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Functional Foods:
Their Role in Disease Prevention
and Health Promotion
A Publication of the Institute of Food Technologists
Expert Panel on Food Safety and Nutrition

Claire M. Hasler, Ph.D.

The tenet "Let food be thy medicine and medicine be thy food," espoused by Hippocrates
nearly 2,500 years ago, is receiving renewed interest. In particular, there has been an
explosion of consumer interest in the health enhancing role of specific foods or
physiologically-active food components, so-called functional foods (Hasler, 1998). Clearly, all
foods are functional, as they provide taste, aroma, or nutritive value. Within the last decade,
however, the term functional as it applies to food has adopted a different connotation -- that of
providing an additional physiological benefit beyond that of meeting basic nutritional needs.

This Scientific Status Summary reviews the literature for the primary plant and animal foods
that have been linked with physiological benefits. Although a plethora of biologically-active
compounds have been identified in this regard (Kuhn, 1998), this review focuses on foods,
rather than specific compounds isolated from foods.

Defining Functional Foods

The term functional foods was first introduced in Japan in the mid-1980s and refers to
processed foods containing ingredients that aid specific bodily functions in addition to being
nutritious. To date, Japan is the only country that has formulated a specific regulatory
approval process for functional foods. Known as Foods for Specified Health Use (FOSHU), these
foods are eligible to bear a seal of approval from the Japanese Ministry of Health and Welfare
(Arai, 1996). Currently, 100 products are licensed as FOSHU foods in Japan. Functional Foods:
Their role in disease prevention and health promotion In the United States, the functional
foods category is not recognized legally. Irrespective of this, many organizations have
proposed definitions for this new and emerging area of the food and nutrition sciences. The
Institute of Medicine's Food and Nutrition Board (IOM/FNB, 1994) defined functional foods as
"any food or food ingredient that may provide a health benefit beyond the traditional nutrients
it contains." Health-conscious baby boomers have made functional foods the leading trend in
the U.S. food industry (Meyer, 1998). Estimates, however, of the magnitude of this market vary
significantly, as there is no consensus on what constitutes a functional food. Decision
Resources, Inc. (Waltham, 1998) estimates the market value of functional foods at $28.9 billion.
More significant, perhaps, is the potential of functional foods to mitigate disease, promote
health, and reduce health care costs.

Functional Foods From Plant Sources

Overwhelming evidence from epidemiological, in vivo, in vitro, and clinical trial data indicates
that a plant-based diet can reduce the risk of chronic disease, particularly cancer. In 1992, a
review of 200 epidemiological studies (Block et al., 1992) showed that cancer risk in people
consuming diets high in fruits and vegetables was only one-half that in those consuming few of
these foods. It is now clear that there are components in a plant-based diet other than
traditional nutrients that can reduce cancer risk. Steinmetz and Potter (1991a) identified more
than a dozen classes of these biologically active plant chemicals, now known as
"phytochemicals."

Health professionals are gradually recognizing the role of phytochemicals in health

enhancement (ADA, 1995; Howard and Kritcheveky, 1997), aided in part by the Nutrition
Labeling and Education Act of 1990 (NLEA). The NLEA required nutrition labeling for most
foods and allowed disease- or health-related messages on food labels.

Oats. Oat products are a widely studied dietary source of the cholesterol-lowering soluble fiber
b-glucan. There is now significant scientific agreement that consumption of this particular
plant food can reduce total and low density lipoprotein (LDL) cholesterol, thereby reducing the
risk of coronary heart disease (CHD). For this, the Food and Drug Administration (FDA)
awarded the first food-specific health claim in January 1997 (DHHS/FDA, 1997), in response to
a petition submitted by the Quaker Oats Company (Chicago, Ill.).

In its health claim petition, the Quaker Oats Company summarized 37 human clinical
intervention trials con-ducted between 1980 and 1995. The majority of these studies revealed
statistically significant reductions in total and LDL-cholesterol in hypercholesterolemic
subjects consuming either a typical American diet or a low fat diet. The daily amount of oat
bran or oatmeal consumed in the above studies ranged from 34 g to 123 g. Quaker Oats
determined that 3 g of b-glucan would be required to achieve a 5% reduction in serum
cholesterol, an amount equivalent to approximately 60 g of oatmeal or 40 g of oat bran (dry
weight). Thus, a food bearing the health claim must contain 13 g of oat bran or 20 g oatmeal,
and provide, without fortification, at least 1.0 g of b-glucan per serving. In February of 1998,
the soluble fiber health claim was ex-tended to include psyllium fiber.

Soy. Soy has been in the spotlight during the 1990s. Not only is soy a high quality protein, as
assessed by the FDA's "Protein Digestibility Corrected Amino Acid Score" method, it is now
thought to play preventive and therapeutic roles in cardiovascular disease (CVD), cancer,
osteoporosis, and the alleviation of menopausal symptoms.

The cholesterol-lowering effect of soy is the most well-documented physiological effect. A 1995
meta-analysis of 38 separate studies (involving 743 subjects) found that the consumption of soy
protein resulted in significant reductions in total cholesterol (9.3%), LDL cholesterol (12.9%),
and triglycerides (10.5%), with a small but insignificant increase (2.4%) in high density
lipoprotein (HDL) cholesterol (Anderson et al., 1995). Linear regression analysis indicated that
the threshold level of soy intake at which the effects on blood lipids became significant was 25
g. Regarding the specific component responsible for the cholesterol-lowering effect of soy,
recent attention has focused on the isoflavones (Potter, 1998). Isoflavones, however, were not
effective in lowering cholesterol in two recent studies (Hodgson et al., 1998; Nestle et al., 1997).
The exact mechanism by which soy exerts its hypocholesterolemic effect has not been fully
elucidated.

On May 4, 1998, Protein Technologies International (PTI, St. Louis, Mo.) petitioned the FDA for
a health claim on soy protein containing products pertaining to reduced risk of CHD. Based on
an effective daily level of 25 g soy protein, PTI proposed that the amount of soy protein
required to qualify an individual food to bear the health claim is 6.25 g with a minimum of
12.5 mg of total isoflavones (aglycone form) per reference amount customarily consumed. On
August 12, the FDA accepted PTI's petition and is in the process of formulating a proposed rule.
Several classes of anticarcinogens have been identified in soybeans, including protease
inhibitors, phytosterols, saponins, phenolic acids, phytic acid, and isoflavones (Messina and
Barnes, 1991). Of these, isoflavones (genistein and daidzein) are particularly noteworthy
because soybeans are the only significant dietary source of these compounds. Isoflavones are
heterocyclic phenols structurally similar to the estrogenic steroids. Because they are weak
estrogens, isoflavones may act as antiestrogens by competing with the more potent, naturally-
occurring endogenous estrogens (e.g., 17b-estradiol) for binding to the estrogen receptor. This
may explain why populations that consume significant amounts of soy (e.g., Southeast Asia)
have reduced risk of estrogen-dependent cancer. However, the epidemiological data on soy
intake and cancer risk are inconsistent at the present time (Messina et al., 1997). To date, there
are no published clinical intervention trials investigating the role of soy in reducing cancer
risk.

Soy may also benefit bone health (Anderson and Garner, 1997). A recent clinical study
involving 66 post-menopausal women conducted at the University of Illinois (Erdman and
Potter, 1997) found that 40 g isolated soy protein (ISP) per day (containing 90 mg total
isoflavones) significantly increased (approximately 2%) both bone mineral content and density
in the lumbar spine after 6 months. The theory that soy may alleviate menopausal symptoms
was prompted by the observation that Asian women report significantly lower levels of hot
flushes and night sweats compared to Western women. Most recently, 60 grams of ISP daily for
3 months reduced hot flashes by 45% in 104 postmenopausal women (Albertazzi et al., 1998).
Although these ob-servations are exciting, there is a significant placebo effect in these studies,
and it is too premature to suggest that soy may substitute for hormone replace-ment therapy.

