Module 13. Functional foods

 

Lesson 46

PHYTOCHEMICALS IN RELATION TO HUMAN HEALTH

 

46.1  Introduction

Increasing awareness among consumers to know which specific molecules present in their food possess disease preventive or curative properties has led to the concept of “Functional Foods”.  In human being there is always temptation to move towards nature and the products that are natural, for every little disturbance related to health. In our country “Ayurveda” system of medicine exists since centuries.  It is mainly based on the preparation or extracts from natural plant products.  

Nutritional significance of plant molecules is well documented and increasing cases of cancers, cardio vascular diseases (CVD), diabetes and many other chronic diseases, have been attributed to under consumption of fruits and vegetables in our diet. But beyond these known nutrients (vitamins, fibers) plants have clearly more to offer and scientists are studying to discover exactly which plant components might fend off specific diseases. The bioactive molecules are commonly termed as plant chemical or phytochemicals.

46.2  Defining Phytochemical 

Consumption of fruits and vegetables has since long been associated with lesser incidences of certain diseases like cataract, scurvy, cancer and CVD in populations consuming them. The disease prevention ability of fruits and vegetables is mainly attributed to the phytochemicals present in minor quantities.

“Phytochemicals”- consisted of two words “Phyto” and “Chemicals”.”Phyto” from Greek word for plants, denoting their plant origins and it refers to the chemicals which are present in plant. These phytochemicals are secreted or developed as a part of the plants own defense mechanism against environmental insult and fortunately beneficial to human beings. These phytochemicals are very effective anti-oxidants thus checks free radical mediated degenerative diseases like cancer, CHD etc.

The number of identified physiologically active phytochemical has increased dramatically in the last decades and overwhelming evidence from epidemiological, in vivo, in vitro and clinical trial indicate that plant rich diet can reduce the risk of certain chronic diseases. Health professionals are gradually recognizing the role of phytochemicals in health improvement.

46.3  Prospective Phytochemicals

Some phytochemicals with proven health benefits can be grouped under following categories.

46.3.1  Phytoestrogens

Phytoestrogens are a broad group of plant-derived compounds that structurally mimics endogenous 17 beta-estradiol. Two major phytoestrogens, which are of great importance from nutritional and health perspectives, include lignans (Flaxseed) and isoflavones (soy bean).

Isoflavones are flavonoids compounds and major flavonoids that have been identified in soybeans are genistein, daidzein and glycitein. These compounds exist naturally in soy bean in several glycoside forms, but it is the aglycone form that is biologically active.  

These compounds either compete with/antagonize estradiol action. Dietary soy products showed antitumor activity, by directly affecting the tumor cell proliferation and reduction in tumor angiogenesis (microvessle density). Research has shown that diets rich in soya help to reduce blood levels of Low Density Lipoprotein (LDL also called as bad) cholesterol by an estimate of 12-15%. The isoflavones in soy foods are converted in the gut to phytoestrogens that may reduce LDL blood cholesterol.

46.3.2  Organosulphur compounds  

These compounds are also called as “Promise of Garlic”.  Garlic and other alliums are popular recipe seasoning, but these also have long been promoted as a medicinal agent. Garlic and other alliums – onions, chives, leeks and scallions contain allylic sulphides.

Garlic has acquired a reputation as a formidable prophylactic and therapeutic medical agents. Plant extracts containing organosulfur compounds have been shown to exhibit antimicrobial, hypolipidemic, hypoglycemic, antithrombotic, antioxidant and anticarcinogenic. The anti-hypertensive properties of garlic are believed to be the major preventive factor. Animal studies indicate that garlic supplementation in diet depressed the hepatic activities of lipogenic and cholesterogenic enzymes such as malic enzyme, fatty acid synthase, glucose-6-phosphate dehydrogenase and 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase.  

Active components identified is a family of thioallyll compounds and the intact garlic bulb contain an odorless amino acid called alliin, which is converted enzymatically by allinase into allicin, when the garlic cloves are crushed. Formation of allicin is responsible for characteristic garlic flavour. Allicin then immediately decomposes to form numerous sulphur-containing compounds.

Epidemiologic studies have established an inverse relationship between garlic consumption and the incidence of certain types of cancer including gastrointestinal, laryngeal, breast and colon cancer. The proposed mechanisms includes, inhibition of N-Nitroso compounds formation, suppression of metabolic activation of carcinogen, enhanced DNA repair, reduced cell proliferations and /or induction of apoptosis. It is believed that many of these events occur simultaneously at cellular level and are responsible for chemoprotection role of garlic compounds.

46.3.3  Glucosinolate

About 100 glucosinolate have been identified in more than 450 plant species including 16 higher plant families, marine sponges and red algae. Cruciferous vegetables comprising of cauliflower, broccoli, radish, horseradish, cabbage, Brussels sprout contain relatively high content of glucosinolate, a potent anti-carcinogen. Glucosinolate (GS) are a group of glycosides stored within cell vacuoles of all cruciferous vegetables. The function of glucosinolate in plants is not very clear but their potent odour and taste suggests a role in herbivore feeding and microbial defense. Glucosinolate consist of a β-D-thioglucose group; a sulfonated oxime group and a side chain derived from methionine, phenylalanine, and tryptophan or a branched chain amino acid. The sulfate group of a GS molecule is strongly acidic and plants accumulate GS by sequestering them as potassium salts in plant vacuoles. GS is not bioactive in animals until they have been enzymatically hydrolyzed to an associated isothiocynates.     

Myrosinase, an enzyme found in plant cell, catalyze these GS to a variety of hydrolytic products, including isothiocynates indoles. Di-indolylmethane (DIM), indole-3-carbinol (I3C), phenethly isothiocynate (PEITC) and sulphoraphane seems to be promising chemo preventive molecules, in Brassica plants. These cause induction of phase I and II xenobiotic metabolizing enzymes that results in the inhibition of the oxidative activation of carcinogens. Phase I enzymes are mainly related with detoxification mechanisms and composed of Cytochrome P450 family of enzymes. These act as first line of defense against foreign compounds. The oxidation product of Phase I enzyme reactions are further transformed into water soluble compounds by the activity of Phase II enzymes, which are ultimately removed from the body via urine or bile. These reactions are conjugation ones. Hence, toxic compounds are removed from the body without affecting the cells, DNA, RNA or proteins. I3C may reduce cancer risk by modulating estrogen metabolism. The C-16 and C-2 hydroxylation of estrogens involve competing cytochrome P-450-dependent pathways, each sharing a common estrogen substrate pool. Another isothiocynate isolated from broccoli, “sulforphane” has been shown to be the principal inducer of a particular type of phase-II enzyme, quinone reductase.

46.3.4  Carotenoids and flavonoids

Carotenoids are major pigments in majority of fruits and vegetables, algae, certain fungi and bacteria. They are responsible for characteristic deep red, yellow or orange colour of foods including tomato, carrots, citrus fruits, egg yolk, cow milk, liver, lobster and salmon. Many green colour plants also contain carotenoids which are masked by the chlorophyll specially in green leafy vegetables like spinach, cabbage, lettuce and mustard leaves.  Structurally carotenoids consist of C-40 poly-isoprenoid with an extensive conjugated double bond system. Of the 600 or so carotenoids that have been identified, about 50 serve as precursors for vitamin A. Out of which 50-60 percent are typically present in diet and around 18 have been identified in human plasma. These carotenoids are grouped into two major classes namely carotenes (hydrocarbon carotenoids) and xanthophyll (oxygenated carotenoids). The various dietary carotenoids are listed in Table 46.1.

Table 46.1 List of various dietary carotenoids and their sources

S. No.

Carotenoids

Source

Remarks

1

α-Carotene

Carrot, Lemon, Water melon, Papaya, Banana, Pumpkins. Squash

Precursor of Vitamin A

2

β-Carotene

Apricot, Oranges, Mango, Papaya, Pumpkin, Carrot, Spinach, Red pepper, Crude Palm oil

Pro-vitamin A activity, Anti-oxidant prevent cancer and check conversion of LDL cholesterol into its atherogenic form

3

Lycopene

Tomato, Water melon, Pink Guava. Red Grapefruit, Pink Papaya

Higher amount in deep red coloured tomatoes, lack Vitamin A activity but higher singlet oxygen scavenging activity, prevent cancer

4

Lutein

Spinach, Egg yolk, Broccoli, green bell pepper

Required for protection of macula in retina, play role in age related macular degeneration (AMD)

5

Cryptoxanthin

Mango,  Tangerine, Orange, Papaya, Apricot,

Possess pro-vitamin A activity and free radical scavenging activity

6

Zeaxanthin

Kale, Collard, Turnip green, Spinach, Brussels Sprout

Similar function as Lutein also assist in prevention of cataract

7

Capsanthin

Paprika, Red Chili

Exhibit anti-oxidant activity and act as Vitamin A precursor

Among the carotenoids as mentioned above β-carotene & lycopene, have been thoroughly investigated for their disease preventing ability. Carotenes are tissue specific in their biological activity. b- Carotene, a–carotene and e-carotene have vitamin A activity. Vitamin A regulates the action of certain genes associated with cellular functions.

