Download Promises and Problems of Functional Foods

Critical Reviews in Food Science and Nutrition, 44:369–377 (2004)
C Taylor and Francis Inc.
Copyright ISSN: 1040-8398
DOI: 10.1080/10408690490509609
Promises and Problems
of Functional Foods
MARTIJN B. KATAN
Wageningen Centre for Food Sciences, Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands
NICOLE M. DE ROOS
University Medical Centre, Utrecht, The Netherlands
“Functional” foods are branded foods, which claim, explicitly or implicitly, to improve health or well being. We review
typical functional foods and their ingredients, efficacy, and safety. We also review regulations for health claims for foods
worldwide. These regulations often allow manufacturers to imply that a food promotes health without providing proper
scientific evidence. At the same time, regulations may ban claims that a food prevents disease, even when it does. We offer
a plea for regulations that will permit all health claims that are supported by the totality of scientific evidence, and ban all
claims that suggest an unproven benefit.
Keywords
functional foods, health claims, regulation, supplements, Nutraceuticals
INTRODUCTION
Functional foods are the food industry’s response to the consumers’ demand for foods that are both attractive and healthy.
Healthy diets offer a number of proven benefits: epidemiological and clinical studies show that a diet rich in fruits, vegetables,
unrefined grains, fish, and low-fat dairy products, and low in
saturated fats and sodium can reduce the risk of coronary heart
disease and hypertension and perhaps even of some types of
cancer (www.health.gov/dietaryguidelines). Some people have
changed their diet accordingly, and have benefited from it with
a much lower risk of heart disease (Hu et al., 2000). However,
for most consumers it is a struggle to meet dietary guidelines.
This is where industry steps in with special foods that promise
to improve health and well-being with less effort and sacrifice.
Such ‘functional’ foods match the spirit of our time. The 1970s
saw an upsurge of ‘natural’ and ‘organic’ foods, and the 1980s
saw the introduction of ‘low’ and ‘light’ foods with less calories,
cholesterol, or salt. Not all of them were palatable, but consumers
were willing to make a sacrifice, because at that time, eating for
long-term prevention of disease fitted the prevailing mood. Although by 1998 94% of US shoppers still said they sometimes
select food for health reasons, only 24% ate healthy for long-
Address correspondence to Martijn B. Katan, Division of Human Nutrition,
Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands.
E-mail: [email protected]
term prevention of disease, which is down from 45% in a 1990
survey (Consumer Motivation, 2000). By 1998, 41% are motivated by expectation of short-term benefits. Thus, consumers
are less willing to sacrifice taste or convenience for long-term
health. This has created a market for foods that combine taste and
convenience with the suggestion of short- or long-term health
benefits, i.e., for functional foods.
It is often questioned whether individual foods can be healthy
or unhealthy, as it is the composition of the entire diet that determines nutritional status. However, changes in diet necessarily
involve adding certain foods and leaving out others. We, therefore, suggest that certain foods could be called healthy, but only
for, a defined population. For instance, increased consumption
of whole-grain foods might prevent constipation and possibly
heart disease in adults, but an excess of whole-grain foods may
cause malnutrition in rapidly growing infants.
WHAT ARE FUNCTIONAL FOODS?
The definition of functional foods is a contentious issue.
Regulatory agencies do not recognize “functional food” as a
nutritional entity. Even in Japan, where functional foods originated, the term itself was not adopted because it was agreed
that all foods are already functional (Baily, 1999). The International Food Information Council (IFIC), which is supported
primarily by food, beverage, and agricultural industries, defines
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M. B. KATAN AND N. M. DE ROOS
functional foods as “foods that provide health benefits beyond
basic nutrition.”
The conundrum that such definitions create is illustrated by
a position paper on Functional Foods of the American Dietetic
Association (Thomson et al., 1999), which appears to accept
the IFIC definition, but also includes “whole foods” with beneficial health effects; examples given are fruits and vegetables,
as well as low fat cheese and low fat snack foods. Such definitions do not provide a clear demarcation between functional
and other foods, because almost any food can have some beneficial effect on some bodily function. By these definitions, even
tap water could be called a functional food, because a liberal
intake of water prevents cystitis, kidney and bladder stones, and
possibly bladder cancer. Therefore, in this study, we avoid definitions of the type “providing a health benefit beyond basic
nutrition.”
A more concrete definition was provided by the Institute of
Medicine of the US National Academy of Sciences, which defined functional foods as, “those foods in which the concentrations of one or more ingredients have been manipulated or
modified to enhance their contribution to a healthful diet (Committee on Opportunities in the Nutrition and Food Sciences,
1994). However, this definition also omits an aspect that is central to the functional foods discussion, namely the intimate connection between the term “functional food” and the marketing of foods with a health claim. In the reality of the market
place, the term “functional foods” is almost exclusively attached
to branded products that claim or suggest to improve health.
We, therefore, define a functional food as follows: A functional
food is a branded food which claims explicitly or implicitly
to improve health or well-being. This is similar to the definition given by Nestle (2002), who described functional foods
as, “products created just so that they can be marketed using
health claims.” Most, but not all, of such foods will also meet
the definition of the Institute of Medicine, “foods in which the
concentrations of one or more ingredients have been manipulated or modified to enhance their contribution to a healthful
diet.”
Most of the functional foods that meet our definition are
derived from existing traditional foods by adding ingredients
or modifiying the composition. The added ingredients are usually common food components. However, compounds usually
viewed as drugs may be present in dietary supplements, e.g.,
lovastatin in red yeast rice or ephedrine in Ma Huang tea. The
incorporation of either natural or synthetic drugs into foods may
become an important issue in future. Genetic modification will
also widen the options for the enrichment of foods with existing
or new ingredients. Classical plant breeding has already yielded
healthier crops, such as high lysine corn and low-erucic higholeic acid rapeseed oil. Until recently, modern genetic modification has typically involved pesticide resistance or shelf life
rather than health effects of foods, but the example of Golden
Rice, a genetically engineered rice strain that is high in provitamin A, shows the potential of genetic modification to produce
new health-promoting foods. The contribution of the present
strain to the eradication of vitamin A deficiency is limited because both the content and the bioavailability of the vitamin A
in it are low, but it offers ‘proof-of-principle’ for a whole new
class of genetically modified functional foods with great potential for human health, especially in populations with nutritional
deficiencies.
However, both Golden Rice and most current functional foods
contain food ingredients whose effects on health have been
known for a long time. A new functional food typically does not
represent a breakthrough in nutrition research—these are few
and far between—but rather a creative combination of existing
nutritional knowledge with new food technology and marketing. The same active ingredients that go into functional foods
can also be sold in a capsule as a dietary supplement. Although
foods and supplements are treated differently by the law in some
countries, the border between them is vague (Swanson, 2002):
a margarine with plant sterols is clearly a food, and a capsule
with plant sterols is a supplement, but what is a chocolate with
plant sterols—a food, or a chocolate-covered pill? The distinction is hard to make, and the active ingredients are the same.
Therefore, the present study deals with both functional foods
and supplements.
CAN FUNCTIONAL FOODS PROMOTE HEALTH?
Functional foods tend to be more expensive than their regular counterparts, but that expense is justified if the product
promotes health. There is an analogy here with the pharmaceutical industry: the cost of pharmaceutical drugs includes a
premium that provides the money needed for the research that
leads to new drugs. In the same way, the food industry could use
the profits from functional foods to fund nutrition research that
leads to healthy new foods, and industry also has the know-how
to produce foods that appeal to customers. This could lead to
healthy foods that actually sell, because functional foods have
been engineered to fit consumers’ taste. This engineering is crucial; drugs will sell whatever their look and taste, but foods
need taste, convenience, and appeal, or else they will not be
consumed. A model for such industry-sponsored research is the
development of foods enriched in plant stanols or sterols, which
lower LDL cholesterol. Functional foods can also help the consumer in reaching recommended dietary intakes; for example,
fruit juices enriched with calcium provide this essential nutrient
for children who refuse to or who cannot drink milk. Table 1
lists examples of such ‘traditional’ micronutrients—vitamins
and minerals—that have been used in functional foods. Functional foods can also help to eradicate nutrient deficiencies in
Third World countries. An example is the iodized salt, which has
proved both a public health and a marketing success in India.
Iodination of salt is a simple, but highly effective measure, to
eradicate goiter and other iodine deficiency disorders. However,
the list of functional foods that have actually been shown to improve health is short; many foods with health claims lack proven
utility.
