Identification of Biomarkers for Acute Intake of Beer and Alcohol and Acute Effects on Plasma and Insulin Response (METABEER)

Metabolomics in Beer Research: Identification of Biomarkers for Acute Intake of Beer and Alcohol in Individuals With a High or Low Habitual Intake, and Acute Effects on Plasma Glucose and Insulin Response Compared to Regular Soda

The objective of the study is to identify biomarkers for acute intake of beer and alcohol in individuals with a high or low habitual intake. Furthermore, we wish to identify compounds and metabolites in different types of beer and alcohol, which can serve as compliance markers for intake under the test conditions (blood tests and urine samples). We also wish to determine the acute effects of these beverages on plasma glucose and insulin response, compared to regular soda.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Alcohol Consumption
• Intervention / Treatment: Other: Beverage sequence ABCD; Other: Beverage sequence CADB; Other: Beverage sequence DACB; Other: Beverage sequence CBAD; Other: Beverage sequence ABDC; Other: Beverage sequence DABC; Other: Beverage sequence DCAB; Other: Beverage sequence DBCA; Other: Beverage sequence ADCB; Other: Beverage sequence BADC; Other: Beverage sequence ACDB

Detailed Description

The study is designed as a randomized, 4-way single-blinded cross-over intervention study. The participants are randomized individually to the order by which they shall receive 4 test meals. There will be implemented a standardized lunch which includes respectively 1) Light/alcohol-free (Tuborg Super Light 0,1% alcohol), 2) Regular lager (4,6% alcohol), 3) Strong beer(7,2% alcohol) and 4) a control drink without alcohol but with the same energy content (carbohydrate and protein) as the average of the other beverages ("sportsdrink"). Besides 330 ml of each test drink, each test meal consists of grilled cheese sandwiches (Tulip Food Company) and the amount of toast adjusted according to the type of drink served with each meal, so the content of macronutrients is the same in each meal.

The study includes 16-20 participants, randomized as to which order they will receive the 4 test meals with a washout period of at least 6 days in between test days. Upon arrival the test persons are asked to urinate (baseline sample), and at the 1st visit they are then weighed, height is measured and body composition (bioimpedance) is measured. After resting briefly, a baseline blood sample is taken and blood pressure is measured (1st and 4th visit). 45 minutes after start of the test meal the first postprandial blood sample is taken, and again after 45, 120 and 180 minutes. Urine is collected again at 0-90 min, 90-180 min and 3-24 hours after the test meal. Participants are provided with containers and equipment for this purpose, and must submit samples on an ongoing basis to the Dept. of Nutrition, Exercise and Sports.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg C, Denmark, 1958
    • Department of Nutrition, Exercise and Sports, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy man or woman in the age group 18-60 years
• Likes and tolerates pasta, tomatoes and cheese, and is not a vegetarian or vegan, since meat (beef and pork) is included in the standardized dinner, breakfast and in the test meal
• Habitual alcohol intake (high: up to 7/14 units per week for women/men) or low: 0-2 units per week for both genders
• Tolerates alcohol

Exclusion Criteria:

