House of Commons - Agriculture - Minutes of Evidence

Select Committee on Agriculture Minutes of Evidence

Memorandum submitted by the Ministry of Agriculture, Fisheries and Food (E6)

1. This Memorandum of Evidence, submitted by the Ministry of Agriculture, Fisheries and Food and the Department of Health, sets out the background to the Government's decision to introduce new controls on dietary supplements containing vitamin B6. It also looks at the proposed controls in the wider context of the existing regulatory regime for vitamin and mineral supplements and various developments in this area.

THE LEGISLATIVE FRAMEWORK

2. Products containing added vitamins and minerals which are intended to be consumed may be regarded in law as either foods or medicines.

3. Those products for which claims are made for the treatment or prevention of disease, or which are administered to restore, correct or modify physiological functions, fall within the definition of a medicine and are subject to the requirements of the Medicines Act 1968 and Directive 65/65/EEC. Such products require a marketing authorisation before they can be sold or supplied. Grant of a marketing authorisation requires evidence of quality, safety and efficacy for the indications proposed. The legal classification of a medicine (prescription only, pharmacy or general sale list) determines the route of sale or supply. The control of medicines is the responsibility of the Medicines Control Agency (MCA).

4. Products that do not fall within the scope of the Medicines Act are automatically regarded as foods and are subject to the requirements of the Food Safety Act 1990 and subsidiary legislation. This applies equally, and without distinction, to most foods, regardless of their nature. The main exceptions are foods for which specific compositional standards are laid down (eg weaning foods where, incidentally, the standards include maximum limits certain on vitamins and minerals) and most additives, which are only permitted if it can be shown that they serve a particular technological need and which are subject to an assessment of safety before they are authorised for use.

5. There are basically two types of foods which contain added vitamins and minerals: fortified foods, eg margarine, bread and some breakfast cereals; and dietary supplements. The following paragraphs of this section apply to dietary supplements sold under food law.

6. Dietary supplements have not previously been defined in either UK or EU legislation. However, the following definition has been used in the draft regulations that would introduce the proposed controls on dietary supplements containing vitamin B6:

" "food supplement" means food, in the form of a capsule, tablet, powder or liquid, which—

(a) contains any vitamin, mineral, fatty acid or amino acid;

(b) if consumed, would supplement the intake of vitamins, minerals, fatty acids or amino acids from the diet; and

The term food supplement has been used in this case in preference to dietary supplement in order to be consistent with the terminology used in EU legislation.

7. There is no legislation which applies specifically to dietary supplements as a separate class of foods. Neither are there any statutory limits on the levels of vitamins and minerals that they may contain. They are subject to the general provisions of the Food Safety Act, which effectively require that products should not be injurious to health, and to the Food Labelling Regulations 1996, which control the labelling and advertising of food. Among other things, the Food Labelling Regulations prohibit claims in labelling or advertising that a food has the property of preventing, treating or curing a human disease, and lay down conditions for the use of nutritional claims and certain descriptions which may mislead. Dietary supplements are thus treated in the same way as most other products subject to food law.

PUBLIC PERCEPTION OF VITAMIN AND MINERAL SUPPLEMENTS

8. A study carried out by the Consumers' Association during March 1996 revealed that 40 per cent of people surveyed considered dietary supplements to be medicines and 26 per cent to be foods. These results appear to be borne out by the views expressed in the letters that we have received about the proposed controls on supplements containing vitamin B6, many of which indicate that such products are being used to self treat medical conditions rather than simply to supplement the intake of vitamin B6 from the diet.

GOVERNMENT'S POLICY ON SUPPLEMENTS SOLD UNDER FOOD LAW

9. The Government believes that supplements containing high doses of vitamins and minerals should continue to be available under food law except where they may pose a risk to health. In cases where limits on the levels of vitamins and minerals are considered to be necessary these should be based on safety considerations. The line taken by the UK in discussions on the Codex draft guidelines, and in its response to the EU Commission's discussion paper on the need for harmonised controls for vitamin and mineral supplements, both of which are discussed below in the context of vitamin B6, is consistent with this policy. Many other EU Member States take a much more restrictive view, limiting the level of vitamins and minerals in supplements sold under food law to the Recommended Daily Allowance or a small multiple thereof.

VITAMIN B6

10. Vitamin B6, also called pyridoxine, is a water-soluble vitamin found in a wide variety of food stuffs. It is an essential nutrient which is involved in the metabolism of protein in the body. Vitamin B6 is found in a wide variety of foods, such as cereals and cereal products, potatoes, milk and milk products, meat and meat products, and beers.