PROMISES AND PROBLEMS OF FUNCTIONAL FOODS
Table 1
371
Examples of established nutrients that are used as functional food ingredients, and the authors’ opinion of the efficacy of the ingredients
Ingredient
Product examples
Health claim
Strength of evidence in humans
Folic acid
Cereals
Protects against neural tube defects
Dietary fibre
Drinks
Relieves constipation
Low in sodium
Unsaturated fatty acids
Sugar alcohols
Soluble fibre from whole oats
or psyllium husk
Soy protein
Drinks, soups
Spreads, cookies
Chewing gum
Cereals, cookies
Calcium
Cereals, fruit juices, milk
products, spreads
Cereals
Reduces blood pressure
Reduces risk of heart disease
Reduce caries risk
Reduces cholesterol and risk of heart
disease
Reduce cholesterol and risk of heart
disease
Protects against osteoporosis/help
maintain bone density
Decreases homocysteine and risk of
cardiovascular disease
Antioxidant; prevents cardiovascular
disease
Prevention/cure of common cold
Protects against cardiovascular disease
++ (From the Centers for Disease Control and
Prevention, 1993)
++ (Marlett et al., 2002; Cummings and Macfarlane,
2002)
++ (Sacks et al., 2001)
++ (Truswell, 1994; Sacks and Katan, 2002)
++ (Hayes, 2001)
++ for cholesterol lowering (Truswell, 2002)
Folic acid, vitamin B6
(pyridoxine)
Vitamin E
Zinc
Vitamin C
Drinks, bars
Supplements
Sweets, lozenges
Drinks, sweets
+ for cholesterol lowering (Lichtenstein, 1998)
+ for consumers with a low calcium intake (Heaney,
2000)
++ for homocysteine, but no hard evidence yet for
cardiovascular disease (Schnyder et al., 2002)
+ for observational studies but − for clinical trials
(Asplund, 2002)
+/− (Marshall, 2000)
+/− in observational studies, – – in clinical trials
(Asplund, 2002)
We graded the evidence according to the Australia New Zealand Food Authority criteria for levels and kinds of evidence for public-health nutrition (Truswell,
2001). The evidence consisted of randomized trials in humans, unless indicated otherwise in the Table. (++, proven efficacy, consistent effect seen in multiple
high quality studies; +, reasonable evidence for efficacy, effect seen in a limited number of studies, or some inconsistency between studies; 0, no solid data;
−, evidence for no effect, absence of an effect evident from a limited number of studies; – –, shown not to be efficacious, absence of an effect evident in multiple
high-quality studies.)
REGULATION OF FUNCTIONAL FOODS
We consider as the defining characteristic of a functional food
that it claims either explicitly or implicitly to improve health
or well-being. Most countries have issued regulations to protect the consumer from misleading claims (Table 2). Thus, both
the United States and the European Union ban claims that a
food can cure a disease. In Europe it is presently also illegal to
state that nutrients reduce disease risk, e.g., folic acid supplements prevent neural tube defects. This legislation is now being
reconsidered.
The United States does allow claims that foods reduce the risk
of disease (US Food and Drug Administration, 2004). The fourteen claims that have been authorized are listed in Table 3. A typical example is, “Frequent between-meal consumption of foods
high in sugars and starches promotes tooth decay. The sugar alcohols in [name of food] do not promote tooth decay.” There are
strict requirements for the foods that are allowed to carry such
claims. [http://www.cfsan.fda.gov/∼dms/hclaims.html, 24 July
2003].
In the United States, dietary supplements (but not foods)
may carry so-called structure/function claims (e.g., “antioxidants maintain cell integrity”; “tea with Echinacea supports the
body’s defense system”) that are largely unregulated. The manufacturer is responsible for ensuring the accuracy and truthfulness
of these claims; they are not approved by the FDA. Dietary supplements can, thus, be sold in the United States with very limited
evidence for their efficacy and safety. The border between foods
and supplements is fuzzy, and companies have repeatedly attempted to market foods as dietary supplements because that
gives them more room for health-oriented claims. Examples include drinks, soups and teas with St John’s Wort, Echinacea
or Ginkgo Biloba (Center for Sciences in the Public Interest,
1999). Thus, until recently, oversight over claims for foods in
the United States was much stricter than oversight over supplements. However, the 1994 Dietary Supplements Health and
Education Act, which largely removed FDA control over supplements, started a gradual erosion of the FDA system for health
claims for foods as well. In 1997, the Food and Drug Administration Modernization Act opened the way for health claims
to be made based on an “authoritative statement” from a United
States scientific body, rather than of a formal FDA review. Importantly, the 1999 United States District Court decision in the case
of Pearson v. Shalala (Shalala being the United States secretary
of Health and Human Services at the time) forced FDA to allow
“qualified” claims in the case that there is more evidence for,
than against, a relationship between a supplement and a disease.
