come elevated in infants with choleostatic liver disease given supplemental manganese in total parenteral nutrition solutions (Kelly, 1998). It is not certain at what age human infants can maintain manganese homeostasis. Neonatal mice were unable to maintain manganese homeostasis until 17 to 18 days of age (Fechter, 1999).

Manganese deficiency has been observed in various species of animals with the signs of deficiency, including impaired growth, impaired reproductive function, impaired glucose tolerance, and alterations in carbohydrate and lipid metabolism. Furthermore, manganese deficiency interferes with normal skeletal development in various animal species (Freeland-Graves, 1994; Hurley and Keen, 1987; Keen et al., 1994). Although a manganese deficiency may contribute to one or more clinical symptoms, a clinical deficiency has not been clearly associated with poor dietary intakes of healthy individuals. One man was depleted of vitamin K and inadvertently of manganese when fed a diet containing only 0.34 mg/day of manganese for 6.5 months. Symptoms included hypocholesterolemia, scaly dermatitis, hair depigmentation, and reduced vitamin K-dependent clotting proteins. Symptoms were not reversed with vitamin K supplementation but gradually disappeared after the study ended (Doisy, 1973).

In a manganese depletion study, seven young men were fed a purified diet containing 0.01 mg/day of manganese for 10 days and 0.11 mg/day of manganese for 30 days after a 3-week baseline period when they consumed 2.59 mg/day (Friedman et al., 1987). After 35 days, five of the seven subjects developed a finely scaling, minimally erythematous rash that primarily covered the upper torso and was diagnosed as Miliaria crystallina. After two days of repletion, the blisters disappeared and the affected areas became scaly and then cleared. Plasma cholesterol concentrations declined during the depletion period, perhaps because manganese is required at several sites in the biosynthetic pathway of cholesterol (Krishna et al., 1966).

Decreased plasma manganese concentrations have been reported in osteoporotic women. Furthermore, bone mineral density was improved when trace minerals, including manganese, were included with calcium in their diets or supplements (Freeland-Graves and Turnlund, 1996; Strause and Saltman, 1987; Strause et al., 1986, 1987).

Penland and Johnson (1993) reported that diets containing only 1 mg/day of manganese altered mood and increased pain during the premenstrual phase of the estrous cycle in young women.