Cellodextrin Tolerability Study
Condition: Obesity
Study type: Interventional

Summary: 
      This is an initial pilot study to assess and investigate if any adverse symptoms occur (and
      also the severity of any symptoms) after consuming a food-grade Cellodextrin preparation.
      Volunteers will attend a short (around 30mins) medical screening visit, to make sure they are
      suitable to take part in the study. They will then attend 4 study visits (separated by at
      least a week) for around 9.5 hours each time. During the study visits 10, 20, 30, or 50g of
      Cellodextrin will be given as a single oral dose, in a milkshake drink, and any symptoms
      experienced will then be monitored via questionnaires during the study day and for the next
      60 hrs, dietary intake will also be measured over this time.
    

Detailed description: 
      Cellodextrins are small-chain, non-absorbable, oligosaccharides that are produced from the
      incomplete hydrolysis of insoluble cellulose. Like other oligosaccharides they escape
      digestion in the small intestine as the human gut lacks the enzymes required to hydrolyse the
      β-links formed among the units of monosaccharides. However, Bifidobacterium in the
      caeco-colon possess the enzymes β-fructosidase and β-galactosidase which are needed to
      breakdown the carbohydrate chains to their constituent sugars, this serves the bacteria by
      providing energy for proliferation and also produces gases (Hydrogen, Carbon dioxide, and
      Methane, which are metabolically useless to the host), and short chain fatty acids (SCFA).
      This breakdown supplies an available energy estimated to be 1.5-2kcal/g, in comparison
      digestible carbohydrate produces 4kcal/g of available energy.

      The prevalence of overweight and obesity is an increasing issue in the developed world and
      reduction of energy intake remains at the heart of the main treatments for obesity. Due to
      this there is an interest in identifying food ingredients that will combat dietary
      overconsumption. By replacing some of the digestible carbohydrates with non-digestible
      oligosaccharides it could be possible to reduce the caloric load of food by approximately
      2kcal/g of carbohydrate, but still keep the taste and 'mouth-feel' of these reduced calorie
      products. Further benefits of the use of non-digestible oligosaccharides against dietary
      overconsumption include the contribution that these compounds could have on reducing appetite
      and voluntary food intake, which could further improve energy intake regulation.
      Oligosaccharides may increase satiety by bulking, by slowing gastric emptying, or by
      increasing production of Peptide-yy (PYY) and Glucagon like peptide-1 (GLP-1). The latter has
      been demonstrated in-vitro, where butyrate, one of the SCFA's produced in oligosaccharide
      break-down, increased PYY and Proglucagon production in rat epithelial cells. Little work has
      been done on the potential oligosaccharide effects on appetite. and assessment of the
      appetite effects and energy regulation potential of Cellodextrin in humans is even more
      limited. However, before studies to investigate this can be carried out, it is important to
      assess any gastro-intestinal disturbances that may occur at the doses which would be
      required.

      The recommendation for total fibre intake is 18g/day in the United Kingdom (UK) although the
      actual UK average intake is lower than this, at an average of 13-15g/day. It is not known
      what the average daily oligosaccharide intake is in the UK, or whether the oligosaccharides
      are included in the total fibre estimates. However, because they are not digested within the
      small intestine, they can have a laxative effect, increasing the ease and/or frequency of
      laxation and excess intakes may cause diarrhoea and other gastrointestinal symptoms such as
      flatulence, bloating and abdominal discomfort. Intolerance symptoms can be due to the osmotic
      effect and/or fermentation; the osmotic effect may cause abdominal pain and eventually
      diarrhoea if the capacity of the colon to absorb water is exceeded. Moreover, fermentation
      produces gases that may also induce abdominal pain, bloating and excessive flatus. The
      tolerance of non-digestible oligosaccharides is usually very good, although the tolerance
      threshold depends on the type of oligosaccharide, the timing of consumption (e.g. after
      fasting or after a meal) and also individual factors such as absorption capacities, motility
      patterns, colonic responses and intestinal sensitivity. Polydextrose has been found to be
      tolerated at doses of 50g/day, resistant starch has a similar tolerability at acceptable
      doses of 45g/day, whereas galacto-oligosaccharide consumption of over 20g/day and
      fructo-oligosaccharide consumption of over 40g/day have been reported to cause diarrhoea.

      The aim is to investigate initially whether Cellodextrin induces gastrointestinal symptoms in
      a UK cohort of healthy men and women and to what extent. This information can then be used to
      inform future volunteers as to the relative risks of developing these gastrointestinal
      problems and the severity of symptoms experienced. A descriptive pilot study will be carried
      out. Twelve healthy individuals (6 males and 6 females, 18-40y, with a BMI between 18 and
      30kg/m2) will be recruited. Interested individuals will contact the investigators and be sent
      a copy of the information sheet before attending a medical screening. At the medical
      screening a full explanation of the study will be given and informed consent gained. A
      medical screening questionnaire will be administered, blood pressure measurements made and a
      10ml blood sample will be taken via venepuncture by suitably qualified staff (analysed for
      full blood count, urea and electrolytes). If suitable, participants will attend the
      laboratory for up to 4 visits and to provide a fecal sample (for microbiota assessment) prior
      to attending the first study visit. Participants will arrive at the laboratory around 8am,
      fasted from midnight the night before, and will then complete a series of appetite and
      gastro-intestinal symptom questionnaires. They will be asked to empty their bladder and a
      24hr urine collection will be started. After resting on a hospital bed for 15 min, a cannula
      will be sited for blood sampling. The participant will then consume 10, 20, 30 or 50g of
      Cellodextrin in a milkshake drink. They will repeat the questionnaires every 30 minutes for
      180 minutes with 1ml of blood taken from the cannula every 15 minutes over this time. The
      cannula will then be removed and a standard snack given to stimulate gut motility and
      questionnaires (as before) will be completed after 210 and 240 minutes. A low fiber sandwich
      lunch will be provided at 240mins,and during the following 2 hours, questionnaires will be
      administered every 30 minutes and then again at 420 and 480mins. Participants will be given a
      diet and symptom diary to complete over the rest of the day and the following 48hrs after
      each study visit. Feedback forms will be administered if a participant withdraws from or
      completes the study. Further fecal samples will be collected between 24 and 48hrs after
      consumption of the 30g and 50g dose.
    

Intervention name(s): Cellodextrin
Intervention type(s): Dietary Supplement
Intervention description(s): Gastrointestinal tolerability of single ascending doses of Cellodextrins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Ascending dose tolerability study
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Oligosaccharide, Tolerability,