Carbohydrate Digestibility and Metabolic Effects1,2

1. Julia M. W. Wong3,5 and 2. David J. A. Jenkins36* + Author Affiliations 1.

3

Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Toronto M5C 2T2, Ontario; 4Department of Medicine, Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto M5C 2T2, Ontario; and Departments of 5 Nutritional Sciences and 6Medicine, Faculty of Medicine, University of Toronto, Toronto M5S 3E2, Ontario

1. *To whom correspondence should be addressed. E-mail: cyril.kendall@utoronto.ca.

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Abstract
There is a history of interest in the metabolic effects of alterations in small intestinal digestion and colonic fermentation of carbohydrate. It is believed that the rate of digestion of carbohydrate determines the place and form in which carbohydrate is absorbed. Slowly absorbed or lente carbohydrate sources may reduce postprandial glucose surges and the need for insulin with important implications for lowering coronary heart disease risk and reducing diabetes incidence. Carbohydrates that are not digested in the small intestine will enter the colon, and those that are fermentable will be salvaged as short-chain fatty acids in the colon and at the same time may stimulate colonic microflora, such as bifidobacteria. This process may have metabolic effects in the gut and throughout the host, possibly related to short-chain fatty acid products, although these effects are less well documented. One important aspect of colonic fermentation is the stimulation of certain populations of the colonic microflora, which may assist in the biotransformation of bioactive food components including the cleaving of plant phenolics from their glycone to produce the more rapidly absorbed aglycone. However, human studies have been limited. Therefore, further studies are required to explore these important aspects of metabolism related to the rate of carbohydrate absorption and fermentation and their implications in health and disease. Previous SectionNext Section

Introduction
Delayed or malabsorbed dietary components, specifically carbohydrates, may have significant implications in the pathogenesis and treatment of metabolic disorders. This is of particular importance at a time when the incidence of the metabolic syndrome, obesity, and diabetes continue to rise in Western societies (1). Dietary carbohydrates that are slowly digested and require less insulin for their disposal may benefit those with impaired

carbohydrate tolerance. Fermentable carbohydrates that are not digested enter the colon, where they are available for bacterial fermentation and alter the environment by enhancing SCFA production (acetate, propionate, and butyrate). In addition, bioactive substances such as phytoestrogens may be converted to more active forms, and their absorption from the colon may be enhanced (2). Specific SCFA have also been linked to reducing the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease (CVD). As a consequence, attention has been drawn to dietary strategies that promote a change to slowly digested carbohydrates to increase fermentation and thereby reduce the risk of coronary heart disease, diabetes, and cancer.

Carbohydrate digestion
Oligofructose and inulin are not digested in the small intestine. The structure consists of (21) fructosyl-fructose linkages with or without a starting -d-glucose moiety (3). Available carbohydrates are -linked sugar units that are initially broken down by salivary and then pancreatic amylase to glucose, maltose, and maltotriose. The maltose and maltotriose, together with sucrose, are further split to component sugars and absorbed through the action of brush border sucrase-isomaltase with lactose split by lactase. Glucose is absorbed by active transport and fructose and galactose by active transport and facilitated diffusion.

Malabsorption of carbohydrates
Traditionally, the amount of carbohydrate available for colonic bacterial fermentation has been determined by the amount of dietary fiber present in foods. However, some of the available carbohydrate (i.e., available for small intestinal absorption: total carbohydrate minus dietary fiber) in many foods may also escape digestion in the small intestine in appreciable amounts and become available for fermentation by colonic microflora (4). Early studies in ileostomates were conducted to determine carbohydrate losses with different types of foods that vary in fiber and available carbohydrate content (5,6). Certain foods have been related to a greater proportionate loss of carbohydrate compared with others: specifically lentils and other legumes, the -glucan-containing cereals oat bran and barley, and also pumpernickel bread, where the whole grain structure is preserved (Fig. 1) (5,6). Other studies have also shown that available carbohydrate of many starchy foods is incompletely digested and absorbed in the normal small intestine (7,8). A significant positive association was also found between carbohydrate malabsorption and fiber content of the food (Fig. 2) (6,9). This suggests that dietary fiber content of foods tends to determine the amount of available carbohydrate entering the colon. Not unexpectedly, a significant inverse association was observed between glycemic indices of foods, a concept that is discussed later, and losses in the ileal effluent (Fig. 3) (6).

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FIGURE 1 Percentage carbohydrate losses for the test food groups. White bread (7 tests); others (whole-meal bread, parboiled rice, instant rice, long-grain rice, macaroni, spaghetti, pumpernickel and rye breads, bulgar wheat, Rice Chex, Corn Chex, instant potato); legumes (romano beans, kidney beans, chick peas, red lentils). Apart from white bread, mean values for repeated tests of a food were taken for calculation of significance level [adapted from Jenkins et al. (6)].

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FIGURE 2 Carbohydrate losses for foods in relation to fiber content per 80-g carbohydrate portion [adapted from Jenkins et al. (6)].

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FIGURE 3 Percentage of carbohydrate loss in relation to GI [adapted from Jenkins et al. (6)].

Many factors may influence the digestion of carbohydrates in the small intestine, including the rate of digestion (10,11), the food form (physical form, particle size) (12), type of preparation (cooking method and processing) (1215), type of starch (amylose or amylopectin) (12,16), presence of antinutrients such as -amylase inhibitors (17,18), transit time (19), and amount of fiber, fat, and proteins (20,21). Prebiotics, such as oligofructose and inulin, are an emerging functional food associated with suggested improvements in health. Administration of these dietary components promotes the growth of specific bacteria, especially bifidobacteria (22) and lactobacillius, which have defined metabolic functions (23). Studies involving patients with ileostomies have shown that 88% and 89% of inulin and oligofructose, respectively, are recovered in the effluent (24,25). These oligosaccharides are examples of carbohydrates that are almost entirely not digested in the small intestine, a characteristic that has led to growing research on their effects on colonic and systemic health.

Concept of glycemic index

The classic view that the overall metabolic significance of the rate of carbohydrate digestion (i.e., postprandial blood glucose response) was determined by chain length (i.e., simple vs. complex carbohydrates) has been questioned. This questioning gave rise to the concept of the glycemic index (GI), and it was suggested that slowly digested carbohydrates, as an extension of the dietary fiber hypothesis first proposed by Burkitt and Trowell (26), may have metabolic benefits in relation to diabetes and to the reduction of coronary heart disease risk (Table 1) (27). The nature of the carbohydrate source may therefore be important, independent of the fiber content. The GI is a quantitative classification of carbohydrate foods based on the rate of carbohydrate absorption as reflected in the glycemic response (10,37). Research in the area of GI and its clinical application has been greatly facilitated by comprehensive GI food tables (38). Furthermore, the concept of glycemic load (GL) has been developed to assess the total glycemic impact of the diet: it is the product of dietary GI and available dietary carbohydrate (39). View this table:

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TABLE 1 Possible effects of prolonged carbohydrate absorption time

GI and chronic diseases

The rising incidence of metabolic disorders such as diabetes and associated disorders has increased interest in nutrition interventions as a means of tackling this growing problem. As a result, there has been renewed interest in the use of the GI and GL as a nutrition strategy to prevent and manage chronic diseases. However, this renewed interest has also stimulated controversy (12,40). Epidemiological studies have suggested that low-GI diets may play a role in reducing the risk of CHD, diabetes, and certain cancers. Low-GI diets have been observed to be negatively

