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Abstract The purpose of this research is to review the recent literature on a specific type of fiber that has gained interest in the field of nutrition. Inulin is used in the food industry as an additive to increase bulk in foods, acting as filler for sugar or fat, and as a fiber supplement. Its nature as a fermentable soluble fiber make it a ‘prebiotic’ - indigestible by the human gastrointestinal tract; it is instead digested by microscopic organisms in the colon known to have beneficial effects on human health. While examining the research utilizing Web of Science, Academic search Premier, and Google Scholar, it was determined that inulin’s most significant effect was on the cardiovascular system. We examined a wide variety of both human and animal studies; although studies have been conflicting, many suggest including inulin fiber into the everyday diet to improve risk factors associated with cardiovascular disease (CVD). Objectives Describe inulin as a specific dietary fiber, its sources, and its uses Demonstrate physiologic mechanisms of inulin and their effects on specific cardiovascular diseases risk factors Coalesce inulin research into implications for human nutrition Introduction Dietary fiber is necessary for movement of food through the digestive tract. Because of its positive implications on various aspects of health, “the recommended intake for total fiber for adults 50 years and younger is set at 38 grams for men and 25 grams for women, while for men and women over 50 it is 30 and 21 grams per day, respectively, due to decreased food consumption.” 1 Research suggest that most Americans do not get the recommended amount of fiber in their diets. 2 Inulin, a soluble fiber, has been studied in particular for its beneficial effects on various conditions, including CVD. 3,4 Recent studies show that inulin has a positive effect on CVD risk factors such as excess body fat, dyslipidemia, and hyperglycemia. 5,6 Inulin Inulin is a carbohydrate polymer, distinguishable by its beta(2-1) linkages and fructose chains ranging from 2-60 residues; oligofructose (OFS) is a specific variety of inulin limited to 2-10 residues. 7,8 These molecules can be found in many foods including banana, onion, leek, Jerusalem artichoke, chicory root, garlic, wheat, rye, barley. 7,8 A majority of commercially used inulin is isolated from chicory root. The process utilizes inulin’s soluble nature, allowing specific polymerization ranges to be isolated for industry use. 7,8 Inulin was granted “Generally Recognized As Safe” status in 2002 stimulating further research and applications. 8 These main applications are as a fiber, its bifidogenic nature, and for drug delivery. Inulin is not digested by human cells, therefore travels through the gastrointestinal tract to the colon where it is fermented by Bifidobacteria. Through the process of fermentation, Bifidobacteria produce short chain fatty acids (SCFA), which are generally considered beneficial for human health. 5-7 Physiological Aspects CVD is a major public health concern and targeting modifiable risk factors such as overweight and obesity, dyslipidemia and diabetes 9 are of importance in managing, treating, and preventing this chronic disease. Inulin consumption may have the capacity to simultaneously affect multiple systems. Animal studies have shown more promising results whereas most human studies show more modest or inconsistent effects. The metabolic pathways that inulin affects have yet to be completely understood but much of its physiological impact may be due to its prebiotic nature. Bifidogenic effect: A symbiotic relationship exists where Bifidobatceria ferment inulin in the colon and produce SCFA, 7 which may have far-reaching benefits to the host such as improved blood lipids, weight loss, and improved glycemic control. 5,6 Stimulates the growth of beneficial Bifidobacteria in adults 10,11 and elderly people 12 Correlated with increased fecal acetate, butyrate, and propionate production in healthy adults 6,10 Weight loss: Increased levels of GLP-1 13,14 and PYY 14,15 (satiety inducing hormones), and decreased ghrelin 14,15 (hunger-inducing hormone) Stimulated production of GLP-1 from endocrine L cells (via SCFAs) 5,14 Increased satiety and decreased hunger may contribute to weight loss and a reduction in fat mass, which in turn contributes to lowered triglycerides 5 Improved blood lipids: Animal studies have resulted in decreased triacylglycerides, improved total cholesterol, LDL-cholesterol, and HDL-cholesterol, 6,16,17 whereas human studies have shown slight improvements 18,19 or inconsistent results. 6 Recent hypotheses of the mechanisms include: Down regulation of hepatic lipogenesis 5 Increased hepatic lipid catabolism 5 Improved blood glucose control 5 Physiological Effects of Colonic Fermentation From Inulin Consumption Conclusions and Implications Risk factors of CVD include obesity, dyslipidemia, and diabetes 9 . Inulin fiber may pose a functional role in improving these risk factors. Animal studies have been useful for proposing specific mechanisms for inulin’s role while human studies have been controversial yet suggestive of positive effects. While inulin’s effect on human physiology is mild, including inulin rich foods as part of a healthy diet, within already established recommendations, may help manage specific modifiable risk factors leading to CVD. 1. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Institute of Medicine Website. http://iom.nationalacademies.org/reports/2002/dietary-reference-intakes-for-energy-carbohydrate-fiber-fat-fatty-acids-cholesterol- protein-and-amino-acids.aspx. Published September 5, 2002. Accessed October 11, 2015. 2. Hoy MK, Goldman JD. Fiber intake of the U.S. population: What We Eat in America, NHANES 2009-2010. Food Surveys Research Group Dietary Data Brief No. 12. http://www.ars.usda.gov/SP2UserFiles/Place/80400530/pdf/DBrief/12_fiber_intake_0910.pdf. Published September 2014. Accessed October 28, 2014. 3. Pereira MA, O'Reilly E, Augustsson K, et al. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Arch Intern Med. 2004;164(4):370-376. Doi: 10.1001/archinte.164.4.370. 4. Threapleton, DE, Greenwood, DC, Evans CE, et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013; 347. Doi: http://dx.doi.org/10.1136/bmj.f6879. 5. Aparecida dos Reis S, Lopes da Conceição L, Diniz Rosa D, Maciel dos Santos Dias M, Gouveia Peluzio M. Mechanisms used by inulin-type fructans to improve the lipid profile. Nutr Hosp. 2015; 31(2): 528-534. Doi: 10.3305/nh.2015.31.2.7706. 6. Wong J, Esfahani A, Signh N, et al. Gut Microbiota, Diet, and Heart Disease. J AOAC Int. 2012; 95(1): 24-30. Doi: 10.5740/jaoacint.SGE_Wong. 7. Niness KR. Inulin and oligofructose: what are they?. J Nutr. 1999; 129(7): 1402s-1406s. http://jn.nutrition.org/content/129/7/1402S.full. 8. Mensink MA, Frijlink HW, Voort Maarschalk K, Hinrichs WLJ. Inulin, a flexible oligosaccharide I: Review of its physiochemical characteristics. Carbohydr Polym. 2015; 130: 405-419. Doi: 10.1016/j.carbpol.2015.05.026. 9. Understand your risk of heart attack. American Heart Association. http://www.heart.org/HEARTORG/Conditions/HeartAttack/UnderstandYourRiskofHeartAttack/Understand-Your-Risk-of-Heart- Attack_UCM_002040_Article.jsp#.VkAPQq6rTeQ. Published August 21, 2015. Accessed November 7, 2015. 10.Holscher H, Bauer L, Gourineni V, Pelkman C, Fahey G, Swanson K. Agave inulin supplementation affects the fecal microbiota of healthy adults participating in a randomized, double-blind, placebo-controlled, crossover trial. J Nutr. 2015; 145(9): 2025-2032. Doi: 10.3945/jn.115.217331. 11.Brighenti F, Casiraghi MC, Canzi E, Ferrari A. Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers. Eur J Clin Nutr. 1999; 53: 726-733. Doi: 10.1038/sj.ejcn.1600841. 12.Phillippe M, Jacobs H, Cazaubiel M, Signoret C, Prevel JM, Housez B. Effects of chicory inulin in constipated elderly people: a double blind controlled trial. Int J Food Sci Nutr. 2011; 62(2): 164–170. Doi: 10.3109/09637486.2010.527323 13.Nilsson AC, Johansson-Boll EV, and Björck IM. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects. Br J Nutr. 2015; 114(06): 899-907. Doi:10.1017/S0007114515002524. 14.Delzenne NM, Cani PD, Neyrinck AM. Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. J Nutr. 2007; 132 (11): 25475-25515. jn.nutrition.org/content/137/11/2547S.full.pdf+html. 15.Parnel JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009; 89(6): 1751-1759. Doi:10.3945/ajcn.2009.27465. 16.Han K, Tsuchihira H, Fukushima M, et al. Inulin-type fructans with different degrees of polymerization improve lipid metabolism but not glucose metabolism in rats fed a high-fat diet under energy restriction. Dig Dis Sci. 2013; 58(8): 2177-2186. Doi: 10.1007/s10620-013-2631-z. 17.Mortensen A, Poulsen M, Frandsen H. Effect of a long-chained fructan Raftiline HP on blood lipids and spontaneous atherosclerosis in low density receptor knockout mice. Nutr Res. 2002; 22(4): 473-480. Doi:10.1016/S0271-5317(02)00358-5. 18.Letexier D, Diraison F, Beylot M. Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans. Am J Clin Nutr. 2003; 77(3): 559-564. http://ajcn.nutrition.org/content/77/3/559.short. 19.Russo F, Chimienti G, Riezzo G, Pepe G, Petrosillo G, Chiloiro M, Marconi E. Inulin-enriched pasta affects lipid profile and Lp (a) concentrations in Italian young healthy male volunteers. Eur J Nutr. 2008; 47(8): 453-459. Doi: 10.1007/s00394-008-0748-1 References Acknowledgments We would like to acknowledge Sarah Hibbs-Shipp, Dr. Leslie Cunningham-Sabo, and James Peth for all of their support, assistance, and encouragement during this project. Mensink MA, Frijlink HW, Voort Maarschalk K, Hinrichs WLJ. Inulin, a flexible oligosaccharide I: Review of its physiochemical characteristics. Carbohydr Polym. 2015; 130: 405-419. Doi: 10.1016/j.carbpol.2015.05.026. Inulin Fiber for the Management of Cardiovascular Disease Risk Factors Sarah Vetter, Sonja Silva, Molly McLellan Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO Fall 2015 Compiled using information from 5,6,14

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Page 1: Poster-final draft (1) (1)

Abstract

The purpose of this research is to review the recent literature on a specific type of fiber that has gained interest in the field of nutrition. Inulin is used in the food industry as an additive to increase bulk in foods, acting as filler for sugar or fat, and as a fiber supplement. Its nature as a fermentable soluble fiber make it a ‘prebiotic’ - indigestible by the human gastrointestinal tract; it is instead digested by microscopic organisms in the colon known to have beneficial effects on human health.

While examining the research utilizing Web of Science, Academic search Premier, and Google Scholar, it was determined that inulin’s most significant effect was on the cardiovascular system. We examined a wide variety of both human and animal studies; although studies have been conflicting, many suggest including inulin fiber into the everyday diet to improve risk factors associated with cardiovascular disease (CVD).

Objectives• Describe inulin as a specific dietary fiber, its sources, and its uses• Demonstrate physiologic mechanisms of inulin and their effects on

specific cardiovascular diseases risk factors• Coalesce inulin research into implications for human nutrition

Introduction

Dietary fiber is necessary for movement of food through the digestive tract. Because of its positive implications on various aspects of health, “the recommended intake for total fiber for adults 50 years and younger is set at 38 grams for men and 25 grams for women, while for men and women over 50 it is 30 and 21 grams per day, respectively, due to decreased food consumption.”1 Research suggest that most Americans do not get the recommended amount of fiber in their diets.2 Inulin, a soluble fiber, has been studied in particular for its beneficial effects on various conditions, including CVD.3,4 Recent studies show that inulin has a positive effect on CVD risk factors such as excess body fat, dyslipidemia, and hyperglycemia.5,6

InulinInulin is a carbohydrate polymer, distinguishable by its beta(2-1) linkages and fructose chains ranging from 2-60 residues; oligofructose (OFS) is a specific variety of inulin limited to 2-10 residues.7,8 These molecules can be found in many foods including banana, onion, leek, Jerusalem artichoke, chicory root, garlic, wheat, rye, barley.7,8 A majority of commercially used inulin is isolated from chicory root. The process utilizes inulin’s soluble nature, allowing specific polymerization ranges to be isolated for industry use.7,8

Inulin was granted “Generally Recognized As Safe” status in 2002 stimulating further research and applications.8 These main applications are as a fiber, its bifidogenic nature, and for drug delivery. Inulin is not digested by human cells, therefore travels through the gastrointestinal tract to the colon where it is fermented by Bifidobacteria. Through the process of fermentation, Bifidobacteria produce short chain fatty acids (SCFA), which are generally considered beneficial for human health.5-7

Physiological AspectsCVD is a major public health concern and targeting modifiable risk factors such as overweight and obesity, dyslipidemia and diabetes9 are of importance in managing, treating, and preventing this chronic disease. Inulin consumption may have the capacity to simultaneously affect multiple systems. Animal studies have shown more promising results whereas most human studies show more modest or inconsistent effects. The metabolic pathways that inulin affects have yet to be completely understood but much of its physiological impact may be due to its prebiotic nature.

Bifidogenic effect:A symbiotic relationship exists where Bifidobatceria ferment inulin in the colon and produce SCFA,7 which may have far-reaching benefits to the host such as improved blood lipids, weight loss, and improved glycemic control.5,6

• Stimulates the growth of beneficial Bifidobacteria in adults10,11 and elderly people12

• Correlated with increased fecal acetate, butyrate, and propionate production in healthy adults6,10

Weight loss:• Increased levels of GLP-113,14 and PYY14,15 (satiety inducing hormones), and decreased

ghrelin14,15 (hunger-inducing hormone) • Stimulated production of GLP-1 from endocrine L cells (via SCFAs)5,14 • Increased satiety and decreased hunger may contribute to weight loss and a reduction in fat

mass, which in turn contributes to lowered triglycerides5

Improved blood lipids:Animal studies have resulted in decreased triacylglycerides, improved total cholesterol, LDL-cholesterol, and HDL-cholesterol,6,16,17 whereas human studies have shown slight improvements18,19 or inconsistent results.6 Recent hypotheses of the mechanisms include:• Down regulation of hepatic lipogenesis5 • Increased hepatic lipid catabolism5 • Improved blood glucose control5 • Increased excretion of bile via lowered intestinal pH5,10 • Propionate may inhibit key enzymes involved in cholesterol synthesis6

Physiological Effects of Colonic Fermentation From Inulin Consumption

Conclusions and ImplicationsRisk factors of CVD include obesity, dyslipidemia, and diabetes9. Inulin fiber may pose a functional role in improving these risk factors. Animal studies have been useful for proposing specific mechanisms for inulin’s role while human studies have been controversial yet suggestive of positive effects. While inulin’s effect on human physiology is mild, including inulin rich foods as part of a healthy diet, within already established recommendations, may help manage specific modifiable risk factors leading to CVD.

1. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Institute of Medicine Website. http://iom.nationalacademies.org/reports/2002/dietary-reference-intakes-for-energy-carbohydrate-fiber-fat-fatty-acids-cholesterol-protein-and-amino-acids.aspx. Published September 5, 2002. Accessed October 11, 2015.

2. Hoy MK, Goldman JD. Fiber intake of the U.S. population: What We Eat in America, NHANES 2009-2010. Food Surveys Research Group Dietary Data Brief No. 12. http://www.ars.usda.gov/SP2UserFiles/Place/80400530/pdf/DBrief/12_fiber_intake_0910.pdf. Published September 2014. Accessed October 28, 2014.

3. Pereira MA, O'Reilly E, Augustsson K, et al. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Arch Intern Med. 2004;164(4):370-376. Doi: 10.1001/archinte.164.4.370.

4. Threapleton, DE, Greenwood, DC, Evans CE, et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013; 347. Doi: http://dx.doi.org/10.1136/bmj.f6879.

5. Aparecida dos Reis S, Lopes da Conceição L, Diniz Rosa D, Maciel dos Santos Dias M, Gouveia Peluzio M. Mechanisms used by inulin-type fructans to improve the lipid profile. Nutr Hosp. 2015; 31(2): 528-534. Doi: 10.3305/nh.2015.31.2.7706.

6. Wong J, Esfahani A, Signh N, et al. Gut Microbiota, Diet, and Heart Disease. J AOAC Int. 2012; 95(1): 24-30. Doi: 10.5740/jaoacint.SGE_Wong.7. Niness KR. Inulin and oligofructose: what are they?. J Nutr. 1999; 129(7): 1402s-1406s. http://jn.nutrition.org/content/129/7/1402S.full.8. Mensink MA, Frijlink HW, Voort Maarschalk K, Hinrichs WLJ. Inulin, a flexible oligosaccharide I: Review of its physiochemical characteristics. Carbohydr Polym. 2015; 130: 405-419. Doi:

10.1016/j.carbpol.2015.05.026.9. Understand your risk of heart attack. American Heart Association. http://www.heart.org/HEARTORG/Conditions/HeartAttack/UnderstandYourRiskofHeartAttack/Understand-Your-Risk-of-Heart-

Attack_UCM_002040_Article.jsp#.VkAPQq6rTeQ. Published August 21, 2015. Accessed November 7, 2015.10.Holscher H, Bauer L, Gourineni V, Pelkman C, Fahey G, Swanson K. Agave inulin supplementation affects the fecal microbiota of healthy adults participating in a randomized, double-blind,

placebo-controlled, crossover trial. J Nutr. 2015; 145(9): 2025-2032. Doi: 10.3945/jn.115.217331.11. Brighenti F, Casiraghi MC, Canzi E, Ferrari A. Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers. Eur J Clin

Nutr. 1999; 53: 726-733. Doi: 10.1038/sj.ejcn.1600841.12.Phillippe M, Jacobs H, Cazaubiel M, Signoret C, Prevel JM, Housez B. Effects of chicory inulin in constipated elderly people: a double blind controlled trial. Int J Food Sci Nutr. 2011; 62(2): 164–

170. Doi: 10.3109/09637486.2010.52732313.Nilsson AC, Johansson-Boll EV, and Björck IM. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study

in healthy middle-aged subjects. Br J Nutr. 2015; 114(06): 899-907. Doi:10.1017/S0007114515002524.14.Delzenne NM, Cani PD, Neyrinck AM. Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. J Nutr. 2007; 132 (11): 25475-25515.

jn.nutrition.org/content/137/11/2547S.full.pdf+html.15.Parnel JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009;

89(6): 1751-1759. Doi:10.3945/ajcn.2009.27465.16.Han K, Tsuchihira H, Fukushima M, et al. Inulin-type fructans with different degrees of polymerization improve lipid metabolism but not glucose metabolism in rats fed a high-fat diet under energy

restriction. Dig Dis Sci. 2013; 58(8): 2177-2186. Doi: 10.1007/s10620-013-2631-z.17.Mortensen A, Poulsen M, Frandsen H. Effect of a long-chained fructan Raftiline HP on blood lipids and spontaneous atherosclerosis in low density receptor knockout mice. Nutr Res. 2002; 22(4):

473-480. Doi:10.1016/S0271-5317(02)00358-5.18.Letexier D, Diraison F, Beylot M. Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans. Am J Clin Nutr. 2003;

77(3): 559-564. http://ajcn.nutrition.org/content/77/3/559.short.19.Russo F, Chimienti G, Riezzo G, Pepe G, Petrosillo G, Chiloiro M, Marconi E. Inulin-enriched pasta affects lipid profile and Lp (a) concentrations in Italian young healthy male volunteers. Eur J

Nutr. 2008; 47(8): 453-459. Doi: 10.1007/s00394-008-0748-1

References

Acknowledgments We would like to acknowledge Sarah Hibbs-Shipp, Dr. Leslie Cunningham-Sabo, and James Peth for all of their support, assistance, and encouragement during this project.

Mensink MA, Frijlink HW, Voort Maarschalk K, Hinrichs WLJ. Inulin, a flexible oligosaccharide I: Review of its physiochemical characteristics. Carbohydr Polym. 2015; 130: 405-419. Doi: 10.1016/j.carbpol.2015.05.026.

Inulin Fiber for the Management of Cardiovascular Disease Risk FactorsSarah Vetter, Sonja Silva, Molly McLellan

Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO Fall 2015

Compiled using information from5,6,14