A risk analysis approach to food supplements safety

As the global discussion on safe upper levels intensifies, David P Richardson looks at the UK where advisory statements on labels are being considered as a proportionate risk management option

Scientific committees around the world in recent years have invested time and resources in assessing the safety of vitamins and minerals. The European Food Safety Authority (EFSA); the Scientific Panel on Dietetic Products, Nutrition and Allergies (formerly the Scientific Committee on Food);1 the US Food and Nutrition Board;2 and, more recently, the UK Food Standards Agency?s (FSA) Expert Group on Vitamins and Minerals (EVM)3 have all undertaken extensive scientific reviews of each essential nutrient in order to establish safe levels of daily intake.

In addition, the food supplements industry has addressed the subject of safety for more than 20 years, publishing its recommendations based on scientific assessments.4,5

Authorities who are responsible for ensuring public health must translate this scientific information into policy, and, where appropriate, legislation. This process is known as risk analysis, and it is particularly challenging with respect to the essential nutrients, as there are clearly two types of risk: that of deficiency and that of adverse effects associated with excessive intakes.

Risk analysis comprises three distinct but clearly linked components. These three elements of risk analysis will underpin European and Codex international regulatory developments relating to maximum levels of vitamins and minerals in food supplements, as well as in foods with added nutrients, respectively.6,7 Any regulatory measure should ensure micronutrient sufficiency and a high level of consumer protection, but it should also facilitate consumer choice and free trade of products sold under food law throughout the European Union.

The EVM risk assessment
The publication of the EVM report in 2003 on safe upper levels of vitamins and minerals in food supplements stimulated much debate by all the interested parties, partly because the published levels differed from those set by the other authorities in the EU and the US.

In some cases, the differences are large. The EVM concluded that, for most food supplements, there were no problems. However, concerns were identified over chromium picolinate and the total intake of dietary vitamin A (preformed retinol). Currently, the Scientific Advisory Committee on Nutrition is considering whether consumer advice is needed on vitamin A intake, and the Committee on Mutagenicity has been asked by the FSA to consider further evidence on whether chromium picolinate is genotoxic.

Although most food supplements contain amounts of vitamins and minerals well below the safe upper levels set by the EVM, a small number of products contain higher amounts, which the group concluded could cause adverse effects in some individuals. These are products containing higher levels of vitamin C, iron, calcium, magnesium, nickel, beta-carotene, nicotinic acid, zinc, manganese, phosphorus and vitamin B6.

Table 1 sets out the definitions of the EVM safe upper levels and guidance levels. These upper levels are:

  • not only safe, but safe by a comfortable margin
  • defined and identified to reflect safety of chronic intakes
  • a value that takes account of identified sensitive populations

They are not:

  • a threshold for adverse effects
  • a ?safety limit?
  • applicable to temporarily elevated intakes

Although there has been a tradition in the UK and EU to separate risk assessment from the process of risk management, there is now recognition that the separation of these two stages of risk analysis may be detrimental to effective outcomes — especially when the interpretation of the scientific evidence is difficult and complex.

For example, the safe upper levels set by different expert committees can differ widely. The phrase ?effective and coherent co-operation between risk assessment, risk management and risk communication functions? is now written into the statutes of the EFSA.

Similarly, the Codex Alimentarius Commission principle of risk analysis recognises that it is an interative process and that interaction between risk managers and risk assessors is essential for practical applications. It also seeks to ensure that conclusions reached by risk managers are proportionate and do not go beyond the scope of the evidence.7 Industry firmly believes that there needs to be closer interaction between these two elements of risk analysis.

Advisory statements
Following the conclusions of its expert group the EVM, the FSA considered that the provision of information on labels would help consumers make informed choices, and that advisory statements would be a proportionate risk management option. The FSA consulted with industry representatives from the UK Council for Responsible Nutrition, the UK Health Food Manufacturers? Association and the Proprietary Association of Great Britain. The objective was to develop advisory information on product labels to reflect the concerns identified by the EVM. The results of these successful discussions resulted in the list of advisory statements, and, for three vitamins, suggested reformulations. (See Table 1, below).

