Experimental Studies
Effects of folate supplementation in hyperhomocysteinemic pigs

https://doi.org/10.1016/S0735-1097(99)00144-8Get rights and content
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Abstract

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 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 a standard 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, all 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 hyperhomocysteinemia (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 lamina dislocation. In this group, one pig died of venous thromboembolism and one of myocardial infarction. The pigs fed a 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.

Abbreviations

M0
basal state
M1
month 1
M4
month 4
C group
control group
M group
pigs receiving a methionine-rich diet
M+F group
pigs receiving a methionine-rich diet+folates
D
external arterial diameter
P
blood pressure
Q
blood flow

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This work was supported by a grant of Rhône-Poulenc Rorer, Paris, France.