associated with HDL-C, suggesting that low-GI diets may preserve HDL-C (41,42). In the Women's Health Study, GI was positively associated with C-reactive protein (43), a marker for systemic inflammation that is associated with an increase in CVD risk (44). Many studies have explored the effect of low-GI diets on coronary heart disease risk factors. In one study, plasminogen activator inhibitor-1 (PAI-1) levels, a marker of impaired fibrinolysis, was reduced (45), and in another concerning hyperlipidemia, 1 mo on a low-GI diet reduced LDL cholesterol (LDL-C) and triglycerides (TG) in those with higher TG levels, despite no significant difference in body weight (46). A low-GL diet has been compared with a low-fat diet during weight loss, where a low-GI diet showed marked improvements in heart disease risk factors such as insulin resistance, TG, C-reactive protein, and blood pressure while subjects consumed the low-GL diet (47). In studies that have assessed its effect on the development of CVD directly, low-GI diets appears to have a protective role. The Nurses' Health Study demonstrated a direct relation between fatal and nonfatal myocardial infarction and GI as well as GL (48). Dietary GI has been suggested to be of greater important in those with insulin resistance because an association was observed with dietary GI and those with body mass index >23 kg/m2. On the other hand, no significant association of GI or GL and coronary heart disease was seen in the Zutphen study of older men (49), possibly because of the smaller sample size and demographics, such as age, at the start of study. Several studies have looked at dietary GI in relation to the development and management of Type 2 diabetes. A recent meta-analysis of low-GI diets compared with conventional or highGI diets in the management of diabetes found that glycated proteins were reduced 7.4% and HbA1c by 0.43% more on the low-GI diet than on the high-GI diet (50). As observed in the UKPDS, any reduction in HbA1c, no matter how small, improves prognosis. It was observed that a 1% reduction in mean HbA1c resulted in a reduction of 21% in any diabetes-related endpoint, 21% in diabetes-related death, 14% in myocardial infarction, and 37% in microvascular complications (51). Other studies, such as the Nurses' Health Study (52) and the Health Professionals Study (39), found an inverse relationship between GI and risk of developing diabetes. However, this was not observed in the Iowa Women's Health Study, where the GI and GL were not associated with Type 2 diabetes (53). This study, however, included an elderly cohort, which could introduce a selection bias. Direct associations between GI and colorectal and breast cancer have been observed in epidemiological studies (5456). McKeown-Eyssen (57) and Giovannucci (58) were among the first to hypothesize a link between hyperinsulinemia and the development of colorectal cancer and possibly other types of cancer such as breast and prostate (59). This is possibly related to increased insulin-like growth factors in conjunction with a sedentary lifestyle including higher intake of energy and refined carbohydrates and lower intake of fruits and vegetables; however, human data are currently limited. Therefore, low-GI and -GL diets show promise for the prevention and treatment of chronic diseases.

Mechanism of action
It has been hypothesized that the metabolic effect of low-GI foods relates to the rate at which carbohydrates are absorbed from the gut (Fig. 4). Low-GI foods are characterized by the slower rate of carbohydrate absorption (slow-release carbohydrate) resulting in a lower rise in blood glucose levels. Some of the metabolic effects caused by reducing the rate of absorption

have been confirmed in studies in healthy men. For example, when a glucose solution was sipped at an even rate over 180 min (sipping) compared with the same amount of glucose taken as a bolus at zero time (28), a marked economy in insulin secretion and lower serum FFA levels were observed with sipping. A similar improvement is also observed with low-GI meals, where a slower rate of glucose absorption reduces the postprandial rise in gut hormones (e.g., incretins) and the demand for insulin. Furthermore, the prolonged absorption of carbohydrate over time will suppress FFA synthesis (28,60) and counterregulatory responses (28,61). Over time, with lower FFA concentrations and sustained tissue insulinization (tissues metabolizing glucose following secretion of insulin), glucose is withdrawn from the circulation at a faster rate. As a result, blood glucose concentrations return toward baseline despite continued glucose absorption from gut. Therefore, a reduction in the rise in peak postprandial and incremental area under the curve for blood glucose are observed. Furthermore, there is a second meal effect such that an IV glucose tolerance test shows more rapid uptake of glucose (increased KG) after sipping than after the bolus drink (28).

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FIGURE 4 Hypothetical effect of feeding diets with a low (A) or high (B) GI on gastrointestinal glucose absorption and postprandial blood glucose [adapted from Jenkins et al. (27)].

Carbohydrates, SCFA, and colonic fermentation

Carbohydrates resistant to digestion and those that escape absorption in the small intestine are available for colonic bacterial fermentation resulting in the production of SCFA (acetic, butyric, and propionic acids) together with gases (CO2, CH4, and H2) and heat (62,63). Butyrate has been hypothesized to reduce the risk of colon cancer and to benefit inflammatory bowel disease (6466). Specifically, increases in SCFA production have been associated with decreased pH, which may reduce potential pathogenic clostridia, decreased solubility of bile acids, increased absorption of minerals (indirectly), and reduced ammonia absorption by the protonic dissociation of ammonia and other amines (i.e., the formation of the less diffusible NH4+ compared with the diffusible NH3) (63,6770).

The major source of fermentable carbohydrates are the resistant starches. It is estimated that 520% of dietary starch is not absorbed in the small intestine (57,71,72). Soluble and insoluble fibers are fermented to varying degrees. However, insoluble fibers (e.g., lignans, cellulose, and some hemicelluloses) that are resistant to colonic fermentation may carry with them fermentable carbohydrate substrate, including starches and sugars, although their major role is in fecal bulking. Soluble fibers (e.g., pectins, gums, mucilages, some hemicelluloses, as well as inulin-type fructans) are generally more completely fermented with little effect in increasing fecal bulk. Most fiber-containing foods contain about one-third soluble and twothirds insoluble fiber (63). The production of SCFA is determined by a number of factors, including the number and types of microflora present in the colon (67), type of substrate (73), and gut transit time (73 75). In general, fecal SCFA production is in the order acetate > propionate > butyrate (62) in a molar ratio of 60:20:20, respectively (76). Absorption of SCFA in the cecum and the colon is a very efficient process with only 510% being excreted in the feces (67,7779). Two proposed mechanisms of absorption are 1) diffusion of protonated SCFA and 2) anion exchange (73). Once absorbed, SCFA are metabolized at 3 major sites in the body: 1) cells of cecocolonic epithelium that use butyrate as the major substrate for maintenance-energyproducing pathways; 2) liver cells that metabolize residual butyrate with propionate used for gluconeogenesis and 5070% of acetate is also taken up by the liver; 3) muscle cells generate energy from the oxidation of residual acetate (67). The primary interest in SCFA has been in relation to colonic function as a result of their uptake and metabolism by colonocytes, specifically butyrate, although SCFA are also metabolic substrates for other tissues of the host.

SCFA and chronic diseases

CVD. Acetate and propionate have been proposed to have opposing effects in hyperlipidemia, a risk factor for coronary heart disease. Subjects given rectal infusions of acetate and propionate in equivalent ratios showed a dose-dependent increase in serum total cholesterol and TG levels, providing indirect evidence that SCFA are utilized for lipid synthesis (80). In a subsequent study by the same research group, rectal infusions of a mixture of acetate and propionate attenuated the serum cholesterol increase observed when acetate infusion was given alone. However, rectal infusions of propionate alone did not affect lipids or TG in healthy young men and women (81). These results support the idea that propionate inhibits the utilization of acetate for cholesterol synthesis. However, dietary trials have been inconsistent. One-week intakes of 2.7 g of sodium propionate given in bread (82) and 7.5 g sodium propionate taken as a capsule (83) did not affect serum lipids, although one study showed that 5.4 g of propionate given daily for 2 wk lowered LDL-C and total cholesterol in subjects with total cholesterol >5.5 mmol/L (84). Animal studies suggest that propionate inhibits cholesterol synthesis by inhibiting both 3-hydroxyl-3-methylglutaryl-CoA synthase and 3-hydroxy-3methylglutaryl-coA reductase (85,86). Inulin-type fructans are bifidogenic and have been associated with hypolipidemic effects. Although a number of mechanisms have been proposed, increased propionate production, resulting in a decreased acetate:propionate ratio, has been one of the suggested modes of action. Increased production of propionate, through fermentation, may inhibit cholesterol synthesis (85,8791). This has been supported in studies with hyperlipidemic experimental

