Acute Glycemic and Insulinemic Response of FOSSENCE™

Determination of the Acute Glycemic and Insulinemic Response of FOSSENCE™ Alone, or When Substituted or Added to a Carbohydrate Challenge: A Three-phase, Acute, Randomized, Cross-over, Double Blind Clinical Trial

Short chain fructooligosaccharide (FOS) is known as a prebiotic fiber/nutrient and has been documented to demonstrate different health benefits including glucose control, gut health, mineral absorption, weight and immunity.

FossenceTM is a short chain fructo-oligosaccharide (scFOS), sweet tasting, soluble prebiotic dietary fibre which is produced through Tata Chemicals Limited's patented process and is currently US GRAS notified (safe for consumption). The formulation and properties of scFOS suggest that the molecule may potentially play a role in glucose and insulin metabolism.

The purpose of this study is to explore the rise of glucose and insulin in the blood after consuming FossenceTM that has been added or substituted into a sugar drink or white bread.

BACKGROUND Short chain fructooligosaccharide (FOS) is known as a prebiotic fiber/nutrient and has been documented to demonstrate different health benefits including attenuation of postprandial glycemia, gut health, mineral absorption, satiety & weight management and immunity.

FossenceTM is short chain fructo-oligosaccharide (scFOS), a sweet tasting, soluble dietary fibre which is produced through Tata Chemicals Limited's patented process. These properties of scFOS suggest that the molecule may potentially play a role in glucose and insulin metabolism. The proposed 3 phase study will therefore explore the properties of FossenceTM with respect to its fibre like properties (not digested in the human small intestine), and its effect on postprandial glycemia when added or substituted into a simple (dextrose) or complex (white bread) carbohydrate load.

OBJECTIVES The purpose of this 3 phase study is to: 1. Demonstrate that consumption of scFOS does not increase postprandial blood glucose levels, 2. Explore the effects when scFOS is either added or substituted into a simple carbohydrate load (dextrose) or 3. Into a complex carbohydrate food (white bread).

PARTICIPANTS Twenty five healthy adult males and non-pregnant, non-lactating females, aged 18-65 years with BMI between 18 and 30 kg/m2 are required for each phase.

DESIGN The study is a double-blind, randomized, cross-over trial.

POWER CALCULATION Using the t-distribution and assuming an average coefficient of variation (CV) of within-individual variation of 2-hour glucose incremental are under the curve (IAUC) values of 23%, n=25 subjects has 90% power to detect a 22% difference in 2-hour glucose IAUC with 2-tailed p<0.05.

Using the t-distribution and assuming an average CV of within-individual variation of 2-hour insulin IAUC values of 25%, n=25 subjects has 90% power to detect a 24% difference in 2-hour insulin IAUC with 2-tailed p<0.05.

RECRUITMENT Participants will be recruited from the pool of participants at Glycemic Index Laboratories (GI Labs) who have indicated that they are willing to be contacted and asked if they wish to participate in new studies. If an insufficient number of subjects can be recruited, then an advertisement will be used to recruit new subjects.

INTERVENTIONS

Phase 1: to assess the glucose and insulin responses to the following test meals:

1. 10g of scFOS
2. A negative control (water)
3. A positive control (10g of dextrose)

Phase 2: to assess the glucose and insulin responses to the following test meals:

1. 50g Dextrose +15g scFOS,
2. 35g Dextrose +15g scFOS,
3. 35g Dextrose and
4. 50g Dextrose.

Phase 3: to assess the glucose and insulin responses to the following test meals:

1. 50g available carbohydrate (avCHO) from white bread +15g scFOS,
2. 35g avCHO from white bread +15g scFOS,
3. 35g avCHO from white bread and
4. 50g of avCHO from white bread

STATISTICAL ANALYSIS

For each study phase the following will be the statistical method:

Data will be presented as mean, standard deviation (SD) and standard error of the mean (SEM) values.

