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Dr Fürst: I would like to emphasize that >400 companies are involved in marketing functional foods. They represent 6% of the total food market, or $7 billion. So functional foods are of enormous commercial value.
Are we satisfied with the existing definition for functional food? Should we try to define functional foods at all? In Europe, we do not look for a definition.
According to the original definition of a nutraceutical, a functional food (tokutei hokenyo shokuhin), or "food for specific health use," is a food—not a capsule or powder—derived from naturally occurring substances. It can and should be consumed as part of the daily diet. When this food is ingested, its particular function is to regulate a specified body process [Hudson BJF. Functional food. New York: Pitman Press, 1990; van den Broek AMWH. Development of the functional food market in Japan. Thesis. Tokyo: Bureau Landbouwraad, 1992]. Subsequently, the terms nutraceuticals and designer food were created as synonyms. Nutraceuticals range from natural nutrients, dietary supplements, herbal products, and processed foods such as cereals, beverages, and soups to genetically engineered designer foods [Caragay AB. Cancer—preventive foods and ingredients. Food Technol 1992;April:65(8)]. Is this definition acceptable, or does it exceed the scope of functional foods? Is it in accord with what we are discussing here, or should we disagree with it?
What about immune function? Should we add immune-promoting substances such as biotechnically produced protein substances enriched with arginine and glutamine? With regard to antioxidants, should we use pharmacologic doses? Or is it possible to use a cocktail such as that used by Chandra [Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992;340:1124–7]? He found significantly improved immune function and significantly decreased frequency of infections with physiologic doses of mixtures of nutrients, vitamins, and minerals.
What about the brain? Docosahexaenoic acid (DHA) is essential in infants, but is it essential in adults? Is it synthesized exclusively in the brain? Is a dietary supplement of DHA useful? Will it be transported to the brain?
Tyrosine is tricky. I think many of the poor results, especially those with parenteral nutrition, are due to its poor solubility (300 mg/L at 20°C in biologic fluids). Is there a question of bioavailability of tyrosine given as a supplement?
Dr Beck's presentation was discussed intensively. I wonder about the role of glutathione. I believe the situation you mentioned is associated with profound depletion of intracellular glutathione stores in muscle and liver. Should we try to supplement or replace glutathione stores by dietary means?
Finally, the discussion about prebiotics and probiotics is fascinating. The intestinal flora is very constant. It is established at birth. Should we try to change it, or is changing it associated with some risk?
Dr Weisburger: With regard to your comments about the solubility of tyrosine, years ago I found that organic solvents given to animals modified the absorption and metabolism of many compounds. Later, I found that simply giving a suspension of many organic chemicals in water would lead to their absorption, because in the body, proteins and various cofactors facilitate the absorption process. My thought, in response to your question about solubility of any functional food, is that in the intestinal tract, many of these substances are absorbed as complexes.
In relation to discussion of brain function, there were no comments on antioxidants. Is it my impression only that some diseases of the brain may stem in part from antioxidant deficiency? We need to think about what we need to do to maintain health. I will reiterate the classic thinking: People need to eat 5–9 servings of vegetables and fruits a day, not just as a supply of vitamins as is so often suggested but also as a source of antioxidants. An additional point in relation to intestinal flora is from my colleague Dr Hara from Japan. He developed a functional product, a polyphenol concentrate from tea. He has data that his intestinal flora changes rather dramatically when these teas are used for some time. When I travel and don't drink tea and don't get fiber, my intestinal flora changes and I become constipated. It is relieved when I go back to my normal high-fiber, tea-drinking diet.
Dr Roberfroid: It is true that the normal flora is established at birth and that if you stop eating substances such as prebiotics, the flora returns to its initial composition. The composition of the flora at the beginning is not necessarily optimal. So it could be important to change it. We know we can manipulate the flora and have the possibility of studying it to determine whether a change is beneficial. I have no information showing that tea changes the flora. It would be interesting to know whether it is beneficial.
We do not know much about the composition of the flora in Europe. We all rely on data from Japan because that is the only country in which extensive studies of this kind have been done. We hope a large survey will be initiated in Europe in 1999 to analyze the composition of the flora in different parts of the continent, because we have different dietary patterns in different countries. We need such studies to determine what percentage of the population has a desirable flora and what percentage does not.
Returning to the question of definition, I would not spend too much time trying to define terms. I much prefer the idea of applying the knowledge that we have and trying to make nutrition a stronger science so as to support better recommendations to improve health.
Dr Fürst: Do you think that previous definitions may influence consumer attitudes?
Dr Roberfroid: Yes, I think we should tell consumers that as we learn more about nutrition, we can give them better advice. We should not speak too much about products. One exception perhaps is in speaking about pharmacologic doses of antioxidants.
Dr Hathcock: I appreciate very much Dr Roberfroid's comment that we need to be careful but not obsessive in delving into definitions when we talk about the health benefits and the scientific evidence to support them. However, definitions are important when regulatory authorities make regulations. Having done that at the FDA [Food and Drug Administration] for a decade, I appreciate the difficulties.
