Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: Possible implications for prevention of vascular disease

To explore interrelations between folic acid and methionine metabolism in chronic renal insufficiency, we measured plasma amino acids in 21 patients with mean serum creatinine ± SD of 560 ± 240 μmol/L, after a ten-hour overnight fast, before and after administration of 5 mg of oral folic acid daily for 15 ± 6 days. Mean plasma homocysteine was 12.9 ± 6.8 μmol/L in the patients and 4.2 ± 0.8 μmol/L in 24 normal controls ( P < .001), and after folic acid administration it declined in the patients to 6.8 ± 2.8 μmol/L ( P < .0001) in linear proportion ( r = .92) to the prefolate homocysteine level. Methionine concentrations were normal in the patients and did not change after folate administration, nor did elevated cysteine and creatinine. Plasma serine was lower (88.3 ± 17.2 v 121 ± 25 μmol/L, P < .41) and declined further to 67.8 ± 16.4 ( P < .0001) after folate, while prefolate glycine levels increased from 273.3 ± 61.2 to 313.2 ± 97.5 μmol/L ( P < .01). Serum and red-cell folate levels were normal in the patients before treatment. The results show that homocysteine levels are increased in chronic renal insufficiency, but may be lowered by folate enhancement of remethylation of homocysteine to methionine. Since elevated plasma homocysteine is associated with premature vascular disease, folic acid may reduce cardiovascular risk in chronic renal insufficiency.