Does long‐term supplementation with folic acid or (6S)‐5‐methyltetrahydrofolate have an impact on plasma vitamin B12 concentrations in healthy subjects?

Abstract

Women with low vitamin B12 status have an increased risk of having an offspring with a neural tube defect (NTD). The objective of this investigation was to determine possible changes in vitamin B12 status after 24 weeks of supplementation with different forms and dosages of folate. Healthy female subjects (n = 144) aged 19 to 33 years with plasma vitamin B12 concentrations above 110pmol/L participated in this 24-week double blind, placebo-controlled intervention trial. Subjects were randomised to receive either 400μg/d folic acid, equimolar 416μg/d (6S)-5-methyltetrahydrofolate, 208μg/d (6S)-5-methyltetra-hydrofolate, or placebo. Fasting blood samples for plasma vitamin B12 determination were taken at baseline and at 8-week intervals. Dietary vitamin B12 intake was constant over the whole study period. Plasma vitamin B12 concentration did not change significantly in any of the four groups after 24 weeks of intervention. However, there was a mean non-significant decrease of between 4.7% and 11.5%. Women using oral contraceptives had significantly lower plasma vitamin B12 concentrations than non-users. In conclusion, plasma vitamin B12 concentrations tend to decrease after long-term folate administration in young, non-pregnant women. With respect to prevention of NTD by periconceptional supplementation and food fortification, the addition of vitamin B12 to folic acid should be considered.