animals (87,92) but not supported in other animal studies (9395). The effect of inulin-type fructans on blood lipids in humans have yielded inconsistent results (96) compared with the animal data; this may be related to species differences. Furthermore, few studies have quantified the synthesis of SCFA, specifically acetate and propionate, with use of prebiotics. The lack of agreement on the relation between increased colonic fermentation and lipid metabolism may be a result of differences in the chemical composition of the substrate source. Studies with resistant starch have been consistent in showing raised fecal butyrate (97100). Starch fermentation primarily yields acetate and butyrate, whereas fermentation of pectin and xylan yields acetate alone as the main product (101). Recent human studies found that acute ingestion of a nondigestible monosaccharide, l-rhamnose (25 g), increased serum propionate without increasing acetate (102), but longer-term studies have not shown reduced serum lipids (103). Lactulose, a rapidly fermented dietary fiber, has been shown to result in higher serum cholesterol levels, possibly as a consequence of increased production and absorption of colonic acetate resulting in increased hepatic lipogenesis (104). Oligofructose and inulin, in common with other fermentable carbohydrates, may improve glucose tolerance through suppression of serum FFA concentrations (105). It has been shown that short-chain organic acids, including -hydroxybutyrate, acetate, and propionate, may suppress FFA release and possibly stimulate increased insulin secretion (80,81,106). Colon cancer. Butyrate is the preferred fuel of the colonic epithelial cells but also plays a major role in regulation of cell proliferation and differentiation (62,64,67,107). Glucose is readily absorbed into the blood and, therefore, is not a major source of energy for enterocytes (i.e., very little is available to colonocytes). Up to 7090% of butyrate is metabolized by the colonocytes. As a result, the vast majority of absorbed glucose is passed to the blood. In vitro and in vivo studies have observed that butyrate has an opposing role, resulting in the butyrate paradox (108,109). Butyrate stimulated cell proliferation in normal colonocytes (64,107), but it suppressed proliferation of colon adenocarcinoma cells (110). This inconsistency between in vitro and in vivo studies may be related to the timing of butyrate administration, the butyrate source (i.e., different dietary fibers), and interaction with dietary fat (109). Butyrate also stimulates immunogenicity of cancer cells (111). Acetate and propionate have been shown to induce apoptosis in colorectal tumor cell lines, but to a much smaller extent than butyrate (112,113). Currently, the mechanisms of action of butyrate in relation to colon cancer are not clearly defined. Butyrate has been shown to inhibit cell proliferation by inducing p21WAFI/Cip1 protein and mRNA levels (114116), which can block the cell cycle at G1. This blockage may allow DNA checkpoint-mediated repair of genomic instability or mutations (108). Through inhibition of histone deacetylase, apoptosis has been shown to be induced by butyrate through hyperacetylation of histones (H3 and H4) (117). As a result, the DNA is in a more open form (118), which would be ideal if DNA damage had occurred and repair enzymes were necessary to approach the damaged DNA. On the other hand, in the presence of a carcinogen, the open form of the DNA may make it more susceptible to mutation (109). Butyrate can also induce differentiation of neoplastic colonocytes in vitro, resulting in a phenotype that is associated with normal mature cells (119). Accumulation of SCFA in the colon leads to a drop in pH, which decreases the solubility of free bile acids and in turn decreases the production of secondary bile acids, which have potential tumor promoter

activity (120). This may be related to the inhibition of colonic bacterial enzyme 7dehydroxylase, which degrades primary bile acids to secondary bile acids (121). Increased colonic acidification also increases the availability of calcium for binding to free bile acids and fatty acids, rendering them insoluble (122). The effect of inulin-type fructans on the risk of cancer is discussed in other articles of this Supplement. Inflammatory bowel. SCFA enemas have been tried as a possible treatment for diversion and ulcerative colitis. Roediger demonstrated that colonocytes of individuals with active and quiescent ulcerative colitis have reduced butyrate oxidation compared with controls (123). It has been suggested that bowel inflammation arises as a result of a lack of luminal SCFA (i.e., state of nutritional deficiency) of the colonic epithelium and a block in the uptake or oxidation of SCFA by colonocytes (124,125). The latter may be related to a reduction in coenzyme A, a requirement for SCFA oxidation (123), from the production of sulfur-containing compounds by colonic microflora. However, this block in uptake and oxidation may be overcome by raising SCFA to higher-than-normal concentrations in the colonic lumen (125). The resupply of nutrients, either by surgical reanastomosis or SCFA irrigation, may correct this deficiency. Studies of SCFA enemas containing 60 mmol/L of sodium acetate, 30 mmol/L of sodium propionate, and 40 mmol/L of sodium n-butyrate to 5 patients with diversion colitis for a period of 26 wk resulted in disappearance of symptoms and the inflammatory changes observed by endoscopic and histological findings (126). However, another study using the same SCFA enema solution in 13 patients with diversion colitis resulted in no endoscopic or histologic changes after 2 wk (127). The treatment of distal ulcerative colitis with SCFA irrigation has produced inconsistent results (128), some studies showing it to be an effective treatment (129131) and others not (131,132). These inconsistencies may be related to the type of SCFA used (mixture or butyrate alone), SCFA concentrations, frequency of administration, and duration of treatment. Therefore, the use of SCFA irrigations for the treatment of bowel inflammation has been pursued further because the research to date has been inconclusive. The effects of inulin-type fructans on inflammatory bowel disease are dealt with in another article in this series. At a time where the rising burden of chronic disease has become a major health concern worldwide related to aging populations and changes in diet and lifestyle, delayed or slowly absorbed carbohydrates as part of the nutrition strategy may play a useful role. Further studies are needed to define possible benefits of low-GI diets, including inulin-type fructans as components of low-GI diets, in long-term randomized controlled trials. The data on increased SCFA production and their health benefits are even more limited. Therefore, although there is a requirement for basic mechanistic studies, most importantly, clinical trials must be undertaken to determine the clinical relevance of diet-induced changes in SCFA production. Previous SectionNext Section

Footnotes

1 Published in a supplement to The Journal of Nutrition. Presented at the conference 5th ORAFTI Research Conference: Inulin and Oligofructose: Proven Health Benefits

and Claims held at Harvard Medical School, Boston, MA, September 2829, 2006. This conference was organized and sponsored by ORAFTI, Belgium. Guest Editors for the supplement publication were Marcel Roberfroid, Catholique University of Louvain, Brussels, Belgium and Randal Buddington, Mississippi State University, USA. Guest Editor disclosure: M. Roberfroid and R. Buddington, support for travel to conference provided by ORAFTI. 2 Author disclosures: J. M. W. Wong, no conflicts of interest; and D. J. A. Jenkins, Research grant and Scientific Advisory Board, Orafti; honoraria from food and pharmaceutical industry.

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Burkitt DP, Trowell HC. Dietary fibre and Western diseases. Ir Med J. 1977;70:272 7. Medline 27. 27. Jenkins DJ, Kendall CW, Augustin LS, Franceschi S, Hamidi M, Marchie A, Jenkins AL, Axelsen M. Glycemic index: overview of implications in health and disease. Am J Clin Nutr. 2002;76:266S73S. Abstract/FREE Full Text 28. 28. Jenkins DJ, Wolever TM, Ocana AM, Vuksan V, Cunnane SC, Jenkins M, Wong GS, Singer W, Bloom SR, et al. Metabolic effects of reducing rate of glucose ingestion by single bolus versus continuous sipping. Diabetes. 1990;39:77581. Medline 29. 29. Jenkins DJ, Ocana A, Jenkins AL, Wolever TM, Vuksan V, Katzman L, Hollands M, Greenberg G, Corey P, et al. Metabolic advantages of spreading the nutrient load: effects of increased meal frequency in non-insulin-dependent diabetes. Am J Clin Nutr. 1992;55:4617. Abstract/FREE Full Text 30. 30. Bertelsen J, Christiansen C, Thomsen C, Poulsen PL, Vestergaard S, Steinov A, Rasmussen LH, Rasmussen O, Hermansen K. Effect of meal frequency on blood glucose, insulin, and free fatty acids in NIDDM subjects. Diabetes Care. 1993;16:4 7. Abstract/FREE Full Text 31. 31. Jones PJ, Leitch CA, Pederson RA. Meal-frequency effects on plasma hormone concentrations and cholesterol synthesis in humans. Am J Clin Nutr. 1993;57:868 74. Abstract/FREE Full Text 32. 32.

Jenkins DJ, Wolever TM, Vuksan V, Brighenti F, Cunnane SC, Rao AV, Jenkins AL, Buckley G, Patten R, et al. Nibbling versus gorging: metabolic advantages of increased meal frequency. N Engl J Med. 1989;321:92934. Medline 33. 33. Jenkins DJ, Khan A, Jenkins AL, Illingworth R, Pappu AS, Wolever TM, Vuksan V, Buckley G, Rao AV, et al. Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids. Metabolism. 1995;44:54955. CrossRefMedline 34. 34. Arnold LM, Ball MJ, Duncan AW, Mann J. Effect of isoenergetic intake of three or nine meals on plasma lipoproteins and glucose metabolism. Am J Clin Nutr. 1993;57:44651. Abstract/FREE Full Text 35. 35. Cohn C. Feeding patterns and some aspects of cholesterol metabolism. Fed Proc. 1964;23:7681. Medline 36. 36. Jenkins DJ, Jenkins AL. Nutrition principles and diabetes. A role for lente carbohydrate? Diabetes Care. 1995;18:14918. Abstract/FREE Full Text 37. 37. Jenkins DJ, Wolever TM, Jenkins AL, Josse RG, Wong GS. The glycaemic response to carbohydrate foods. Lancet. 1984;2:38891. Medline 38. 38. Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002;76:556. Abstract/FREE Full Text

39. 39. Salmeron J, Ascherio A, Rimm EB, Colditz GA, Spiegelman D, Jenkins DJ, Stampfer MJ, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care. 1997;20:54550. Abstract/FREE Full Text 40. 40. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrates, fiber, protein and amino acids (macronutrients). Washington, DC: National Academy Press; 2002. 41. 41. Ford ES, Liu S. Glycemic index and serum high-density lipoprotein cholesterol concentration among us adults. Arch Intern Med. 2001;161:5726. Abstract/FREE Full Text 42. 42. Frost G, Leeds AA, Dore CJ, Madeiros S, Brading S, Dornhorst A. Glycaemic index as a determinant of serum HDL-cholesterol concentration. Lancet. 1999;353:10458. CrossRefMedline 43. 43. Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity Creactive protein in middle-aged women. Am J Clin Nutr. 2002;75:4928. Abstract/FREE Full Text 44. 44. Ridker PM. High-sensitivity C-reactive protein, inflammation, and cardiovascular risk: from concept to clinical practice to clinical benefit. Am Heart J. 2004;148:S19 26. CrossRefMedline 45. 45. Jarvi AE, Karlstrom BE, Granfeldt YE, Bjorck IE, Asp NG, Vessby BO. Improved glycemic control and lipid profile and normalized fibrinolytic activity on a lowglycemic index diet in type 2 diabetic patients. Diabetes Care. 1999;22:108.

Abstract/FREE Full Text 46. 46. Jenkins DJ, Wolever TM, Kalmusky J, Guidici S, Giordano C, Patten R, Wong GS, Bird JN, Hall M, et al. Low-glycemic index diet in hyperlipidemia: use of traditional starchy foods. Am J Clin Nutr. 1987;46:6671. Abstract/FREE Full Text 47. 47. Pereira MA, Swain J, Goldfine AB, Rifai N, Ludwig DS. Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss. JAMA. 2004;292:248290. Abstract/FREE Full Text 48. 48. Liu S, Willett WC, Stampfer MJ, Hu FB, Franz M, Sampson L, Hennekens CH, Manson JE. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr. 2000;71:145561. Abstract/FREE Full Text 49. 49. van Dam RM, Visscher AW, Feskens EJ, Verhoef P, Kromhout D. Dietary glycemic index in relation to metabolic risk factors and incidence of coronary heart disease: the Zutphen Elderly Study. Eur J Clin Nutr. 2000;54:72631. CrossRefMedline 50. 50. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care. 2003;26:22617. Abstract/FREE Full Text 51. 51. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:40512. Abstract/FREE Full Text

52. 52. Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA. 1997;277:4727. Abstract/FREE Full Text 53. 53. Meyer KA, Kushi LH, Jacobs DR, Jr., Slavin J, Sellers TA, Folsom AR. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr. 2000;71:92130. Abstract/FREE Full Text 54. 54. Slattery ML, Benson J, Berry TD, Duncan D, Edwards SL, Caan BJ, Potter JD. Dietary sugar and colon cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:67785. Abstract/FREE Full Text 55. 55. Franceschi S, Dal Maso L, Augustin L, Negri E, Parpinel M, Boyle P, Jenkins DJ, La Vecchia C. Dietary glycemic load and colorectal cancer risk. Ann Oncol. 2001;12:1738. Abstract/FREE Full Text 56. 56. Augustin LS, Dal Maso L, La Vecchia C, Parpinel M, Negri E, Vaccarella S, Kendall CW, Jenkins DJ, Francesch S. Dietary glycemic index and glycemic load, and breast cancer risk: a case-control study. Ann Oncol. 2001;12:15338. Abstract/FREE Full Text 57. 57. McKeown-Eyssen G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev. 1994;3:68795. Abstract 58. 58. Giovannucci E. Insulin and colon cancer. Cancer Causes Control. 1995;6:16479.

CrossRefMedline 59. 59. Boyd DB. Insulin and cancer. Integr Cancer Ther. 2003;2:31529. Abstract/FREE Full Text 60. 60. Wolever TM, Jenkins DJ, Ocana AM, Rao VA, Collier GR. Second-meal effect: lowglycemic-index foods eaten at dinner improve subsequent breakfast glycemic response. Am J Clin Nutr. 1988;48:10417. Abstract/FREE Full Text 61. 61. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB. High glycemic index foods, overeating, and obesity. Pediatrics. 1999;103:E26. CrossRefMedline 62. 62. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:103164. Abstract/FREE Full Text 63. 63. Cummings JH. Short chain fatty acids in the human colon. Gut. 1981;22:76379. FREE Full Text 64. 64. Roediger WE. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980;21:7938. Abstract/FREE Full Text 65. 65. Jenkins DJ, Kendall CW, Vuksan V. Inulin, oligofructose and intestinal function. J Nutr. 1999;129:1431S3S. Medline

66. 66. Floch MH, Hong-Curtiss J. Probiotics and functional foods in gastrointestinal disorders. Curr Treat Options Gastroenterol. 2002;5:31121. CrossRefMedline 67. 67. Roberfroid MB. Inulin-type fructans: functional food ingredients. Boca Raton, FL: CRC Press; 2005. 68. 68. Vince A, Killingley M, Wrong OM. Effect of lactulose on ammonia production in a fecal incubation system. Gastroenterology. 1978;74:5449. Medline 69. 69. Jackson AA. Aminoacids: essential and non-essential? Lancet. 1983;1:10347. Medline 70. 70. Jenkins DJ, Wolever TM, Collier GR, Ocana A, Rao AV, Buckley G, Lam Y, Mayer A, Thompson LU. Metabolic effects of a low-glycemic-index diet. Am J Clin Nutr. 1987;46:96875. Abstract/FREE Full Text 71. 71. Stephen AM, Haddad AC, Phillips SF. Passage of carbohydrate into the colon. Direct measurements in humans. Gastroenterology. 1983;85:58995. Medline 72. 72. Englyst HN, Cummings JH. Non-starch polysaccharides (dietary fiber) and resistant starch. Adv Exp Med Biol. 1990;270:20525. Medline 73. 73.

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Wolever TM, Brighenti F, Royall D, Jenkins AL, Jenkins DJ. Effect of rectal infusion of short chain fatty acids in human subjects. Am J Gastroenterol. 1989;84:102733. Medline 81. 81. Wolever TM, Spadafora P, Eshuis H. Interaction between colonic acetate and propionate in humans. Am J Clin Nutr. 1991;53:6817. Abstract/FREE Full Text 82. 82. Todesco T, Rao AV, Bosello O, Jenkins DJ. Propionate lowers blood glucose and alters lipid metabolism in healthy subjects. Am J Clin Nutr. 1991;54:8605. Abstract/FREE Full Text 83. 83. Venter CS, Vorster HH, Cummings JH. Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers. Am J Gastroenterol. 1990;85:54953. Medline 84. 84. Amaral L, Hoppel C, Stephen AM. Effect of propionate on lipid metabolism in healthy human subjects. Falk Symposium 1993;73:E2. 85. 85. Bush RS, Milligan LP. Study of the mechanism of inhibition of ketogenesis by propionate in bovine liver. Can J Anim Sci. 1971;51:1217. 86. 86. Rodwell VW, Nordstrom JL, Mitschelen JJ. Regulation of HMG-CoA reductase. Adv Lipid Res. 1976;14:174. Medline 87. 87. Chen WJ, Anderson JW, Jennings D. Propionate may mediate the hypocholesterolemic effects of certain soluble plant fibers in cholesterol-fed rats. Proc Soc Exp Biol Med. 1984;175:2158. Abstract/FREE Full Text

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Steinhart AH, Hiruki T, Brzezinski A, Baker JP. Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial. Aliment Pharmacol Ther. 1996;10:72936. CrossRefMedline Karbohidrat Kecernaan dan Metabolik Effects1, 2 1. Julia M. W. Wong3, 5 dan 2. David J. A. Jenkins3-6 * + Penulis Afiliasi 1. 3Clinical Gizi dan Faktor Risiko Modifikasi Center, Rumah Sakit St Michael, Toronto M5C 2T2, Ontario, 4Department Kedokteran, Divisi Endokrinologi dan Metabolisme, Rumah Sakit St Michael, Toronto M5C 2T2, Ontario, dan Departemen Ilmu 5Nutritional dan 6Medicine, Fakultas Kedokteran, Universitas Toronto, Toronto M5S 3E2, Ontario 1. * Kepada siapa korespondensi harus ditangani. E-mail: cyril.kendall @ utoronto.ca. Selanjutnya Bagian Abstrak Ada sejarah yang menarik dalam efek metabolik dari perubahan dalam pencernaan usus kecil dan usus fermentasi karbohidrat. Hal ini diyakini bahwa laju pencernaan karbohidrat menentukan tempat dan bentuk di mana karbohidrat diserap. Perlahan-lahan diserap atau

lente sumber karbohidrat dapat mengurangi glukosa postprandial lonjakan dan kebutuhan insulin dengan implikasi penting untuk menurunkan risiko penyakit jantung koroner dan mengurangi timbulnya diabetes. Karbohidrat yang tidak dicerna dalam usus kecil akan memasuki usus besar, dan mereka yang difermentasi akan diselamatkan sebagai rantai pendek asam lemak dalam usus besar dan pada saat yang sama dapat merangsang mikroflora kolon, seperti bifidobacteria. Proses ini mungkin memiliki efek metabolik dalam usus dan seluruh tuan rumah, kemungkinan berhubungan dengan rantai pendek asam lemak produk, meskipun efek ini kurang baik didokumentasikan. Salah satu aspek penting dari fermentasi kolon adalah rangsangan dari populasi tertentu dari mikroflora usus, yang dapat membantu dalam biotransformasi komponen bioaktif makanan termasuk membelah fenolat tanaman dari glycone mereka untuk menghasilkan aglikon lebih cepat diserap. Namun, penelitian pada manusia telah terbatas. Oleh karena itu, penelitian lebih lanjut diperlukan untuk mengeksplorasi aspek-aspek penting dari metabolisme yang berkaitan dengan tingkat penyerapan karbohidrat dan fermentasi dan implikasinya dalam kesehatan dan penyakit. Sebelumnya Bagian Bagian Pengantar Tertunda atau malabsorbed komponen makanan, khususnya karbohidrat, mungkin memiliki implikasi yang signifikan dalam patogenesis dan pengobatan gangguan metabolisme. Ini sangat penting terutama pada saat kejadian sindrom metabolik, obesitas, dan diabetes terus meningkat di masyarakat Barat (1). Karbohidrat makanan yang lambat dicerna dan membutuhkan sedikit insulin untuk pembuangan mereka dapat bermanfaat bagi mereka dengan toleransi karbohidrat terganggu. Fermentasi karbohidrat yang tidak dicerna memasuki usus besar, di mana mereka yang tersedia untuk fermentasi bakteri dan mengubah lingkungan dengan produksi ALRP meningkatkan (asetat, propionat, butirat dan). Selain itu, zat bioaktif seperti fitoestrogen dapat dikonversi menjadi bentuk yang lebih aktif, dan penyerapan mereka dari usus besar dapat ditingkatkan (2). ALRP khusus juga telah dikaitkan dengan mengurangi risiko mengembangkan gangguan pencernaan, kanker, dan penyakit kardiovaskular (CVD). Akibatnya, perhatian telah tertarik pada strategi diet yang mempromosikan perubahan ke karbohidrat dicerna perlahan untuk meningkatkan fermentasi dan dengan demikian mengurangi risiko penyakit jantung koroner, diabetes, dan kanker. Karbohidrat pencernaan Oligofructose dan inulin tidak dicerna dalam usus kecil. Struktur ini terdiri dari -(2 1) fructosyl-fruktosa hubungan dengan atau tanpa bagian -d-glukosa mulai (3). Karbohidrat yang tersedia adalah unit gula -linked yang awalnya dipecah oleh amilase pankreas ludah dan kemudian menjadi glukosa, maltosa, dan maltotriosa. The maltosa dan maltotriosa, bersama-sama dengan sukrosa, selanjutnya dibagi menjadi gula komponen dan diserap melalui aksi perbatasan sikat sukrase-isomaltase dengan perpecahan laktosa oleh laktase. Glukosa diserap oleh transportasi aktif dan fruktosa dan galaktosa oleh transpor aktif dan difusi difasilitasi. Malabsorpsi karbohidrat Secara tradisional, jumlah karbohidrat yang tersedia untuk fermentasi bakteri kolon telah ditentukan oleh jumlah yang hadir serat dalam makanan. Namun, beberapa "karbohidrat yang tersedia" (yaitu, "tersedia" untuk penyerapan usus kecil: karbohidrat total dikurangi dietary fiber) dalam banyak makanan juga dapat menghindari pencernaan dalam usus kecil dalam jumlah yang cukup dan menjadi tersedia untuk fermentasi oleh mikroflora usus (4 ). Studi awal di ileostomates dilakukan untuk menentukan kerugian karbohidrat dengan berbagai jenis makanan yang bervariasi dalam kandungan karbohidrat serat dan tersedia (5,6). Makananmakanan tertentu telah berhubungan dengan kerugian proporsional lebih besar dari karbohidrat dibandingkan dengan orang lain: khusus lentil dan kacang-kacangan lain, glukan yang mengandung sereal oat bran dan gandum, serta roti pumpernickel, di mana

struktur gandum yang diawetkan (Gambar 1 ) (5,6). Penelitian lain juga menunjukkan bahwa karbohidrat yang tersedia dari makanan bertepung yang tidak sempurna dicerna dan diserap di usus kecil normal (7,8). Sebuah hubungan positif yang signifikan juga ditemukan antara malabsorpsi karbohidrat dan kadar serat makanan (Gambar 2) (6,9). Hal ini menunjukkan bahwa kadar serat diet makanan cenderung untuk menentukan jumlah karbohidrat yang tersedia memasuki usus besar. Tak disangka, hubungan terbalik yang signifikan diamati antara indeks glisemik makanan, sebuah konsep yang dibahas nanti, dan kerugian dalam limbah ileum (Gambar 3) (6). Lihat versi yang lebih besar: Pada halaman ini Dalam jendela baru Download sebagai Slide PowerPoint GAMBAR 1 Persentase karbohidrat kerugian bagi kelompok uji makanan. Roti putih (7 tes); "orang lain" (whole-makan roti, beras setengah matang, beras instan, lama-beras, makaroni, spaghetti, dan roti pumpernickel rye, gandum bulgar, Beras Chex, Jagung Chex, kentang instan); " kacangkacangan "(romano kacang, kacang merah, kacang polong cewek, lentil merah). Selain roti putih, nilai mean untuk tes berulang makanan yang diambil untuk perhitungan tingkat signifikansi [diadaptasi dari Jenkins et al. (6)]. Lihat versi yang lebih besar: Pada halaman ini Dalam jendela baru Download sebagai Slide PowerPoint GAMBAR 2 Kerugian karbohidrat untuk makanan dalam kaitannya dengan kandungan serat per porsi 80-g karbohidrat [diadaptasi dari Jenkins et al. (6)]. Lihat versi yang lebih besar: Pada halaman ini Dalam jendela baru Download sebagai Slide PowerPoint GAMBAR 3 Persentase kehilangan karbohidrat dalam kaitannya dengan GI [diadaptasi dari Jenkins et al. (6)]. Banyak faktor yang dapat mempengaruhi pencernaan karbohidrat di usus kecil, termasuk laju pencernaan (10,11), bentuk makanan (bentuk fisik, ukuran partikel) (12), jenis persiapan (metode memasak dan pengolahan) (12 - 15), jenis pati (amilosa atau amilopektin) (12,16), keberadaan antinutrients seperti -amilase inhibitor (17,18), waktu transit (19), dan jumlah serat, lemak, dan protein (20, 21). Prebiotik, seperti oligofructose dan inulin, merupakan makanan fungsional yang muncul terkait dengan perbaikan yang disarankan dalam kesehatan. Administrasi komponen diet mendorong pertumbuhan bakteri tertentu, terutama bifidobacteria (22) dan LACTOBACILLIUS, yang telah didefinisikan fungsi metabolisme (23). Studi yang melibatkan pasien dengan ileostomi telah menunjukkan bahwa 88% dan 89% dari inulin dan oligofructose, masing-masing, yang ditemukan dalam limbah (24,25). Ini oligosakarida adalah contoh dari karbohidrat yang hampir seluruhnya tidak dicerna dalam usus kecil, karakteristik yang telah menyebabkan penelitian tumbuh di efeknya pada kesehatan kolon dan sistemik.

Konsep indeks glikemik Pandangan klasik bahwa signifikansi metabolisme keseluruhan laju pencernaan karbohidrat (misalnya, darah respon glukosa postprandial) ditentukan oleh panjang rantai (yaitu, "sederhana" vs "kompleks" karbohidrat) telah dipertanyakan. Pertanyaan ini memunculkan konsep indeks glikemik (GI), dan itu menunjukkan bahwa karbohidrat dicerna perlahanlahan, sebagai perpanjangan hipotesis serat makanan pertama kali diusulkan oleh Burkitt dan Trowell (26), mungkin memiliki manfaat metabolik dalam kaitannya dengan diabetes dan pengurangan risiko penyakit jantung koroner (Tabel 1) (27). Sifat dari sumber karbohidrat karena itu mungkin penting, tergantung pada kadar serat. GI adalah klasifikasi kuantitatif makanan karbohidrat berdasarkan tingkat penyerapan karbohidrat seperti tercermin dalam respon glikemik (10,37). Penelitian di bidang GI dan aplikasi klinis telah sangat difasilitasi oleh komprehensif tabel makanan GI (38). Selain itu, konsep beban glikemik (GL) telah dikembangkan untuk menilai dampak glikemik total diet: itu adalah produk dari karbohidrat makanan diet GI dan tersedia (39). Lihat tabel ini: Dalam jendela ini Dalam jendela baru TABEL 1 Kemungkinan efek waktu penyerapan karbohidrat berkepanjangan GI dan penyakit kronis Meningkatnya insiden gangguan metabolisme seperti diabetes dan gangguan terkait telah meningkatkan minat pada intervensi gizi sebagai sarana untuk mengatasi masalah ini berkembang. Akibatnya, ada telah minat baru dalam penggunaan GI dan GL sebagai strategi nutrisi untuk mencegah dan mengelola penyakit kronis. Namun, minat baru juga merangsang kontroversi (12,40). Studi epidemiologis menunjukkan bahwa diet rendah GI mungkin memainkan peran dalam mengurangi risiko PJK, diabetes, dan kanker tertentu. Rendah-GI diet telah diamati secara negatif terkait dengan HDL-C, menunjukkan bahwa diet rendah GI dapat mempertahankan HDL-C (41,42). Dalam Health Study Perempuan, GI adalah positif berhubungan dengan Creactive protein (43), sebuah penanda untuk peradangan sistemik yang dikaitkan dengan peningkatan risiko CVD (44). Banyak studi telah meneliti efek dari diet rendah GI pada faktor-faktor risiko penyakit jantung koroner. Dalam satu studi, plasminogen activator inhibitor-1 (PAI-1) tingkat, penanda gangguan fibrinolisis, berkurang (45), dan di lain hiperlipidemia mengenai, 1 mo pada diet rendah GI mengurangi LDL kolesterol (LDL-C) dan trigliserida (TG) pada mereka dengan tingkat TG yang lebih tinggi, meskipun ada perbedaan signifikan dalam berat badan (46). Sebuah diet rendah GL telah dibandingkan dengan diet rendah lemak selama penurunan berat badan, di mana diet rendah GI menunjukkan perbaikan ditandai faktor risiko penyakit jantung seperti resistensi insulin, TG, C-reaktif protein, dan tekanan darah saat subyek dikonsumsi diet rendah GL (47). Dalam studi yang telah dinilai efeknya pada perkembangan CVD secara langsung, low-GI diet tampaknya memiliki peran protektif. Studi Nurses 'Health menunjukkan hubungan langsung antara infark miokard fatal dan nonfatal dan GI serta GL (48). GI diet telah disarankan untuk menjadi penting lebih besar pada mereka dengan resistensi insulin karena asosiasi diamati dengan GI diet dan mereka dengan indeks massa tubuh> 23 kg/m2. Di sisi lain, tidak ada hubungan yang signifikan dari GI atau GL dan penyakit jantung koroner terlihat dalam studi Zutphen laki-laki yang lebih tua (49), mungkin karena ukuran sampel yang lebih kecil dan demografi, seperti usia, pada awal studi. Beberapa studi telah melihat GI makanan dalam kaitannya dengan pengembangan dan pengelolaan diabetes tipe 2. Sebuah meta-analisis ini rendah-GI diet dibandingkan dengan

diet konvensional atau tinggi-GI dalam pengelolaan diabetes menemukan bahwa protein terglikasi berkurang 7,4% dan HbA1c sebesar 0,43% lebih pada diet rendah-GI dibandingkan pada diet tinggi GI (50). Seperti yang diamati dalam UKPDS, setiap penurunan HbA1c, tidak peduli seberapa kecil, meningkatkan prognosis. Itu mengamati bahwa penurunan 1% dalam HbA1c rata-rata menghasilkan pengurangan 21% dalam setiap endpoint terkait diabetes, 21% pada diabetes-terkait kematian, 14% di infark miokard, dan 37% pada komplikasi mikrovaskuler (51). Studi-studi lain, seperti Studi Nurses 'Health (52) dan Health Study Profesional (39), menemukan hubungan terbalik antara GI dan risiko terkena diabetes. Namun, ini tidak diamati dalam Studi Kesehatan Perempuan Iowa, di mana GI dan GL tidak terkait dengan diabetes tipe 2 (53). Penelitian ini, bagaimanapun, termasuk sebuah kohort tua, yang bisa memperkenalkan bias seleksi. Asosiasi langsung antara GI dan kolorektal dan kanker payudara telah diamati dalam studi epidemiologi (54-56). McKeown-Eyssen (57) dan Giovannucci (58) berada di antara yang pertama untuk berhipotesis hubungan antara hiperinsulinemia dan perkembangan kanker kolorektal dan mungkin jenis kanker lainnya seperti kanker payudara dan prostat (59). Hal ini mungkin berkaitan dengan peningkatan insulin-seperti faktor pertumbuhan dalam hubungannya dengan gaya hidup termasuk asupan energi yang lebih tinggi dan karbohidrat olahan dan asupan lebih rendah dari buah-buahan dan sayuran, namun, data manusia saat ini terbatas. Oleh karena itu, low-GI dan GL-diet menunjukkan menjanjikan untuk pencegahan dan pengobatan penyakit kronis. Mekanisme tindakan Telah dihipotesiskan bahwa efek metabolisme rendah GI makanan berkaitan dengan tingkat di mana karbohidrat diserap dari usus (Gbr. 4). Rendah GI makanan dicirikan oleh laju lebih lambat penyerapan karbohidrat (lambat-release karbohidrat) menghasilkan kenaikan yang lebih rendah kadar glukosa darah. Beberapa efek metabolik yang disebabkan oleh mengurangi tingkat penyerapan telah dikonfirmasi dalam studi pada pria sehat. Sebagai contoh, ketika solusi glukosa menghirup pada tingkat yang lebih lebih dari 180 menit (menghirup) dibandingkan dengan jumlah yang sama glukosa diambil sebagai bolus pada waktu nol (28), ekonomi ditandai sekresi insulin dan menurunkan kadar serum FFA diamati dengan menghirup. Perbaikan serupa juga diamati dengan rendah GI makanan, di mana tingkat penyerapan glukosa lebih lambat mengurangi kenaikan postprandial dalam hormon usus (misalnya, incretins) dan permintaan insulin. Selain itu, penyerapan karbohidrat berkepanjangan dari waktu ke waktu akan menekan sintesis FFA (28,60) dan tanggapan counterregulatory (28,61). Seiring waktu, dengan konsentrasi FFA rendah dan insulinization jaringan berkelanjutan (jaringan metabolisme glukosa sekresi insulin berikut), glukosa ditarik dari peredaran pada tingkat yang lebih cepat. Akibatnya, konsentrasi glukosa darah kembali ke dasar meskipun penyerapan glukosa dari usus terus. Oleh karena itu, penurunan kenaikan di daerah postprandial dan incremental puncak di bawah kurva untuk glukosa darah diamati. Selain itu, ada "makan kedua" efek seperti bahwa glukosa IV tes toleransi menunjukkan serapan lebih cepat glukosa (KG meningkat) setelah menghirup daripada setelah minum bolus (28). Lihat versi yang lebih besar: Pada halaman ini Dalam jendela baru Download sebagai Slide PowerPoint GAMBAR 4 Hipotesis efek makan diet dengan rendah (A) atau tinggi (B) GI pada penyerapan glukosa gastrointestinal dan glukosa darah postprandial [diadaptasi dari Jenkins et al. (27)]. Karbohidrat, ALRP, dan fermentasi kolon

Tahan terhadap pencernaan dan mereka yang melarikan diri penyerapan di usus kecil tersedia untuk fermentasi bakteri kolon mengakibatkan produksi ALRP (asetat, butirat, dan asam propionat) bersama-sama dengan gas (CO2, CH4, dan H2) dan panas (62 Karbohidrat, 63). Butirat telah diduga mengurangi risiko kanker usus besar dan menguntungkan penyakit radang usus (64-66). Secara khusus, peningkatan produksi ALRP telah dikaitkan dengan penurunan pH, yang dapat mengurangi Clostridia patogen potensial, penurunan kelarutan asam empedu, meningkatkan penyerapan mineral (secara tidak langsung), dan penyerapan amonia berkurang oleh disosiasi protonat amonia dan amina lainnya (yaitu, pembentukan + NH4 kurang diffusible dibandingkan dengan NH3 diffusible) (63,67-70). Sumber utama karbohidrat difermentasi adalah pati resisten. Diperkirakan bahwa 5-20% dari pati makanan tidak diserap dalam usus kecil (5-7,71,72). Serat larut dan tidak larut difermentasi untuk berbagai derajat. Namun, serat tidak larut (misalnya, lignan, selulosa, dan beberapa hemiselulosa) yang tahan terhadap fermentasi kolon dapat membawa bersama mereka substrat karbohidrat difermentasi, termasuk pati dan gula, meskipun peran utama mereka dalam tinja bulking. Serat larut (misalnya, pectins, gusi, Lendir, beberapa hemiselulosa, serta inulin tipe fruktan) umumnya lebih lengkap difermentasi dengan sedikit efek dalam meningkatkan massal tinja. Kebanyakan makanan yang mengandung serat mengandung sekitar sepertiga serat tidak larut larut dan dua-pertiga (63). Produksi ALRP ditentukan oleh sejumlah faktor, termasuk jumlah dan jenis hadir mikroflora dalam usus besar (67), jenis substrat (73), dan usus waktu transit (73-75). Secara umum, fecal produksi ALRP adalah dalam rangka asetat> propionat> butirat (62) dengan rasio molar ~ 60:20:20, masing-masing (76). Penyerapan ALRP di sekum dan usus besar adalah proses yang sangat efisien dengan hanya 5-10% yang diekskresikan dalam feses (67,77-79). Dua mekanisme yang diusulkan penyerapan adalah 1) difusi ALRP terprotonasi dan 2) anion exchange (73). Setelah diserap, ALRP dimetabolisme di 3 situs utama dalam tubuh: 1) sel-sel epitel cecocolonic yang menggunakan butirat sebagai substrat utama untuk pemeliharaanyang menghasilkan energi jalur, 2) sel-sel hati yang memetabolisme butirat residual dengan propionat digunakan untuk glukoneogenesis dan 50 -70% asetat juga diambil oleh hati; 3) sel otot menghasilkan energi dari oksidasi asetat sisa (67). Kepentingan utama dalam ALRP telah dalam kaitannya dengan fungsi kolon sebagai akibat dari penyerapan dan metabolisme oleh colonocytes, khususnya butirat, meskipun ALRP juga substrat metabolik untuk jaringan lain dari tuan rumah. ALRP dan penyakit kronis CVD. Asetat dan propionat telah diusulkan telah menentang efek di hiperlipidemia, merupakan faktor risiko untuk penyakit jantung koroner. Subjek diberi infus dubur asetat dan propionat dalam rasio setara menunjukkan peningkatan dosis-tergantung dalam kolesterol total serum dan tingkat TG, memberikan bukti langsung bahwa ALRP yang digunakan untuk sintesis lipid (80). Dalam sebuah studi berikutnya oleh kelompok riset yang sama, infus dubur dari campuran asetat dan propionat dilemahkan peningkatan kolesterol serum diamati ketika infus asetat diberikan saja. Namun, infus dubur dari propionat saja tidak mempengaruhi lipid atau TG pada pria muda dan wanita sehat (81). Hasil ini mendukung gagasan bahwa propionat menghambat pemanfaatan acetate untuk sintesis kolesterol. Namun, uji makanan telah tidak konsisten. Satu minggu konsumsi dari 2,7 g natrium propionat diberikan dalam roti (82) dan 7,5 g natrium propionat diambil sebagai kapsul (83) tidak mempengaruhi lipid serum, meskipun satu studi menunjukkan bahwa 5,4 g propionat diberikan setiap hari selama 2 minggu menurunkan LDL -C dan kolesterol total pada subyek dengan kolesterol total> 5,5 mmol / L (84). Penelitian terhadap hewan menunjukkan propionat yang menghambat sintesis kolesterol dengan menghambat baik sintase 3-hidroksil-3-methylglutaryl-CoA dan 3hidroksi-3-methylglutaryl-CoA reduktase (85,86).

Inulin tipe fruktan yang bifidogenic dan telah dikaitkan dengan efek hipolipidemik. Meskipun sejumlah mekanisme telah diusulkan, peningkatan produksi propionat, mengakibatkan penurunan asetat: rasio propionat, telah menjadi salah satu mode menyarankan tindakan. Peningkatan produksi propionat, melalui fermentasi, dapat menghambat sintesis kolesterol (85,87-91). Hal ini telah didukung dalam studi dengan hewan percobaan hiperlipidemia (87,92), tetapi tidak didukung dalam studi hewan lainnya (93-95). Pengaruh inulin tipe fruktan pada lipid darah pada manusia telah menghasilkan hasil yang tidak konsisten (96) dibandingkan dengan data hewan, hal ini mungkin berkaitan dengan perbedaan spesies. Selain itu, beberapa studi telah dihitung sintesis ALRP, khususnya asetat dan propionat, dengan menggunakan prebiotik. Kurangnya kesepakatan mengenai hubungan antara fermentasi kolon meningkat dan metabolisme lipid mungkin akibat dari perbedaan dalam komposisi kimia dari sumber substrat. Studi dengan pati resisten telah konsisten dalam menunjukkan butirat tinja dibangkitkan (97-100). Fermentasi Pati terutama menghasilkan asetat dan butirat, sedangkan fermentasi pektin dan xilan asetat hasil sendiri sebagai produk utama (101). Studi terbaru menemukan bahwa manusia konsumsi akut dari monosakarida nondigestible, l-rhamnosa (25 g), meningkat propionat serum tanpa asetat meningkat (102), tapi lagi-studi jangka belum menunjukkan lipid serum berkurang (103). Laktulosa, serat makanan cepat difermentasi, telah terbukti menghasilkan lebih tinggi kadar kolesterol serum, mungkin sebagai akibat dari peningkatan produksi dan penyerapan asetat kolon mengakibatkan lipogenesis hepatik meningkat (104). Oligofructose dan inulin, yang sama dengan fermentasi karbohidrat lainnya, dapat meningkatkan toleransi glukosa melalui penekanan konsentrasi serum FFA (105). Telah menunjukkan bahwa rantai pendek asam organik, termasuk -hidroksibutirat, asetat, dan propionat, dapat menekan pelepasan FFA dan mungkin merangsang sekresi insulin meningkat (80,81,106). Kanker usus besar. Butirat adalah bahan bakar yang disukai sel-sel epitel kolon tetapi juga memainkan peran utama dalam regulasi proliferasi sel dan diferensiasi (62,64,67,107). Glukosa mudah diserap ke dalam darah dan, oleh karena itu, bukan merupakan sumber utama energi untuk enterosit (yaitu, sangat sedikit tersedia untuk colonocytes). Hingga 70-90% dari butirat dimetabolisme oleh colonocytes. Akibatnya, sebagian besar glukosa diserap akan diteruskan ke darah. In vitro dan in vivo telah mengamati bahwa butirat memiliki peran yang berlawanan, sehingga dalam "paradoks butirat" (108.109). Butirat dirangsang proliferasi sel di colonocytes normal (64.107), tetapi menekan proliferasi sel adenokarsinoma kolon (110). Ini inkonsistensi antara in vitro dan in vivo mungkin berhubungan dengan waktu administrasi butirat, sumber butirat (yaitu, serat diet yang berbeda), dan interaksi dengan lemak makanan (109). Butirat juga merangsang imunogenisitas sel-sel kanker (111). Asetat dan propionat telah ditunjukkan untuk menginduksi apoptosis pada sel tumor kolorektal baris, tetapi pada tingkat yang jauh lebih kecil daripada butirat (112.113). Saat ini, mekanisme aksi butirat dalam kaitannya dengan kanker usus besar tidak jelas. Butirat telah terbukti dapat menghambat proliferasi sel dengan menginduksi p21WAFI/Cip1 protein dan tingkat mRNA (114-116), yang dapat memblokir siklus sel di G1. Penyumbatan ini memungkinkan DNA pos-dimediasi perbaikan ketidakstabilan genomik atau mutasi (108). Melalui penghambatan deacetylase histone, apoptosis telah terbukti disebabkan oleh butirat melalui hyperacetylation histon (H3 dan H4) (117). Akibatnya, DNA berada dalam bentuk yang lebih terbuka (118), yang akan ideal jika kerusakan DNA telah terjadi dan enzim perbaikan yang diperlukan untuk mendekati DNA yang rusak. Di sisi lain, dengan adanya karsinogen, bentuk terbuka dari DNA dapat membuatnya lebih rentan terhadap mutasi (109). Butirat juga dapat menginduksi diferensiasi colonocytes neoplastik in vitro, menghasilkan

fenotipe yang terkait dengan sel matang yang normal (119). Akumulasi ALRP di usus besar menyebabkan penurunan pH, yang menurunkan kelarutan asam empedu bebas dan pada gilirannya menurunkan produksi asam empedu sekunder, yang memiliki aktivitas promotor potensi tumor (120). Hal ini mungkin terkait dengan penghambatan enzim bakteri kolon 7dehydroxylase, yang menurunkan asam empedu utama untuk asam empedu sekunder (121). Pengasaman kolon meningkat juga meningkatkan ketersediaan kalsium untuk mengikat asam empedu bebas dan asam lemak, membuat mereka tidak larut (122). Pengaruh inulin tipe fruktan pada risiko kanker dibahas dalam artikel lain dari Tambahan ini. Radang usus. Enema ALRP telah dicoba sebagai pengobatan mungkin untuk pengalihan dan kolitis ulserativa. Roediger menunjukkan bahwa colonocytes individu dengan kolitis ulseratif aktif dan diam telah mengurangi oksidasi butirat dibandingkan dengan kontrol (123). Ia telah mengemukakan bahwa peradangan usus muncul sebagai akibat dari kurangnya luminal SCFA (yaitu, keadaan kekurangan gizi) dari epitel kolon dan blok pada penerimaan atau oksidasi ALRP oleh colonocytes (124.125). Yang terakhir ini mungkin terkait dengan penurunan koenzim A, persyaratan untuk oksidasi ALRP (123), dari produksi yang mengandung sulfur senyawa oleh mikroflora usus. Namun, blok penyerapan dan oksidasi dapat diatasi dengan menaikkan ALRP lebih tinggi-dari normal konsentrasi dalam lumen usus (125). The memasok nutrisi, baik oleh reanastomosis bedah atau irigasi ALRP, dapat memperbaiki kekurangan ini. Studi enema ALRP mengandung 60 mmol / L asetat natrium, 30 mmol / L natrium propionat, dan 40 mmol / L natrium n-butirat ke 5 pasien dengan kolitis pengalihan untuk jangka waktu 2-6 minggu mengakibatkan hilangnya gejala dan inflamasi perubahan yang diamati oleh temuan endoskopi dan histologi (126). Namun, sebuah penelitian menggunakan solusi ALRP sama enema pada 13 pasien dengan kolitis pengalihan mengakibatkan tidak ada perubahan endoskopi atau histologis setelah 2 minggu (127). Perlakuan kolitis ulserativa distal dengan irigasi ALRP telah menghasilkan hasil yang tidak konsisten (128), beberapa studi menunjukkan itu menjadi pengobatan yang efektif (129-131) dan lain-lain tidak (131.132). Inkonsistensi ini mungkin terkait dengan jenis ALRP digunakan (campuran atau butirat saja), konsentrasi ALRP, frekuensi pemberian, dan durasi pengobatan. Oleh karena itu, penggunaan irigasi ALRP untuk pengobatan peradangan usus telah ditempuh lebih lanjut karena penelitian sampai saat ini tidak meyakinkan. Efek dari inulin tipe fruktan pada penyakit radang usus dibahas dalam artikel lain dalam seri ini. Pada saat di mana meningkatnya beban penyakit kronis telah menjadi masalah kesehatan utama di seluruh dunia terkait dengan penuaan populasi dan perubahan pola makan dan gaya hidup, tertunda atau karbohidrat diserap perlahan-lahan sebagai bagian dari strategi gizi mungkin memainkan peran yang berguna. Penelitian lebih lanjut diperlukan untuk menentukan manfaat kemungkinan rendah GI diet, termasuk inulin tipe fruktan sebagai komponen rendah GI diet, dalam jangka panjang uji coba terkontrol secara acak. Data produksi ALRP meningkat dan manfaat kesehatan mereka bahkan lebih terbatas. Oleh karena itu, meskipun ada persyaratan untuk studi mekanistik dasar, yang paling penting, uji klinis harus dilakukan untuk menentukan relevansi klinis diet-induced perubahan dalam produksi ALRP. Sebelumnya Bagian Bagian Catatan kaki 1 Diterbitkan dalam suplemen untuk The Journal of Nutrition. Dipresentasikan pada konferensi "5th ORAFTI Penelitian Konferensi: Inulin dan Oligofructose: Manfaat Kesehatan Terbukti dan Klaim" diadakan di Harvard Medical School, Boston, MA, September 28-29 2006. Konferensi ini diselenggarakan dan disponsori oleh ORAFTI, Belgia. Editor tamu untuk publikasi suplemen adalah Marcel Roberfroid, Catholique University of Louvain, Brussels, Belgia dan Randal Buddington, Mississippi State University, USA. Guest Editor

pengungkapan: M. Roberfroid dan R. Buddington, dukungan untuk perjalanan ke konferensi yang disediakan oleh ORAFTI. pengungkapan Penulis 2: JMW Wong, tidak ada konflik kepentingan, dan DJA Jenkins, Penelitian hibah dan Dewan Penasehat Ilmiah, Orafti, honorarium dari makanan dan industri farmasi. Sebelumnya Bagian Undo edits New! Click the words above to edit and view alternate translations. Dismiss Google Translate for Business:Translator ToolkitWebsite TranslatorGlobal Market Finder