46.3.4.1  Lycopene and cancer prevention

Tomatoes with their distinctive nutritional attributes may play an important role in reducing the risk of cardiovascular and associated disease through their bioactivity in modulating disease process pathway.

Cis–isomers of lycopene are more readily absorbed through the intestinal wall into the plasma because of the greater solubility in micelles, preferential incorporation into chylomicrons, lower tendency to aggregate and crystallize more efficient volatilization in lipophilic solutions, and easier transport within cells, across plasma membrane and tissue matrix. The greatest increase in cis-isomer formation occurs when tomato products are heated at very high temperatures. Likewise, lycopene bioavailability increases in the presence of oil.

Lycopene’s ability to act as an anti-oxidant and scavenger of free radicals that are often associated with carcinogenesis is potentially a key for mechanism for its beneficial effects on human health. Lycopene may prevent carcinogenesis and athrogenesis by interfering passively with oxidative damage to DNA & lipoproteins. Lycopene is the most effective quencher of singlet oxygen in biological system.

46.3.4.2  Flavanoids

Flavonoids are polyphenolic compounds and were originally regarded as nutritionally inert, are implicated in anticarcinogenic properties. A great deal of attention has been directed to the polyphenolic constituents of tea, particularly green tea. Catechins are the predominant and most significant of all tea polyphenols. The four major green tea catechins are epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate and epicatechin. 

However, epidemiological studies are inconclusive; on the other side research findings in laboratory animals clearly support a cancer chemopreventive effect of tea components. Other flavonoids, with promising health stimulating effects include quercetin, kaempferol, myricetin, apigenin and luteolin. Source of these compounds are chocolate, cocoa, fruit juices, nuts, red wine, raspberry, blackberry and citrus fruits.

46.3.5  Phytosterols

Phytosterols are another important terpenes subclass. Two sterol molecules that are synthesized by plants are b-sitosterol and its glycoside. In animals, these two molecules exhibit anti-inflammatory, anti-neoplastic, anti-pyretic and immune-modulating activities. A proprietary mixture of b-sitosterol and its glycoside were tested in vitro, in animals and in human clinical trials.  Phytosterols were reported to block inflammatory enzymes, for example by modifying the prostaglandin pathways in a way that protected platelets. In the body, phytosterols can compete with cholesterol in the intestine for uptake, and aid in the elimination of cholesterol from the body. Saturated phytosterol appears to be more effective than unsaturated ones in decreasing cholesterol concentration in the body.  These actions reduce serum or plasma total cholesterol and LDL cholesterol. In mammals, concentrations of plasma phytosterol are low because of their poor absorption from the intestine and their faster excretion from liver, and metabolism to bile acids, compared to cholesterol.

46.4  Other Phytochemicals

There are certain other compounds present in plant foods, with significant health promoting effect include plant fatty acids, tocotrienols, phenolic derivatives and dietary fibers etc. Docosahexaenoic acid (DHA), which is one of the most important structural component of brain and retina, and de-novo synthesis of DHA, is very rare. The decline in DHA intake could have serious implications for public health, since low plasma, DHA concentrations have been correlated with increased incidence of a number of chronic diseases such as depression, attention deficit disorders and Alzheimer’s dementia. Crypthecodinium cohmii a marine algae is used for the commercial production of DHA rich oil. Spirulina, termed as wonder alga is one of rich source of ω-3-fatty acids, quality protein and many other therapeutic molecules.

Plant polyphenols are secondary metabolites widely distributed in higher plants. These are water soluble and varying molecular weight.  Polyphenols historically have been considered as anti-nutrients, because some of them such as tannins may affect the activities of digestive enzymes and adversely affect the digestibility of starch, protein and amino acid. Many polyphenol inhibit mineral uptake and have toxic effects. Recognition of the antioxidant activities of many polyphenols has created interests among the researchers for evaluating their prospective health benefits.

46.5  Promising Functional Foods Based on Phytochemicals

Nutrients dense foods that provide benefits beyond basic nutrition have been already developed and commercially available.  Such foods can be defined as “An accepted and tolerable food that has natural, naturally concentrated phytochemical derived from fruits and vegetables or related food ingredients that are:

·         indicated to be epidemiologically important in disease prevention,

·         have shown to be useful in preventing cancer or other chronic diseases in animal bioassays,

·         are unique in structure, class, pattern and metabolism. 

