Folic acid, vitamin B supplements did not reduce mortality in patients with advanced CKD, ESRD.
Using high doses of folic acid and B vitamins to lower elevated homocysteine levels in patients with advanced CKD (ACKD) or end-stage renal disease (ESRD) does not improve survival or decrease the incidence of vascular disease, data show.
Epidemiologic studies have confirmed that high homocysteine levels increase cardiovascular risk.
Rex L. Jamison, MD, of the Veterans Affairs Palo Alto Health Care System in Palo Alto, Calif., and his colleagues studied 2,056 patients with high homocysteine levels (15 µmol/L or higher). Of these patients, 1,305 had ACKD (estimated creatinine clearance of less than 30 mL/min per 1.73 m2) or 751 had ESRD.
Researchers randomly assigned 1,032 patients to receive a daily capsule containing 40 mg of folic acid, 100 mg of vitamin B6, and 2 mg of vitamin B12 and 1,024 to receive placebo. The primary outcome measure was all-cause mortality. The patients had a median follow-up of 3.2 years.
Patients in the vitamin and placebo groups had mean baseline homocysteine levels of 24.0 and 24.2 µmol/L, respectively. At three months, the level was reduced 6.3 µmol/L (25.8%) in the vitamin group and 0.4 µmol/L (1.7%) in placebo recipients, the investigators reported in the Journal of the American Medical Association (2007;298:1163-1170).
The researchers observed no significant effect on mortality, with 448 patients dying in the vitamin group and 436 deaths in the placebo arm. In addition, the study revealed no significant effects on MI, strokes, and amputations, or a composite of these events.
“Our findings do not support the administration of folic acid and vitamin B supplements to prevent vascular injury or improve survival in patients with ACKD or ESRD,” the authors wrote.
In a discussion of what might account for the study’s failure to show a mortality benefit from lowering homocysteine, the authors observed: “Possibly the underlying burden of disease was too great for a measurable benefit from lowering homocysteine.”
In an accompanying editorial (pp.1212-1214), Colin Baigent, MD, and Robert Clarke, MD, of the University of Oxford in England, noted that, based on existing data, including the findings of Dr. Jamison and his colleagues, “there is insufficient evidence to justify routine use of homocysteine-lowering vitamin supplements for the prevention of vascular events among individuals at high risk for vascular disease.”