100 Participants Needed

Nicotinamide Riboside + Ketogenic Diet for Fatty Liver Disease

NZ
KH
ST
Overseen ByStephanie T Chung, M.D.
Age: 18+
Sex: Any
Trial Phase: Academic
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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. ...

Will I have to stop taking my current medications?

Yes, participants must stop taking prescription medications or other drugs or supplements that may affect energy metabolism or nutrient digestion or absorption.

What data supports the effectiveness of the treatment involving a ketogenic diet and nicotinamide riboside for fatty liver disease?

Research suggests that low carbohydrate ketogenic diets can rapidly decrease liver fat content and improve metabolic issues related to non-alcoholic fatty liver disease (NAFLD). Additionally, weight loss through dietary changes is strongly associated with improvements in liver health.12345

Is the combination of a ketogenic diet and nicotinamide riboside safe for humans?

Research suggests that ketogenic diets, including variations like the Spanish Ketogenic Mediterranean Diet, are generally safe for treating conditions like metabolic syndrome and nonalcoholic fatty liver disease. However, specific safety data on the combination of a ketogenic diet with nicotinamide riboside is not provided in the available studies.23678

How does the treatment of Nicotinamide Riboside and Ketogenic Diet for Fatty Liver Disease differ from other treatments?

This treatment is unique because it combines Nicotinamide Riboside, a vitamin B-3 supplement that boosts NAD+ levels to improve liver health, with a Ketogenic Diet, which is high in fats and low in carbohydrates, to potentially reduce liver fat and improve metabolism. Unlike other treatments, this approach targets both cellular energy production and dietary changes to address fatty liver disease.910111213

Research Team

ST

Stephanie T Chung, M.D.

Principal Investigator

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

Eligibility Criteria

This trial is for healthy men aged 18-65 and pre-menopausal women aged 18-50 with a BMI of 25 or more, including those with MODY2 diabetes. Participants should be weight stable and able to perform moderate cycling without heart issues. Exclusions include heavy alcohol use, liver disease indicators, significant medical conditions, drug use, certain psychological conditions, strict dietary restrictions, inability to follow study procedures or give consent.

Inclusion Criteria

Able to cycle at a moderate rate and intensity with a HR equal to or greater than 0.3(SqrRoot) (220-age-HRest)+HRest but not exceeding 0.4(SqrRoot) (220-age-HRest)+HRest with no signs of arrhythmia
I am an adult with MODY2, male (18-65) or female (18-50) and not in menopause.
I am a woman aged 18-50 and have not gone through menopause.
See 4 more

Exclusion Criteria

My hematocrit level is below 37%.
You are currently involved in a regular exercise program, doing more than 2 hours of intense activity each week, as reported by you.
You drink more than 300 mg of caffeine per day, according to what you tell us.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit
1 visit (in-person)

Baseline Diet

Participants consume a standard high-carbohydrate diet to establish baseline measurements

2 days
Part of clinic stay

Ketogenic Diet with NR or Placebo

Participants consume a ketogenic low-carb diet for 5 days, with healthy volunteers taking NR or placebo

5 days
Part of clinic stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Ketogenic Diet
  • Nicotinamide Riboside
  • Placebo
  • Standard Diet
Trial Overview The trial examines the effects of a ketogenic diet and nicotinamide riboside (NR) supplement on fat usage in the body. Healthy volunteers will take NR pills for two weeks during one clinic stay and placebos during another. All participants will switch from a standard American diet to a low-carb ketogenic diet while undergoing various tests like physical exams, blood/urine tests, activity monitoring, glucose level tracking and imaging scans.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Women with overweight or obesityExperimental Treatment4 Interventions
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
Group II: Men with overweight or obesityExperimental Treatment4 Interventions
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
Group III: MODY2 PatientsExperimental Treatment3 Interventions
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

Find a Clinic Near You

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials
2,513
Recruited
4,366,000+

Findings from Research

Hypocaloric diets, especially low carbohydrate ketogenic diets, are effective in rapidly reducing liver fat and improving metabolic issues associated with non-alcoholic fatty liver disease (NAFLD).
Diets high in saturated fats are particularly harmful, as they increase liver fat and insulin resistance, while vitamin E supplementation can reduce liver fat and fibrosis but does not improve insulin resistance.
Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance.Yki-Järvinen, H.[2018]
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing alongside obesity and metabolic syndrome, making it the most common chronic liver disease, which can progress to severe conditions like cirrhosis and liver cancer.
A ketogenic diet (KD), which is very low in carbohydrates, may help alleviate oxidative stress and restore mitochondrial function, suggesting it could be a potential therapeutic approach for managing NAFLD.
Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review.Paoli, A., Cerullo, G.[2023]
In a study of 240 adults (120 with NAFLD and 120 without), low carbohydrate diets (LCDs) did not show a significant association with the risk of developing non-alcoholic fatty liver disease, suggesting that higher protein and fat intake alone may not contribute to NAFLD risk.
Patients with NAFLD had significantly higher intakes of protein, carbohydrates, and cholesterol compared to controls, indicating that while these dietary factors are prevalent in NAFLD, they do not correlate with the consumption of low carbohydrate diets.
Adherence to low carbohydrate diets and non-alcoholic fatty liver disease: a case control study.Yaghoubi, F., Darand, M., Vasmehjani, AA., et al.[2023]

References

Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. [2018]
Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review. [2023]
Adherence to low carbohydrate diets and non-alcoholic fatty liver disease: a case control study. [2023]
Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial. [2022]
Dietary Approaches for Management of Non-Alcoholic Fatty Liver Disease: A Clinician's Guide. [2021]
Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults. [2021]
The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. [2018]
The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. [2017]
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. [2023]
Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis. [2021]
Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Nicotinamide supplementation in diabetic nonalcoholic fatty liver disease patients: randomized controlled trial. [2022]
Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway. [2022]