11. The Government's Committee on Medical Aspects of Food and Nutrition Policy (COMA), which comprises of independent experts, advised that the Reference Nutrient Intake (see below) for vitamin B6 is 1.2 mg/day for adult women and 1.4 mg/day for adult men. (Infants and children require less.) These levels are comparable with the reference amounts independently established by the EU Scientific Committee for Food, and similar to those used in the United States. The table below gives one example of how an intake of 1.4 mg of vitamin B6 can be obtained from food.

Example foods providing a total of
1.4 mg of B6

Portion (g) B6 (mg)

1 bowl of cornflakes (fortified) 30 0.54

2 slices of wholemeal bread 88 0.1

1 roast breast of chicken 130 0.46

1 scoop mashed potato 120 0.36

1.46

12. The Reference Nutrient Intake (RNI) is the amount of a nutrient that is enough to meet the nutritional needs of almost all healthy people, even those with high needs. In practice it is very unlikely that anyone consuming this much would be deficient. Surveys show that average intakes of vitamin B6 in the UK from food (excluding supplements) are well above the RNI, and that symptoms of deficiency are rare.

13. The RNI is derived from information on the nutritional needs of the healthy population, including evidence of the link between low intakes and clinical or biochemical problems. Such nutrient deficiencies to which all individuals exposed to low intakes would be vulnerable should be distinguished from conditions not caused by low nutrient intake but which might benefit from high doses of a nutrient. Such medicinal uses of nutrients were not used to estimate the RNI. An example is the medicinal use of high doses of vitamin B3 (nicotinic acid) in the treatment of high blood cholesterol; there is no suggestion that high blood cholesterol is caused by deficiency of vitamin B3.

14. Some people believe that much higher doses are effective in treating a range of medical conditions, including Pre-menstrual Syndrome (PMS), although many of the benefits ascribed to vitamin B6 are not proven. It would appear that levels taken by those suffering from PMS typically range between 50 and100 mg per day. However, high doses taken over a prolonged period are associated with peripheral neuropathy, the symptoms of which include nerve damage in the extremities which leads to tingling, numbness and clumsiness, particularly in the hands and feet. Generally, individuals recover once they stop taking vitamin B6 supplements.

REVIEW OF THE SAFETY OF VITAMIN B6

15. The decision to review the safety of vitamin B6 was taken by the previous Government in the light of concerns expressed by the Consumers' Association about the safety of high dose supplements. In this context, the Consumers' Association drew attention to the availability on the market of one particular supplement which contained 100 mg of vitamin B6—over 70 times the RNI for adult men and 80 times that for women. (We have subsequently become aware of supplements being sold as foods that contain daily doses of 250 mg.)

16. Advice on the safety of vitamin B6 was sought from the Department of Health's advisory Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT). The COT is a committee of independent experts whose role is, among other things, to advise the Government on the toxic risk to man of chemicals in food. It is chaired by Professor Frank Woods, Dean of the Medical School at Sheffield University. Its members are all eminent experts in toxicology and related disciplines, including nutrition and pharmacology, who are appointed by the Chief Medical Officer on the basis of their specialist skills and knowledge.

17. The COT considered data on the safety of vitamin B6 on two separate occasions. Prior to the first occasion, the COT Secretariat wrote to the manufacturers of the 100 mg supplement to which the Consumers' Association had referred, inviting them to provide data to aid the COT's consideration. The letter was copied to the Health Food Manufacturers' Association.

18. After its initial consideration of the available data, the COT recommended that the level of vitamin B6 in dietary supplements sold under food law should be limited to 10 mg per daily dose. This advice was referred to the Minister's Food Advisory Committee (FAC), which is made up of independent members from academia, the food industry, food law enforcement and consumer interests. The FAC asked officials to explore with industry the possibility of a voluntary restriction of 10 mg, an idea which the industry rejected because it considered there to be no scientific justification for the proposed limit. Officials also sought the views of other interest groups, including mainstream consumer interests and organisations representing consumers of high-dose supplements and complementary medicine practitioners.

19. In view of the concerns expressed during these consultations the COT invited interested organisations to submit any further data that they might have on the safety of vitamin B6. Having reviewed the evidence for a second time and considered the additional data that had been submitted, the COT concluded that the lowest dose reported to have adverse effects in humans is 50 mg per day. Allowing for a safety factor, and bearing in mind supporting animal toxicity data, the COT once again recommended that the maximum daily intake of vitamin B6 from dietary supplements should be limited to 10 mg per day—over seven times the RNI for adult men and eight times that for adult women. Further information on the scientific basis for the recommendation is given in the statement issued by the COT [see p.48].