As a result, the FDA now allows foods to make qualified health
claims in four categories: (a) for scientifically proven claims;
(b) where the science is good but not conclusive; (c) when there’s
limited science to support a claim; (d) when there is little scientific evidence supporting this claim [http://www.cfsan.fda.gov/
∼dms/hclmgui3.html; visited 10 August 2004.]. Originally, supplements could not make explicit claims referring to diseases,
but as of 2000, supplements may also claim to help common
conditions like acne, morning sickness in pregnancy, or memory loss.
The European Union recently proposed new rules that for
the first time would allow claims for foods to reduce risk
factors for disease; such claims would be evaluated by the
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M. B. KATAN AND N. M. DE ROOS
Table 2
Health claims and their definitions in the United States (US), United Kingdom (UK), European Community (EC) and the Netherlands
US, Food and Drug Administration1
Nutrient content claims
Example
Describe the level of a nutrient or dietary substance in the product, using
“Low in sodium”
terms such as “good source,” “high,” or “free”
Structure-function claims
Example
Indicates that a nutrient plays a role in a particular biological process
“Calcium aids in the growth and maintenance of bones” or
“Calcium builds strong bones”
Health claims
Example
Describe a relationship between a food substance and a disease or
“Diets low in sodium may reduce the risk of high blood
health-related condition
pressure, a disease associated with many factors”
UK, Joint Health Claims Initiative2
Health claims
Example
Direct, indirect or implied claims in food labelling, advertising and
“Calcium aids in the development of strong teeth and bones”
promotion that consumption of a food carries a specific health benefit
or avoids a specific health detriment.
Medicinal claims
Example
Health claims which state or imply that a food has the property of
“Calcium prevents osteoporosis”
treating, preventing, or curing human disease (injury, ailment or
adverse condition, whether of body or mind) or makes any reference
to such a property
EU, Directorate General Health and Consumer Protection (SANCO D4)3
Nutrition claims
Example
Claims describing the presence, absence or level of a nutrient contained
“Low in saturated fat”
in a foodstuff
[functional] health claims
Example
Health claims that describe the roles of nutrients or other substances in
“High in protein. Protein helps build and repair body tissues.”
growth, development and normal physiological functions of the body,
based on long-established and non-controversial science
Reduction of disease risk claim
Example
Any health claim that states, suggests or implies that the consumption of
“Sufficient calcium intake may reduce the risk of
a food category, a food or one of its constituents significantly reduces
osteoporosis in later life. Food A is rich in calcium.”
a risk factor in the development of a human disease
Netherlands, KAG/KOAG4
Health recommendation
Example
Indicates the maintenance or promotion of health, without making or
“Good for blood pressure”
suggesting a medical claim
Medical claim
Example
Claim to prevent, treat or cure disease
“For a good blood pressure”
1 www.cfsan.fda.gov/∼dms/hclaims.html
accessed 17 February 2004.
Health Claims Initiative, established in 1997 as a joint venture between consumer organisations, enforcement authorities and industry
bodies to establish a code of practice for the use of health claims on foods. Website www.jhci.org.uk/code.pdf accessed 17 February 2004.
3 European Commission ((http://europa.eu.int/comm/food/fs/fl/fl07 en.pdf visited 24 July 2003).
4 Code of practice for advertising and labelling for foods and drugs, as worked out by the industries involved. www.koagkag.nl accessed
17 February 2004.
2 Joint
proposed European Food Safety Authority. These proposals are
a step in the right direction, and they deserve the support of
nutrition scientists. However, the existing EU system for nutrition and health claims is complex and fragmented, with different member states having different rules. Changing these
rules will take quite a while. In contrast, the EU does have an
extensive system for checking the safety of foods, especially
of so-called ‘novel foods,’ which include genetically modified
foods.
The United States, Europe, and Japan all allow ‘nutrient content’ and ‘structure-function’ or ‘enhanced function’ claims,
which require less evidence than do outright health claims
[www.cspinet.org/reports/functional foods/, 11 February 2004].
