nutraceutical
nutraceutical
nutraceutical
Topic-1
NUTRACEUTICAL
4.1 General Aspects
Nutraceuticals are a group of products that are more than food but less than pharmaceuticals.
Unfortunately there is still no internationally accepted definition of these products therefore their
judgment varies country by country. In most countries nutraceuticals are taken as part of dietary
supplements. Frequency of nutraceuticals use is 50%–70% in developed countries’ population
and this number is increasing by the age. Ladies use more nutraceuticals than men. From a safety
point of view nutraceuticals are trusted products even if they are not approved by authorities like
pharmaceuticals. With a lot of nutraceuticals clinical studies have been carried out and results
originating from these trials support their effectiveness as well as their general safety.
Nutraceuticals represent however a certain risk if they were to be used without medical control
as interactions with medication can be harmful, especially in vulnerable (old, very young,
chronically sick) populations. Examples from fish oil preparations, prebiotics, and probiotics are
reviewed. The term 'Nutraceutical' was coined from 'nutrition' and 'pharmaceutical' in 1989 by
DeFelice and was originally defined as ‘a food (or part of the food) that provides medical or
health benefits, including the prevention and/or treatment of a disease.
A Nutraceutical may be a naturally nutrient- rich food such as spirulina, garlic, soy or a specific
component of a food like omega-3 oil from salmon. They are also known as medical foods,
nutritional supplements and dietary supplements. It ranges from isolated nutrients, dietary
supplements, genetically engineered ‘designer’ foods, herbal products, and processed products
such as cereals and soups. They have received considerable interest because of their presumed
safety and potential nutritional and therapeutic effects. People can improve their health by
supplementation and by consuming foods that have been formulated or fortified. Another reason
for the growing trend of Nutraceuticals is public education, renewable source, cultivation and
processing, environmental friendliness and local availability. United Kingdom, Germany and
France were the first who considered that diet is more important factor than exercise or
hereditary factors in achieving a good health. Canada defined them as ‘a product produced from
foods but sold in pills, powders, (potions) and other medicinal forms not generally associated
with food’. In India, Nutraceutical are the food components made from herbal or botanical raw
materials, which are used for preventing or treating different types of acute and chronic maladies.
The functional foods revolution, which has swept through human nutrition over the past decade, is
now also happening in companion animal nutrition. This is not surprising, since it is estimated
that between 50-60% of households in the US own at least one cat or dog and a large portion of
these pet owners will be health conscious individuals who not only are particular about their own
diets but also those of their pets. Powerful market forces are fuelling the interest in functional
foods; with rapid advances in scientific knowledge supporting the vital role of diet in health and
disease prevention. This, combined with an increase in consumer demand and the change in
perspective on food (no longer viewed as merely a means of providing sustenance), along with
technical advances that are allowing the development of health-promoting foods that can be
marketed to health-conscious consumers at a premium, means that it is not surprising that the
functional food/Nutraceutical industry is booming. As a consequence, the need for high quality
diets and dietary supplements, nutraceuticals and functional foods specifically formulated for
companion animals has grown, along with the need for information detailing the evidence
supporting claimed health benefits, recommended dosages and safety. Most important, this
evidence must be in the target species, and it is therefore essential that the regulatory environment
is adequate to cope with the wealth of new products and hence health claims that are likely to be
associated with them.
Nutraceuticals and functional foods
As defined by the American Dietetic Association, a Nutraceutical is “any substance that may be
considered a food or part of a food and provides medical or health benefits, including the
prevention and treatment of disease”. A functional food is defined as “any modified food or food
ingredient that may provide a health benefit beyond the traditional nutrients it contains”. A
Nutraceutical therefore is not a functional food. It is a dietary supplement that encompasses non-
nutritive food components such as phytochemicals, vitamins and minerals, amino acids or
botanical compounds such as bioflavonoids or phytochemicals. It is consumed simply for its
health promotional or nutritional benefits rather than for its taste, flavor or aromatic attributes.
One class of such substances are phytochemicals, which are physiologically active, naturally
occurring compounds synthesized by plants that are not classified as nutrients but nonetheless
impart a health benefit when consumed. Medicinal herbs, too, have long been valued for their
health protecting compounds. Scientists are now working to create nutraceuticals that have higher
and more consistent levels of bioactive compounds.