• Systematic infections, psychiatric conditions and metabolic disease, and any clinical condition and other condition/situation, which according to the experimenter's assessment makes the person unfit to participate in the study
• Donation of a larger amount of blood (more than 24 ml) e.g. in connection with donation or other scientific research study, during the study and 3 months before start of the study
• Alcohol intake above the Danish Health and Medicines Authority's recommended 7 respective 14 drinks (units) per week for women and men
• Have or have had a drug addiction
• Allergy or intolerance to any of the tested drinks, or to any other foods included in the study. The participant will be specifically screened for possible alcohol allergy or intolerance
• Nursing, pregnancy or planned pregnancy.
• Not capable of complying with the procedures stipulated in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beverage sequence ABCD; Each participant randomized to this arm is exposed to 4 test meals in the order ABCD with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence ABCD; Participants receive test beverages in the randomised order ABCD
Experimental: Beverage sequence CADB; Each participant randomized to this arm is exposed to 4 test meals in the order CADB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence CADB; Participants receive test beverages in the randomised order CADB
Experimental: Beverage sequence DACB; Each participant randomized to this arm is exposed to 4 test meals in the order DACB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence DACB; Participants receive test beverages in the randomised order DACB
Experimental: Beverage sequence CBAD; Each participant randomized to this arm is exposed to 4 test meals in the order CBAD with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence CBAD; Participants receive test beverages in the randomised order CBAD
Experimental: Beverage sequence ABDC; Each participant randomized to this arm is exposed to 4 test meals in the order ABDC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence ABDC; Participants receive test beverages in the randomised order ABDC
Experimental: Beverage sequence DABC; Each participant randomized to this arm is exposed to 4 test meals in the order DABC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence DABC; Participants receive test beverages in the randomised order DABC
Experimental: Beverage sequence DCAB; Each participant randomized to this arm is exposed to 4 test meals in the order DCAB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence DCAB; Participants receive test beverages in the randomised order DCAB
Experimental: Beverage sequence DBCA; Each participant randomized to this arm is exposed to 4 test meals in the order DBCA with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence DBCA; Participants receive test beverages in the randomised order BDCA
Experimental: Beverage sequence ADCB; Each participant randomized to this arm is exposed to 4 test meals in the order ADCB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence ADCB; Participants receive test beverages in the randomised order ADCB
Experimental: Beverage sequence BADC; Each participant randomized to this arm is exposed to 4 test meals in the order BADC with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence BADC; Participants receive test beverages in the randomised order BADC
Experimental: Beverage sequence ACDB; Each participant randomized to this arm is exposed to 4 test meals in the order ACDB with a washout period of at least a week between each meal. Each meal consisted of a standardized lunch of Parisian toast (sandwichbread, ham, cheese) together with a beverage. Each beverage is assigned a letter, A, B, C, or D. The letter assignment is blinded. The following four drinks were used Placebo: 330 ml of a soft drink (Sports drink), Beer 1 - 330 ml of an alcohol-free beer (<0.1% alcohol), Beer 2 - 330 ml of a regular lager beer (4.6% alcohol), and Beer 3 - 330 ml of a strong beer (7.2% alcohol)	Other: Beverage sequence ACDB; Participants receive test beverages in the randomised order ACDB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) for glucose	Glucose is measured at 0, 45, 90, 120, and 180 min after the test meal and the area is determined by the trapezoid method.	0-180 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve for insulin	Insulin is measured at 0, 45, 90, 120, and 180 min after the test meal and the area is determined by the trapezoid method.	0-180 min
Plasma concentration of fatty acid ethyl esters (FAEE)	Change in FAEE from baseline to 180min by LC-MS/MS analysis of plasma.	Change from 0-180min
Blood level of ethanol	The amount of ethanol is measured via a breath test using an alcoholmeter.	180 min
Plasma beer metabolites (metabolic profiling with NMR and mass spectrometry).	Explorative marker to identify new beer intake-related metabolites in plasma.	After the intervention
Urinary content of paraaminobenzoic acid (PABA)	Total PABA metabolites by colorimetric assay to account for completeness of urine collection.	24hour pooled urine from each volunteer
Urinary content of ethyl glucuronide (EtG) and ethyl sulphate (EtS)	EtG and EtS by quantitative LC-MS/MS	0-24 hours
Blood content of ethyl glucuronide (EtG) and ethyl sulphate (EtS)	EtG and EtS are measured at 0, 45, 90, 120 and 180 minutes and the difference between treatments is determined by multivariate ANOVA followed (if significantly different) by t-tests for each time point.	0-180 min
Urinary content of acetaldehyde (ethanal)	Ethanal is measured by a kit and compared between treatments.	0 -24 hrs
Urinary compounds of beer metabolites	Metabolic profiling of urine by NMR and mass spectrometry.	0-24 hrs
Blood pressure	Measurement of supine systolic and diastolic blood pressure	baseline and at time -30min on the last day of intervention.
Body fat mass and body fat percentage	Measurement of body fat mass and fat percentage by bioimpedance	baseline
Urinary creatinine	Creatinine is measured by standard clinical chemistry.	0-24hrs

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Carlsberg Breweries A/S
• Investigators: Principal Investigator: Lars O. Dragsted, Professor, Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: May 19, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Biomarker; Metabolomics; Beer; Insulin response; Glucose response
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Drinking Behavior; Hyperinsulinism; Alcohol Drinking; Insulin Resistance
• Other Study ID Numbers: M212