Nutraceuticals and Functional Foods in - World Food Science

Nutraceuticals and Functional Foods in
Health Promotion and Disease Risk Reduction
by Fereidoon Shahidi, Department of Biochemistry,
Memorial University of Newfoundland, Canada
Based on Keynote presentation at IUFoST Conference held in conjunction with
Fi Asia/China, Shanghai, March 2007.
Introduction
Epidemiological and clinical studies have demonstrated the relationship between diet and
health status. It is well known that populations consuming a large proportion of plant-based foods,
including fruits, vegetables, whole grains and cereals or those with a high intake of seafoods,
have a lower incidence of cardiovascular diseases and certain types of cancer. Therefore,
interest has been expressed in functional foods, nutraceuticals and dietary supplements.
Functional foods are defined as being similar in appearance to conventional foods, are consumed
as part of a usual diet, and are known to improve health status and render physiological effects
beyond basic nutritional function expected of conventional foods. However, nutraceuticals are
products produced from foods, but sold in the medicinal form of capsule, tablet, powder, solution,
or potion. They are not generally associated with food and have demonstrated physiological
benefits and/or provide protection against chronic diseases; these are now referenced as “natural
health products” in Canada. Thus, the optimum well-being expected to be rendered by functional
foods and nutraceuticals in the short term is to provide a disease-free life with the same span as
is currently the case. The long-term goals may include expanding of a healthy life span beyond its
current limits.
In the case of plant foods, phenolics and polyphenolics constitute a main group of
compounds that render beneficial effects, in part, due to their antioxidant potential, among other
mechanisms of action. For marine oils, their omega-3 fatty acid constituents are known to affect
health status by influencing eicosanoid metabolism or by other mechanisms. The highly unsaturated
fatty acids (HUFAs) present in marine oils are responsible for their many beneficial effects.
Docosahexaenoic acid (DHA; C22:6n-3) is indeed a major fatty acid constituent of the grey matter
of the brain and the retina of the eye, among others (Shahidi and Finley 2001). The organs most
influenced by long-chain omega-3 fatty acids are those with electrical activity such as the brain,
the heart and the eye.
This article provides a cursory account of nutraceuticals and functional foods with emphasis
on phenolics and polyphenolics as well as the omega-3 fatty acids.
Health benefits of nutraceuticals and functional foods
The health benefits are primarily in several areas, including cancer, atherosclerosis and other
cardiovascular disease (CVD), the aging process and immune response-enhancing effect,
diabetes and mental health. The effects rendered by nutraceuticals and functional foods are due
to a cocktail or a soup of phytochemicals and bioactives present in the products of interest. Thus
phytates, phenolic acids, flavonoids/isoflavonoids, coumarins, lignans, carotenoids, terpenes,
enzyme inhibitors, and saponins are present in soybean. Phenolic compounds function as
antibiotics, natural pesticides, signaling substances for the establishment of symbiosis with
rhizobia, attractants for pollinators, protective agents against UV light, insulating materials to
make cell walls impermeable to gas and water, and structural material to give plants stability
(Shahidi and Naczk 2004).
The mechanism by which anticarcinogenic effects of phytochemicals in plant foods are
rendered are varied but generally include one or a combination of possibilities: antioxidant effect,
effect on cell differentiation, increased activity of enzymes that detoxify carcinogens, inhibition of
N-nitrosamine formation, change of estrogen metabolism, change of colonic milieu, preservation
of integrity of intracellular matrices, effect on DNA methylation, maintenance of DNA repair,
increase in apoptosis of cancer cells and decrease in cell proliferation.
Phenolics and Polyphenolics

Phenolic compounds are among phytochemicals that may render their effects via
antioxidation and relief from oxidative stress and its consequences. In general, free radicals are
part of life as we consume some 3.5 kg of oxygen each day, some of which is not completely
reduced, thus leading to the formation of free radicals and other reactive oxygen species (ROS)
such as superoxide, hydroxyl radical, peroxyl radical, and alkoxyl radical, as well as hydrogen
peroxide and other peroxides. Therefore, several kilograms of peroxides and other ROS may be
produced in our body each year. Many diseases are caused by excess ROS. In healthy
individuals, free radicals and other ROS are neutralized by antioxidant defence mechanisms in
the body, including superoxide dismutase and glutathione, among others. However, endogenous
systems may not provide sufficient protection in individuals suffering from certain diseases; in
such cases help from dietary sources is important.
The antioxidative effect of phenolics (Shahidi 1997) in functional foods is due to a direct free
radical scavenging activity (Halliwell 1996; Shahidi 2000; Shahidi and Ho 2007; Wettasinghe and
Shahidi 1999a,b), reducing activity and an indirect effect arising from chelation of prooxidant
metal ions. The chelation of metal ions generally requires ortho-dihydroxylation on the phenyl ring
in phenolic acids and flavonoids or the presence of a 3- or 5-hydroxyl group in flavonoids.
