The HotFacets study is a randomized, controlled, cross-over meal study that investigates the acute effects of alcohol consumption on short-chain fatty acids dynamics, energy metabolism, and biomarkers. Despite the negative health consequences of chronic alcohol abuse, observational and cohort studies associate moderate alcohol consumption with a 20-30 % lower risk of cardiovascular diseases (CVD) and Type 2 Diabetes Mellitus (T2DM), compared to abstainers. Based on the J-shaped relationship between alcohol intake and the risk of cardiometabolic diseases, ½-2 standard drinks/day can be considered as moderate alcohol consumption. The interpretation of the J-shaped relationship has been criticized mainly due to potential confounding from the selected reference group and uncontrolled lifestyle factors. Longer, well-designed randomized controlled trials are lacking to infer causality and to clarify the mechanism of action for the acute and chronic effects of moderate alcohol consumption on cardiometabolic health and energy homeostasis. However, some aspects of alcohol metabolism and biomarker validation could inform such a study. HotFacets is set to generate insight into the effects of acute alcohol intake on SCFA dynamics in blood, urine, and faeces; into the dose-response relationship with REE, thermogenesis, substrate oxidation, and alcohol biomarkers; and to explore potential low levels of alcohol produced in the gut.
A randomized, controlled, four times cross-over, single-blinded, meal study with 24 healthy fasting subjects will be conducted with a) placebo (water), b) a metabolic acetate generator (triacetin), and c) a half or d) one unit of isotope labelled ethanol, provided in a randomized order. Volunteers will be confined in a metabolic chamber overnight before each test drink (in 250mL water with lemon and juniper taste) and energy production and expenditure will be measured initially using seven ventilated hood measurements. After the test drinks and ventilated hood measurements an ad libitum lunch will be served before the participants will be admitted to the metabolic chamber, where metabolic measurements will be continued until the following day. Participants will go through a 2-week run-in period before each test drink and a 2-week wash out period afterwards, both with alcohol abstention. From two days before the test day in each period until one day after the test days, standardized foods will be provided. Anthropometrics, DXA, heart rate, blood pressure and all movements will be recorded before and/or during the test days. Before, during, and after the test day repeated biological samples (i.e., urine, blood, feces, hair) will be collected. The study will be divided into a pre-trial (8 subjects, 50-75y) and a main trial (16 subjects, 25-75y).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
24
Crossover meal study
Department of Nutrition, Exercise and Sports, University of Copenhagen
Copenhagen, Frederiksberg C, Denmark
RECRUITINGLars Ove Dragsted
Frederiksberg, Denmark
RECRUITINGSCFA dynamics
Difference in isotope labelled and unlabelled SCFA (mainly acetate, butyrate and propionate) concentration time course in feces, blood and urine following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-48 hours after intake
Resting energy expenditure
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-3 hours after intake
substrate oxidation rate
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-3 hours after intake
diet induced thermogenesis
Difference in resting energy expenditure, diet induced thermogenesis, and substrate oxidation following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-3 hours after intake
Biomarkers of alcohol intake in hair
Difference in alcohol biomarker levels of ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters in hair following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in urine
Difference in alcohol biomarker levels in urine following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in red blood cells
Difference in alcohol biomarker levels in red blood cells following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-1 month after intake
Biomarkers of alcohol intake in blood serum or plasma
Difference in alcohol biomarker levels in blood serum or plasma following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-1 month after intake
Low-level endogenous alcohol production measured as biomarkers of ethanol exposure during strict abstention in a metabolic chamber
Difference in low-level baseline alcohol production by the yeast and bacteria in the gut following one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-48 hours after intake
Isotope labelled metabolites
Difference in metabolites of (non-radioactive) isotope-labelled ethanol compared with triacetin ingestion in blood, red blood cells, urine, faeces and hair; these metabolites are measured by liquid chromatography time-of-flight mass spectrometry as an increase in the third isotope peak for any molecular mass feature in the chromatogram.
Time frame: 0-48 hours after intake
Heart rate and blood pressure
Difference in heart rate and BP including diurnal biphasic systolic and diastolic fluctuations measured through 24-hour ambulatory BP after one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-24 hours after intake
Alcohol levels in breath
Difference in alcohol levels measured by an alcohol breath analyzer after one unit of alcohol intake compared with half a unit, triacetin or water.
Time frame: 0-8 hours after intake
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