F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Component – I (A)
Role Name Affiliation Principal Investigator Dr. Sheela Ramachandran Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore. Co-Principal Dr. S.Kowsalya Avinashilingam Institute for Home Investigators Dr.M.Sylvia Subapriya Science and Higher Education for Dr.G. Bagyalakshmi Women, Coimbatore. Mrs.E.Indira Paper Coordinator Dr. S. Thilakavathy Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore. Content Writer Dr. K. Bhaskarachary Senior Research Officer Dept. Food Chemistry National Institute of Nutrition Jamai Osmania, Hyderabad – 500007. Content Reviewer Dr. K. Bhaskarachary Senior Research Officer Dept. Food Chemistry National Institute of Nutrition Jamai Osmania, Hyderabad – 500007. Language Editor Dr. K. Bhaskarachary Senior Research Officer Dept. Food Chemistry National Institute of Nutrition Jamai Osmania, Hyderabad – 500007. Component-I (B) Description of Module
Items Description of Module Subject Name Foods and Nutrition Paper Name Functional Foods and Nutraceuticals Module Name Carotenoids: Beta carotene, Lycopene and Lutein Module ID F11FN04 Pre-requisites Physiological and biological functions of Carotenoids Objectives • To know the concepts of carotenoids, its structure, functions and distribution /sources. • To learn the different types of carotenoids such as carotenes and xanthophylls , their dietary sources and functions Keywords Biochromes, xanthophores, photooxidative processes, Carotenoids, antioxidant activity, chemopreventive and antiatherosclerotic
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F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Introduction
This module deals with pigments called carotenoids which have various physiological and biological functions. Thus, this module will introduce the learner to the carotenoids
Objectives
After completing this module, the learner will be able to
• know the concepts of carotenoids , its structure , functions and distribution /sources. • learn the different types of carotenoids such as carotenes and xanthophylls , their dietary sources and functions.
Overview
Carotenoids are the second most abundant class of biochromes discovered in the nineteenth century which is present in photosynthetic plants and non photosynthetic tissues within special pigment cells called xanthophores. Carotenoids are localised in sub cellular organelles which includes chloroplasts and chromoplasts. Most the carotenoids occur in the Trans isomeric form in plants and get isomerised to cis forms during food processing. The carotenoid composition and content in fruits and vegetables are affected by many factors, including cultivar or variety, the part of the plant consumed, stage of maturity climate or geographic site of production, harvest- and post-harvest processing, and storage.
Carotenoids are not evenly distributed in the food. Carotenoids are usually more concentrated in the peel than in the pulp of fruits and fruit vegetables. Carotenoids are pigments which play a major role in the protection of plants against photooxidative processes. They are efficient antioxidants scavenging singlet molecular oxygen and peroxyl radicals. In the human organism, carotenoids are part of the antioxidant defence system. They interact synergistically with other antioxidants; mixtures of carotenoids are more effective than single compounds. According to their structure most carotenoids exhibit absorption maxima at around 450 nm. Filtering of blue light has been proposed as a mechanism protecting the macula lutea against photooxidative damage. There is increasing evidence from human studies that carotenoids protect the skin against photooxidative damage.
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F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Structure of carotenoids
Carotenoids are a class of structurally related 40-carbon compounds made of eight repeating isoprene units. About 600 different carotenoids have been identified; the human body can readily absorb, metabolize, and use 40 to 50 of these carotenoids. Carotenoids are tetraterpenoids with a basic structure consisting of eight isopenoid residues arranged in two, 20-carbon units formed by head-to-tail condensation .This symmetrical molecule provides the basic C40 skeleton structure of all carotenoids. Based on their structure, carotenoids may contain various functional groups that distinguish them from one another. Carotenoids are subdivided into two major subgroups based on chemical structure, • those containing carbon and hydrogen are termed carotenes • those having at least one oxygen molecule in addition to carbon and hydrogen are termed xanthophylls. The deep yellow, orange, and red characteristic colors of carotenoids are due to the large amounts of conjugated carbon-carbon double bonds, exhibiting absorption maxima in the region of 400 to 500 nm. They play wide role in the biological functioning of living organisms, which includes provitamin A activity, antioxidant activity, modulation of detoxifying enzymes, regulating gene expression, cell communication, immune function enhancement, UV skin protection, and visible color. In photosynthetic organisms, carotenoids serve as accessory pigments for light harvesting and prevention of photooxidative damage. Non photosynthetic animals cannot synthesize carotenoids on their own, so they acquire carotenoids through their diet.
3 F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Carotenes Xanthophylls
Functions of carotenoids Epidemiological studies have report that foods rich in carotenoids and antioxidant vitamins are associated with reduced risk of cardiovascular disease and decrease in the incidence of chronic disease. Certain carotenoids can be converted to retinoids and have provitamin A activity and antioxidants properties while some can modulate the enzymatic activities of lipoxygenases (proinflammatory and immunomodulatory molecules), some activate the expression of genes which encode the message for production of a protein, connexin, which is an integral component of the gap junctions required for cell to cell communication. Such gene activation is not associated with antioxidant capacity and is independent of pro-vitamin A activity. Other health benefits of carotenoids that may be related to their antioxidative potential include enhancement of immune system function protection from sunburn, and inhibition of the development of certain types of cancers. Carotenoids may act as antioxidants and may exhibit chemopreventive, antiatherosclerotic effects and anticancer effects in some specific animal models, using specific carcinogens.
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Occurrence and distribution in plants and animals
They are found in plants, algae, photosynthetic bacteria, yeasts, and molds, where they have a protective effect against damage by light and oxygen. The red orange and yellow colour in plants and in some insects, birds, fishes and crustaceans are mainly due to the presence of carotenoid pigments. Green leafy vegetables such as broccoli, spinach, and green beans contain diverse carotenoids including both xanthophylls and carotenes. Fruits which are red and yellow and vegetables such as plums, carrots, melons and tomatoes contain primarily carotenes while yellow and orange fruits such as pumpkins, oranges and peaches contain more of xanthophylls esters. Carotenoids from fruits and vegetables exist as protein
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
carotenoid complex in green leafy vegetables, or as crystals in carrots and tomatoes or in oil solutions in mango and papaya. In humans, the carotenoids are not present naturally and need to be supplemented through diet.
Carotenes: β- Carotene
Beta-carotene is the major source of vitamin A which is necessary for normal development, growth, and eyesight. β-carotene is the most widely studied carotenoid and is one of the major carotenoids in our diet and in human blood and tissues. Beta-carotene is a pro-vitamin which the body converts into vitamin A. It is the major, most active precursor of vitamin A. β-Carotene is the most abundant form of vitamin A in fruits and vegetables.
Structurally, retinol is essentially one half of the molecule of β-carotene with an added molecule of water at the end of the lateral polyene chain. An unsubstituted β ring with a C11 polyene chain is the minimum requirement for vitamin A activity.
Sources of β carotene
Beet root, apricots, cantaloupe, carrots, pumpkin, sweet potato, pink grapefruit, tomatoes, watermelon, mango, papaya, peaches, prunes, squash and oranges green fruits and vegetables such as green beans, broccoli, brussel sprouts, cabbage, kale, kiwi, lettuce, peas and spinach , Capsicum annuum var. lycopersiciforme rubrum, rosa mosqueta hips (Rosa rubiginosa, Rosa eglanteria).
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Functions of β carotene
Beta-carotene is a major source for Vitamin A formation in humans essential for normal growth and development, immune system function and vision. β-carotene inhibits lipoxygenases which are involved in arachidonic acid metabolism which is co- oxygenation of fatty acids Beta-carotene may exert chemopreventive effects by inhibiting CoA reductase. Beta-carotene increases cell to cell communication by stimulating connexin 43 to increase gap junction formation. Beta-carotene has antioxidant properties that can help neutralize free radicals – reactive oxygen molecules potentially damaging lipids in cell membranes and genetic material, which may lead to the development of cardiovascular diseases and cancer . At present, it is unclear whether some beneficial effects of beta-carotene and other carotenoids in humans are a result of their antioxidant activity or other non-antioxidant mechanisms. In vitro studies indicate that carotenoids can also inhibit the oxidation of fats under certain conditions. They may have anti-atherosclerotic potential, but their effects in humans appear to be more complex. Beta- carotene and other carotenoids can facilitate communication between neighbouring cells by stimulating the synthesis of proteins that form pores in cell membranes, allowing communication through the exchange of small molecules. This effect appears unrelated to the vitamin A or antioxidant activities of various carotenoids .Some clinical trials have found that beta-carotene supplementation improves several parameters of immune function, such as increasing the number of white blood cells and the activity of natural killer cells. Nevertheless, as vitamin A is essential for normal immune system function, it is difficult to
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
determine whether the effects of beta-carotene are related to their vitamin A activity or other activities of carotenoids. Beta-carotene is also in used in malnourished (underfed) women to reduce the chance of death and night blindness during pregnancy, as well as diarrhoea and fever after giving birth. Some people who sunburn easily, including those with an inherited disease called erythropoietic protoporphyria (EPP), use beta-carotene to reduce the risk of sunburn.