Also, I have been watching the effort of the Codex Alimentarius to make definitions in relation to guidelines for vitamins and minerals. The working definition of functional foods proposed this morning was applied to tea, polyphenolics, garlic, sulfur compounds, vitamin E, and selenium. I want to emphasize a problem with the last 2. Vitamin E and selenium are functional foods when they are used at intakes that are higher than necessary to support the usual essential nutrient functions. Such benefits, unrelated to their essential nutrient functions, deserve attention as effects of functional foods.
For essential nutrients of this type, the Codex Alimentarius, as a regulatory authority, is proposing to set specific limits—for example, limiting such products to 100% or perhaps 200–300% of the RDA [recommended dietary allowance], which would probably not provide the beneficial effects from higher intakes. These restrictive limits would greatly complicate use of vitamin E as a functional food. Thus, we need to make sure that the accepted definitions are good ones. The functional definitions we have seen here in practice this morning seem quite appropriate. We need to make sure that regulatory definitions treat vitamin E and similar nutrients the same way.
Dr Roberfroid: We also have to define with the regulators the requirements for and definitions of claims. I can comment on the way some of the European countries are handling this. In Europe, it is not legal to make any claims, and probably no decision will be made about claims at the European level for the next 5 y. Each country will do its own experiments.
In Belgium, the authority or expert committee has agreed that claims could be allowed. In the first stage, it made a proposal that the authority be informed before the industry is allowed to make any claim. The industry did not agree with this proposal and has been challenged to make a proposal of its own. Recently, the expert committee received a proposal for a code of conduct from the industry that would be signed by all of the food industries in Belgium. The code defined the rules that they will follow before they will make any claims. This proposal would allow the industry to make its own claims.
I believe that the United Kingdom, Holland, and France are working on similar proposals. Thus, in Europe, the industry might be in a position to make claims as long as it has signed such a code of conduct in which rules are defined, especially with regard to scientific evidence. A committee of experts will be set up to be able to react rapidly. If that committee considers that the claim is misleading, one proposal is that the committee will release a different opinion to be published in the lay media, which refutes the claim. This is a good stimulus for the industry to act appropriately.
A committee of experts will be set up to be able to react rapidly. If that committee considers that the claim is misleading, one proposal is that the committee will release a different opinion to be published in the lay media, which refutes the claim. This is a good stimulus for the industry to act appropriately.
Dr Green: Dr. Roberfroid, your comments with regard to fructose polymers recalled the studies of Burkitt and Trowell [Burkitt DP, Trowell HC. Refined carbohydrate foods and disease: some implications of dietary fiber. San Diego: Academic Press, 1975] on the effect of fiber, most of which came from roots, in rural Africans. They remarked that the Africans would typically have 6–7 stools a day, and that their stools did not have a foul odor. Also, while my son was exclusively breast-fed, I noticed that his stools did not smell, but later, when he began to eat regular food, the odor changed. This brings up the question of bifidus. Do you think that Burkitt and Trowell were largely studying probiotic effects of what they called fiber?
Dr Roberfroid: That is possible. We know that many foods eaten in that part of Africa and some parts of Australia have a very high content of inulin—up to 75% of the dry weight.
Dr Arab: In discussing nutritionally induced oxidative stress, Dr Beck, you addressed 2 situations in which pathogenesis was induced in viruses. Has other work been done in relation to higher levels of iron in the diet, which is controversial for other reasons?
Dr Beck: The effect of excess iron was one of the things that Levander wanted to study [unpublished observations]. We did a study involving diets with 3 different levels of iron. Animals given the avirulent virus and fed the diet with the highest amount of iron (1050 ppm) developed myocarditis. So, there probably is a reason to study the effect of iron excess; we are just now beginning to examine these results.
Dr Arab: Dr Fernstrom, it is disappointing that after 20 y of research on nutrients and the brain, the science has been so poorly developed and the studies are so limited. What is your opinion of observations in the cognitive area? Do you think that the 2 studies that have been done primarily on vitamin supplementation and cognitive function are strong enough to lead to further advances?
Dr Fernstrom: I have looked at a few of the studies on cognitive effects. I am not trained as a psychologist, but I believe that there is an absence of remarkable effects. In some of the aging studies involving folate, for example, the effects did not seem dramatic. In other studies, such as dementia treated with choline, although an occasional effect may occur, the body of findings is not particularly impressive. Also, it is difficult to grasp the relevance of some of the tests, such as remembering strings of numbers backwards, when many of the patients have difficulty recalling essential features of their everyday lives.
Dr Fürst: We are speaking a lot about supplementation and not about functional food. Is it a problem that we cannot deal with this subject directly?
Dr Harper: I have a problem with the term functional food; it does not seem to have any specificity. If we talk about vitamin E, we must distinguish between an adequate intake for normal function versus a higher than adequate intake for some second function. Unless we have definitions to distinguish between special health benefits and nutritional needs, I think we shall get into difficulty.
