MIRACULOUS HEALTH BENEFITS OF PREBIOTICSHTML Full Text
MIRACULOUS HEALTH BENEFITS OF PREBIOTICS
Sheel Sharma*, Nidhi Agarwal and Preeti Verma
Food Science and Nutrition, Banasthali University, P.O.- Banasthali Vidyapith- 304 022, Rajasthan, India
A prebiotic is a living microorganism that, when administered in sufficient numbers is beneficial to the host and exerts health benefits beyond inherent basic nutrition. Prebiotics include foods, medicines and dietary supplements. In general, the benefits of the regular consumption of prebiotics include enhanced immune function, improved colonic integrity, decreased incidence and duration of intestinal infections, down-regulated allergic response, and improved digestion and elimination. Pharmaceutical and nutritional industries are exploring more natural treatments for health conscious consumers as natural treatments have been effective since immemorial and are staging a comeback and natural ‘renaissance’ is happening all over the globe.
INTRODUCTION:Prebiotics are defined as “selectively fermented ingredients that allow specific changes, both in the composition and or activity in the gastrointestinal microflora that confer benefits upon host well-being and health 1.
Prebiotics are also defined as non-digestible to low-digestible food ingredients that benefit the host organism by selectively stimulating the growth or activity of one or more than but limited number of probiotic bacteria in the colon 2, 3, 4, 5. This role is played by Fermentable carbohydrates, which are not digested or poorly digested in the small intestine and stimulate, preferentially, the growth of bifidobacteria and some Gram-positive bacteria, belonging to the probiotic bacteria administered to humans play this role.
Complex carbohydrates traverse through the small intestine to the lower gut where they become available for some colonic bacteria but are utilized by only certain microbial types out of the majority of the bacteria present in the colon.
Lactulose, galactooligosaccharides (GOS), Fructooligo saccharides (FOS), inulin and its hydrolysates, maltooligo-saccharides, and resistant starch are the prebiotics commonly used in human nutrition. The main end products of carbohydrate metabolism by the way of fermentation by enzymes of Probiotic origin are short-chained fatty acids, namely acetate, butyrate and propionate, which are further used by the host organism as an energy source. In practice, the most common oligosaccharides are inulin and its hydrolysates and oligofructans.
The majority of studies have so far focused on inulin, FOS and GOS 6, 7. These saccharides have now a long history of safe use and are generally regarded as safe, although there is some concern over increased gas production with some compounds, particularly when ingested in higher amounts or during the first few days of intake. They can be found in chicory, topinambuco, onion, garlic, asparagus, artichoke, leek, bananas, tomatos and many other plants.
Prebiotic oligosaccharides can be produced in three different ways: by extraction from plant materials, microbiological synthesis or enzymatic synthesis, as well as by enzymatic hydrolysis of polysaccharides 2, 8. In practice, combined mixtures of probiotics and prebiotics are often used because their synergic effects are conferred onto food products. For this reason, such mixtures are called synbiotics. In conclusion, prebiotics are dietary substances (mostly consisting of nonstarch polysaccharides and oligosaccharides poorly digested by human enzymes) that nurture a selected group of microorganisms living in the gut. They favor the growth of beneficial bacteria over that of harmful ones.
History: The term “prebiotic” was coined in 1995 by Gibson and Roberfroid 9, although prebiotics were recognized as early as the 1950s when György and coworkers described “bifidus factor”, a bifidogenic substance that selectively promoted the growth of bifidobacteria (called Lactobacillus bifidus at that time) 10, 11. Human milk and colostrum were found to contain large amounts of “bifidus factor”. Multiple substances in human milk were found to be bifidogenic and were shown to stimulate the growth of bifidobacteria when administered to bottle-fed infants 12, 13.In the 1970s and ’80s, Japanese investigators pioneered the use of digestion-resistant saccharides to favorably modify the intestinal microbiota using fructooligosaccharides, galactooligosaccharides, and lactulose 14, 15.Prebiotics offer the ability to enhance the healthful strains of bacteria including beneficial strains not available as probiotics, such as Eubacterium species16.
Types of Prebiotics: Most prebiotics are used as food ingredients- in biscuits, cereals, chocolate, spreads, and dairy products, for example. Commonly known prebiotics are:
- Breast milk oligosaccharides
Lactulose is a synthetic disaccharide used as a drug for the treatment of constipation and hepatic encephalopathy.
