Correlates of total plasma homocysteine: folic acid, copper, and cervical dysplasia.
We examined correlates of total plasma homocysteine (tHcy) in 294 subjects with cervical intraepithelial neoplasia and 170 control subjects. Associations of tHcy with risk factors for cervical intraepithelial neoplasia and 24-h intakes and biochemical indices of nutrients were examined. Plasma and red blood cell folate and plasma B(12) were strong inverse correlates of tHcy (r = -0.35, -0. 31, and -0.27, respectively). Plasma copper and severity of dysplasia were positively correlated with tHcy (r = 0.14 and 0.21, respectively). A stepwise regression model that included red blood cell folate, plasma copper, grade of dysplasia, ethnicity, intake of polyunsaturated fatty acids, plasma vitamin B(12), intake of fat, and oral contraceptive use explained 29% of the variation in tHcy. Two hundred thirty-five subjects with cervical intraepithelial neoplasia were randomized to receive folic acid (10 mg/d) or placebo for 6 mo. After 2, 4, and 6 mo, mean tHcy in the folate-supplemented group (7.2 +/- 1.8, 7.0 +/- 1.9, and 7.0 +/- 2.3 micromol/L, respectively) was significantly lower than baseline and the placebo group at 2, 4, and 6 mo (8.9 +/- 3.1, 8.4 +/- 3.0, and 8.9 +/- 3.1 micromol/L, respectively). Supplementation lowered tHcy even in subjects in the highest quintile of baseline folate. Folate, vitamin B(12), copper, and severity of dysplasia are associated with tHcy. Folate supplementation significantly lowers tHcy even in folate-replete subjects.