Manganese is an essential trace mineral in animal nutrition and is believed to be an essential trace mineral in human nutrition, as well. Manganese is a metallic element with atomic number 25 and an atomic weight of 54.94 daltons. Its chemical symbol is Mn. Manganese exists in the oxidation states Mn2+ or Mn(II) and Mn3+ or Mn(III) under physiological conditions.
Dietary manganese-deficiency in animals results in a wide variety of structural and physiological defects, including growth retardation, skeletal and cartilage malformations, impaired reproductive function, congenital ataxia due to abnormal inner ear development, optic nerve abnormalities, impaired insulin metabolism and abnormal glucose tolerance, alterations in lipoprotein metabolism and an impaired oxidant defense system.
Manganese deficiency states have not been well documented in humans. There is one report of a man maintained for four months on a manganese-deficient diet and also given magnesium-containing antacids. The symptoms which occurred included a decrease in serum cholesterol, depressed growth of hair and nails, scaly dermatitis, weight loss, reddening of his black hair and beard and impaired blood clotting. He responded to a diet containing manganese. In another report, men fed a low-manganese diet manifested low serum cholesterol levels and dermatitis. Short-term manganese supplementation did not reverse these symptoms.
In still another report, young women fed a manganese-poor diet were found to have mildly abnormal glucose tolerance and increased menstrual losses of manganese, calcium, iron and total hemoglobin. Finally a child on long-term total parenteral nutrition (TPN) lacking manganese manifested bone demineralization and impaired growth that were corrected by supplementation with manganese.
Manganese is the preferred metal cofactor for glycosyltransferases. Glycosyltransferases are important in the synthesis of glycoproteins and glycosaminoglycans (GAGs or mucopolysaccharides). Glycoproteins are involved in the synthesis of myelin and the clotting factors, among other things. Manganese-containing metalloenzymes include manganese superoxide dismutase, the principal antioxidant enzyme of mitochondria, arginase, pyruvate carboxylase and glutamine synthetase.
The richest dietary sources of manganese include whole grains, nuts, leafy vegetables and teas. Manganese is concentrated in the bran of grains which is removed during processing. Mean intakes of manganese worldwide range from 0.52 to 10.8 milligrams daily.
Actions & Pharmacology
Manganese may have antioxidant activity. Manganese has putative anti-osteoporotic and anti-arthritic activities.
Mechanism of Action
Manganese ions have been found to scavenge hydroxyl and superoxide radicals. The mechanism of binding of manganese ions to these reactive oxygen species is not known. Manganese is a crucial component of the metalloenzyme manganese superoxide dismutase (MnSOD). MnSOD is found in mitochondria and is the principal constituent of the mitochondrial oxidant defense system. Rats and mice fed manganese-deficient diets are found to have reduced MnSOD activity in heart muscle and nervous tissue. They also have mitochondrial abnormalities and pathological changes in these tissues. The pathological changes are thought to result from oxidative damage due to the decreased activity of MnSOD which normally would protect against this damage.
Dietary manganese deficiency results in skeletal and cartilage malformations in animals and in one human report. It is thought that this is due to decreased activity of the manganese-dependent glycosyltransferases which, among other things, are involved in the synthesis of glycosaminoglycans or GAGs. GAGs are crucial for healthy cartilage and bone. However, there is as yet only very preliminary evidence that supplemental manganese has any effect on the promotion of bone or cartilage formation in humans who are not manganese-deficient. One study reported that manganese when taken in combination with calcium, copper and zinc may improve bone mineral density in postmenopausal women with osteoporosis.
There is scant information on the pharmacokinetics of manganese in humans. The efficiency of absorption (fractional absorption) of ingested manganese appears to be low, about 5%. Absorption efficiency appears to decrease as dietary intake of manganese increases. It increases with low dietary intake of manganese. Absorption appears to occur throughout the small intestine and appears to occur by both active-transport and passive diffusion mechanisms. Manganese ions are transported via the portal circulation to the liver. In what forms manganese is transported to the liver—bound to albumin, alpha2-macroglobulin, hydrated manganese complexes, etc.—is also unclear. A fraction of manganese is taken up by hepatocytes and a fraction is transported by the systemic circulation to the various tissues of the body. Some manganese is bound to the plasma protein transferrin, but there also appear to be other carriers that transport manganese in the systemic circulation. Manganese is found principally in the mitochondria of cells. Absorbed manganese is excreted primarily via the biliary route. Very little manganese is excreted in the urine.
Indications & Usage
Apart from its uses in rare overt deficiency disorders, manganese might have some efficacy in osteoporosis and osteoarthritis as well as in some with premenstrual syndrome (PMS). Evidence for these benefits is preliminary.
There are several forms of supplementary manganese, including manganese gluconate, manganese sulfate, manganese ascorbate and manganese amino acid chelates. Manganese is available as a stand-alone supplement and also in combination products. One combination product used for bone/joint health contains chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate.
Typical supplemental intake of manganese ranges from 2 to 5 milligrams daily.
