Introduction - IUFoST



BIOACTIVE COMPOUNDS AND FUNCTIONAL FOODS

It is now widely recognized that some foods, called functional foods, not only provide basic nutrition, but can also prevent diseases and ensure wellness and longevity. This concept is not new in some parts of Asia, where it has always been believed that certain foods are beneficial to health and some even therapeutic. However, these beliefs were primarily anecdotal, based on centuries of tradition and lacking scientific evidence.

Functional food has been defined as “any food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains.” It is similar in appearance to ordinary food and should be consumed as part of the usual diet. The beneficial effects are due to its bioactive components, which can be nutrients, such as vitamin C, vitamin E, folate and provitamin A carotenoids. Others are not nutrients, such as vitamin A-inactive carotenoids, flavonoids, nondigestible carbohydrates and organosulfur compounds. Unmodified whole foods, such as fruits and vegetables rich in the physiologically active compounds, represent the simplest form of functional foods. Modified foods, including those that have been enhanced with bioactive substances, also fall into the category of functional foods.

Learning Objectives

After reading this chapter, you should be able to answer the following questions:

• What compounds have beneficial effects on health beyond basic nutrition and are important in the prevention of diseases?

• In which foods are they found?

Bioactive Compounds

Numerous bioactive compounds, called phytochemicals, have been identified in plant derived foods. Some phytochemicals which appear to have significant health potentials are: carotenoids, phenolic compounds (flavonoids, phytoestrogens, phenolic acids), phytosterols and phytostanols, tocopherols and tocotrienols, organosulfur compounds and nondigestible carbohydrates (dietary fiber and prebiotics). Zoochemicals, coming from foods of animal origin (e.g. ω-3 fatty acids, peptides), are much fewer.

Carotenoids

Carotenoids are natural pigments responsible for the yellow, orange and red color of many fruits (e.g., mango, papaya, guava, watermelon, peach), vegetables (e.g., carrot, squash, pumpkin, tomato), a few roots (e.g., yellow cassava, yellow or orange sweetpotato), egg yolk, some fish (e.g. salmon and trout) and crustaceans (e.g. shrimp, crab and lobster). Green leafy and non-leafy vegetables are rich sources of carotenoids, although their color is masked by the green chlorophyll.

The carotenoids most commonly found in foods are (-carotene, (-carotene, lycopene, (-cryptoxanthin, lutein and zeaxanthin. These are also the principal carotenoids encountered in human blood and are the most investigated in terms of human health.

Some carotenoids have provitamin A activity (e.g., (-carotene, (-carotene, (-cryptoxanthin), i.e., they can be converted to vitamin A in the human body. (-carotene is the most potent provitamin A and is the most widely distributed carotenoid in foods.

In more recent years, both provitamin A and vitamin-inactive carotenoids have been credited with other health-promoting effects: enhancement of the immune system and reduction of the risk of developing degenerative diseases such as cancer, cardiovascular diseases (diseases of the heart and the circulatory system), cataract and macular degeneration. These physiological activities have been widely attributed to an antioxidant property, but other mechanisms of action against chronic diseases have been increasingly cited: modulation of carcinogen metabolism, regulation of cell growth, inhibition of cell proliferation, enhancement of cell differentiation, stimulation of cell-to-cell gap junctional communication, retinoid-dependent signaling, modulation of DNA repair mechanisms, induction of detoxifying enzymes and filtering of blue light. An antioxidant is a substance that significantly delays or prevents the oxidation of another substance even when present at a low concentration.

Lycopene’s possible role in the prevention of cancer has drawn considerable attention, with special emphasis on prostate cancer. This carotenoid has also been associated with the prevention of cardiovascular diseases. Lutein and zeaxanthin make up the yellow pigment in the macula of the human retina and have been associated with the reduced risk for macular degeneration, the major cause of irreversible blindness in the elderly. These two carotenoids have also been consistently linked to the lowering of the risk for cataract.

Although numerous studies support the protective effect of carotenoids against chronic diseases, there have been some inconsistencies in the results. The consumption of carotenoid-rich foods is widely recommended, but caution and more investigations are recommended to evaluate the benefits and risks of supplements.

