Effect of protein and methionine intakes on plasma homocysteine concentrations: a 6-mo randomized controlled trial in overweight subjects

Background: A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease. Homocysteine concentrations are thought to be raised by high protein and methionine intakes. Objective: Our goal was to investigate the effects of high and low protein and methionine intakes on homocysteine in overweight subjects. Design: Sixty-five overweight subjects were randomly assigned to a 6-mo intervention with a low-protein, low-methionine diet (LP: 12% of total energy, 1.4 g methionine/d; n = 25); a high-protein, high-methionine diet (HP: 22% of total energy, 2.7 g methionine/d; n = 25), both of which had similar fat contents (30% of total energy); or a control diet with an intermediate protein content (n = 15). All food was self-selected at a shop at the department. Protein intake was increased in the HP group mainly through lean meat and low-fat dairy products. Dietary compliance was evaluated by urinary nitrogen excretion. Results: Homocysteine concentrations did not change significantly in the LP or control groups but were 25% lower in the HP group (NS). Homocysteine concentrations after the 3-mo intervention were inversely associated with vitamin B-12 intake and with weight change (by multivariate analysis performed for all subjects), but not with methionine or protein intake. Sixty-nine percent of the variation could be explained by baseline homocysteine (P < 0.001), 2% by vitamin B-12 (P = 0.02), and another 2% by weight change (P = 0.06). The plasma homocysteine concentration after 6 mo was associated only with baseline homocysteine (P < 0.001). Conclusion: A high-protein, high-methionine diet does not raise homocysteine concentrations compared with a low-protein, lowmethionine diet in overweight subjects.