The endogenous phenolics in plant foods are the largest group of secondary metabolites
originating from phenylalanine and, to a lesser extent, in some plants from tyrosine via the action
of phenylalanine ammonia lyase (PAL) and tyrosine ammonia lyase (TAL), respectively (Shahidi
and Naczk 2004). The respective products are cinnamic acid and p-couramic acid that serve as
the main phenylpropanoid (C6-C3) compounds and these lead to the formation of benzoic acid
(C6-C1) derivatives by loss of a 2-carbon moiety as well as to chalcones (C6-C3-C6), stilbenes
(C6-C2-C6), and flavonoids (C6-C3-C6) by combination with 3 molecules of malonyl coenzyme A.
However, tannins, both condensed and hydrolyzable, produced via condensation of flavan-1,3-
diol molecules with one another or via reaction of gallic acid with sugars, respectively, are among
phenolics that are better known for their effect on precipitating proteins and, hence, their antinutritional
effect. However, even these latter compounds are known to exert health benefits which
generally follow a mechanism similar to that known for their anti-nutritional activity.
Among plant materials, fruits and vegetables contain phenolics, mainly belonging to the
flavonoids family, but also phenolic acids. Meanwhile, cereals contain a wide range of phenolic
acids, belonging mainly to the benzoic acid and cinnamic acid groups. Phenolic acids are different
from other phenolic compounds by bearing acidic properties due to the presence of a
carboxylic acid group. Ferulic acid and p-coumaric acid are the major phenolic acids found in
many cereals, including barley (Liyana-pathirana and Shahidi 2004). A significant proportion of
these phenolic acids are linked to lignans and arabinoxylans (Nordkvist et al. 1984). Ferulic acid
is highly concentrated in the cell walls of aleurone layer that is rich in arabinoxylan. Phenolic
compounds in cereal grains can be found in the free, soluble conjugate or esterified, and
insoluble-bound forms. It is reported that 74 and 69% of total phenolics present in rice and corn,
respectively, are in the insoluble-bound form (Adom and Liu, 2002). Most of the studies found in
the literature so far have not looked into insoluble-bound phenolic compounds, hence results
reported are often underestimated.
Phenolic esters can be hydrolyzed to release phenolic acids by different means. Alkaline,
acidic or enzymatic hydrolysis methods are adopted in order to release insoluble-bound phenolics
from the cereal matrix (Liyanapathirana and Shahidi 2004). Generally, alkaline hydrolysis is the
method mostly used for extracting esterified or bound phenolics at room temperature and we also
used alkaline hydrolysis to release phenolic acids present in the insoluble-bound form.
We have demonstrated that while free phenolics in barley extracts are present at 0.18-0.42
mg ferulic acid equivalents per gram of material, the soluble conjugates occur at 0.42-0.81 and
insoluble-bound fraction at 2.03-3.36 mg/g as ferulic acid equivalents. Meanwhile, wheat and its
by-products contained >80% of their total phenolics in the bound form. The content of bound
phenolics in the whole grain in hard and soft wheat was 22 and 18.5 times higher than the total of
free and soluble esters, respectively.
Adom and Liu (2002) analyzed a number of cereals, namely corn, wheat, oat and rice and
reported that corn had the highest free phenolic content (0.411 mg/g of grain), followed by rice
(0.407 mg/g of grain), then wheat (0.368 mg/g of grain), and oat (0.343 mg/g of grain). The
content of insoluble-bound phenolic was significantly higher among all of the above cereals.

LDL cholesterol oxidation, DNA nicking and proliferation
Oxidation of cholesterol leads to the formation of a plaque in the arteries and, hence, is a
leading cause of cardiovascular disease. Phenolics and polyphenolics in foods and plant-based
source materials are expected to have a positive effect on prevention of low-density lipoprotein
(LDL) cholesterol oxidation which may be exerted by a free radical scavenging mechanism
(Siriwardhana and Shahidi 2002). In a study on almond and hazelnut, we found that extracts of
almond and hazelnut, to a large extent, inhibited copper-induced LDL cholesterol oxidation.
Brown skins over almond and hazelnut flesh had a much higher activity than the whole nuts,
presumably due to the presence of a large proportion of polyphenolic compounds in them than
those in the flesh. The beneficial effects of a hazelnut-enriched diet on plasma cholesterol profile
of hypercholesterolemic men was recently reported (Mercerligil et al. 2007). Similarly, mutation of
deoxyribonucleic acid (DNA) and its breakdown may serve as a main cause of cancer in humans.
We found that nicking of DNA, induced by peroxyl radical, in an in vitro study, was largely
inhibited by extracts of nuts such as almond and their products. Again, results demonstrated that
certain components of food that are usually removed and discarded during bleaching, refining,
and processing are essential for health promotion and disease prevention. Finally, whole barley
extracts were found to be effective against proliferation of Caco-2- human cancer cells. The
inhibition effect of whole barley extract was 20.5-42.6% at a 0.5 mg/mL and values so obtained
correlated well with Trolox equivalent antioxidant capacity (TEAC) and total phenolic contents
(TPC). Parry et al. (2006) also found that extracts of fruit seed flours were effective against
proliferation of Caco-2 cells.
