Effect of Nicotinamide Riboside on Ketosis, Fat Oxidation & Metabolic Rate

NCT06044935 | Recruiting

• 2 other identifiers: 10001690001690-DK
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: At least 30% of Americans have fatty liver disease. This means that they store too much fat in the liver. At the moment lifestyle changes are the only way to treat this problem. Objective: To test how (1) a low-carbohydrate diet and (2) a supplement called nicotinamide riboside (NR) affect how a person s body uses dietary fat. Eligibility: Men aged 18 to 65 and women aged 18 to 50 who are healthy volunteers with a body mass index (height to weight ratio) of 25 or more. Adults with maturity-onset diabetes of the young type 2 (MODY2) are also needed. Design: Participants with diabetes will have 1 screening visit and a 9-day clinic stay. Healthy volunteers will have 1 screening visit and 2 clinic stays of 1 to 2 weeks each. During screening, all participants will have a physical exam with blood and urine tests. They will have their heart rhythm measured while riding a gym bike. NR is a pill taken by mouth. Only healthy volunteers will take the NR, for 14 days at a time, during 1 clinic stay. During their other stay, they will take placebos; these are pills that look like the study supplement but contain no NR. During each clinic stay, all participants will eat a normal American diet. Then they will eat a ketogenic "low-carb" diet for 5 days. Participants will have many tests, including: Sleeping every night and having two 24-hour stays in a special room that measures the gases their body uses and produces. Drinking a high-fat shake, then remaining seated for 5 hours while their blood and breath are monitored. Having a substance injected into the arm and remaining seated for 3 hours while their blood is measured. Wearing monitors to measure their activity levels. Another monitor will measure their blood glucose levels. Having imaging scans. ...

Conditions

Overweight; Obesity

Keywords

Ketogenic Diet; Sleep; Energy Expenditure; Supplement; Calories

Outcome Measures

Primary Outcomes (2)

• Mean change in sleeping energy expenditure between the ketogenic diet and the baseline run-in diet

  Mean change in sleeping energy expenditure measured by room calorimetry from 2 days of standard run-in diet to 5 days of ketogenic diet

  7 days

• Mean difference in sleeping energy expenditure between NR and placebo during the ketogenic diet

  Mean difference in sleeping energy expenditure measured by room calorimetry during 5 days of ketogenic diet with NR supplementation or placebo

  5 days

Secondary Outcomes (2)

• Mean change in sleeping fat oxidation rate between the ketogenic diet and the baseline run-in diet

  7 days

• Mean difference in fat oxidation rate between NR and placebo during the ketogenic diet

  5 days

Study Arms (3)

Men with overweight or obesity

EXPERIMENTAL

To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity

Other: Standard Diet; Other: Ketogenic Diet; Dietary Supplement: Placebo; Dietary Supplement: Nicotinamide Riboside

MODY2 Patients

EXPERIMENTAL

To measure changes in sleeping energy expenditure and fat oxidation rate after transitioning from a baseline diet to an isocaloric ketogenic diet similar to our previous study in men

Other: Standard Diet; Other: Ketogenic Diet; Dietary Supplement: Placebo

Women with overweight or obesity

EXPERIMENTAL

To investigate whether NR supplementation augments the sleeping energy expenditure and fat oxidation rate during the ketogenic diet in men and women with overweight and obesity

Other: Standard Diet; Other: Ketogenic Diet; Dietary Supplement: Placebo; Dietary Supplement: Nicotinamide Riboside

Interventions

Placebo DIETARY_SUPPLEMENT

Subjects without MODY2 will take either placebo or NR (1 g BID, 2 g per day total) supplements for 7 days during this Run-in phase

MODY2 Patients; Men with overweight or obesity; Women with overweight or obesity

Standard Diet OTHER

Consisting of 15% protein, 35% fat, and 50% carbohydrate, matching the macronutrient composition of a typical American diet

MODY2 Patients; Men with overweight or obesity; Women with overweight or obesity

Ketogenic Diet OTHER

Consisting of a macronutrient composition of 15% protein, 80% fat, and 5% carbohydrate

MODY2 Patients; Men with overweight or obesity; Women with overweight or obesity

Nicotinamide Riboside DIETARY_SUPPLEMENT

Subjects without MODY2 will take either placebo or NR (1 g BID, 2 g per day total) supplements for 7 days during this Run-in phase

Men with overweight or obesity; Women with overweight or obesity

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Meet one of the following:
• Adult males aged 18-65 years
• Pre-menopausal adult females aged 18-50 years
• Adult males aged 18-65 years with diagnosed maturity-onset diabetes of the young type 2 (MODY2) or pre-menopausal adult females aged 18-50 years with diagnosed MODY2
• Weight stable (\< +/- 5 % body weight change over past 6 months) as determined by volunteer report
• Body mass index (BMI) \>= 25 kg/m\^2 (of \>=18.5 kg/m\^2 for patients with MODY2)
• Able to cycle at a moderate rate and intensity with a HR equal to or greater than 0.3x(220-age-HRrest)+HRrest but not exceeding 0.4x(220-age-HRrest)+HRrest with no signs of arrhythmia

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Taking prescription medications or other drugs or supplements that may influence energy metabolism or nutrient digestion or absorption (including, but not limited to, diet/weight-loss medication or other medications at the discretion of the PI and/or study team)
• Indicators of liver disease; combination of both albumin \< 2.8 mg/mL and bilirubin \> 3 mg/mL
• Individuals with significant medical comorbidities (e.g., non-MODY2 diabetes, NYHA Class \>II heart failure, or CKD Stage II or worse, or American Society of Anesthesiologists Physical Status Class 3 or above)
• Individuals taking prescription medications to treat hypertension in participants without MODY2
• Participating in a regular exercise program (\> 2h/week of vigorous activity) as determined by volunteer report
• Positive pregnancy test (only for people who can get pregnant)
• Hematocrit \< 40% (men only)
• Hematocrit \<37% (women only)
• Caffeine consumption \> 300 mg/day as determined by volunteer report
• Alcohol consumption \> 3 drinks per day for men or \> 2 drinks per day for women as determined by volunteer report
• Regular use of tobacco (smoking or chewing), e-cigarettes (a.k.a. vapes), nicotine patches, or illicit drugs over past 6 months as determined by volunteer report. Subjects may also be excluded based on a urine drug test.
• Psychological conditions as determined by volunteer report such as (but not limited to) eating disorders, depression, bipolar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators
• Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies) or a reported dislike of a significant fraction of the study foods
• Unwilling or unable to comply with or perform all study procedures (e.g. cycling or activities of daily living), or unavailability for the duration of the study, as determined by participant or investigator discretion

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Hall KD, Chen KY, Guo J, Lam YY, Leibel RL, Mayer LE, Reitman ML, Rosenbaum M, Smith SR, Walsh BT, Ravussin E. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. Am J Clin Nutr. 2016 Aug;104(2):324-33. doi: 10.3945/ajcn.116.133561. Epub 2016 Jul 6.

  PMID: 27385608 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Overweight; Obesity

Interventions

Diet, Ketogenic; nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Stephanie T Chung, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nan Zhai, C.R.N.P.

CONTACT

(301) 827-3324; nan.zhai@nih.gov

Stephanie T Chung, M.D.

CONTACT

(240) 479-8137; stephanie.chung@nih.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: September 21, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04-17

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Upon publication in peer reviewed journal
• Access Criteria: Open

Locations

US (1)