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V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info - type : A Review

V. Sridevi+, V. Sumathi#, M. Guru Prasad*§ and Satish Kumar.M. *§¶ + Department of Biotechnology, Sri Venkateswara University,Tirupati - 517 502, A.P,India. # Department of Biotechnology, Sri Padmavati Mahila Visva Vidyalayam,Tirupati - 517 502, A.P,India. * Department of Biochemistry, Bharathiyar University, Coimbatore - 641046, T.N. ,India. § Vidya Vikas Institute of Engineering & Technology, Alanahalli, Mysore 570028. Karnataka. ,India. ¶ Department of Chemistry, P.E.S.College Of Engineering, Mandya - 571401, Karnataka. ,India.

Received on:12-01-2014; Revised on: 06-02-2014; Accepted on:18-02-2014

ABSTRACT The main advantage of prebiotic is that they are natural functional ingredients. Prebiotics are being used in the food industry as functional ingredients in beverages, milk products, and symbiotic products. Fructooligosaccharides (FOS) are oligosaccharides that occur naturally in Medicinal plants such as , , , , , artichoke, among many others. FOS are not digested by the human , and when they reach the colon, they beneficially stimulate the growth and strengthening of specific bacteria in the intestine. Several studies have demonstrated the functional properties of FOS, such as the reduction of cholesterol levels and blood levels, lowering of blood pressure, better absorption of and magnesium and to inhibit production of the reductase enzymes that can contribute to cancer. Currently FOS are increasingly included in food products and infant formulas due to their prebiotic effect stimulate the growth of nonpathogenic (bifidobacteria) intestinal microflora and decreases growth of potentially pathogenic bugs and enhances the .

Key words: Biomedical and industrial importance, Fructooligosaccharides, Prebiotics

INTRODUCTION: Prebiotics are generally defined as non-digestible resistance to digestion; (2) fermentation by the intestinal microflora; and oligosaccharides (NDO), which promote the growth of beneficial and (3) a selective effect on the flora that promote health. Their up- in the colon and exert antagonism to Salmonella dated definition is: “A prebiotic is a selectively fermented ingredient sp. or , limiting their proliferation. The term prebiotics that allows specific changes, both in the composition and/or activity was coined by Gibson and Roberfroid1. Gibson et al.,2 elaborated the in the gastrointestinal microflora that confers benefits upon host well- prebiotics concept by certain criteria viz. resistance to gastric acidity, being and health”. The key words in both definitions are “selective” by mammalian enzymes and gastrointestinal absorption; and “benefit/improve...host...health”. Therefore, a prebiotic substrate fermentation by intestinal microflora and selective stimulation of the must be particularly readily available to some groups of bacteria of growth, and/or activity of intestinal bacteria associated with health which lactobacilli and bifidobacteria are considered indicator organ- and wellbeing. There exists an array of prebiotics with various origin isms that are beneficial to intestinal health, but less available to po- and chemical properties. In particular, many food oligosaccharides tentially pathogenic bacteria, such as toxin-producing Clostridia, and polysaccharides (including ) have been claimed to proteolytic Bacteroides and toxygenic E. coli3. In this manner, a have prebiotic activity, but not all dietary are prebiotics. “healthier” microbiota composition is obtained whereby the bifidobacteria and/or lactobacilli become predominant in the intestine 2 Gibson and colleagues have reviewed their original prebiotic con- and exert possible health promoting effects. cept in the light of much research that has been published in the past decade, and in particular the three key aspects of their definition: (1) The principal concept associated with both of these definitions is that the prebiotic has a selective effect on the intestinal microbiota *Corresponding author. which results in an improvement in health of the host. The definitions Dr. M. Satish Kumar, arose from observations that particular dietary prebiotics as func- Associate Professor, tional ingredients bring about a specific modulation of the GI ecosys- Vidya Vikas Institute of Engineering and Technology, tem, particularly increased numbers of beneficial bacteria, and de- Visvesvaraya Technological University, creased numbers of potential pathogenic species, which associated Alanahalli, with improved host health. These are not absorbed in small intestine Mysore – 570028. Karnataka. ,India.

Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330 of healthy individuals but later are fermented by natural microflora of major determining factor in whether to purchase a food item. The the colon to produce short-chain fatty acids (SCHFA)4. The main food industry has invested in some great innovations, mainly in the advantage of prebiotic oligosaccharides is that they are natural func- formulation of ingredients and additives, functional foods, transgenic tional ingredients. Their incorporation in the diet does not require foods and packaging22. The increased demand for functional foods in particular precautions, and their authorization as food/feed additives recent years is closely related to the growing concern of society with may be more easily obtained, in spite of some concerns about their health and quality of life. Moreover, consumers are more informed safety and efficacy5. Stowell6 reviewed the existing prebiotics and and aware about the foods that can benefit health. Prebiotic are in- classified them based on a set of common criteria. , creasingly added to foods for their health benefits. Several industrial fructooligosaccharides (FOS), (GOS), products containing added prebiotics can be found in the consumer and polydextose are recognized as the established market: products, breads, fruit juices, margarine, pasta, dairy prebiotics, whereas isomaltooligosaccharides (IMO), desserts, ice creams, cereals, milk, , biscuits, soft drinks in xylooligosaccahrides (XOS), and lactitol are categorized as emerging general, isotonic drinks, liquid and modified sugar, chocolates prebiotics. Chicory root inulin-derived (FOS), -derived and candies in general. arabinoxylooligosaccharides (AXOS) and (XOS) proved to have huge applications7-9. Prebiotics can be found in some In prebiotic studies, fructooligosaccharides -type prebiotics have vegetables, such as leeks, , chicory, tomatoes, asparagus, arti- been studied as an isolated intervention in field of health concern. chokes, , and alfalfa. It can also be added to industrial prod- This review focuses on the beneficial effect on human concern; how- ucts such as foods for children, dairy and confectionery products, ever, a summary fructooligosaccharides prebiotic research is pro- beverages, light mayonnaise and low-fat cheese, and they can be vided. used as dietary supplements10,11. Fructooligosaccharides (FOS) Prebiotics are being used in the food industry as functional ingredi- Several studies have demonstrated the functional properties of ents in beverages (fruit juices, coffee, cocoa, tea, soft drinks and fructooligosaccharides (FOS), such as the reduction of cholesterol alcoholic beverages), milk products (fermented milk, milk powder and levels and blood glucose levels, lowering of blood pressure, better ice cream), probiotic yogurts and symbiotic products12,13 . Other ap- absorption of calcium and magnesium and to inhibit production of plications include desserts (e.g., jellies, puddings, fruit-flavored ice the reductase enzymes that can contribute to cancer23,24. FOS are not cream), confectionery items (e.g., sweets), biscuits, breakfast cereals, digested by the human gastrointestinal tract, and when they reach chocolates, breads and pastas, meat products (e.g., fish paste) and the colon, they beneficially stimulate the growth and strengthening tofu. Prebiotics can also be used in cosmetics, pharmaceuticals and of specific bacteria in the intestine12. The bifidobacteria secrete ß- products for people with diabetes13. fructosidase, which would be the enzyme responsible for FOS hy- drolysis25. The average counts of bifidobacteria increased, whereas Prebiotics may exhibit the following properties: there were significant reductions in Bacteroides, Fusobacteriumand · Maintenance of intestinal flora and stimulation of intestinal sp. transit11; · Change in colonic microflora, contributing to normal stool Structure: consistency, preventing diarrhea and constipation14-16; Their chemical structure consists of a chain of units with · Elimination of excess substances such as glucose and cho- a terminal glucose unit linked by ß(3-(2-1) glycosidic bonds, which lesterol, favoring only the absorption of substances means they cannot be hydrolysed by human digestive enzymes needed17; which are specific for a glycosidic bonds. The length of the chain · Stimulation of the growth of bifidobacteria18; ranges from 2 m 60. There are three categories of FOS, each of which · Stimulation of the absorption and production of B is structurally distinct: inulin, has a polymerization degree of 2 to (B1, B2, B3, B6, B9, B12)19; about 60 monomers of fructose, with an average of 12 units (57): · Support of the immune system20; oligofrumose is produced by the enzymatic hydrolysis of inulin · Contribution to the control of obesity21; and and is defined as a fraction of oligosaccharides with degree of poly- · Contribution to the decrease of the risk of osteoporosis17 merization lower than 20, although commercial products tend to have a mean value of 9; these FOS are produced by the enzymatic Due to poor nutrition, tobacco and alcohol consumption, the past hydrolysis of inulin and consists of frucrosyl chains of different few decades have seen alarming increase in morbidity and mortality. lengths, with glucose and fructose terminals. Finally, scFOS (short With instances of chronic obesity, gastrointestinal disorders, diabe- chain fructooligosaccharides) are specifically defined as mixed chains tes, coronary diseases, cancers, and degenerative diseases on the of fructosyl with a glucose terminal unit; they have a maximum of 5 rise, growing numbers of consumers are looking up to companies units and are derived from sugar through natural fermentation pro- manufacturing prebiotics. Cashing in on the consumer craze for low- cesses, producing 1-kestose (CF 2), nistose (CF 3) and 1-fructosyl high-fiber diet, nutraceutical market is being dominated - nistose (GF 4) in which the fructosyl units (F) are linked at ß-(2-1) by a wide range of prebiotic products. The health effect of food is a position of (Fig1).

Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330

1-Kestose Nystose 1 Fructofuranosyl Nystose Fig.1 Chemical structure of short chain fructooligosaccharides Fructooligosaccharides (FOS) belong to the group of oligosaccha- bifidobacteria recovery36. In vitro and in vivo studies have suggested rides and are isolated from plants. In the extraction commercialization the lack of genotoxicity and mutagenicity of FOS. Evaluations con- process, FOS can be obtained from inulin by means of the ducted in rats showed no adverse effects with quantities lower than transfructosylation enzymatic reaction in sucrose residues by the 2.17 g/kg/day34, 37. action of the ß-fructofuranosidase enzyme, with the DP of these prod- ucts varying between 1 and 7 fructosyl units26. Source: FOS are available in some foods such as bananas, garlic, onion, to- Requirement: mato, wheat, asparagus, artichoke, leek, honey, rye, brown sugar, Flamm et al.,27 have evaluated the caloric value of FOS and found that , triticale, beer, lettuce, chicory, burdock, beetroot, apples, bulbs the energy yield for the host would be in the range of 1.5 kcal/g to 2.0 like red lilies, yacon and oats, with onion being the food with the kcal/g. By using another method based on lipogenesis balance, highest levels of FOS (Table 1). Roberfroid28 stated that the caloric value of FOS is around 1.0 kcal/g to 1.5 kcal/g. In Holland, it is estimated that the consumption of FOS Table 1. Amount of FOS (%) per 100g raw in some natural foods. is 2 g to 12 g per day. In Japan, the estimate is between 13.7 mg/kg of body weight per day. However, for the approval of FOS, the Japanese Food Percentage law established the amount of 0.8 g/kg of body weight per day as an acceptable daily intake29,30. The average per capita daily consump- Chicory root 22.9 g tion of FOS is 2 - 4 g for North Americans and 2 - 12 g for Europeans31. 13.5 g In Brazil, there are no relevant data regarding the amount consumed Dandelion greens 10.8 g or the dietary recommendations. The law considers FOS as ingredi- Garlic 5 g ents of products, not additives. FOS are considered as dietary fiber, Leek 5.2 g and in the United States, they have a GRAS status (Generally Recog- Asparagus 2.5 g nized As Safe). Ingestion may cause , especially in indi- Banana 0.5 g viduals who have intolerance, but the severity of this symp- tom is associated with the amount of FOS consumed: the higher the Production: 32 quantity, the greater the symptom . The intake of 20 g to 30 g per day After extraction of native inulin, the product then undergoes either can promote severe discomfort in an individual, and thus, the optimal industrial physical separation of long-chain fructans38 or is partially 30 intake level is 10 g per day . For the promotion of colon floral bal- hydrolyzed by endoinulinase to produce short-chain oligosaccha- ance, the amount of FOS needed has been determined to be 2 g to 2.5 rides, mainly oligofructose (Fig. 2). Oligofructose produced from inu- 33 g per day . The minimum dose of FOS for the induction of diarrhea is lin may or may not have a terminating glucose molecule, may contain 34, 35 44 g for men and 49 g for women . For enteral nutrition, several longer-chain fructans39 , and has a DP of 2–10 (average 5)40. Alterna- clinical studies suggest the amount of 5 - 10 g/day for the mainte- tively, short-chain fructooligosaccharides can be produced syntheti- nance of normal flora and from 12.5 g/day to 20.0 g/day for cally through transfructosylation of sucrose using the b -

Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330

Fig.2 Commercial production of fructooligosaccharides from extracts of natural sources fructofuranosidase enzyme39 from Aureobasidium pullulans or As- the administration of 8 g/day of Neosugar in the human diet increased pergillus niger41 . These compounds contain 2–4 fructosyl units the production of fatty acids. Wang and Gibson51 found the follow- with a terminal glucose unit and an average DP of 3.540. Synthetic ing benefits could be attributed to bifidobacteria: they are fructooligosaccharides contain only Gpy Fn oligomers. These prod- immunomodulatory against malignant cells, produce B vitamins and ucts may contain free glucose, fructose, and sucrose, which can be folic acid, stimulate the production of digestive enzymes and lysozyme removed via chromatographic procedures to increase the purity of and restore normal intestinal biota after therapy. Regarding the fi nal product. It should be noted, however, that a large amount of the bifidogenic dose of FOS, authors like Roberfroid et al52 estab- starting material is needed to achieve efficient transglycosylation41. lished that about 4 g per day would be enough for an adult. Bouhnik53 demonstrated that FOS ingestion at doses of 12.5 g/day for three are perhaps the most well-established prebiotics42 and the days (clinically tolerated dose) produced a decrease in the total count most extensively studied. They meet the three key criteria defi ning a of anaerobes in the feces, in pH, in the activity of nitroreductase, in prebiotic, that inulin-type fructans are nondigestible43, are fermented bile acid concentrations and in serum levels of total cholesterol and in the large bowel, and lead to selective growth of bacteria associated lipids. with health in vitro44 and in vivo [human subjects, including infants45, adults 46 and the elderly47. Beneficial Health Effects

Mode of action: Infant Health: The mechanism by which the inhibition of pathogens occurs (exog- Exclusive breastfeeding is strongly recommended for newborn in- enous or endogenous) can be explained by the lowering of the pH in fants with a family history of allergy, as breastfeeding reduces the the intestinal lumen as a consequence of the formation of short chain likelihood that the infant will develop atopic disease. One study in fatty acids (SCFA) by FOS fermentation19,25. The decrease in the num- infants directly evaluated whether infant formula supplementation ber of harmful bacteria (such as Escherichia coli, Clostridium, Strep- with prebiotics could replicate the protective effect of breastfeeding. tococcus faecallis and Proteus) results in the decrease in toxic me- In this study, 259 infants at risk for atopic disease were randomized to tabolites, such as ammonia, indoles, phenols and nitrosamines48. receive either control formula or formula supplemented with a blend Modler49 verified that adding NeosugarR (a trade name of of FOS (9:1 ratio; 8 g/L)54. Fecal microbiota were analyzed in a sub- fructooligosaccharides) to the human diet (15 g/day) caused a ten- group of 98 infants. Levels of bifidobacteria were significantly higher fold increase in the population of bifidobacteria in the , among infants who received the prebiotics compared to control in- as well as increasing the occurrence of bifidobacteria from 87% to fants; levels of lactobacilli did not differ between the groups. Over 100%. Concomitantly, there was a reduction of 0.3 intestinal pH units the 6 month course of the study, fewer infants in the supplemented and a decrease in the enterobacteria count. Hidaka et al.,50 found that group developed atopic dermatitis compared to the control group,

Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330 suggesting that prebiotics may modulate postnatal immune develop- were challenged by injecting Vibrio splendidus. The results revealed ment in part by altering the GI microbiota; there may be other mecha- that the specific growth rates (SGR) of sea cucumbers were not af- nisms as well. This study supports a potentially positive role for fected by TC22 and FOS, or the interaction between TC22 and FOS prebiotics in managing symptoms of allergy during infancy, but addi- (P > 0.05). However, there were significant interactions between TC22 tional studies are still needed. One clinical study in children sug- and FOS for immune response and disease resistance in sea cucum- gested that supplementation with FOS (2 g/d) for 21 days could im- bers (P < 0.05). When sea cucumbers were fed with TC22 at 109 CFU prove their immunological status, based on a lower incidence of fe- g-1 feed and 0.5% FOS alone or in combination, the phagocytosis, ver, vomiting, and diarrhea in those taking the supplement55. respiratory burst and phenoloxidase activity of sea cucumber coelomocytes were significantly enhanced; the disease resistance Another study, conducted among breastfed infants living in a com- against V. splendidusinfection was also increased significantly. This munity near Lima, Peru with a high prevalence of GI and other infec- study confirms FOS involved in boosting up of immunity and disease tions, found that feeding infant cereal supplemented with oligofructose resistance of sea cucumbers. at 0.55 g/15 g cereal for 6 months was not associated with change in incidence of diarrhea, use of health care resources, or response to a fl Vos et al.,61 studied the the immunemodulatory effect of specific pre- u vaccination. A high prevalence of breastfeeding in the study popu- biotic oligosaccharides viz. GOS, FOS and -derived acidic oli- lation was thought to contribute to the lack of effect with prebiotics gosaccharides. The supplementation exerted immunemodulatory ef- observed56. Further studies in infants and children are needed to fect during the early phase of a murine immune response. Prebiotics clarify these findings. may reduce the incidence of degenerative diseases, such as neoplasias, diabetes, coronary diseases and infections. They also seem to pro- A randomized, placebo-controlled trial, involving 134 infants less than mote a positive modulation of the immune system62. Stam et al., 63 6 months old whose parents suffered from allergies, found that those conducted a RCT on the effect of a prebiotic mixture supplementation fed a prebiotic combination of FOS/GOS experienced a significant in formula food on the antibody responses to Influenza and tetanus reduction in both allergy symptoms and minor infections that lasted vaccination in infants during the first year of life. It was hypothesized at least through age 2. The researchers suggested that the favorable that a prebiotic mixture of short-chain GOS, long-chain FOS and pec- effects of prebiotics on intestinal bacteria early in life may produce tin-derived acidic oligosaccharides, resembling the composition of lasting benefits to the immune system57. One study found that use of oligosaccharides in human milk, promote T Helper 1 (Th1) and regu- inulin promoted growth of probiotic bacteria in the bifidobacteria latory T cell (Treg)-dependent immune responses and induce down family58. regulation of IgE mediated allergic responses. Additionally, the prebi- otic administration does not interfere with the desired vaccinespecific Immune boosters: serum antibody responses in healthy term infants63. Studies of Babu et al.,59 confirmed that FOS has an anti inflammatory effect in chickens. This study, Salmonella Enteritidis (SE) is used as Improve absorption: test organism and it is one of the leading causes of food-borne salmo- A naturally sweet, indigestible fiber derived from chicory roots, FOS nellosis, and macrophages play an essential role in eliminating this (fructooligosaccharides) are one of the best-documented, natural pathogen. They study on tested the influence of a prebiotic for promoting the growth of Lactobacilli and bifidobacteria (FOS)-inulin on the ability of the chicken mac- bacteria, a key to sound health. FOS has also been clinically studied rophage HD11 cell line to phagocytose and kill SE, and express se- for its ability to increase magnesium and calcium absorption. Be- lected inflammatory cytokines and chemokines in an in vitro model. cause FOS can increase magnesium absorption, it can also lead to There were significantly fewer viable intracellular SE in HD11 cells lowered blood pressure and better cardiovascular health. FOS is one treated with FOS-inulin than the untreated cells. However, SE phago- of the most powerful prebiotics to be researched in the last decade (a cytosis, nitric oxide expression or production were not influenced by “prebiotic” feeds intestinal flora; a “probiotic” adds more actual cul- the prebiotic treatment. Among the inflammatory markers tested, IL- tures to existing intestinal flora). The subject of over 100 clinical stud- 1ß expression was significantly lower in HD11 cells treated with FOS- ies, FOS is one of the best-documented natural nutrients for improv- inulin. These results suggest that FOS-inulin has the ability to modu- ing the healthy balance of bacteria in intestines and stimulating the late the innate immune system as shown by the enhanced killing of growth of the beneficial bifidobacteria also called “friendly flora” that SE and decreased inflammasome activation. reside in the colon.

