Dietary Egg Protein Prevents Hyperhomocysteinemia via Upregulation of Hepatic Betaine-Homocysteine S-Methyltransferase Activity in Folate-Restricted Rats.

ABSTRACT

BACKGROUND: Hyperhomocysteinemia is associated with increased cardiovascular disease risk. Whole eggs contain several nutrients known to affect homocysteine regulation, including sulfur amino acids, choline, and B vitamins. OBJECTIVE: The aim of this study was to determine the effect of whole eggs and egg components (i.e., egg protein and choline) with respect to 1) homocysteine balance and 2) the hepatic expression and activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine ß-synthase (CBS) in a folate-restricted (FR) rat model of hyperhomocysteinemia. METHODS: Male Sprague Dawley rats (n = 48; 6 wk of age) were randomly assigned to a casein-based diet (C; n = 12), a casein-based diet supplemented with choline (C + Cho; 1.3%, wtwt; n = 12), an egg protein-based diet (EP; n = 12), or a whole egg-based diet (WE; n = 12). At week 2, half of the rats in each of the 4 dietary groups were provided an FR (0 g folic acid/kg) diet and half continued on the folate-sufficient (FS; 0.2 g folic acid/kg) diet for an additional 6 wk. All diets contained 20% (wtwt) total protein. Serum homocysteine was measured by HPLC and BHMT and CBS expression and activity were evaluated using real-time quantitative polymerase chain reaction, Western blot, and enzyme activity. A 2-factor ANOVA was used for statistical comparisons. RESULTS: Rats fed FR-C exhibited a 53% increase in circulating homocysteine concentrations compared with rats fed FS-C (P < 0.001). In contrast, serum homocysteine did not differ between rats fed FS-C and FR-EP (P = 0.078). Hepatic BHMT activity was increased by 45% and 40% by the EP (P < 0.001) and WE (P = 0.002) diets compared with the C diets, respectively. CONCLUSIONS: Dietary intervention with egg protein prevented elevated circulating homocysteine concentrations in a rat model of hyperhomocysteinemia, due in part to upregulation of hepatic BHMT. These data may support the inclusion of egg protein for dietary recommendations targeting hyperhomocysteinemia prevention.