Low dietary folate impairs glucose tolerance and plasma lipid profile in oral contraceptive-treated rats

Estrogen–progestogen oral contraceptive (OC) use is associated with abnormal lipid metabolism, impaired glucose tolerance and high prevalence of vascular complications. OC use has been shown to alter the requirements for folic acid. Therefore, the aim of the present study was to clarify the influence of dietary folic acid on OC-induced impaired glucose tolerance and abnormal plasma lipid profile in female Sprague–Dawley rats. Vehicle-treated and OC-treated rats were fed for 6 weeks with a control diet (750 μg folic acid/kg diet) while OC-treated folic acid deficient (FD) rats were fed for 6 weeks with a folic acid-deficient diet (250 μg folic acid/kg diet). OC receiving rats were treated with a combination of OC steroids (ethinyl estradiol and norgestrel) by oral gavage. OC treatment resulted in rats receiving folic acid deficient diet in impaired glucose tolerance, decreased high-density lipoprotein (HDL)-cholesterol and increased low-density lipoprotein (LDL)-cholesterol when compared with control rats. However, OC treatment did not result in impaired glucose tolerance or disturbed plasma lipid profile in rats receiving the same folic acid level as the controls. OC treatment led to significant decreases in plasma levels of 17β-estradiol and testosterone in both groups. OC administration in rats with folic acid deficient diet significantly lower HDL-cholesterol and higher LDL-cholesterol levels while plasma levels of 17β-estradiol and testosterone were similar in both OC-treated groups. Conclusion: These results demonstrate impaired glucose tolerance and disturbed plasma lipid profile induced by OC treatment in folic acid deficient rats and suggest that inadequate folic acid intake might contribute to increased cardiovascular risk during OC use that could be prevented by proper oral folic acid intake.