Functional Foods: The US Perspective: John A Milner
Functional Foods: The US Perspective: John A Milner
Functional Foods: The US Perspective: John A Milner
John A Milner
ABSTRACT Widespread interest in the possibility that state, behavior pattern, and genetic background. People through-
1654S Am J Clin Nutr 2000;71(suppl):1654S–9S. Printed in USA. © 2000 American Society for Clinical Nutrition
FUNCTIONAL FOODS: THE US PERSPECTIVE 1655S
is important, wisdom about how and when to use this informa- belief that foods and their components have unusual health bene-
tion is critical. Unfortunately, consequences other than those fits is one possible explanation for the expanding use of supple-
intended have been documented when intake of foods or their ments among Americans. A large percentage of apparently healthy
components is excessive (3, 4). people residing in the United States are using supplements (14,
15), with use influenced by several factors, including age, sex, and
previous medical condition.
FUNCTIONAL FOOD Coronary heart disease is the most common cause of death
Widespread interest in the possibility that selected foods today. It accounts for <44% of the mortality and much of the
might promote health has resulted in the coining of the generic morbidity in the United States (13). It accounts for two-thirds of
term functional food. The Food and Nutrition Board (FNB) of deaths from heart disease and accounts for <70% of all deaths
the National Academy of Sciences defines a functional food as among persons older than 75 y. As the world’s population
one that encompasses potentially healthful products, including increases in age, concerns will certainly intensify about how best
“any modified food or food ingredient that may provide a health to reduce the risk of death and disability from this disease. A
benefit beyond that of the traditional nutrients it contains” (5). recent estimate put the economic cost of atherosclerotic cardio-
TABLE 1 fruit, vegetables, nuts, and grains; and indoles and isothio-
Partial list of functional foods and their physiologic effects cyanates, both found in cruciferous vegetables.
Food Physiologic effect An enormous number of carotenoids are found throughout the
plant kingdom. These compounds, many of which do not possess
Apple, barley, blackberry, blueberry, carrot, Lipid lowering
vitamin A activity, can influence numerous biological functions
eggplant, oats, garlic, ginger, ginseng, mushroom,
onion, soybean, tea
by serving as antioxidants, modulators of cell growth regulation,
Lemon, apple, cranberry, garlic, beet, cucumber, Enhanced drug regulators of gene expression, and immunoregulators (31, 32).
squash, soybean, cabbage, Brussels sprouts, detoxification Indole-3-carbinol is one of several carotenoids found in cabbage,
cauliflower, kale, broccoli, spinach broccoli, Brussels sprouts, and other Brassica vegetables reported
Ginseng, licorice, oats, parsley Antiinflammatory to exhibit anticarcinogenic properties in experimental animals. In
Cranberry, garlic, onion, green tea Antimicrobial addition, recent studies suggest indole-3-carbinol may be a safe,
Anise, fennel, soybean, cabbage Antiestrogenic well-tolerated, and efficacious treatment for recurrent respiratory
Orange, green tea, garlic Antiproliferative papillomatosis (33).
More than 100 sulfur-containing glycosides known collec-
CHARACTERIZATION OF FOODS
A partial list of foods that have been proposed to provide ben- BIOMARKERS
efits by altering one or more physiologic processes is presented Almost any measurement that reflects a change in a bio-
in Table 1. Nuts, whole grains, fruit, and vegetables contain a chemical process, structure, or function that results from an
variety of compounds associated with reduced risk of heart dis- interaction between a biological system and an environmental
ease, cancer, diabetes, hypertension, and a variety of other med- agent, including a dietary component, can serve as a biomarker.
ical conditions. Although substantial evidence exists that foods Biomarkers are needed not only to assess the value of func-
such as grains, garlic, and soybeans can decrease the risk of both tional foods and their biological components as modifiers of
heart disease and cancer, evidence for other foods is equivocal disease, but also to evaluate their ability to promote health,
(25–27). Widely diverse components in whole grains that may growth, and well-being. Evidence is emerging that several bio-
provide protection by influencing the environment of the gas- markers may be used successfully to distinguish between dis-
trointestinal tract include dietary fiber and other indigestible ease and nondisease states and, in some instances, to predict
components; several types of antioxidants, such as trace miner- future susceptibility to disease (35). Use of such biomarkers as
als and phenolic compounds; and several phytoestrogens that indicators of biological responses to selected foods and food
may alter hormonal homeostasis (28, 29). components is critical because long-term dietary interventions
Cabbage, onions, garlic, celery, cucumber, endive, parsley, are virtually impossible to conduct for numerous reasons,
radish, and legumes are among the nongrains that have been including cost.
reported to have some health benefits (25, 29). The benefits of Several sensitive, reliable biomarkers are likely needed to ade-
functional foods are not limited to natural foods, however, quately assess the benefits and risks associated with increased
because they can result from the generation of novel foods as consumption of specific foods and their bioactive components,
well. For example, low-fat foods may provide some benefits in but without question these biomarkers must not be extremely
reducing the risk of heart disease. Gould (30) suggested that vig- expensive. Intake, biological effect, and susceptibility biomark-
orous lowering of cholesterol by using low-fat foods and lipid- ers will probably be needed to evaluate adequately the effective-
active drugs, controlling hypertension, and abstaining from ness of functional foods and their bioactive components (Figure 1).
smoking stabilizes plaque and markedly reduces coronary events Intake biomarkers are useful for reflecting the amount of food
and angina pectoris, with greater improvement in survival than or metabolite present in cells, tissues, or body fluids. With these
reported for elective, invasive revascularization procedures. biomarkers, differences between absorption and accumulation
Many types of compounds found in foods may be responsible must be considered. Assessment of intake indicators is relatively
for the health benefits attributed to functional foods. Allyl com- straightforward analytically, but their use is complicated by the
pounds, such as those found in garlic and related foods, have need to know the best time for their measurement after con-
been used in various parts of the world not only for aroma and sumption and by variability in rates of metabolism and accumu-
flavor but also as antimicrobials, insect repellants, and modifiers lation across tissues and biological fluids (36).
of the risks of cancer and heart disease (27). Other compounds The usefulness of biological effect biomarkers can also be
that may contribute to observed protection include carotenoids, influenced by several methodologic issues. Among the most
which are found in vegetables and fruit; flavonoids, found in germane of these issues are the association of these biomark-
FUNCTIONAL FOODS: THE US PERSPECTIVE 1657S
ers with causal pathways and their probability of detecting single-gene mutations have been shown to cause problems in
effects coinciding with either the maintenance of health or experimental animal models, such as those that occur in some
progression to a disease state. Effect biomarkers are particu- causes of obesity, the situation in humans is likely to be consider-
larly useful if they can predict a potentially detrimental ably more complex. Interactions among several genes, environ-
response long before it occurs. Unfortunately, at present, few mental factors, and behavior make the search for appropriate gene
biomarkers are universally accepted as being this reliable. The markers especially challenging. Nevertheless, new markers are
range of effect biomarkers required is immense because they being developed that should offer exciting opportunities for clari-
are needed to detect a variety of metabolic events that alter fication of the effect of genes and the environment.
cognitive and physical performance or change the risk of dis- Overall, a variety of biomarkers will probably be needed to
ease. Associating genetic polymorphisms with carcinogen- develop a profile for an individual that reflects the effect of diet
DNA adduct measurements to assess cancer risk is beginning on performance and health. To assess the benefits of foods or
to show promise (37). Other creative approaches will likely be their components, additional attention must be paid to examining
needed to develop a battery of biomarkers that can be used to the variability in response among populations and individuals,
evaluate the effectiveness of the food supply in influencing the the strengths of any association or correlation, the specificity of
overall quality of life. the relation, the reversibility of the response, and the biological
Many biomarkers are beginning to emerge that might be basis for any proposed benefits.
used effectively to monitor the impact of dietary habits on The development and application of biomarkers have enor-
growth and development, including platelet-derived growth mous importance not only in improving health but also in demon-
factor, transforming growth factor, basic fibroblast growth fac- strating the importance of dietary habits. Without question, any
tor, epidermal growth factor, insulin-like growth factor, and information related to a biomarker must be consistent with scien-
hepatocyte growth factor (38). New approaches will be tific standards for statistical significance. Before a claim is made
required to unravel the effects of dietary habits on these and about the benefits of a particular functional food or bioactive
other effect biomarkers. component, the following types of information must be evaluated:
Susceptibility biomarkers are also critical for evaluating the epidemiologic evidence (25%), intervention studies (35%), ani-
merits of changing one’s dietary habits. These biomarkers allow the mal models (25%), and mechanism of action (15%). These esti-
measurement of individual differences associated with genetic mates (percentages in parentheses) of the weighting that might
background, or variation associated with many environmental fac- appropriately be given to each type of evidence in evaluating the
tors (35, 39). The ability of genetic differences to activate or detox- totality of information are presented to initiate debate rather than
ify genotoxic agents is becoming increasingly recognized as an to establish a meaningful basis for evaluation. This is in no way a
appropriate susceptibility biomarker. Many genes, associated prod- novel approach; it was used in preparing 6 consensus statements
ucts, or receptors are now under investigation as markers of sus- about chronic disease (42). The opinion reflected here repre-
ceptibility, including those associated with OB, UCP, erbB-2, ras, sents the thoughts of one individual (with no statistical freedom)
myc, p53, BCL-2, Ki-67, and HNF-1-a (39–41). Although several and, therefore, is not an expression of an official position. The
1658S MILNER
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