Scientific opinion on the tolerable upper intake level for folate

D Turck; T Bohn; J Castenmiller; S de Henauw; KI Hirsh-Ernst; Helle Katrine Knutsen; A Maciuk; I Mangelsdorf; HJ McArdle; K. Pentieva; A Siani; F Thies; S Tsabouri; M Vinceti; M Crous-Bou; A Molloy; L Ciccolallo; A de Sesmaisons Lecarré; L Fabiani; Z Horvath; N Karavasiloglou; A Naska

doi:10.2903/j.efsa.2023.8353

Scientific opinion on the tolerable upper intake level for folate

D Turck
, T Bohn
, J Castenmiller
, S de Henauw
, KI Hirsh-Ernst
, Helle Katrine Knutsen
, A Maciuk
, I Mangelsdorf
, HJ McArdle
, K. Pentieva
, A Siani
, F Thies
, S Tsabouri
, M Vinceti
, M Crous-Bou
, A Molloy
, L Ciccolallo
, A de Sesmaisons Lecarré
, L Fabiani
, Z Horvath

N Karavasiloglou, A Naska

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

35 Citations (Scopus)

135 Downloads (Pure)

Abstract

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose–response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1–3 years, 300 μg/day for 4–6 years, 400 μg/day for 7–10 years, 600 μg/day for 11–14 years and 800 μg/day for 15–17 years. A UL of 200 μg/day is established for infants aged 4–11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyl-tetrahydrofolic acid salts.

Original language	English
Article number	e8353
Pages (from-to)	1-119
Number of pages	120
Journal	EFSA Journal
Volume	21
Issue number	11
Early online date	13 Nov 2023
DOIs	https://doi.org/10.2903/j.efsa.2023.8353
Publication status	Published (in print/issue) - 30 Nov 2023

Bibliographical note

Funding Information:
The Panel wishes to thank for their contribution to this output the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Reginald Fitzgerald, Susan Lanham New, Georg Lietz, Harry J. McArdle, Anne Molloy, Androniki Naska, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; and EFSA staff members: Irene Muñoz Guajardo, Franco Neri, Roanne Marie Saad and Angeliki Sofroniou. The Panel also wishes to thank Carmen Peláez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Agneta Åkesson, Linnea Bärebring, Jacob Juel Christensen, Thomas Olsen, Fredrik Söderlund and Cornelia Witthöft for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output and the authors of published papers on folate who provided additional information upon request.

Publisher Copyright:
© 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.

Funding

Funding Information: The Panel wishes to thank for their contribution to this output the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Reginald Fitzgerald, Susan Lanham New, Georg Lietz, Harry J. McArdle, Anne Molloy, Androniki Naska, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; and EFSA staff members: Irene Muñoz Guajardo, Franco Neri, Roanne Marie Saad and Angeliki Sofroniou. The Panel also wishes to thank Carmen Peláez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Agneta Åkesson, Linnea Bärebring, Jacob Juel Christensen, Thomas Olsen, Fredrik Söderlund and Cornelia Witthöft for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output and the authors of published papers on folate who provided additional information upon request. Publisher Copyright: © 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

folate
folic acid
5-methyltetrahydrofolic acid salt
tolerable upper intake level

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10.2903/j.efsa.2023.8353Licence: CC BY-ND

EFSA Journal - 2023 - - Scientific opinion on the tolerable upper intake level for folateFinal published version, 5.52 MBLicence: CC BY-ND

https://www.efsa.europa.eu/sites/default/files/2023-11/EFS2_8353_Rev.pdf

Cite this

Turck, D., Bohn, T., Castenmiller, J., de Henauw, S., Hirsh-Ernst, KI., Knutsen, H. K., Maciuk, A., Mangelsdorf, I., McArdle, HJ., Pentieva, K., Siani, A., Thies, F., Tsabouri, S., Vinceti, M., Crous-Bou, M., Molloy, A., Ciccolallo, L., de Sesmaisons Lecarré, A., Fabiani, L., ... Naska, A. (2023). Scientific opinion on the tolerable upper intake level for folate. EFSA Journal, 21(11), 1-119. Article e8353. https://doi.org/10.2903/j.efsa.2023.8353

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title = "Scientific opinion on the tolerable upper intake level for folate",

abstract = "Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose–response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1–3 years, 300 μg/day for 4–6 years, 400 μg/day for 7–10 years, 600 μg/day for 11–14 years and 800 μg/day for 15–17 years. A UL of 200 μg/day is established for infants aged 4–11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyl-tetrahydrofolic acid salts.",