Phenolic compounds

Phenolic compounds comprise one of the most numerous and widely distributed groups of substances in the plant kingdom, ranging from simple phenolic acids to polymerized compounds like tannins. The most common group of plant phenolics consists of the flavonoids, which are found in fruits, vegetables, coffee, tea and wine. Flavonoids are widely recognized as antiallergenic, anti-inflammatory, antiviral, antimicrobial, anti-thrombotic, antiproliferative and hepatoprotective.

The health-promoting properties of phenolic compounds, particularly flavonoids, are believed to be based on their antioxidant activity, particularly the ability to scavenge free radicals. The primary target of free radicals are proteins (including enzymes), lipids (relevant to the induction of heart disease), DNA (relevant to the induction of cancer) and RNA. The oxidative event that occurs most frequently inside the body is the oxidation of the unsaturated fatty acid components of cell membranes, forming lipid peroxides. Many researchers have shown that lipid peroxides and reactive oxygen species are involved in the development of a variety of diseases, including cancer, atherosclerosis, heart disease, kidney damage and even accelerated aging. Flavonoids are also metal chelators and have been found to bind metals, such as copper and iron, which catalyze lipid oxidation.

Aside from their antioxidative properties, flavonoids may act in other ways, such as deactivating carcinogens, inhibiting the expression of mutated genes, inhibiting the activity of enzymes that promote carcinogenesis, suppression of the proliferation of cancer cells and promoting detoxification of xenobiotics. The major modes of action against cardiovascular diseases are reduction of blood pressure, inhibition of LDL oxidation, inhibition of platelet aggregation and adhesion, inhibition of enzymes involved in lipid and lipoprotein metabolism.

Although flavonoids in general are widely distributed in plant foods, the isoflavones (e.g., genistein and daidzein) are found in just a few botanical families with soybean as the principal dietary source. Major potential beneficial effects of isoflavones are prevention of cancer and heart disease, increase of bone mass density (thus preventing osteoporosis), reduction of postmenopausal syndromes in women.

Isoflavones, lignans and stilbenes are phytoestrogens, a group of nonsteroid plant constituents that exhibit estrogen-like biological activities. Phytoestrogens may alter steroid hormone metabolism and may inhibit growth and proliferation of hormone-dependent cancer. They also have potential protective effects against cardiovascular diseases.

Dietary sources of lignans, which are diphenols, are oilseeds, cereal grains, vegetables, fruits and legumes. Food lignans are converted in the colon into active mammalian lignans, which are associated with a reduced risk of cardiovascular diseases and hormone-related cancer.

Among monomeric stilbenes, the major active compound is trans-resveratrol, the main dietary sources of which are grape, peanut and their products. Resveratrol appears to be a very promising molecule for the development of anticancer treatments as well as for inhibiting lymphocyte proliferation during immunosuppressive therapies. Evidence also suggests that resveratrol may decrease cardiovascular disease risk by multiple mechanisms, such as inhibition of LDL oxidation and of platelet aggregation.

Phytosterols and phytostanols

Plant sterols (phytosterols) are bioactive components of all vegetable foods. β-sitosterol, stigmasterol and campesterol are the most abundant phytosterols and are predominantly supplied by vegetable oils, although they are also found in seeds, legumes, cereals, nuts and vegetables.

A less abundant class of related compounds consists of the plant stanols or phytostanols, which are saturated forms of phytosterols. Phytostanols are derived primarily from corn, wheat, rye and rice, but their concentrations are generally lower than those of phytosterols.

Phytosterols and phytostanols decrease total cholesterol and LDL-cholesterol levels, by reducing the absorption of dietary and endogenously produced cholesterol from the gut, thus protecting against cardiovascular diseases. In addition to the blood cholesterol-lowering effect, phytosterols have also been reported to have anti-cancer properties (inhibiting colon cancer development) and antiatherosclerotic, anti-inflammatory and anti-oxidative effects.

As of September 2000, the US FDA has allowed a health claim for reducing the risk of coronary heart disease for foods (spreads and salad dressings) containing phytosterol and phytostanol esters. Spreadable fats, yoghurts and milk with added free phytosterol or phytosterol esters or phytostanol esters are also available in the markets of several European countries.

