Responsiveness of one-carbon metabolites to a high protein diet in older men: Results from a 10-week randomized controlled trial.

Abstract Dietary strategies to promote successful ageing are divergent. Higher protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation due to the supply of B vitamins (folate, riboflavin, vitamins B6 and B12) and methyl donors (choline) despite higher methionine intake, this study explored the impact of a higher protein diet on 1C metabolite status in elderly males compared to current protein recommendations. Elderly men (74 ± 3 years) were randomised to receive a diet for 10-weeks containing either the recommended dietary allowance of protein (RDA, 0.8g protein/kg body weight/day, n=14), or double protein recommendations (2RDA, n=15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to individual's energy requirements based on the Harris-Benedict equation, and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10-weeks of intervention. Plasma homocysteine concentrations were reduced from baseline to the 10-week follow-up with both diets. Changes in metabolite ratios, reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in betaine/choline and a decline in dimethylglycine/betaine. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with betaine/choline for those in the 2RDA group. Adding to the known benefits of higher protein intake in the elderly, this study supports a reduction of Hcy with increased consumption of animal-based protein, thought the health impacts of differential response of choline metabolites to a higher protein diet remains uncertain.