Dietary supplements and functional foods: 2 sides of a coin?
1–3
Charles H Halsted
ABSTRACT Dietary supplements are used by more than
one-half of the adult US population. In contrast to pharmaceuti-
cals, dietary supplements may be sold in the United States with
little regulation other than listing of ingredients and the potential
health benefits. By contrast, herbal products in Germany are
carefully regulated by the same standards as drugs, and efforts
are under way to standardize their regulation in the entire Euro-
pean Union. Most herbal users do not inform their physicians
that they are taking these supplements, and most physicians do
not inquire. Although some herbal products have clinically
proven benefits, it is increasingly apparent that many contain
potentially toxic substances, particularly in relation to interac-
tions with drugs. Hence, it is essential that practicing physicians
develop a working knowledge of herbals—specifically, about
claims for their usage and potential or proven efficacies and
toxicities—and that they incorporate such knowledge into the
evaluation and management of their patients. By contrast, func-
tional foods—integral components of the diet that are under-
stood to contribute added health benefits—are the subject of
intense and widespread research in food and nutritional science.
Examples include many polyphenolic substances, carotenoids,
soy isoflavones, fish oils, and components of nuts that possess
antioxidant and other properties that decrease the risk of vascu-
lar diseases and cancer. Practicing physicians are advised to stay
abreast of these emerging findings in order to best advise their
patients on the value of health-promoting diets in disease pre-
vention. Am J Clin Nutr 2003;77(suppl):1001S–7S.
KEY WORDS Dietary supplements, herbal products, functional
foods, challenges to medical practitioners
INTRODUCTION
In 1994 the US Congress enacted the Dietary Supplement
Health and Education Act (DSHEA) (1). This act defines a
dietary supplement as “a product (other than tobacco) that is
intended to supplement the diet and that bears or contains one or
more of the following dietary ingredients: a vitamin, a mineral,
an herb or other botanical, an amino acid, a dietary substance for
use by man to supplement the diet by increasing the total daily
intake, or a concentrate, metabolite, constituent, extract or com-
binations of these ingredients.” Furthermore, a dietary supple-
ment is intended for ingestion in pill, capsule, tablet, or liquid
form; is not represented for use as a conventional food or as the
sole item of a meal or diet; and is labeled as a dietary supplement
(1). In a recent Science forum, Zeisel (2) provided 2 additional,
useful working definitions. A neutraceutical can be defined as “a
diet supplement that delivers a concentrated form of a biologi-
cally active component of food in a non-food matrix to enhance
health.” The US Food and Drug Administration (FDA) does not
Am J Clin Nutr 2003;77(suppl):1001S–7S. Printed in USA. © 2003 American Society for Clinical Nutrition
recognize the term neutraceutical. Functional foods, according
to Zeisel, are not dietary supplements but rather “are consumed
as part of a normal diet and deliver one or more active ingredi-
ents (that have physiologic effects and may enhance health)
within the food matrix” (2).
Dietary supplements
Among his “bedside teachings,” Sir William Osler stated,
“The desire to take medicines is one feature which distinguishes
man, the animal, from his fellow creatures” (3), a viewpoint
recently corroborated by the finding of medicinal herbs in the
intestine of the 5300-y-old frozen “iceman” who was recently
discovered in the Swiss Alps (4). Botanicals with medicinal
properties have been used from time immemorial in all cultures
and, with the introduction of ingredient assays and standards in
the early 20th century, form the foundation for modern Western
pharmacology (5). On the other hand, the consumption and mar-
ket value of herbs and other nutritional supplements has reached
astonishing proportions in the United States. According to recent
FDA testimony, dietary supplements, including vitamins, were con-
sumed by 158 million Americans in the year 2000—that is, more
than half the US population (6). This compares with a 1997 survey
that showed that alternative medical therapies, principally herbals,
were used by 83 million people (7). In 2000, the total dietary sup-
plement market included 32% as herbals and 38% as vitamins. The
sales of dietary supplements in the United States doubled after pas-
sage of the DSHEA in 1994, to $17.1 billion in 2000, and are antic-
ipated to continue increasing by 10% per year (5).
