Metabolic Changes Induced by NMN in Healthy Subjects With Acute Binge Drink

Study Overview
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Brief Summary
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The goal of this double-blinded, randomized, crossover trial is to investigate the effects of NMN supplementation on liver function, liver fat content and lipid metabolism in healthy young subjects with acute binge drink. The main questions it aims to answer are: if NMN administration could accelerate alcohol metabolism and alleviate hangover symptom; if NMN administration could alleviate alcohol-induced liver injury and hepatic steatosis.

Detailed Description
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The goal of this double-blinded, randomized, crossover trial is to investigate the effects of NMN supplementation on liver function, liver fat content and lipid metabolism in healthy young subjects with acute binge drink. The main questions it aims to answer are: if NMN administration could accelerate alcohol metabolism and alleviate hangover symptom; if NMN administration could alleviate alcohol-induced liver injury and hepatic steatosis. Participants will be randomized into two groups (n=20), and take 4 NMN capsules (250mg/capsule) or 4 placebo capsules (maltodextrin), respectively. 15 minutes later, they are successively provided with same breakfast and then vodka with a dose of 1g/kg body weight. Venous blood are collected at 0h, 1h, 2h, 3h, 4h, 8h, 12h and 24h from each subject, respectively. In addition, nuclear magnetic resonance imaging (MRI) are taken at 0h, 4h and 24h after alcohol intake. After a 7-day washout period, volunteers are crossed over to another alternative group to receive the corresponding capsules and the test protocol repeats twice.

Official Title
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Effect of β-nicotinamide Mononucleotide Intervention on Healthy Young Subjects With Acute Binge Drink: a Double-blinded, Randomized, Crossover Trial

Conditions
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Binge Drinking, Liver Injury, Nutritional Supplementation, Hepatic Steatosis

Intervention / Treatment
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* Dietary Supplement: β-nicotinamide Mononucleotide
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a. Sign informed consent Exclusion Criteria: Neurological disorders Alcohol allergy Alcohol addiction Gastrointestinal diseases Liver, kidney, cardiovascular or systemic diseases Antibiotics were administered within 2 weeks prior to the trial Participants who ate a vegetarian diet Unable to use a smartphone or computer with Internet access Participate in another intervention study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

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: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: maltodextrin group<br>4 capsule with 1000mg ''maltodextrin'' | Dietary Supplement: Maltodextrin<br>* After an 8-hour overnight fast, the participants ingested maltodextrin capsules with a single morning dose of 1000mg.<br>|
| Experimental: β-nicotinamide mononucleotide group<br>4 capsule with 1000mg ''β-nicotinamide mononucleotide'' | Dietary Supplement: β-nicotinamide Mononucleotide<br>* After an 8-hour overnight fast, the participants ingested β-nicotinamide Mononucleotide capsules with a single morning dose of 1000mg. The purity of β-nicotinamide Mononucleotide capsules was no less than 97% according to high-performance liquid chromatography analysis.<br>* Other names: NMN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethanol concentration | Ethanol concentration change in mg/dL of each set | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| Acetaldehyde concentration | Acetaldehyde concentration change in mg/dL of each set | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| Hepatic fibrosis change | Research blood hepatic fibrosis include:Hyaluronicacid in ng/mL;Laminin in ng/mL;type Ⅲ in ng/mL;precollagen in ng/mL;type Ⅳ collagen in ng/mL;Fibronect in ng/mL | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| hepatic function change | Research blood hepatic function include:TBIL in μmol/L;Direct bilirubin in μmol/L;Indirect bilirubin in μmol/L;Total bile acid in μmol/L | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| hepatic injury change | Research blood hepatic injury include:Alanine Aminotransferase in U/L;Aspartate Aminotransferase in U/L;Gamma-Glutamyltransferase in U/L;Alpha-Fucosidase in U/L;Alkaline Phosphatase in U/L;cholinesterase in U/L;Lactate Dehydrogenase Enzyme in U/L | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| Lipid metabolism change | Research blood Fat metabolism include:Triglycerides in mmol/L;HDL-Cholesterol in mmol/L;LDL--Cholesterol in mmol/L;Apolipoprotein A in mmol/L;Apolipoprotein B in mmol/L;Lipoprotein(a) in mmol/L | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| hangover cognition assessment tools after drinking | The survey tool consisted of many questions addressing cognition headache, nausea,vomiting,fatigue,concentration,thirst or dehydration,light sensitivity,sleeping difficulty,excessive sweating,anxiety,feelings of depression,trembling or shaking,dizziness,stomachache,and memory loss after drinking | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory markers of inflammation | Research blood Inflammatory factor include:Interleukin-2 in pg/ml;Interleukin-4 in pg/ml;Interleukin-6 in pg/ml;Interleukin-8 in pg/ml;Interleukin-10 in pg/ml;Tumor necrosis factor in pg/ml;Interferon gamma in pg/ml;Human IL-1 beta protein in pg/ml;High Sensitivity C-reactive Protein in mg/L | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| nicotinamide adenine dinucleotide metabolism change | NAD+ metabolism will be analysed by performing Liquid Chromatography Mass Spectrometer（LC-MS） on serum | day1-2 and day 8-9 of each 30minutes and 1hour and 2 hours and 3 hours and 4 hours and 5 hours and 6 hours and 12 hours and 24 hours | 
| Fecal metabolites | Gut microbial communities and their abundant features will be analysed based on shotgun metagenomic sequencing. | day1-2 and day 8-9 of each set | 
| Metabolomics profiling | Targeted metabonomics are analyzed based on urine and faeces at all visits | day1-2 and day 8-9 of each set | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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β-nicotinamide mononucleotide, Acute alcohol intake, Nutritional supplementation, Liver