Clinical trial NCT03993418: Physiological Effects of Stevia Consumption in Humans
Official title: Physiological Effects of Long-term Consumption of Non-nutritive Sweeteners in Humans: a Pilot 12 Week Randomised Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Intolerance
Obesity
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: Lancaster University
First posted: 2019-06-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-group parallel 12-week intervention study with control group
Primary purpose: BASIC_SCIENCE

Brief summary: This study will evaluate whether long-term consumption of the low calorie sweetener stevia affects glucose tolerance in healthy participants. With regard to this aim, we will recruit 2 study groups, the stevia group where participants will be required to add stevia drops twice daily in their habitual drinks and the control group where participants will be asked not to change anything in their diet and lifestyle.

Detailed description: Excess consumption of caloric sweeteners contributes to the alarming rates of overweight and obesity, whereas non-nutritive sweeteners (NNS) are non-caloric alternatives offering sensory and health benefits. NNS are widely used to moderate energy intake and postprandial glycaemia, but there is controversial evidence about their role and effects. Stevia, a natural NNS, has been suggested to assist with glucose regulation but data on glucose tolerance after daily consumption of stevia are lacking. The investigators plan to undertake a pilot randomized 2-parallel arm open-label 12-week trial, where participants will start consuming stevia with their habitual drinks. Thirty healthy volunteers (not habitual consumers of stevia or other NNS) will be recruited. The intervention group (n=15) will consume 5 drops of stevia with their habitual drinks twice daily whereas the control group (n=15) will not be required to change anything in their diet, but avoid consuming NNS or diet beverages for the study duration.

Key measures in glucose homeostasis including glucose response to an oral glucose tolerance test will be performed before and after the intervention period. Serum and plasma samples will be stored for potential analysis of insulin and gut hormones levels.

Participants will have to attend 3 study visits, visit week 0, visit week 6 and visit week 12, but the primary outcome will be assessed in visit week 0 and visit week 12.

Participants will be weighed; dietary intake, physical activity and appetite will be also assessed. Faecal samples will be collected and gut microbiome analysis may be performed. Gut microbiome has been considered to be a key linked topic, since it has been suggested that saccharin consumption may induce glucose intolerance in humans through alterations in gut microbiota in humans.

The trial will assess whether regular use of stevia in realistic amounts has any effects on glucose homeostasis, and aims to elucidate our understanding of long-term physiological effects of NNS.

Eligibility criteria: Inclusion Criteria:

* Age 18-40 years
* BMI 18.5-25 kg/m2
* No or low NNS consumers (up to 1 can of diet soda per week or 1 sachet of NNS per week)
* DEBQ for restraint eating ≤ 3
* Healthy - general good health
* Not taking medications that affect metabolism or appetite (i.e. thiazide diuretics, glucocorticoids or beta blockers)
* Stable weight, ≤ 5 kg last 12 months
* Fasting blood glucose ≤6.0 mmol/L
* Willing to comply with the study protocol
* No self-reported food allergy or intolerance to foods supplied during the study
* The participant is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* The participant is able to read, comprehend and record information written in English.
* A signed and dated written informed consent is obtained from the participant.

Exclusion Criteria:

* Age under 18 years or over 40 years old.
* BMI \>25 kg/m2 and \<18.5kg/m2
* Participants who are not willing to comply with study procedures (including expression of dislike for NNS)
* Habitual NNS consumers, \>1 can of diet beverage or \>1 sachet of low calorie sweeteners per week.
* Fasting blood glucose measured \> 6 mmol/L
* Subjects who are currently dieting and having ceased a diet in \< 4 weeks
* DEBQ score for restraint eating \> 3
* Subjects who follow special diets for weight maintenance, such as Atkins Diet, Weight Watchers, gluten-free diet, The Zone diet, Vegetarian Diet, Raw Food Diet etc.
* Vegetarians, vegans
* Subjects who take recreational substances such as cannabis.
* Presence of any chronic condition requiring medication that might affect our results (e.g. diabetes, mental diseases, gastrointestinal diseases)
* Subjects with eating disorders (binge eating disorder, bulimia etc)
* Subjects who are currently experiencing anxiety or depression
* Participants who drink alcohol more than the NHS guidelines (14 units per week)
* \>10 h of vigorous physical activities per week and/or planning to increase/decrease physical activity levels in the next months.
* Having ceased smoking in the last six months
* Female participants who are, or may be, pregnant, or currently lactating.
* Subjects who regularly consume dietary supplements for weight loss, muscle building etc.
* Subjects with food allergies or intolerances related to the study.
* Subjects who have given blood elsewhere within the last month.
* The participant cannot read, comprehend and record information written in English.

Primary outcomes:
measure: Glucose response to an oral glucose tolerance test (OGTT) measured as incremental area under the curve (iAUC)
timeFrame: Week 0 and week 12
Secondary outcomes:
measure: Change in body weight
timeFrame: Week 0, visit week 6 and week 12
measure: Change in dietary intake
timeFrame: Week 0, visit week 6 and week 12
measure: Change in waist circumference
timeFrame: Week 0, visit week 6 and week 12
measure: Change in appetite
timeFrame: Week 0 and week 12
measure: Change in fasting blood glucose
timeFrame: Week 0 and week 12
measure: Change in the 75-OGTT 2-hour blood glucose
timeFrame: Week 0 and week 12
Other outcomes:
measure: Physical activity
timeFrame: Week 0, visit week 6 and week 12
measure: Physical activity
timeFrame: Week 0, week 6, week 12
measure: Blood pressure
timeFrame: Week 0, visit week 6 and week 12
measure: Composition of gut microbiome
timeFrame: Week 0 and week 12
measure: Fasting plasma insulin
timeFrame: Week 0 and week 12
measure: 75g OGTT derived iAUC plasma insulin
timeFrame: Week 0 and week 12
Locations:
city: Manchester
country: United Kingdom
facility: University of Manchester
Study officials:
affiliation: University of Manchester
name: John McLaughlin
role: PRINCIPAL_INVESTIGATOR
References: