• 1
    Hopkins MJ, Cummings JH, Macfarlane GT. Inter-species differences in maximum specific growth rates and cell yields of bifidobacteria cultured on oligosaccharides and other simple carbohydrate sources. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. J Appl Microbiol 1998; 85: 3816..
  • 2
    Gaby AR. Adverse effects of dietary fructose. Altern Med Rev 2005; 10: 294306.
  • 3
    Park YK, Yetley EA. Intakes and food sources of fructose in the United States. Am J Clin Nutr 1993; 58 (Suppl.): 737S47S.
  • 4
    Nicklas TA, Webber LS, Srinivasan SR, Barenson G. Secular trends in dietary intakes and cardiovascular risk factors of 10-y-old children: the Bogalusa Heart Study (1973–1983). Am J Clin Nutr 1993; 57: 9307.
  • 5
    Gibney M, Sigman-Grant M, Stanton JL, Keast DR. Consumption of sugars. Am J Clin Nutr 1995; 62 (Suppl.): 178S93S.
  • 6
    Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004; 79: 53743.
  • 7
    Virtanen SM, Rasanen L, Maenpaa J, Akerblom HK. Dietary survey of Finnish adolescents and non-diabetic controls. Acta Paediatr Scand 1987; 76: 8018.
  • 8
    Beyer PL, Caviar EM, McCallum RW. Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults. J Am Diet Assoc 2005; 105: 155966.
  • 9
    Van Nieuwenhoven MA, Brouns F, Kovacs EMR. The effect of two sports drinks and water on GI complaints and performance during an 18-km run. Int J Sports Med 2005; 26: 2815.
  • 10
    Mitsui T, Shimaoka K, Kanao Y, Kondo T. Colonic fermentation after ingestion of fructose-containing sports drink. J Sports Med Phys Fitness 2001; 41: 1213.
  • 11
    Campbell JM, Bauer LL, Fahey GC, Hogarth AJCL, Wolf BW, Hunter DE. Selected fructooligosaccharide (1-kestose, nystose, and 1F-β-fructofuranosylnystose) composition of foods and feeds. J Agric Food Chem 1997; 45: 307682.
  • 12
    Roberfroid MB, Delzenne NM. Dietary fructans. Annu Rev Nutr 1998; 18: 11743.
  • 13
    Van Loo J, Coussement P, De Leenheer L, Hoebregs H, Smits G. On the presence of inulin and oligofructose as natural ingredients in the western diet. Crit Rev Food Sci Nutr 1995; 35: 52552.
  • 14
    Moshfegh AJ, Friday JE, Goldman JP, Ahuja JK. Presence of inulin and oligofructose in the diets of Americans. J Nutr 1999; 129: 1407S11S.
  • 15
    Nielsen SM, Siega-Riz AM, Popkin BM. Trends in energy intake in U.S. between 1977 and 1996: similar shifts seen across age groups. Obesity Res 2002; 10: 3708.
  • 16
    Popkin BM, Nielsen SM. The sweetening of the world's diet. Obesity Res 2003; 11: 132532.
  • 17
    Kennedy ET, Shanthy SA, Powell R. Dietary-fat intake in the US population. J Am Coll Nutr 1999; 18: 20712.
  • 18
    Alexy U, Sichert-Hellert W, Kersting M. Fifteen-year time trends in energy and macronutrient intake in German children and adolescents: results of the DONALD study. Br J Nutr 2002; 87: 595604.
  • 19
    Osler M, Heitmann BL, Schroll M. Ten year trends in the dietary habits of Danish men and women. Cohort and cross-sectional data. Eur J Clin Nutr 1997; 51: 53541.
  • 20
    Wong D. Hereditary fructose intolerance. Mol Genet Metab 2005; 85: 1657.
  • 21
    Gibson PR, Shepherd SJ. Personal view: Food for thought – western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis. Aliment Pharmacol Ther 2005; 21: 1399409.
  • 22
    Ferraris RP. Dietary and developmental regulation of intestinal sugar transport. Biochem J 2001; 360: 2656.
  • 23
    Pessin JE, Bell GI. Mammalian facilitative glucose transporter family: structure and molecular regulation. Annu Rev Physiol 1992; 54: 91130.
  • 24
    Jiang L, David ES, Espina N, Ferraris RP. GLUT-5 expression in neonatal rats: crypt-villus location and age-dependent regulation. Am J Physiol 2001; 281: G66674.
  • 25
    Thorens B, Cheng ZQ, Brown D, Lodish HF. Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am J Physiol 1990; 259: C27985.
  • 26
    Kellett GL, Brot-Laroche E. Apical GLUT2. A major pathway of intestinal sugar absorption. Diabetes 2005; 54: 305662.
  • 27
    Helliwell PA, Richardson M, Affleck J, Kellett GL. Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the extracellular signal-regulated kinase, p38 mitogen-activated kinase and phosphatidylinositol 3-kinase intracellular signalling pathways: implications for adaptation to diabetes. Biochem J 2000; 250: 1639.
  • 28
    Helliwell PA, Richardson M, Aflleck J, Kellett GL. Stimulation of fructose transport across the intestinal brush-border membrane by PMA is mediated by GLUT2 and dynamically regulated by protein kinase C. Biochem J 2000; 350: 14954.
  • 29
    Madara JL, Pappenheimer JR. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol 1987; 100: 14964.
  • 30
    Truswell AS, Seach JM, Thorburn AW. Incomplete absorption of pure fructose in healthy subjects and the facilitating effect of glucose. Am J Clin Nutr 1988; 48: 142430.
  • 31
    Cheeseman CI. Intestinal hexose absorption: transcellular or paracellular fluxes. J Physiol 2002; 544: 336.
  • 32
    Wasserman D, Hoekstra H, Tolla V, et al. Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption. J Clin Invest 1996; 98: 2398402.
  • 33
    Castello A, Guma A, Sevilla L, et al. Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes. Biochem J 1995; 309: 2717.
  • 34
    Kishi K, Tanaka T, Igawa M, Takase S, Goda T. Sucrase-isomaltase and hexose transporter gene expressions are coordinately enhanced by dietary fructose in rat jejunum. J Nutr 1999; 129: 9536.
  • 35
    Hoekstra JH, Van Den Aker JH. Facilitating effect of amino acids on fructose and sorbitol absorption in children. J Pediatr Gastroenterol Nutr 1996; 23: 11824.
  • 36
    Thiesen A, Wild GE, Keelan M, Clandinin MT, Thomson AB. Locally and systemically active glucocorticosteroids modify intestinal absorption of sugars in rats. J Appl Physiol 2003; 94: 58390.
  • 37
    Garcia-Herrera J, Navarro MA, Marca MC, De La Osada J, Rodriguez-Yoldi MJ. The effect of tumor necrosis factor-alpha on D-fructose intestinal transport in rabbits. Cytokine 2004; 25: 2130.
  • 38
    Gudmand-Hoyer E, Skovbjerg H. Disaccharide digestion and maldigestion. Scand J Gastroenterol Suppl 1996; 216: 11121.
  • 39
    Molis C, Flourie B, Ouarne F, et al. Digestion, excretion and energy value of fructooligosaccharides in healthy humans. Am J Clin Nutr 1996; 64: 3248.
  • 40
    Bach Knudsen KE, Hessov IB. Recovery of inulin from Jerusalem artichoke (Helianthus tuberosus L.) in the small intestine of man. Br J Nutr 1995; 74: 10113.
  • 41
    Ellegård L, Andersson H, Bosaeus I. Inulin and oligofructose do not influence the absorption of cholesterol, or the excretion of cholesterol, Ca, Mg, Zn, Fe, or bile acids but increase energy excretion in ileostomy subjects. Eur J Clin Nutr 1997; 51: 15.
  • 42
    Rumessen JJ. Fructose and related food carbohydrates. Sources, intake, absorption and clinical implications. Scand J Gastroenterol 1992; 27: 81928.
  • 43
    Stone-Dorshow T, Levitt MD. Gaseous response to ingestion of poorly absorbed fructo-oligosaccharides sweetener. Am J Clin Nutr 1987; 46: 615.
  • 44
    Rumessen JJ, Gudmand-Hoyer E. Fructans of chicory: intestinal transport and fermentation of different chain lengths and relation to fructose and sorbitol malabsorption. Am J Clin Nutr 1998; 68: 35764.
  • 45
    Madsen JL, Linnet J, Rumessen JJ. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers. Dig Dis Sci 2006; 51: 14753.
  • 46
    Cherbut C, Aube AC, Blottiere HM, Galmiche JP. Effects of short-chain fatty acids on gastrointestinal motility. Scand J Gastroenterol 1997; 222 (Suppl.): 5861.
  • 47
    Ropert A, Cherbut C, Roze C, et al. Colonic fermentation and proximal gastric tone in humans. Gastroenterology 1996; 111: 28996.
  • 48
    Fukumoto S, Tatewaki M, Yamada T, et al. Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 2003; 284: R126976.
  • 49
    Abrams SA, Griffin IJ, Hawthorne KM, et al. A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 2005; 82: 4716.
  • 50
    Davidson MH, Maki KC. Effects of dietary inulin on serum lipids. J Nutr 1999; 129 (Suppl.): 1474S7S.
  • 51
    Greene SA, Dalton RN, Turner C, Haycock GB, Chantler C. Hyperglycemia with and without glycosuria: effect on inulin and para-amino hippurate clearance. Kidney Int 1987; 32: 8969.
  • 52
    Reddy BS, Hamid R, Rao CV. Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 1997; 18: 13714.
  • 53
    Lindsay JO, Whelan K, Stagg AJ, et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut 2006; 55: 34855.
  • 54
    Rozen R, Bachrach G, Bronshteyn M, Gedalia I, Steinberg D. The role of fructans on dental biofilm formation by Streptococcus sobrinus, Streptococcus mutans, Streptococcus gordinii and Actinomyces viscosus. FEMS Microbiol Lett 2001; 195: 20510.
  • 55
    Kleesen B, Hartmann L, Blaut M. Fructans in the diet cause alterations of intestinal mucosal architecture, released mucins and mucosa-associated bifidobacteria in gnotobiotic rats. Br J Nutr 2003; 89: 597606.
  • 56
    Langlands SJ, Hopkins MJ, Coleman N, Cummings JH. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut 2004; 53: 16106.
  • 57
    Bovee-Oudenhoven IMJ, Ten Bruggencate SJM, Lettink-Wissink MLG, et al. Dietary fructo-oligosaccharides and lactulose inhibit intestinal colonisation but stimulate translocation in rats. Gut 2003; 52: 15728.
  • 58
    Lu Z-X, Gibson PR, Muir JG, et al. Arabinoxylan fiber from a by-product of wheat flour processing behaves physiologically like a soluble, fermentable fiber in the large bowel of rats. J Nutr 2000; 130: 198490.
  • 59
    Hughes R, Rowland IR. Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon. Carcinogenesis 2001; 22: 437.
  • 60
    Gibson PR. Apoptosis or necrosis – colonic epithelial cell survival. In: JewellDP, ed. Inflammatory Bowel Disease – Crossroads of Microbes, Epithelium and Immune Systems. Chichester: Wiley, 2004: 13350.
  • 61
    Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Katan MB, Van Der Meer R. Dietary fructooligosaccharides affect intestinal barrier function in healthy men. J Nutr 2006; 136: 704.
  • 62
    Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000; 95: 35036.
    Direct Link:
  • 63
    Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2003; 98: 4129.
  • 64
    Pimentel M, Constantino T, Kong Y, Bajwa M, Rezaei A, Park S. A 14-day elemental diet is highly effective in normalizing the lactulose breath test. Dig Dis Sci 2004; 49: 737.
  • 65
    Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin. Minerva Gastroenterol Dietol 2006; 52: 8995.
  • 66
    Nucera G, Gabrielli M, Lupascu A, et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2005; 21: 13915.
  • 67
    Piche T, Des Varannes SB, Sacher-Huvelin S, et al. Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology 2003; 124: 894902.
  • 68
    Ledochowski M, Widner B, Sperner-Unterweger B, et al. Carbohydrate malabsorption syndromes and early signs of mental depression in females. Dig Dis Sci 2000; 45: 12559.
  • 69
    Ledochowski M, Widner B, Bair H, et al. Fructose- and sorbitol-reduced diet improves mood and gastrointestinal disturbances in fructose malabsorbers. Scand J Gastroenterol 2000; 35: 104852.
  • 70
    Ledochowski M, Widner B, Murr C, et al. Fructose malabsorption is associated with decreased plasma tryptophan. Scand J Gastroenterol 2001; 36: 36771.
  • 71
    Andersson DE, Nygren A. Four cases of long-standing diarrhoea and colic pains cured by fructose-free diet – a pathogenetic discussion. Acta Med Scand 1978; 203: 8792.
  • 72
    Cummings JH, Macfarlane GT. Gastrointestinal effects of prebiotics. Br J Nutr 2002; 87 (Suppl. 2): S14551.
  • 73
    Shepherd SJ, Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc 2006; 106: 16319.
  • 74
    Romagnuolo JM, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterological practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 2002; 97: 111326.
    Direct Link:
  • 75
    Simren M, Stotzer P-O. Use and abuse of hydrogen breath tests. Gut 2006; 55: 297303.
  • 76
    Karcher RE, Truding RM, Stawick LE. Using a cutoff of <10 ppm for breath hydrogen testing: a review of five years’ experience. Ann Clin Lab Sci 1999; 29: 18.
  • 77
    Hoekstra JH, Van Kempen AA, Bijl SB, Kneepkens CM. Fructose breath hydrogen tests. Arch Dis Child 1993; 68: 1368.
  • 78
    Kneepkens CM, Vonk RJ, Fernandes J. Incomplete intestinal absorption of fructose. Arch Dis Child 1984; 59: 7358.
  • 79
    Fernandez-Banares F, Esteve-Pardo M, De Leon R, et al. Sugar malabsorption in functional bowel disease: clinical implications. Am J Gastroenterol 1993; 88: 204450.
  • 80
    Symons P, Jones MP, Kellow JE. Symptom provocation in irritable bowel syndrome. Effects of differing doses of fructose-sorbitol. Scand J Gastroenterol 1992; 27: 9404.
  • 81
    Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology 1990; 99: 101620.
  • 82
    Rumessen JJ, Gudmand-Hoyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 1988; 95: 694700.
  • 83
    Rumessen JJ, Gudmand-Hoyer E. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut 1986; 27: 11618.
  • 84
    Mishkin D, Sablauskas L, Yalovsky M, Mishkin S. Fructose and sorbitol malabsorption in ambulatory patients with functional dyspepsia: comparison with lactose maldigestion/malabsorption. Dig Dis Sci 1997; 42: 25918.
  • 85
    Beaugerie L, Flourie B, Pernet P, Achour L, Franchisseur C, Rambaud JC. Glucose does not facilitate the absorption of sorbitol perfused in situ in the human small intestine. J Nutr 1997; 127: 3414.
  • 86
    Teuri U, Vapaatalo H, Korpela R. Fructooligosaccharides and lactulose cause more symptoms in lactose maldigesters and subjects with pseudohypolactasia than in control lactose digesters. Am J Clin Nutr 1999; 69: 9739.
  • 87
    Johlin FC Jr, Panther M, Kraft N. Dietary fructose intolerance: diet modification can impact self-rated health and symptom control. Nutr Clin Care 2004; 7: 924.
  • 88
    Fernandez-Banares F, Rosinach M, Esteve M, Forne M, Espinos JC, Viver JM. Sugar malabsorption in functional abdominal bloating: a pilot study on the long-term effect of dietary treatment. Clin Nutr 2006; 25: 82431.
  • 89
    Goldstein R, Braverman D, Stankiewicz H. Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints. Isr Med Assoc J 2000; 2: 5837.
  • 90
    Shepherd S, Willett I, Fone D, Gibson PR. The value of the ‘fructose malabsorption’ (FM) diet and the fructose breath hydrogen test in patients with irritable bowel syndrome (IBS). J Gastroenterol Hepatol 2003; 18 (Suppl.): B43.
  • 91
    Nathan DM, Shepherd SJ, Berryman M, Muir JG, Iser JH, Gibson PR. Fructose malabsorption in Crohn's disease: a common contributor to symptoms that benefit from dietary modification. J Gastroenterol Hepatol 2005; 20: A27.
  • 92
    Croagh C, Shepherd S, Berryman M, Gibson PR. Dietary manipulation for patients with a J-pouch or ilieorectal anastomosis (IRA): a pilot study. J Gastroenterol Hepatol 2005; 20 (Suppl.): A43.
  • 93
    Krauss N, Schuppan D. Monitoring nonresponsive patients who have celiac disease. Gastrointest Endosc Clin N Am 2006; 16: 31727.
  • 94
    Roberfroid MB. Introducing inulin-type fructans. Br J Nutr 2005; 93 (Suppl. 1): S1325.
  • 95
    Gouyon F, Caillaud L, Carriere V, et al. Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice. J Physiol 2003; 552: 82332.
  • 96
    Dyer J, Wood IS, Palejwala A, Ellis A, Shirazi-Beechey SP. Expression of monosaccharide transporters in intestine of diabetic humans. Am J Physiol 2002; 282: G2418.
  • 97
    Walker J, Jijon HB, Diaz H, Salehi P, Churchill T, Madsen KL. 5-Aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK. Biochem J 2005; 385: 48591.
  • 98
    Marks J, Carvou NJ, Debnam ES, Srai SK, Unwin RJ. Diabetes increases facilitative glucose uptake and GLUT2 expression at the rat proximal tubule brush border membrane. J Physiol 2003; 553: 13745.
  • 99
    Au A, Gupta A, Schembri P, Cheeseman CI. Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2. Biochem J 2002; 367: 24754.
  • 100
    Shepherd EJ, Helliwell PA, Mace OJ, Morgan EL, Patel N, Kellett GL. Stress and glucocorticoid inhibit apical GLUT2-trafficking and intestinal glucose absorption in rat small intestine. J Physiol 2004; 560: 28190.
  • 101
    Ravich WJ, Bayless TM, Thomas M. Fructose: incomplete intestinal absorption in humans. Gastroenterology 1983; 84: 269.
  • 102
    Born P, Zech J, Lehn H, Classen M, Lorenz R. Colonic bacterial activity determines the symptoms in people with fructose-malabsorption. Hepatogastroenterology 1995; 42: 77885.
  • 103
    Ladas SD, Grammenos I, Tassios PS, Raptis SA. Coincidental malabsorption of lactose, fructose, and sorbitol ingested at low doses is not common in normal adults. Dig Dis Sci 2000; 45: 235762.
  • 104
    Choi YK, Johlin FC Jr, Summers RW, Jackson M, Rao SS. Fructose intolerance: an under-recognized problem. Am J Gastroenterol 2003; 98: 134853.
    Direct Link:
  • 105
    Hyams JS. Sorbitol intolerance: an unappreciated cause of functional gastrointestinal complaints. Gastroenterology 1983; 84: 303.