Fish oils and their health effects
A close scrutiny of the dietary fat intake of Eskimos and Danish populations showed that,
while the energy from fat intake was similar in both groups, and despite a higher intake of
cholesterol (790 mg/day) by Eskimos compared to Danes (420 mg/day), the incidence of myocardial
infarction (MI) in the former group was only 7% of that in the latter one (Dyerberg et al.
1975; Bang et al. 1976). Further analysis of lipid constituents in the two groups indicated that,
indeed, the Eskimos consumed a much higher level of n-3 PUFA, mainly from dietary intake of
marine foods, principally fish and seal, than the Danish population; the latter group used only
10% of n-3 PUFA that was consumed by the Eskimos. To elaborate on the beneficial effects of
marine oils in the prevention of MI, one may consider 3 stages associated with heart attacks.
These include injury to the coronary artery wall, build-up of a fatty fibrous plaque in the arteries,
known as atherosclerosis, and formation of a blood clot, known as thrombosis. If a clot forms in
an artery which is already constricted by atherosclerosis, a heart attack may occur. Consumption
of marine oils leads to thinning of blood, lowering of triacylglycerol and, possibly, cholesterol
levels and, hence, clot formation as well as fat deposition. Thus, intake of 24 g of fish/day
increased the survival rate from coronary heart disease by some 20% over a period of 16 years.
In another study, it was found that breast-feeding had a direct positive effect on verbal skill,
performance skill, and overall IQ of infants in comparison with their formula-fed counterparts. The
difference in all of these was 8.1 to 8.9%. Furthermore, DHA status of maternal plasma
phospholipids decreased by some 40% during pregnancy, especially during the last trimester.
This is due to the essentiality of DHA in the development of the grey matter of the brain as well as
the retina of the eye and the components of the heart of the fetus (Shahidi and Finley 2001).
Omega-3 fatty acids, including DHA, originate from phytoplankton and algae and are
transferred to fish through the food web. Marine species are, hence, rich in omega-3 fatty acids
and the corresponding oils are obtained from the flesh of fatty fish such as herring and mackerel,
liver of white lean fish such as cod and halibut and blubber of marine mammals such as seals
and whales. Marine oils contain a generally high level of long-chain omega-3 PUFA (Shahidi
2000b). This leads to high sensitivity of the oil to oxidative deterioration and off-flavor formation.
Thus the oils need to be subjected to refining, bleaching, and deodorization (RBD). The final RBD
oil needs to be stabilized by appropriate antioxidants in order to eliminate the deleterious effects
of oxidized compounds and to take advantage of the beneficial health effects of their omega-3
components without changes in their sensory quality (Shahidi and Kim 2002).
Products in which marine oils may be incorporated include bread, cereal products, spread,
milk, mayonnaise and salad dressing, crackers and bars, as well as infant formulas. The oils may

e microencapsulated and then used in different applications. However, the solid microcapsule
particles must be washed properly with a nonpolar solvent to remove any unencapsulated oil that
may otherwise be oxidized. However, application of the oil is most successful in products that are
usually consumed within a short period of time. Our experience shows that bread and milk
products, commonly used within 2 weeks from their production date, may well serve as the best
carriers for omega-3 fatty acids (Alasalvar et al. 2002).
Multi-component Systems Containing Phenolics
In an effort to produce multi-component nutraceutical ingredients containing both marine oils
and polyphenols, we used dechlorophyllized green tea extracts and seal oil as well as menhaden
oil. The products obtained were found to be more stable to oxidation than oils devoid of tea
catechins. However, if the samples were not dechlorophyllized, the stabilizing effect of catechins
was counteracted by the photosensitizing effect of chlorophylls, hence destabilization of the oils
(Wanasundara and Shahidi 1998).
A considerable amount of minor components in the oils with bioactivity may be removed by
over-processing of edible oils. Although removal of off-flavor components and environmental
pollutants from edible products by processing is essential, the bioactives present could be
recovered and returned to the oils. Similarly, debranning of cereal grains would lead to the
removal of bioactives that are concentrated in the outer layers, mainly the bran. Addition of
seeds, raisin and nuts to whole grain bread would also enhance its antioxidant potential and its
health benefits.
Conclusions
Functional foods and nutraceuticals may provide a means to reduce the increasing burden on
the health care system by a continuous preventive mechanism. A large number of
phytochemicals and bioactives are present in foods of plant origin as well as seafoods and other
animal-based products. The synergistic effects rendered by a combination of bioactives present
in source materials and the complementary nature of phytochemicals from different sources are
important factors to consider in the formulation of functional foods and in the choice of a healthy
diet.
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