Global view on functional foods: European perspectives.

In the context of this presentation, European means the European scientific community, which, over the last decade, has been working on the concepts for functional foods, producing a number of documents including a consensus paper, guidelines and scientific publications. The Functional Food Science in Europe (FUFOSE) project has been quite a unique attempt to establish a strong scientific framework to justify the functional food concept, to discover and develop new functional foods that are primarily function-driven, and to substantiate claims scientifically. Being clearly positioned as part of nutrition, the functional food concept is, however, quite distinct from other approaches like food supplementation or food fortification, and functional foods are different from nutraceuticals, pharmafoods, vitafoods and 'alicaments', all terms that are not defined conceptually. Functional foods are food products to be taken as part of the usual diet in order to have beneficial effects that go beyond what are known as traditional nutritional effects. Moreover, these beneficial effects have to be demonstrated scientifically to justify two specific types of claim: the enhanced function claim or the reduction of disease risk claim. Functional food is a key concept for the future of nutrition as a science because it results from the implementation in nutrition of all the basic scientific knowledge that has accumulated over the past two or three decades. To the benefit of public health this progress cannot be ignored, it needs to be recognized fully and used. But, today, functional food is still mainly a scientific concept that serves to stimulate research and the development of new products.

Experimental evidences on the potential of prebiotic fructans to reduce the risk of colon cancer.

Inulin is extracted from the chicory root. It is a set of fructans with its monomers linked by means of beta(2-1) bonds. This linkage cannot be hydrolysed by either pancreatic or by brush border digestive enzymes in the upper intestinal tract of humans. As such the carbohydrates arrive in the colon, where they are fermented by bifidobacteria and other lactic acid producing bacteria, thus enhancing their relative populations in the gut. Recent research in experimental animal models revealed that inulin has significant anticarcinogenic properties. It acts chemopreventively by reducing the incidence of azoxymethane (AOM) - induced aberrant crypt foci and tumours in the colon. These effects may be due to the stimulation of bifidobacteria, which themselves have been shown to act as antigenotoxic in the colon and to reduce AOM-induced tumours. Also fermentation products, including the short-chain fatty acid butyrate, could contribute to the protective effects. In this case a mechanism may be the induction of apoptosis of already transformed cells. The experimental evidence from animal studies and from studies elucidating potential mechanisms strongly supports the possibility that inulin will contribute to reducing risks for colon cancer in humans. In order to obtain more insight into this possibility, human dietary intervention studies relating biomarkers of reduced risk to inulin consumption are needed.

Inulin/oligofructose and anticancer therapy.

The results of our investigations indicate that dietary treatment with inulin or oligofructose incorporated in the basal diet for experimental animals: (i) reduced the incidence of mammary tumors induced in Sprague-Dawley rats by methylnitrosourea; (ii) inhibited the growth of transplantable malignant tumors in mice; and (iii) decreased the incidence of lung metastases of a malignant tumor implanted intramuscularily in mice. Moreover, besides such cancer risk reduction effects, the dietary treatment with inulin or oligofructose significantly potentiated the effects of subtherapeutic doses of six different cytotoxic drugs commonly utilized in human cancer treatment. If confirmed, such dietary treatment with inulin or oligofructose potentiating cancer therapy might become an interesting approach to complement classical protocols of human cancer treatment without any additional risk for the patients.

Prebiotics: preferential substrates for specific germs?

A prebiotic is "a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or the activity of one or a limited number of bacteria in the colon." The premise is based on the hypothesis that the large gut in humans contains bacteria that are beneficial or detrimental to health. Although this generalization probably gives too simplistic a view of gut microbiology, it is a feasible working concept. Currently, food components that seem to exert the best prebiotic effects are inulin-type fructans. In pure culture, most species of bifidobacteria are adapted to the utilization of these nondigestible oligosaccharides but many other bacteria are also capable of metabolizing them. Clearly, these studies of pure bacteria are of limited use unless their results are supported by the results of studies using mixed cultures. Indeed, as many components of the gut microbiota as possible should be measured to indicate a true prebiotic effect. Simple stimulation of bifidobacteria is insufficient to demonstrate an effect; the effects on other gut microorganisms in vivo with human volunteers is necessary. Adjustment of the composition and activities of the colonic microflora so that health-promoting activities are optimized remains key in functional food development. New methods are being applied extensively to human gut microbiology and promise the degree of reliability required to detect subtle changes in colonic microflora composition and to correlate such changes with health benefits. This is a review of the present state of knowledge concerning prebiotics, with emphasis on the criteria used for classification, mechanisms of selective growth stimulation, and physiologic effects.