These claims offer opportunities to mislead the public. Take the
statement, “This product is rich in calcium. Calcium helps to
build strong bones.” Legally these are two unconnected statements that are both true. One statement is about the composition
of the food, and the other about basic physiology. However, consumers may interpret such structure/function claims as claims
to reduce the risk of disease (United States General Accounting
Office, 2000; Andrews et al., 1998). Therefore they will assume
that eating the product will reduce the risk of fractures. In its
report on functional foods the US General Accounting Office
(2000) stressed that “the differences between health claims and
structure/function claims are not apparent to consumers and can
lead to possible misuse.” It would be naive to think that manufacturers are unaware of that. It may, in fact, be the reason why
the manufacturer put the claim on the package in the first place.
PROMISES AND PROBLEMS OF FUNCTIONAL FOODS
Table 3 Health claims that may be used in labelling a food or dietary
supplement in the United States [http://www.cfsan.fda.gov/∼dms/flg-6c.html
visited 24 July 2003]
Claims based on FDA’s review of the scientific literature
Calcium and Osteoporosis
Sodium and Hypertension
Dietary Fat and Cancer
Dietary Saturated Fat and Cholesterol and Risk of Coronary Heart Disease
Fiber-Containing Grain Products, Fruits, and Vegetables and Cancer
Fruits, Vegetables and Grain Products that contain Fiber, particularly
Soluble Fiber, and Risk of Coronary Heart Disease
Fruits and Vegetables and Cancer
Folate and Neural Tube Defects
Dietary Sugar Alcohol and Dental Caries
Soluble Fiber from Certain Foods and Risk of Coronary Heart Disease
Soy Protein and Risk of Coronary Heart Disease
Plant Sterol/stanol esters and Risk of Coronary Heart Disease
Claims based on ‘Authoritative Statements By Federal Scientific Bodies’
Whole Grain Foods and Risk of Heart Disease and Certain Cancers
Potassium and the Risk of High Blood Pressure and Stroke
Manufacturers also use the functional foods boom to reposition foods high in saturated fat, sugar, and calories as healthy.
Thus, producers stress the ‘natural goodness’ of ice cream because of its calcium content, or of candy bars because of the
energy (i.e., calories) that they provide.
There are, thus, plenty of opportunities for suggesting that
foods promote health without breaking the law, and these opportunities are vigorously exploited (Hagenmeyer, 2000). Thousands of companies offer supplements and “health” foods on
the Internet with fanciful and largely unfounded promises. Promotional materials, such as leaflets and press releases, are less
regulated than food labels and offer additional possibilities to
spread health messages. These methods may seem misleading, but it is unfair to lay the blame entirely with industry. The
present regulations (Table 2) leave ample room for misleading
Table 4
373
health claims, and some companies will inevitably exploit that
room.
The fuzziness that surrounds the requirements for health
claims is in sharp contrast with government regulations for
mandatory food fortification, such as the addition of iodine to
bread, fluoride to drinking water, vitamin D to margarines and
milk, or folic acid to cereal products. These measures are all
based on thorough research; they are effective and safe; they
are well policed and maintained. Also, fortified bread, milk,
and water reach the entire population, while functional foods do
not. A study in Finland showed that stanol-enriched margarines
are bought mostly by well-educated, high-income consumers
(Anttolainen et al., 2001).
FUNCTIONAL FOODS IN PRACTICE
Table 1 lists functional foods that use established vitamins
and minerals as their special ingredients; we also included our
opinion of their effectiveness. The health claims for some of
these ingredients are well substantiated, e.g., low-sodium foods
reduce hypertension, and high-fiber foods are effective against
common forms of constipation. For others, the evidence is
weaker; thus, the effect of zinc lozenges in preventing common colds is controversial (Marshall, 2000). Intakes of vitamins
and minerals from functional foods, and especially from supplements, may be much higher than from regular foods. Adverse
effects of such high intakes are a cause for concern (Hathcock,
1997). For example, mega doses of vitamin B6 are known to
cause peripheral neuropathy, and some authors have listed concern about excessive intakes of calcium (Giovannucci et al.,
1998).