The concept of fortification is not new and some new formulations based on phytochemicals are discussed here:

46.5.1  Functional drinks & beverage

The beverage market is on the cutting edge in functional food development. Energy drinks, isotonic (spare) beverages, herbal and green teas, fortified waters, smart drugs, caffeinated drinks and fringe. Beverages are relatively cheap to blend, fortify, bottle and distribute. Tea and coffee, constituents can be incorporated into new formulations with other phytochemical to develop herbal drinks. Recently the anti-oxidants or free radial scavenging ability of ascorbic acid, β-carotene, lycopene and tocopherols has been exploited in development of fortified drinks. Free radicals are formed by auto-oxidation, photosensitization, enzymatic reactions and due to pollutants. Some of the fruits and vegetables more important ones from beverage formulation standpoint include licorice, ginger, tea, citrus, carrots, tomatoes berries, mint and other herbs and spices.

46.5.2  Functional dairy products

In recent years, yogurts with oligosaccharides have been developed. These cultured dairy products may also incorporate isoflavones from soy protein, β-glucan of oat, carotenoids and flavonoids of certain fruits in their formulation. Blackberry and raspberry as fruits or their extracts added in ice creams, dairy drinks, frozen desserts, not only as flavouring component, but also as source of anthocyanin and other phenolic derivatives.  Similarly imitation dairy products may also include ω-3-fatty acids from flaxseed oil and DHA from algae. Some infant formula have already available in market containing DHA. Dairy analogue, primarily based on soymilk, may be modified to increase the level of phytoestrogens, particularly isoflavones

46.5.3  Confectionery products

Bars either based on fruits or on cereals may serve as vehicle of phytonutrients. Commercially a wide variety of nutritional bars has been developed for specific purpose. These bars can be enriched with fibers, anti-oxidants, phenolic substances and glucosinolate. Oat bar, based on soluble oat fibers, also contain ω-3-fatty acids to further strengthen its heart health image. Fruit preserves, fruit spreads, have been developed, using traditional herbs and products were further enriched by adding other phytonutrients. 

Chocolate considered as a culprit for CHD, obesity and dental problems, also moves into healthy arena. The chocolate has neutral effect on cholesterol levels and posses lower levels of caffeine, as compared to beverages. The anti-oxidant activity of polyphenols and potential benefit of procyanidins and epi-catechins on CHD could be an added advantage in consuming chocolate products.

46.5.4  Breakfast cereals

Raspberries and blackberries, reservoirs of phytonutrients are considered as good option available for cereal product formulations. Initial studies conducted with DHA in bread are encouraging. Likewise, breads with garlic compounds and isothiocynates from cruciferous vegetables are prospective options. Soy flour is already an important ingredient in bread, not only because of its nutritional significance, but excellent functional properties it imparts.

However, the incorporation of these phytochemicals in processed food product is a challenging task. Various issues associated with utilization of phytochemicals in development of novel food formulations are as follows:-

·        Isolation and efficacy of active components

·        Stability in new product system (oraganoleptic acceptability, interaction with food constituents and possible implications)

·        Safety and bioavailability

·        Minimum dose required; no information is available regarding the minimum amount which must be consumed to get the desired health benefit

·        Economics; definitely novel foods with phytochemicals will be costly if compared with their counterparts.

Therefore future research should be targeted to address above-mentioned issues. It would be possible by identifying the optimal marker (i.e. bioactive component) that can be quantifying easily in processed foods at different stage of production, processing, storage and marketing. A detailed investigation related to mechanism of action is also desirable that could provide information pertaining to their absorption, metabolism, interaction with other dietary components and excretion.

46.6  Safety Issues

The optimal levels of the majority of the biologically active components currently under investigation have yet to be determined. In addition, a number of animal studies show that some of the same phytochemicals (e.g.allyl isothiocynate) highlighted in this lesson for their cancer-preventing properties have been shown to be carcinogenic at high concentrations.

The benefits and risks to individuals and populations as a whole must be weighed carefully when considering the widespread use of physiologically-active functional foods. For example, what are the risks of recommending an increased intake of compounds (e.g. isoflavones) that may modulate estrogen metabolism? Soy phytoestrogens may represent a “double-edged sword” because of reports that Genstein may actually promote certain types of tumors in animals. Knowledge of toxicity of functional food components is crucial to decrease the risk: benefit ratio.