foods and nutraceuticals are assuming a middle ground between food and
drugs due to a growing body of evidence that supports their role in
maintaining health and contributing to the treatment of diseases. Since
Hippocrates advised to "Let food be thy medicine and medicine be thy
food," we have defined medicines and foods based on what is known about
each substance in terms of efficacy, safety and the significance of its
perceived contribution to health. Over time, we tend to redefine these
substances as our experience and expectations change. The ancient Greeks,
for example, looked upon garlic as a performance-enhancing drug and
officially sanctioned it for this use during the first Olympic games.
During the age of sailing
ships, lemons were dispensed to sailors to prevent and treat scurvy. John
Woodall, the father of naval hygiene and a "Master in Chirurgerie,"
published "The Surgeon's Mate" in 1636 in which he wrote, "The juyce of
lemmons is a precious medicine… It is to be taken each morning two or
three teaspoonfuls, and fast after it two hours."
Modern functional foods
became available in the 1920’s, when iodine was added to salt to prevent
goiter. This was followed by vitamin D milk. Today, many Americans start
their day with calcium-fortified orange juice (to strengthen their bones).
Then, they spread a margarine that lowers cholesterol on folate-enriched
toast (to protect their hearts and prevent birth defects).
Distinguishing between functional foods
It is not surprising that the
terminology to define and promote these products is escalating (Table 1).
For practical purposes however, two terms (functional food and
nutraceutical) can be used to distinguish among nutritional products that
make health claims beyond basic nutrition.
1. Categories of healthful foods and dietary supplements
Category / example
Products containing one of more of the
Vitamin, mineral, herb
or other botanical
An amino acid or
Any combination of the
(other than tobacco) intended to supplement the diet
be marketed in a food form if not "represented" as a conventional
food and labeled as a dietary supplement
health or structure/function claims* can be made if the FDA deems
adequate scientific substantiation exists
Vitamin B added to
enriched with vitamins and minerals, usually up to 100% of the DRI
mandated by law to replace nutrients lost during processing
Salad dressing with
omega-3 polyunsaturated fatty acids
Carrots with 170% of
daily requirement of vitamin A
food or ingredient that may provide a health benefit beyond the
"traditional nutrients" it contains†
health or structure/function claims can be made if the FDA deems
adequate scientific substantiation exists
fortified foods have more than 100% of the DRI and/or foods with
added botanicals or other supplements
to treat diabetes, obesity, or heart disease, sold through
physicians, not by conventional retailers
formulated to be consumed or administered internally while under
the supervision of a physician
for specific dietary management of a disease or condition for
which distinctive nutritional requirements are established
juice with calcium
substances in pharmaceutical dosage forms
supplements and fortified foods enriched with nutrients not
natural to the food
Structured snacks ("fusion
On Me for weight loss
Best for Type 2 diabetes
people with potentially serious medical conditions
more than some prescription medications
mostly to physicians
DRI = dietary reference intake
* Structure/function claims state that a product may
affect the structure or function of the body (eg, calcium builds
strong bones, antioxidants maintain cell integrity, fiber maintains
bowel regularity), but may not claim that a therapy can prevent or
cure a disease (eg, alleviates constipation).
nutrients" refer to vitamins and minerals considered essential to the
diet and/or to correct a classical nutritional deficiency disease. For
example, foods containing vitamin C to correct scurvy or vitamin D to
alleviate rickets are not functional foods. However, soy, which
contains soy protein and is associated with a reduced cardiovascular
risk, is a functional food (Source: Modified from Mulry, 2000).
Functional foods, as defined by the American Dietetic
Association, are products whose nutritional value is enhanced by the
addition of natural ingredients. Functional foods may provide specific
health benefits beyond basic nutrition when consumed as part of a varied
Nutraceuticals, according to the American Nutraceutical
Association, are functional foods with potentially disease-preventing and
health-promoting properties. They also include naturally occurring dietary
substances in pharmaceutical dosage forms. Thus, they include "dietary
supplements" as defined by the Dietary Supplement Health and Education Act
of 1994 (DSHEA).
Figure 1. Options for categorizing
functional foods and nutraceuticals.
