Nutrition versus toxicology of manganese in humans: evaluation of potential biomarkers.

Manganese intake can vary greatly with food choices, water composition, and supplement use. Thus, individuals consuming Western diets consume from < 1 to > 10 mg Mn/d. The levels of manganese intake associated with adverse effects (both deficient and toxic) are debatable. Moreover, many of the symptoms of manganese deficiency (growth retardation, changes in circulating HDL cholesterol and glucose levels, reproductive failure) and manganese toxicity (growth depression, anemia) are non-specific. The bone deformities observed in manganese-deficient animals and neurological symptoms of individuals who have inhaled excess manganese are permanent and illustrate the need to identify sensitive biomarkers of manganese status that appear before these symptoms. Manganese balance and excretion data are not useful biomarkers of manganese exposure but demonstrate that the body is protected against manganese toxicity primarily by low absorption and/or rapid presystemic elimination of manganese by the liver. Serum manganese concentrations in combination with lymphocyte manganese-dependent superoxide dismutase (MnSOD) activity and perhaps blood arginase activity, appear to be the best ways to monitor ingestion of insufficient manganese. Serum manganese concentrations in combination with brain MRI (magnetic resonance imaging) scans, and perhaps a battery of neurofunctional tests, appear to be the best ways to monitor excessive exposure to manganese.