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Prebiotics as “Good Carbs”
By Carol Ann Brannon, MS, RD, LD
Today’s Dietitian
Vol. 8 No. 8 P. 12

CDR Learning Code 5250, Level II
(see related charts)

“Carbs are bad” is out; being “carbohydrate selective” is in. We know whole grains and fiber-rich foods are beneficial. Another category of carbohydrates, prebiotics, have long been left out of the spotlight. U.S. consumers are somewhat familiar with probiotics (foods and beverages containing live, beneficial bacteria, such as yogurt), but most are unfamiliar with prebiotics.1 Elsewhere, probiotics and prebiotics are well accepted. Dietitians can help educate consumers about the connection between gut health and overall whole-body health.1,2

Probiotics, Prebiotics, and Synbiotics
Probiotics, prebiotics, and synbiotics —foods and beverages containing both probiotics and prebiotics—are “functional” by definition. They extend beyond meeting nutritional needs by promoting wellness and potentially reducing disease risk.2-4 A useful term is multitiered functionality, which means containing ingredients that provide numerous, diverse health benefits. Probiotics and prebiotics deliver multitiered functionality.2

Although probiotics and prebiotics appear to have a synergistic effect, they are distinctly unique and are two separate categories of functional foods. Prebiotics are the focus of this article; however, a brief review of probiotics may be helpful in understanding the difference.

The beneficial role of living microorganisms in food has been known since Roman times.3 Early last century, Elie Metchnikoff, a Russian zoologist, documented the health benefits of friendly bacteria and hypothesized that yogurt contributed to the long, healthy lives of Bulgarian peasants.3,4 Overwhelming evidence supports the view that probiotics promote health and wellness and may be used therapeutically in the treatment of selected conditions.3-7 Although the understanding of probiotics continues to evolve, we may use the following as a working definition: “a live microbial feed supplement, which beneficially affects the host animal by improving its intestinal microbial balance.”6-8

The human body has 10 times as many bacterial cells as human cells, and the digestive tract harbors more than 400 different species of microorganisms. Some are benign or beneficial while others are pathogenic. Researchers theorize that maintaining a positive balance of probiotics in the colon displaces pathogenic bacteria, such as Bacteroides and clostridia, making them unable to proliferate and cause disease.3,5,9

Approximately 20 species of bacteria are considered probiotic.3-6,9 The most common are strains of lactobacilli and bifidobacteria. The predominant specie in the human colon is bifidobacteria, accounting for roughly one fourth of the colonic bacteria in healthy adults. Different probiotics have unique and specific actions in the gastrointestinal (GI) tract. Each species of bacteria yields unique health benefits.9 The positive effects of probiotics on the immune system, as well as on overall health, are well documented and summarized below4,5,9:

• inhibit the growth of pathogenic bacteria;

• synthesize vitamins, primarily B vitamins;

• enhance the bioavailability of nutrients;

• decrease lactose intolerance;

• boost nonspecific and specific immune response;

• decrease prevalence of allergies;

• improve serum cholesterol levels; and

• decrease the risk of certain cancers.4

Research indicates that diet may play a role in modulating intestinal microflora (IM) to favor probiotics, thereby improving overall health.3,4,10,11 Three mechanisms are proposed:

• Consume fermented foods (yogurt, cottage cheese, buttermilk, kefir, soy sauce, miso, tempeh, and fresh sauerkraut) and a variety of dietary supplements.4,6 Dairy foods are the best medium in which to place probiotics for consumption.

Probiotic bacteria are sensitive to heat, light, moisture, oxygen, and acidic environments, and thus struggle to survive manufacturing processes. Ingested probiotics must survive exposure to gastric and bile acids before they can attach to the intestinal wall. Thus, simply consuming probiotics may not be enough to ensure their ability to thrive in the colon.1-4

• “Feed” or stimulate the growth of existing probiotic bacteria by consuming prebiotics, defined as “a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon.”1,2,11-13

• Combine the two tactics by ingesting synbiotics.9,14,15

Oligosaccharides
Some researchers have argued that prebiotic intake, rather than probiotic intake, is a more practical and efficient way to manipulate the IM since orally ingested probiotic bacteria have an uncertain and unpredictable survivability/viability rate through the GI tract. In contrast, prebiotics are not sensitive to digestive acids or enzymes.13