Tocopherols and tocotrienols (vitamin E)

Vitamin E is suggested to have protective effects against the progression of coronary heart disease, the inhibition of LDL oxidation being the main mechanism for such action. α-Tocopherol supplement was reported to decrease lipid peroxidation, reduce platelet aggregation and function as anti-inflammatory agent. However, because of some inconsistent results in some studies, it is considered better to obtain α-tocopherol from dietary sources. Vitamin E, especially tocotrienols, may also protect against coronary heart disease by lowering LDL-cholesterol through their ability to inhibit a rate-limiting enzyme in cholesterol biosynthesis. Although the evidence is weaker, vitamin E may also block or suppress mutation, promotion and proliferation in different types of cancer.

Oil and cereal grains are the richest sources of vitamin E. Rice bran oil and palm oil are the most significant sources of tocotrienols. A number of plant foods, ranging from kale and broccoli to cereal grains and nuts, have also been found to contain tocotrienols.

Organosulfur compounds

Organosulfur compounds, found in such vegetables as garlic, onion, scallion, chive, shallot and leek, account for the distinctive flavor and aroma as well as the reported medicinal effects of these vegetables.

The organosulfur compounds in Allium vegetables (e.g., onion, garlic) have been reported to exert various physiological activities, including antimicrobial, lipid-lowering, hypocholesterolemic, antithrombic and hypoglycemic effects, as well as inhibition of platelet aggregation, lipoxygenase and tumor.

Glucosinolates are sulfur-containing glucosides prevalent in the cruciferous family of vegetables, especially the Brassicas (e.g., cabbage, broccoli, Brussels sprouts, cauliflower), and are also present at relatively high levels in oilseeds such as rapeseed and in condiments such as mustard seed. They become bioactive only after being enzymatically hydrolyzed to isothiocyanates.

When the plant tissue is damaged by food preparation or chewing, the glucosinolates are brought into contact with and are hydrolyzed by the endogenous enzyme myrosinase to yield a complex mixture of products, mainly isothiocyanates, nitriles and thiocyanates. Glucosinolate breakdown products exert a variety of antinutritional and toxic effects in higher animals, the most thoroughly studied of which is the goitrogenic effect of some products. At present, however, there is little or no epidemiological evidence of this goitrogenic effect causing a disease in humans.

On the other hand, in vitro and in vivo studies have reported that isothiocyanates affect many steps of cancer development, including modulation of phase I and II detoxifying enzymes, modulating cell signaling, induction of apoptosis (programmed cell death), control of the cell cycle and reduction of Helicobacter infections. Apoptosis and modulation of phase I and phase II detoxification pathways have been considered the most important mechanisms by which glucosinolate/isothiocyanates inhibit carcinogenesis.

Dietary fiber and prebiotics

Dietary fiber refers to plant materials that resist digestion in the human body. The most commonly used definition of this food constituent is: dietary fibers are oligosaccharides, polysaccharides and their hydrophilic derivatives, and lignin, which cannot be digested by the human digestive enzymes to absorbable components in the upper alimentary tract. Food sources of fiber are fruits, vegetables, legumes, cereals and whole grains.

Nondigestible oligosaccharides may prevent cardiovascular diseases, type 2 diabetes and intestinal infectious diseases. The most prominent example is fructans (e.g. inulin), which occur in edible parts of various plant foods like onion, artichoke, chicory, leek, garlic, banana, rye, barley and yacon. Galactosyl sucroses (raffinose and stachyose) are found in soybean and other leguminous seeds.

Nondigestible oligosaccharides have been described as prebiotics. A prebiotic is a nondigestible food ingredient that positively affects the host by selectively stimulating the growth and/or activity of one or a limited number of beneficial bacterial species residing in the colon.

Dietary fiber has several recognized physiological effects: modulation of glucose absorption, regulation of gastrointestinal transit time, fecal bulking and lowering of serum total cholesterol and LDL cholesterol levels. Prebiotics selectively modify the colonic microbiota and modulate hepatic lipogenesis. A balanced intestinal flora allows improved bowel regularity, reduction of bacteria, protection against a wide range of toxins and increased nutrient absorption.

Omega-3 fatty Acids

Consumption of ω-3 fatty acids, especially EPA (C20:5 eicosapentaenoic acid) and DHA (C22:6 docosahexaenoic acid), may reduce the risk of coronary heart disease and also protect against cancer. The physiological effects of these fatty acids are lowering of plasma triacylglycerols (formerly called triglycerides), relaxing blood vessels, increased aggregation time for platelets, decreased viscosity of blood, lowering of blood pressure, reduction of inflammation, reduction of tumors.