Flaxseed. Among the major seed oils, flaxseed oil contains the most (57%) of the omega-3 fatty
acid, a-linolenic acid. Recent research, however, has focused more specifically on fiber-
associated compounds known as lignans. The two primary mammalian lignans, enterodiol and
its oxidation product, enterolactone, are formed in the intestinal tract by bacterial action on
plant lignan precursors (Setchell et al., 1981). Flaxseed is the richest source of mammalian
lignan precursors (Thompson et al., 1991). Because enterodiol and enterolactone are
structurally similar to both naturally-occurring and synthetic estrogens, and have been shown
to possess weakly estrogenic and antiestrogenic activities, they may play a role in the
prevention of estrogen-dependent cancers. However, there are no epidemiological data and
relatively few animal studies to support this hypothesis. In rodents, flaxseed has been shown
to decrease tumors of the colon and mammary gland (Thompson, 1995) as well as of the lung
(Yan et al., 1998).

Fewer studies have evaluated the effects of flaxseed feeding on risk markers for cancer in
humans. Phipps et al. (1993) demonstrated that the ingestion of 10 g of flaxseed per day elicited
several hormonal changes associated with reduced breast cancer risk. Adlercreutz et al. (1982)
found that the urinary lignan excretion was significantly lower in postmenopausal breast
cancer patients compared to controls eating a normal mixed or a lactovegetarian diet.

Consumption of flaxseed has also been shown to reduce total and LDL cholesterol
(Bierenbaum et al., 1993; Cunnane et al., 1993), as well as platelet aggregation (Allman et al.,
1995).

Tomatoes. Selected by Eating Well magazine as the 1997 Vegetable of the Year, tomatoes have
received significant attention within the last three years because of interest in lycopene, the
primary carotenoid found in this fruit (Gerster, 1997), and its role in cancer risk reduction
(Weisburger, 1998).
In a prospective cohort study of more than 47,000 men, those who consumed tomato products
10 or more times per week had less than one-half the risk of developing advanced prostate
cancer (Giovannucci et al., 1995). Interestingly, lycopene is the most abundant carotenoid in
the prostate gland (Clinton et al., 1996). Other cancers whose risk have been inversely
associated with serum or tissue levels of lycopene include breast, digestive tract, cervix,
bladder, and skin (Clinton, 1998) and possibly lung (Li et al., 1997). Proposed mechanisms by
which lycopene could influence cancer risk are related to its antioxidant function. Lycopene is
the most efficient quencher of singlet oxygen in biological systems (Di Mascio et al., 1989). The
antioxidant function of lycopene may also explain the recent observation in a multi-center
European study that adipose tissue levels of carotenoids were inversely associated with risk
for myocardial infarction (Kohlmeier et al., 1997b).

Garlic. Garlic (Allium sativum) is likely the herb most widely quoted in the literature for
medicinal properties (Nagourney, 1998). Thus, its not surprising that garlic has ranked as the
second best selling herb in the United States for the past two years (Anon., 1998). The
purported health benefits of garlic are numerous, including cancer chemopreventive,
antibiotic, anti-hypertensive, and cholesterol-lowering properties (Srivastava et al., 1995).

The characteristic flavor and pungency of garlic are due to an abundance of oil-and water-
soluble, sulfur-containing elements, which are also likely responsible for the various medicinal
effects ascribed to this plant. However, intact, undisturbed bulbs of garlic contain only a few
medicinally active components. The intact garlic bulb contains an odorless amino acid, alliin,
which is converted enzymatically by allinase into allicin when the garlic cloves are crushed
(Block, 1992). This latter compound is responsible for the characteristic odor of fresh garlic.
Allicin then spontaneously decomposes to form numerous sulfur-containing compounds, some
of which have been investigated for their chemopreventive activity.

Garlic components have been shown to inhibit tumorigenesis in several experimental models
(Reuter et al., 1996). However, additional reports have shown garlic to be ineffective.
Inconclusive results are likely due to differences in the type of garlic compounds or
preparations used by various investigators. Considerable variation in the quantity of
organosulfur compounds available in fresh and commercially available garlic products has
been demonstrated (Lawson et al., 1991).

Several epidemiologic studies show that the garlic may be effective in reducing human cancer
risk (Dorant et al., 1993). A relatively large case-control investigation conducted in China
showed a strong inverse relationship between stomach cancer risk and in-creasing allium
intake (You et al., 1988). More recently, in a study of more than 40,000 postmenopausal women,
garlic consumption was associated with nearly a 50% reduction in colon cancer risk
(Steinmetz et al., 1994). Not all epidemiological studies, however, have shown garlic to be
protective against carcinogenesis. A 1991 review of 12 case-control studies (Steinmetz and
Potter, 1991b), found that eight showed a negative association, one showed no association, and
three studies showed a positive association. A more recent review of 20 epidemiological
studies (Ernst, 1997) suggests that allium vegetables, including onions, may confer a protective
effect on cancers of the gastrointestinal tract.

