Propionate and Energy Homeostasis

Study Overview
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Brief Summary
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The research project aims to examine the effect of a dietary supplement called propionate on how the human body in healthy adults aged (18- 65 years) responds to during fasting, exercise and following a liquid mixed meal test and how that would affect energy homeostasis and substrate oxidation.

Detailed Description
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Dietary fibres have long been recognised for their important role in a healthy diet due to their negative association with, and even management of, chronic diseases such as obesity, diabetes, metabolic syndrome, cardiovascular disease and inflammatory-bowel disease among others.Emerging evidence has suggested that these benefits could largely be attributed to short chain fatty acids (SCFA) (acetate, propionate and butyrate), the main by-products of fibre fermentation in the gut. Previous research has demonstrated that a long-term elevation in the SCFA propionate significantly reduced body weight gain in overweight adults and reduced liver fat storage. The current project will examine potential mechanisms for the positive effect of propionate on energy homeostasis and metabolic profile.The effects of propionate on circulating glucose, insulin, gut hormones and lipid levels at rest, following moderate-intensity exercise and mixed meal tolerance test will be examined. To acutely increase propionate absorption from the gut the present project will use a simple nutritional supplement: sodium propionate in a hydroxypropylmethyl cellulose (HPMC) capsule. This capsule is coated with an enteric film which prevents gastric digestion until the capsule reaches the intestine. This nutritional supplement has been used in human volunteers in a previously approved ethics application (12/LO/1769: Oral propionate and glucose homeostasis). A 5g acute dose of sodium propionate had previously been tested and reported no adverse effects . The MHRA have confirmed that encapsulated sodium propionate is not classed as an investigative medicinal product.

Official Title
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The Acute Effect of Propionate on Energy Homeostasis

Conditions
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Obesity

Intervention / Treatment
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* Other: Placebo (Sodium Chloride)
* Other: Exercise
* Dietary Supplement: Sodium Propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers (body mass index (BMI) of 18-35 kg/m2) Age between 18-65 years (inclusive) Exclusion Criteria: Weight change of ≥ 3kg in the preceding 2 months Current smokers Substance abuse Excess alcohol intake Pregnancy Diabetes Cardiovascular disease Cancer Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome Kidney disease Liver disease Pancreatitis Started new medication within the last 3 months likely to interfere with energy metabolism, appetite regulation and hormonal balance, including: anti-inflammatory drugs or steroids, antibiotics, androgens, phenytoin, erythromycin or thyroid hormones. Involved in current research or have recently been involved in any research prior to recruitment in the past 12 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This protocol consisted of three individual trials. Participants will complete only a single trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Fasting<br>Sodium Chloride tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes). | Other: Placebo (Sodium Chloride)<br>* Participant receive Placebo (Sodium Chloride)<br>|
| Placebo Comparator: Placebo + Exercise<br>Sodium Chloride tested in an exercise state. Participants will have the placebo then exercise will be performed at 40% of maximal aerobic capacity for one hour. | Other: Placebo (Sodium Chloride)<br>* Participant receive Placebo (Sodium Chloride)<br>Other: Exercise<br>* 1 hour exercise<br>|
| Placebo Comparator: Placebo + Post-prandial<br>Sodium Chloride tested in a post-prandial state. Participants will have the placebo then a mixed liquid meal test is given. | Other: Placebo (Sodium Chloride)<br>* Participant receive Placebo (Sodium Chloride)<br>|
| Experimental: Propionate and Fasting<br>Sodium Propionate tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes). | Dietary Supplement: Sodium Propionate<br>* Participant receive Sodium Propionate<br>|
| Experimental: Propionate and Exercise<br>Sodium Propionate tested in an exercise state. Participants will have the sodium propionate then exercise will be performed at 40% of maximal aerobic capacity for one hour. | Other: Exercise<br>* 1 hour exercise<br>Dietary Supplement: Sodium Propionate<br>* Participant receive Sodium Propionate<br>|
| Experimental: Propionate and Post-prandial<br>Sodium Propionate tested in a post-prandial state. Participants will have the sodium propionate then a mixed liquid meal test is given. | Dietary Supplement: Sodium Propionate<br>* Participant receive Sodium Propionate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Resting Energy Expenditure | Changes in Resting Energy Expenditure between sodium propionate and sodium chloride (control). | 6 hours | 
| Changes in Resting Lipid Oxidation | Changes in Resting Lipid Oxidation between sodium propionate and sodium chloride (control). | 6 hours | 
| Changes in Energy Expenditure during Exercise | Changes in Energy Expenditure between sodium propionate and sodium chloride (control) during exercise. | 240 minutes | 
| Changes in Lipid Oxidation during Exercise | Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) during exercise. | 240 minutes | 
| Changes in Energy Expenditure post-prandially | Changes in Energy Expenditure between sodium propionate and sodium chloride (control) post-prandially. | 300 minutes | 
| Changes in Lipid Oxidation post-prandially | Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) post-prandially. | 300 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in GLP-1 Concentration | Changes in GLP-1 concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in Insulin Concentration | Changes in insulin concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in glucose concentration | Changes in glucose concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in free fatty acid concentration | Changes in free fatty acid concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in subjective nausea | Changes in subjective nausea between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in subjective hunger | Changes in subjective hunger between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 
| Changes in subjective thirst | Changes in subjective thirst between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially. | 360, 240 and 300 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short Chain Fatty Acids, Propionate, Energy Expenditure, Lipid Oxidation