Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents

Abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt (collectively called 5-MTHF hereafter) into dietary folate equivalents (DFE). Following a systematic review, the conclusions of the opinion are based on one intervention study in adults for intakes < 400 μg/day and three intervention studies in adults for intakes ≥ 400 μg/day. At intakes below 400 μg/day, folic acid (FA) is assumed to be linearly related to responses of biomarkers of intake and status and is an appropriate comparator for deriving a DFE conversion factor for 5-MTHF. It is proposed to use the same factor as for folic acid for conversion of 5-MTHF into DFE for intakes < 400 μg/day. As such intake levels are unlikely to be exceeded through fortified food consumption, the conversion factor of 1.7 relative to natural food folate (NF) could be applied to 5-MTHF added to foods and to food supplements providing < 400 μg/day. At 400 μg/day, 5-MTHF was found to be more bioavailable than folic acid and a conversion factor of 2 is proposed for this intake level and for higher intakes. The derived DFE equations are DFE = NF + 1.7 × FA + 1.7 × 5-MTHF for fortified foods and food supplements providing intakes < 400 μg/day; and DFE = NF + 1.7 × FA + 2.0 × 5-MTHF for food supplements providing intakes ≥ 400 μg/day. Although this assessment applies to calcium-L-methylfolate and 5-MTHF glucosamine salt, it is considered that the influence of the cation on bioavailability is likely to be within the margin of error of the proposed DFE equations. Therefore, the proposed equations can also be applied to 5-MTHF associated with other cations.

Keywords: 5‐MTHF glucosamine; CaLMF; DFE; bioavailability; food for specific groups; food supplements; fortified food.

Figure 1

Structures of folic acid, CaLMF and 5‐MTHF

1. glucosamine5‐MTHF‐glucosamine: (6S)‐5‐methyltetrahydrofolic acid glucosamine salt, Ca: calcium.

Figure 2

Folate and one‐carbon metabolism (EFSA NDA Panel, 2014), figure kindly provided by J.J. Strain

1. DMG: dimethylglycine, DNA: deoxyribonucleic acid, FAD: flavin adenine dinucleotide, MTHFR: methylene tetrahydrofolate reductase, PLP: pyroxidal 5′‐phosphate, THF: tetrahydrofolate.

Figure 3

Dose–response meta‐regression of the ratio of mean changes in RBC folate concentrations (5‐MTHF/folic acid supplementation) from baseline to end of supplementation and the daily dose (nmol, administered once per day)

1. The red dashed line corresponds to a ratio equal to one (i.e. similar effect of 5‐MTHF and folic acid on RBC folate concentrations). The size of the point is proportional to the weight of the study as defined by the inverse of its variance in the meta‐regression model.

Figure 4

Dose–response meta‐regression of the ratio of mean changes in PTF concentrations (MTHF/folic acid supplementation) from baseline to end of supplementation and the daily dose (nmol, administered once per day)

1. The red dashed line corresponds to a ratio equal to one (i.e. similar effect of 5‐MTHF and folic acid on PTF concentrations). The size of the point is proportional to the weight of the study as defined by the inverse of its variance in the meta‐regression model.

Figure A.1

Methodological steps followed for the scientific assessment