How proposals for EU, US and Codex regulation could destroy natural healthcare: the critical need for a new regulatory paradigm

Presentation by Robert Verkerk PhD, executive director, Alliance for Natural Health

American College for Advancement in Medicine (ACAM) Conference, Sheraton Hotel and Marina, San Diego, California

19 November 2004


1.1 The average diet is micronutrient deficient

There is a growing body of evidence demonstrating that significant and probably growing numbers of people in industrialised countries, who rarely suffer from protein/energy malnutrition, are nonetheless micronutrient deficient. Large sectors of the population in developing countries tend to be both macronutrient and micronutrient deficient.

Micronutrient insufficiency is likely to be an under-reported phenomenon in industrialized countries given the continued reliance on Recommended Daily Allowances (RDAs), Recommended Nutritional Intakes, or their equivalents, as the perceived threshold for micronutrient sufficiency, despite RDAs having been discredited scientifically[1] more than a decade ago. Such values appear to be particularly inappropriate as a means of assessing dietary intakes of individuals, or specific population groups1 such as older persons, those with very active (or inactive) lifestyles, those with a high risk of disease, or those suffering some form of chronic, degenerative disease.

If micronutrient levels associated with optimum health were considered as the threshold for micronutrient sufficiency as compared with RDAs, it would be very likely that the majority of western people would be shown to be deficient in at least one, but frequently multiple, micronutrients.

Furthermore, if preventative healthcare is to be embraced by governments, it is essential that the paradigm for assessment of micronutrient sufficiency is altered.

1.2 The need to establish new guidelines for optimum micronutrient intake

A number of workers have attempted to provide guidelines for optimum micronutrient intake, most notable being Drs Emanuel Cheraskin and WM Ringsdorf at the University of Alabama, whose work was published in over 100 papers during the 1960s and 1970s. Since this time, a very large body of new data has become available and there is great need to evaluate it and consolidate findings in new guidelines, which should become health targets both for governments and individuals. These guidelines should at least to some degree be population group specific.

1.3 The basis for health promotion using healthy diets and micronutrient supplements

The diseases contributing to the majority of deaths in industrialized countries, namely cardiovascular disease, cancer, obesity, osteoporosis and diabetes, all of which are the major, current World Health Organisation disease targets worldwide[2], can be ameliorated or prevented by means of nutritional management or intervention. Although this fact is accepted by some governments, and the World Health Organisation itself, barring limited examples (e.g. folic acid vs neural tube defects), there is lack of consensus on the role of micronutrient supplements as a means of bolstering depleted nutritional contents of diets and gaining health promotional benefits as a consequence.

There are many reasons for this, including:

· The varying role of micronutrients in protein/energy malnourished populations, common in many developing countries, as compared with populations which are not protein/energy malnourished, the typical situation in industrialized countries.

· There have been an extremely limited number of properly conducted and controlled studies using appropriate combinations and forms of micronutrients. This is caused, among other reasons, by a) the prohibitive costs of such trials for some companies, with no commercial protection being available for unpatented combinations of natural substances; b) a disincentive to undertake such studies in the event that potent health benefits will be demonstrated, which would encourage regulators to deem the product medicinal. Medicinal licenses/pre-market authorizations are considered excessively costly for most small to medium sized enterprises which dominate innovation in the clinical nutrition field.

· A number of studies have suggested that micronutrient supplementation may confer some health risks to certain population groups (e.g. ATBC[3] and CARET[4] studies). In these cases, there are generally good reasons for the findings which in turn bear little relevance to the mainstream population, while in some cases, the results have been misinterpreted by the study authors or the media publicizing the findings.

· Recent meta-analyses (e.g. antioxidants[5] and Vitamin E[6]) have been used to reinforce very limited and often irrelevant data and are extremely damaging to laypersons and consequently negatively skew public and regulator opinion. Such meta-analyses need to be rebutted and there is a strong case for the conduct of further meta-analyses, using different and more relevant criteria for study inclusion as well as proper interpretation. New research in this field should be prioritized by the natural products industry.