Concepts and strategy of functional food science: the European perspective.

Recent knowledge supports the hypothesis that, beyond meeting nutrition needs, diet may modulate various functions in the body and play detrimental or beneficial roles in some diseases. Concepts in nutrition are expanding from emphasis on survival, hunger satisfaction, and preventing adverse effects to emphasizing the use of foods to promote a state of well-being and better health and to help reduce the risk of disease. In many countries, especially Japan and the United States, research on functional foods is addressing the physiologic effects and health benefits of foods and food components, with the aim of authorizing specific health claims. The positive effects of a functional food can be either maintaining a state of well-being and health or reducing the risk of pathologic consequences. Among the most promising targets for functional food science are gastrointestinal functions, redox and antioxidant systems, and metabolism of macronutrients. Ongoing research into functional foods will allow the establishment of health claims that can be translated into messages for consumers that will refer to either enhanced function or reduction of disease risk. Only a rigorous scientific approach that produces highly significant results will guarantee the success of this new discipline of nutrition. This presents a challenge for the scientific community, health authorities, and the food industry.

Prebiotics and probiotics: are they functional foods?

A probiotic is a viable microbial dietary supplement that beneficially affects the host through its effects in the intestinal tract. Probiotics are widely used to prepare fermented dairy products such as yogurt or freeze-dried cultures. In the future, they may also be found in fermented vegetables and meats. Several health-related effects associated with the intake of probiotics, including alleviation of lactose intolerance and immune enhancement, have been reported in human studies. Some evidence suggests a role for probiotics in reducing the risk of rotavirus-induced diarrhea and colon cancer. Prebiotics are nondigestible food ingredients that benefit the host by selectively stimulating the growth or activity of one or a limited number of bacteria in the colon. Work with prebiotics has been limited, and only studies involving the inulin-type fructans have generated sufficient data for thorough evaluation regarding their possible use as functional food ingredients. At present, claims about reduction of disease risk are only tentative and further research is needed. Among the claims are constipation relief, suppression of diarrhea, and reduction of the risks of osteoporosis, atherosclerotic cardiovascular disease associated with dyslipidemia and insulin resistance, obesity, and possibly type 2 diabetes. The combination of probiotics and prebiotics in a synbiotic has not been studied. This combination might improve the survival of the bacteria crossing the upper part of the gastrointestinal tract, thereby enhancing their effects in the large bowel. In addition, their effects might be additive or even synergistic.

Comparison of viable cell counts and fluorescence in situ hybridization using specific rRNA-based probes for the quantification of human fecal bacteria.

Conventional cultivation and fluorescence in situ hybridization (FISH) using 16S rRNA-based probes were compared for the enumeration of human colonic bacteria. Groups of common intestinal anaerobic bacteria were enumerated in slurries prepared from fecal samples of three healthy volunteers. To introduce variation between the samples, they were incubated for 48 h in batch culture (anaerobic) fermenters at 37 degrees C, and pure cultures of Bifidobacterium infantis, Clostridium perfringens, or Lactobacillus acidophilus were added. Samples were taken from the fermenters at different times. Total anaerobes, bifidobacteria, bacteroides, clostridia, and lactobacilli were enumerated by both plating and FISH. The results showed that plate counts of total anaerobes, bifidobacteria, lactobacilli and bacteroides were approximately ten-fold lower than the corresponding FISH counts. Numbers of clostridia were higher using the plating method, probably because the clostridia probe used in FISH analyses was designed to only detect part of the genus Clostridium. The introduced variation in the methods could be detected by both methods and was comparable.

Fructo-oligosaccharide malabsorption: benefit for gastrointestinal functions.

Fructo-oligosaccharides or inulin-type fructans are mixtures of oligomers that are composed primarily of beta-D-fructose monomers linked by beta2-1 osidic bonds. They are natural constituents of many edible plants. They resist digestion and are not absorbed in the upper part of the gastrointestinal tract, but they are fermented in the colon. That fermentation produces short-chain fatty acids, which acidify the colonic content; increase bacterial biomass and, consequently, fecal mass; and modify the composition of the microflora, especially by stimulating the growth of bifidobacteria. Fructo-oligosaccharides are thus prebiotics and a method of the Association of Official Analytical Chemists exists to measure them in food products. Because of this behavior in the gastrointestinal tract, inulin-type fructans have a low caloric value compared with carbohydrate absorbed in the small intestine, they improve Ca absorption and Ca balance, and, at least in experimental models, they inhibit the development of chemically induced aberrant crypt foci. Moreover, at a systemic level, they may contribute to modulating lipogenesis and reducing triglyceridemia. The data reviewed in this article support the classification of inulin-type fructans as functional food ingredients for which claims will or should become authorized when data for humans become available.