Although the FDA was charged with implementing stringent
governmental regulations for ensuring the accurate labeling,
safety, and efficacy of drugs, the food supplement industry was
under no specific regulations until the Nutrition Labeling and
Education Act of 1990, which permitted health claims for
nutritional supplements that were restricted to several cate-
gories, including osteoporosis, hypertension, heart disease, and
cancer. Spurred by intensive industry lobbying, Congress passed
the DHSEA in 1994 to broaden the availability of all dietary
supplements by authorizing their claims for functional specific
health benefits, but not specific disease prevention or cure. The
FDA established a Center for Food Safety and Applied Nutrition
1
From the Department of Internal Medicine and Nutrition, University of
California, Davis.
2
Presented at the Third Heelsum International Workshop, held in Heel-
sum, the Netherlands, December 10–12, 2001.
3
Reprints not available. Address correspondence to CH Halsted, Depart-
ment of Internal Medicine and Nutrition, University of California, Davis, TB
156, One Shields Avenue, Davis, CA 95616, United States. E-mail: chhalsted@
ucdavis.edu.
1001S
1002S HALSTED
(CFSAN) with responsibility for oversight of new supplemental
products, including the marketing of clearly identified products
declared to be of known composition and strength. New dietary
supplements are reviewed by the FDA under the rubric of the
same good manufacturing practice regulations that apply to con-
ventional foods. The manufacturer is responsible for ensuring
that the “supplement facts” label and ingredient lists are accu-
rate, that the dietary ingredients are safe, and that the content
matches the amount declared on the label. However, the FDA
does not require accurate chemical analyses as a basis for the
identification and quantification of ingredients. The label must
also contain the disclaimer, “This product is not intended to
diagnose, treat, cure, or prevent any disease.” This policy
bypasses the usual FDA procedures of requiring proof of safety
from the manufacturer before approval of a drug for public con-
sumption, and puts the postmarketing burden of proving signifi-
cant risk on the FDA. Supplements that were produced before
1994 are assumed safe, whereas the safety of those marketed
after 1994 is the responsibility of the manufacturers. The
specifics of the role of the FDA in regulating dietary supple-
ments can be found in a recently posted website: http://www.
cfsan.fda.gov/dms/ds-oview.html (8).
How frequently do people use dietary supplements? A 2001
survey of 376 randomly selected adults living in Minneapolis
found that 61.2% used supplements, most commonly ginseng.
Few were advised by their physicians, and most obtained infor-
mation on herbs from family, friends, or the Internet. Although
the promotion of well-being was given as the main reason for
herbal usage, fewer than 60% found satisfaction (9). A survey of
118 patients attending 16 different family practices in Calgary,
Canada, found vitamin, mineral, or herbal supplement usage
among 79% of women and 44% of men, and that 25% of those
over age 50 and 70% of those under age 50 chose not to inform
their physicians. Based on Internet information, the younger
patients believed that supplements were safer and more effec-
tive than prescription drugs (10). Among 242 pregnant women,
25% had used herbals on a regular basis—typically garlic, echi-
nacea, and ginseng—before pregnancy, and 9% continued
herbal use during pregnancy (11). A study of women with early-
stage breast cancer found that the usage of alternative medicine
had increased from 10.6% before diagnosis to 28.1% after diag-
nosis and initiation of therapy, and that that increase was asso-
ciated with depression and fear of cancer recurrence. Of inter-
est, one-third of this group hid their alternative approaches from
their physicians (12). An accompanying editorial suggested that
widespread marketing and a lack of physician interest in dealing
with or time to address illness-related anxieties are the main
reasons that cancer patients turn to alternative remedies (13).
Among 201 patients with established Parkinson’s disease, 40%
used various forms of alternative medicine, most commonly
herbals (14). An informal non-peer-reviewed survey of arthritis
patients and their physicians found that 79% used or were inter-
ested in using alternative therapies, including herbs, chon-
droitin, glucosamine, massage, or chiropractic, but only 40% of
users informed their physicians, and only 40% of physicians
asked their patients about their alternative treatments. Reasons
given for patients’ having not informed their physicians
included fear of disapproval and the perception that the physi-
cian would be unable to provide advice on alternative
approaches. One-third of the physicians felt they did not know
enough to provide meaningful advice and 20% considered that
alternative therapies were fraudulent, potentially harmful
because they supplanted conventional therapy, and/or a waste of
time and money. Most patients derived their information from
advertising or Internet sources (15).