Mechanisms of Action
The antioxidant function of beta-carotene is due to its ability to quench singlet oxygen, scavenge free radicals and protect the cell membrane lipids from the harmful effects of oxidative degradation .The quenching involves a physical reaction in which the energy of the excited oxygen is transferred to the carotenoid, forming an excited state molecule. Quenching of singlet oxygen is the basis for beta-carotene's well known therapeutic efficacy in erythropoietic protoporphyria (a photosensitivity disorder). The ability of beta-carotene and other carotenoids to quench excited oxygen, however, is limited, because the carotenoid itself can be oxidized during the process (autoxidation). Scientists have shown that beta-carotene autoxidation in vitro is dose-dependent and dependent upon oxygen concentrations. At higher concentrations, it may function as a pro-oxidant and can activate proteases. In addition to singlet oxygen, carotenoids are also thought to quench other oxygen free radicals. It is also suggested that beta carotene might react directly with the peroxyl radical at low oxygen tensions; this may provide some synergism to vitamin E which reacts with peroxyl radicals at higher oxygen tensions. Carotenoids also have been reported to have a number of other biologic actions, including immuno-enhancement; inhibition of mutagenesis and transformation; and regression of premalignant lesions.
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F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Lycopene
Lycopene is an antioxidant found in natural and processed foods. Lycopene is a naturally occurring antioxidant and a micronutrient with important health benefits. Lycopene exhibits antioxidant action by exerting its strong affinity for singlet oxygen quenching, protecting cells from lipid peroxidation and enhancing cellular gap junction communication. Lycopene may actually stimulate the endogenous enzymatic antioxidant system. Lycopene is the most predominant carotenoid in human plasma. Sources of lycopene Tomatoes and tomato products are a major source of lycopene in the diet. Tomatoes are well known for being cholesterol free, low in calories and fat, good sources of vitamins A, C & E, as well as potassium and lycopene is a carotenoid found naturally in plant sources. Fruits and vegetables that are high in lycopene include autumn olive, watermelon, pink grapefruit, pink guava, papaya, sea buckthorn, wolfberry (goji, a berry relative of tomato), and rosehip. Other sources of lycopene are apricot, cranberry, peaches.
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Structure of lycopene It has a chemical structure with a highly unsaturated straight chain hydrocarbon and a total of 13 double bonds with 11 linearly arranged conjugated double bonds and 2 non-conjugated double bonds. Because of the high number of conjugated double bonds, lycopene is considered one of the most potent antioxidants due to its singlet oxygen-quenching ability. Lycopene is a symmetrical tetraterpene assembled from 8 five-carbon isoprene units. Because it consists entirely of carbon and hydrogen, is also a carotene, a class of related organic compounds with the formula C40H56. Carotenes exist in several isomers that have the same formula but different molecular structures. Lycopene lacks the terminal β-ionic rings, and unlike β-carotene, lacks pro-vitamin A activity. Several cis-isomers of lycopene have been identified in processed tomato products and biological fluids and tissues.
Functions of lycopene Lycopene is one of the most potent antioxidants and has been suggested to prevent carcinogenesis and atherogenesis by protecting critical biomolecules including lipids, low- density lipoproteins (LDL), proteins and DNA. Several studies have indicated that lycopene
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
is an effective antioxidant and free radical scavenger. Lycopene, because of its high number of conjugated double bonds, exhibits higher singlet oxygen quenching ability compared to β-carotene or α-tocopherol. Lycopene was found to inactivate hydrogen peroxide and nitrogen dioxide .The chemistry of lycopene is unique because it has no pro-vitamin A activity, due to lack of the ß-ionone ring structure and is therefore devoid of provitamin A activity. Other mechanisms of chemoprevention by lycopene include the up-regulation of the antioxidant response element leading to synthesis of cytoprotective enzymes, the enhancement of intercellular gap junction communication, the modulation of hormonal, inflammatory and immune system. Lycopene has strong antioxidant properties, which means that it helps to remove free radicals from your body. Free radicals can harm cells and DNA and are thought to cause many different types of cancers, and other diseases as well as some signs of aging. Free radicals can result from smoking, alcohol, excessive sun exposure and exposure to pollution. They are also a by product of natural metabolic functions. As lycopene isn't used by the body in other ways, it is left to mop up free radicals. For example, lycopene can collect in the tissues of the lungs, and '"quench" free radicals there, stopping them before they can damage the cells. Lycopene is thought to be particularly effective in preventing prostate cancer, but it may also be effective in preventing lung, stomach, breast and endometrial cancers. Lycopene may be able to provide internal protection from damaging sun radiation and thus helps to prevent sunburn and skin cancer. It is also thought to help prevent heart disease. Lycopene is non-toxic and although it is not an essential nutrient for human life, it doesn't appear to do much harm in higher doses. At worst, people who have excess lycopene in their blood will turn an orange color, but limiting consumption generally returns the skin to normal in a few week. However, as it does little to no harm, and most studies seem to show that it does lower the risk of cancer, it is generally promoted as a highly beneficial nutrient.