EPA and DHA enhance visual, cognitive and motor skills, and behavioral development in children. There are also studies reporting beneficial effects of ω-3 fatty acids in alleviating rheumatoid arthritis, diabetes and mental disorders, including schizophrenia and bipolar disorders.

Omega-3 fatty acids are acquired mainly from seafoods, especially fatty fish. Mackerel, herring and salmon are rich sources of EPA and DHA.

Functional Foods

Research strongly indicates that the protection against degenerative diseases cannot be attributed to single classes of compounds but to the range of bioactive compounds contained in foods. While the evidence for individual classes of bioactive compounds is often inconclusive or inconsistent, compelling evidence demonstrate that a plant-based diet can reduce the risk of degenerative diseases, especially cancer and cardiovascular diseases. It is estimated that plant-based diets prevent 20-50% of all cases of cancer. Thus, dietary recommendations for the prevention of cancer and other chronic diseases have always emphasized the consumption of a variety of plant foods. Examples are given below of plant foods that are established or emerging functional foods, each one with a body of scientific evidence on the positive impact on health that the constituent bioactive compounds confer.

Broccoli and other cruciferous vegetables

Cruciferous vegetables contain little fat, are low in energy, and are sources of micronutrients (provitamin A, vitamins C and E, folic acid, selenium), fiber and other phytochemicals (carotenoids, coumarins, flavonoids and other phenolic compounds, and glucosinolates).

There is increasing evidence that greater consumption of cruciferous vegetables, such as broccoli, cabbage, kale, mustard greens, Brussel sprouts and cauliflower, reduces the risk of several types of cancer. These vegetables are also implicated in the prevention of cardiovascular diseases.

The indolyl glucosinolate, glucobracissin, found at high levels especially in Brussels sprouts, is hydrolyzed by the enzyme myrosinase to give indole-3-carbinol. This indole is believed to have chemopreventive property, especially toward the mammary gland. It may reduce cancer risk by increasing 2-hydroxylation over 16-hydroxylation of estrogen; this shift in hydroxylation represents a reduction in estrogenic activity and may be protective against estrogen-related cancers.

Oat

Among the food grains, oat is the most concentrated source of β-glucan, a soluble non-starch polysaccharide known to reduce risk of coronary heart disease. Various components such as phytates, phenolics, vitamins and minerals, which confer physiological benefits, are also present.

Oat was the first specific food allowed to have a health claim under the US Nutrition Labeling and Education Act. FDA allowed the claim “soluble fiber from oatmeal, as part of a low saturated fat, low cholesterol diet, may reduce the risk of heart disease.” FDA has acknowledged that β-glucan is the main active ingredient responsible for this health claim.

About 3 g per day of soluble fiber from oat products can achieve a clinically relevant serum cholesterol-lowering effect, the reduction being greater in individuals with higher initial blood cholesterol levels.

Flaxseed

Flaxseed or linseed is a rich source of the essential (-3 fatty acid α-linolenic acid, viscous fiber components and mammalian lignan precursors, which have been associated with many potential health benefits.

Studies support the protective effect of α-linolenic acid of flaxseed oil against cardiovascular disease, concluding that consumption of raw or defatted flaxseed reduced total and LDL- cholesterol.

Studies in women showed a role of flaxseed in mediating bone health and its phytoestrogenic and therapeutic effects in reducing the risk of hormone-related cancers. The flaxseed’s potential action against mammary and colon cancer has been attributed to lignans.

Soluble fiber and other components of flaxseed can potentially affect insulin secretion and its mechanisms of action in maintaining plasma glucose homeostasis, thereby preventing diabetes.

Tomato

Tomato and tomato products have been the focus of intense investigation in recent years, especially in relation to prostate cancer. Evidence for a benefit was strongest for cancers of the lung, stomach and prostrate gland. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast and cervix.

Tomatoes and tomato-based products is the major source of lycopene in the diet of many countries and lycopene has been considered the primary phytochemical responsible for the reduction in the risk of prostate cancer. Tomato, however, is also a rich source of nutrients such as folate and vitamins C and E, and of other potentially beneficial phytochemicals including phenolic acids, phytosterols and flavonoids. Thus, the possibility that it is the combination of these compounds that is responsible for the influence on prostrate carcinogenesis has been raised.

