European Food Safety Authority (EFSA)

5’-deoxyadenosylcobalamin and methylcobalamin as sources for Vitamin B12 added as a nutritional substance in food supplements[1] - Scientific opinion of the Scientific Panel on Food Additives and Nutrient Sources added to food

Question number: EFSA Q-2005-165, EFSA Q-2005-173, EFSA Q-2006-280

Summary  (0.1Mb)

Opinion  (0.2Mb)

Summary

Following a request from the Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) has been asked to evaluate the safety and bioavailability of methylcobalamin and 5’-deoxyadenosylcobalamin, as sources for vitamin B12 when added for nutritional purposes in food supplements.

The present opinion deals only with the safety and bioavailability of two particular sources of vitamin B12, intended for the general population, to be added in food supplements. While the safety of cobalamin itself, in terms of amounts that may be consumed, is outside the remit of this Panel, it is necessary for the evaluation of the sources to read across from the safety data on the vitamin, because the sources evaluated are vitamers of vitamin B12.

Methylcobalamin may be produced from genetically modified micro-organisms but the Panel concludes that this source is not part of the present opinion because it would require a separate submission under Regulation no 1829/2003.

Vitamin B12 is the name given to a group of related compounds containing cobalt as the central ion in a corrin ring. The cobalt ion can be coordinated to a methyl, 5’-deoxyadenosyl-, hydroxy- or cyano- group. Hydroxycobalamin and cyanocobalamin used in food supplements are transformed in the human body by coordinating with other ligands into methylcobalamin and 5’-deoxyadenosylcobalamin. The latter two are actively involved in endogenous metabolism. Thus, 5’-deoxyadenosylcobalamin and methylcobalamin can be considered to represent naturally occurring endogenous derivatives of vitamin B12.

Assuming that in case of vitamin B12 the ligand will not influence the biological activity of the main molecule significantly, the Panel concludes that methylcobalamin and 5’-deoxyadenosylcobalamin will be bioavailable, and that the metabolic fate and biological distribution of methylcobalamin and 5’-deoxyadenosylcobalamin are expected to be similar to that of other sources of vitamin B12 in the diet.

Furthermore, following absorption, vitamin B12, whatever source, is transformed to either methylcobalamin or 5’-deoxyadenosylcobalamin.
The quantity of methylcobalamin or 5’-deoxyadenosylcobalamin proposed to be used in food supplements amounts to levels up to 500 µg vitamin B12/day for adults.

The petitioner of a second dossier on methylcobalamin indicates that methylcobalamin is intended to be used in food supplements, e.g. in capsules, tablets, ampoules or powders at a proposed level of use of 2 µg/day.

The Scientific Committee on Food (SCF) concluded that average intakes of vitamin B12 are about 2-6 µg/day from food and that intakes up to 32 µg/day have been reported for the total intake including supplements in elderly Dutch subjects. For the UK upper intake levels (97.5th percentile) from food sources were reported to be 22.9 and 17.8 µg/day for males and females respectively. The SCF concluded that upper intake levels from all sources were hardly higher, i.e. 23.0 and 18.2 µg/day respectively.

The proposed levels of use amounting up to 500 µg vitamin B12/day will substantially increase normal daily intake which has been estimated to amount on average to less than 10 µg/day.

According to the SCF, the majority of vitamin B12 that enters the body via nutrition is stored in the liver. Normally the liver stores a vitamin B12 supply of several milligrams of which only 0.1 - 0.2% is lost per day, and therefore is sufficient to cover the daily need for a longer period without supplementation.

The SCF has issued an opinion on the Tolerable Upper Intake level of vitamin B12 and concluded that it is not possible to derive an Upper Intake Level, mainly because no clearly defined adverse effect could be identified. The Panel noted that the proposed levels of use amounting up to 500 µg vitamin B12/day are below the guidance value of 2000 µg/day defined by the UK Expert Group on Vitamins and Minerals (EVM).

The Panel concludes that the use of 5’-deoxyadenosylcobalamin and methylcobalamin as a source of vitamin B12 in food supplements for the general population at the proposed uses and use levels is not of safety concern.

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[1] For citation purposes: Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food on a request from the Commission on adenosylcobalamin and methylcobalamin as sources for Vitamin B12. The EFSA Journal (2008) xxx, 1-2.