In summary, dietary supplement usage is widespread because
of successful marketing strategies and popularization by word of
mouth, advertising, and Internet information sources. Although
certain patient groups, such as pregnant women, tend to have
lower herbal usage than the average person, others with
intractable chronic and/or fatal diseases, such as Parkinson’s,
arthritis, and cancer, are more likely to turn to alternative thera-
pies, particularly herbal supplements. Most striking, physicians
are unlikely to ask and unlikely to be told of their patients’ herbal
habits. In view of the uncertain composition of most herbs, their
potential interaction with prescription drugs, and their propen-
sity to cause side effects, widespread herbal usage poses a poten-
tially significant risk to the health of patients.
What should practicing physicians be concerned about
regarding herbals and other dietary supplements? A lot, as sum-
marized in a recent editorial that emphasizes the differences
between conventional and nonconventional medicine (16).
Before the application of science to medicine in the early 20th
century, botanicals were the major source of nonsurgical ther-
apy. Practitioners of herbal medicine had no way of knowing
the concentrations or purity of their remedies, and toxicities
from such medicines as foxglove, opium, and cinchona bark
were common. Proving the safety and efficacy of botanicals
was not feasible until the advent of chemical approaches to
identifying and ensuring the purity of active ingredients and of
the scientific approach of well-controlled randomized clinical
trials. Nevertheless, the burgeoning dietary supplement indus-
try, with its lack of rigorous scientific testing, threatens to
inundate the public with ineffective and potentially harmful
remedies. In the absence of patent opportunities for dietary
supplements, manufacturers have little incentive to prove the
efficacy and safety of their products.
The literature on dietary supplements is vast and rife with
reports of unsuspected toxicities from unregulated dietary sup-
plements. The issue is complicated by the variety of regulations
in different countries, where a botanical product may be classi-
fied as an approved medicine, a dietary supplement, or a recre-
ational herb (17). Most nation members of the European Union
regulate vitamins and minerals as foods if provided within the
accepted recommended dietary allowances, but they have no spe-
cific regulations on dietary supplements as long as no medicinal
claims are made (18). Several countries have established com-
missions to assess the safety and efficacy of herbals. For exam-
ple, Commission E of the German Federal Health Agency has
published more than 300 monographs that evaluate the efficacy
and safety of different herbal products according to acceptable
clinical trials (19). Ongoing reports of herbal toxicities may not
appear in recent book form and must be sought in the current lit-
erature. For example, it has only recently been appreciated that
fulminant hepatic failure may occur during the chronic use of
kava (20, 21). Understanding potential efficacies and hazards of
dietary supplements is a daunting task for practitioners. For
example, the Physicians’ Desk Reference for Herbal Medicines
lists 80 under letter A alone in its common name index and lists more
than 350 side effects for all herbals (22). The recently published
Physicians’ Desk Reference for Nuritional Supplements describes
more than 200 nonherbal supplements (vitamins, minerals, amino
 DIETARY SUPPLEMENTS AND FUNCTIONAL FOODS
acids, and other products) cross-referenced to more than 300
potential side effects (23). Given that herbals and nutritional sup-
plements are taken by mouth, it is not surprising that the most
common side effects relate to the gastrointestinal tract, including
diarrhea, nausea, and vomiting. Because many plants have nat-
ural toxins that were developed for survival, hepatocellular dam-
age is not uncommon after ingesting herbs, including comfrey,
senna, and mixtures of ill-defined Chinese herbs (24). Additional
problems arise from the presence of unregulated or unknown
amounts of toxic substances within herbal preparations. For
example, in a 1998 analysis of 251 Asian patent medicines per-
formed by the California Department of Health Services, 10%
were found to contain lead, 14% arsenic, and 14% mercury at
potentially toxic levels (25). Others found toxic amounts of mer-
cury in Chinese imported “herbal balls” and arsenic at levels that
could result in daily accumulation of 73 mg arsenic and more
than 1200 mg mercury (26). Aristolochia fangchi, or “birthwort,”
used for gastrointestinal symptoms, was strongly associated with
nephropathy and development of urothelial carcinoma in women
attending a Belgian weight reduction clinic (27, 28). Underscor-
ing the problem of lack of quality control, 2 case reports
described the symptoms and laboratory evidence of digitalis tox-
icity after ingestion of plantain, an herbal ingredient of a mixture
claimed to “cleanse the body,” that was contaminated with Digi-
talis lanata (29).