The theory that prebiotics can selectively stimulate the growth and/or activity of beneficial bacteria (usually bifidobacteria and lactobacilli) emerged approximately 25 years ago in Japan, where researchers seeking to explain the longevity and good health of isolated populations focused on a short-chain fructooligosaccharide (scFOS) in their diet.11,14 Since then, numerous in vitro, animal, and human studies have confirmed that prebiotics are beneficial.14,16-20 A commercially prepared scFOS (Neosugar) is currently used in more than 500 Japanese food products—from infant formulas to health foods.14 Criteria for classification as a prebiotic are:

• resistant to digestion;

• fermented by colonic microflora;

• able to selectively stimulate growth of beneficial bacteria; and

• beneficial to the host’s health.

Nondigestible oligosaccharides (NDOs) meet all the requirements. These short-chain carbohydrates vary in number, type, and sequence of their monosaccharide (glucose, fructose, xylose, and galactose) moieties. The FOS, or fructans, which include inulin and oligofructose, are the best-studied prebiotics.14,16-18 Other NDOs, including lactulose, galactooligosaccharides, glucooligosaccharides, and soybean oligosaccharides, need further study.14

Inulin and oligofructose are present in varying amounts in more than 36,000 plant foods as plant storage carbohydrates.14,17 Excellent food sources are chicory root (Cichorium intybus; roughly 15% to 20% inulin and 5% to 10% oligofructose) and Jerusalem artichokes. Others include wheat, barley, rye, flax, oatmeal, other whole grains, onions, garlic, leeks, legumes, asparagus, greens (dandelion, spinach, collard greens, chard, kale, mustard greens), berries, bananas, and honey.14,17 Most inulin used commercially in foods is extracted from chicory or synthesized from sucrose. Oligofructose is a partial hydrolysate of inulin.1,2,16,17

Resistant Starches
Resistant starch (RS), found in whole grains, fruits, and some processed foods, differs from other starches in that it resists digestion in the small intestine. Rather, probiotics ferment it in the colon. RS is similar to inulin and oligofructose; but unlike fructans, RS is fermented slowly, resulting in less flatulence. In addition, RS is well tolerated in larger amounts than the fructans.

One promising and potential health benefit of dietary intake of RS is improvement in insulin sensitivity.21-23 RS is categorized as a low-glycemic ingredient and is often added to foods to “top off” the fiber content. RS is becoming more popular as a functional ingredient. The most commonly used RS is a high amylase corn RS. More research is needed, but you will no doubt be hearing more about RS and its functionality.

Metabolism
Prebiotics arrive intact in the colon, where they are digested through bacterial activity. They are selectively fermented by probiotics, specifically bifidobacteria, which possess beta-fructofuranosidase, an enzyme that allows preferred utilization of FOS over sucrose.24 Fermentation, an anaerobic process, results in the release of short-chain fatty acids (SCFAs), organic acids, short-chain carboxyl acids, and products of IM.14,16-20

SCFAs have a variety of positive physiological effects and health benefits. They decrease the pH level in the colon, which enhances mineral absorption, especially for calcium. An acidic environment is favorable for probiotics but detrimental to the survival of pathogenic bacteria. SCFAs are also the preferred energy source for colonic epithelial cells and they increase bacterial growth and cell mass, resulting in increased fecal bulk and weight. An increase in stool bulk has a laxative effect, increases the excretion of nitrogen and energy, and aids in diluting genotoxic substances in the colon.3,25

Each of the SCFAs—propionate, acetate, and butyrate—has different metabolic effects and functions. Propionic acid, in vitro, decreases serum low-density lipoprotein (LDL) cholesterol levels by inhibiting hepatic fatty acid synthesis.26,27 Acetate is a strong acid that effectively lowers the pH level.27 In vitro studies indicate that butyrate is the preferred fuel for colon cells and may prevent colon carcinogenesis by suppressing cancer cell growth.28

Flatulence, bloating, and abdominal cramps are undesirable byproducts of fermentation. The amount of prebiotics that causes discomfort varies among individuals. One study found that a daily intake of 14 grams of FOS caused GI distress, while 10 grams per day was well tolerated in another.11,18 Prebiotics may be developed with different chemical configurations to reduce flatulence.13

Inulin and oligofructose have many fiberlike properties: They are water-soluble and thus increase the colonic water volume. They increase fecal bulk and weight. In one human study, oligofructose increased fecal weight by 1.3 grams for every gram consumed, while inulin produced a 2-gram increase for every gram consumed.11 Population studies demonstrate an inverse relationship between stool weight and risk of colon cancer.25

Inulin and oligofructose are not viscous or gel-forming. Thus, they do not bind bile acids or decrease serum cholesterol levels like viscous polysaccharides (pectins, gums, and some hemicelluloses).11

Health Benefits
Benefits include inhibiting pathogenic bacteria growth, producing a laxative effect, inhibiting diarrhea, preventing colon carcinogenesis, enhancing mineral absorption, decreasing serum triglycerides, and decreasing postprandial glucose and insulin levels (reported in animal studies).13,17

Prebiotics appear to exert positive effects on colonic microflora, immune functions, mineral bioavailability, and lipid metabolism and may prevent colon carcinogenesis.3,26 Future research may prove that prebiotics help prevent and treat diseases caused by pathogenic bacteria, colonic diseases, certain cancers, osteoporosis, hyperlipidemia, and possibly diabetes.26

In vitro studies suggest that inulin and oligofructose inhibit the growth of certain pathogenic microorganisms, including clostridia, which is associated with encephalopathy, sudden infant death syndrome, diarrhea, and antibiotic-associated diarrhea.17 Prebiotics may inhibit diarrhea, especially diarrhea caused by intestinal infections.28

Various animal (rat) studies have found that inulin, oligofructose, glucooligosaccharide, and galactooligosaccharide enhance the absorption of minerals, particularly calcium and magnesium and possibly iron and zinc. Some animal studies found that oligofructose intake increased bone mineral density of the femur and tibia.29-31 These studies indicate that the positive effect of oligofructose on calcium absorption is more prominent when there is a higher dietary intake of calcium.31

One area of interest is calcium absorption in adolescents. Various short-term studies have been inconsistent, but a recent year-long study involving adolescents suggested that daily consumption of prebiotics (short- and long-chain inulin-type) may significantly increase calcium absorption and enhance bone mineralization during puberty.32 One group received 8 grams of an inulin-type fructan; the control group did not receive prebiotics. Calcium absorption was greater, as was whole-body bone mineral content and bone mineral density, in the prebiotic-treated group.

Animal studies suggest that inulin and oligofructose may prevent or inhibit colon cancer, a leading cause of death in the United States.33 Butyrate may inhibit colon cancer cell growth and increase cancer cell apoptosis.33 Animal (rat) studies have found that these prebiotics inhibit the formation of aberrant crypt foci, which are precancerous lesions.32 The role of prebiotics in preventing colon cancer looks promising, but more human studies are needed.28,32,33

Oligofructose-fed rats demonstrated decreased triacylglycerol in very low-density lipoproteins, which are converted to LDLs. Elevated LDL levels are a risk factor for cardiovascular disease. The exact mechanism for this lipid-lowering effect is unknown.34 Oligofructose is associated with low postprandial insulin and glucose levels in oligofructose-fed rats.34 Currently, it is unclear whether this finding has implications for persons with hypertriglyceridemia and/or type 2 diabetes.35

Caution should be exercised when applying the results of animal studies to humans. Human studies confirm the positive effect of prebiotics on calcium absorption and balance but do not support enhancement of iron, magnesium, or zinc absorption.30 Conflicting results and discrepancies from human studies have been reported. These may be due to differences in study design, specific prebiotics investigated, dosage, duration of intake, and amount of dietary calcium intake. More clinical research is needed.30

Using Prebiotics
Prebiotics fall into many ingredient categories. Inulin and oligofructose, as naturally occurring macronutrients, are considered foods, not additives. They are assumed safe because they have been part of man’s diet for centuries with no documented harmful or toxic effects.35,36

As food ingredients, prebiotics provide texture and bulk to foods without adding calories. As noted, they are a source of functional fiber. In addition, prebiotics, unlike probiotics, are versatile and can be added to a variety of foods because of their high solubility. However, they cannot be used in acidic foods, such as soft drinks or fruit jams, because in an acidic environment they are hydrolyzed into fructose.36 Within the past decade, food manufacturers have begun to utilize prebiotics for their functionality, which includes enhancing calcium absorption, immune function, and digestive health.

Inulin and oligofructose provide only 1 to 1.5 kilocalories per gram. Their low caloric value and other physical properties make them ideal for use as fat and carbohydrate substitutes. Carbohydrate and fat replacers are popular in our weight-conscious culture. The shorter chain oligosaccharides, such as oligofructose, can contribute sweetness. Oligofructose is used as a sugar replacer because its technical properties make it comparable to sugar and glucose syrups. Although oligofructose is only approximately 30% as sweet as sucrose (table sugar), it can be combined with other more intense sweeteners. Oligofructose is used in dairy products and baked goods in the amounts of 2 to 6 grams per portion.36

Longer chain oligosaccharides mimic the mouthfeel of fats. Inulin is commonly used as a fat replacer in dairy products and table spreads. When processed and combined with water, it has a texture and mouthfeel similar to fat. Generally, 1 gram of fat is replaced with 0.25 grams of inulin.16,36

To increase the fiber content of foods, inulin and oligofructose are commonly added in the range of 3 to 6 grams per portion or serving size.36 However, these prebiotics are not included as part of the “dietary fiber” content on food labels mandated by the FDA, which uses the dietary fiber analysis method accepted by the Association of Analytical Chemists. This method does not count nondigestible carbohydrates (eg, RS, nonstarch polysaccharides, sugar alcohols, polydextroses, and FOS) as fiber. In most of Europe and Japan, they are classified as dietary fiber.36

Prebiotics are also available as dietary supplements, either in tablet form or as powders to be mixed with water or other beverages. The most common types of prebiotics in supplements are FOS, inulin, and galactooligosaccharides.17

Synbiotics
Synbiotics are foods or dietary supplements that contain a mixture of probiotics and prebiotics.15,37 The premise behind developing synbiotics is that a combination of probiotics and prebiotics may improve the survival of organisms as they pass through the stomach and small intestine, thus enhancing their effects in the colon. It is suggested that to improve a probiotic’s viability and vitality, as well as its survival chances in the digestive tract and its subsequent attachment and growth rate, a prebiotic ingredient should be included.1 Currently, the best synbiotic combinations are bifidobacteria and FOS, Lactobacillus GG and inulins, and Bifidobacteria and lactobacilli with FOS or inulin.38,39 Fermented milks, yogurt, kefir, and some cheeses are the most popular synbiotic foods. However, not all fermented milks contain prebiotics.39

Pediatrics
The future role of prebiotics, probiotics, and synbiotics in pediatrics looks very promising. A four-month, double-blind, randomized study conducted in Brazil, Mexico, Portugal, and Spain involving 626 children aged 1 to 5 from 13 different day care centers reported that oral supplementation with a nutritionally complete formula can improve catch-up growth and immune function. The improvement in immune function was determined by a decrease in the average number of sick days per month. Both formulas, one with synbiotics and one without, yielded these results; however, children aged 3 to 5 who received the synbiotic formula had fewer episodes of constipation and a more significant decrease in sick days.40

Although the effects of a combination of probiotics and prebiotics appear to be synergistic, currently there is limited scientific evidence to support a synergistic effect.15,39,41 However, preliminary studies have researchers and food companies intrigued and hopeful.

In my opinion, probiotics, prebiotics, and synbiotics have the greatest potential to positively affect the nutritional status and overall health of infants and young children, especially those in day care settings who are at high risk for GI infections. There is increasing interest in adding prebiotics to infant formulas. Many are in the development stage. I anticipate more emphasis and research to be done in this area.

Researchers have estimated that most Americans consume 1 to 4 grams of FOS per day, while Europeans have an average daily intake of 3 to 10 grams.14,36 Human studies indicate that daily intake of 5 to 20 grams of inulin and oligofructose selectively promotes the growth of bifidobacteria.8 Although there is no set standard, a minimum intake of 5 grams per day is recommended, but intake of 10 grams or more may result in flatulence, bloating, and other forms of GI distress.10,14,18,29

It is common for people to discuss their cholesterol levels; however, most people consider it impolite and socially unacceptable to discuss concerns about digestion and excretion. Dietitians are uniquely positioned and qualified to initiate conversations about gut health. As dietitians, we can educate our clients and patients about the influence of gut health on overall health. If something as simple as nourishing intestinal flora can keep significant portions of the population healthy, shouldn’t we be advocating dietary intake of prebiotics loudly and clearly?

— Carol Ann Brannon, MS, RD, LD, is a consulting dietitian at Fowler YMCA and in private practice in Georgia.

Examination
1. In the digestive tract, prebiotics:
a. are easily destroyed by stomach acid.
b. are destroyed by digestive enzymes.
c. are fermented to short-chain fatty acids.
d. adhere to the lining of the colon.
e. all of the above

2. The criteria to be considered a prebiotic include all of the following except:
a. resistance to digestion in the upper digestive tract.
b. naturally occurring.
c. stimulate growth and activity of beneficial bacteria.
d. decrease production of SCFA and increase pH level.
e. are readily fermented.

3. The end products of prebiotic metabolism include:
a. butyrate.
b. bile acid.
c. long-chain fatty acids.
d. bicarbonate.

4. The health benefits of prebiotics include all of the following except:
a. increase calcium absorption.
b. decrease hypertension.
c. decrease the development of aberrant crypt foci.
d. prevent constipation.
e. aid in the treatment of diarrhea, especially in children.

5. Inulin and oligofructose:
a. are viscous and bind bile acids.
b. increase stool weight and fecal bulk.
c. yield approximately 4 calories per gram.
d. are nonfermentable in the colon.

6. Inulin and oligofructose are:
a. generally regarded as safe food ingredients.
b. found in a variety of plant foods.
c. added to increase the soluble fiber content of foods.
d. available in dietary supplements.
e. all of the above

7. Inulin and oligofructose are often used in foods:
a. to enhance the flavor.
b. as fat and sugar substitutes.
c. to increase the insoluble fiber content.
d. to increase the protein content.
e. all of the above

8. Resistant starch:
a. is fermented more slowly in the colon than fructans.
b. appears to be beneficial by improving insulin sensitivity in insulin-resistant persons.
c. has versatile uses and is a safe food ingredient.
d. does not appear to have any adverse effects when large amounts are ingested.
e. all of the above

9. The SCFA that is the preferred fuel for colon cells is:
a. butyrate.
b. acetate.
c. propionate.
d. linolenic acid.
e. none of the above

10. The predominant species of probiotics in the human colon are:
a. lactobacilli.
b. Bacteroides.
c. clostridia.
d. bifidobacteria.
e. fusobacteroides.

References
1. Wade MA. The secret garden. Prepared Foods. August 1, 2005.

2. Keating B, Leigh E. Multi-talented ingredient: Tout benefit. NutraSolutions of Prepared Foods. June 1, 2005. Available at: http://www.nutrasolutions.com

3. Mcfarlane GT, Cummings JH. Probiotics and prebiotics: Can regulating the activities of intestinal bacteria benefit health? BMJ. 1999;318(7189):999-1003.

4. Koop-Hoolihan L. Prophylactic and therapeutic uses of probiotics: A review. J Am Diet Assoc. 2001;101(2):229-241.

5. Cichoke A. Probiotics balance digestion and improve overall health. Nutrition Science News. August 1997. Available at: http://www.vitamintrader.com/articles/1997_08_Probio.html

6. Immunity and Probiotics. An initiative of the Danone Research Centers, Danone Nutrition and Health Collection. Second Symposium Danone, Bonn, Germany, 1998. Available at: http://www.danonevitapole.com

7. Lilly DM, Stillwell RH. Probiotics: Growth-promoting factors produced by microorganisms. Science. 1965;147:747-748.

8. Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics—approaching a definition. Am J Clin Nutr. 2001;73(2 Suppl):316S-364S.

9. Rolfe RD. The role of probiotic cultures in the control of gastrointestinal health. J Nutr. 2000;130 (2S Suppl):396S-402S.

10. Gibson GR, Wang X. Regulatory effects of bifidobacteria on other colonic bacteria. J Appl Bacteriol. 1994;77(4):412-420.

11. Gibson GR, Beatty ER, Wang X, et al. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology. 1995;108(4):975-982.

12. Gibson GR, Fuller R. Aspects of in vitro and in vivo research approaches directed toward identifying probiotics and prebiotics for human use. J Nutr. 2000;130(2S Suppl):391S-395S.

13. Cummings JH, Macfarlane GT, Englyst HN. Prebiotic digestion and fermentation. Am J Clin Nutr. 2001;73(2 Suppl):415S-420S.

14. Guarner F. Inulin and oligofructose: Impact on intestinal diseases and disorders. Br J Nutr. 2005;93(Suppl 1):S61-65.

15. Synbiotics. Available at: http://www.innvista.com/health/nutrition/biotics/synbiot.htm. Accessed June 21, 2006.

16. Gibson GR. Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin. J Nutr. 1999;129:1438S-1441S.

17. Prebiotics. PDR Health. Available at: http://www.pdrhealth.com. Accessed June 4, 2006.

18. Nadeau DA. Oligosaccharides play important health role. The Soy Connection Interactive. 1999;7(3).

19. Roberfroid MB, Van Loo J, Gibson GR. The bifidogenic nature of chicory inulin and its hydrolysis products. J Nutr. 1998;128(1):11-19.

20. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125(6):1401-1412.

21. Robertson MD, Bickerton AS, Dennis AL, et al. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005;82(3):559-567.

22. Weickert MO, Mohlig M, Koebnick C, et al. Impact of cereal fibre on glucose-regulating factors. Diabetologia. 2005;48(11):2343-2353.

23. New peer-reviewed studies highlight positive health benefits of natural resistant starch. National Starch and Chemical Company (news release). March 28, 2006.

24. Muramatsu K, Onodera S, Kikuchi M, et al. Substrate specificity and subsite affinities of beta-fructofuranosidase from Bifidobacterium adolescentis G1. Biosci Biotechnol Biochem. 1994;58:1642-1645.

25. Cummings JH, Bingham SA, Heaton KW, et al. Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber). Gastroenterology. 1992;103(6):1783-1789.

26. Schneeman BO. Fiber, inulin and oligofructose: Similarities and differences. J Nutr. 1999;129(7 Suppl):1424S-1427S.

27. Brandt LA. Prebiotics enhance gut health. Issue Ingredients for health. Prepared Foods; September 2001. Available at: http://www.preparedfoods.com/archives/2001/2001_9/0901ns_ingredients.htm

28. Roberfroid MB. Concepts in functional foods: The case of inulin and oligofructose. J Nutr. 1999;129(7 Suppl):1398S-1410S.

29. Delzenne N, Aertssens J, Verplaetse H, et al. Effect of fermentable fructo-oligosacchrides on mineral, nitrogen and energy digestive balance in the rat. Life Sci. 1995;57(17):l579-1587.

30. Scholz-Ahrens KE, Schaafsma G, van den Heuvel EGHM, et al. Effects of prebiotics on mineral metabolism. Am J Clin Nutr. 2001;73(2 suppl):459S-464S.

31. Scholz-Ahrens KE, van Loo J, Schrezenmeir J. Effect of oligofructose on bone mineralization in ovariectomized rats is affected by dietary calcium. Am J Clin Nutr. 2001;73:498S(abstr).

32. Abrams SA, Griffin IJ, Hawthorne KM, et al. A combination of prebiotic short-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr. 2005;82(2):471-476.

33. Wollowski I, Rechkemmer G, Pool-Zobel BL. Protective role of probiotics and prebiotics in colon cancer. Am J Clin Nutr. 2001;73(2 Suppl):451S-455S.

34. Reddy BS. Possible mechanisms by which pro- and prebiotics influence colon carcinogenesis and tumor growth. J Nutr. 1999; 129(7 Suppl): 1478S-1482S.

35. Delzenne NM, Kok N. Effects of fructans-type prebiotics on lipid metabolism. Am J Clin Nutr. 2001;73(2 Suppl):456S-458S.

36. Roberfroid MB. Prebiotics and probiotics: are they functional foods? Am J Clin Nutr. 2000;71(6 Suppl):1682S-1687S.

37. Coussement PA. Inulin and oligofructose: Safe intakes and legal status. J Nutr. 1999;129(7 Suppl):1412S-1417S.

38. Innvista. Available at: http://www.innvista.com Accessed June 4, 2006.

39. Anthony M. Inulin: The “in” fiber. Wellness Foods, FoodProcessing.com; April 3, 2005. Available at: http:// www.foodprocessing.com. Accessed June 15, 2006.

40. Fisberg M, Maulen-Radovan IE, Tormo R, et al. Effect of oral nutritional supplementation with or without synbiotics on sickness and catch-up growth in preschool children. Int Pediatr. 2002;17(4):216-222.

41. Madley R. Probiotics, prebiotics, and synbiotics: Harnessing enormous potential. Nutraceuticals World. September 2001. Available at: http://www.nutraceuticalsworld.com