Complete agreement was reached in the cases of vitamin C, iron, calcium, magnesium, nickel, nicotinic acid, zinc and vitamin B6. However, differences of opinion still exist with respect to the thresholds to trigger the advisory statement, as in the cases of beta-carotene and manganese, and for the wording of the advisory statement in the case of phosphorus. The FSA is currently awaiting further advice on phosphorus from the Committee on Toxicology.

Safe Upper Levels represent an intake that can be consumed daily over a lifetime without significant risk to health on the basis of available evidence.

Guidance Levels represent an approximate indication of levels that would not be expected to cause adverse effects but have been derived from limited data and are less secure than safe upper limits.

Both levels are the amounts of vitamins and minerals that susceptible individuals could take on a lifelong basis without medical supervision.
In the case of manganese, industry considers that there is no scientific case to set the threshold at 0.5mg/day and maintains that the threshold for manganese should be 4mg for the whole population. The industry has pointed out that the dietary intake of this essential nutrient appears to have declined over the past 10 years and that, since the publication of the EVM report, the Scientific Panel on Dietetic Products, Nutrition and Allergies has established a new Reference Labelling Value for manganese of 2mg per day. According to the UK National Diet and Nutrition Survey 1998 data, 20 per cent of older men and 27 per cent of older women fall below this value for manganese. 6 The industry has urged the FSA to reconsider its current position and to utilise a ?feedback loop? from the risk managers back to the risk assessors, following the very principle set out by Codex and used by the EU.

Similarly, with respect to beta-carotene, all the scientific evaluations conclude that any potential risk of supplementary intakes is limited to heavy smokers. The scientific evidence is conflicting, and the safe upper limit set at 7mg by the EVM had been derived from data on smokers and extrapolated to a ?No Observed Adverse Effect Level? in smokers. Therefore, industry believes that there is no justification for an advisory statement on food supplements containing between 0 and 7mg beta-carotene.

The international perspective
The UK industry is part of a much wider international trade in food supplements. The whole industry supports the use of risk assessments to determine safe upper levels for vitamins and minerals consistent with the EU and Codex approaches. However, some of the safe upper levels vary widely, and this situation is confusing.

The industry believes that the risk managers in the UK need to consider the totality of the evidence and the risk assessments carried out in the EU and US. In November 2003, Codex Alimentarius stated categorically that risk assessment should seek and incorporate relevant data from different parts of the world and select measures that are no more trade restrictive than necessary. There is also a tendency for risk managers to be overcautious, resulting in a disproportionate escalation of precautions.

Until the EU generates its own maximum levels for all of the vitamins and minerals in food supplements, the FSA and manufacturers are aware that the EVM safe upper levels may change. Moreover, these levels may change as a result of new research publications, as in the case of preformed retinol determined by the EVM.

Despite the various differences of opinion in the international scientific risk assessments and in the formulation of the exact text and conditions for the advisory statements for three nutrients, the FSA and UK industry have made remarkable progress in developing this risk management approach. The FSA and industry have created a ?UK position? on the use of advisory statements incorporating a risk management approach in advance of the EU deliberations on maximum levels of vitamins and minerals sold as food supplements. Whether this approach is acceptable to the European Commission remains to be seen. Nevertheless, the use of advisory statements is supported by the UK government and industry as an important element of safety-based regulation, and as a proportionate risk management measure.

The Council for Responsible Nutrition, the Health Food Manufacturers? Association and the Proprietary Association of Great Britain are disseminating the FSA advice and making it widely known to their memberships.

Ensuring safety is all about minimising risk. The risk managers have to translate the scientific assessments into measures in such a way as to ensure consumer protection and freedom of choice. In all cases, the scientific risk assessments assume that the micronutrient on offer as a food supplement will be consumed daily for an entire life span. In many cases, nutrients such as vitamin C and vitamin B6 are used intermittently.