1.4 The nutrient status of diets is declining

There is a growing body of evidence to suggest that the micronutrient content (e.g. selenium, zinc, magnesium, iron, carotenoids, vitamin C) of the average diet in industrialised countries is declining. This appears to be caused by numerous factors including:

· Consumption of increasing amounts of processed foods

· Long-term decline in mineral content of agricultural soils caused by intensification of cultivation methods

· Changes in crop cultivars

· Geographic shifts in produce sources

· Post-harvest treatment of produce and storage methods

In the UK, levels of a range of important dietary nutrients have declined by between 15% and 76% during the period 1940 to 1991 (see successive editions of McCance and Widdowson's The Composition of Foods, Food Standards Agency, UK).[7] The amount of selenium in the European diet has declined dramatically, owing to mineral depletion of agricultural soils over the past decades, as well as owing to changes in wheat supply from North America (high selenium content in soil and wheat products) to Europe (low selenium content). Leading scientists have revealed that selenium levels have declined to such an alarming extent even between 1983 and 1993, that a wide range of health problems are likely to arise in the population as a result of selenium deficiency.[8]

A failure by governments to anticipate the health consequences of micronutrient depletion in the human population is likely to provide a very large, increasing and unnecessary burden on society. Additionally, there are, potentially, legal implications for such neglect in the face of the available evidence.

1.5 Supplemental needs vary individually and geographically

Owing to genetic, cultural, geographic and other differences, the micronutrient requirements between individuals vary considerably. Accordingly it is inappropriate to provide restrictive upper limits via regulation.

In Europe, the health benefits of the Mediterranean diet have been the subject of extensive research and the lower risk of cardiovascular disease and even certain cancers has been attributed to specific micronutrients present in the southern European diet.

One study has shown that the typical French diet, considered by many nutritionists to be exemplary, is seriously deficient in some micronutrients. The authors of the study concluded: “The intakes of magnesium, copper and manganese were between 80 and 100% of the RDA [Recommended Daily Allowance]. For zinc, iron and selenium, the intakes were lower (50-80% of the RDA). The iron deficiency observed in women is serious, and the selenium deficit in men may induce real biochemical subdeficiencies with clinical consequences.”[9]

The relative healthiness of the Mediterranean diet is perhaps one reason that supplemental intake has traditionally been considerably lower in southern European countries, as compared with northern ones. On this basis, it is possible to hypothesise that the technological development of micronutrient supplementation by humans may be an evolutionary adaptation to the low micronutrient status of northern diets, given the difficulty of acquiring consistent intakes during all seasons.


2.1 Harmonisation or safety: which is the ultimate driver of regulation?

Since 1994, the Dietary Supplement Health and Education Act (DSHEA) provided US companies with the freedom to research, develop and innovate a wide array of nutritional products, many of which have conferred substantial benefits on the population. These benefits have spawned the rapid development of clinical nutrition and functional medicine which are increasingly well accepted branches of medicine. Additionally, the evolution of natural products has made self-care approaches to health economically feasible for large numbers of people. Based particularly on disproportionate concerns over the safety of ephedra, much of it hyped by the media, DSHEA is now very likely to be repealed or modified and there are a number of legislative initiatives in progress that would have this effect.

In Europe, there has been a much more varied legislative climate with regard to food (dietary) supplements, with a small number of countries such as the UK and the Netherlands regarding food supplements as a category of food, while the majority have only been prepared to accept low doses of limited nutrients (including synthetic forms of vitamins and inorganic minerals) as foods. Higher dosage nutrients in the majority of European countries are regarded as medicines. The stated intent of the EU Food Supplements Directive is to harmonise laws between the now 25 EU Member States under Article 95 of the European Treaty. However, this Directive, passed in to European law in 2002 and which comes into effect in August 2005, will ban up to 75% of vitamin and mineral forms presently on the UK and Dutch markets.

In contrast to the stated intent of the Directive, it has been stated repeatedly by regulators in Europe that the primary purpose of the law is consumer safety. The media regularly report stories which are intended to raise concerns over the safety of food supplements and other complementary health products, when detailed analysis of the basis of these stories would suggest that at best they are disproportionate, and frequently they are misrepresentations of scientific facts.

In the global context, the Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU) has been attempting to develop international guidelines for vitamins and minerals since 1991 (17th session). In November 2004, these guidelines were finalised. At their centre will be a ‘nutrient-appropriate' risk assessment system which is presently open to consultation.[10] Given that the guidelines are likely to be adopted either on a voluntary or compulsory basis in many countries around the world, it is of key importance that such a risk assessment does not deem dosages and forms of nutrients that give rise to health benefits as excessive and ‘unsafe'. Constraints of existing models are considered in Section 2.3 b) of this paper.

There is a strong suggestion that safety has become the ultimate driver of regulation in this sector, yet there has been very little consideration of the costs, economic and otherwise, of regulation.

2.2 Cost of regulation

The development of any regulation involves cost. The cost must in some capacity be compared against the benefit incurred by the proposed regulation. Of particular relevance to the raft of regulations in the field of supplemental nutrition, there has been almost no attempt by regulators to evaluate total costs or assess impact on health or business.

The costs that should be considered prior to the development of any regulation that is likely to disallow certain micronutrients at beneficial dosage ranges include:

· The economic cost to industry of implementing the regulation, as compared with the benefits derived

· The cost to consumers of restricted choice

· The change in healthcare costs given the impact on consumer self-care and patient access to complementary healthcare products

2.3 Key regulatory problem areas

In this and following sections, reference will be made in particular to EU legislation, given that this legislation is set to become the template for legislation affecting micronutrient supplements worldwide.

a) Regulation of nutrient ingredients

The interrelationship between the EU Food Supplements Directive (FSD) (Directive 2002/46/EC) and the Human Medicines (Pharmaceuticals) Directive (HMD) (Directive 2001/83/EC) is critical to whether ingredients be considered as foods or as medicines.

The FSD has been developed as a ‘total harmonisation' directive, in which all ingredients, initially only vitamins and minerals, but subsequently other forms of nutrients such as amino acids, essential fatty acids, phytonutrients, fibre, etc. are banned unless specifically allowed. In essence, such a regime implies that freedom is prescriptive, rather than residual as is presently the case in countries such as the UK, the Netherlands and the USA.

The FSD has been created as a ‘safe harbour' outside a medicinal regime, in which ‘food supplements', defined appropriately as “concentrated sources of nutrients or other substances with a nutritional or physiological effect” are regarded as a category of food rather than as medicines. However, despite the broad definition, only food supplement ingredients which are specifically listed in the annexes of this Directive will be allowed.

As with many EU directives, the FSD is framework in nature, applying initially to only one category of ingredients, namely vitamins and minerals. The ‘positive list' of allowed vitamin and mineral forms is very limited, excluding 75% of forms currently on the UK and Netherlands markets, most of which are commonly found in foods. In fact, ironically, the ‘positive list' appears to give preference to synthetic forms of vitamins over the natural complexes, and inorganic minerals, over food-form organic ones.

If such a ‘total harmonisation' schema is applied to other nutrients, such as phytonutrients, enzymes, amino acids, pro-/pre-biotics, fibre, fatty acids, etc., it is likely to massively limit availability of ingredients for use in food supplements.

Critically, any ingredient unable to benefit from the ‘safe harbour' conferred by the FSD, would either be banned or would be forced through the drugs regime offered by the HMD. There is accordingly a great risk that a great many ingredients would be banned and not get to the market at all, given the often prohibitive costs of medicinal licensing. It is an irony that a large number of such ingredients would be found commonly in foods and have been shown to be beneficial to human health.

b) Regulation of nutrient dosages

Article 5 of the FSD stipulates the procedure to be implemented to restrict dosages of food supplement ingredients. The approach is identical in principle to that which has been adopted by the Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU).

The procedure involves setting maximum levels per daily dosage, taking account of:

· “Upper safe levels of vitamins and minerals established by scientific risk assessment based on generally accepted scientific data, taking into account, as appropriate, the varying degrees of sensitivity of different consumer groups”;

· “intake of vitamins and minerals from other dietary sources.”

In essence, this would imply that the maximum levels allowed in a supplement would be the difference between the upper safe levels and the amounts consumed in conventional foods.

The principle of setting upper safe levels “by scientific risk assessment based on generally accepted scientific data” is precisely that agreed by the CCNFSDU in July 2004. Although seen as a significant step forward by sectors of the natural products industry, given its significant departure from the previously debated RDA-based levels, such a system is far from a panacea and could seriously restrict access to higher levels of nutrients required for health promotion.

There is a wide range of factors that may contribute to the establishment of inappropriate maximum levels. Some of the most important are considered below:

· Study selection criteria. Study selection criteria for the development of upper safe levels have not been adequately prescribed. There is therefore a risk that key scientific data are ignored, as in the case of the UK Expert Group on Vitamins and Minerals in its 2003 report on Safe Upper Levels of Vitamins and Minerals. Critical missing data were identified by the Alliance for Natural Health in its consultation response to the Food Standards Agency in November 2002.

· Paucity of relevant human data. The bulk of published data from human studies available for use in such risk assessments are derived from studies of interventions with single or very limited numbers of nutrients, frequently in synthetic form. This is almost certainly one reason why some of these intervention studies on supplements have failed to show the same health benefits as studies on foods, where nutrients are delivered in complex combinations. Nutritional science, clinical nutrition, functional medicine and related disciplines are young sciences and there may be insufficient data in the published arena on which to undertake meaningful risk assessments.

· Overuse of animal data. Owing to the paucity of relevant human studies, risk assessments conducted on nutrients tend to be over-reliant on animal data, which have sometimes been shown to be non-applicable to human risk.

· Nutrient categories vs forms. Upper safe levels are proposed for nutrient categories, such as individual vitamins or minerals. However, both toxicity and therapeutic range vary considerably between different forms, so a risk assessment procedure based on nutrient categories would inevitably select for the ‘most toxic' forms of nutrients and thereby may prevent ‘safer' nutrients being used at appropriate dosages. For example sodium selenite and selenate are considered to be more toxic than organically-bound forms of selenium present in food, so the safe upper levels for food forms will be derived, at least partially, from the more toxic, inorganic forms.

· High susceptibility groups. The No Observable Adverse Effect Level (NOAEL), used as a key statistic in the proposed risk assessment protocol, will be set on the basis of the most susceptible population groups. This implies, in some cases, that the majority of the population is unable to consume dosages which are optimum. In the case of beta-carotene, this means that the safety of beta-carotene, even when delivered in its natural context alongside other carotenoids, would be based on two trials on beta-carotene (ATBC and CARET: see Section 1.3), in which marginal adverse effects were noted in smokers and asbestos workers. Effectively, all population groups would be treated as if they were smokers or asbestos-workers.

· Inappropriate estimation of dietary intakes. The proposed upper safe levels (USLs) will be moderated to maximum permitted levels (MPLs) following assessment of dietary intakes. This will take into account highest intake scenarios which might be derived from consumption of fortified foods. There is no evidence that those that consume higher levels of supplemental nutrients also consume the highest levels of fortified foods. Therefore, such an approach is irrational and would prevent those wishing to supplement a healthy whole-food diet with optimum dosages of micronutrients.

· Lack of weighting of adverse effects. In most risk assessments, different types of adverse effect are considered equally, triggering a NOAL or a Lowest Observable Adverse Effect Level (LOAEL). However, flushing from niacin or stomach discomfort from Vitamin C, should not be regarded in the same way as liver toxicity or other serious adverse effects.

· Lack of consideration of benefits. Health benefits of food supplements are ignored in risk assessments, despite the fact that risk/benefit evaluation is a standard criterion used in risk assessment science. At least within the European Union, avoidance of benefits is linked to the inability for any health claims to be made for food supplements, in turn linked to long-standing medicinal laws which state that claims can only be made for medicinal products. Such barriers are irrational given that health benefits can clearly be attributed to foods and food supplements. For benefits to be considered fully, it would be necessary to modify existing definitions for medicinal products (see Section 3.4).

Furthermore, the primitive models being contemplated for risk assessment do not adequately cater for some of the key processes that should properly be considered in any risk assessment. Of particular concern is the treatment of uncertainty and proportionality.

There appears to be inadequate scientific justification for the development of costly risk assessment procedures in the overall context of evidence of adverse effects of nutritional supplements as compared with other sources of risk such as conventional foods.

There are extremely low numbers of reported adverse events related to vitamin and mineral supplementation. In the UK, the Medical Toxicology Unit studies[11] represent a very valuable database of adverse events for pharmaceutical products and food supplements.

Data sets are generally more complete in the US than elsewhere. A very comprehensive survey by the US government[12] showed that approximately 40% of the US population took supplements in the month prior to being interviewed.

The US FDA has on file (data collected over a 20 year period) approximately 2,500 adverse event reports (AERs), including 79 deaths, that may be related to dietary supplements.[13] Forty four of the 79 reported deaths were apparently attributable to ephedrine-containing products.[14]

Further data on the frequency of reported adverse events in the US can be found in reports of the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers, the only comprehensive poisoning surveillance database in the United States. These data show that vitamin and mineral supplements are among the safest products taken orally. They are many times safer than alcoholic beverages, tobacco and even caffeine.[15] These data show clearly that pharmaceutical products present by far the greatest risk of poisoning, as supported by Lazarou et al 1998, see below).

In terms of proportionality, it is important to assess the risks posed by food supplements by comparison with other sources of risk, especially those arising from consumption of conventional foods.

It is estimated that food-borne diseases contribute to approximately 76 million illnesses, 323,000 hospitalisations, and 5,200 deaths in the United States each year.[16]

For comparative purposes, it is worth considering that properly prescribed and administered prescription and over-the-counter drugs are estimated in the USA to cause annually 2.2 million serious adverse events, and some 106,000 deaths.[17]

The concept of risk assessment and setting of USLs and MPLs for vitamins and minerals presupposes that these nutrients taken as supplements or in fortified foods are inherently toxic at levels ingested by the population and are responsible for significant adverse events. As shown above, this is simply not borne out by available data. It can therefore be argued that substantial legislative efforts to control dosages of micronutrients is disproportionate and is an inefficient use of public funds.

Additionally, regulators have not responsibly communicated the nature of risk to the public[18], allowing instead ‘hyped-up' media stories, often with very limited factual, scientific basis, to be the primary flow of information to the public. This is at odds with stated good practice in government in the area of risk and public health.18

c) Regulation of health claims

A further critical legislative problem area is the EU's proposed Nutrition and Health Claims Regulation. Unlike European Directives, which need to be transposed into national laws, European Regulations become law in all 25 European Member States once they have successfully passed through the European Commission, Council of Ministers and Parliament.

In brief, based on the prescriptive freedom posed by many EU laws, the Regulation will ban all health claims, including implied health claims given as product trade names (e.g. Slim ****, Cardio ****, Joint ***) unless they are specifically allowed. In principle, this would not be such a burden if approvals of health claims were within reach of a wide range of companies. Unfortunately, this is not the case and, just as the complex dossiers which theoretically allow derogation of non-positive list ingredients in the FSD have acted as a major obstacle to smaller, innovative companies, the procedure for provision of scientific substantiation of health claims is also extremely onerous. Large transnational companies looking to make health claims for ingredients in food products (e.g. phytosterols in margarine) will almost certainly have little difficulty in providing the necessary data. However, smaller companies, often the key innovators in the natural health field, will simply not have the financial capacity to meet the data requirements.

Bizarrely, under Article 11 of the proposed Regulation, no claims of any sort for any weight loss product would be allowed, and any claims implying psychological or behavioural effects would also be disallowed. This seems completely out of step with the nature of the current healthcare crisis, in which obesity and psychological disorders, both of which have been shown to be in many cases strongly associated with nutritional status, are major and ever-increasing health concerns.


In section 2.3 of this paper, I have addressed some of the major regulatory constraints to the continued development and growth of the nutritional supplement industry (in Europe and beyond) and have considered some of the potential impacts on consumers and patients.

The Alliance for Natural Health has developed a large and growing network of leading-edge interests in natural healthcare. This includes doctors, practitioners, scientists, lawyers, companies and consumers with specific expertise or interests in this broad field.

In the following section, I briefly consider some of the key projects being undertaken by the Alliance for Natural Health to counter the effects of sometimes irrational and disproportionate EU regulation which has the potential to be costly both in economic and health terms.

It is critically important that such regulation is ameliorated given its potential to act as a model or template for regulatory systems in other countries, either through Codex Alimentarius or independently.

3.1 Legal challenge to the EU Food Supplements Directive

Given the urgent need to alter the regime set to govern food supplements in Europe, the Alliance for Nat