Low Circulating Folate and Vitamin B ₆ Concentrations

TLDR

High plasma homocysteine is a known risk factor for atherosclerosis and its levels correlate with folate and vitamin B6 concentrations. The study sought to investigate the relationships among homocysteine, folate, and vitamin B6 with vascular disease risk and to underscore the need for clinical trials testing these vitamins for prevention. Researchers performed a multicenter European case‑control study of 750 vascular‑disease patients and 800 matched controls, measuring plasma homocysteine before and after methionine loading as well as red‑cell folate, vitamin B12, and vitamin B6 levels. High homocysteine, low red‑cell folate, and low vitamin B6 levels were each independently associated with increased vascular disease risk, with folate’s effect partly mediated by homocysteine and vitamin B6’s effect remaining independent.

Abstract

Background —A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B 6 . This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. Methods —In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B 12 , and vitamin B 6 . Results —In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 μmol/L) or after a methionine load (38.0 μmol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In addition, concentrations of red cell folate below the lowest 10th percentile (<513 nmol/L) and concentrations of vitamin B 6 below the lowest 20th percentile (<23.3 nmol/L) for control subjects were also associated with increased risk. This risk was independent of conventional risk factors and for folate was explained in part by increased homocysteine levels. In contrast, the relationship between vitamin B 6 and atherosclerosis was independent of homocysteine levels both before and after methionine loading. Conclusions —Lower levels of folate and vitamin B 6 confer an increased risk of atherosclerosis. Clinical trials are now required to evaluate the effect of treatment with these vitamins in the primary and secondary prevention of vascular diseases.