The prebiotic oligofructose is found naturally in many foods, such as wheat, onions, bananas, honey, garlic, and leeks. Oligofructose can also be isolated from chicory root or synthesized enzymatically from sucrose.
Fermentation of oligofructose in the colon results in a large number of physiologic effects, including:
- Increasing the numbers of bifidobacteria in the colon
- Increasing calcium absorption
- Increasing fecal weight
- Shortening gastrointestinal transit time
- Possibly, lowering blood lipid levels
The increase in colonic bifidobacteria has been assumed to benefit human health by producing compounds to inhibit potential pathogens, by reducing blood ammonia levels, and by producing vitamins and digestive enzymes.
Major Prebiotics and their characteristics: Prebiotics can be classified as a type of digestion-resistant carbohydrate or dietary fiber 17, 18. Like all fibers, prebiotics resist breakdown by human digestive secretions and arrive relatively unchanged in the lower regions of the intestinal tract where they can be utilized as an energy source by the resident microflora. What distinguishes prebiotics from other fibers is that prebiotics by definition selectively stimulate the growth of only beneficial microfloral organisms such as lactobacilli and bifidobacteria. Prebiotic properties have been ascribed to many types of carbohydrates, but they have been best documented for digestion-resistant oligosaccharides (DGOs) 19, 9.
DGOs include inulin-type fructans, galactooligo saccharides, lactulose, isomaltooligo saccharides, xylooligosaccharides, soyoligosaccharides, gentiooligo saccharides and nigeroligo saccharides 1. They may be found naturally occurring in foods or milk or they may be synthesized. Most DGOs are composed of 3 to 10 sugar moieties, although the number of linked sugar molecules (degree of polymerization) varies. Chicory inulin may have up to 60 linked fructose molecules while lactulose, a synthetic prebiotic, consists of only galactose linked with fructose 20.
DGOs do not have uniform chain length, but are a mix ofoligosaccharides with variable degrees of polymerization. They generally have glycosidic bonds in the β configuration and resist hydrolysis by human salivary and pancreatic digestive enzymes which are specific for α glycosidic bonds 18. Ingested DGOs reach the colon largely intact where they are fermented by specific colonic microbial strains possessing a wide assortment of carbohydrolytic enzymes 21. The rate of fermentation is strongly influenced by the constituent monomeric sugars, the degree of polymerization, type of linkage between monomeric units, and the general complexity of the molecule. Of the many forms of DGOs, only inulin-type fructans, galactooligo saccharides, and lactulose fully meet the criteria established for classification as prebiotics 22, 23.
Inulin-type Fructans: Inulin is arbitrarily defined as a mixture oligosaccharides with chain lengths of 2-60 fructose molecules24 with or without an initial glucose.Inulin-type fructans are storage carbohydrates commonly found in wheat, onions, asparagus, bananas, garlic, artichokes, and leeks 25.
Galactooligosaccharides- Galactooligosaccharides: Galactooligosaccharides are digestion-resistant oligosaccharides naturally found in both human and cow’s milk 19. They can also be derived from specific microbial fermentation of lactose or synthesized using the enzyme β galactosidase and lactose syrup. Galactooligosaccharides selectively augment Bifidobacterium and Lactobacillus numbers within the human intestinal microbiota. Prebiotic applications of galactooligosaccharides are of great interest because of their natural occurrence in human milk.
Administration of galactooligosaccharides to formula fed infants has been shown to engender an intestinal flora similar to that of breast-fed infants Bifidobacteria populations are enhanced, pathogen numbers decrease; short-chain fatty acid production increases, fecal pH decreases, and stool characteristics such as frequency and consistency are improved. Galactooligosaccharides appear to offer well-documented prebiotic support, especially in infants, and are only now in the early stages of clinical acceptance.
Lactulose: Lactulose is synthetic galacto-fructose made by the isomerization of lactose 26.Although technically a disaccharide, lactulose is generally grouped together with the DGOs. Lactulose is not usually present in nature although very small amounts may be found in heat-treated milk products as a result of non-catalyzed isomerization. Use of lactulose as a prebiotic dates to the late 1950s when it was found to be bifidogenic and for a time was dubbed “the bifidus factor” 27. Lactulose cannot be split by human intestinal enzymes and is preferentially metabolized by colonic lactic acid bacteria with lactate and short-chain fatty acids as major end products. Human studies reveal prebiotic effects at daily doses of 3 grams with significant increases in Bifidobacterium and Lactobacillus numbers and reductions in Clostridium perfringens, Bacteroides, Enterobacteriaceae, and Streptococcus populations 28, 22.
Mechanisms of Action: Prebiotics affect intestinal bacteria by increasing the numbers of beneficial anaerobic bacteria and decreasing the population of potentially pathogenic microorganisms. Probiotics affect the intestinal ecosystem by stimulating mucosal immune mechanisms and by stimulating nonimmune mechanisms through antagonism/competition with potential pathogens. These phenomena are thought to mediate most beneficial effects, including reduction of the incidence and severity of diarrhea, which is one of the most widely, recognized uses for probiotics. Probiotics reduce the risk of colon cancer in animal models, probably due to their role in suppressing the activity of certain bacterial enzymes that may increase the levels of procarcinogens, but this has not been proven in humans. Well-designed, randomized clinical studies are still required in order to define the role of probiotics as therapeutic agents in inflammatory bowel disease.
Mechanism of Prebiotics:
MECHANISMS OF PROBIOTIC/HOST INTERACTION. SYMBIOSIS BETWEEN MICROBIOTA AND THE HOST CAN BE OPTIMIZED BY PHARMACOLOGICAL OR NUTRITIONAL INTERVENTIONS IN THE GUT MICROBIAL ECOSYSTEM USING PROBIOTICS OR PREBIOTICS
Health Benefits of Prebiotics:
Promotion of Normal Colon Transit Time: Constipation is an exceedingly common clinical problem affecting large segments of the population including the elderly, pregnant and nursing women, people on weight loss diets, and people with disrupted daily schedules such as variable shift workers and business travelers 29, 30. Prebiotics increase fecal bulk and optimize stool consistency primarily by increasing fecal microbial mass. This increase in fecal bulk stimulates passage through the colon, shortening transit time. Colonic water resorption is reduced, stool becomes softer and heavier, and stool frequency increases. Together these factors alleviate constipation and improve colon evacuation. In a study of constipated elderly adults, 20 grams per day of inulin-type fructans had a significantly better laxative effect than lactose 31.
A mixture of inulin-type fructans and galactooligosaccharides has been repeatedly shown to improve the stool frequency and consistency of bottle-fed infants similar to that of breast-fed infants 32. Administration of isomaltooligosaccharides has been shown to increase stool frequency and wet stool output in constipated elderly men 33. Xylooligosaccharides have been shown to reduce severe constipation in pregnant woman 34 and lactulose administration has a long clinical history of alleviating constipation26.
Production of Short-Chain Fatty Acids: Prebiotics are primarily energy sources for healthful intestinal bacteria that ferment them into short-chain fatty acids. Many of the benefits of prebiotics derive from increased bacterial production of short chain fatty acids. Much of the increase in short-chain fatty acids comes about through metabolic cross-feeding in which prebiotics are fermented by certain species, such as Bifidobacterium, into end products that are in turn metabolized by other microorganisms resulting in an increased quantity and diversity of short-chain fatty acids35, 36. Acetate is usually the dominant short-chain fatty acid in the colon followed by approximately equal concentrations of propionate and butyrate 37, 38. Short-chain fatty acids play essential roles in the growth and physiology of intestinal tissue as well as in systemic metabolism 39, 40.
Acetate is an important energy source for the body and is metabolized by skeletal muscle, 41 the heart, 42and the brain43. Gut microflora fermentation is the primary source of blood acetate. Propionate stimulates proliferation of normal crypt cells in human cecal biopsy specimens, while having an anti-proliferative effect on HT-29 adenocarcinoma cell lines 44. Propionate has been shown to reduce hepatic glucose output and cholesterol biosynthesis45, 46. Butyrate is accepted as the most important short-chain fatty acid produced by the intestinal microflora. It is the preferred energy source for colonocytes and its metabolism accounts for 70% of colonic oxygen consumption.
Butyrate modulates colonocyte differentiation and proliferation, and regulates gene expression and transcriptional proteins. Of great importance to human health, butyrate upregulates glutathione S-transferase and catalase expression in colon cells, thereby enhancing cellular detoxification and antioxidant defenses47while reducing cell cycle progression and possibly suppressing DNA repair mechanisms in cancer cells 48, 49.