Garlic has also been advocated for the prevention of CVD, possibly through antihypertensive
properties. According to Silagy and Neil (1994a), however, there is still insufficient evidence to
recommend it as a routine clinical therapy for the treatment of hypertensive subjects. The
cardioprotective effects are more likely due to its cholesterol-lowering effect. In a meta-
analysis, Warshafsky et al. (1993) summarized the results of five randomized, placebo-
controlled clinical trials, involving 410 patients. They showed that an average of 900 mg
garlic/day (as little as one half to one clove of garlic) could decrease total serum cholesterol
levels by approximately 9%. In a second meta-analysis involving 16 trials, Silagy and Neil
(1994b) reported that 800 mg garlic/day reduced total cholesterol levels by 12%. The validity of
both of these reports, however, is reduced by methodological shortcomings, including the fact
that dietary intake, weight, and/or exogenous garlic ingestion was not always well-controlled.
In a recent multi-center, randomized, placebo-controlled trial in which dietary assessment and
supervision were strictly controlled, 12 weeks of garlic treatment was ineffective in lowering
cholesterol levels in subjects with hypercholesterolemia (Isaacsohn et al., 1998). It is currently
unclear which component in garlic is responsible for its cholesterol-lowering effect.

Broccoli and other Cruciferous Vegetables. Epidemiological evidence has associated the
frequent consumption of cruciferous vegetables with decreased cancer risk. In a recent review
of 87 case-control studies, Verhoeven et al. (1996) demonstrated an inverse association
between consumption of total brassica vegetables and cancer risk. The percentages of case-
control studies showing an inverse association between consumption of cabbage, broccoli,
cauliflower, and Brussels sprouts and cancer risk were 70, 56, 67, and 29%, respectively.
Verhoeven et al. (1997) attributed the anticarcinogenic properties of cruciferous vegetables to
their relatively high content of glucosinolates.

Glucosinolates are a group of glycosides stored within cell vacuoles of all cruciferous
vegetables. Myrosinase, an enzyme found in plant cells, catalyzes these compounds to a
variety of hydrolysis products, including isothiocyanates and indoles. Indole-3 carbinol (I3C) is
currently under investigation for its cancer chemopreventive properties, particularly of the
mammary gland. In addition to the induction of phase I and II detoxification reactions, I3C
may reduce cancer risk by modulating estrogen metabolism. The C-16 and C-2 hydroxylations
of estrogens involve competing cytochrome P-450-dependent pathways, each sharing a
common estrogen substrate pool. Studies suggest that the increased formation of 2-
hydroxylated (catechol) estrogen metabolites relative to 16-hydroxylated forms, may protect
against cancer, as catechol estrogens can act as antiestrogens in cell culture. In contrast, 16-
hydroxyestrone is estrogenic and can bind to the estrogen receptor. In humans, I3C
administered at 500 mg daily (equivalent to 350-500 g cabbage/day) for 1 week significantly
increased the extent of estradiol 2-hydroxylation in women (Michnovicz and Bradlow, 1991),
suggesting that this compound may be a novel approach for reducing the risk of breast cancer.
However, since I3C has also been shown to enhance carcinogenesis in vivo, caution has been
urged be-fore proceeding with extensive clinical trials (Dashwood, 1998), although such phase
I trials are currently ongoing (Wong et al., 1998).

Although a wide variety of naturally occurring and synthetic isothiocyanates have been shown
to prevent cancer in animals (Hecht, 1995), attention has been focused on a particular
isothiocyanate isolated from broccoli, known as sulforaphane. Sulforaphane has been shown
to be the principal inducer of a particular type of Phase II enzyme, quinone reductase. Fahey et
al., (1997) recently demonstrated that 3-day-old broccoli sprouts contained 10-100 times higher
levels of glucoraphanin (the glucosinolate of sulforaphane) than did corresponding mature
plants. However, in view of the importance of an overall dietary pattern in cancer risk
reduction, the clinical implications of a single phytochemical in isolation has been questioned
(Nestle, 1998).

