The PRECISE pilot trial: Investigating the relationship between selenium, homocysteine and folate in an elderly UK population

Colorectal cancer risk is associated with folate status (1), whereas selenium was shown to modify the risk of several cancers (2). Both play an important role in 1-carbon metabolism that involves the remethylation of homocysteine to methionine, which in turn is an important modifier of DNA methylation in neoplasia (3). We investigated the interaction among the 3 dietary factors in 501 healthy UK volunteers aged 60–74 y to determine the effect of selenium (Se) supplementation on folate and homocysteine (tHcy) concentrations. Volunteers were randomly assigned to receive placebo or 100, 200, or 300 μg/d of Se-enriched yeast for 6 mo in a double-blind, placebo-controlled trial. There was no significant effect of Se supplementation on the change in tHcy in any treatment groups in accordance with the findings of Venn et al. (4). At 6 mo, folate levels remained inversely correlated with tHcy in all treatment groups. Baseline folate concentration was significantly different between men and women (11.44 vs. 13.35 nmol/L, respectively, P = 0.013), and men had higher tHcy concentrations than women (mean ± SD, 11.59 ± 4.75 vs. 10.56 ± 4.68 μmol/L, P = 0.0002). Baseline plasma tHcy correlated inversely with both plasma folate and plasma Se in men, with folate accounting for 2.6% and Se for 1.8% of the variance. The inverse correlation of baseline Se and homocysteine in this elderly population agrees with results of other human studies (4–6), although the magnitude of the effect explained by Se when folate is taken into account was much lower and was seen only in men. Protein intake was inversely correlated with tHcy (7) and could explain the inverse relation between Se and tHcy at baseline. Dietary protein intake of the population will be investigated because high-protein foods such as meat and poultry are the major sources of Se in the UK.status: publishe