Additionally, receptors for butyrate, as well as for acetate and propionate, have recently been identified on leucocytes, suggesting a role of short-chain fatty acids in enhancing immune function. Enhanced butyrate production may explain why dietary fiber intake is associated with a reduced risk of colon cancer. Although one in vitro study has suggested that under conditions of prolonged inflammation, as in ulcerative colitis, accumulation of intestinal butyrate may overload DNA repair and apoptotic mechanisms and facilitate mutations that may contribute to tumorigenesis,50.
Enhancement of Mineral Absorption: Several animal studies have demonstrated that inulin-type fructans51, galactooligosaccharides 52, isomaltooligosaccharides 53, lactitol,54 and lactulose55 substantially enhance mineral absorption, especially calcium and magnesium. The combination of inulin and oligofructose has been shown to increase calcium and magnesium absorption more effectively than either oligosaccharide alone. Inaddition to augmenting calcium and magnesium absorption, inulin type fructans have been shown to protect animals from developing symptoms associated with magnesium deficiency and to correct osteopenia. A number of clinical trials involving adolescents, postmenopausal women, and adult men have confirmed an enhancement of mineral absorption mediated by inulin-type fructans56. Increased colonic mineral absorption results from fermentation of inulin-type fructans which leads to higher concentrations of short-chain fatty acids, a lower colon pH, and enhanced mineral solubility and bioavailability.
Studies show that only modest consumption (8 to 10 grams/day) of prebiotics such as inulin-type fructans and lactulose can significantly increase calcium absorption in adolescent girls and boys as well as in postmenopausal women 57. Improved magnesium absorption has also been observed in postmenopausal women following supplementation with 8 grams/day of fructooligosaccharides. In addition to increasing mineral absorption, research suggests inulin-type fructans enhance calcium accretion and improve bone mineralization and density in young adults 58.
Favorable Modulation of Lipid Levels: Most of the results on the effects of prebiotics and lipid metabolism are derived from research with inulin-type fructans. Inulin-type fructans modulate the digestion, absorption, and metabolism of lipids resulting in reductions of serum lipid levels as well as favorable redistributions of lipids among the various lipoproteins. Animal studies show inulin-type fructans decrease both fasting and postprandial plasma triglyceride levels mostly due to a decrease in the concentration of plasma VLDL-triglyceride in the postabsorptive state59.
Oligofructose has also been shown to prevent hypertriglyceridemia induced by both fructose 60 and high-fat61 feeding in rats. The principal hypotriglyceridemic mechanism of action appears to be a decrease in liver lipogenesis through increased production of short-chain fatty acids in the large bowel. Short-chain fatty acid production leads to increased portal concentrations of propionate relative to acetate which inhibits lipogenesis in hepatocytes62. Reduced lipogenic enzyme activity may also result from a prebiotic-mediated decrease in postprandial glucose and insulin concentrations that has been observed in some studies.
The effect of prebiotics on cholesterol levels is less consistent in animals and reductions are usually mild59, 63. In human studies, inulin is more effective than oligofructose in reducing triglyceride and cholesterol levels and the effects are more pronounced in diabetic and hyperlipidemic subjects. Administration of 7 to 20 grams/day of inulin-type fructans has been shown to reduce blood triglyceride and cholesterol levels by as much as 27% and 20%, respectively, in studies involving normal, diabetic, and hyperlipidemic human subjects64, 65.
While the exact mechanism underlying inulin’s hypocholesterolemic effect is not clear, evidence suggests it may result from propionate-induced inhibition of hepatic cholesterol synthesis. Galactooligo saccharides and xylooligosaccharides have also been shown to decrease serum cholesterol and triglycerides, respectively, in animal models 52.
Improved Gut Mucosal Barrier & Immune Function: The gastrointestinal tract is one of the most important components of the body’s defensive system. In addition to providing non-specific protection in the form of a physical barrier against toxins and pathogenic organisms, the intestinal tract also provides specific protection in the form of gut-associated lymphoid tissue, or GALT. GALT represents the largest immune organ in the body and consists of a highly complex network of aggregated and non-aggregated immune cells66. Research indicates prebiotics modulate both intestinal and systemic immunity largely through their association with gut microflora.
