Effects of folate supplementation in hyperhomocysteinemic pigs

OBJECTIVES The aim of this study was to evaluate the therapeutic effects of folic acid in the pig model of hyperhomocysteinemia. BACKGROUND We have previously shown that pigs fed methionine-rich diet develop hyperhomocysteinemia, arterial lesions and thrombotic events. Elevated homocysteine level is an independent risk factor for atherosclerosis that can be markedly lowered with daily folic acid administration. However, it is not known whether this treatment can prevent arterial lesions. METHODS Three groups of pigs were studied: 8 control subjects received standard diet; 8 received methionine-rich diet for four months; 8 received methionine-rich diet for 1 month and then the methionine-rich diet + 5 mg/day folic acid for 3 months. At month 4 after hemodynamic investigation, all the pigs were sacrificed. RESULTS Control animals developed few usual vascular streaks. All the pigs fed methionine-rich diet without folic acid treatment developed hyperhomocysteinemi (10.3 ± 1.3 μmol/liter at basal state, 18.2 ± 2.5 μmol/liter at one month and 14.6 ± 3.8 μmol/liter at four months), hemodynamic abnormalities and diffuse arterial lesions with smooth muscle cell hyperplasia, endothelial alterations and elastic lamin dislocation. In this group, one pig died of venous thromboembolism and one of myocardial infarction. The pigs fed methionine-rich diet + folic acid displayed similar arterial lesions and two had thrombotic events (one myocardial infarction and one pulmonary embolism), despite normalization of homocysteine levels (10.9 ± 1.3 μmol/liter at basal state, 19.5 ± 2.5 μmol/liter at one month and 11.4 ± 3.8 μmol/liter at four months). CONCLUSIONS In the pig model of hyperhomocysteinemia, 5 mg/day folic acid did not prevent arterial lesions or thrombotic events.