From the FDA regulatory perspective, all substances that
influence our health can be divided into two groups: food and drugs, with
food further divided into conventional food and dietary supplements (Figure
1). Despite the fact that many terms are used to describe nutritional
substances that influence health, each of these terms fits into one of these
categories. When viewed in this way, healthcare professionals will be less
susceptible to the vague claims that tend to characterize this growing field
Examples of functional foods
All foods are
functional; however, the term "functional" refers to an additional
physiological benefit beyond meeting basic nutritional needs (Table 2). For
example, epidemiological data tend to show that cancer risk in people
consuming diets high in fruits and vegetables is about one-half that seen
among people consuming few of these foods (Block et al, 1992). Certain
components from animal sources make similar contributions to health,
including omega-3 fatty acids found in fish, calcium in dairy products, and
the anticarcinogenic fatty
Examples of functional foods, their key components, and potential health
Black and green tea
risk for cancer
Broccoli and other cruciferous vegetables
risk for cancer
risk for cancer
Omega-3 fatty acids
risk for heart disease
Fruits & vegetables
Many different phytochemicals
risk for cancer & heart disease
risk for cancer & heart disease
Oats & oat-containing foods
Soluble fiber beta glucan
Purple grape juice & red wine
normal, healthy cardiovascular function
Tomatoes & tomato products
risk for cancer
Yogurt & fermented dairy products
Once the benefits of a key component in food are documented,
the challenge is to increase its concentration, and presumably its benefits,
while maintaining safety. For example, isoflavones in soy are phytoestrogens
with a chemical structure similar to estrogen. Isoflavones may reduce
cholesterol, but what is the risk of increasing the intake of a compound
that may modulate estrogens? Knowledge of the toxicity of functional food
components is crucial to improve their benefit:risk ratio. The efforts that
go in to making these determinations are costly. As a result, companies that
are successful can be expected to market products that will be branded and
extensively promoted (Table 3).
Examples of products marketed or planned to be marketed as functional foods
by pharmaceutical companies
Novartis: Aviva product line
Breakfast bars, cereals, and
Claims: Benefits the heart, bones, and
Marketed in United Kingdom and Switzerland
US launch planned
McNeil Consumer Health, Division of
Johnson & Johnson
Benecol brand margarine, salad dressing,
and health bars in US
Claim: Reduce LDL cholesterol up to 14%,
within two weeks of product use
In first few months, Benecol margarine
captured ~2% of US margarine sales
Mead Johnson division of Bristol-Myers
EnfaGrow nutrient-enriched oatmeal and
snack line for toddlers, marketed primarily to physicians
Allergy alert: EnfaGrow Nutritional
Oatmeal for Toddlers in Maple Brown Sugar & Cinnamon and Strawberry
flavors may contain trace amounts of milk protein, not listed in the
Viactiv Soft Calcium Chews sold in US
grocery and drug stores
Claim: To meet women’s special nutritional
* SafetyAlerts.com, 2000.
Challenges facing nutraceuticals
Some of the most popular nutraceutical products marketed
today are botanicals such as St. John’s wort, echinacea, ginkgo biloba, saw
palmetto, and ginseng. Unfortunately, manufacturers are not required to
prove their safety or efficacy before marketing them. Dosages are not
standardized. The quality of the raw source and the plant parts used are not
regulated. And, unlike prescription drugs or over-the-counter medicines,
there is no federal quality control standard to ensure that the label
reflects what is in the bottle.
The problem is illustrated by reports that labeled
concentrations of active ingredients often significantly overestimate the
content in the dosage form. In one report, nearly one-third of the brands
tested did not contain what their manufacturers claimed (Hemphill, 2000).
In another test of 14 samples from over-the-counter products containing
ginkgo biloba, 11 did not contain all of the active ingredients associated
with ginkgo biloba as specified by the World Health Organization (WHO). When
levels of a possible allergen, ginkgolic acid, were tested, the levels of
this compound in 13 products ranged from 16 to 733 times more than the WHO
recommendation. Only one sample met the limit for the possible allergen, but
this product failed in terms of its active ingredient content (Reuters,
This is a serous problem that undermines the nutraceutical
market, encourages skeptics who criticize the value and role of
nutraceuticals, and (most importantly) is potentially harmful to the public.
An organization that conducts assays of supplements and reports the results
versus the labeled ingredients is
www.consumerlab.com. Manufacturers are charged a fee to participate in
this service. Products that pass the test are permitted to include the
ConsumerLab.com seal on their products.
Significance for pharmacists
The issues surrounding nutraceuticals and functional foods
are important to pharmacists for two reasons. It is important to their
patients and is certain to be the source of questions. Also, the growing
field of nutraceuticals and functional foods is likely to change the
practice of pharmacy over the next decade.
More than 100 million Americans regularly use dietary
supplements, and in the year 2000, consumers spent about $16 billion on them
(Augsburger, 2000). Furthermore, 39% of Americans say they have made
dietary changes to reduce their risk of getting cancer, 43% claim to take a
daily multi-vitamin for cancer protection, while 21% take another form of
nutritional or dietary supplement (ie, concentrated doses of single
vitamins, minerals or herbal substances) to lower their cancer risk (AICR,
Americans are concerned about their health and they view
their pharmacist as an important resource for health matters. Almost
two-thirds of respondents in one sample stated that they regularly talk with
their pharmacist when choosing an OTC product, and 58% have come to think of
their local pharmacist in the same terms as their family doctor (AICR,
In the future, according to Dr. Benadette Marriott, who is
vice president of programs and communications at the Burroughs Wellcome
Fund, the need to guide consumers through the maze of functional foods and
nutraceuticals may lead to significant changes in pharmacy practice. Food
stores will continue to evolve into "one-stop wellness centers," where
consumers go for basic wellness screening activities, nutritional counseling
and medication advice. At the center will be the pharmacy, where pharmacists
will work with nutritionists and others to help consumers recognize their
options and select among several sources of an ingredient in order to safely
treat or lower their risk for disease (Marriott, 2000).
