Manganese is a trace element. It occurs widely in plant and animal tissues and is an essential element for many animal species. Manganese absorption occurs throughout the small intestine. The exact mechanism of absorption is unknown, although it is thought to occur by a two-step mechanism that involves an initial uptake from the lumen followed by active transport across the mucosal cells. A specific manganese-carrying plasma protein called transmanganin has been identified. Almost all absorbed manganese is excreted with the feces; only trace amounts are found in the urine. Absorption efficiency is estimated to be roughly 5% and may decline as dietary intake increases. The retention of manganese is estimated to be 10%, 14 days after feeding. The human body contains a mere 20 mg of manganese, mostly in cell mitochondria. Organs rich in mitochondria, such as liver, kidney, and pancreas have relatively high manganese concentrations. Bone has the highest concentration of manganese.
Manganese serves two primary biochemical functions in the body, (1) it activates specific enzymes, and (2) it is a constituent of several metalloenzymes. The enzymes manganese activates include hydrolases, decarboxylases, kinases, and transferases. Certain other ions (cobalt, magnesium) can replace its function in this capacity. The manganese metalloenzymes include arginase, pyruvate carboxylase, glutamine synthetase, and manganese superoxide dismutase.
Manganese participates in numerous biochemical functions in the body including steroid and sulfomucopolysacchride biosynthesis, carbohydrate and lipid metabolism, and bone, blood clot, and protein formation. It is also essential for normal brain function, possibly through its role in biogenic amine metabolism. Many of the precise biochemical roles of manganese have not been determined.
Manganese deficiency has been induced in several animal species, but not in humans. Deficiency symptoms in animals include skeletal abnormalities, impaired growth, disturbed or depressed reproductive function, ataxia of the newborn, and defects in lipid and carbohydrate metabolism. Although frank deficiency symptoms have not been observed in humans, biochemical evidence has established its essentiality in humans. Impaired fertility, growth retardation, birth defects, bone malformations, seizures, and general weakness may result from manganese deficiencies.
Nuts (especially pecans, almonds)
Wheat germ and whole grains
Refined grains, meats, and dairy products contain only small amounts of manganese. Highly refined diets contain significantly less manganese (0.36 to 1.78 mg) than diets high in unrefined foods (8.3 mg).
Mn2+ is the characteristic oxidative state of manganese in solution, in metal enzyme complexes, and in metalloenzymes. Mn3+ is the oxidative state in the enzyme manganese superoxide dismutase (MnSOD), and the form that binds to transferrin and interacts with Fe3+.
Manganese is available commercially in a wide variety of forms including manganese salts (sulfate and chloride) and manganese chelates (gluconate, picolinate, aspartate, fumarate, malate, succinate, citrate, and amino acid chelate). Preparation doses are typically between 2 and 20 mg.
Diabetes: Type I and II diabetics have significantly less manganese than healthy individuals. Diabetics with liver disorders and those not on insulin therapy may excrete more manganese. Manganese appears to have a hypoglycemic effect and may decrease blood glucose levels in insulin-resistant diabetics.
Rheumatoid arthritis: RA, as well as other inflammation brought on by strains and sprains may respond well to manganese treatment. Levels of MnSOD may be significantly decreased in individuals with rheumatoid arthritis. Manganese supplementation increases MnSOD activity.
Epilepsy: An important study in the early 1960s demonstrated that manganese-deficient rats were more susceptible to seizures, and had EEG tracings consistent with seizure activity. People who have schizophrenia may also respond well to magnesium supplementation.
Osteoporosis: Manganese, and other trace elements, increase spinal bone mineral density in postmenopausal women.
Immunocompetence and cancer: Adequate manganese is necessary for normal antibody production. Excessive or inadequate manganese intakes may affect neutrophil and macrophage function.
Cadmium toxicity: Manganese reduces toxic effects of cadmium in rats.
Other conditions: Manganese is also used to treat atherosclerosis, hypercholesterolemia, tinnitus, and hearing loss.
Total parenteral nutrition (TPN): Bone changes may occur in patients given TPN solutions containing inadequate quantities of manganese. In contrast, cholestatic and nervous system disorders have been associated with high blood concentrations of manganese from long-term TPN treatment. Children’s TPN solutions should contain low-dose manganese (0.018 mucmol/kg per 24 hours).
Dosage Ranges and Duration of Administration
The exact amount of manganese required by the human body is not known. The Food and Nutrition Board (FNB) of the National Research Council (NRC) has established estimated safe and adequate daily intakes for manganese as follows:
Infants 0 to 0.5 years: 0.3 to 0.6 mg
Infants 0.5 to 1 year: 0.6 to 1.0 mg
Children 1 to 3 years: 1.0 to 1.5 mg
Children 4 to 6 years: 1.5 to 2.0 mg
Children 7 to 10 years: 2.0 to 3.0 mg
Adolescents 11+ years: 2.0 to 5.0 mg
Adults: 2.0 to 5.0 mg.
These estimates are based on the assumption that most dietary intakes fall in this range and do not result in deficiency or toxicity signs. The estimates may be modified as additional information becomes available. More manganese (10 mg/day) should be consumed if the diet contains high amounts of substances that inhibit manganese absorption. In therapeutic use for epilepsy, inflammation, or diarrhea, the dose may be increased three-to-sixfold.
Manganese is one of the least toxic of the trace elements, though excessive intake may produce toxic effects. There are only a few reports of oral manganese poisoning in man. Manganese toxicity is more common in humans chronically exposed to manganese dust found in steel mills and mines and certain chemical industries. Toxicity principally affects the brain, causing severe psychiatric abnormalities, but may also increase blood pressure in the doses used to treat schizophrenia.
The FNB of the NRC recommends that the upper limits for the trace elements should not be habitually exceeded because the toxicity levels may be only several times usual intakes.
HaloperidolIn one case report, a patient with progressive hepatic failure who received haloperidol and manganese as part of total parenteral nutrition exhibited neuropsychiatric symptoms (Mehta and Reilly 1990). Toxic manganese levels may have increased the patient’s susceptiblity to haloperidol toxicity.
PhenobarbitalSimultaneous administration of phenobarbital and manganese (5 mg/kg) prevented manganese-induced prolongation of hexobarbital hypnosis in male rats (Deimling and Schnell 1983).
Davis CD, Greger JL. Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. Am J Clin Nutr.1992;55:747-752.
Deimling MJ, Schnell C. Interaction between manganese and phenobarbital on hexobarbital hypnosis in the male rat. Res Commun Chem Pathol Pharmacol. 1983;41(1):165-168.
el-Yazigi A, Hannan N, Raines DA. Urinary excretion of chromium, copper, and manganese in diabetes mellitus and associated disorders. Diabetes Res. 1991;18:129-134.
Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet.1996;347:1218-1221.
Friedman E, ed. Biochemistry of the Essential Ultratrace Elements. New York, NY: Plenum Press; 1984.
Goering PL, Haassen CD. Mechanism of manganese-induced tolerance to cadmium lethality and hepatotoxicity. Biochem Pharmacol. 1985;34:1371-1379.
Itokawa Y. Trace elements in long-term total parenteral nutrition [in Japanese]. Nippon Rinsho. 1996;54:172-178.
Johnson MA, Smith MM, Edmonds JT. Copper, iron, zinc, and manganese in dietary supplements, infant formulas, and ready-to-eat breakfast cereals. Am J Clin Nutr. 1998;67(suppl):1035S-1040S.
Krause MV, Mahan LK. Food, Nutrition, and Diet Therapy. 7th ed. Philadelphia, Pa: WB Saunders Co; 1984.
Mehta R, Reilly JJ. Manganese levels in a jaundiced long-term total parenteral nutrition patient: Potentiation of haloperidol toxicity?: Case report and literature review. J Parenter Enter Nutr. 1990;14(4):428-430.
Orten JM, Neuhaus OW, eds. Human Biochemistry. 10th ed. St. Louis, Mo: CV Mosby Co; 1982.
Pasquier C, Mach PS, Raichvarg D, Sarfati G, Amor B, Delbarre F. Manganese-containing superoxide-dismutase deficiency in polymorphonuclear leukocytes of adults with rheumatoid arthritis.Inflammation. 1984;8:27-32.
Saltman PD, Strause LG. The role of trace minerals in osteoporosis. J Am Coll Nutr. 1993;12:384-389.
Shils ME, Olsen JA, Shike M, eds. Modern Nutrition in Health and Disease. 8th ed. Media, Pa: Williams & Wilkins Co; 1994:1.
Shvets NV, Kramarenko LD, Vydyborets SV, Gaidukova SN. Disordered trace element content of the erythrocytes in diabetes mellitus [in Russian]. Lik Sprava. 1994;1:52-55.
Somer E. The Essential Guide to Vitamins & Minerals. New York, NY: HarperCollins Publishers; 1992.
Whitney EN, Hamilton EN. Understanding Nutrition. 3rd ed. St. Paul, Minn: West Publishing Co; 1984.