Prebiotic support of health-promoting intestinal microorganisms leads to increased competition with pathogens for colonization sites, up regulated GALT expression of secretory IgA and immune-stimulating cytokines, and enhanced production of short chain fatty acids and other antimicrobial substances that create an inhospitable environment for pathogen growth67, 68. Prebiotics have been shown to further enhance the integrity of the intestinal mucosa by increasing villous height, augmenting mucin release, and enhancing healthy mucosal biofilm composition69. The morphological and functional enhancements prebiotics bring to the gut all improve colonization resistance and reduce the risk of pathogen translocation.
Prebiotics such as inulin, inulin-type fructans, galactooligosaccharides, and lactulose have been shown to enhance colonization resistance against a variety of enteropathogenic organisms, including Clostridium difficile, Clostridium perfringens, E. Coli70, 71and other coliforms 72. Research indicates some prebiotic-like substances may also be able to directly stimulate immune cells. Yeast beta-glucans have been shown to activate receptors on phagocytes, NK cells, and certain classes of T- and B-lymphocytes and a novel class of oligosaccharides known as nigeroligosaccharides has been found to augment splenocyte proliferation and production of immune-potentiating cytokines such as interleukin-12 and interferon-γ 73.
Leukocytic receptors for short chain fatty acids have been identified suggesting that immune cells located within the GALT may be stimulated by enhanced production of these fatty acids following prebiotic supplementation. Prebiotic augmentation of both gastrointestinal and systemic immunity helps to reduce the risk of cancers and infections throughout the body. In animal models, the administration of inulin-type fructans has been shown to lower the incidence ofchemically-induced aberrant crypt foci in the distal colon, diminish levels of Candida albicans in the small intestine and reduce mortality from systemic infection with Listeria monocytogenes and Salmonella typhimurium 74.
Human studies examining the effects of prebiotics on systemic immunity involving elderly residents of a nursing facility, shows that supplementation with 8 grams/day of fructooligosaccharides for 3 weeks resulted in a significantly increased percentage of peripheral T lymphocytes and CD4 and CD8 lymphocyte subsets75. Paradoxically, a decrease in phagocytic activity of granulocytes and monocytes was also observed, along with a diminution of pro-inflammatory IL-6 mRNA expression.
The authors speculate these effects may have resulted from a reduced intestinal pathogen load leading to an attenuated inflammatory response. This is a plausible explanation as anti-inflammatory effects of prebiotics havebeen noted in both animals and humans.
Administration of short-chain fructooligosaccharides was shown to reduce multiple chemical mediators of inflammation such as myeloperoxidase, inducible nitric oxide synthase, and leukotriene B4 in rats with experimentally-induced colitis 76. In an open trial examining the effects of prebiotics on a small group of patients with Crohn’s disease, supplementation with fructooligosaccharides for 3 weeks brought about a significant reduction in disease activity concomitant with a marked increase in mucosal bifidobacteria and a shift in dendritic cell function away from pro-inflammatory and towards immunoregulatory activity 77 and in a study involving infants, a formula containing a mixture of galactooligosaccharides and fructooligo saccharides was shown to significantly reduce the incidence of atopic dermatitis compared to the same formula without the prebiotics78.
Influences on Glucose & Insulin Levels: Evidence suggests prebiotics can favorably influence serum glucose and insulin levels in a variety of ways. DGOs and other prebiotics can reduce the amount of glucose available for absorption into the bloodstream. Prebiotics also prevent excessive blood glucose elevations after a meal by delaying gastric emptying and/or shortening small intestine transit time. Bacterial fermentation yielding short-chain fatty acids is another mechanism whereby prebiotics can modulate glycemia and insulinemia.
Propionate has been shown to reduce hepatic gluconeogenesis and enhance hepatic glycolysis,79and fermentation end products, mainly butyrate, are believed to be responsible for increases in the glucose-regulating and satiety-inducing hormone glucagon-like peptide-1 (GLP-1) observed in prebiotic-fed animals 80. Consumption of 20 grams/day of inulin-type fructans by healthy volunteers did not modify fasting plasma glucose and insulin concentrations, but decreased basal hepatic glucose production after 4 weeks.65
Another study examining the effects of 10 grams/day of inulin in healthy middle-aged men and women reported significantly decreased insulin concentrations after 4 weeks81. A study of non-insulin-dependent diabetic subjects administered 8 grams/day of inulin-type fructans reported significantly lower blood glucose levels after 4 weeks 65.
