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 a methionine-rich diet de velop hyperhomocysteinemia, arterial lesions and thrombotic events. Elevate d 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 a st andard diet; 8 received a methionine-rich diet for four months; 8 received a 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, a ll the pigs were sacrificed. RESULTS Control animals developed few usual vascular streaks. All the pigs fed a methionine-rich diet without folic acid treatment developed hyperhomo cysteinemia (10.3 +/- 1.3 mu mol/liter at basal stale, 18.2 +/- 2.5 mu mol/ liter at one month and 14.6 +/- 3.8 mu mol/liter at four months), hemodynam ic abnormalities and diffuse arterial lesions with smooth muscle cell hyper plasia, endothelial alterations and elastic lamina dislocation. In this gro up, one pig died of venous thromboembolism and one of myocardial infarction . The pigs fed a methionine-rich diet + folic acid displayed similar arteri al lesions and two had thrombotic events (one myocardial infarction and one pulmonary embolism), despite normalization of homocysteine levels (10.9 +/ - 1.3 mu mol/liter at basal state, 19.5 +/- 2.5 mu mol/liter at one month a nd 11.4 +/- 3.8 mu mol/liter at four months). CONCLUSIONS In the pig model of hyperhomocysteinemia, 5 mg/day folic acid d id not prevent arterial lesions or thrombotic events. (C) 1999 by the Ameri can College of Cardiology.