Soybean

Soybean is not only a source of high quality proteins but also of phytosterols, saponins, phenolic acids, phytic acid and isoflavones. It has been known to have a protective role in women’s health, particularly the alleviation of menopausal symptoms and promotion of bone health, suggesting that it may prevent osteoporosis. Asian women have significantly lower levels of hot flashes and night sweats compared to western women

Studies indicate that consumption of tofu and other soy foods may be associated with the low incidence of breast cancer in Japanese women. Several classes of anticarcinogenic compounds have been identified in soybeans, of which the isoflavones genistein and daidzein are considered the most important.

Countries consuming diets high in soy products have been shown to have the lowest rates of cardiovascular diseases. An inverse association between soy food product consumption and cholesterol level has been observed in Japanese men and women.

The most well-documented physiological effect of soybean is its cholesterol-lowering effect. Investigations on the specific components responsible for this effect of soybean have focused on the isoflavones. Animal studies indicate that the cardioprotective effect of soybeans goes beyond cholesterol-lowering, such as decreases of atherosclerotic lesion, thrombus formation and atherosclerotic plaque. In 1999, the Food and Drug Administration of the U.S. approved a health claim for soy protein in reducing the risk of heart disease.

Citrus

Citrus fruits are a principal source of vitamin C, folate, fiber, flavonoids, phenolic acids, monoterpenes, carotenoids and limonoids. The various health benefits of citrus fruits have been attributed to the antioxidant activity of their constituent flavonoids (flavanones, flavones, flavonols and anthocyanins). In biological studies, citrus flavonoids demonstrated anticarcinogenic (antimutagenic and antiproliferative effects, inhibition of carcinogenic cell invasion) and cardiovascular (effects on capillary fragility, platelet aggregation, coronary heart disease) properties. Citrus flavonoids have also been found to have anti-inflammatory, antiallergic and antiviral activities.

The monoterpene D-limonene, which is the major component of the oil from citrus peel, has also been shown to protect against cancer.

Citrus fruits are particularly rich in another class of phytochemicals, the highly oxidized triterpenes called limonoids. Research suggests that these compounds may have substantial anticancer activity.

Berries

Berries are delicious, low energy food, which are rich sources of fiber, antioxidant vitamins and various phenolic compounds (flavonoids, phenolic acids, stilbenes). Berries, such as bilberry, blackberry, blackcurrant, blueberry, cranberry, raspberry, strawberry and the Brazilian açai, are particularly rich sources of antioxidants. Various potential health benefits from berries have been attributed to flavonoids, specially its ability to act as free radical scavengers. The main flavonoids in berries are the red/bluish anthocyanins, proanthocyanidins, flavonols and catechins. Anthocyanin-rich berries have been demonstrated to have antioxidant, cardioprotective, neuroprotective, anti-inflammatory and anticancer properties.

Cranberry and blueberry have been shown to prevent urinary tract infections. This protective effect has been attributed to condensed tannins or proanthocyanidins, which are said to act as anti-adhesive agents preventing bacterial colonization.

Fruit extract of wild bilberry inhibited LDL oxidation, exhibited astringent and antiseptic properties, decreased permeability and fragility of capillaries, inhibited platelet aggregation, inhibited urinary tract infection, and strengthened collagen matrices via cross linkages.

Tea

Now a popular beverage worldwide, tea has been consumed in China for its medicinal properties for centuries. The three main types of tea are green (unfermented), oolong (semi-fermented) and black (fully fermented) teas. Green tea contains significant amounts of catechins, which are easily extracted from the leaves into hot water infusions. During the manufacture of black tea, the dimeric theaflavins and thearubigens are formed by enzyme-catalyzed oxidation of catechins. Green tea contains catechins (90%) and flavonols (10%); black tea has catechins (30%), flavonols (10%), theaflavins (13%), and thearubigens (47%).

Tea is believed to possess antiviral, antifungal and antibacterial properties, and to provide protection against cancer and cardiovascular diseases. Epidemiological evidence for a protective effect of tea against cancer is still considered inconclusive, but research findings from animal and in vitro studies clearly support a cancer preventive effect, which spans the whole process of carcinogenesis. Similarly, the alleged protection against cardiovascular diseases has also rested heavily on cellular and animal experiments.

