Increased homocysteinemia is associated with beneficial effects on body weight after long-term high-protein, low-fat diet in rats

ObjectiveDiets rich in protein are often used for weight loss in obese patients, but their long-term effects are not fully understood. Homocysteine (Hcy) is considered to be a risk factor for cardiovascular diseases, and its levels are influenced by diet, particularly the protein and fat content. We studied the effect of diets with varying fat/protein content on body weight and composition, food intake, Hcy, B vitamins, leptin, and several pro-inflammatory cytokines.MethodsFor 2 mo, Long-Evans rats were fed either a low protein/high fat (LP), a standard control (C), or a high protein/low fat (HP) diet containing 5, 15, or 40% protein, respectively, and normal carbohydrate content (55% of total energy).ResultsThe HP rats ingested 12 to 15% fewer calories (P < 0.001), gained less weight (P < 0.04), and were less fatty (P < 0.01) than the other groups. Plasma Hcy was increased in HP rats compared to C (+23%) and LP (+29%) rats (P < 0.03). It was positively correlated with protein intake (r = 0.386; P < 0.01). No obvious signs of inflammation were observed in any of the groups. Hcy increase was related directly to decrease in plasma folate (r = −0.372; P < 0.02).ConclusionThese data confirm the beneficial effects of HP diets on body weight but bring attention to the control of folate allowance to limit the adverse effects of elevated Hcy. Ingestion of folate-rich foods or even folate supplementation should be considered when using these HP diets over the long term for weight loss.