As scientific research identifies more substances with medical or health benefits, further
nutraceuticals will be identified. A functional food is one derived from naturally occurring
ingredients that is consumed as part of the normal diet and is beneficial to health. It may reduce
the risk of acquiring a disease (but generally not prevent it), reduce the severity of symptoms of a
disease, and/or enhance physical performance or mental dexterity. If the diet is sufficient already,
no effect at all may be seen. A functional food must remain a food, it is not a pill or a capsule, and
its benefits must be demonstrable at a normal level of consumption.
Probiotics
Probiotics are defined as live microbial food supplements that beneficially influence the health of
the host. Generally this was considered to occur by improving the microbial balance; however it is
becoming increasingly clear that probiotics elicit at least some of their health benefits via
immunomodulation. The gastrointestinal tract fulfills many functions aside from digesting and
absorbing nutrients. One of these is that the gut is host to a complex mixture of microbes that
make up our resident gut micro flora, some of which may play a key role in maintaining human
health. Bifid bacterium and Lactobacillus are strongly associated with optimum microbial balance
in the gut, and it is for these two genera that the greatest body of evidence for health promoting
properties of probiotics exists.
Requirements of Probiotics
For a microbe to act as a probiotic it must satisfy a number of important criteria. It must not be
toxic or cause disease; it must be capable of resisting the acids and bile involved in the digestive
processes of the animal’s stomach (microencapsulation); the microbe must be able to establish
itself and ‘colonize’ the gut of the target animal; it should be able to show an ability to inhibit the
growth of pathogens or to have some other benefit in laboratory conditions; and it must be
capable of surviving manufacturing process and have a reasonable shelf life.
Probiotics effectively flood the gut with billions of live, beneficial bacteria to help boost the gut’s
normal micro flora. In this way they are able to improve various aspects of growth and
performance of animals by aiding digestion, by breaking down cellulose and other indigestible
substances, promoting the synthesis and absorption of vitamins and minerals, which can in turn
stimulate both nonspecific and certain specific host defense mechanisms of the immune system.
Probiotics are also able to prevent the proliferation of potential disease causing pathogens such as
E. coli and Salmonella. This can occur in two ways. Firstly, by generating increased resistance to
infectious diseases either by direct antagonism or by stimulating immunity (e.g., increased
phagocytic activity and elevation of secretory IgA levels). Probiotics have therefore been
proposed for use in animals to establish a healthy gut micro flora and prevent establishment of
pathogenic bacteria immediately following birth; to re-establish beneficial micro flora depleted by
antibiotics and prevent re-infection by pathogens; to treat or prevent scouring by suppression and
exclusion of pathogenic bacteria; and to reduce the effects of stress such as fear, transportation,
change of environment, diet changes, training, competition, temperature extremes, injury, surgery
or vaccination.
A number of probiotic-containing products are currently being sold specifically for use in
companion animal diets. Despite this fact, there appears to be a scarcity of relevant literature to
support their current usage. Probiotic products are often sold with unsubstantiated or very general
health claims, and it is becoming increasingly clear that all probiotic strains are not created equal.
In addition, there appears to be some controversy as to the quantity of viable probiotic organisms
required to confer health benefits in both man and animals. Levels ranging from 106 to 109 CFU
at the time of consumption have been suggested, and various minimum standards have been set
around the world.
Further controversy has arisen following reports that a number of probiotic products either did not
contain the listed species, contained extra species, or the levels of viable probiotics were less than
one tenth of that stated on the package. Since daily consumption of probiotics is recommended, it
is of vital importance that information detailing the probiotic strains (including accurate viability
counts, dose, delivery medium and safety), for which specific health benefits have been
conclusively demonstrated, and information on the species tested, be made available to the pet
owner.
Of the limited studies carried out in companion animals, one aimed to investigate a number of the
factors critical for demonstrating that a particular microorganism can act as a probiotic. The
authors investigated the effects of the expansion-extrusion process required for pet food
manufacture on spore survival of Bacillus CIP 5832 in the production of a dry dog food. Not
surprisingly, this process resulted in over 99% losses of spores.
More success was achieved by spray-drying the potential probiotic strain onto a previously
extruded product. The stability of the product was then studied over a 12 month period. As has
been found for a number of probiotic strains, the initial preparation of the product resulted in an
immediate drop in the expected level of spores; in this case only 60% of the expected levels were
detected, with further losses of greater than 25% occurring over the following 12 months. Such a
study highlights the potential problems inherent with the production of probiotic products. A trial
aimed at evaluating the ability of Lactobacillus rhamnosus strain GG (a strain for which there is
considerable evidence supporting its use as a probiotic in humans), to survive passage through the
intestinal tract of dogs concluded that faecal colonization in dogs is variable. This serves to
further emphasize that the ability of a potential probiotic strain to survive passage through the
gastrointestinal tract and beneficial health effects cannot be extrapolated from one species to
another.
Future Developments in Probiotics
Using biotechnology, genetically modified microbes can be made that are more effective in
improving health or nutrition than the organisms that occur naturally in the digestive system. The
first successful genetic modifications of this type of organism have already been reported.
Therefore in the future it is likely that custom-designed probiotics will be created to either directly
improve digestive function or improve health. However, before such technological advancements
are continued, it is essential that information detailing the effective dose, viability counts, safety,
delivery medium, along with properly controlled trials carried out in target populations for
probiotic strains for which specific health claims are made, should be provided. Further studies
are also needed to increase our understanding of the mechanisms of action of probiotics on the
gastrointestinal tract and the immune system.
Prebiotics
Prebiotics are “non-digestible food ingredients that beneficially affect the host by selectively
stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can
improve host health”. The most commonly known prebiotics include inulin,
fructooligosaccharides and manna oligosaccharides. The latter is considered more extensively
elsewhere in this volume.
Inulin and fructooligosaccharides (FOS) are natural components of many edible plant materials.
They are non-digestible oligosaccharides and therefore classified as dietary fiber. There is a large
body of evidence supporting the role of inulin and oligofructose as prebiotics in humans. The data
from well-designed human trials has shown significant changes in the composition of faecal
micro florawith FOS promoting beneficial bacteria such as bifid bacteria, which aid in the
suppression of potentially pathogenic bacteria. Other reported benefits resulting from the
ingestion of inulin and FOS include a bulking effect, increase in stool frequency due to an
increase in the microbial biomass resulting from increased fermentation, increased calcium
bioavailability and possibly a role in the reduction in the risk of colon cancer.This is reportedly
due to supplementation with FOS causing a reduction in the level of toxic metabolites and
detrimental enzymes that result from colonic fermentation.
However, data supporting the use of inulin and FOS in companion animals is somewhat limited
and also contradictory in nature. One trial in dogs failed to demonstrate any difference in the
levels of total anaerobic bacteria, Bifid bacteria or Lactobacilli between animals fed 1-3 g of
oligofructose per day; however in a second trial by the same group animals fed oligofructose at
the highest concentration of 9 g/kg had higher levels of Bifid bacteria in faeces compared to the
control group. Faecal Bifid bacteria levels have been reported to significantly increase following
lacto sucrose supplementation along with a decrease in levels of Clostridium perfringens. In a
different study lactobacilli numbers were shown to significantly increase following supplemental
feeding of healthy dogs with FOS. A number of groups have demonstrated in dogs that faecal E.
coli concentrations do not change significantly following ingestion of a FOS-supplemented diet or
lacto sugar. There are several studies investigating the effects of prebiotic supplementation on
faecal characteristics and digestibility parameters or in vitro fermentation characteristics.
Issues
As with probiotics, there is currently limited conclusive published evidence detailing the benefits
of prebiotic use in cats and dogs. Studies demonstrating health benefits in the target species are
required along with information on optimum inulin and/or oligofructose inclusion levels, whether
the fructans can be used interchangeably, and whether combinations of inulin and FOS would
have any synergistic benefit. Further knowledge of how prebiotics elicit their action is also
needed, although there is strong evidence to suggest that inulin and oligofructose fermentation
lead to an increase in short chain fatty acids (SCFA) in the gut, primarily acetate, butyrate and
propionate, and there is evidence that SCFA have immune-modulatory and anti-inflammatory
properties. SCFA also lower the gut pH to levels below which some pathogens such at E. coli
cannot survive.