Polyphenols found in tea are powerful antioxidants and may play an important role in the prevention of cancer through a range of mechanisms such as reducing damage of DNA and the activation of cancer cells leading to malignancy.

Consumption of tea, particularly green tea, has been associated with lower serum triacylglycerols and cholesterol. Studies have also indicated that the polyphenols in tea inhibit blood coagulation and inflammatory processes, and have vasorelaxant effects.

Grapes and wine

Grapes and wines contain large amounts of phenolic compounds including flavonoids (catechins, epicatechin, quercetin, anthocyanins), phenolic acids (hydroxycinnamates) and tannins. Substantial evidence suggests that moderate consumption of red wine may protect against cardiovascular disease, loss of bone density and dementia.

In France, the low mortality from coronary heart disease despite diets high in saturated fat and cigarette smoking, a phenomenon referred to as the “French Paradox”, is attributed, at least in part, to high intake of red wine, specifically to its phenolic compounds (i.e., flavonoids and resveratrol). The phenolic content of red wine is 20–50 times that of white wine. Collectively, phenolic compounds appear to have anti-thrombic effects as a result of reduced susceptibility to platelet aggregation, reduced synthesis of prothrombotic and proinflammatory mediatos, decreased expression of adhesion molecules and tissue factor activity.

Aside from its antioxidant activity, resveratrol, a widely recognized red wine polyphenol, induces quinone reductase, a phase II detoxifying enzyme. It has anti-inflammatory activity and inhibits the hydroperoxidase activity of cyclooxygenase, thereby inhibiting the arachidonic pathway that produces prostaglandins. In a dose-dependent manner, resveratrol inhibits the development of preneoplastic lesions, slowing down the progression of carcinogenesis.

Garlic

For centuries garlic has been valued for its alleged medicinal properties. Investigations on the possible health benefits of this spice has intensified in recent years, reporting antimicrobial and anticarcinogenic (especially of the gastrointestinal tract) properties and protective effects against cardiovascular diseases.

Studies have indicated that the allyl sulfur compounds in garlic act primarily on the initiation phase of carcinogenesis, inhibiting development of tumor in various sites through the induction of detoxifying enzymes and inhibition of an enzyme responsible for the metabolic activation of carcinogens. The ability of garlic to inhibit the synthesis of N-nitroso compounds and its antibacterial activity against Helicobacter pylori, a risk factor in stomach cancer, are two other possible mechanisms.

Garlic’s possible role against cardiovascular diseases has been attributed to a variety of biological responses, including a decrease in total and LDL-cholesterol, increase in HDL-cholesterol, reduction of serum triacyglycerol and fibrinogen concentrations, inhibited platelet aggregation and reduced blood pressure. There is lower cardiovascular incidence in high-garlic consuming populations in the Mediterrenean region and some places in Asia, compared to populations who have similar life and dietary styles.

Fish and seafoods

Fish and shellfish are important sources of high-quality protein and other essential nutrients. Low in saturated fat, these foods contain beneficial ω-3 fatty acids. The polyunsaturated fatty acids of fish, particularly the ω-3 fatty acids EPA and DHA, are associated with neurological development and reduced risk of coronary heart disease. Not all fish are rich in ω-3 fatty acids, and marine fish are generally richer sources of these fatty acids than freshwater fish.

The American Heart Association and the British Heart Foundation recommend eating fatty fish at least twice a week.

Dairy products

Dairy products provide essential nutrients, such as calcium, potassium, phosphorus, protein, vitamins A, D and B12, riboflavin and niacin. Recent studies show the presence of other components, such as whey, peptides and milk fat, which have positive effects on bone health, digestive health and weight management.

Milk-derived peptides have been studied intensely in recent years. They have been found to positively affect the functioning of the digestive tract, the cardiovascular system, the immune system, the central nervous system and the hormones, being reported to be antihypertensive, antioxidative, antithrombotic, hypocholesterolemic, mineral-binding, anti-appetizing, antimicrobial, immunomodulatory and cytomodulatory.

Indigenous fruits and vegetables

The few studies on the bioactive compounds of native fruits and vegetables, particularly of developing countries, indicate high levels of these compounds (e.g., carotenoids, flavonoids, folates). In Brazil, for example, a list of functional foods would include those mentioned above, which are produced in the country in substantial amounts, but would also include native fruits and vegetables rich in bioactive substances.

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