Carcinogenesis & Reduction in Colon Cancer Risk: Carcinogenic substances introduced into the intestinal tract from exogenous dietary sources, or produced endogenously by the gut microflora, represent an environmental insult thought to play a role in the initial stages of cancer. In vitro and animal studies have revealed the potential of prebiotics to enhance detoxification processes in colon cells, reduce toxic metabolite production in the gut, and protect against colonic tumor development. In animal models, inulin-type fructans, galactooligosaccharides, and xylooligosaccharides have been shown to suppress chemically induced colon cancer and precancerous colon lesions 82, 83, 84.
This effect is potentiated by the presence of lactic acid bacteria and associated with microflora fermentation and production of butyrate. Health-promoting bacteria inhibit the growth of pathogenic bacteria and thus decrease the production of carcinogenic substances such as ammonia, and tumor-promoting bacterial enzymes such as beta-glucuronidase. At the same time, bacterial growth increases biomass and thus stool bulk and accelerates colonic transit time decreasing exposure of the colon to potential carcinogens. Prebiotics reduce both the incidenceand multiplicity85, 86of aberrant crypt foci and colon tumors in animal models and research indicates synbiotics have an even more pronounced preventive effect 87.
In addition to reducing the risk of colon cancer, dietary supplementation with inulin and oligofructose reduces the incidence of chemically-induced mammary cancer, slows the growth of implanted tumors, decreases metastases of implanted cancers, and enhances the efficacy of cancer chemotherapy88. Two recent human studies demonstrate the potential benefit of prebiotic feeding in chemoprevention. In a 3-month trial, administration of 10 grams/day of short-chain fructooligosaccharides to healthy individuals significantly reduced the level of toxic bile acids in fecal samples89. In another trial, a synbiotic combination of 12 grams of oligofructose-enriched inulin, Bifidobacterium lactis, and Lactobacillus rhamnosus significantly reduced DNA damage to colon cells and the cytotoxicity of fecal water in a group of subjects with a history of adenomatous colon polyps (but not those with extant colon cancer)90.
Prebiotics & Infant Microflora: Formula-fed infants often have an altered balance of microorganisms in their gastrointestinal tract characterized by lower numbers of bifidobacteria and higher numbers of bacteroides, clostridia, enterobacteria, and staphylococci 91, 92. Formula-fed infants also have a higher risk of intestinal infections. Human breast-milk contains numerous antibodies and a very highconcentration of oligosaccharides that contribute to the natural defense against infection and promote a bifidobacteria-dominant microflora in the infant. Efforts to replicate the immunoprotective and bifidogenic effects of human breast milk on the intestinal tract of bottle-fed infants have led to research examining the effects of incorporating prebiotics into infant formulas.
Formulas containing a mixture of galactooligosaccharides and fructooligo-saccharides in a ratio of 9:1 have been shown to promote a microflora in infants similar to that seen in breast-fed infants93. Infants consuming this prebiotic mixture have significantly higher levels of fecal bifidobacteria, lower fecal pH, reduced levels of fecal pathogens, improved stool characteristics such as frequency and consistency, and short-chain fatty acid patterns more characteristic of breast-fed infants compared to infants fed a control formula.
One recent study also shows this type of prebiotic supplementation can reduce the incidence of both intestinal and systemic infections during infancy94. These data suggest that supplementing formula-fed infants with prebiotics can have significant beneficial effects on intestinal microbial ecology,immune development, and protection against infection.
CONCLUSIONS: The emerging area of prebiotics points towards the holistic role of nature in the health and nutrition of human being. We seem to be heading for coming a full circle from the times the aboriginal human was using tree bark as apparel and all vegetation along with animal flesh as its food, speedingly delineating health and nutrional effects of prebiotics has begun to underscore the role of non nutritive vegetation in our life. Probiotics have potential applications in many areas of human health. Probiotic products are widely marketed, and consumer interest in probiotics is growing rapidly.
The commercial use of probiotics has proceeded because essentially no risk is associated with consumption of well-defined probiotics in foods and many benefits are possible.
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Sheel Sharma*, Nidhi Agarwal and Preeti Verma
Food Science and Nutrition, Banasthali University, P.O.- Banasthali Vidyapith- 304 022, Rajasthan, India
22 January, 2012
15 March, 2012
13 May, 2012
01 June, 2012