Chondroitin sulphate is able to protect existing cartilage from premature breakdown and promote
the healing of bone. It does this by inhibiting certain enzymes that destroy cartilage and enzymes
that prevent the transport of nutrients.
Glucosamine is an amino sugar, which is synthesized within the body from glucose and amino
acids. Once synthesized it is used directly for the synthesis of glycosaminoglycan’s and hence
cartilage matrix synthesis. It stimulates the manufacture of collagen, which is the protein portion
of a fibrous substance that holds joints together. It helps to produce more collagen and also
normalizes cartilage metabolism, which helps to keep the cartilage from breaking down, and
therefore can help the body repair eroded and damaged cartilage.
Chondroitin sulphate and glucosamine, either individually or together are the most commonly
used chondroprotective agents in dogs and cats. A combination of the two has a synergistic effect
since the low molecular weight glucosamine, and the high molecular weight chondroitin sulphate
have unique and overlapping functions, which prevent damage to the connective tissue.
Principal of action
Increased repair processes in degenerating cartilage may require a larger demand for raw
materials than that available. The mechanism of action of glucosamine is therefore simple;
providing the building blocks and regulatory stimulus, which are necessary for the synthesis of
cartilage. Chondroitin sulphate works together with glucosamine to block the action of cartilage-
damaging enzymes and to promote the healthy flow of water and nutrients into cartilage-
producing cells.
Issues
Osteoarthritis and joint injury are common in animals, particularly in dogs, where osteoarthritis is
reported as being one of the most frequently encountered joint diseases. Sources of chondroitin
sulphate in pet foods are generally from animal-derived ingredients such as meat and bone meal,
and offal’s, which however, comprise only a small fraction of a dry diet. Cats, which generally
have a lower incidence of osteoarthritis, tend to have a less refined diet containing offal products,
which are more likely to contain cartilage and hence chondroitin sulphate.
In addition, cats often supplement their own diet by catching and eating small animals such as
birds and rodents. It is interesting to speculate that a dog 50 years ago would have obtained ample
chondroitin sulphate from its diet, whereas nowadays intake may be marginal to deficient for
optimal joint health, therefore inadvertently increasing the propensity of dogs to develop
osteoarthritis.
Omega-3 and omega-6 fatty acids
The potential therapeutic benefits of dietary supplementation with ω-3 eicosapentaenoic acid and
the ratio of ω-3 to ω-6 fatty acids (arachidonic acid), which are found primarily in fish oils, has
raised great interest in the functional foods arena. Interest in these fatty acids was first raised
following the observation that Inuit people, who normally have a diet high in fish, also have a low
incidence of heart disease. Since then, investigations into the effects of ω-3 and ω-6 fatty acids on
immune function, eicosanoid production, inflammatory responses, and lipid peroxidation amongst
others have been carried out in a number of species, including dogs.
The ability of ω-3 fatty acids to prevent or reduce the severity of arrhythmias has been
demonstrated in a number of species including the rat and marmoset monkeys. Using an
experimentally-induced model of myocardial infarction in dogs, were able to show that an
intravenous infusion of ω-3 fatty acids was able to prevent the occurrence of ventricular
fibrillation, whereas a similar infusion of soya bean oil was not.
Omega-3 fatty acids have also been shown to reduce wound inflammation in dogs. Omega-3 fatty
acids reportedly act as substrates for eicosanoid metabolism, resulting in the production of
eicosanoids with lower inflammatory potential than those produced from ω-6 fatty acids. Studies
in dogs have also shown that dietary adjustments of ω-3 to ω-6 fatty acids result in altered
eicosanoid metabolism.
In some studies in dogs specific ratios of ω-3: ω- 6 fatty acids have also been shown to enhance
immune responses such as T- and B-cell mitogenic responses, whereas in others suppression of
cell-mediated immune responses were reported. The reasons for such differences are unclear,
although the age and breed of the subject animals used may have had an effect.
