. de Berranger E, Colinet S, Michaud L, et al. Severe selenium deficiency secondary to chylous loss. JPEN J Parenter Enteral Nutr 2006; 30:173.
  144. Loscalzo J. Keshan disease, selenium deficiency, and the selenoproteome. N Engl J Med 2014; 370:1756.
  145. Look MP, Rockstroh JK, Rao GS, et al. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol Trace Elem Res 1997; 56:31.
  146. Spallholz JE, Boylan LM, Larsen HS. Advances in understanding selenium's role in the immune system. Ann N Y Acad Sci 1990; 587:123.
  147. Kiremidjian-Schumacher L, Roy M, Wishe HI, et al. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol Trace Elem Res 1994; 41:115.
  148. Mazokopakis EE, Papadakis JA, Papadomanolaki MG, et al. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis. Thyroid 2007; 17:609.
  149. Vogt TM, Ziegler RG, Patterson BH, Graubard BI. Racial differences in serum selenium concentration: analysis of US population data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2007; 166:280.
  150. Combs GF Jr, Gray WP. Chemopreventive agents: selenium. Pharmacol Ther 1998; 79:179.
  151. Nève J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk 1996; 3:42.
  152. Yang GQ, Wang SZ, Zhou RH, Sun SZ. Endemic selenium intoxication of humans in China. Am J Clin Nutr 1983; 37:872.
  153. MacFarquhar JK, Broussard DL, Melstrom P, et al. Acute selenium toxicity associated with a dietary supplement. Arch Intern Med 2010; 170:256.
  154. Centers for Disease Control (CDC). Selenium intoxication--New York. MMWR Morb Mortal Wkly Rep 1984; 33:157.
  155. Hambidge KM, Casey CE, Krebs NF. Zinc in trace elements. In: Human and animal nutrition, 5th, Mertz W (Ed), Academic Press, Orlando 1986. Vol 2, p.1.
  156. Prasad AS. Clinical manifestations of zinc deficiency. Annu Rev Nutr 1985; 5:341.
  157. Prasad AS. Clinical, endocrinological and biochemical effects of zinc deficiency. Clin Endocrinol Metab 1985; 14:567.
  158. King, JC, Klein, CL. Zinc. In: Modern nutrition in health and disease, Shils ME, Olson JA, Shike M, et al. Lippincott, Philadelphia 2000. p.223.
  159. Briefel RR, Bialostosky K, Kennedy-Stephenson J, et al. Zinc intake of the U.S. population: findings from the third National Health and Nutrition Examination Survey, 1988-1994. J Nutr 2000; 130:1367S.
  160. Cousins RJ. Zinc. In: Present knowledge in nutrition, Ziegler EE, Filer LJ Jr (Eds), ILSI Press, Washington 1996. p.293.
  161. Lee HH, Prasad AS, Brewer GJ, Owyang C. Zinc absorption in human small intestine. Am J Physiol 1989; 256:G87.
  162. Weigand E. Absorption of trace elements: zinc. Int J Vitam Nutr Res Suppl 1983; 25:67.
  163. Sandström B. Bioavailability of zinc. Eur J Clin Nutr 1997; 51 Suppl 1:S17.
  164. Cousins RJ, Lee-Ambrose LM. Nuclear zinc uptake and interactions and metallothionein gene expression are influenced by dietary zinc in rats. J Nutr 1992; 122:56.
  165. Berg JM, Shi Y. The galvanization of biology: a growing appreciation for the roles of zinc. Science 1996; 271:1081.
  166. King JC, Klein CL. Zinc. In: Modern nutrition in health and disease, Shils ME, Olson JA, Shike M, et al (Eds), Lippincott, Philadelphia 2000. p.223.
  167. Zalewski PD, Forbes IJ, Giannakis C. Physiological role for zinc in prevention of apoptosis (gene-directed death). Biochem Int 1991; 24:1093.
  168. Color atlas and synopsis of clinical dermatology, 3rd, Fitzpatrick TB, Johnson RA, Wolf K (Eds), McGraw Hill, New York 1997. p.442.
  169. Ruz M, Carrasco F, Rojas P, et al. Zinc absorption and zinc status are reduced after Roux-en-Y gastric bypass: a randomized study using 2 supplements. Am J Clin Nutr 2011; 94:1004.
  170. Jakubovic BD, Zipursky JS, Wong N, et al. Zinc deficiency presenting with necrolytic acral erythema and coma. Am J Med 2015; 128:e3.
  171. VALLEE BL, WACKER WE, BARTHOLOMAY AF, HOCH FL. Zinc metabolism in hepatic dysfunction. II. Correlation of metabolic patterns with biochemical findings. N Engl J Med 1957; 257:1055.
  172. Macdonald JB, Connolly SM, DiCaudo DJ. Think zinc deficiency: acquired acrodermatitis enteropathica due to poor diet and common medications. Arch Dermatol 2012; 148:961.
  173. King JC. Assessment of techniques for determining human zinc requirements. J Am Diet Assoc 1986; 86:1523.
  174. Walter RM Jr, Uriu-Hare JY, Olin KL, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care 1991; 14:1050.
  175. Cunningham JJ, Fu A, Mearkle PL, Brown RG. Hyperzincuria in individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of high-dose zinc supplementation. Metabolism 1994; 43:1558.
  176. Goldenberg RL, Tamura T, Neggers Y, et al. The effect of zinc supplementation on pregnancy outcome. JAMA 1995; 274:463.
  177. Mahomed K, Bhutta Z, Middleton P. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev 2007; :CD000230.
  178. Iannotti LL, Zavaleta N, León Z, et al. Maternal zinc supplementation reduces diarrheal morbidity in peruvian infants. J Pediatr 2010; 156:960.
  179. Küry S, Dréno B, Bézieau S, et al. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 2002; 31:239.
  180. Wang K, Pugh EW, Griffen S, et al. Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal region 8q24.3. Am J Hum Genet 2001; 68:1055.
  181. Wastney ME, Ahmed S, Henkin RI. Changes in regulation of human zinc metabolism with age. Am J Physiol 1992; 263:R1162.
  182. Turnlund JR, Durkin N, Costa F, Margen S. Stable isotope studies of zinc absorption and retention in young and elderly men. J Nutr 1986; 116:1239.
  183. Prasad AS, Brewer GJ, Schoomaker EB, Rabbani P. Hypocupremia induced by zinc therapy in adults. JAMA 1978; 240:2166.
  184. Oakes EJ, Lyon TD, Duncan A, et al. Acute inflammatory response does not affect erythrocyte concentrations of copper, zinc and selenium. Clin Nutr 2008; 27:115.
  185. Foote JW, Delves HT. Albumin bound and alpha 2-macroglobulin bound zinc concentrations in the sera of healthy adults. J Clin Pathol 1984; 37:1050.
  186. World Health Organization. Vitamin and mineral requirements in human nutrition (2e), 2004 http://www.who.int/vmnis/en/ (Accessed on January 27, 2009).