Table 4 lists more novel or exotic ingredients of functional
foods. Most of the claims for the benefits from novel or
‘exotic’ ingredients have not been substantiated in studies of
A selection of newer functional food ingredients, and the authors’ opinion of their efficacy1
Ingredient
Product examples
Health effect or claim
Evidence in humans
Plant stanols and sterols
Margarine, yoghurt, cereal
bars
Lowers cholesterol and risk of coronary
heart disease
Lactobacillus GG bacteria
Yoghurt
Reduces diarrhea
Lactobacillus GG bacteria
Other ‘probiotic’ live
bacteria, plus fermentable
sugars (‘prebiotics’)
Isoflavones (phyto-estrogens)
Yoghurt
Yoghurt
Reduced risk of early atopic disease
Enhanced immunity
++ for LDL cholesterol lowering; effect on
coronary heart disease is by implication (Katan
et al., 2003)
+ for rotavirus-induced diarrhea in infants (Isolauri
et al., 1994)
− for antibiotic-induced infections (Thomas et al.,
2001)
+/0 (Kalliomäki et al., 2001)
0 Some effects on biomarkers but none on disease
(De Roos and Katan, 2000)
Soy products
Catechins
Conjugated linoleic acid
(CLA)
Tea
Supplements (small
amounts occur naturally
in milk, beef and lamb)
Reduce menopausal symptoms;
osteoporosis; cardiovascular disease
Reduce cardiovascular risk
Reduces body weight; protects against
cancer
0 Little evidence from clinical trials (van der
Schouw et al., 2000; Glazier and Bowman, 2001)
+/0 (Mukamal et al., 2002; Hollman et al., 1999)
0/− Minimal effects on body weight in humans
(Belury, 2002)
footnote to Table 1 for grading criteria. (++, proven efficacy; + reasonable evidence for efficacy; 0, no solid data; −, evidence for no effect; – – shown not
to be efficacious).
1 See
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M. B. KATAN AND N. M. DE ROOS
the kind required to prove efficacy and safety in drugs (Linde
et al., 2001). However, a few have been well investigated and
show promise of reducing disease risk. One example is sterols
and stanols. Margarines and other foods have been enriched
with plant stanols or sterols, which lower LDL cholesterol by
10% and could, thus, make an important contribution to the prevention of coronary heart disease. Many well controlled trials
have documented the efficacy of sterols and stanols for lowering
LDL, and no major adverse effects have been noted. However,
long-term safety and clinical efficacy have not been evaluated
in large-scale clinical trials of the size and duration customary
for new drugs. The Health Council of the Netherlands, therefore, discourages the use of plant sterols by consumers who do
not benefit from a cholesterol-lowering effect, especially children and pregnant women (Health Council of the Netherlands,
2001), and other regulatory agencies have suggested similar
limitations.
Pre- and probiotics are another example of well-researched
functional ingredients. Probiotics are viable bacteria that survive
passage through the gastrointestinal tract and exert beneficial effects on the consumer (Schrezenmeir and De Vrese, 2001). Some
health effects have been well documented, e.g., foods with lactic
acid bacteria may reduce the severity of some types of diarrhea
(De Roos and Katan, 2000), and there are indications that they
reduce the risk of atopic eczema in high-risk infants (Isolauri et
al., 2000; Kalliomäki et al., 2001). However, little evidence is
available for effects such as cancer prevention and serum cholesterol lowering (De Roos and Katan, 2000). Prebiotics are nondigestible food ingredients—usually carbohydrates—that bene-
Table 5
ficially affect the host by selectively stimulating some of the
bacterial species already resident in the colon, and thus, attempt
to improve host health (Gibson and Roberfroid, 1995). Health
effects, however, appear to be limited to improved bowel function; no adequate scientific support in the form of randomized
trials in humans exists for other proposed health effects, such
as cancer prevention, lipid lowering, and prevention of diarrheal
diseases (Duggan et al., 2002).
A third well-investigated ingredient is polyphenols. High intakes of tea rich in catechins and other flavonoid polyphenols
have been associated with a reduced risk of coronary heart disease (Mukamal et al., 2002). A clinical trial to evaluate these
effects would seem justified and feasible. Whether polyphenols explain the so-called French paradox is questionable, as red
wine and olive oil are not particularly good sources of phenolic
compounds when compared with tea or coffee (De Vries et al.,
2001).