Citrus Fruits. Several epidemiological studies have shown that citrus fruits are protective
against a variety of human cancers. Although oranges, lemons, limes, and grapefruits are a
principal source of such important nutrients as vitamin C, folate, and fiber, Elegbede et al.
(1993) have suggested that another component is responsible for the anticancer activity. Citrus
fruits are particularly high in a class of phytochemicals known as the limonoids (Hasegawa
and Miyake, 1996).

Over the last decade, evidence has been accumulating in support of the cancer preventative
effect of limonene (Gould, 1997). Crowell (1997) showed this compound to be effective against
a variety of both spontaneous and chemically- induced rodent tumors. Based on these
observations, and because it has little or no toxicity in humans, limonene has been suggested
as a good candidate for human clinical chemoprevention trial evaluation. A metabolite of
limonene, perrillyl alcohol, is currently undergoing Phase I clinical trials in patients with
advanced malignancies (Ripple et al., 1998).

Cranberry. Cranberry juice has been recognized as efficacious in the treatment of urinary
tract infections since 1914, when Blatherwick (1914) reported that this benzoic acid-rich fruit
caused acidification of the urine. Recent investigations have focused on the ability of
cranberry juice to inhibit the adherence of Escherichia coli to uroepithelial cells (Schmidt and
Sobota, 1988). This phenomenon has been attributed to two compounds: fructose and a
nondialyzable polymeric compound. The latter compound, subsequently isolated from
cranberry and blueberry juices (Ofek et al., 1991), was found to inhibit adhesins present on the
pili of the surface of certain pathogenic E. coli.

Avorn et al. (1994) published the results of the first randomized, double-blind, placebo-
controlled clinical trial de-signed to determine the effect of a commercial cranberry juice
beverage on urinary tract infections. One hundred-fifty three elderly women consuming 300
mL cranberry beverage per day had significantly reduced (58%) incidence of bacteriuria with
pyuria compared to the control group after six months. Based on the results of these studies,
prevailing beliefs about the benefits of cranberry juice on the urinary tract appear to be
justified.

Tea. Tea is second only to water as the most widely consumed beverage in the world. A great
deal of attention has been directed to the polyphenolic constituents of tea, particularly green
tea (Harbowy and Balentine, 1997). Polyphenols comprise up to 30% of the total dry weight of
fresh tea leaves. Catechins are the predominant and most significant of all tea polyphenols
(Graham, 1992). The four major green tea catechins are epigallocatechin-3-gallate,
epigallocatechin, epicatechin-3-gallate, and epicatechin.

In recent years, there has been a great deal of interest in pharmacological effects of tea (AHF,
1992). By far, most re-search on health benefits of tea has focused on its cancer
chemopreventive effects, although the epidemiological studies are inconclusive at the present
time (Katiyar and Mukhtar, 1996). In a 1993 review of 100 epidemiological studies (Yang and
Wang, 1993), approximately 2/3 of the studies found no relationship between tea consumption
and cancer risk, while 20 found a positive relation-ship and only 14 studies found that tea
consumption reduced cancer risk. A more recent review suggests that benefits from tea
consumption are restricted to high intakes in high-risk populations (Kohlmeier et al., 1997a).
This hypothesis supports the recent finding that the consumption of five or more cups of green
tea per day was associated with decreased recurrence of stage I and II breast cancer in
Japanese women (Nakachi et al., 1998).

In contrast to the inconclusive results from epidemiological studies, research findings in

laboratory animals clearly support a cancer chemopreventive effect of tea components. In fact,
Dreosti et al.(1997) stated that "no other agent tested for possible chemoprevention effects in
animal models has elicited such strong activity as tea and its components at the concentrations
usually consumed by humans."
There is some evidence that tea consumption may also reduce the risk of CVD. Hertog and
coworkers (1993) reported that tea consumption was the major source of flavonoids in a
population of elderly men in the Netherlands. Intake of five flavonoids (quercetin, kaempferol,
myricetin, apigenin, and luteolin), the majority of which was derived from tea consumption,
was significantly inversely associated with mortality from CHD in this population. Although
several other prospective studies have demonstrated a substantial reduction in CVD risk with
tea consumption, the evidence is not presently conclusive (Tijburg et al., 1997).

