(P10-076-24) Analytical Testing of 5-Methyltetrahydrofolate in Dietary Supplements: Label Accuracy, and Dosage Form Performance

Objectives: Adequate folate intake prevents fetal neural tube defects, adverse birth outcomes, and supports fetal growth and development and prevents folate deficiency anemia in pregnancy.  The Centers for Disease Control (CDC) recognizes folic acid as effective, but not 5-methyltetrahydrofolate (5-MTHF), which is replacing folic acid in prenatal multivitamin/mineral (MVM) dietary supplements (DS). This shift underscores the need to assess 5-MTHF quality and stability in DS. The study objective was to assess the accuracy of labelled 5-MTHF amounts, examine 5-MTHF stability over its shelf life, and evaluate dosage form performance quality in various MVMs (prenatal, adult, child) and single ingredient DS.

Methods: Forty-three commonly sold DS containing 5-MTHF sold over-the-counter (OTC) were identified for testing by searching for such products in surveys of retail/online stores, the NIH's Dietary Supplement Label Database, and in the National Health and Nutrition Examination Survey. The prenatal DS was chosen over other popular products with the same brand name. 5-MTHF was measured using high-performance liquid chromatography in two laboratories on three occasions during each DS's shelf life. DS dosage units underwent disintegration and dissolution testing per United States Pharmacopeia guidelines.

Results: HPLC testing of 5-MTHF with duplicate samples, in-house control materials and spike recovery studies produced results of 92-103%, indicating that HPLC testing quality for 5-MTHF was satisfactory. All 43 OTC products tested contained 5-MTHF.
Over a third of the products failed to fully disintegrate and 42.5% failed dissolution criteria. Initial shelf-life testing revealed variances in 5-MTHF amounts from labels from -42.8% to + >100%. Three products were >30% below and 4 were >10% below label claims. Twenty-one exceeded label claims by >10% and 10 by >30%.

Conclusions: Failures in disintegration and dissolution testing raise bioavailability concerns. Discrepancies in analytical vs labeled 5-MTHF raise questions about dose accuracy. MTHF substitution with folic acid was uncommon. Continued testing to assess  changes in shelf life of these products and prescription prenatal MVMs will provide more data on amounts and stability of MTHF in DS.

Funding Sources: NIH ODS and USDA ARS