20. The FAC returned to this issue in June 1997 after the COT had looked at the additional data supplied by interested parties. It considered the COTs advice alongside the outcome of the consultations with interested parties. It also considered information obtained from industry and by market research on the range of supplements on the market that contained vitamin B6. The FAC endorsed the COTs statement and recommended that the maximum level of vitamin B6 in dietary supplements should be limited to 10 mg per daily dose. It also recommended that supplements containing vitamin B6 should carry a warning about the risk of harmful intakes above this level. A copy of the FAC's statement on this matter is attached [see Annex B p.163].

21. The Government has accepted these recommendations and has issued for consultation the draft regulations that would be required to implement them.

PROPOSED CONTROLS

22. A copy of the proposed regulations is attached at Annex C [not printed] together with a copy of the consultation letter. The controls that they would introduce closely reflect the COT's and FAC's recommendations. They would restrict the level of vitamin B6 in dietary supplements sold under food law to a maximum of 10 mg per daily dose and require such products to carry a warning about the risk of harmful intakes above this level. They would also apply equivalent limits to the amount of vitamin B6 that could legally be added to foods other than supplements in order to prevent these being used as an alternative means of delivering high doses of the vitamin. It is unlikely that this additional control would have a significant effect on products that are currently on the market as it is thought that the amount of vitamin B6 added to foods other than supplements is generally well below the daily requirement.

CONSIDERATION BY THE COMMITTEE ON THE SAFETY OF MEDICINES

23. Because some licensed medicines also contain vitamin B6, the risk:benefit of such products was considered by the Committee on Safety of Medicines (CSM). In the light of the concerns about neurological adverse reactions, the CSM advised that vitamin B6 products sold as medicines with a daily dose of 10 mg should be classified as general sale list (ie they may be sold in shops, supermarkets and health food stores), those providing 11-49 mg daily should be sold under the supervision of a pharmacist, and those providing50 mg and above should be prescription only medicines. These recommendations have been the subject of public consultation as required under the Medicines Act. The Medicines Commission has considered responses to consultation and has concurred with the CSM advice. It is proposed that legislation implementing the measures for sale and supply of medicines containing vitamin B6 should come into effect at the same time as legislation applying to supplements sold under food law.

SUMMARY OF THE EFFECT OF THE PROPOSED CONTROLS ON AVAILABILITY OF VITAMIN B6 PRODUCTS

24. The result of the proposed changes on the availability of supplements and medicines containing vitamin B6 is summarised below.

0-10mg 11-49mg 50mg and above

Foods Medicines Medicines

On sale in shops, supermarkets, health food shops and pharmacies. x x

Sold under the supervision of a pharmacist x

Available only on prescription x

CRITICISM OF THE COT'S CONCLUSIONS AND OF THE PROPOSED CONTROLS

25. Opponents of the proposed controls have questioned the basis of the COT's recommendations and some of the science on which they were based, in particular a study by Dalton and Dalton (which showed adverse effects in humans at intakes of 50mg per day), and the safety factor used when considering animal toxicity data. The Chairman and members of the COT are aware of these criticisms and have considered points made by various parties. However, they have not been persuaded that the issue needs to be looked at for a third time. For its part, the Government has every confidence in the rigour with which the COT reviewed the data on the safety of vitamin B6.

26. The COT's conclusion that the lowest dose of vitamin B6 reported to have adverse effects in humans is 50mg per day is consistent with that of a number of other expert groups. The European Union Scientific Committee on Food has stated that 50mg per day must be regarded as being potentially harmful: a recent study commissioned by the French authorities used this adverse effect level as a basis to derive a maximum safe dose of 5mg per day—half the level proposed by the COT; a limit of 5 mg per daily dose for supplements sold under food law has been proposed by the Swedish Government following a toxicological assessment; and COMA, in its report on Dietary Reference Values, noted that peripheral sensory neuropathy had been reported in women taking 50mg of vitamin B6 per day, and that the safety of high intakes in human pregnancy has not been established.

27. The Government is aware of advice issued by the United States National Academy of Sciences (NAS) on 7 April which recommends a tolerable upper intake level for vitamin B6 of 100 mg per daily dose. Whilst the NAS is an independent organisation, its advice is likely to weigh heavily with the US Government, who will consider the report. The NAS recommendation, and the science on which it is based, will be evaluated by appropriate bodies in the UK and taken into account alongside comments received in reply to the consultation exercise.