Wine and Grapes. There is growing evidence that wine, particularly red wine, can reduce the
risk of CVD. The link between wine intake and CVD first became apparent in 1979 when St.
Leger et al. (1979) found a strong negative correlation between wine intake and death from
ischemic heart disease in both men and women from 18 countries. France in particular has a
relatively low rate of CVD despite diets high in dairy fat (Renaud and de Lorgeril, 1992).
Although this "French Paradox" can be partly explained by the ability of alcohol to in-crease
HDL cholesterol, more recent investigations have focused on the non-alcohol components of
wine, in particular, the flavonoids.

The high phenolic content of red wine, which is about 20-50 times higher than white wine, is
due to the incorporation of the grape skins into the ferment-ing grape juice during production.
Kanner et al. (1994) showed that the black seedless grapes and red wines (i.e., Cabernet
Sauvignon and Petite Sirah) contain high concentrations of phenolics: 920, 1800, and 3200
mg/L, respectively, while green Thomson grapes contain only 260 mg/kg phenolics. Frankel and
coworkers (1993) attributed the positive benefits of red wine to the ability of phenolic
substances to prevent the oxidation of LDL, a critical event in the process of atherogenesis.

Although the benefits of wine consumption on CVD risk reduction seem promising, a recent
prospective study of 128,934 adults in Northern California concluded that the benefits of
alcohol consumption on coronary risk were not especially associated with red wine (Klatsky et
al., 1997). Moreover, a note of caution is in order, as alcoholic beverages of all kinds have been
linked to increased risk of several types of cancer, including breast cancer (Bowlin et al., 1997).
Moderate wine consumption has also been associated with a de-creased risk of age-related
macular degeneration (Obisesan et al., 1998).

Those who desire health benefits of wine without potential risk may wish to consider alcohol-
free wine, which has been shown to increase total plasma antioxidant capacity (Serafini et al.,
1998). Furthermore, Day et al. (1998) showed that commercial grape juice is effective in
inhibiting the oxidation of LDL isolated from human subjects. Red wine is also a significant
source of trans-resveratrol, a phytoalexin found in grape skins (Creasy and Coffee, 1988).
Resveratrol has also been shown to have estrogenic properties (Gehm et al., 1997) which may
explain in part the cardiovascular benefits of wine drinking, and it has been shown to inhibit
carcinogenesis in vivo (Jang et al., 1997).

Functional Foods From Animal Sources

Although the vast number of naturally occurring health-enhancing substances are of plant
origin, there are a number of physiologically-active components in animal products that
deserve attention for their potential role in optimal health.

Fish. Omega-3 (n-3) fatty acids are an essential class of polyunsaturated fatty acids (PUFAs)
derived primarily from fish oil. It has been suggested that the Western-type diet is currently
deficient in n-3 fatty acids, which is reflected in the current estimated n-6 to n-3 dietary ratio of
20:25-1, compared to the 1:1 ratio on which humans evolved (Simopoulos, 1991). This has
prompted researchers to examine the role of n-3 fatty acids in a number of diseases --
particularly cancer and CVD -- and more recently, in early human development.

That n-3 fatty acids may play an important role in CVD was first brought to light in the 1970s
when Bang and Dyerberg (1972) reported that Eskimos had low rates of this disease despite
consuming a diet which was high in fat. The cardioprotective effect of fish consumption has
been observed in some prospective investigations (Krumhout et al., 1985), but not in others
(Ascherio et al., 1995). Negative results could be explained by the fact that although n-3 fatty
acids have been shown to lower triglycerides by 25-30%, they do not lower LDL cholesterol. In
fact, a recent review of 72 placebo- controlled human trials, showed that n-3 fatty acids
increased LDL cholesterol (Harris, 1996).

Although eating large amounts of fish has not unequivocally been shown to reduce CVD risk in
healthy men, consumption of 35 g or more of fish daily has been shown to reduce the risk of
death from nonsudden myocardial infarction in the Chicago Western Electric Study (Daviglus
et al., 1997), and as little as one serving of fish per week was associated with a significantly
reduced risk of total cardiovascular mortality after 11 years in more than 20,000 U.S. male
physicians (Albert et al., 1998).

