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

K. Pentieva; D Turck; T Bohn; J Castenmiller; S De Henauw; KI Hirsch-Ernst; HK Knutsen; A Maciuk; I Mangelsdorf; HJ McArdle; A Naska; C Pelaez; A Siani; F Thies; S Tsabouri; M Vinceti; F Cubadda; JC Abrahantes; C Dumas; V Ercolano; A Titz

doi:10.2903/j.efsa.2022.7452

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

K. Pentieva, D Turck, T Bohn, J Castenmiller, S De Henauw, KI Hirsch-Ernst, HK Knutsen , A Maciuk , I Mangelsdorf, HJ McArdle , A Naska , C Pelaez , A Siani , F Thies, S Tsabouri , M Vinceti , F Cubadda , JC Abrahantes , C Dumas , V Ercolano A Titz

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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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.

Original language	English
Article number	e07452
Pages (from-to)	1-56
Number of pages	56
Journal	EFSA Journal
Volume	20
Issue number	8
Early online date	24 Aug 2022
DOIs	https://doi.org/10.2903/j.efsa.2022.7452
Publication status	Published (in print/issue) - 31 Aug 2022

Bibliographical note

Funding Information:
The Panel wishes to thank for their contribution to this output: the Working Group on Dietary Folate Equivalents: Francesco Cubadda and Kristina Pentieva; and EFSA staff members: Ester Artau Cortacans, Fulvio Barizzone, Angelo Cafaro, Janusz Ciok, Ionut Craciun, Irene Muñoz Guajardo, Estefania Noriega Fernandez, Charlotte Salgaard Nielsen and Angeliki Sofroniou. The Panel also wishes to acknowledge the contribution of Anne Molloy as hearing expert and all European competent institutions, Member State bodies and other organisations that provided data for this scientific output and the authors of published articles on folate who provided individual data or additional information upon request.

Publisher Copyright:
© 2022 Wiley-VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.

Funding

Funding Information: The Panel wishes to thank for their contribution to this output: the Working Group on Dietary Folate Equivalents: Francesco Cubadda and Kristina Pentieva; and EFSA staff members: Ester Artau Cortacans, Fulvio Barizzone, Angelo Cafaro, Janusz Ciok, Ionut Craciun, Irene Muñoz Guajardo, Estefania Noriega Fernandez, Charlotte Salgaard Nielsen and Angeliki Sofroniou. The Panel also wishes to acknowledge the contribution of Anne Molloy as hearing expert and all European competent institutions, Member State bodies and other organisations that provided data for this scientific output and the authors of published articles on folate who provided individual data or additional information upon request. Publisher Copyright: © 2022 Wiley-VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.

Keywords

5-MTHF glucosamine
CaLMF
DFE
bioavailability
food for specific groups
food supplements
fortified food

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2903/j.efsa.2022.7452

Conversion of 5-MTHF into Dietary Folate EquivalentsFinal published version, 6.37 MBLicence: CC BY-ND

Cite this

Pentieva, K., Turck, D., Bohn, T., Castenmiller, J., De Henauw, S., Hirsch-Ernst, KI., Knutsen , HK., Maciuk , A., Mangelsdorf, I., McArdle , HJ., Naska , A., Pelaez , C., Siani , A., Thies, F., Tsabouri , S., Vinceti , M., Cubadda , F., Abrahantes , JC., Dumas , C., ... Titz , A. (2022). Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents. EFSA Journal, 20(8), 1-56. Article e07452. https://doi.org/10.2903/j.efsa.2022.7452

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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.",

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Pentieva, K, Turck, D, Bohn, T, Castenmiller, J, De Henauw, S, Hirsch-Ernst, KI, Knutsen , HK, Maciuk , A, Mangelsdorf, I, McArdle , HJ, Naska , A, Pelaez , C, Siani , A, Thies, F, Tsabouri , S, Vinceti , M, Cubadda , F, Abrahantes , JC, Dumas , C, Ercolano , V & Titz , A 2022, 'Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents', EFSA Journal, vol. 20, no. 8, e07452, pp. 1-56. https://doi.org/10.2903/j.efsa.2022.7452

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AU - Turck, D

AU - Bohn, T

AU - Castenmiller, J

AU - De Henauw, S

AU - Hirsch-Ernst, KI

AU - Knutsen , HK

AU - Maciuk , A

AU - Mangelsdorf, I

AU - McArdle , HJ

AU - Naska , A

AU - Pelaez , C

AU - Siani , A

AU - Thies, F

AU - Tsabouri , S

AU - Vinceti , M

AU - Cubadda , F

AU - Abrahantes , JC

AU - Dumas , C

AU - Ercolano , V

AU - Titz , A

N1 - Funding Information: The Panel wishes to thank for their contribution to this output: the Working Group on Dietary Folate Equivalents: Francesco Cubadda and Kristina Pentieva; and EFSA staff members: Ester Artau Cortacans, Fulvio Barizzone, Angelo Cafaro, Janusz Ciok, Ionut Craciun, Irene Muñoz Guajardo, Estefania Noriega Fernandez, Charlotte Salgaard Nielsen and Angeliki Sofroniou. The Panel also wishes to acknowledge the contribution of Anne Molloy as hearing expert and all European competent institutions, Member State bodies and other organisations that provided data for this scientific output and the authors of published articles on folate who provided individual data or additional information upon request. Publisher Copyright: © 2022 Wiley-VCH Verlag GmbH & Co. KgaA on behalf of the European Food Safety Authority.

PY - 2022/8/31

Y1 - 2022/8/31

N2 - 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.

AB - 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.

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KW - CaLMF

KW - DFE

KW - bioavailability

KW - food for specific groups

KW - food supplements

KW - fortified food

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ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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