A recent survey indicated that 30% of patients undergoing
surgery use herbal medications, about twice the usage in the gen-
eral US population (30), and that 70% of herbal users failed to
mention their use of dietary supplements in the routine preoper-
ative evaluation (31). Preoperative herbal use is particularly haz-
ardous, because different herbs may influence operative survival
and/or alter the metabolism and pharmacologic effects of con-
ventional anesthesia and postoperative drugs. For example, pro-
longed preoperative use of the immunostimulant echinacea may
result in immunosuppression with prolonged wound healing and
postoperative infections (32). Ephedra, a stimulant and the source
of ephedrine and methamphetamine, increases blood pressure,
heart rate, and risks of arrhythmias and vasospasm, which
together increase the risks of myocardial infarction and stroke
(33). In 1997 the FDA issued a warning on the use of ephedra as
an herbal weight loss drug because of its potential adverse stim-
ulant effects on both the circulatory and nervous systems (34).
Although garlic lowers serum cholesterol to a modest amount
(35), ajoene, a constituent of garlic, may potentiate platelet
inhibitors and thereby increase the risk of bleeding complica-
tions of surgery (30). Ginkgo, used to enhance memory and
improve peripheral vascular circulation, also has platelet-inhibit-
ing properties that may result in intracellular hemorrhage and
subdural hematomas (36, 37). Ginseng may lower postprandial
blood glucose in type II diabetic patients but can induce hypo-
glycemia and inhibit platelet aggregation (38, 39). Kava, used
for its sedative and antianxiety properties, can interact with bar-
biturates and benzodiazepines, prolonging sleep and even induc-
ing coma (40), and has recently been associated with fulminant
hepatic failure requiring liver transplantation (20, 21). A 2002
FDA consumer advisory cited 25 reports of liver-related injury in
kava users and advises caution on its use, particularly in individ-
uals with known liver disease (41). St John’s wort, used to pre-
vent depression, inhibits serotonin reuptake, which results in sero-
tonin excess and increases the metabolic rate of many cytochrome
P450 drugs, including cyclosporin, midazolam, lidocaine, and
1003S
warfarin, leading to their ineffectuality in therapeutic situa-
tions (30). Valerian, used for its sedative properties, potenti-
ates the effects of benzodiazepines and may result in with-
drawal delirium (42).
The health claims and potential side effects of some of the most
commonly used herbals are shown in Table 1 (19, 22, 43, 44).
Functional Foods
In contrast to most dietary supplements, functional foods are
components of the usual diet that may have special disease pre-
vention attributes and are the topic of current traditional scien-
tific investigation. According to the Food and Nutrition Board of
the Institute of Medicine, a functional food is “any food or food
ingredient that may provide a health benefit beyond the tradi-
tional nutrients it contains” (45). Unlike dietary supplements that
can claim only general health benefits, functional foods may
claim specific health benefits because they are considered part of
the diet (46). The literature on functional foods is vast and grow-
ing exponentially, and this review can touch on only a few points
that are essential for the practitioner. A recently published hand-
book provides excellent summaries (45).
Polyphenols and flavonoids
The term polyphenol encompasses simple phenols and flavon-
oids, which are found in fruits, vegetables, and nuts and their
products, and possess important antioxidant properties. Flavon-
oids include proanthocyanidins, quercetin, and epicatechin, found
mainly in chocolate, tea, and wine. Red wine also contains resver-
atrol, a nonpolyphenol antioxidant product of grape skins. The
“French paradox” refers to the epidemiologic finding that the
incidence of coronary heart disease was significantly lower in
wine-drinking regions of France than in areas where wine was not
the main alcoholic beverage (47). Subsequently, it was shown that
wine phenols inhibited the oxidation of low-density lipoprotein
(LDL) (48), an accepted reason for the preventive effect of
polyphenols on the development of atherosclerosis. More recent
studies demonstrate that the attenuation of coronary heart dis-
ease risk in wine drinkers is probably due as much to their
lifestyle consumption of high amounts of polyphenol-containing
fruits and vegetables as to wine (49). A 5-y prospective Dutch
study of 800 elderly men found that the ingestion of flavonoids,
mainly in tea, onions, and apples, was associated with significant
reduction in mortality from coronary heart disease (50). In addi-
tion to antioxidant effects on LDL, other potentially cardiopro-
tective effects of polyphenols include inhibition of platelet aggre-
gation and vascular relaxation through the production of nitric
oxide (51). Although polyphenols have the capacity to decrease
LDL oxidation, inhibit platelet aggregation, and induce vascular
relaxation, their clinical efficacy is modulated by many factors
that include differences in wine and tea preparation, volatility,
and absorbability. For example, green tea has a higher concentra-
tion of polphenols than black tea, which may be affected by the
method of brewing (52). Wine should be consumed in moderation
only, to avoid the chronic effects of alcohol. The year 2000
Dietary Guidelines for Americans identifies moderation as no
more than 1 drink per day for women and 2 drinks per day for
men, where a drink constitutes 5 oz of wine (53). Although these
studies support the principle that fruits and vegetables should pro-
vide the main staple of a healthy diet, varied amounts of polyphe-
nols in different foods and effects of food preparation and absorp-
tion hinder the establishment of clear-cut dietary and clinical
1004S HALSTED

TABLE 1
Herbal supplements
Common name Formal name Claim, current use Possible mechanisms Efficacy, clinical evidence Adverse effects
Black cohosh (black Cimicifuga Improves menopausal Suppresses lutenizing Many clinical studies Gastric discomfort
snakeroot, rattle- racemosa symptoms, premen- hormone secretion in showed favorable results
weed, rattleroot, strual syndrome, and menopausal women;
bugbane, bugwort, dysmenorrhea weak binding to
squaw root) (19, 44) estrogen receptors
Comfrey (19, 44) Symphytum Heals skin wounds Allantoin promotes cell Uncertain Liver failure, death. Pyrrolizidine
officinale growth; Tannins are alkaloids are hepatoxoic
vaso-constrictive when taken by mouth;
may be absorbed through skin
Echinacea (cone Echinacea Stimulates immune Stimulates leukocyte Positive clinical trials Immune suppression during
flower) (19, 44) angustifolia response; promotes mobility, phagocytosis, showing shortened surgery (30)
wound healing; treats and T-cell functions duration of common cold
common cold and yeast but not prevention
infections
Ephedra (ma huang) Ephedra sinica Relieves nasal Active constituent is Traditional use for Increases blood pressure and
(19, 34, 44) congestion and asthma, ephedrine, a 2000 years in Chinese heart rate and can cause
promotes weight loss, sympathomimetic medicine to treat headache, insomnia, dizzi-
and enhances athletic bronchospasm ness, seizures, arrhythmias,
performance addiction, and death (34)

Garlic (19, 44) Allium sativum Reduces cardiovascular Inhibits platelet Lowers LDL cholesterol Can potentiate other platelet
risk and serves as aggregation, reduces and triacylglycerols in inhibitors or cause
anti-inflammatory cholesterol (35), clinical trials; antibacterial bleeding
and has antioxidant in vitro (19)
properties
Ginkgo (43, 44) Ginkgo biloba Improves memory, Promotes vasodilation, Clinical trials show that it Diarrhea, nausea, vomiting;
cognition, intermittent modulates neuro- may improve cognitive intracranial bleeding
claudication, vertigo, transmitter activity, performance and memory reported (30, 37)
tinnitus, and sexual and inhibits platelet in the morning; mixed
performance aggregation results in Alzheimer’s
disease
Ginseng (43, 44) Panax ginseng Improves physical Unknown; possible Mixed data on regulation Insomnia, diarrhea and
performance, energy pharmacologic effects of blood glucose and hyperactivity
level; cancer prevention; attributed to steroidal cancer prevention
blood sugar reduction saponins
Kava-kava Piper Elevates mood and May interact with brain Positive clinical studies Weakness, allergies, inter-
(19, 41, 44) methysticum relieves anxiety and -aminobutyric acid action with benzodiazepines
menopausal symptoms receptors (19) (40, 41)

Saw palmetto Serenoa repens Reduces prostatic hyper- Has antiandrogenic Similar to finasteride in Feminization
(22, 44) (sabal fructus) trophy, builds sexual action reducing symptoms of
vigor, and increases prostatitis, but with fewer
sperm production side effects

St John’s wort Hypericum Serves as mild to Inhibits serotonin, Positive clinical trials for Causes photosensitivity;
(19, 43, 44) performatum moderate antidepressive, norepinephrine, and mild to moderate may interact with
and as antiviral dopamine reuptake; depression benzodiazepines and
(22) inhibits monoamine warfarin (30)
(MAO)
Yohimbe Pausinystalia Works as aphrodisiac Dilates blood vessels of Several studies show Active MAO inhibitor; may
(19, 44) yohimbe and improves athletic skin and mucous positive value for erectile activate psychosis;
performance membranes dysfunction increases anxiety, blood
pressure, sleeplessness,
tachycardia, tremor, and
vomiting; ruled unsafe by
US Food and Drug
Administration (8)
 DIETARY SUPPLEMENTS AND FUNCTIONAL FOODS
recommendations of polyphenol-rich fruits and vegetables in the
nutritional prevention of heart disease.
Soy isoflavones
Soy isoflavones are phytoestrogens that are derived from the
protein fraction of the soybean and its food products (eg, soy milk,
soy flour, tofu, miso), include genistein and daidzein, and possess
estrogenic properties because of the similarities of their chemical
structures to estrogenic compounds. Clinical trials identified the
potential efficacy of soy isoflavones in the prevention of coronary
heart disease, osteoporosis, and breast and prostate cancer. A
meta-analysis of 37 clinical studies suggested that soy protein up
to 45 g per day can lower serum cholesterol levels by 10% (54),
but the long-term effects of soy on cardiac risk are unknown.
Because phytoestrogens compete with estrogen for binding to
estrogen receptors, their use could have beneficial effects in pre-
venting osteoporosis and sex hormone–mediated malignancy, such
as breast and prostate cancer. The clinical data are mixed and
inconclusive on the effect of soy isoflavones on bone turnover and
bone density (55). Data are mixed on whether soy isoflavones pro-
mote or protect against breast cancer (56–58), and one retrospec-
tive study of 1300 non-Asian women with breast cancer history
found no association of phytoestrogen use and breast cancer risk
(59). Although prostate cancer rates are lower in Eastern cultures
where soy products play a major role in the diet, and although
genistein inhibits the growth of prostate cancer cells, clinical stud-
ies to date have failed to demonstrate positive effects of dietary
soy products on reducing the risk of prostate cancer (60).
Carotenoids
There are several plant-derived carotenoids in the human diet,
of which -carotene, -carotene, lutein, zeaxanthin, and lyco-
pene appear to have the most significance for health. Being lipid
soluble, carotenoids are absorbed with fats and circulate bound
to different lipoproteins. -carotene is a limited precursor of
vitamin A, and excessive amounts of -carotene lead to
reversible carotenemia but not to vitamin A toxicity. The princi-
pal biological effects of carotenoids relate to their antioxidant
properties, which form the basis of potential protection against
lipid peroxidation, atherogenesis, DNA oxidation, and cancer
(61). Clinical studies suggest but have not yet proven that either
-carotene or lycopene is cardioprotective (62, 63). Aortic ather-
osclerosis incidence was significantly inversely correlated with
the intake of dietary lycopene in the Rotterdam study of
108 patients and control subjects (64). A review of more than
30 studies concluded that there is an inverse relationship
between lycopene in tomato products and the risk of cancers of
the prostate, lung, and stomach (65), and one study demonstrated
a 21% reduction in prostate cancer with consumption of diets
high in tomato-derived lycopene (66). A study of more than
25 000 middle-aged male Finnish smokers found that the inci-
dence of lung cancer was increased in those receiving -carotene
supplements (67). In large cohorts followed over time, cataract
formation was reduced significantly by dietary intake of fruits
and vegetables rich in lutein and zeaxanthin (68, 69). Recent
data suggest a potential preventive relationship between intake
of these carotenoids and risk of macular degeneration (70).
Fish oils
Dietary fish oils appear as n3 polyunsaturated fatty acids
mainly in cold water fish, compared with n6 polyunsaturates
1005S
mainly from plants and saturated fatty acids from animal sources.
Diets in which cold water fish such as mackerel, salmon, halibut,
and trout are the main staple are associated with reduced inci-
dence of coronary heart disease but increased risk of hemor-
rhage. Studies of susceptible men from Holland, Japan, and the
United States showed that sudden death from coronary artery
disease is reduced by half when 1–2 fish meals are consumed
weekly (71–73). The biological effects of fish oils include inhi-
bition of hepatic synthesis and secretion of triacylglycerol and
very low density lipoprotein with reduced postprandial lipemia,
increased circulating high-density lipoprotein, inhibition of
platelet aggregation, and prevention of cardiac arrhythmias (73).
