Associations Between Genetic Markers of Caffeine Metabolism, Appetite Hormones and Body Weight

The effect of caffeine on appetite and body weight is controversial. Mostly epidemiological studies exist that show either a negative effect (reduction of appetite and body weight) or no effect. In this trial we are going to study the results of the consumption of 5mgr/kgr body weight of caffeine on appetite, food consumption and hormones ghrelin, asprosin, leptin and pancreatic polypeptide in relation to gene polymorphisms that affect caffeine metabolism and body weight. Seventy subjects will participate in a cross sectional study consisting of two trials (with or without the consumption of caffeine) in order to study the aforementioned parameters. Differences of total calories consumption between fast metabolizers of caffeine and the rest of the participants is the primary outcome.

Study Overview

• Status: Unknown
• Conditions: Caffeine; Food Habits; Food Consumption and Appetite
• Intervention / Treatment: Dietary supplement: caffeine consumption

Detailed Description

In more detail, participants will be recruited through local advertisements in the university campus so that to be of normal weight (BMI<25) and apparently healthy. Smokers, special population groups, i.e. athletes, pregnant women etc., those having a chronic or acute disease and those on medication will be excluded from the study.

Experimental protocol. Each volunteer will take part in 2 trials (with 7days interval between them) in a random order (using a random-number table). Female participants will be on the follicular phase of their menstrual cycle during the experiments to avoid variability in appetite [doi.org/10.1016/j.appet.2018.01.029.]. The week preceding each experimental day, participants will be instructed to abstain from any caffeine. Furthermore, the day preceding each experimental day participants will be instructed to abstain from alcohol source and physical exercise, to get enough sleep (~7 h) and to come to the lab after an overnight fast of 10 h. Furthermore, the days before the experiment, volunteers will be asked to consume similar foods and quantities, keeping more or less constant eating patterns. Participants will arrive at the lab in the morning 9 am after an overnight fast of 10 h. They will consume a breakfast snack along with one of the three experimental drinks within 5 min. The snack will consist of 1 slice of white bread, 5 g of butter and 10 g of white sugar, providing 142 kcal (6.5% of energy from proteins, 62.5% from carbohydrates and 31.0% from lipids). The experimental drinks will be either (a) 200 mL of instant coffee providing 5 mg caffeine/kg body weight or (b) 200 mL of water (Control). After a 3-h period, participants will be offered an ad libitum lunch meal from a buffet, consisting of common Greek diet foods (pasta, tomato sauce, beef, salad, cheese, yogurt, fruit and juice). They will be instructed to consume as much food as they desire until they feel satiated, within 30 min. Researchers will record the exact amount of food consumed by weighting the foods that will be chosen and their remnants. In addition, a detailed recording of the foods participants are going to consume later in the evening will be performed from a registered dietician through recall questionnaires.

Molecular and biochemical parameters that are going to be recorded with the utilization of standardized generally accepted protocols are blood pressure, body weight and other anthropometric parameters, blood levels of ghrelin, asprosin, leptin, pancreatic polypeptide, insulin and glucose, and genetic markers that are related to caffeine metabolism (CYP1A2 rs2069514 και CYP1A2 rs762251), as well as to an obesity genetic risk score (32SNPs).

Primary and secondary outcomes Based on genotype data, participants will be categorized as fast, medium and slow metabolizers of caffeine. For sample size calculation differences of total calories consumptions between groups will be utilized as primary outcome. More specifically, since a small participation of slow metabolizers are expected, these subjects will be grouped together with medium metabolizers. A difference of total calories consumption that exceeds 20% between the two groups is considered clinically significant. Taking into account an attrition rate of 10% between the two trials (caffeine and control) a total of about 70 participants are required for the study.

Macronutrients (protein, carbohydrates and lipids) consumption, responses on visual analog scales for satiety and appetite, hormones concentrations will be studied as secondary outcomes

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kalliopi Gkouskou, PhD; Phone Number: +30693855379; Email: gkouskoukal@med.uoa.gr
• Study Contact Backup: Name: Aristides Eliopoulos, Prof; Phone Number: 30 210 7462341; Email: eliopag@med.uoa.gr

Study Locations

• Greece
  • Attica
    • Aigáleo, Attica, Greece
      • Recruiting
      • University of West Attica
      • Contact: Dimitrios Haniotis, prof; Email: dchaniotis@uniwa.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• normal weight (BMI<25)
• apparently healthy participants

Exclusion Criteria:

• smokers,
• special population groups, i.e. athletes, pregnant women etc.,
• people with a chronic or acute disease and
• those on medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: caffeine consumption and metabolism; Participants will take part in two trials. Each trial will last one day at least one week apart. During the first trial half of the participants will consume caffeine (5mgr/kgr) and the rest only water. During the second trial a crossover design will be applied	Dietary supplement: caffeine consumption; In this trial we are going to study the results of the consumption of 5mgr/kgr body weight of caffeine on appetite, food consumption and hormones ghrelin, asprosin, leptin and pancreatic polypeptide in relation to gene polymorphisms that affect caffeine metabolism and body weight
Other: control; Control group will consume only water (not coffee) and the same parameters will be recorded as previously	Dietary supplement: caffeine consumption; In this trial we are going to study the results of the consumption of 5mgr/kgr body weight of caffeine on appetite, food consumption and hormones ghrelin, asprosin, leptin and pancreatic polypeptide in relation to gene polymorphisms that affect caffeine metabolism and body weight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total calories consumption change	a detail recording of foods and their quantities during the day of the trial will take place	two trials (caffeine and control) two weeks apart each lasting one day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hormones concentrations change	insulin, ghrelin, asprosin, leptin and pancreatic polypeptide	two trials (caffeine and control) two weeks apart each lasting one day
VAS (visual analog scale-11-likert scale with greater numbers indicating greater appetite) change for appetite	visual analog scales administered in specific time frames 15 min before and 15, 30, 60, 90, 120, 150, 180 min after the consumption of breakfast with or without caffeine	two trials (caffeine and control) two weeks apart each lasting one day
VAS (visual analog scale 11-likert scale with greater numbers indicating greater satiety) change for satiety	visual analog scales administered in specific time frames 15 min before and 15, 30, 60, 90, 120, 150, 180 min after the consumption of breakfast with or without caffeine	two trials (caffeine and control) two weeks apart each lasting one day
various macronutrients consumption change	a detail recording of foods and their quantities during the day of the trial will take plac	two trials (caffeine and control) two weeks apart each lasting one day

Collaborators and Investigators

• Sponsor: Gkouskou Kalliopi
• Investigators: Study Chair: Aristides Eliopoulos, prof, University of Athens

Publications and helpful links

General Publications

• Gkouskou KG, Georgiopoulos G, Vlastos I, Lazou E, Chaniotis D, Papaioannou TG, Mantzoros CS, Sanoudou D, Eliopoulos AG. CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study. Int J Obes (Lond). 2022 Jan;46(1):162-168. doi: 10.1038/s41366-021-00972-6. Epub 2021 Sep 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: August 2, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: AP336.30.06.2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No