Toxicity of Methionine in Humans

The literature has been searched to identify evidence relating to the possible toxicity of the amino acid methionine in human subjects. Nutritional and metabolic studies have employed amounts of methionine, including the d and dl isomers, both below and above the requirement and have not reported adverse effects in adults and children. Although methionine is known to exacerbate psychopathological symptoms in schizophrenic patients, there is no evidence of similar effects in healthy subjects. The role of methionine as a precursor of homocysteine is the most notable cause for concern. A "loading dose" of methionine (0.1 g/kg) has been given, and the resultant acute increase in plasma homocysteine has been used as an index of the susceptibility to cardiovascular disease. Although this procedure results in vascular dysfunction, this is acute and unlikely to result in permanent damage. However, a 10-fold larger dose, given mistakenly, resulted in death. Longer-term studies in adults have indicated no adverse consequences of moderate fluctuations in dietary methionine intake, but intakes higher than 5 times normal resulted in elevated homocysteine levels. These effects of methionine on homocysteine and vascular function are moderated by supplements of vitamins B-6, B-12, C, and folic acid. In infants, methionine intakes of 2-5 times normal resulted in impaired growth and extremely high plasma methionine levels, but no adverse long-term consequences were observed.