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Metallochemical and biochemical studies completed in the Department of Ophthalmology at the University of California, Irvine, offer a new perspective in understanding MS. Low plasma zinc levels were observed in MS patients, and this has been confirmed in laboratories elsewhere in the world. Generalized malabsorption could not be demonstrated in MS patients when using a double-blind, randomized study of 72-hours fecal fat. A double-blind, randomized zinc tolerance test confirmed the low plasma zinc levels in fasting MS patients, but once an oral zinc load had been given, the 7-hour post treatment levels were elevated to that of control patients. Intracellular erythrocyte zinc concentration was measured in controls and in MS patients. The controls had no change over 7 hours despite a large zinc load with consequent elevation in plasma levels. However, MS patients demonstrated a gradual elevation of intracellular zinc concentration over the 7-hour period, with P less than 0.01. Thus, the erythrocyte membranes of controls were able to maintain the zinc gradient between the extracellular and the intracellular compartments, while MS patients were not, suggesting a functional abnormality in plasma membranes outside of central nervous system. Erythrocyte membrane-bound CNP was observed to be abnormality low in MS patients when compared to controls. The study has been confirmed by a different laboratory using a different substrate on MS erythrocytes. The rationale for considering MS as a possible systemic disease is presented.