Effect of Fructose on Colonic Microflora
Condition: Healthy
Study type: Interventional

Summary: 
      Fructose is the principal carbohydrate in fruits and is added to many food products. This 6
      carbon sugar is associated with a number of ill effects, like promotion of high
      triglycerides,precipitation of gout in men,possible depression in women and symptoms of
      intolerance in a non ethnic dose dependent fashion.However, high fruit and vegetable intake
      is associated with some epidemiologic evidence in prevention of some cancers like stomach and
      colorectum.The principal protectors in these products are thought to be antioxidants and
      other protective chemicals like polyphenols.In addition long chain polymers of
      fructose:inulin are thought to help protect against cancer through prebiotic effects. In fact
      poly-fructose molecules are used as prebiotic food supplements and are promoted as aids for a
      healthy intestine with "balanced microflora".

      Polyfructose prebiotics induce some gastrointestinal symptoms of cramps gas bloating and
      sometimes diarrhea.To date repeated consumption of these polyfructose molecules have not been
      shown to induce colonic adaptation. Nor is there evidence that fructose intolerant people
      "adapt " to prolonged ingestion.

      These findings are in contrast to findings with lactose intolerance where prolonged ingestion
      leads to both symptomatic and physiological adaptation.In this interventional study we
      evaluate whether fructose intolerant people can adapt to moderate dose daily fructose
      ingestion.The desired outcome is symptomatic, physiological and colonic microfloral
      adaptation. A failure to detect an increase in bifidobacteria on retesting may suggest that
      in humans like in some other mammals GLUT5 fructose transport could be induced.
    

Detailed description: 
      The concept of Colonic Adaptation(CA) to regular carbohydrates has been linked mainly to
      lactose disaccharide(galactose,glucose) and lactulose(galactose, fructose), a manufactured
      derivative of lactose. CA is achieved in both cases by short term regular consumption of the
      targeted sugar which is not digested by the host. The clinical definition of CA includes a
      measured change in breath hydrogen, reduction of clinical symptoms (Bloat, gas, cramps and at
      times diarrhea) and an associated increase of bacterial lactase(β-galactosidase. The putative
      mechanism is through bacterial action which results in enhanced metabolism or expanded
      bacterial population of specific genus and species of bacteria. The act of CA may incur
      health benefits through physicochemical changes and especially promotion of health promoting
      bacteria.

      Maldigestion of fructose occurs in the population probably in a dose dependent fashion. The
      sugar content overwhelms the principal GLUT5 intestinal carrier. In the presence of glucose
      this non energy dependent system works better(11). In a previous publication we found that
      the pre test graded ingestion of fructose had no impact on test results. These results were
      dramatically different from that found for pretest lactose ingestion. The investigators
      interpreted the results from the fructose study as being consistent with a failure to show CA
      to regular fructose consumption.

      More recently Rao et al however, showed that there may be a threshold level of intake beyond
      which fructose maldigestion may rapidly increase. This value was thought to be 15-20g. In the
      case of lactose this was 10g(15). Since in both our studies we used the same dose response
      analysis(<10,11-19, and >20g/d), it is possible that fructose consuming individuals might not
      have spilt adequate quantities of fructose into the colon to properly induce and maintain CA.
      Moreover, there is to our knowledge no information on a possible prebiotic effect of the
      monosaccharide fructose. Since polymers of fructose are very good prebiotics it may be of
      interest to determine whether this sugar is capable of prebiotic function in its own right.

      The investigators propose to carry out a short term study on 20-30 healthy participants to
      determine whether a 2 week period of fructose consumption alters clinical CA and intestinal
      microflora.

      Study Outline After an overnight fast, except for water(ad libitum), participants present
      themselves to the GI lab around 9 am. A 50 gm fructose solution (this dose is associated with
      a 65% chance of maldigestion(14))will be administered. Breath hydrogen and symptoms will be
      recorded for 4.5 Hrs at ½ hr intervals. Participants will be asked to fill out a short 3 day
      diet recall questionnaire targeting fructose ingestion.

      Participants will be asked to consume 30g fructose in 150ml of water (lemon juice may be
      added) twice a day for 14 days.They will then return for a repeat50 g fructose challenge. A
      small stool sample will be asked from participants at each test period.Another similar group
      will undergo the same tests but without taking intervening fructose.
    

Intervention name(s): Fructose powder
Intervention type(s): Dietary Supplement
Intervention description(s): 30g in 250ml water twice a day
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Fructose; Intolerance; Adaptation; Prebiotic; Healthy men or women 18-40