Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome

Abstract

Objective: In preclinical reports, restriction of dietary methionine intake was shown to enhance metabolic flexibility, improve lipid profiles, and reduce fat deposition. The present report is the outcome of a "proof of concept" study to evaluate the efficacy of dietary methionine restriction (MR) in humans with metabolic syndrome.

Methods: Twenty-six obese subjects (six male and 20 female) meeting criteria for metabolic syndrome were randomized to a diet restricted to 2 mg methionine/kg body weight per day and were provided capsules containing either placebo (n = 12) or 33 mg methionine/kg body weight per day (n = 14). Energy expenditure, body composition, insulin sensitivity, and biomarkers of metabolic syndrome were measured before and after 16 wk on the respective diets.

Results: Insulin sensitivity and biomarkers of metabolic syndrome improved comparably in both dietary groups. Rates of energy expenditure were unaffected by the diets, but dietary MR produced a significant increase in fat oxidation (MR, 12.1 ± 6.0% increase; control, 8.1 ± 3.3% decrease) and reduction in intrahepatic lipid content (MR liver/spleen attenuation ratio, 8.1 ± 3.3% increase; control ratio, 2.2 ± 2.1% increase) that was independent of the comparable reduction in weight and adiposity that occurred in both groups.

Conclusions: Sixteen weeks of dietary MR in subjects with metabolic syndrome produced a shift in fuel oxidation that was independent of the weight loss, decreased adiposity, and improved insulin sensitivity that was common to both diets.

Trial registration: ClinicalTrials.gov NCT00640757.

Fig. 1.

A, Percentage differences between plasma methionine and cystine concentrations at W0 and W16. B and C, Percentage differences between body composition, L/S ratio, and markers of glucose metabolism at W0 and W16. L/S attenuations were calculated as previously described (14, 15). Glucose disposal rate was calculated as the mean rate of exogenous glucose infusion during steady-state insulin infusion during the last 30 min of the hyperinsulinemic-euglycemic clamp. D, Group differences in EE were evaluated by deriving a prediction equation relating lean body mass to EE using all 26 subjects at W0. The sum of the squared residuals of the W16 observations were then calculated relative to the regression line to test for evidence of a systematic change in EE within the groups. E, RQ was calculated as the ratio of volume of CO₂ produced to volume of O₂ consumed. Changes in the percentage of fat, carbohydrate, and protein oxidation were estimated using the change in RQ from W0 in both groups. The percentage change between W0 and W16 characteristics were calculated for each subject in the Control and methionine-restricted (MR) groups, analyzed using a paired t test to compare group changes, and means annotated with different letters in A–E differ at P < 0.05. LBW, Lean body weight; AdipoQ, adiponectin; CHO, carbohydrate.