Dr Fernstrom: You are raising the important issue of the pharmacologic use of nutrients. At high doses, nutrients may produce effects unrelated to their actions when they are present only in nutritionally relevant amounts. A further issue is the possibility of toxicologic actions when ingested at extremely high doses.
Dr Milner: In the old days when we used to talk about functional foods, they were nonessential nutrients. Today the discussion is less clear because the functional effects of essential nutrients are included as well.
Dr Harper: That is part of the problem. The other part is the question of distinguishing between a nutritional effect and a pharmacologic effect. My favorite example of this is niacin. There is both an obvious pharmacologic effect in its cholesterol-lowering activity at high levels of intake and a nutritional function at a low level of intake. What about fluoride? Is it a nutrient? A functional food? Is it just a natural product? We are not quite sure. Nevertheless, it is a substance that has an obvious and well-established beneficial health effect. I would separate the health effect from the pharmacologic effect. Thus, I might put protection of fluoride against tooth decay as a nonpharmacologic, but beneficial, health effect, and its effects at higher levels, in staining teeth or causing bone deterioration, as pharmacologic effects.
Dr Fernstrom: If it is not a nutrient per se, then that definition is not valid.
Dr Harper: That's the debate. We are not going to resolve it today, but some of us are not convinced that fluoride is an essential nutrient, yet we are convinced that it has a health effect.
Dr Fernstrom: Would you then call this, by definition, a pharmacologic effect?
Dr Hathcock: From a scientific viewpoint, it may not make much difference what we call it, but from a regulatory viewpoint, it is critically important. The definition can determine whether there is free access to a product or whether access will be by prescription only.
I agree with Dr Harper's example of niacin. There seem to be 2 kinds of functions, 1 of them pharmacologic and the other nutritional. Vitamin C, however, presents a much more difficult problem in terms of definition and regulation. One can obtain perhaps up to 1 g from foods by selecting foods high in vitamin C. Different levels are required for the prevention of scurvy, for maximum activities of various hydroxylation reactions, and the requirement for pharmacokinetic saturation of tissues, the significance of which remains to be determined. In addition, there is the synergism with vitamin E and also inhibition of nitrosamine synthesis in the GI tract. Inhibition of nitrosamine synthesis seems to begin at well below RDA levels and does not reach a maximum until intake reaches 1 g. Where do we draw the line on vitamin C between physiologic and pharmacologic effect?
Dr Craig: When we first began to develop this conference, we were going to call it a conference on functional foods. As we discussed the topic further, we changed the topic to functional food components. Finally, the title evolved to physiologically active food components to acknowledge questions of this type: Might vitamin E as a component of foods at concentrated levels do something beyond its accepted nutrient function? So I am not really concerned, in the scientific sense, that we keep all these in the equation. Dr Milner, do you agree?
Dr Milner: In the Dietary Guidelines Committee several years ago, we proposed quantifying fat intake at 30% of calories. Over the years, the percentage has shifted from 30% to <30%. These are regulatory issues; they have an impact.
I do not like the term functional foods, but I do not know a better term to replace it. I think most of us are looking for a term that indicates a benefit over and beyond the usual nutritional function. I am not sure the term functional food will suffice legally.
Dr Weisburger: Functional is good. Sam Rayburn said, "If it ain't broke, don't fix it."
Dr Milner: Consumers like that term. They don't particularly like the term nutraceutical.
Dr Roberfroid: We must not forget that we are speaking about foods, something that is part of the diet. This does not have to do with pharmacology. There are no drugs in food. We don't eat drugs. We take drugs when we are ill. Food is normally for all the population, although we have foods for special dietary uses. This is a well-defined area in relation to regulation.
Dr Craig: Dr. Fernstrom, what have we learned from iron fortification and its impact on school performance? Can we use that knowledge as a model for our thinking about nutrition and mental performance?
Dr Fernstrom: In reality, we do not know the underlying biochemical and neurophysiologic mechanisms for this benefit of iron supplementation. Hence, we have no rationale at present for the addition of still other dietary supplements to improve on the effect. This is the problem with most such diet-brain connections. For example, current data indicate that we should supplement pregnant women with folic acid during the first trimester to diminish the occurrence of neural tube defects. The treatment works, but we do not know why. We also don't know why essential fatty acid supplementation can improve visual acuity in premature infants. It turns out that it is difficult to identify underlying mechanisms for demonstrated functional effects of nutrients on the brain. There is an element of searching for the "needle in the haystack." It will be some time before we discover the underlying mechanisms and thus some time before we can use such knowledge to improve treatment for functional brain deficits that result from nutritional deficiencies.
Dr Fürst: I would like to propose that there is a diet to which humans are adapted. This diet includes regular exposure to substances on which human metabolism is dependent. Only some of these substances have been labeled essential nutrients. I think many other substances are included in this diet. A natural balance of these substances does not always occur. Perhaps functional foods can be seen as a way to achieve the natural balance.