A summary of DRIs for various age groups is as follows:
|DRI values (milligrams/day)|
|Infants||Adequate Intake (AI)|
|Older than 70 years||2.3|
|Older than 70 years||1.8|
The following summarizes the Tolerable Upper Intake Level (UL) for various age groups and conditions:
|19 years and older||11|
|19 years and older||11|
|19 years and older||11|
The DV (Daily Value) for manganese, which is used for determining percentage of nutrient daily values on nutritional supplement and food labels, is 2 mg. The basis for the DV for manganese is the1989 Estimated Safe and Adequate Daily Dietary Intake (ESADDI).
LiteratureBaly DL, Schneiderman JS, Garcia-Welsh AL. Effect of manganese deficiency on insulin binding, glucose transport and metabolism in rat adipocytes. J Nutr. 1990;120:1075-1079.Fell JME, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet. 1996;347:1218-1221.Gong H, Amemiya T. Optic nerve changes in manganese-deficient rats. Exp Eye Res. 1999;68:313-320.Hussain S, Ali SF. Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats. Neuroscience Letters. 1999;261:21-24.Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.Keen CL, Ensunsa JL, Watson MH, et al. Nutritional aspects of manganese from experimental studies. Neurotoxicol. 1999;20:213-223.Krieger D, Krieger S, Jansen O, et al. Manganese and chronic hepatic encephalopathy. Lancet. 1995;346:270-274.Nagatomo S, Umehara F, Hanada K, et al. Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature. J Neurol Sci. 1999;162:102-105.Nielsen FH. Ultratrace minerals. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins;1999:283-303.Strause L, Saltman P, Glowacki J. The effect of deficiencies of manganese and copper on osteo-induction and on resorption of bone particles in rats. Calcif Tissue Int. 1987;41:145-150.Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr. 1994;124:1060-1064.Strause LG, Hegenauer J, Saltman P, et al. Effects of long-term dietary manganese and copper deficiency on rat skeleton. J Nutr. 1986;116:135-141.
Research & Summary
Manganese supplementation, in combination with calcium, zinc and copper, showed some efficacy in postmenopausal osteoporosis. Manganese ascorbate, in combination with glucosamine hydrochloride and chondroitin sulfate, was helpful in treating knee osteoarthritis pain in a recent randomized, double-blind, placebo-controlled pilot study. Follow-up on these studies is needed. Similarly, there is an isolated study needing follow-up that suggested some possible benefit from manganese in alleviating some PMS symptoms, including anxiety, depression, irritability and mood swings.
Contraindications, Precautions & Adverse Reactions
Manganese supplements are contraindicated in those with liver failure. Some patients with end-stage liver disease have been found to accumulate manganese in their basal ganglia. It is thought that manganese may play a role in the hepatic encephalopathy in those with liver failure. Manganese is eliminated primarily through the bile, and hepatic dysfunction leads to depressed manganese excretion.
Manganese supplements are contraindicated in those hypersensitive to any component of a manganese-containing supplement.
Pregnant women and nursing mothers should avoid intakes of manganese above the upper limit of the estimated safe and adequate daily dietary intake (ESSADI). The ESSADI for those 11 years and older is 2.0 to 5.0 milligrams daily.
Oral manganese supplements are generally well tolerated. Oral manganese, however, may be neurotoxic in those with liver failure. Manganese is primarily eliminated via the biliary route, and hepatic dysfunction leads to depressed manganese excretion. Manganese may accumulate in the basal ganglia of those with liver failure and may exacerbate hepatic encephalopathy and/or cause Parkinson's disease-like symptoms.
Manganese is toxic under certain conditions. Hepatic failure was discussed above. Mine workers exposed to high concentrations of manganese dust develop what is known in the mining villages of northern Chile, where this disorder has been found, as ""locura manganica'' or manganese madness. In later stages of this disease, symptoms similar to those of Parkinson's disease are observed. Levodopa is the treatment of the later stages of manganese madness.
There are a few reports of manganese intoxication occurring in those on long-term total parenteral nutrition (TPN) who developed parkinsonism which was treated with levodopa.
Antacids: Magnesium-containing antacids, such as aluminum hydroxide/magnesium hydroxide, aluminum hydroxide/magnesium carbonate and aluminum hydroxide/magnesium trisilicate, may decrease the absorption of manganese if taken concomitantly.
Laxatives: Magnesium-containing laxatives may decrease the absorption of manganese if taken concomitantly.
Tetracycline: Tetracycline may reduce the absorption of manganese if taken concomitantly.
Calcium: Calcium supplements may decrease the absorption of manganese if taken concomitantly.
Iron: Non-heme iron supplements may reduce the absorption of manganese if taken concomitantly.
Magnesium: Magnesium supplements may decrease the absorption of manganese if taken concomitantly.
Concomitant intake of manganese with foods rich in phytic acid (unleavened bread, raw beans, seeds, nuts and grains and soy isolates) or oxalic acid (spinach, sweet potatoes, rhubarb and beans) may depress the absorption of manganese.