Calcium l‐methylfolate as a source of folate added for nutritional purposes to infant and follow‐on formula, baby food and processed cereal‐based food

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 extension of use of calcium L-methylfolate to be used as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food pursuant to Regulation (EU) 609/2013. In 2004, EFSA assessed the use of calcium L-methylfolate as a source of folate in foods for particular nutritional uses, food supplements and foods intended for the general population. The new alternative synthetic step proposed to produce the nutrient source, using platinum as a catalyst, did not raise any safety concern and the production process was found to consistently yield a product in line with the proposed specifications. Based on the studies assessed in the previous evaluation, it was concluded that calcium L-methylfolate is non-genotoxic and that subchronic and embryotoxicity/teratogenicity studies in rats did not reveal any adverse effects up to the highest doses tested. The Panel considered that no additional toxicological studies are required on the nutrient source. The intervention study in healthy infants provided by the applicant did not indicate differences in growth and tolerance parameters in infants who consumed either an infant formula supplemented with calcium L-methylfolate or with folic acid, and did not raise concerns regarding safety or tolerability of the infant formula with the proposed nutrient source. The study also provided further supporting evidence for the bioavailability of calcium L-methylfolate. The Panel considers that calcium L-methylfolate is a source from which folate is bioavailable and concludes that calcium L-methylfolate is safe under the proposed uses and use levels for infants and young children. A and Knutsen HK, 2020. Scientific Opinion on calcium L-methylfolate as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cerealbased food.

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

“…For this scientific assessment, a protocol (Appendix A) has been developed in line with existing methodology (EFSA, 2020).…”

“…EFSA AFC Panel (2004) and EFSA NDA Panel (2020) The EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) and the EFSA NDA Panel assessed the safety of CaLMF for addition to foods. With respect to bioavailability, the AFC Panel concluded that in aqueous media, CaLMF dissociates readily and completely into Ca and L-5-MTHF ions and that its bioavailability is similar or even slightly higher than that of folic acid (EFSA AFC Panel, 2004), while the NDA Panel confirmed that CaLMF is a source from which folate is bioavailable (EFSA NDA Panel, 2020).…”

Profile of Folate in Breast Milk from Chinese Women over 1–400 Days Postpartum

“…However, infants receiving formula containing 5-methyl-THF had lower UMFA levels in plasma (0.73 vs. 1.15 nmol/L, p < 0.0001) than infants fed with folic-acid-fortified formula [ 37 ]. As supported by its safety, high proportion in breast milk and clinical studies, 5-methyl-THF has already been approved as a source of folate in infant formulas by the EFSA [ 38 ]. The reduced folate accounted for 87.9~97.0% of the total folate in breast milk at all lactating periods, in which 17.0~31.9% was the minor reduced folate.…”

[6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

“…Diets were custom made by Research Diets Inc. (New Brunswick, NJ, USA) ( Supplementary Materials Table S1 ) and stored at 4 °C and in the dark until provided fresh weekly. The additions of the MTHF form of folate into foods has been shown to be stable at both 4 °C and room temperature for up to 24 months [ 39 ]. Analytical testing of the high folate diets following a 36-month storage at −80 °C showed >80% retention of folates ( Table S1 ), further confirming their long-term stability.…”