The U.S.

Congress, in the Dietary Supplement Health and Education Act (DSHEA) established a framework for regulation of dietary supplements by the U.S. Food and Drug Administration. For dietary supplements, the FDA regulates labeling to limit health claims, but is not empowered to insist on rigorous studies establishing safety before marketing (as would be required for drugs or food additives). This creates a substantial potential risk to the health of the public, and serious adverse effects have been reported from some dietary supplements that are currently being marketed. The author recommends that a new category of dietary supplements, called "nutraceuticals," be established for supplements to be administered at doses that exceed normal human exposure to these agents in foods. Regulations should require that these nutraceuticals be judged safe before they are marketed. Phytochemicals, as plant
components with discrete bio-activities towards animal biochemistry and metabolism are being widely examined for their ability to provide health benefits. It is important to establish the scientific rationale to defend their use in foods, as potential nutritionally active ingredients. Phytochemicals could provide health benefits as: (1) substrates for biochemical reactions; (2) cofactors of enzymatic reactions; (3) inhibitors of enzymatic reactions; (4) absorbents/sequestrants that bind to and eliminate undesirable constituents in the intestine; (5) ligands that agonize or antagonize cell surface or intracellular receptors; (6) scavengers of reactive or toxic chemicals; (7) compounds that enhance the absorption and or stability of essential nutrients; (8) selective growth factors for beneficial gastrointestinal bacteria; (9) fermentation substrates for beneficial oral, gastric or intestinal bacteria; and (10) selective inhibitors of deleterious intestinal bacteria. Such phytochemicals include terpenoids, phenolics, alkaloids and fiber. Research supporting beneficial roles for phytochemicals against cancers, coronary heart disease, diabetes, high blood pressure, inflammation, microbial, viral and parasitic infections, psychotic diseases, spasmodic conditions, ulcers, etc is based on chemical mechanisms using in vitro and cell culture systems, various disease states in animals and epidemiology of humans. However, it must be emphasized that a distinction needs to be drawn between the types of information that can be obtained from studies in vitro, in animals and in humans. Mechanisms of action must certainly be established in vitro; however, the efficacy of these same ingredients with their mechanisms of action, must also be demonstrated in vivo. The rapid growth in the use of phytochemicals in nutraceutical and functional foods requires that the food and pharmaceutical industries face new challenges: in addressing worldwide public concern over the efficacy and safety of supplements and foods claimed to be health-promoting; in government regulations related to safety, labeling and health claims for products that contain phytochemicals; in the manufacturing of foods with different qualities and stabilities; and in marketing issues, particularly as they relate to

We live in an age when good nutrition practiceseat lots of whole grains, fresh fruits and fresh vegetables; hold the fatty meat and hydrogenated vegetable oilsare simple, straightforward and widely available. But visit a well-stocked health food store, pharmacy or supermarket, and youd never know it. The variety of dietary supplements can be overwhelming, with dozens of vitamins, minerals and extracts offered alone and in combinations targeted at every possible intersection of age,
consumers' recognizing added value.

sex and activity. And that selection is a nutritional desert compared to the tropical rain forestlevel diversity of supplements at more specialized stores. Dietary supplements are big business in the U.S.: consumer sales in 2006 were estimated at $22.5 billion, with some 60 percent of Americans taking at least a daily multivitamin. But thanks to a regulatory structure designed more to promote the availability of supplements than to ensure that they deliver on their promises, it can seem impossible to figure out whatif anythingyou should be taking. The options range from the almost appetizing juxtaposition of garlic, cranberry and soy concentrates to the downright macabre glandulars. And if cramming pituitary, prostate and pancreas extracts into a single pill doesnt count as overkill, then surely another product containing vitamins, minerals and most of the biochemical intermediates of the cellular Krebs cycle must. The skeptical browser could be tempted to ask where to find the snake oil aisle. Healthy eating now means more than just eating your greens. New types of foods are increasingly being seen on the shelves of health stores and supermarkets, touting health-boosting effects. These nutritionally or medicinally enhanced foods--so-called nutraceuticals--are proving more and more popular with consumers, empowered by the ability to influence their own health and well-being through what they eat. In tandem, an increasing number of companies are eager to capitalize on the quick financial returns and comparatively relaxed regulation of nutraceuticals, which offer significant advantages over the long development times and high costs of making drugs. However, concerns have been raised as to whether nutraceuticals blur the line between foods and drugs. A recent ruling by the US Food and Drug Administration (FDA; Rockville, MD) banning the dietary supplement Cholestin highlights the need for companies to be scrupulous about the types of claims they make for their products.
The term nutraceutical was coined in 1989 by the Foundation for Innovation in Medicine (New York, US), to provide a name for this rapidly growing area of biomedical research. A nutraceutical was defined as any substance that may be considered a food or part of a food and provides medical or health benefits including the prevention and treatment of disease. Nutraceuticals may range from isolated nutrients, dietary supplements and diets to genetically engineered designer foods, herbal products and processed products such as cereals, soups and beverages. Doubtlessly, many of these products possess pertinent physiological functions and valuable biological activities. The ongoing research will lead to a new generation of foods, which will certainly cause the interface between food and drug to become increasingly permeable. The present accumulated knowledge about nutraceuticals represents undoubtedly a great challenge for nutritionists, physicians, food technologists and food chemists. Public

health authorities consider prevention and treatment with nutraceuticals as a powerful instrument in maintaining health and to act against nutritionally induced acute and chronic diseases, thereby promoting optimal health, longevity and quality of life. Epidemiological studies show a link between the consumption of plant-derived foods and a range of health benefits. These benefits have been associated, at least partially, to some of the phytochemical constituents, and, in particular, to polyphenols. In the last few years, nutraceuticals have appeared in the market. These are pharmaceutical forms (pills, powders, capsules, vials, etc.) containing food bioactive compounds as active principles. The bioactive phytochemicals have become a very significant source for nutraceutical ingredients. Scientific research supports the biological activity of many of these food phytochemicals, but the health claims attributed to the final marketed nutraceutical products have often little or doubtful scientific foundation. This is due to the fact that a lot of the scientific evidence is derived from animal testing and in vitro assays, whereas human clinical trials are scarce and inconclusive. Some key issues such as bioavailability, metabolism, dose/response and toxicity of these food bioactive compounds or the nutraceuticals themselves have not been well established yet. Amongst the phytochemicals, several groups of polyphenols (anthocyanins, proanthocyanidins, flavanones, isoflavones, resveratrol and ellagic acid) are currently used in the nutraceutical industry. In this report, we have reviewed the most recent scientific knowledge on the bioavailability and biological activity of these polyphenols (fact), as well as the health claims (which are not always supported by scientific studies) ascribed to the polyphenols-containing nutraceuticals (fiction). Thein vitro antioxidant capacity, often used as a claim, can be irrelevant in terms of in vivo antioxidant effects. Bioavailability, metabolism, and tissue distribution of these polyphenols in humans are key factors that need to be clearly established in association to the biological effects of these polyphenols-containing nutraceuticals. The future trends of phytochemistry research regarding nutraceuticals are discussed.

Graphical abstract
Nutraceuticals are pharmaceutical forms containing food phytochemicals as active principles. Scientific research supports the biological activity of many of these food phytochemicals, but the health claims attributed to the marketed nutraceuticals have often doubtful scientific foundation. Bioavailability and metabolism are key factors to understand the biological effects of these nutraceuticals.