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

J Clin Endocrinol Metab. 2011 May;96(5):E836-40. doi: 10.1210/jc.2010-2493. Epub 2011 Feb 23.


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: NCT00640757.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Biomarkers / blood
  • Body Composition / physiology
  • Cohort Studies
  • Cystine / blood
  • Diet*
  • Dietary Fats / metabolism
  • Double-Blind Method
  • Energy Metabolism / physiology
  • Fats / metabolism*
  • Female
  • Glucose / metabolism
  • Humans
  • Insulin Resistance / physiology
  • Kinetics
  • Liver / metabolism
  • Male
  • Metabolic Syndrome / metabolism*
  • Methionine / blood
  • Methionine / pharmacology*
  • Middle Aged
  • Obesity / metabolism*
  • Oxidation-Reduction
  • Waist Circumference / physiology


  • Biomarkers
  • Dietary Fats
  • Fats
  • Cystine
  • Methionine
  • Glucose

Associated data