Elevation of folate status in humans by 5‐methyl‐6S‐tetrahydrofolate

Several earlier studies have examined the ability of folic acid or 5‐methyl‐6S‐tetrahydrofolate (5MTHF) to elevate folate status. Typically, these involved doses in the range of 0.45 to 1.8 micromoles/d (e.g., 0.2 to 0.8 mg/d of folic acid). Even with a 0.8 mg/d dose of folic acid, fasting plasma total folate reaches a new plateau only after 4 weeks. Although moderately high doses of 5MTHF are currently used for many applications, little is known about the properties of this natural vitamer in repleting body stores of folate when administered in successive daily doses. Moreover, the ability to maintain plasma levels on low (e.g., Daily Value) doses of folate subsequent to brief administration of 5MTHF has not been previously examined. We selected volunteers with fasting total serum folate <25 nM, who were then given 7.5 mg of 5MTHF at various intervals over two to three days along with vitamin B12. Subjects were next switched to either 0.4 or 0.8 mg/d of folate and followed for another two weeks. Serum 5MTHF and total folate were measured over the course of the experiment. The results show that particular regimes of 5MTHF administration can significantly raise serum folate in just a few days. Further, this new status can then be maintained by consumption of the Daily Value for folate.