Eicosapentaenoic acid (EPA) and its elongated product docosa-
hexaenoic acid are the predominant fatty acids in fish, whereas
-linolenic acid, the precursor of EPA, is found in canola,
flaxseed, and walnut oils. A Mediterranean diet rich in these oils
was found to reduce cardiac deaths by 70% in France (74). By
virtue of anti-inflammatory properties and effects on cell mem-
branes, fish oils are also thought to have a beneficial effect in the
treatment of rheumatoid arthritis, although conclusive clinical
studies are lacking (75).
Nuts
Although nuts are relatively high in fat, most of this fat is in the
mono- or polyunsaturated form. Beneficial nuts include almonds,
Brazil nuts, peanuts, walnuts, pistachios, and pecans. Three large
prospective studies demonstrated that the consumption of 1–4
servings of nuts per week was associated with about a 40% reduc-
tion in risk of coronary heart disease, even after adjusting for con-
ventional risk factors such as hypertension, smoking, diabetes, and
hyperlipidemia (76–78). The purported beneficial effects of nuts
include improvement of serum lipid profiles with a predicted 16%
reduction in LDL cholesterol and presence of relatively high
amounts of the nitric oxide precursor arginine, dietary fiber, and
antioxidant vitamin E (78). Walnuts are particularly noteworthy
for having a high content of n3 linolenic acid (78).
Probiotics and prebiotics
Probiotics can be defined as “live microbial food supplements
which benefit the host by improving the intestinal microbial
form” (79). As such, probiotics can be consumed as either a
functional food, such as a fermented milk product, or a supple-
ment if provided separately in capsule or pill form. The rationale
for probiotics is to improve intestinal immune tolerance to ben-
eficial proteins and to maintain a normal immune intestinal
barrier and permeability to exogenous foreign antigens (80).
Intestinal organisms constitute the greatest cell population of the
body, existing in 500 different species. Provision of normal
human organisms that resist acid and bile destruction and adhere
to the gut mucosa triggers a healthy immune response. The most
beneficial organisms include those of the Lactobacillus and Bifido-
bacterium genera. Whereas controlled clinical trials are ongoing,
beneficial effects have been reported in the treatment of food
allergies, acute infant diarrheas, traveler’s diarrhea, antibiotic-
associated colitis, and, potentially, inflammatory bowel disease
(81). Prebiotics are “non-digestible food ingredients that selec-
tively stimulate the growth of a limited number of bacteria in the
colon” (82). More specifically, prebiotics are short-length carbo-
hydrates, such as fructooligosaccharides, that resist digestion or
are fermented in the colon to produce short-chain fatty acids,
such as acetate, butyrate, and propionate, which have positive
1006S
effects on colonic cell growth and stability, generate many of the
same bacteria as provided in probiotics, and may promote
improved bowel habit but also increased flatus (83).
SUMMARY AND CONCLUSIONS
There are striking differences between dietary supplements
and functional foods. Whereas dietary supplements, herbs in par-
ticular, are considered time-tested but are in most cases scientif-
ically unproven, functional foods are components of the normal
human diet that are increasingly shown by rigorous science to be
inherently valuable for maintaining human health. Whereas
herbal sales skyrocket and feed false public perception of the
irrelevance of science to health, the era of functional foods
promises to propel nutritional science to the forefront of preven-
tive medicine for the most common diseases of humans.
Together, this new era of nutrition presents imposing challenges
to practitioners of medicine. It is incumbent on them to become
fluent in the knowledge of commonly used herbals, including
recognition of their potential benefits, side effects, and life-
threatening effects when combined with certain drugs. Although
advice-seeking patients typically have rudimentary knowledge
of the ingredients and rationales for the herbs they ingest, physi-
cians must be in a position of knowledge to maintain their
patients’ confidence as a prerequisite to providing credible coun-
sel. Furthermore, because most patients are curious and some-
what knowledgeable about their diets, physicians must establish
a basic knowledge of conventional functional foods, which is
viewed increasingly as an adjunct to sound medical advice.
These are heady days for nutritional scientists as newer under-
standings of food and health promise to bring clinical nutrition
to the forefront of clinical medicine. Practitioners must become
nutritionally educated and oriented if they are to maintain their
patients’ confidence and stay abreast of this aspect of continu-
ously evolving modern medicine.
The author has no financial or personal potential or actual conflicts of
interest with any manufacturer of herbal products or supplemental foods.
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