The healthy option?

Are nutraceuticals food or pharmacy? That is a question that EU and US regulators are grappling with Nick Hawker, from Vitafoods International, discusses the issues involved

Within 10-15 years it is conceivable that people will be able to get their blood pressure medication within a food.This is the view of Gene Grabowski, spokesman for the Grocery Manufacturers of America. And some heavyweight pharmaceutical and food companies, such as GSK, Novartis, Bayer, Johnson & Johnson, Kellogg, Unilever, Pillsbury, Nestle, Valio and Quaker Oats, agree.

They are developing, or have developed, nutraceuticals and functional foods. Millions of consumers already eat functional foods containing nutraceutical ingredients and take nutraceutical dietary supplements. In the US, 47% of men and 50% of women say they take vitamin, mineral, herbal and other supplements every day - that is some 140m consumers.

So what is wrong with adding vitamins, fibre, herbs and extracts to foods that ordinarily do not contain them? Maybe nothing - if research shows that they are safe and that they work. Unfortunately, there is no guarantee of either in many products currently, but this is expected to change with a raft of legislation from both the US and the EU.

Nutraceuticals are bioactive compounds, either naturally occurring or synthesised by chemical or biological means, that have health benefits and can be found in foods (e.g. garlic) or more concentrated in supplement form (e.g. garlic pills).

The bioactive compound may be isolated from a non-food source (e.g. pine tree in pulp production), which is then incorporated, with or without further chemical modification, as an ingredient into a functional food delivery system, such as margarine, salad dressing or a food bar.

benefits and credibility

The developing nutraceuticals industry arises at the intersection of the food, pharmaceutical and agricultural sectors, and is likely to have a significant influence on the future of each - in many ways similar to the widespread impact and rate of development of the biotechnology industry.

Many foods and traditional remedies have offered health benefits. However, they have lacked credibility and acceptance among health professionals; but this is where nutraceuticals differ and how the current movement began.

Calcium, fibre and fish oil sparked the beginnings of the era, and what made this different from the situation in the past, according to Dr Stephen DeFelice, chairman of the Foundation for Innovation in Medicine, was that for the first time clinical trials of such supplements were published in respected journals such as the New England Journal of Medicine and the Journal of the Americal Medical Association. 'Previously, it was inconceivable that the New England Journal of Medicine would publish such things,' he says.

'Nutraceuticals are a dual market,' says De Felice. 'Drugs typically are marketed to doctors, foods to consumers. This is different. It is a doctor market as well as a consumer market, and the basis for the nutraceutical revolution is clinical research.

'You need to have clinical trials, and they must be published in the media so that physicians, scientists and consumers believe it,' he asserts

The nutraceutical business has opened the doors for a variety of partnerships between the food and pharmaceutical industries that would not have been considered years ago. This has provided entry into new consumer markets, with new value propositions. For food companies it has provided a means to meet increased revenue targets through higher market share, penetration into new markets, and the potential for greater margins.

For pharmaceutical companies, it also provides penetration into new consumer markets, as well as a direct channel into life science developments through licensing arrangements that enable them to turn in a profit.

A good example of this type of partnership arose when the McNeil consumer products division of Johnson & Johnson was chosen by the Finnish group Raisio as the worldwide marketing partner for Benecol, the cholesterol-lowering margarine.

Another reason for forming partnerships between food and pharmaceutical companies will be the future potential for creating products that are nutraceutical/drug combinations. Vitamin E presents one such opportunity.

Certain cholesterol-lowering drugs have very strong side effects. Because Vitamin E is effective at lipid reduction, it may be incorporated into a food designed to be used with the drug. In this way, dosage of the drug may be reduced and the side effects minimised, while the overall cholesterol-lowering effect remains the same. 'Increasing the efficacy and safety of drugs will be a big market for nutraceuticals,' says DeFelice. 'That is where it's going to go as drug companies realise the potential.'

So what can be achieved? In the US, Tropicana Products, a division of PepsiCo, increased orange juice sales with a product line extension containing Procter & Gamble's FruitCal - a patented calcium citrate malate clinically tested and shown to be absorbed as well as or better than calcium from milk. The product has proven so popular because consumers have been bombarded with messages about calcium's impact on bone density for years.

They have understood this message, and are eager to increase their consumption. This was an especially easy switch for consumers who were already drinking orange juice, and presented a new delivery vehicle for non-milk lovers and the lactose intolerant.

The big media story in this sector is the global battle which has raged over the cholesterol-lowering margarines Becel/Flora Pro-Activ, launched by Unilever and the Benecol spread which was launched by a partnership between Finland's Raisio Group and Johnson & Johnson. The active ingredients in the Benecol product are stanol esters, which can be extracted from pine tree pulp or soybeans.

The product is scientifically proven to reduce cholesterol and a product health claim to this effect has been allowed under EU regulations - one of the first such claims allowed.

scientifically proven

According to DeFelice the success of the nutraceutical revolution will depend on three factors:

• clinical data;

• support from medical experts;

• the delivery of nutraceutical information to the public and physicians through the mass media.

All three of these elements are essential to the successful creation of an informed public and medical community, and a true clinical research-based nutraceutical and functional foods industry. Other important challenges exist in the areas of regulation and proprietary positioning.

With the exception of those products which fall into one of the categories of dietetic foods given in the European Council Directive on Foods for Particular Nutritional Uses, all nutraceutical products, functional foods, and dietary supplements that are not licensed as medicines have to comply with the relevant EU food legislation.

At present there is no EU legislation specifically relating to food supplements and products have to comply with both the EU legislation on food products plus any individual state's internal legislation on supplements.

As there is no consistency in legislation between the 15 member states, it is almost impossible to market a range of dietary supplements on a pan-European basis as, invariably, formulation changes are required to meet the different national requirements.

In March 2002, the European Parliament voted in favour of a proposed directive that would harmonise national rules on the sale of food supplements in the form of pills and capsules and introduce safety rules for food supplements that contain vitamins and minerals.

Some consider that this proposal plays to the strengths of pharmaceutical companies that have a good record in safety and efficacy testing and complying with primary legislation. Increasingly it is seen that nutraceutical products are supported by the results of clinical research, which dominate the headlines and are being accepted by physicians and the public.

From a purely economic standpoint, companies desire to make health medical claims for nutraceuticals because they increase sales. Since many of the claims at present are not proprietary, however, the vast percentage of industry spending for such products is allocated to promotion instead of research and development.

On the other hand, in the traditional pharmaceutical industry, where exclusive claims are usually created by the patent protection available to new molecular entities, investment in research and development is robust.

A select few in the nutraceuticals industry are lobbying for a change in the regulations to create some new proprietary protection for nutraceutical products and create a research-based industry. An example of what is envisaged is found in the US Orphan Drug Act, designed to facilitate the commercial development and availability of drugs for rare diseases.

Under the Orphan Drug system, testing requirements may be reduced and exclusive claims can be made based on company-sponsored research for a period of seven years after FDA approval - regardless of patent protection. There is no question that the Orphan Drug Act has been successful in creating a new research-driven health industry in the US.

Companies currently considering proprietary protection for their nutraceutical products can look to raw material control, special breeding, special analytics, technology patents, indication patents and proprietary blends.

Of particular interest in this debate is the area of herbal extracts in all their forms. These offer arguably the greatest potential for both food formulators and pharmaceutical companies alike. However, they fall into an increasingly grey area between what is considered a food and what is a medicine.

flavourings directive

Peter Berry Ottaway, director of Berry Ottaway & Associates in the UK, is quick to point out that although the herbals market appears to have great potential, the Biologically Active Principles (BAPs) found in such extracts as the popular St John's Wort, Dong Quai etc could well see them banned within the next year.

The backdrop to such a threat is the directive that governs the use of herbs and spices specifically as flavourings. Debate within the EC is now focused on extending the scope of this Flavouring Directive to cover such substances whether they are acting as flavourings or not; adding new BAPs to the list; and on lowering the upper limits permitted for the presence of BAPs. Interpretation of this legislation in its current form is already ambiguous.

The use of herbal ingredients in new food products is increasing, and consumer knowledge and acceptance of them is growing. According to Zenith International, European consumption of herbal drinks alone has tripled since 1993 and stood at 100m litres in 1999.

Awareness of herbs has increased along with the interest in self medication which is fuelling this category. Although herbs are predominantly used for their flavour, their functional aspects are rising fast, seeing their use extended into yoghurts, breads and health bars.

To illustrate the promise of herbs and other natural-based products, Swiss pharma giant Novartis has registered patent rights in 41 countries for a new malaria drug based on a derivative of the Chinese herb artemisinin - the result of a decade-long collaborative effort with China's Institute of Microbiology and Epidemiology and the Kunming Pharmaceutical Corporation. The drug won its first approval to be sold in Switzerland in January 1999.

In a sense there is nothing surprising about the newfound attention traditional cures are winning. After all, a drug is a drug, and 60% of the best selling prescription drugs in Europe's pharmacies are based on compounds taken directly from Mother Nature's well stocked armamentarium: Aspirin from the willow bark, Taxol from the pacific yew tree, Digitalis from the foxglove plant, Opiates from poppies.

chinese alternatives

But the nature of traditional applications makes research according to orthodox scientific standards difficult. Any given herb contains a multitude of chemical compounds, and Western medicine demands evidence that an ingredient acts in measurable ways on a specific disease in a large number of patients before approval. Contract drug developer Covance opened an office in Beijing a few years ago and hopes to shepherd two traditional Chinese medicines to treat cardiovascular diseases through the FDA approval process.

Even though the cures are widely used in China, Covance reckons that getting even one of them approved as a prescription drug in the US could take eight years and $40-60m. In fact, no traditional Chinese medicine has ever won approval as a drug - natural Chinese products in US are sold as dietary supplements, like vitamins, which come under much less stringent rules.

In spite of the positive indications for entering the nutraceutical market, growth of the category will not happen overnight. Not only do regulatory issues need to be finalised, but scientific and technical issues remain to be addressed and conquered.

Still, no one denies that nutraceuticals are coming - possibly faster than anyone realises.