28. The Government's decision to introduce controls on dietary supplements containing vitamin B6 has been the subject of a letter-writing campaign. Since the decision was announced in July last year, Ministers have received approximately 13,000 letters on the subject. Most have come from consumers of high-dose supplements, individuals connected with the health food trade and complementary medicine practitioners. Almost all have either opposed, questioned the basis of, or expressed reservations about the proposed controls. However, it is far from clear whether all of those making representations are familiar with the background to the issue. Much of the correspondence from consumers has been in the form of various standard letters distributed in health food shops. Those received have included a number from women who claim that they take 100 mg of vitamin B6 daily to ease the discomfort of pre-menstrual tension.

29. The Government accepts that many people genuinely believe that high doses of vitamin B6 are safe. However, there has been little criticism of the COT's review in the mainstream scientific community, as evidenced by a marked lack of correspondence in the pages of the Lancet and BMJ. Neither have mainstream consumer groups, or organisations such as the Nutrition Society, the British Dietetic Association and the British Medical Association, expressed concern about the proposed controls despite having been given an opportunity to do so.

DEGREE OF RISK

30. Reports of adverse reactions to vitamin B6 outside of the scientific literature are limited. A recent study of toxicological problems resulting from exposure to traditional medicines and food supplements carried out by the Medical Toxicology Unit of Guy's and St Thomas' Hospital noted only one case. However, this was based on a review of the limited data that was readily available to the researchers. As there is no established reporting procedure for adverse effects caused by supplements sold under food law, obtaining data is not easy. Moreover, because the adverse reactions associated with vitamin B6 only occur after prolonged use the link between the two may not be apparent to the user.

31. There are reports under the Medicines Control Agency's voluntary Yellow Card Adverse Drug Reaction reporting scheme of adverse reactions associated with medicinal products containing vitamin B6. Between 1964 and July 1997 there were 649 reports of 1,181 spontaneously-reported adverse reactions associated with such products, of which 16 were fatal. The majority of these were associated with products containing a number of constituents, but 410 reactions were associated with products containing only vitamin B6. This data needs to be treated with a certain amount of caution as the reported reactions might not necessarily have been caused by vitamin B6. Other factors such as the temporal relationship between medicine and reaction, any concomitant medication and the possibility of underlying disease must also be considered. Equally, because the scheme is voluntary, and because most vitamin B6 products are sold and supplied without a doctor's prescription, there is likely to be a significant degree of under-reporting.

32. The Government believes that the proposed controls are a sensible precaution given the advice that it has received and the nature of the risk posed by vitamin B6. They are also proportionate. There is no question of vitamin B6 being banned. Most people will continue to obtain all they need from the food that they eat. Those who believe that they need to supplement their diet will be able to purchase dietary supplements containing daily doses of up to 10 mg from existing outlets. Such products will carry a warning about the risk of harmful effects from consuming high doses of vitamin B6 over extended periods. Products containing up to 49 mg per daily dose licensed as medicines will continue to be available under the supervision of a pharmacist, and 50 mg per daily dose and above on prescription. These arrangements will ensure that consumers have access to information on the risks associated with vitamin B6 that will allow them to make an informed personal choice about its use.

ROLE OF THE EXPERT GROUP ON VITAMINS AND MINERALS

33. The Government announced in December 1997 its intention to establish an ad hoc Expert Group on vitamins and minerals to look at the need for safety-based limits on vitamins and minerals in dietary supplements. Its terms of reference will be to:

— establish principles on which controls for ensuring the safety of vitamin and mineral supplements sold under food law can be based;

— review the levels of individual vitamins and minerals associated with adverse effects;

— recommend maximum levels of intakes of vitamins and minerals from supplements if appropriate;

— report to the Food Advisory Committee.

The group will also be able to advise on the levels of vitamins and minerals in fortified foods.

34. The chairman and members of the new group will be drawn from the existing membership of the COT, FAC, COMA and CSM. Provision has been made for observers nominated by industry, complementary medicine and consumer interest to play a part in the group's work. Interested organisations will also have an opportunity to make submissions on matters that are being considered. It is expected that the group will take 18 months or two years to complete its task and make its report to the FAC. The FAC will consider in the light of the Expert Group's report whether any recommendations should be made to Government or, if it is established by then, the Food Standards Agency. The report will also be considered by the CSM in view of the possible implications of any recommendations for licenced medicines containing vitamins and minerals.

35. The Government does not intend to ask the new group to look again at the evidence on the safety of vitamin B6. This issue has already been considered very carefully by the COT and the FAC on two separate occasions. The Chairman and the members of the COT have also considered criticisms of their review. In view of this the Government does not consider that any useful purpose would be served by asking the Expert Group to undertake a further review.

DEVELOPMENTS IN EU POLICY ON THE ADDITION OF VITAMINS AND MINERALS TO FOOD