Issues
The apparent broad spectrum of effects that ω-3 fatty acids seem able to elicit, along with unclear
effects on immune responses suggests that caution is needed when supplementing diets with ω-3
fatty acids. In stimulating one function, such as controlling inflammatory responses, other
deleterious effects may result.
Antioxidants
Antioxidants have been included in animal feeds in order to protect the nutritional value and
improve palatability and the quality of the diets for over 30 years. Nowadays however, it is
recognized that antioxidants may play a key role in slowing the aging process, in reducing the risk
of cancer and heart disease, and generally improving health and well-being. This explains the
interest in the isolation of natural antioxidants, which can be utilized for improving health status
by stimulation of the immune system.
There are many nutrients with antioxidant properties. Some of the major dietary antioxidants
include vitamin E, carotenoids, vitamin C and flavonoids. Several nutrients, which are important
for the endogenous synthesis of other compounds with antioxidant capacity, include sulphur
amino acids, selenium and zinc. These nutrients are required for the synthesis of glutathione
(GSH), glutathione peroxidase, superoxide dismutase and many other enzyme systems.
The antioxidants most studied in cats and dogs include vitamin E, ascorbic acid, ß-carotene, lutein
and isoflavonoids. Antioxidants (vitamin E and ascorbate) have a minimal effect on Heinz body
anemia induced by dietary onion powder or propylene glycol. However, they concluded that
antioxidants may have subclinical biochemical effects, e.g. GSH-sparing may be important
against milder forms of oxidative stress. Oral administration of bioflavonoid antioxidants may
assist cat erythrocytes in resisting oxidative injury. The latter two studies showed a limited effect
of antioxidant addition to an oxidative challenge.
A greater benefit of antioxidants in companion animal diets can be expected during conditions of
increase oxidative stress such as exercise. Sled dogs with a higher plasma vitamin E concentration
have enhanced endurance, compared to dogs having lower plasma vitamin E levels. Dogs with
higher plasma vitamin E concentrations were less likely to be withdrawn from a race, although
teams with higher plasma vitamin E concentrations did not travel faster than other teams. Others
have shown that dietary antioxidant (α-Tocopherol, ß-carotene and lutein) supplementation of sled
dogs can reduce exercise-induced oxidative damage. There is good evidence that a ‘cocktail’ of
antioxidants may be more beneficial than individual antioxidants when included in companion
animal diets. Oxidative damage impairs cognitive function in dogs and that antioxidant addition to
diets can improve cognitive function. Two studies by the same group showed that inclusion of a
broad-based antioxidant and mitochondrial cofactor supplement can partially counteract/reverse
the deleterious effect of aging on cognitive function in canines.
Interest in the potential use of vitamin E as a Nutraceutical for companion animals, aside from its
antioxidant properties, has been increased by observations in other animals that lymphocyte
proliferation to B-cell and T-cell mitogens is affected by the dietary level of vitamin E. The
dietary vitamin E requirement to obtain optimal immunological health of animals has been found
to be approximately 4- 10 times higher than the dietary vitamin E level to prevent vitamin E
deficiency. In a study in young (2.65 years) and older (9.92 years) cats, the effect of vitamin E
supplementation on the immune response was measured.
In dogs, vitamin E has been shown to increase a number of immune parameters when included at
supraphysiological levels, although the control diet in this study was below AAFCO
requirements. Other dietary antioxidants shown to have immune-modulating effects in cats and
dogs include lutein and ß-carotene.
If a functional food or Nutraceutical is to bear a claim, then that claim should be scientifically
substantiated, even in the absence of regulatory requirements. This means that randomized,
double-blind trials in the specified test group need to be conducted. The results cannot be
extrapolated to other age groups or other species. A recommended dose based on experimental
evidence should also be stated, and naturally the product must have been proven safe for
consumption. Safety testing involves a large array of testing including feeding high doses, and
feeding the normal dose for long periods of time.
When a functional food contains novel ingredients or is produced by a novel process, it becomes
particularly important that safety as well as acceptability be considered. With traditional foods,
safety assurance comes from a long history of safe use by large populations over a number of
generations. Such history is lacking for novel ingredients and novel processes, and a safety
assessment is required.
Different species often have different metabolic pathways, and different levels of certain enzymes
etc., which can therefore affect the potential function of a putative functional food or
Nutraceutical. In certain circumstances, a compound deemed to be a Nutraceutical in one species
or age group may be considered as a toxin in others. Therefore it is very important that data not be
extrapolated from one species or age group to another.
Particularly for immune claims, the parameters measured are not directly translatable into a health
outcome. Enhancement of, for example, lymphocyte proliferative responses or phagocytic activity
may not necessarily translate into increased resistance to disease. Trials to determine such effects
are very difficult to run, requiring large numbers of test subjects, considerable time and hence
money.
The primary aim of dietary guidelines and food guides is to make recommendations on the
requirements of essential nutrients in order to prevent deficiencies and support body growth,
maintenance and development.
Recently though, recommendations have also been made to avoid excessive consumption of
certain nutrients, due to their adverse effects on some diseases. A number of essential nutrients are
likely to result in improved health when consumed at higher levels and therefore in the current
climate can be considered as functional foods, e.g., vitamin E where consumption at
supraphysiological levels enhances immune function. As new evidence on the roles of vitamins
and minerals comes to light, nutrient requirement recommendations are likely to be revised to take
into account effects on factors such as immune function.
It is also important to realize that including several nutraceuticals in a diet in an effort to achieve
combined benefits may not necessarily be successful. Combinations of nutraceuticals cannot be
assumed to have synergistic effects, and in fact, when used in combination could interact with
each other so as to negate any potential benefit. Any diets containing ‘cocktails’ of nutraceuticals
therefore must also go through thorough testing to substantiate any claimed health benefits.
Expectation
as pet owners worldwide become more health conscious, not only for themselves but also for their
pets, the demand for health-promoting foods and food components for use in companion animals
is expected to grow. The market for such foods is predicted to expand significantly, with the range
of products being offered likely to increase dramatically in the future as manufacturers can be
expected to seek the extra profit arising from sales of these high-value products. However, before
the full market potential can be realized, consumers will need to be assured of the safety and
efficacy of functional foods. Future scientific studies are therefore essential to provide this
assurance and to inspire confidence in the functional foods in the minds of pet owners worldwide.
Summary
Functional foods and nutraceuticals are purported to be efficacious in the prevention and/or
treatment of disease and the promotion of health due to the presence of specific concentrations of
physiologically active components. The number of functional foods is potentially very large and
encompasses natural foods, isolated components from these foods that are added to other foods
or packaged as dietary supplements, and food components synthesized in the laboratory.
Although there is evidence to support the use of certain functional foods and nutraceuticals in
companion animals, for a number of products beneficial effects are yet to be conclusively proven.
Furthermore, it is important for the pet owner to realize that in the context of a balanced diet, no
benefit may be gained from consumption of functional foods/nutraceuticals.
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Nutraceuticals are non-toxic food components which claimed to possess multiple therapeutic
benefits. Some popular Nutraceuticals include glucosamine, ginseng, Echinacea, folic acid, cod
liver oil, omega-3 fatty acid (MUFA, PUFA), calcium-enriched orange juice, green tea, plant
phenols etc. Nutraceuticals can be organized in several ways depending upon its easier
understanding and application, i.e. for academic instruction, clinical trial design, functional food
development or dietary recommendations. Some of the most common ways of classifying
Nutraceuticals can be based on food sources, mechanism of action, chemical nature etc.
It has been scientifically proved and supported that Nutraceutical are efficacious to treat and
prevent various disease conditions. About 2000 years ago, Hippocrates correctly emphasized
“Let food be your medicine and medicine be your food". In the past five years, the world has
witnessed the explosive growth of a multibillion dollar industry known as Nutraceutical. The
term “Nutraceutical” combines the word “nutrient” (a nourishing food or food component) with
“pharmaceutical” (a medical drug). “Nutraceutical” is a term coined in 1979 by Stephen De
Felice. It is defined “as a food or parts of food that provide medical or health benefits, including
the prevention and treatment of disease.” Nutraceuticals may range from isolated nutrients,
dietary supplements, and diets to genetically engineered “designer” food, herbal products, and
processed products such as cereals, soups, and beverages. A Nutraceutical is any nontoxic food
extract supplement that has scientifically proven health benefits for both the treatment and
prevention of disease.