Preparatory work for the update of the tolerable upper intake levels for vitamin B6

Tetens, Inge; Petersen, Caroline Filskov; Christensen, Sine Højlund; Wilkens, Trine Levring; Mikkelsen, Lasse Sommer

doi:10.2903/sp.efsa.2023.en-7814

Cited by 6 publications

(73 citation statements)

References 134 publications

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“…Hadtstein and Vrolijk (2021) recently reviewed four prevailing theories on the potential mechanisms by which high intakes of vitamin B6 could cause peripheral neuropathy. These have been summarised by the Tetens et al (2023) based on Hadtstein and Vrolijk (2021) and are described in the following: PL and PLP each contain an aldehyde group. Aldehydes are highly reactive and capable of altering structures and functions of macromolecules such as proteins and DNA (LoPachin and Gavin, 2014), not necessarily confined to neurons.…”

Section: Mechanisms Of Toxicitymentioning

confidence: 99%

Scientific opinion on the tolerable upper intake level for vitamin B6

Turck¹,

Bohn²,

Castenmiller³

et al. 2023

EFS2

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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 tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest-observed-effect-level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case-control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2-2.5 mg/day (4-11 months), 3.2-4.5 mg/day (1-6 years), 6.1-10.7 mg/day (7-17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6.

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Section: Mechanisms Of Toxicitymentioning

confidence: 99%

Scientific opinion on the tolerable upper intake level for vitamin B6

Turck¹,

Bohn²,

Castenmiller³

et al. 2023

EFS2

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“…Reasons for references excluded at full‐text screening, or during data extraction, are outlined in Annexes D, H and M of the technical report (Lamberg‐Allardt et al., 2023).…”

Section: Data and Methodologiesmentioning

confidence: 99%

“…Additional data were requested from study authors when this information was pertinent to the interpretation of the study results. See Annex C of the technical report (Lamberg‐Allardt et al., 2023) for details on data requested.…”

Section: Data and Methodologiesmentioning

confidence: 99%

“…Specific search strings were used in the aforementioned databases to limit by type of study and publication type, and with no date limitations, as described in the protocol (Annex A of the opinion). The search strategy is further detailed in Annex B of the technical report (Lamberg‐Allardt et al., 2023). The searches covered literature published up to March 17, 2022 for sQ1, March 14, 2022 for sQ3a, and March 25, 2022 for sQ4a/b/c.…”

Section: Data and Methodologiesmentioning

confidence: 99%

“…On the contrary, some studies suggested positive associations between higher serum 25(OH)D concentrations and these endpoints (del Puente et al., 2002; Lehtonen‐Veromaa et al., 2002; Ensrud et al., 2009; Breen et al., 2011; Sayers et al., 2012; Steingrimsdottir et al., 2014; Swanson et al., 2015; Zhu et al., 2017; Yang et al., 2019; Bevilacqua et al., 2021; Thompson et al., 2021). For a detailed description of these studies see section 3.3.3.4 of the technical report (Lamberg‐Allardt et al., 2023).…”

Section: Assessmentmentioning

confidence: 99%

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Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

Turck¹,

Bohn²,

Castenmiller³

et al. 2023

EFS2

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Following two requests 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 vitamin D and to propose a conversion factor (CF) for calcidiol monohydrate into vitamin D 3 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D 2 ), cholecalciferol (vitamin D 3 ), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D 3 on serum 25(OH)D concentrations, and for priority adverse health effects of excess vitamin D intake, namely persistent hypercalcaemia/hypercalciuria and endpoints related to musculoskeletal health (i.e. falls, bone fractures, bone mass/density and indices thereof). Based on the available evidence, the Panel proposes a CF for calcidiol monohydrates of 2.5 for labelling purposes. Persistent hypercalciuria, which may be an earlier sign of excess vitamin D than persistent hypercalcaemia, is selected as the critical endpoint on which to base the UL for vitamin D. A lowest-observed-adverse-effect-level (LOAEL) of 250 μg/day is identified from two randomised controlled trials in humans, to which an uncertainty factor of 2.5 is applied to account for the absence of a no-observed-adverse-effect-level (NOAEL). A UL of 100 μg vitamin D equivalents (VDE)/day is established for adults (including pregnant and lactating women) and for adolescents aged 11-17 years, as there is no reason to believe that adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults. For children aged 1-10 years, a UL of 50 μg VDE/day is established by considering their smaller body size. Based on available intake data, European populations are unlikely to exceed the UL, except for regular users of food supplements containing high doses of vitamin D.

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Scientific opinion on the tolerable upper intake level for folate

Turck,

Bohn,

Castenmiller

et al. 2023

EFS2

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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 |

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Preparatory work for the update of the tolerable upper intake levels for vitamin B6

Cited by 6 publications

References 134 publications

Scientific opinion on the tolerable upper intake level for vitamin B6

Scientific opinion on the tolerable upper intake level for vitamin B6

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

Scientific opinion on the tolerable upper intake level for folate

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