13TSB_N4L2CRD: CELLDEX-Developement of a low calorie bulk sugar replacer
Lead Research Organisation:
University of Nottingham
Department Name: School of Life Sciences
Abstract
Study 1 - Tolerability of cellodextrins
This is primarily a descriptive study to characterise the tolerability of single, ascending doses (10g, 20g, 30g, 50g) of cellodextrin, consumed in a food matrix. Six healthy, non-obese male and 6 female volunteers (age 18-40yrs, BMI 18-30kg/m2) would be recruited to allow estimation of a tolerance threshold with respect to adverse GI symptoms.
Protocol Summary;
Medical screening visit.
4x Study visits
Consumption of food product containing 10, 20, 30 or 50g of cellodextrin (on study visits 1-4 respectively)
Visits to be separated by at least a week
Completion of visual analogue scales for appetite and bowel symptoms for 9hrs after consumption
Diet and bowel symptom diary kept on the day before and for 48hrs after each visit
Study 2 - Digestion and fermentation of cellodextrins
In addition to artificial gut studies, it is proposed to conduct an in vivo study assessing digestion and fermentation of cellodextrin in comparison with sucrose and polydextrose in 16 healthy, non-obese volunteers (M/F, age 18-40yrs, BMI 18-30kg/m2). Dose of cellodextrin would be determined from the tolerability study (Study 1). Breath samples will be collected for hydrogen assessment, and arterialised venous blood will be collected for glucose and insulin analysis.
Protocol Summary;
Medical screening visit.
3x Study visits
Randomised, cross-over, double-blinded study design
Consumption of food product containing cellodextrin, polydextrose or sucrose (carbohydrate content matched)
Collection of breath and blood samples
Completion of visual analogue scales for appetite and bowel symptoms for 5hrs after consumption
Diet and bowel symptom diary kept for 48hrs after each visit
Study 3 - Cellodextrins and appetite
This study would test the effect of cellodextrin, consumed as a midmorning snack, on subjective appetite, subsequent energy intake at the next meal and incretin hormones, in 16 healthy non-obese male volunteers (age 18-40yrs, BMI 18-30kg/m2). Dose of cellodextrin would be determined from the tolerability study (Study 1). A food product containing cellodextrin would be compared with ones containing digestible (sucrose) and indigestible (polydextrose) carbohydrate (matched carbohydrate content). The product would otherwise be the same on each occasion with a protein /fat/carbohydrate content reflecting a normal snack and an energy content of 200-250 kcal. This product would then be consumed once a day for 2 weeks, with the impact on energy intake at an ad-libitum lunch assessed on day 1 and day 14. Food diaries would also be kept during the 2nd week of each supplementation period and body weight measured before and after each 2wk period.
Protocol Summary;
Medical screening visit.
6x Study visits (pre- and post a 2wk supplementation period)
3x supplementation periods with a 2wk 'wash-out' in between
Randomised, cross-over, double-blinded study design
Consumption of food product containing cellodextrin, polydextrose or sucrose(carbohydrate content matched)
Acute and acute-on-chronic response to the products
Completion of visual analogue scales for appetite and bowel symptoms for 4hrs after consumption
Diet and bowel symptom diary kept for 48hrs after each visit
Three-day diet diary kept during week 2 of each intervention period
This is primarily a descriptive study to characterise the tolerability of single, ascending doses (10g, 20g, 30g, 50g) of cellodextrin, consumed in a food matrix. Six healthy, non-obese male and 6 female volunteers (age 18-40yrs, BMI 18-30kg/m2) would be recruited to allow estimation of a tolerance threshold with respect to adverse GI symptoms.
Protocol Summary;
Medical screening visit.
4x Study visits
Consumption of food product containing 10, 20, 30 or 50g of cellodextrin (on study visits 1-4 respectively)
Visits to be separated by at least a week
Completion of visual analogue scales for appetite and bowel symptoms for 9hrs after consumption
Diet and bowel symptom diary kept on the day before and for 48hrs after each visit
Study 2 - Digestion and fermentation of cellodextrins
In addition to artificial gut studies, it is proposed to conduct an in vivo study assessing digestion and fermentation of cellodextrin in comparison with sucrose and polydextrose in 16 healthy, non-obese volunteers (M/F, age 18-40yrs, BMI 18-30kg/m2). Dose of cellodextrin would be determined from the tolerability study (Study 1). Breath samples will be collected for hydrogen assessment, and arterialised venous blood will be collected for glucose and insulin analysis.
Protocol Summary;
Medical screening visit.
3x Study visits
Randomised, cross-over, double-blinded study design
Consumption of food product containing cellodextrin, polydextrose or sucrose (carbohydrate content matched)
Collection of breath and blood samples
Completion of visual analogue scales for appetite and bowel symptoms for 5hrs after consumption
Diet and bowel symptom diary kept for 48hrs after each visit
Study 3 - Cellodextrins and appetite
This study would test the effect of cellodextrin, consumed as a midmorning snack, on subjective appetite, subsequent energy intake at the next meal and incretin hormones, in 16 healthy non-obese male volunteers (age 18-40yrs, BMI 18-30kg/m2). Dose of cellodextrin would be determined from the tolerability study (Study 1). A food product containing cellodextrin would be compared with ones containing digestible (sucrose) and indigestible (polydextrose) carbohydrate (matched carbohydrate content). The product would otherwise be the same on each occasion with a protein /fat/carbohydrate content reflecting a normal snack and an energy content of 200-250 kcal. This product would then be consumed once a day for 2 weeks, with the impact on energy intake at an ad-libitum lunch assessed on day 1 and day 14. Food diaries would also be kept during the 2nd week of each supplementation period and body weight measured before and after each 2wk period.
