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Overview of human studies with Natural RS2 Resistant Starch
The benefits of natural RS2 resistant starch from high amylose corn are attributed to both the reduced glycemic and insulin response within the small intestine, as well as to the fermentation effects within the large intestine. While all dietary fibers decrease the glycemic and insulin response when they substitute for digestible carbohydrates, the fermentation effects distinguish resistant starch from other types of dietary fiber. The fermentation of natural resistant starch promotes a healthy colon but has also been shown to significantly improve metabolism (i.e., increases insulin sensitivity and increases lipid oxidation). In other words, its health benefits range far beyond the colon – its helps to maintain overall health and wellness through multiple mechanisms.
Summary of published human clinical studies with natural RS2 resistant starch from high amylose corn (RS2):
§ 9 studies have shown beneficial effects on outcomes relevant to weight management and metabolism. One study confirmed the caloric contribution of RS2 resistant starch (2.8 kilocalories/gram). (Behall, JACN 1996). Four out of five studies have shown increased insulin sensitivity in healthy individuals and Type II diabetics (Robertson D 2003, Robertson AJCN 2005, Zhang CJPM 2007, Johnston DM 2010, Penn-Marshall JMF 2010). Another study showed increased fat burning (lipid oxidation) in healthy individuals (Higgins, NM 2004), while three studies have demonstrated increased satiety (van Amelsvoort, AJCN 1992, Nilsson, JN 2008 and Willis NR 2009). One study found that healthy individuals consumed 10% fewer calories in the 24 hours following Hi-maize consumption. (Bodinham, PNAS 2008) Finally, another study found that healthy young men consumed fewer calories two hours following consumption of Hi-maize resistant starch (Anderson, AJCN 2010)
§ 23 studies have shown beneficial effects of RS2 from high amylose corn on glucose and/or insulin response. When substituted for flour, it lowers the glycemic and/or insulin response of foods in a dose-dependent manner. (Anderson, AJCN 2002; Behall, AJCN 1988 - reduced peak; Behall, AJCN, 1989 - significant reduction within first hour; Behall & Howe, AJCN 1995; Behall & Hallfrisch, EJCN, 2002; Behall & Scholfield, CC, 2005; Behall, DC 2006; Behall, NR 2006; Brighenti, AJCN 2006; Brown, FA 1995; Giacco, DNM 1998; Granfeldt, JN 1995; Hoebler, EJCN 1999; Hospers, JFS 1996 - significant reduction within first hour; Howe, JN 1996; Krezowski, DC 1987; Noakes, AJCN 1996; Olesen, EJCN 1994; Reader, JADA 2002; van Amelsvoort & Weststrate, AJCN 1992; Vonk, AJCN 2000; Weststrate & van Amelsvoort, AJCN 1993; Zhang, CJPM 2007)
§ 5 studies have shown decreased glycemic or insulin response of the subsequent meal. (Behall, AJCN 1989; Robertson, D 2003; Robertson, AJCN 2005; Brighenti, AJCN 2006, Nilsson, JN 2008)
§ 5 out of six studies have shown increased insulin sensitivity in healthy people, in individuals with insulin resistance and metabolic syndrome and in individuals with diabetes. (Robertson D 2003; Robertson AJCN 2005; Zhang CJPM 2007; Johnston 2010, Maki 2011). One additional study found no significant effect on insulin sensitivity after feeding subjects at risk for type 2 diabetes 12 grams of Hi-maize 260/day for 6 weeks (Penn-Marshall JMF 2010). The authors found significant improvements in glucose homeostasis in one male subject diagnosed with prediabetes and suggested that the quantity of resistant starch may not have been sufficient for the other subjects.
§
13 out of 14 studies have demonstrated beneficial effects on biomarkers for colon health such as the production of short-chain fatty acids, lower pH, lower concentrations of ammonia and phenolics, decreased bile acids, and increased fecal weight. (Alles, AJCN 1997; Birkett, AJCN 1996; Grubben, DDS, 2001; Heijnen, AJCN 1996; Heijnen, AJCN 1998; Hylla, AJCN 1998; Jenkins, JACN 1998; Muir, AJCN 2004; Noakes, AJCN 1996; Phillips, AJCN 1995; Silvester, NC 1997; van Munster, DDS 1994; Wacker, CEBP 2002, Worthley, AJCN 2009). The authors of the study which did not demonstrate beneficial effect suggested that they did not achieve sufficient quantity of resistant starch in the diet, (Worthley, AJCN, 2009)
§
2 studies have been published out of the CAPP2 study (Colorectal Adenoma/Carcinoma Prevention Program 2, in which
727 individuals participated in 43 centers around the world over an average of 29 months). They found that 30 grams of resistant starch - a combination of Novelose 330 (RS3) and Hi-maize 240 (RS2) resistant starch- did not reduce the risk for colorectal cancer in individuals with Lynch syndrome (hereditary non-polyposis colon cancer). Up to 5% of colorectal cancers result from the Lynch syndrome.
(Burn, NEJM 2008) A second study examined a sub-segment of 65 patients with colorectal cancer and found
reduction in markers for colon cancer in normal tissue as well as increased genetic expression of cell cycle regulatory genes. (Dronamraju, G 2008)
§
4 out of 5 published studies have shown reduced duration and severity of diarrhea in adults and children when Hi-maize was added to oral rehydration solutions. The one study not demonstrating effectiveness (Alam 2009) suggested that the children may have had insufficient bacteria in their large intestines due to antibiotic treatments.
(Alam JPGN 2009, Monira JPGN 2009, Ramakrishna, PLoS ONE 2008, Rangupathy, JPGN 2006; Ramakrishna, NEJM 2000)
References for the Clinical Studies Cited Above:
Alam NH, Islam S, Sattar S, Monira S, Desjeux JF. Safety of rapid intravenous rehydration and comparative efficacy of 3 oral rehydration solutions in the treatment of severely malnourished children with dehydrating cholera. Journal of Pediatric Gastroenterology & Nutrition. 2009 Mar;48(3):318-27.
Alles MS, Katan MB, Salemans JMJI, Van Laere KMJ, Gerichhausen MJW, Rozendaal MJ, Nagengast FM. Bacterial fermentation of fructooligosaccharides and resistant starch in patients with an ileal pouch – anal anastomosis. The American Journal of Clinical Nutrition 1997;66:1286-92.
Anderson GH, Cho CE, Akhavan T, Mollard RC, Luhovyy BL, Finocchiaro ET. Relation between estimates of cornstarch digestibility by the Englyst in vitro method and glycemic response, subjective appetite, and short-term food intake in young men. American Journal of Clinical Nutrition (February 17, 2010) Epub ahead of print. doi:10.3945/ajcn.2009.28443.
Anderson GH, Catherine NLA, Woodend DM, Wolever TMS. Inverse association between the effect of carbohydrates on blood glucose and subsequent short-term food intake in young men. The American Journal of Clinical Nutrition 2002;76:1023-30.
Behall KM, Scholfield DJ, and Canary J. Effect of starch structure on glucose and insulin responses in adults. The American Journal of Clinical Nutrition 1988; 47(3): 428-32.
Behall KM, Scholfield DJ, Yuhaniak I, Canary J. Diets containing high amylose vs. amylopectin starch: effects on metabolic variables in human subjects. The American Journal of Clinical Nutrition 1989;49(2): 337-44.
Behall KM, and Howe JC. Effect of long-term consumption of amylose vs amylopectin starch on metabolic variables in human subjects. The American Journal of Clinical Nutrition 1995;61(3): 334-340.
Behall KM, Howe JC. Resistant starch as energy. Journal of the American College of Nutrition 1996;15(3): 248-54.
Behall KM, and Hallfrisch J. Plasma glucose and insulin reduction after consumption of breads varying in amylose content. European Journal of Clinical Nutrition 2002;56(9): 913-20.
Behall KM, Howe JC, and Anderson RA. Apparent mineral retention is similar in control and hyperinsulinemic men after consumption of high amylose cornstarch. Journal of Nutrition 2002;132:1886-91.
Behall KM, Scholfield DJ. Food amylose content affects postprandial glucose and insulin responses. Cereal Chemistry. 2005;82(6):654-659.
Behall KM, Hallfrisch JG, Scholfield DJ, Liljeberg-Elmstahl HGM. Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women. Diabetes Care. 2006;29(5):976-981.
Behall, K.M., Scholfield, D.J., Hallfrisch, J.G., Barley beta-glucan reduces plasma glucose and insulin responses compared with resistant starch in men Nutrition Research December, 2006;26(12):644-650.
Birkett A, Muir J, Phillips J, Jones G, O'Dea K. Resistant starch lowers fecal concentrations of ammonia and phenols in humans. The American Journal of Clinical Nutrition 1996;63(5):766-72.
Bodinham CL, Frost GS, Robertson MD. The acute effects of resistant starch on appetite and satiety Proceedings of the Nutrition Society May 2008; 67(OCE):E157. Presented at the joint meeting of the Société Francaise de Nutrition and The Nutrition Society, 6-7 December 2007.
Brighenti F, Benini L, Del Rio D, Casiraghi D, Pellegrini N, Spazzina F, Jenkins DJA., Vantini I. Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect. Am J Clin Nutr. 2006; 83:817-822.
Brown IL, McNaught KJ, Moloney E. Hi-maize™: new directions in starch technology and Nutrition. Food Australia, June 1995;47(6):272-5.
Burn J. Bishop T, Mecklin JP, Macrae F, Moslein G, Olschwang S, Bisgaard ML, Ramesar R, Eccles D, Maher ER, Bertario L, Jarvinen HJ, Lindblom A, Evans G, Lubinski J, Morrison P, Ho JWC, Vasen HFA, Side L, Thomas HJW, Scott RJ, Dunlop M, Barker G, Elliott F, Jas JR, Fodde R, Lynch HT, Mathers JC. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch Syndrome New England Journal of Medicine, 2008;359;24:2567-78.
Dronamraju SS, Coxhead JM, Kelly SB, Burn J, Mathers JC. Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch – A randomized controlled trial. Gut Online Online First article available Oct 31, 2008. doi: 10.1136/gut.2008.162933.
Giacco R, Clemente G, Brighenti F, Mancini M, D’Avanzo A, Coppola S, Ruffa G, La sorella G, Rivieccio AM, Rivellese AA, Riccardi G. Metabolic effects of resistant starch in patients with Type 2 diabetes. Diabetes, Nutrition & Metabolism 1998;11:330-5.
Granfeldt Y, Drews A, and Bjorck I. Arepas made from high amylose corn flour produce favorably low glucose and insulin responses in healthy humans. Journal of Nutrition 1995;125(3): 459-65.
Grubben MJ, van den Braak CC, Essenberg M, Olthof M, Tangerman A, Katan MB, Nagengast FM. Effect of resistant starch on potential biomarkers for colonic cancer risk in patients with colonic adenomas: a controlled trial. Digestive Diseases and Science 2001;46(4):750-6.
Heijnen M-LA, van Amelsvoort JMM, Deurenberg P, Beynen AC. Neither raw nor retrograded resistant starch lowers fasting serum cholesterol concentrations in healthy normolipidemic subjects. The American Journal of Clinical Nutrition 1996;64:312-8.
Heijnen M-LA, van Amelsvoort JMM, Deurenberg P, Beynen AC. Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men. The American Journal of Clinical Nutrition 1998;67:322-31.
Higgins JA, Higbee DR, Donahoo WT, Brown IL, Bell ML, Bessesen DH. Resistant starch consumption promotes lipid oxidation. Nutrition & Metabolism 2004;1:8.
Hoebler C, Karinthi A, Chiron H, Champ M, Barry J-L. Bioavailability of starch in bread rich in amylose: metabolic responses in healthy subjects and starch structure. European Journal of Clinical Nutrition 1999;53(5): 360-6.
Hospers JJ, van Amelsvoort JMM, and Weststrate JA. Amylose-to-amylopectin ratio in pastas affects postprandial glucosee and insulin responses and satiety in males. Journal of Food Science 1994;59(5): 1144-9.
Howe JC, Rumpler WV, and Behall KM. Dietary starch composition and level of energy intake alter nutrient oxidation in "carbohydrate-sensitive" men. Journal of Nutrition 1996;126(9): 2120-9.
Hylla S, Gostner A, Dusel G, Anger H, Bartram HP, Christl SU, Kasper H, Scheppach W. Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. The American Journal of Clinical Nutrition 1998;67(1):136-42.
Jenkins DJA, Vuksan V, Kendall CWC, Wursch P, Jeffcoat R, Waring S, Mehling CC, Vigden E, Augustin LSA, Wong E. Physiological effects of resistant starches on fecal bulk, short chain fatty acids, blood lipids and glycemic index. Journal of the American College of Nutrition 1998;17(6):609-16.
Johnson KL, Thomas EL, Bell JD, Frost GS, Robertson MD. Resistant starch improves insulin sensitivity in metabolic syndrome. Diabetic Medicine (2010):27(4):391-397. [Epub ahead of print April 7, 2010].
Kendall, CWC, Jenkins DJA, Emam A. Assessment of resistant starch tolerance: a dose response study. Abstract presented at 9th European Nutrition Conference, October 1-4, 2003, Rome, Italy.
Krezowski PA, Nuttall FQ, Gannon MC, Billington CJ, Parker S. Insulin and glucose responses to various starch-containing foods in Type II diabetic subjects. Diabetes Care 1987;10(2): 205-12.
Magee EA, Edmond LM, Tasker SM, Kong SC, Curno R, Cummings JH. Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis. Nutrition Journal 2005;4:7.
Maki KC, Pelkman CL, Kelley KM, Lawless AL, Schild A, Rains TM. Effects of Type 2 resistant starch consumption on insulin sensitivity in men and women. #587.9 Poster presented at Experimental Biology, April 10, 2011. Available online at
http://www.fasebj.org/cgi/content/meeting_abstract/25/1_MeetingAbstracts/587.9?sid=f92de866-73b9-4549-ae7a-ca3417713fb4
Monira S, Alam NH, Suau A, Magne F, Nair GB, Karmakar PC, Rahman M, Pochart P, Desieux JF. Time course of bacterial diversity in stool samples of malnourished children with cholera receiving treatment. Journal of Pediatric Gastroenterology & Nutrition 2009 Feb 25 (Epub ahead of print)
Muir JG, Yeow EG, Keogh J, Pizzey C, Bird AR, Sharpe K, O'Dea K, Macrae FA. Combining wheat bran with resistant starch has more beneficial effects on fecal indexes than does wheat bran alone. The American Journal of Clinical Nutrition 2004;79(6):1020-8.
Nilsson AC, Östman EM, Holst JJ, Björck IME. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. The Journal of Nutrition 2008;138:732-9.
Noakes M, Clifton PM, Nestel P, Le Leu R, McIntosh G. Effect of high-amylose starch and oat bran on metabolic variables and bowel function in subjects with hypertriglyceridemia. The American Journal of Clinical Nutrition 1996;64(6):944-51.
Olesen M, Rumessen JJ, Gudmand-Hoyer E. Intestinal transport and fermentation of resistant starch evaluated by the hydrogen breath test. European Journal of Clinical Nutrition 1994;48(10):692-701.
Penn-Marshall M,Holtzman GI, Barbeau WE. African Americans may have to consumer more than 12 grams a day of resistant starch to lower their risk for Type 2 diabetes. Journal of Medicinal Food (2010) 13(4):1-6. [Epub ahead of print May 18, 2010.]
Phillips J, Muir JG, Birkett A, Lu ZX, Jones GP, O’Dea K. Effect of resistant starch on fecal bulk and fermentation-dependent events in humans. The American Journal of Clinical Nutrition 1995;62:121-30.
Quílez J, Bulló M, Salvadó-Salas J. Improved postprandial response and feeling of satiety after consumption of low-calorie muffins with maltitol and high-amylose corn starch. Journal of Food Science 2007;72(6):S407-S411.
Ramakrishna BS, Venkataraman S, Srinivasan P, Dash P, Young GP, Binder HJ. Amylase-resistant starch plus oral rehydration solution for cholera. The New England Journal of Medicine 2000;342(5):308-313.
Raghupathy P, Ramakrishna BS, Oommen SP, Ahmed MS, Priyaa G, Dziura J, Young GP, Binder HJ. Amylase-resistant starch as adjunct to oral rehydradation therapy in children with diarrhea. Journal of Pediatric Gastroenterology and Nutrition 2006;42(4):362-368.
Ramakrishna, BS, Subramanian V, Mohan V, Sebastian BK, Young GP, Farthing MJ, Binder HJ. (2008) A randomimzed controlled trial of glucose versus amylase resistant starch hypo-osmolar oral rehydration solution for adult acute dehydrating diarrhea. PLoS ONE 3(2): e1587. Published February 13, 2008.
Reader DM, O’Connell BS, Johnson ML, Franz M. Glycemic and insulinemic response of subjects with type 2 diabetes after consumption of three energy bars. Journal of the American Dietetic Association 2002;102: 1139-42.
Robertson MD, Currie JM, Morgan LM, Jewell DP, Frayn KN. Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects. Diabetologia 2003;46(5):659-65.
Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. The American Journal of Clinical Nutrition 2005;82:559-567.
Nutrition 2005;82:559-567.
Robertson MD, Wright JW, Batt J. Russell-Jones D, and Umpleby AM. Dietary resistant starch in an insulin sensitizer A37(P37). Diebetic Medicine March 2009;26(1)(Suppl. 1):14.
Silvester KR, Bingham SA, Pollock JRA, Cummings JH, O’Neill IK. Effect of meat and resistant starch on fecal excretion of apparent N-nitroso compounds and ammonia from the human large bowel. Nutrition and Cancer 1997;29(1):13-23.
Slavin, Joanne, "Fibre and satiety – not all fibre is alike" Presented at National Starch’s "Resistant Starch Revealed" symposiums in Melbourne and Sydney, Australia, September 15 and 18, 2008. Presentation available on www.ResistantStarch.com.
Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. The American Journal of Clinical Nutrition 2005;82:559-567.
Van Amelsvoort JMM, Weststrate JA. Amylose-amylopectin ratio in a meal affects postprandial variables in male volunteers. The American Journal of Clinical Nutrition 1992;55:712-8.
Van Munster IP, Tangerman A, Nagengast FM. Effect of resistant starch on colonic fermentation, bile acid metabolism, and mucosal proliferation. Digestive Diseases and Sciences 1994:39(4):834-842.
Vonk RJ, Hagedoorn RE, de Graaff R, Elzinga H, Tabak S, Yang YX, Stellaard F. Digestion of so-called resistant starch sources in the human small intestine. The American Journal of Clinical Nutrition 2000;72(2):432-8.
Wacker M, Wanek P, Eder E, Hylla S, Gostner A, Scheppach W. Effect of enzyme-resistant starch on formation of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal and cell proliferation in the colonic mucosa of healthy volunteers. Cancer Epidemiology, Biomarkers and Prevention 2002;11:915-20.
Weststrate JA, and van Amelsvoort JMM. Effects of the amylose content of breakfast and lunch on postprandial variables in male volunteers. The American Journal of Clinical Nutrition 1993;58: 180-6.
Willis HJ, Eldridge AL, Beiseigel J, Thomas W, Slavin JL. Greater satiety response with resistant starch and corn bran in human subjects. Nutrition Research. February 2009; 29(2):100-105.
Worthley DL, Le Leu RK, Whitehall VL, Conlon M, Christophersen C, Belobrajdic D, Mallitt K-A, Hu Y, irahara N, Ogino S, Leggett BA, Young GP. A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and symbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. American Journal of Clinical Nutrition [Epub ahead of print July 29, 2009] doi:10.3945/ajcn.2009.28106.
Zhang W, Wang H, Zhang Y, Yang Y. Effects of resistant starch on insulin resistance of type 2 mellitus patients. Chinese Journal of Preventive Medicine March 2007;41(2):101-104.
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