Dairy Products. There is no doubt that dairy products are functional foods. They are one of
the best sources of calci-um, an essential nutrient which can prevent osteoporosis and possibly
colon cancer. In view of the former, the National Academy of Sciences recently increased
recommendations for this nutrient for most age groups. In addition to calcium, however,
recent research has focused specifically on other components in dairy products, particularly
fermented dairy products known as probiotics. Probiotics are defined as "live microbial feed
supplements which beneficially affect the host animal by improving its intestinal microbial
balance" (Fuller, 1994).

It is estimated that over 400 species of bacteria, separated into two broad categories, inhabit
the human gastrointestinal tract. The categories are: those considered to be beneficial (e.g.,
Bifidobacterium and Lactobacillus and those considered detrimental (e.g., Enterobacteriaceae
and Clostridium spp.). Of the beneficial microorganisms traditionally used in food
fermentation, lactic acid bacteria have attracted the most attention (Sanders, 1994). Although a
variety of health benefits have been attributed to probiotics, their anticarcinogenic,
hypocholesterolemic and antagonistic actions against enteric pathogens and other intestinal
organisms have received the most attention (Mital and Garg, 1995).

The hypocholesterolemic effect of fermented milk was discovered more than 30 years ago
during studies con-ducted in Maasai tribesmen in Africa (Mann et al., 1964). The Maasai have
low levels of serum cholesterol and clinical coronary heart disease despite a high meat diet.
However, they consume daily 4 to 5 L of fermented whole milk. Although a number of human
clinical studies have assessed the cholesterol-lowering effects of fermented milk products
(Sanders, 1994), results are equivocal. Study outcomes have been complicated by inadequate
sample sizes, failure to control nutrient intake and energy expenditure, and variations in
baseline blood lipids.

More evidence supports the role of probiotics in cancer risk reduction, particularly colon
cancer (Mital and Garg, 1995). This observation may be due to the fact that lactic acid cultures
can alter the activity of fecal enzymes (e.g., b-glucuronidase, azoreductase, nitroreductase) that
are thought to play a role in the development of colon cancer. Relatively less attention has
been focused on the consumption of fermented milk products and breast cancer risk, al-
though an inverse relationship has been observed in some studies (Talamini et al., 1984; van't
Veer et al., 1989).

In addition to probiotics, there is growing interest in fermentable carbohydrates that feed the
good microflora of the gut. These prebiotics, defined by Gibson and Roberfroid (1995) as
"nondigestible food ingredients that beneficially affect the host by selectively stimulating the
growth and/or activity of one or a limited number of bacteria in the colon and thus improves
host health," may include starches, dietary fibers, other non-absorbable sugars, sugar alcohols,
and oligosaccharides (Gibson et al., 1996). Of these, oligosaccharides have received the most
attention, and numerous health benefits have been attributed to them (Tomomatsu, 1994).
Oligosaccharides consist of short chain polysaccharides composed of three and 10 simple
sugars linked together. They are found naturally in many fruits and vegetables (including
banana, garlic, onions, milk, honey, artichokes). The prebiotic concept has been further
extended to encompass the concept of synbiotics, a mixture of pro- and prebiotics (Gibson and
Roberfroid, 1995). Many synbiotic products are currently on the market in Europe.

Beef. An anticarcinogenic fatty acid known as conjugated linoleic acid (CLA) was first isolated
from grilled beef in 1987 (Ha et al., 1987). CLA refers to a mixture of positional and geometric
isomers of linoleic acid (18:2 n-6) in which the double bonds are conjugated instead of existing
in the typical methylene interrupted configuration. Nine different isomers of CLA have been
reported as occurring naturally in food. CLA is unique in that it is found in highest
concentrations in fat from ruminant animals (e.g., beef, dairy, and lamb). Beef fat contains 3.1
to 8.5 mg CLA/g fat with the 9-cis and 11-trans isomers contributing 57- 85% of the total CLA
(Decker, 1995). Interestingly, CLA increases in foods that are cooked and/or otherwise
processed. This is significant in view of the fact that many mutagens and carcinogens have
been identified in cooked meats.