Case history: year 2010
Mr. D is a 50 year-old man with a family history of prostate
cancer and a personal history that is remarkable for a diet high in
saturated fats. He comes to the pharmacy knowing that his family and
dietary history place him at risk. He has no symptoms or laboratory values
consistent with prostate cancer but is committed to making changes in his
life that will lower his risk.
Part of his strategy includes eating more tomatoes to
increase his intake of the antioxidant, lycopene. However, he is confused
because of a news story in which researchers reported that lycopene
administered to mice as a supplement acted as a pro-oxidant and encouraged
tumor growth (Moyad, 2000).
In addition to wanting to take an effective source of
lycopene, Mr. D wants to know which is safest and most economical. In the
year 2010, there are no fewer than five sources of lycopene, listed here in
order of increasing cost.
- Nutritional lycopene: Vine-ripened tomatoes (and other foods)
- Organically grown sources of lycopene: Organically grown tomatoes
- Lycopene-enhanced functional foods: Genetically enhanced tomatoes with
guaranteed high levels of lycopene*
- Nutraceuticals: Dietary supplements that isolate and contain high
levels of lycopene.
- Prescription drugs: Pharmaceutical grade lycopene containing the
highest concentrations of lycopene and clinically tested to meet FDA
standards for safety and efficacy.*
The challenge facing the pharmacist is to guide this patient
through the maze of study results and conflicting claims. There are few
absolute answers, but there are guidelines that can help consumers make
intelligent decisions (Moyad, 2000). And it is likely that the guidelines
for today will be valid a decade from now.
Advertising and Articles about Supplements with Caution
Be cautious of any
product that claims to "boost" the immune system or "rejuvenate" health.
Advise consumers to look for specific findings, not vague claims.
have side effects under certain circumstances and should be thoroughly
tested before being used by the public.
Remember, if it
doesn’t have side effects, it probably hasn’t been thoroughly tested.
Natural first, supplement second
When there is a
choice between a vegetable and a pill, recommend to eat the vegetable.
products that isolate recognized active ingredients. It is often not clear
whether the active ingredient is as effective when taken in the absence of
other nutrients found in food.
supplements, consumers should take them with food to aid absorption and
minimize the risk of GI upset.
label. Then, get a second opinion
anything, read the label.
Confirm the value of
the supplement with a healthcare advisor.
Moderation is best
More is not always
better, vitamin C, selenium, and vitamin D are examples where too little
has no effect, but too much has adverse effects.
Start with low doses
and work up. A commitment to taking nutraceuticals is a long-term
strategy. Starting doses that are too high increase the risk of side
effects, which will dampen the consumers resolve to continue treatment.
Supplements are only
part of the picture. They are not substitutes for a healthy diet, stress
reduction, exercise, weight control, and (when needed) prescription drug
Nutraceuticals do not
offset the negative effects of smoking.
Finally, remind consumers to not become obsessed by one
disease. For example, men concerned about prostate cancer, and women
concerned about breast cancer, should not ignore their risk factors for
Note: * Currently, not marketed.
Seniors prefer taking supplements to changing diet. American Institute for
Cancer Research (AICR). 31 August 2000 [Accessed 12 November 2000.]
Augsburger LL. Introduction
and welcoming remarks. AAPS Dietary Supplements Forum: Exploring the
Science of Nutraceuticals. Washington, DC, June 28–30, 2000.
Patterson, B.; Subar. A.: Fruit, vegetables, and cancer prevention: A review
of the epidemiological evidence. Nutr Cancer. 1992, 18,1-29.
M.: Functional foods: Their role in disease prevention and health promotion.
Food Technology. 1998; 52 (2), 57-62.
C.: Putting dietary supplements to the test. The New York Times. June 20,
2000. [Accessed 20 June 2000.] Available at URL:
Lewis CL. Keynote address:
Dietary supplements: The regulatory interface. AAPS Dietary Supplements
Forum: Exploring the Science of Nutraceuticals. Washington, DC, June 28–30,
Marriott B. M.: Dietary
supplements: Clinical studies and trials to evaluate the efficacy and safety
of nutraceuticals and dietary supplements: Approaches, stumbling blocks and
the consumer quandary. AAPS Dietary Supplements Forum: Exploring the Science
of Nutraceuticals. Washington, DC, June 28–30, 2000.
Moyad, M. A.: The ABC’s of
Nutrition and Supplements for Prostate Cancer; Sleeping Bear Press: Chelsea,
Mulry, M.: Functional foods
and nutraceuticals. Nutrition Science News. July 2000, 5 (7), 292-296.
Reuters. Ginkgo remedies fail
WHO standards. 17 November 2000. [Accessed 27 November 2000]. Available at http://dailynews.yahoo.com/h/nm/20001117/hl/gingko_1.html.
SafetyAlert.com. Mead Johnson Issues Allergy Alert for Two Flavors of
EnfaGrow Nutritional Oatmeal For Toddlers. 10 January 2000. [Accessed 13
November 2000]. Available at URL: