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-methyltetrahydrofolic acid salts. K E Y W O R D S folate, folic acid, 5-methyltetrahydrofolic acid salt, tolerable upper intake level 2 of 119 |

Assessment of the feed additive consisting of folic acid for all animal species for the renewal of its authorisation (Chr. Olesen A/S and DSM Nutritional Products Ltd)

“…The EFSA Scientific Panel on Nutrition, Novel Foods and Food Allergens (NDA) has recently set ULs for folates for supplemental uses, i.e. when added to foods (fortified foods) and used in food supplements (EFSA NDA Panel, 2023).…”

Safety of monosodium salt of l‐5‐methyltetrahydrofolic acid as a novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006

“…Since no relevant toxicity data were retrieved, the applicant performed a read‐across from the molecule morpholine (CAS 110‐91‐8), for which Health Canada has established an acceptable daily intake (ADI) of 0.48 mg/kg bw per day (Health Canada, 2002 ). Assuming that the daily intake of the NF is at the level of ULs for supplemental folates for infants (200 μg/day) and adults (1000 μg/day) (EFSA NDA Panel, 2023 ) and based on the LOQ established for HEM analysis in the batches of the NF (0.001% w/w), the daily exposure to HEM for infants (5 kg bw) and adults (70 kg bw) would be 0.0004 and 0.000014 mg/kg bw, respectively, which are orders of magnitude lower than the ADI.…”

“…As mentioned under Section 1.2 Information on existing evaluations and authorisations , the NDA Panel (EFSA NDA Panel, 2023 ) reiterated the previously established ULs for supplemental folate of: 200 μg/day (1–3 years), 300 μg/day (4–6 years), 400 μg/day (7–10 years), 600 μg/day (11–14 years), 800 μg/day (15–17 years), 1000 μg/day (all adults including pregnant and lactating women) (SCF, 2000 ), while adding the UL of 200 μg/day for infants aged 4–11 months. These ULs apply to the combined intake of folic acid and currently authorised forms [(6S)‐5‐methyltetrahydrofolic acid glucosamine and l ‐5‐methyltetrahydrofolic acid calcium salts] under their authorised conditions of use.…”

“…The Panel notes that the applicant proposes to use the NF as a partial or complete substitute for folic acid and other sources of added folate (Section 3.7 ). The Panel considers that the use of the NF in these food categories is not nutritionally disadvantageous as long as the combined intake of the NF and the other supplemental forms of folate under their authorised conditions of use is below the ULs established for the different age groups of the general population (EFSA NDA Panel, 2023 ).…”

“…In its recent assessment of tolerable upper intake levels (UL) for folate (EFSA NDA Panel, 2023 ), the Panel retained the previously established ULs for supplemental intake of 200 μg/day (1–3 years), 300 μg/day (4–6 years), 400 μg/day (7–10 years), 600 μg/day (11–14 years), 800 μg/day (15–17 years), 1000 μg/day (all adults including pregnant and lactating women) (SCF, 2000 ). The Panel also set a UL of 200 μg/day for infants aged 4–11 months.…”