Clear labelling, including advisory statements and well-informed advice to the consumer, are key in ensuring the safe and effective use of food supplements in the future.

David P Richardson is scientific advisor to the UK Council for Responsible Nutrition. Respond: [email protected] All correspondence will be forwarded to the author.

1. Scientific Committee on Food (2003) Opinions of the Scientific Committee on Food on tolerable upper intake levels. Web site: europa.eu.int/comm/food/fs/sc/scf/index_en.html
2. Food and Nutrition Board (1997, 2000, 2001) Dietary Reference Intakes: Applications in dietary assessment. USA, Washington, DC: National Academy Press.
3. Food Standards Agency Expert Vitamins and Minerals Group, Safe upper levels for vitamins and minerals. 2003. Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6BH.
4. Shrimpton DH. Essential Nutrients in Supplements. 1995. European Federation of Associations of Health Product Manufacturers, Office of the President, PO Box 223 A, Thames Ditton, Surrey KT7 0LT.
5. Shrimpton DH. Vitamins and Minerals: A scientific evaluation of the range of safe intakes. 1997. Council for Responsible Nutrition, 63 Hampton Court Way, Thames Ditton, Surrey KT7 0LT.
6. Department of Health NDNS (National Diet and Nutrition Surveys) People aged 65 years and over. Young people aged 4-18 years. Adults aged 19-64 years. London: The Stationery Office. 1998, 2000, 2001.
7. Codex Alimentarius Commission Joint FAO/WHO Food Standards Programme. Report of the 26th session, Rome, 2003, 30 June-7 July. ALINORM 03/41 2003, p127?131.

Table 1. Label advisory statements and reformulations in response to EVM?s findings1


Threshold to
trigger statement
(recommended daily amount)

Label advisory statement/reformulation

Vitamin C

> 1000mg

"[This amount of vitamin C]* may cause mild stomach upset in sensitive individuals."


> 20mg

"[This amount of iron]* may cause mild stomach upset in sensitive individuals."


> 1500mg

"[This amount of calcium]* may cause mild stomach upset in sensitive individuals."


> 400mg

"[This amount of magnesium]* may cause mild stomach upset in sensitive individuals."


All nickel-containing products

"[Nickel]* may cause a skin rash in sensitive individuals."


> 7mg

See note 1: Encourage reformulation to

Nicotinic acid

> 20mg

Encourage reformulation to nicotinamide. If nicotinic acid is used, label statement: "[This amount of nicotinic acid]* may cause skin flushes in sensitive individuals."


> 25mg

Label statement: "Long-term intake [of this amount of zinc]* may lead to anaemia."


See note 2

Label statement: "Long term intake [of this amount of manganese]* may lead to muscle pain and fatigue."


> 250mg

Label statement: "[This amount of phosphorus]* may cause mild stomach upset in sensitive individuals."(See note 3)

Vitamin B6

> 10mg

Label statement: "Long term intakes [of this amount of vitamin B6]* may lead to mild tingling and numbness."

Vitamin B6

> 100mg

Encourage reformulation to lower daily amount.

* For single nutrient products, the words in square brackets may be deleted.
1. The Food Standards Agency considers that the labels of all food supplements containing beta-carotene should carry the advisory statement ?[Beta-carotene]* should not be taken by heavy smokers.? Industry considers that this should only be on products recommending a daily amount > 7mg. This footnote is for information here; it will not appear on labels.
2. The Food Standards Agency says a daily amount greater than 0.5mg manganese should carry this advisory statement. Industry believes the limit should be 4mg.
3. The Food Standards Agency wants a second sentence ?Long term intake [of this amount of phosphorus] may weaken bones? to be included in the advisory statement for phosphorus. Industry disagrees. The Agency has asked the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) to look at phosphate intake on parathyroid hormone and bone metabolism including new data on phosphate regulation.

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