Manganese

Discovery of Nutritional Importance

Between 1913 and 1921, manganese was found to be a constant component of plant and animal tissues, and in 1923, it was shown to be required by plants and microorganisms (McHargue 1923). Attempts to demonstrate that manganese was required by laboratory animals were unsuccessful, however, because the purified diets employed were so deficient in other essential nutrients that even the addition of manganese did not result in normal growth and survival. In 1931, it was found that manganese was essential for the growth of mice and also for normal ovarian activity in both mice and rats; it was vital to preventing testicular degeneration in rats as well (Kemmerer, Elvehjem, and Hart 1931; Orent and McCollum 1931; Waddell, Steenbock, and Hart 1931). Five years later, researchers learned that perosis (“slipped tendon”) and nutritional chondrodystrophy in poultry were caused by inadequate manganese intake (Wilgus, Norris, and Heuser 1936, 1937; Lyons and Insko 1937). The identification of a specific biochemical function for manganese remained elusive for many years, but finally, in 1962, the mineral was found to have a specific role in the synthesis of the mucopolysaccharides of cartilage (Leach and Muenster 1962). The first report of a possible case of human manganese deficiency appeared in 1972 (Doisy 1972).

Manganese deficiency symptoms have been induced in many species of animals. They include impaired growth, skeletal abnormalities, disturbed or depressed reproductive function, ataxia of the newborn, and defects in lipid and carbohydrate metabolism (Free-land-Graves and Llanes 1994; Finley and Johnson 1996). Establishing the signs of manganese deficiency in humans, however, has been difficult.

The first possible description of manganese deficiency in humans was that of a man who had been fed a semipurified diet for an extended period of time (Doisy 1972). He developed weight loss, depressed growth of hair and nails, dermatitis, and low blood cholesterol. Moreover, his black hair developed a reddish tinge, and his clotting protein response to vitamin K supplementation was abnormal. Subsequent to the appearance of these signs, it was realized that manganese had been left out of his diet, and the subject responded to a mixed hospital diet containing manganese. Unfortunately, no supplementation with manganese alone was tried, and thus, although this case is often cited as an example of human manganese deficiency, the experimental design does not permit this to be stated conclusively.

Another report indicated that men fed only 0.11 mg/day of manganese for 35 days exhibited decreased cholesterol concentrations in serum, a fleeting dermatitis, and increased calcium, phosphorus, and alkaline phosphatase in blood (Friedman et al. 1987). Shortterm manganese supplementation for 10 days, however, failed to reverse these changes, and consequently, whether the observed changes were caused by manganese deprivation can be questioned. Probably the most convincing report of a human manganese deficiency is that concerning a girl, age 4 years, who had been maintained on total parenteral nutrition that was low in manganese since she was 9 days old. She developed short stature, brittle bones, and low serum manganese; manganese supplementation improved bone density and longitudinal growth (Norose 1992). In addition to the symptoms just discussed, a low manganese status has been associated with osteoporosis and epilepsy; that is, patients with these conditions often have low serum or plasma manganese concentrations (Freeland-Graves and Turnlund 1996). Although such limited findings have made it difficult to establish the nutritional importance of manganese, most scientists do not doubt that it is essential for humans.