Yancui Zhao et al.,60 studied the effects of probiotic Bacillus TC22 Besides building up the beneficial bacteria in the body, FOS has also (isolated from intestine of infected sea cucumber) and prebiotic been shown to improve blood sugar control, liver function, and cal- fructooligosaccharide (FOS) on growth, immunity and disease resis- cium and magnesium absorption. A 1997 animal study conducted at tance in sea cucumberApostichopus japonicas. Six experimental di- the Nutritional Research Center in Japan found that a 5 percent FOS ets were formulated with combinations of three levels of TC22 (0, diet increased magnesium and calcium absorption substantially. A 107 and 109 CFU g -1 diet) and two levels of FOS (0 and 0.5%) in a 3 × 2 1998 Showa University study, obtained similar results64, 65. Magne- factorial experiment. At the end of the 8-week feeding trial, animals sium is one of the most important nutrients we obtain from our diet,

Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330 being involved in over 300 enzyme reactions in the body. As we age, placebo, and returned conflicting results83. According to some mea- our magnesium levels drop markedly, which creates a deficiency that sures of symptom severity employed by the researchers, use of FOS increases the risk of angina, atherosclerosis, cardiac arrhythmias, led to an improvement in symptoms. However, according to other depression, and diabetes66. A study conducted by National Research measures, FOS actually worsened symptoms. Conflicting results, Council of Canada showed that long-term marginal magnesium defi- though of a different kind, were also seen in a 12-week, double-blind, ciency can reduce the life span of laboratory animals by almost 40 placebo-controlled study of 98 people86. Treatment with FOS at a percent67. dose of 20 g daily initially worsened symptoms, but over time this negative effect wore off. At no time in the study were clear benefits Small double-blind studies found that FOS at a dose of 10 g daily may seen, however. On a positive note, one study did find benefit with a improve magnesium absorption in postmenopausal women.68Whether combination prebiotic-probiotic formula84, and another study found this is beneficial remains unclear, since magnesium deficiency is not the combination beneficial for women with constipation when taken believed to be a widespread problem. FOS may also slightly increase in yogurt 87. copper absorption , but does not appear to affect absorption of calcium , zinc , or selenium 69,70. Cancer studies Fabrice et al.,88 studied effect of short chain FOS on colon cancer, Reduction of cholesterol levels: which might reduced the occurrence of colon tumors and developed Animal studies hint that FOS, GOS, and inulin can significantly gut-associated lymphoid tissue in min mice. This study shown that improve cholesterol profile; however, study outcomes in humans have sc-FOSs did not reduce the occurrence of tumors in the small intes- been inconsistent at best.71-77. One study found that while inulin might tine96, immunosurveillance was specifically generated in the colon produce a short-term benefit, any such benefit disappears after six and implicated the local immune system. As most ?,d-receptor-bear- months of use.78 At most, it appears that FOS might improve choles- ing intraepithelial lymphocytes are CD4– CD8– (11) and thus not af- terol profiles by 5%, an amount too small to make much of a difference fected by depletion, it is unlikely that these cells were the main effec- in most circumstances. These relatively poor results might be due to tor subset. Immunosurveillance appeared to be specifically gener- that fact that humans cannot tolerate doses of FOS much above 15 g ated by the diet since the Min phenotype was independent of the daily without developing