NAD⁺ and NAFLD - caution, causality and careful optimism

Area of Science:

• Hepatology
• Metabolic Diseases
• Biochemistry

Background:

• Non-alcoholic fatty liver disease (NAFLD) prevalence is rising globally, necessitating novel therapeutic strategies.
• Nicotinamide adenine dinucleotide (NAD+) plays a crucial role in cellular energy metabolism, redox balance, and antioxidant defense.
• NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), are investigated for their therapeutic potential in NAFLD.

Purpose of the Study:

• To review preclinical evidence on NAD+ supplementation for NAFLD treatment and prevention.
• To reconcile findings from preclinical models with initial human clinical trial data.

Main Methods:

• Review of preclinical investigations into NAD+ supplementation in NAFLD models.
• Analysis of data from early-phase clinical trials of NAD+ precursors in humans.

Main Results:

• Preclinical studies demonstrate that NAD+ precursor supplementation increases hepatic NAD+ levels, prevents fat accumulation, improves mitochondrial function, and reduces oxidative stress in NAFLD models.
• NAD+ repletion in preclinical models also inhibits progression to non-alcoholic steatohepatitis (NASH) by reducing hepatic stellate cell activation and fibrosis.
• Initial clinical trials in individuals with obesity have reported only modest effects of NAD+ precursor administration.

Conclusions:

• NAD+ precursor supplementation holds significant preclinical promise for targeting NAFLD pathogenesis.
• Further research is needed to bridge the gap between promising preclinical findings and the modest outcomes observed in initial human studies for NAFLD treatment.