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author = "D Turck and T Bohn and J Castenmiller and \{de Henauw\}, S and KI Hirsh-Ernst and Knutsen, \{Helle Katrine\} and A Maciuk and I Mangelsdorf and HJ McArdle and K. Pentieva and A Siani and F Thies and S Tsabouri and M Vinceti and M Crous-Bou and A Molloy and L Ciccolallo and \{de Sesmaisons Lecarr{\'e}\}, A and L Fabiani and Z Horvath and N Karavasiloglou and A Naska",

note = "Funding Information: The Panel wishes to thank for their contribution to this output the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Reginald Fitzgerald, Susan Lanham New, Georg Lietz, Harry J. McArdle, Anne Molloy, Androniki Naska, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; and EFSA staff members: Irene Mu{\~n}oz Guajardo, Franco Neri, Roanne Marie Saad and Angeliki Sofroniou. The Panel also wishes to thank Carmen Pel{\'a}ez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Agneta {\AA}kesson, Linnea B{\"a}rebring, Jacob Juel Christensen, Thomas Olsen, Fredrik S{\"o}derlund and Cornelia Witth{\"o}ft for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output and the authors of published papers on folate who provided additional information upon request. Publisher Copyright: {\textcopyright} 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.",

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doi = "10.2903/j.efsa.2023.8353",

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Turck, D, Bohn, T, Castenmiller, J, de Henauw, S, Hirsh-Ernst, KI, Knutsen, HK, Maciuk, A, Mangelsdorf, I, McArdle, HJ, Pentieva, K, Siani, A, Thies, F, Tsabouri, S, Vinceti, M, Crous-Bou, M, Molloy, A, Ciccolallo, L, de Sesmaisons Lecarré, A, Fabiani, L, Horvath, Z, Karavasiloglou, N & Naska, A 2023, 'Scientific opinion on the tolerable upper intake level for folate', EFSA Journal, vol. 21, no. 11, e8353, pp. 1-119. https://doi.org/10.2903/j.efsa.2023.8353

TY - JOUR

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AU - Turck, D

AU - Bohn, T

AU - Castenmiller, J

AU - de Henauw, S

AU - Hirsh-Ernst, KI

AU - Knutsen, Helle Katrine

AU - Maciuk, A

AU - Mangelsdorf, I

AU - McArdle, HJ

AU - Pentieva, K.

AU - Siani, A

AU - Thies, F

AU - Tsabouri, S

AU - Vinceti, M

AU - Crous-Bou, M

AU - Molloy, A

AU - Ciccolallo, L

AU - de Sesmaisons Lecarré, A

AU - Fabiani, L

AU - Horvath, Z

AU - Karavasiloglou, N

AU - Naska, A

N1 - Funding Information: The Panel wishes to thank for their contribution to this output the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Reginald Fitzgerald, Susan Lanham New, Georg Lietz, Harry J. McArdle, Anne Molloy, Androniki Naska, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; and EFSA staff members: Irene Muñoz Guajardo, Franco Neri, Roanne Marie Saad and Angeliki Sofroniou. The Panel also wishes to thank Carmen Peláez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Agneta Åkesson, Linnea Bärebring, Jacob Juel Christensen, Thomas Olsen, Fredrik Söderlund and Cornelia Witthöft for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output and the authors of published papers on folate who provided additional information upon request. Publisher Copyright: © 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.

PY - 2023/11/30

Y1 - 2023/11/30

N2 - Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose–response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1–3 years, 300 μg/day for 4–6 years, 400 μg/day for 7–10 years, 600 μg/day for 11–14 years and 800 μg/day for 15–17 years. A UL of 200 μg/day is established for infants aged 4–11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyl-tetrahydrofolic acid salts.

AB - Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose–response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1–3 years, 300 μg/day for 4–6 years, 400 μg/day for 7–10 years, 600 μg/day for 11–14 years and 800 μg/day for 15–17 years. A UL of 200 μg/day is established for infants aged 4–11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyl-tetrahydrofolic acid salts.

KW - folate

KW - folic acid

KW - 5-methyltetrahydrofolic acid salt

KW - tolerable upper intake level

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DO - 10.2903/j.efsa.2023.8353

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VL - 21

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JO - EFSA Journal

JF - EFSA Journal

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ER -

Scientific opinion on the tolerable upper intake level for folate

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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