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F11FN Functional foods and Nutraceuticals
F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Xanthophylls
Lutein
Among the carotenoids, lutein and zeaxanthin are xanthophyll which plays a major role in ocular function. They help in the prevention of age-related macular degeneration and cataract. The structure of lutein has one β-ring and one ε-ring while zeaxanthin has two β- rings. Chemically lutein and zeaxanthin are isomers, which occur naturally as all-trans geometric isomers. Lutein can exist in possible eight stereoisomeric forms because of three chiral centers, but in nature it exists mainly in Z (cis)-form (R,R,R). Zeaxanthin, on the other hand, has two chiral centers but, because of symmetry exists only in 3-stereoisomeric forms (R,R), (S,S) and (R,S-meso) .
Lutein
Dietary Sources
The main dietary sources of Lutein are green leafy vegetables such as spinach, broccoli, and lettuce and egg yolk. Xanthophylls are usually present in esterified form in flower petals like
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
Tagetes sp., where more than 90% of total carotenoids are present as lutein esters. Lutein and zeaxanthin are widely distributed in foods in the free form, bound to protein, or esterifies at one (mono-) or both (di-) hydroxyl groups on the cyclohexene rings. The xanthophylls are located predominantly in the matrix of leaves of green plants which is usually complex, consisting of fiber, digestible polysaccharides, and protein. Lutein and zeaxanthin are found rich in dark green leafy vegetables. They impart yellow or orange colour to foods such as cantaloupe, pasta, corn, carrots, orange/yellow peppers, fish, salmon and eggs. These are relatively polar carotenoid pigments found at high levels in parsley, spinach, kale, egg yolk and lutein-fortified foods. Chicken egg yolk is a good source of lutein and zeaxanthin compared to fruits and vegetables because of its increased bioavailability due to the high fat content in eggs. Lutein is found red peppers, mustard, broccoli, zucchini, corn, garden peas, spinach, leek, collard greens and kale. Lutein is responsible for the colouring of many fruits and vegetables. They are also found at relatively high levels in durum wheat and corn and their food products. Lutein is normally present in plant tissues at considerably higher levels than is zeaxanthin.
Functions of lutein
Lutein has beneficial health effects due to their ability to act as scavengers for reactive oxygen species and to bind with physiological proteins in humans. Lutein is found in high amounts in human serum. They constitute the main pigments found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration (AMD) and cataracts. The macular carotenoids are dietary lutein and zeaxanthin, and their conversion isomer meso-zeaxanthin, which are non- provitamin A carotenoids, (i.e., it cannot be converted into vitamin A). Lutein appears to
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
undergo limited epoxidation. Because lutein is fat soluble, a deficiency may occur if fat digestion is impaired. Studies have also indicated that lutein improves heart health, protects our skin against UV damage, reduces diabetes induced oxidative stress, and possesses anti- inflammatory and anti-cancer properties. Lutein protects the skin from UV damage, as well as free-radical damage. Studies have also shown that lutein reduces inflammation and redness in the skin, and help prevent skin cancer. In addition to the eyes and skin, lutein is deposited in the breast and cervix. Studies indicate that lutein and other carotenoids may have protective benefits against breast cancer risk. Lutein may also help to prevent or slow down atherosclerosis, a condition that causes the arteries to clog and often leads to cardiovascular disease. Lutein doesn’t have an established Recommended Dietary Allowance (RDA) but as per the study by AREDS (Age related eye disease study) 10 mg of lutein was recommended to prevent eye disease. Most researchers have concluded that a diet rich in carotenoids plays a major role in preventing a variety of ailments, including heart disease, strokes, and lung, stomach and cervix cancer. Lutein cannot be manufactured by the body so the advantage of lutein’s antioxidant benefits is by consuming it.
Conclusions
Carotenoid functions are dependent upon their chemical structures. Of the 500-600 known carotenoids, approximately 50 have some capacity to act as pre cursors of vitamin A. Based on epidemiological studies a positive link is suggested between higher dietary intake and tissue concentrations of carotenoids and lower risk of chronic diseases. β-Carotene and lycopene have been shown to be inversely related to the risk of cardiovascular diseases and
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F11FN04 Carotenoids: Beta carotene, Lycopene and Lutein
Dr.K. Bhaskarachary
certain cancers where as lutein and zeaxanthin to the disorders related to the eye .The antioxidant properties of carotenoids have been suggested as being the main mechanism by which they afford their beneficial effects. Recent studies are also showing that carotenoids may mediate their effects via other mechanisms such as gap junction communication, cell growth regulation, modulating gene expression, immune response and as modulators of Phase I and II drug metabolizing enzymes. However, carotenoids such as α and β-carotene and β- cryptoxanthin have the added advantage of being able to be converted to Vitamin A and its related role in the development and disease prevention.
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