Inhibitory effect of dietary inulin or oligofructose on the development of cancer metastases.

The possible influence of continuous dietary treatment with 15% inulin or oligofructose on the development of lung metastases of a transplantable liver tumor in young male C3H mice was investigated. Microscopical examination demonstrated a distinct inhibitory effect of this dietary treatment on the development of lung metastases of this tumor. There were 59% of mice bearing lung metastases in the control group, 36% in the inulin fed group and 35% in the oligofructose fed group. The total number of lung metastases was 37 in the control group, 18 in inulin fed and 6 in oligofructose fed mice. Several possible, mechanisms hypothetically involved in this astonishing inhibition of the development of lung metastases by dietary treatment with inulin or oligofructose are discussed.

Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin.

Our previously published results indicated that dietary treatment with oligofructose or inulin inhibited malignant tumor growth in experimental animals. Thus it appeared to be interesting to investigate whether the same treatment could have a positive influence on tumor chemotherapy. The chemotherapy-potentiating effect of 15% oligofructose or inulin incorporated into the basal diet for experimental animals was investigated on a transplantable mouse liver tumor. This dietary adjuvant therapy was started seven days before intraperitoneal transplantation of transplantable liver tumor and was continued until the end of experiments. A single, subtherapeutic dose of six different cytotoxic drugs commonly utilized in treatment of human cancer was intraperitoneally injected 48 hours after tumor transplantation. In all experiments, dietary oligofructose or inulin significantly potentiated the therapeutic effects of six different cytotoxic drugs. Such dietary treatment potentiating cancer chemotherapy could be introduced into classical protocols of human cancer treatment as a new, nontoxic, and easily applicable adjuvant cancer therapy without any supplementary risk for patients.

What is beneficial for health? The concept of functional food.

'Functional Food' is now a very popular term. The conceptual approach developed in the EU-founded FUFOSE (Functional Food Science in Europe) project is rather restrictive, making functional food a food product to be part of the usual dietary pattern. Functional food science that supports the development of functional foods is and must remain part of the science of nutrition. Finally, all that exercise, that extended over the last 3 years, was function-driven because the functions and their modulation are universal, as opposed to a food or food component-driven approach,which is likely to be very much influenced by local, traditional or cultural characteristics.

Concepts in functional foods: the case of inulin and oligofructose.

Recent advances in biosciences support the hypothesis that diet modulates various body functions. Diet may maintain well-being and reduce the risk of some diseases. Such discoveries have led to the concept of "functional food" and the development of the new discipline, i.e., "functional food science." A practical and simple definition of a "functional food" is a food for which a claim has been authorized. The food components to be discussed as potential "functional food ingredients" are the inulin-type fructans, i.e., chicory inulin and oligofuctose. The targets for their effects are the colonic microflora, the gastrointestinal physiology, the immune functions, the bioavailability of minerals, the metabolism of lipids and colonic carcinogenesis. Potential health benefits include reduction of risk of colonic diseases, noninsulin-dependent diabetes, obesity, osteoporosis and cancer. The documentation of such benefits requires scientific evidence that must be evaluated in terms of "health claims." Previous assessments have concluded that, in terms of "functional claims," strong evidence exists for a prebiotic effect and improved bowel habit. The evidence for calcium bioavailability is promising, and positive modulation of triglyceride metabolism is undergoing preliminary evaluation. Scientific research still must be done to support any "disease risk reduction claim," but sound hypotheses do already exist for designing the relevant human nutrition trials.

Caloric value of inulin and oligofructose.

Dietary carbohydrates, which are absorbed as hexose, (glucose, fructose) have a caloric value of 3.9 kcal/g (16.3 kJ/g), and their cellular metabolism produces approximately 38 mol ATP/mol. However, chicory inulin and oligofructose resist digestion and they are not absorbed in the upper part of the gastrointestinal tract. After oral ingestion, they reach the colon intact where they become hydrolyzed and extensively fermented by saccharolytic bacteria, which produce short-chain carboxylic and lactic acids as electron sinks. Depending on both the degree of their colonic fermentation and the assumptions of the model used, the caloric value of such nondigested but fermented carbohydrates varies between 0 and 2.5 kcal/g. Through the catabolism of the absorbed short-chain carboxylic and lactic acids, they may produce up to 17 mol ATP/mol of fermented sugar moiety. Because the daily intake of these dietary carbohydrates is likely to remain relatively small (<10% and probably often not >5% of total daily calorie intake), it is of low relevance nutritionally to give them a precise caloric value. On the basis of biochemical balance charts for carbon atoms, metabolic pathways and energy yields to the host, the caloric value of a fructosyl residue in chicory inulin and oligofructose has been calculated to be approximately 25-35% that of a fully digested and absorbed fructose molecule. For the purpose of food labeling, it is recommended that chicory inulin and oligofructose, like all the other carbohydrates that are more or less completely fermented in the human colon, should be given a caloric value of 1.5 kcal/g (6.3 kJ/g).

