Study Description:
This is a randomized, double-blind, placebo-controlled crossover study of adults with overweight or obesity to determine whether nicotinamide riboside supplementation increases sleeping energy expenditure and fat oxidation rate during a ketogenic diet.
Objectives:
Primary Aim 1: Determine whether sleeping energy expenditure increases after transitioning to a low carbohydrate ketogenic diet as compared to a baseline high carbohydrate run-in diet in men
Primary Aim 2: Determine whether sleeping energy expenditure is affected by NR supplementation during a ketogenic diet in men
Secondary Aim 1: Determine whether fat oxidation during sleep increases after transitioning to a low carbohydrate ketogenic diet as compared to a baseline high carbohydrate run-in diet in men
Secondary Aim 2: Determine whether fat oxidation during sleep is affected by NR supplementation during a ketogenic diet from the baseline run-in diet in men
Exploratory Aims: Exploratory comparison of the above endpoints between men and women without MODY2.
Exploratory comparison of the above diet-related endpoints between patients with MODY2 and those obtained during the Placebo period in other participants.
Several exploratory measurements are planned to help comprehensively phenotype the effects of the diets and nicotinamide riboside supplementation and are intended to be hypothesis-generating. We will assess the following:
* Liver TG
* Daily ketosis, insulin secretion, and protein utilization
* Rates of ketogenesis and lipolysis
* Physical activity and sleep assessment
* Body composition assessment
* Fasting and postprandial blood measurements of various metabolites, hormones, cytokines, markers of inflammation , and other circulating signaling factors.
* Microbiome composition
* Hunger and satiety before and after meals
* Eating rate
* Chronotype and sleep quality
* Usual food intake
* 24-h and exercise energy expenditure
Endpoints:
Primary:
Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet
Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet
Secondary:
Mean change in sleeping fat oxidation rate between the ketogenic diet and the baseline run-in diet Mean difference in fat oxidation rate between NR and placebo during the ketogenic diet
Exploratory:
* H magnetic resonance spectroscopy
* 24hr urine ketones, C-peptide, nitrogen
* Stable isotope infusions of 13C beta-hydroxybutyrate and 2H glycerol
* Daily accelerometry and wireless EEG headband
* DXA scans
* Fasting and postprandial blood concentrations of various metabolites, hormones, cytokines, inflammatory markers and other circulating signaling factors
* Blood glucose variability and mean concentration as measured by Continuous Glucose Monitoring
* Daily fasting glucose and beta-hydroxybutyrate concentrations by finger-prick
* Microbiome composition
* Hunger and satiety visual analogue scores
* Meal duration
* Pittsburg sleep quality index, morningness-eveningness questionnaire, and subjective sleep visual analogue scores
* Usual food intake as measured by Food frequency questionnaire
* 24-h and exercise energy expenditure from respiratory chamber