Table 5 lists herbal ingredients that have been used in both
supplements and foods, although amounts in foods are usually
much lower. Safety is a concern, as exemplified by herbal teas
with Aristolochia, which causes renal cancer (Kessler, 2000)
and products with ephedra, which causes hypertension, strokes,
and seizures (Haller and Benowitz, 2000). The use of herbal
medications with Echinacea, ephedra, garlic, ginkgo, ginseng,
kava, St. John’s Wort, and valerian is discouraged in presurgical
patients (Ang-Lee et al., 2001). Complications may arise from
herb-drug interactions, as well as from direct effects such as
bleeding and hypoglycemia. A report from the United States
General Accounting Office also concluded that unsafe products
Herbs and herbal extracts typically used in supplements that are sometimes also added to foods, and the authors’ opinion of their efficacy1
Ingredient
Product examples
Health effect or claim
Evidence in humans
Guarana (Paulinia cupana)
Drinks
Ginkgo (from Ginkgo biloba)
Drinks, cereals
Extra energy, improved cognitive
performance
Enhances memory and alertness
Kava (from Piper
methysticum)
St. John’s Wort (Hypericum
perforatum)
Drinks, cereals
Echinacea
Drinks
Supports immune system, antibiotic
Ginseng
Drinks, teas,
cereals
Extra energy, reduces body weight,
mind-supporting
Red yeast rice
(Not used in foods)
Lowers cholesterol
++
Efficacy is due to high caffeine content
+ for halting cognitive decline in senile dementia (Beaubrun
and Gray, 2000; Ernst, 2002; Le Bars and Kastelan, 2000).
− for enhancing memory or alertness in healthy individuals
(Ernst, 2002; Le Bars and Kastelan, 2000; Solomon et al.,
2002)
+/0 for anxiolytic effect (Beaubrun and Gray 2000; Ernst,
2002), though not at the levels found in drinks and cereals
+/0 for mild to moderate depression (Gaster and Holroyd,
2000), but effect smaller in recent trials (Shelton et al.,
2001)
+/0 for common cold (Melchart et al., 2000) but trial data
weak and inconclusive (Ernst, 2002)
0
Inconclusive (Kitts and Hu, 2000; Bucci, 2000); no
evidence of efficacy for any condition (Ernst, 2002)
++
Effect largely due to lovastatin produced by the yeast
(Havel, 1999)
Drinks, cereals
Relaxation, mental balance, reduces
stress
Mental balance, lifts the spirits, reduces
anxiety
footnote to Table 1 for grading criteria. ++, proven efficacy; + reasonable evidence for efficacy; 0, no solid data; −, evidence for no effect; − shown not to
be efficacious.
2 Most of these ingredients are illegal in conventional foods in the USA; when added to foods the amount is often so low that effects may be much less than from
supplements.
1 See
PROMISES AND PROBLEMS OF FUNCTIONAL FOODS
may reach consumers because of a lack of standards, a lack of
warnings on the label (for example, St. John’s Wort may decrease
the efficacy of HIV drugs), and poor reporting and investigation of health problems caused by supplements and functional
foods (United States General Accounting Office, 2000). A new
report also recommends caution about the use of herbal “antiaging” therapies by seniors, especially those who have underlying diseases (United States General Accounting Office, 2001).
The same concerns hold for foods containing these ingredients,
although supplements are a more important source and provide
much higher doses.
The safety situation is not likely to improve, and there is also
not much impetus for manufacturers to show that their functional foods are efficacious. There are now functional foods and
supplements on the market for just about any disease and organ,
including immune response, cancer, gastro-intestinal diseases,
mood, memory and alertness, energy, strength and stamina, and
aging. Some of these products sell well and create profits for
their manufacturers, although evidence for efficacy is marginal.
As Southon stated, “Although evidence of benefit is not necessary for effective marketing of a product, marketing would be
more ethical if benefit could be demonstrated” (2000). It may
seem cynical to market foods with suggestions of health benefits when the evidence is clearly inadequate. But, can we hold
food and supplement producers to standards of ethics that society has not codified by law? It takes a lot of money and stamina
to prove that a food ingredient really prevents or cures a disease,
and recent experience has not been encouraging. For example,
beta-carotene was widely believed to reduce cancer risk in smokers, because intake of carotene-rich foods was associated with
less cancer, as were high levels of carotene in blood. As it is,
carotene supplements increased risk of lung cancer in smokers
(The Alpha-Tocopherol Beta Carotene Cancer Prevention Study
Group, 1994; Omenn et al., 1996). Large clinical trials of antioxidants have also yielded disappointing outcomes (Yusuf et al.,
2000), although a recent high-quality clinical trial showed that
they can slow down macular degeneration when taken in combination with zinc (Age-Related Eye Disease Study Research
Group, 2001). The most positive exception is fish oil which
proved to be remarkably effective in preventing sudden cardiac
death (Gissi-Prevenzione Investigators, 1999). Due to the many
negative results, manufacturers may think twice before investing huge amounts of money into research that may well kill a
successful product. Even if the research shows that the product
works, the manufacturer may not recover his investment, because foods are difficult to patent. Again, it is the legislative system that works against the emergence of new health-promoting
foods.
