Level 2: Mid-level evidence
Nephropathy is a common complication of diabetes and has been associated with high plasma homocysteine levels. Because B vitamin formulations with B12 and high doses of folate and B6 have been used to reduce homocysteine levels, the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial examined the effects of B vitamin therapy in 238 adult patients with diabetic nephropathy. Patients were randomized to a daily vitamin B tablet (folic acid 2.5 mg, vitamin B6 25 mg, and vitamin B12 1 mg) vs. placebo and followed for a mean of 32 months. While B vitamin therapy did reduce mean homocysteine levels compared with placebo (-2.2 μmol/L vs. +2.6 μmol/L, P <0.001), it was associated with an increase in the composite outcome of myocardial infarction, stroke, revascularization, and all-cause mortality (23.5% vs. 14.4%, P=0.04, NNH 11). The trial was inadequately powered to show differences in individual cardiovascular outcomes. Treatment with B vitamins also had a detrimental effect on kidney function, significantly reducing the mean glomerular filtration rate (16.5 mL/minute/1.73 m2 vs. 10.7 mL/minute/1.73 m2, P=0.02). Due to these adverse outcomes, the authors recommend that B vitamins not be used to lower homocysteine levels (JAMA. 2010;303:1603-1609).