Clinical trial NCT01561235: Protein Dose-repsonse Effect on GLP-1, PYY and Appetite in Male Subjects
Official title: The Contribution of Gastrointestinal Appetite Hormones to Protein-induced
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Protein
Appetite
Satiety
Energi intake
Appetite regulating hormones
Dose-response
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
First posted: 2012-03-22
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Dietary protein appears to be the most satiating and thermogenic macronutrient. However, how protein exerts its effect on appetite is not fully known. The effect have been suggested to be related to a higher oxidation rate of protein compared to carbohydrate and fat, and also to a greater thermogenic effect causing greater increase in core temperature. The involvement of peripheral appetite-regulating hormones has only been sparingly investigated.

The objective is to investigate the satiating effects of meals with varying content of meat-based protein and whether a dose-response effect can be found on appetite-regulating hormones and appetite ratings.

Design: 25 men will participate in the 3-way, randomized, double-blind, crossover study. The test meals is isocaloric with 30E% fat and increasing protein content at the expense of carbohydrate. Test meals are: normal protein content (NP, 14E% protein), medium-high protein content (MHP, 25E%), and high protein content(HP, 50E%). Four-hour subjective appetite ratings and blood samples will be assessed every half-hour. Subsequently, the subjects will served an ad libitum lunch.

Detailed description: Dietary protein appears to be the most satiating and thermogenic macronutrient (7-11). However, how protein exerts its effect on appetite is not fully known. The effect have been suggested to be related to a higher oxidation rate of protein compared to carbohydrate and fat (12), and also to a greater thermogenic effect causing greater increase in core temperature (13). The involvement of peripheral appetite-regulating hormones has only been sparingly investigated (14). These studies have only included two preloads of different concentrations of protein. This is not an optimal design for investigating the protein dose-dependent effect as the threshold can have been reached in between the two concentrations. The effect of protein has mainly been investigated on glucagon-like peptide-1 (GLP-1), ghrelin, cholecystokinin (CCK), and generally after intake of protein below 35% of the energy content (35E%) (5;15-18). The relationship between these appetite-regulating hormones and appetite is still elusive due to contradicting results. Only one study has investigated the effect of protein preloads above 50E%. Bowen et al. (19) found that the high protein preloads could decrease the concentration of CCK and the rate of gastric emptying, which have been shown to enhance the satiating effect of food (20-22). Thus there is a need to examine the effect of protein on appetite-regulating hormones in a dose-response manner in order to detect whether there is an interaction between them and if they can be related to changes in subjective sensations of appetite and EI (14). This should be examined by comparing more than two isocaloric meals in which the protein content and one other macronutrient should vary whereas the third macronutrient should be kept fixed.

Thus, the objective of this study is to investigate the mechanisms responsible for the satiating effects of protein in three isocaloric test meals with a protein content of 14, 25 or 50 E% protein. A possible dose-response effect of protein is investigated on a number of appetite-regulating hormones/peptides, together with changes in ad libitum energy intake.

Design: 25 men will participate in the 3-way, randomized, double-blind, crossover study. The test meals is isocaloric with 30E% fat and increasing protein content at the expense of carbohydrate. Test meals are: normal protein content (NP, 14E% protein), medium-high protein content (MHP, 25E%), and high protein content(HP, 50E%). Four-hour subjective appetite ratings and blood samples will be assessed every half-hour. Subsequently, the subjects will served an ad libitum lunch.

Eligibility criteria: Inclusion Criteria:

* Healthy,
* BMI: 18.5-40 kg/m2,
* Weight stable (within +/- 3 kg) two months prior to study inclusion,
* Non-smoking,
* Nonathletic,

Exclusion Criteria:

* BMI \> 40 kg/m2,
* Change in smoking status,
* Daily or frequent use of medication,
* Suffering from metabolic diseases,
* Suffering from psychiatric diseases,
* Suffering from any other clinical condition, which would make the subject unfit to participate in the study,
* Blood pressure was above 150/90 mmHg,
* Hemoglobin \< 8 mmol/l.

Primary outcomes:
measure: Acute 4-h changes from baseline in the postprandial concentration of GLP-1
timeFrame: Measured on 3 seperate test days in a crossover design. Each test day was seperated by >4 weeks. On each test day GLP-1 was measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake
Secondary outcomes:
measure: Acute 4-h changes from baseline in subjective appetite sensations using visual analogue scales
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day appetite sensations were measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.
measure: Acute 4-h changes from baseline in the postprandial concentration of appetite regulating hormones/peptides
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.
measure: Acute 4-h changes from baseline in the postprandial concentration of glucose
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes post intake.
measure: Acute 4-h changes from baseline in the postprandial concentration of insulin
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes post intake.
measure: Acute 4-h changes from baseline in the postprandial concentrations of lipids
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.
measure: Acute 4-h changes from baseline in the body temperature
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day temperature was measured prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 210, 240 minutes post intake.
measure: Rate of gastric emptying (4-h change from baseline in postprandial concentration of paracetamol)
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day blood samples were collected prior to the test meal (time 0) and 30, 60, 90, 120, 150, 180, 240 minutes post intake.
measure: Rating of the organoleptic quality of the test meals
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the test meal (approximately) time 15 minutes post intake) subjects rated the test meals
measure: Rating of the organoleptic quality of the ad libitum meal
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the ad libitum meal subjects rated the meal
measure: Subjective appetite sensations (visual analogue scales) after ad libitum meal
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. On each test day after completion of the ad libitum meal subjects rated their subjective sensation of appetite (approximately 4.5-h post intake of the test meal)
measure: ad libitum energy intake (EI)
timeFrame: Measured on 3 seperate test days in a crossover design. Each test seperated by >4 weeks. EI was measured 240 min after intake of the test meal
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: Department of human Nutrition
Study officials:
affiliation: Depertment of Human Nutrition, University of Copenhagen, Denmark
name: Arne Astrup, Professor, Dr Med
role: PRINCIPAL_INVESTIGATOR
References:
citation: Belza A, Ritz C, Sorensen MQ, Holst JJ, Rehfeld JF, Astrup A. Contribution of gastroenteropancreatic appetite hormones to protein-induced satiety. Am J Clin Nutr. 2013 May;97(5):980-9. doi: 10.3945/ajcn.112.047563. Epub 2013 Mar 6.