Protocol Summary;
Medical screening visit.
6x Study visits (pre- and post a 2wk supplementation period)
3x supplementation periods with a 2wk 'wash-out' in between
Randomised, cross-over, double-blinded study design
Consumption of food product containing cellodextrin, polydextrose or sucrose(carbohydrate content matched)
Acute and acute-on-chronic response to the products
Completion of visual analogue scales for appetite and bowel symptoms for 4hrs after consumption
Diet and bowel symptom diary kept for 48hrs after each visit
Three-day diet diary kept during week 2 of each intervention period
Technical Summary
The purpose of this project is to investigate the possibility of developing cellulose derived molecules as substitutes for sucrose in food and confectionery and then assess the gastrointestinal tolerability of these products and the impact on appetite and body weight.
After initial food chemistry studies and in vitro assessments of fermentability of the cellulose derivatives produced, we will undertake a series of human studies to determine the effects in vivo.
A series of studies will be performed in healthy human volunteers to assess 1) the tolerability of cellodextrins after oral consumption,2) the effect of chosen single doses of cellodextrin on plasma insulin and glucose and on colonic fermentation (assessed by measuring breath hydrogen generated by the colonic fermentation process), and 3) the acute (single dose) and chronic (14 days repeated consumption) effects of cellodextrin consumption on appetite, satiety and voluntary food intake and overall effects on body weight. The chronic effect of the cellulose products will also be compared with the effect of routinely consuming polydextrose, as we have shown potentialy beneficial effects of this substance on appetite and food intake.
After initial food chemistry studies and in vitro assessments of fermentability of the cellulose derivatives produced, we will undertake a series of human studies to determine the effects in vivo.
A series of studies will be performed in healthy human volunteers to assess 1) the tolerability of cellodextrins after oral consumption,2) the effect of chosen single doses of cellodextrin on plasma insulin and glucose and on colonic fermentation (assessed by measuring breath hydrogen generated by the colonic fermentation process), and 3) the acute (single dose) and chronic (14 days repeated consumption) effects of cellodextrin consumption on appetite, satiety and voluntary food intake and overall effects on body weight. The chronic effect of the cellulose products will also be compared with the effect of routinely consuming polydextrose, as we have shown potentialy beneficial effects of this substance on appetite and food intake.
Planned Impact
This project aims to produce a new low calorie bulk sugar replacer from a sustainable source, which out-performs currently available alternatives in providing high quality chocolate confections without undesirable side effects at a reasonble price. This would provide an opportunity to develop a range of snacks which are lower in sugar and calories, without sacrifcing taste attributes. If this is successful then the potential commerical and societal impact is substantial. Not only would the new ingredient be used to produce lower calorie confectionery, but it will also be available to the food industry to enable the formulation of a range of healthier reduced sugar foods.
This would help the food industry to contribute to the UK Government Calorie Reduction initiative, which is part of the Food Network-Responsibility deal and seeks to remove 100kcal/day/person from the food supply. The availability of tasty but healthy and lower energy foods and snacks has a role to play in fighting the trend of increasing obesity and type 2 diabetes.
This would help the food industry to contribute to the UK Government Calorie Reduction initiative, which is part of the Food Network-Responsibility deal and seeks to remove 100kcal/day/person from the food supply. The availability of tasty but healthy and lower energy foods and snacks has a role to play in fighting the trend of increasing obesity and type 2 diabetes.
Publications
Tooley M
(2020)
The gastrointestinal tolerability of a non-digestible carbohydrate; an ascending dose trial in healthy volunteers
in Proceedings of the Nutrition Society
| Description | The Industrial partners to this Innovate UK/BBSRC project eventually succeeded in producing a Cellulose derived, small molecular weight, indigestible product that could be used as a bulk sugar replacer. This Celldex product was then used by us in a dose escalating study to determine the tolerability of acute ingestion by healthy volunteers. This study involved consuming the Celldex in water and was successfully completed, with doses of up to 50g being consumed with only minor gastrointestinal discomfort in a few participants, and fecal samples were obtained to assess potential effects of the Celldex on the fecal microbiota. There were some acute effects of the Celldex on appetite, as would be expected from the consumption of a fibre-type product. These fecal measurements have been undertaken in Aberdeen by our academic collaborators on this project. We have now received the fecal data and are in the process of preparing a manuscript for submission for publication which combines the human participant responses to, and the fecal microbiota effects of, the Celldex. An oral communication of this work was presented to the Nutrition Society in Dec 2019 - title and authors were: Tooley, M., Simpson, E., & Macdonald, I. (2020). The gastrointestinal tolerability of a non-digestible carbohydrate; an ascending dose trial in healthy volunteers. Proceedings of the Nutrition Society, 79(OCE1), E17. doi:10.1017/S0029665119001381 |
| Exploitation Route | It is possible that one or more food companies will be interested in producing more of this Celldex material to explore whether it can be used in food or confectionery as a replacement for some of the sucrose (sugar) in their products. For this to be viable it would be necessary top show that the Celldex has similar functional characteristics to sucrose in baking/manufacture, and that an economically viable way of producing the Celldex is developed. |
| Sectors | Agriculture, Food and Drink |
| URL | https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/gastrointestinal-tolerability-of-a-nondigestible-carbohydrate-an-ascending-dose-trial-in-healthy-volunteers/35E71119DE416069C3E0286C2F6B7B47 |