gastrointestinal side effects. immune system, as shown by Dove et al.,89 and Dudley et al., 90. This study shows that sc-FOSs may provide an immunocompetent host Diarrhea with a mechanism of tumor surveillance, operative against spontane- FOS has also been suggested for preventing traveler’s diarrhea . ously arising colon tumors. However, in a large (244-participant) double-blind study, FOS at a dose of 10 g daily again offered only minimal benefits79. Endogenous or exogenous bile acids, as well as dietary cholesterol themselves might be a better bet. Another study found are carcinogenic factors involved in colon cancer in laboratory ani- that use of FOS might help reduce incidents of diarrhea, flatulence, mals92,93. Various epidemiological studies suggest those steroids could and vomiting in preschoolers80. also be involved in colon cancer in men94,95. According to these stud- ies, low scFOS dose ingestion by humans, which prevented microbial Type 2 diabetes conversion of cholesterol into cytotoxic molecule, (coprostanol, po- According to most studies, FOS at 10-20 g daily do not improve tentially carcinogenetic), could be interesting for humans. In Yoram blood sugar control in people with type 2 diabetes81,82. In a prelimi- Bouhnik et al.,96 study, the intake of 8 g/d scFOS led to increasing nary trial, supplementation with fructo-oligosaccharides (FOS) (8 faecal cholesterol. The mechanism of such increase could be related grams per day for two weeks) significantly lowered fasting blood- to decreasing cholesterol bacterial transformation, although failed to sugar levels and serum total-cholesterol levels in people with type 2 find any significant sc-FOS effect on cholesterol bacterial metabo- diabetes79. However, in another trial, supplementing with FOS (15 lism. Moreover, the low scFOS dose used in this study was also grams per day) for 20 days had no effect on blood-glucose or lipid probably not sufficient to significantly reduce microbial conversion levels in people with type 2 diabetes83. In addition, some double- of bile acids, which is commonly increased in elderly living in blind trials showed that supplementing with FOS or galacto-oligosac- industrialised countries and they found significant change in choles- charides (GOS) for eight weeks had no effect on blood-sugar levels, terol metabolism, which could potentially exert protective action insulin secretion, or blood lipids in healthy people84,85. Because of against colon cancer. these conflicting results, more research is needed to determine the effect of FOS on diabetes and lipid levels. Safety Issues FOS appear to be generally safe. However, they can cause , Bowel syndrome: flatulence, and intestinal discomfort, especially when taken at doses FOS have been advocated as a treatment for irritable bowel syndrome . of 15 g or higher daily. 6,7 People with lactose intolerance may par- However, research results are currently inconsistent at best. For ex- ticularly suffer from these side effects97. ample, a 6-week, double-blind study of 105 people with mild irritable bowel syndrome compared 5 g of fructo-oligosaccharides daily against CONCLUSIONS: Several studies have demonstrated the functional properties of Journal of Pharmacy Research Vol.8 Issue 3.March 2014 321-330 V. Sridevi et al. / Journal of Pharmacy Research 2014,8(3),321-330 fructooligosaccharides (FOS), such as the reduction of cholesterol charides: A Review,” Carbohydrate Polimers, Vol. 68, No. 3, levels and blood glucose levels, lowering of blood pressure, better 2007, pp. 587-597. doi:10.1016/j.carbpol.2006.12.011. absorption of calcium and magnesium and to inhibit production of 14. Bosscher D, Loo-Van J and Franck A, “Inulin and the reductase enzymes that can contribute to cancer. 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