Differences in erythrocyte folate concentrations in older adults reached steady-state within one year in a two-year, controlled, 1 mg/d folate supplementation trial

Daily supplementation with folate increases erythrocyte folate concentrations; however, the time to reach steady-state concentrations has not been empirically demonstrated. Previous predictions of time to steady state or time to 90% steadystate concentration, based on modeling changes in erythrocyte folate during short-term trials, range widely from 40 to 86 wk. We sought to determine the time to steady-state erythrocyte folate concentrations following the initiation of daily folate supplementation using data collected from a 2-y, double-blind, placebo-controlled, randomized trial involving 276 participants aged 65 y or older. The daily supplement contained 1 mg of folate. Erythrocyte folate concentrations were measured, using a microbiological assay, at baseline and at 6, 12, 18, and 24 mo. The mean plasma and erythrocyte folate concentrations in the folate-supplemented group were higher than in the placebo group at 6, 12, 18, and 24 mo (P < 0.001). Adjusted for baseline differences, the difference in erythrocyte folate concentrations between the folate and placebo group at 6 mo was 1.78 μmol/L (95% CI: 1.62-1.95 μmol/L). The difference increased significantly to 2.02 μmol/L (95% CI: 1.85-2.18 μmol/L) at 12 mo. This difference (between the folate and placebo groups) did not significantly change after a further year of folate supplementation; at 18 mo, it was 2.09 μmol/L (95% CI: 1.92-2.27 μmol/L) and at 24 mo it was 1.98 μmol/L (95% CI: 1.18-2.15 μmol/L). Twelve months of daily folate supplementation with 1 mg is sufficient time to cause erythrocyte folate concentrations to reach a new steady state.