Dietary fructans.

Fructan is a general term used for any carbohydrate in which one or more fructosyl-fructose link constitutes the majority of osidic bonds. This review focuses on the fate of inulin-type fructans (namely native chicory inulin, oligofructose produced by the partial enzymatic hydrolysis of chicory inulin, and synthetic fructans produced by enzymatic synthesis from sucrose) in the gastrointestinal tract, as well as on their systemic physiological effects on mineral absorption, carbohydrate and lipid metabolism, hormone balance, and nitrogen homeostasis. The scientific evidence for the functional claims of inulin-type fructans is discussed, as well as their potential application in risk reduction of disease, namely constipation, infectious diarrhea, cancer, osteoporosis, atherosclerotic cardiovascular disease, obesity, and non-insulin dependent diabetes.

Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats.

The addition of oligofructose as a dietary fiber decreases the serum concentration and the hepatic release of VLDL-triglycerides in rats. Because glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper analyzes their putative role in the hypolipidemic effect of oligofructose. Male Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30 d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of rats after eating. GIP and GLP-1 contents were also assayed in small intestine and cecal extracts, respectively. A glucose tolerance test was performed in food-deprived rats. Serum insulin level was significantly lower in oligofructose-fed rats both after eating and in the glucose tolerance test, whereas glycemia was lower only in the postprandial state. IGF-I serum level did not differ between groups. GIP concentration was significantly higher in the serum of oligofructose-fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we have shown that cecal proliferation induced by oligofructose leads to an increase in GLP-1 concentration. This latter incretin could be involved in the maintenance of glycemia despite a lower insulinemia in the glucose tolerance test in oligofructose-fed rats. We discuss also the role of hormonal changes in the antilipogenic effect of oligofructose.

The bifidogenic nature of chicory inulin and its hydrolysis products.

Research data on the bifidogenic effect of beta(2-1)fructans, which at present are commercialized in the U.S., Japan and Europe as food ingredients, are presented. These food ingredients originate from two different sources. Short-chain fructo-oligosaccharides are synthesized from sucrose and are composed of GFn [n beta(2-1) linked fructose moieties bound to a glucose molecule; 2 10 are fermented on average half as quickly as molecules with a DP < 10. All beta(2-1)fructans are bifidogenic and classified as biobiotics.

Prebiotics and synbiotics: concepts and nutritional properties.

The main role of diet is to provide enough nutrients to meet the requirements of a balanced diet, while giving the consumer a feeling of satisfaction and well-being. The most recent knowledge in bioscience supports the hypothesis that diet also controls and modulates various functions in the body, and, in doing so, contributes to the state of good health necessary to reduce the risk of some diseases. It is such an hypothesis which is at the origin both of the concept of 'functional food' and the development of a new scientific discipline of 'functional food science'. In the context of this paper the potential 'functional foods' to be discussed are the prebiotics and the synbiotics. The prebiotics developed so far are the non-digestible oligosaccharides and especially the non-digestible fructans among which chicory fructans play a major role. The chicory fructans are beta (2-1) fructo-oligosaccharides classified as natural food ingredients. They positively affect various physiological functions in such a way that they are already or may, in the future, be classified as functional food ingredients for which claims of functional effects or of disease risk reduction might become authorized. They are classified as prebiotic and have been shown to induce an increase in the number of bifidobacteria in human faecal flora. As part of a synbiotic-type product, they are already bifidogenic at a dose of 2.75 g/d and the effect lasts for at least 7 weeks. The other potential functional effects are on the bioavailability of minerals, but also, and more systemically, on the metabolism of lipids. Potential health benefits may concern reduction of the risk of intestinal infectious diseases, cardiovascular disease, non-insulin-dependent diabetes, obesity, osteoporosis and cancer. However, except for the prebiotic effect, and tentatively the improvement of calcium bioavailability, the evidence to support such effects is still missing in humans though hypotheses already exist to justify nutrition studies.