WHAT EVIDENCE SHOULD WE DEMAND
FOR FUNCTIONAL FOODS?
Well tested systems for evaluating the validity of health
claims for foods exist in many countries. Examples are the
375
“Significant Scientific Agreement” criteria of the United States
Food and Drug Administration (U.S. Food and Drug Administration, 2004), the Dutch Code of Practice (Netherlands Nutrition Centre, 2004), and the UK Joint Health Claims Initiative
(Joint Health Claims Initiative, 2004). Such evaluations should
become mandatory for all explicit or implied claims that a food
promotes health. The criteria for the safety and efficacy of functional foods do not need to be the same as for drugs, because there
is an important distinction between food ingredients and drugs.
Drug research isolates or synthesizes molecules that are new to
human metabolism, but nutrition deals with molecules that have
been part of the diet of large populations for many centuries.
Studying associations between diet and health in such populations is a powerful way to generate leads for health-promoting
foods and to investigate their efficacy and safety. Nutritional epidemiology has generated numerous leads, many of which have
led to healthy foods, such as the examples in Table 1. However,
controlled experiments must also be used to show that a functional food ingredient is effective and safe. For functional foods
that contain widely consumed nutrients in moderate amounts,
it may be enough to demonstrate that the nutrients are properly
absorbed in humans. Examples are foods fortified with folic
acid or calcium. For more exotic components, or for dosages
much higher than usual, the evidence required may be closer to
that required for new drugs, i.e., short- and long-term controlled
experiments showing safety and efficacy in animal models, in
healthy volunteers, and in the population at risk to which the
functional food is targeted. It is often stated that clinical trials showing actual reduction of disease in humans (so-called
‘phase III trials’) are prohibitively expensive. However, most
major food industries or commodity associations could easily
bear the cost of such trials, provided that the outcomes would
increase sales or profit margins. For instance, epidemiological
data (Mukamal et al., 2002) suggest that consumption of tea is
associated with a 30% reduction of cardiac death in myocardial
infarction survivors. A clinical trial to test this hypothesis would
require 2500 patients to reach a power of 80% at α = 0.05. Such
a trial might cost about $2 million per year for 5 years. In comparison, the advertising budget of the major United States tea brand
in 1998 was $41.8 million in one year (Nestle, 2002). Thus, the
worldwide tea industry could easily fund a clinical trial if the
outcome were expected to assist marketing. Such research is
more likely to happen if governments provide the perspective of
a health claim should the trial be successful. Such claims may
not be exclusive to the company that funded the research, but that
does not necessarily make the research unprofitable. A company
may want to prove the health effect of an ingredient because it
expects to beat its competitors in creating tasty, convenient, and
competitively priced foods with that ingredient. Also, producers
may collectively fund research on commodities from which they
all may profit.
Proper legislation is essential to the success of evidencebased functional foods. If a claim has been properly proven,
e.g., through a clinical trial, then manufacturers should be free to
advertise it; if the claim is untrue, it should be suppressed by law.
376
M. B. KATAN AND N. M. DE ROOS
DO FUNCTIONAL FOODS HAVE A FUTURE?
On a short-term basis, functional foods do have a future.
There is plenty of demand. In 1999, United States consumers
spent about $15 billion for dietary supplements and $16 billion
for functional foods (United States General Accounting Office,
2000). However, the system for ensuring the validity of health
claims (or in legal terms: structure/function claims or statements
of nutritional support) in the United States is eroding, and regulations in most of the rest of the world are even weaker. As
a result, consumers are exposed to unfounded claims and allusions to health benefits of foods and supplements. But, that is
not a solid basis for long-term commercial success. Sooner or
later, consumers will realize that they have been misled. This
may explain why the sales of dietary supplements in the United
States have seen some decline since their peak years of the midlate 1990s. If governments do not set clear and strict standards
for efficacy and safety of functional foods, then the field has no
real future.
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