Over the past decade, CLA has been shown to be effective in suppressing forestomach tumors
in mice, aberrant colonic crypt foci in rats, and mammary carcinogenesis in rats (Ip and
Scimeca, 1997). In the mammary tumor model, CLA is an effective anticarcinogen in the range
of 0.1-1% in the diet, which is higher than the estimated consumption of approximately 1 g
CLA/person/day in the United States. These results are not due to displacement of linoleic acid
in cells, suggesting that there may be unique mechanism(s) by which CLA modulates tumor
development. Thus, there has been research designed to increase the CLA content in dairy cow
milk through dietary modification (Kelly et al., 1998).

More recently, CLA has been investigated for its ability to change body com-position,
suggesting a role as a weight-reduction agent. Mice fed CLA-supplemented diets (0.5%)
exhibited 60% lower body fat and 14% increased lean body mass relative to controls (Park et
al., 1997), possibly by reducing fat deposition and increasing lipolysis in adipocytes.

Safety Issues

Although "increasing the availability of healthful foods, including functional foods, in the
American diet is critical to ensuring a healthier population" (ADA, 1995), safety is a critical
issue. The optimal levels of the majority of the biologically active components currently under
investigation have yet to be determined. In addition, a number of animal studies show that
some of the same phytochemicals (e.g., allyl isothiocyanate) highlighted in this review for their
cancer-preventing properties have been shown to be carcinogenic at high concentrations
(Ames et al., 1990). Thus, Paracelsus' 15th century doctrine that "All substances are poisons . . .
the right dose differentiates a poison from a remedy" is even more pertinent today given the
proclivity for dietary supplements.

The benefits and risks to individuals and populations as a whole must be weighed carefully
when considering the widespread use of physiologically-active functional foods. For example,
what are the risks of recommending the increased intake of compounds (e.g., isoflavones) that
may modulate estrogen metabolism? Soy phytoestrogens may represent a "double-edged
sword" because of reports that genistein may actually promote certain types of tumors in
animals (Rao et al., 1997). Knowledge of toxicity of functional food components is crucial to
decrease the risk: benefit ratio.

Conclusion

Mounting evidence supports the ob-servation that functional foods containing physiologically-
active components, either from plant or animal sources, may enhance health. It should be
stressed, however, that functional foods are not a magic bullet or universal panacea for poor
health habits. There are no "good" or "bad" foods, but there are good or bad diets. Emphasis
must be placed on over-all dietary pattern -- one that follows the current U.S. Dietary
Guidelines, and is plant-based, high in fiber, low in animal fat, and contains 5-9 servings of
fruits and vegetables per day. Moreover, diet is only one component of an overall lifestyle that
can have an impact on health; other components include smoking, physical activity, and stress.

Health-conscious consumers are increasingly seeking functional foods in an effort to control

their own health and well-being. The field of functional foods, however, is in its infancy. Claims
about health benefits of functional foods must be based on sound scientific criteria
(Clydesdale, 1997). A number of factors complicate the establishment of a strong scientific
foundation, however. These factors include the complexity of the food substance, effects on the
food, compensatory metabolic changes that may occur with dietary changes, and, lack of
surrogate markers of disease development. Additional research is necessary to substantiate
the potential health benefits of those foods for which the diet-health relationships are not
sufficiently scientifically validated.

Research into functional foods will not advance public health unless the benefits of the foods
are effectively communicated to the consumer. The Harvard School of Public Health (Boston,
Mass.) and the International Food Information Council Foundation (Washington, D.C.) recently
released a set of communication guidelines, aimed at scientists, journal editors, journalists,
interest groups, and others for improving public understanding of emerging science. The
guidelines are intended to help ensure that research results about nutrition, food safety, and
health are communicated in a clear, balanced, and nonmisleading manner (Fineberg and
Rowe, 1998). Finally, those foods whose health benefits are supported by sufficient scientific
substantiation have the potential to be an increasingly important component of a healthy
lifestyle and to be beneficial to the public and the food industry.

About the Author

Dr. Hasler is executive director of the Functional Foods for Health Program, Department of
Food Science and Human Nutrition, University of Illinois, Urbana, Illinois. This article can be
downloaded in PDF format as originally published in Food Technology 52(2):57-62, 1998.

References