The mean glucose or insulin concentration in the 2 fasting blood samples will be used as the fasting concentration for the purposes of calculating incremental areas under the glucose and serum insulin response curves (IAUC), ignoring area below fasting17. Glucose and insulin concentrations, glucose and insulin IAUC (from 0 to 120 minutes) will be subjected to repeated measures analysis using the General Linear Model of variance (GLM-ANOVA). After demonstration of significant heterogeneity, the significance of differences among individual means will be determined using Tukey's method with p<0.05. In addition, differences at individual time points for glucose and insulin will be assessed. Differences will be considered to be statistically significant if 2-tailed p<0.05.

OUTCOMES

The primary analysis of each phase will be:

Phase 1: to compare the incremental area under the glucose curve elicited by

1. 10g of scFOS
2. A negative control (water)
3. A positive control (10g of dextrose)

Phase 2: to compare the incremental areas under the glucose curve elicited by

1. 50g Dextrose +15g scFOS,
2. 35g Dextrose +15g scFOS,
3. 35g Dextrose and
4. 50g Dextrose.

Phase 3: to compare the incremental areas under the glucose curve elicited by

1. 50g available carbohydrate (avCHO) from white bread +15g scFOS,
2. 35g avCHO from white bread +15g scFOS,
3. 35g avCHO from white bread and
4. 50g of avCHO from white bread

The secondary analyses of each phase will be:

Phase 1: to compare the glucose and insulin levels at individual time points, and the incremental area under the serum insulin curve elicited by 10g of scFOS with a negative control (water) or positive control (10g of dextrose)

Phase 2: to compare the glucose and insulin levels at individual time points, and the incremental area under the serum insulin curve elicited by:

(4) 50g Dextrose +15g scFOS, (5) 35g Dextrose +15g scFOS, (6) 35g Dextrose and (7) 50g Dextrose.

Phase 3: to compare the glucose and insulin levels at individual time points and the incremental area under the serum insulin curve elicited by:

1. 50g available carbohydrate (avCHO) from white bread +15g scFOS,
2. 35g avCHO from white bread +15g scFOS,
3. 35g avCHO from white bread and
4. 50g of avCHO from white bread

Subjects (N= 25) will be men (at least N= 12) and non-pregnant, non-lactating women (at least N= 12), 18 - 65 years of age each with a BMI of 18 - 30 kg/m2 inclusive and

Inclusion Criteria:

• Blood pressure < 140/90 mmHg
• No major illness or surgery requiring hospitalization within 3 months of the first study visit after screening
• No history of cardiovascular, metabolic, respiratory, renal, gastrointestinal or hepatic disease
• Subject may be a male or a non-pregnant, non-lactating female, at least 6 weeks postpartum prior to screening visit
• Willing to maintain habitual diet, physical activity pattern, and body weight throughout the study
• Subjects must be eligible to receive income in Canada and must demonstrate Ontario Health Insurance Program coverage

Exclusion Criteria:

• Failure to meet all the inclusion criteria
• Previous bariatric procedure
• No chronic disease such as type-1 or type-2 diabetes mellitus (fasting blood sugar levels <100 mg/dL (or <5.6 mmol/L) as assessed at the first visit)
• No gastro-intestinal disorder such as Crohn's disease, coeliac disease, irritable bowel syndrome
• Medications known to affect glucose tolerance -but stable doses of oral contraceptives, acetylsalicylic acid, thyroxin, vitamins and mineral supplements or drugs to treat hypertension, hyperlipidemia, anxiety/depression or osteoporosis are acceptable
• Any known food allergies or intolerances
• No strong dislike of or intolerance to sweetened beverages or inulin
• Smokers
• Alcohol consumption of no more than 10 drinks per week for women and 15 drinks per week for men. One drink is defined as either 5oz wine, 341ml of beer/cider or 1.5 oz distilled alcohol
• History of cancer in the prior two years, except for non-melanoma skin cancer
• Participants who do not understand English
• Presence of any condition, illness or drug use, which in the opinion of Dr. Wolever, increases the risk to the subject or to others or may affect the results