Methionine and S‐adenosylmethionine are potential biomarkers to determine safe intake levels for methionine

Abstract

Although mammals maintain homeostasis in response to various intake levels of nutrients by controlling their metabolic activities, their excessive intakes cause adverse effects. Since intake levels within homeostatic range are considered to be safe, determination of metabolic upper limit for each nutrient could provide information for their safe intake levels. In this study we tried to identify the rate‐limiting step for methionine (Met) in its excess and to find biomarkers for Met excess determination.F344 male rats were fed a basal diet or diets containing additional Met (0.3, 0.6, 0.9, 1.2 and 2.4%) for 2 weeks. Postprandial plasma and liver samples were collected to measure Met metabolites. More than 0.9% of additional Met increased hepatic Met and S‐adenosylmethionine (SAM) markedly. Met loading at the same doses also decreased the ratio of S‐adenosylhomocysteine (SAH) to SAM, indicating that metabolism from SAM to SAH would be one of rate‐limiting steps for disposal of excessive Met and that both SAM and its upstream Met are possible biomarkers to assess metabolic upper limit of Met. Since NOAEL and LOAEL of additional Met in growing rats were 0.6 and 0.9%, respectively, hepatic SAM, plasma and hepatic Met concentrations discriminated safe intake levels from potentially toxic levels well. These suggest that both Met and SAM are potential biomarkers to determine safe intake level of Met.