Key Points
- Nicotinamide boosted liver cell regeneration
- NAD+ levels increased in liver cells
- Liver damage was reversed with NAM
- NAM improved mitochondrial dysfunction
Methods
9-week-old mice were kept in temperature-regulated rooms with a 12-hour light/dark cycle for 10 days. Weight and food intake were monitored daily to ensure adequate intake. Mice were split into four groups:
- Control group (CTRL): control diet (normal liquid diet, no alcohol)
- Ethanol group (EtOH): alcohol-containing liquid diet (ethanol diet)
- Ethanol + NAM group (EtOH+NAM): alcohol diet + 250 mg/kg NAM daily
- Control + NAM group (NAM): control diet + 250 mg/kg NAM daily
On Day 11, all mice were given a single large oral dose of ethanol (5 g/kg body weight) to simulate binge drinking.
NAM Protected Against Harmful Alcohol Effects
Excessive fat buildup in the liver was completely reversed in NAM-supplemented subjects.
"In some ethanol‐fed mice, microsteatosis and inflammatory cell accumulation were also frequently observed. In contrast, alcoholic steatosis was completely abolished when the mice were given NAM in the EtOH+NAM group."
Similarly, NAM lowered markers related to liver damage, appearing protective against alcohol's harmful effects…
"Ethanol consumption raised serum AST and ALT, while NAM significantly decreased their values… NAM markedly showed its effects by lowering the serum GGT and TG in the EtOH+NAM group."
…and lowered oxidative stress levels to that of the control group.
"Oxidative stress was also elevated in the EtOH group… NAM treatment saved this situation, the level of MDA and GSH showed no significant difference between EtOH+NAM group and the CTRL group."
Liver Cell NAD+ Levels Improved With NAM
Nicotinamide significantly increased NAD+ in the liver for the EtOH+NAM group.
- NAM group NAD+ levels were 9.32 ± 0.19 nmol/mg
- EtOH group NAD+ levels were 6.83 ± 0.14 nmol/mg
- EtOH+NAM group NAD+ levels were 8.01 ± 0.30 nmol/mg
Nicotinamide phosphoribosyltransferase (NAMPT), the limiting ingredient for NAD+ production, was found to be inhibited in EtOH mice, which was reversed and even enhanced with NAM treatment.
"NAM supplement also increased the NAMPT levels in the liver and serum of normal mice (NAM group)."
This restoration of NAD+ biosynthesis supports DNA repair and cellular resilience provides broader context for NAM's protective effects in alcohol-induced liver injury.
Mitochondria Protected From Structural Damage and Dysfunction
Alcohol-induced liver injury is often due to the inability of cells to produce quality energy to regenerate and repair. NAM, as a precursor to NAD+, was found to mitigate alcohol-induced mitochondrial damage, supporting proper energy production and function.
The EtOH group exhibited various forms of mitochondrial damage, including:
- Small holes and cavities in the cell cytoplasm, likely due to protein degradation.
- Swelling in a large number of the mitochondria.
- Structural damage in the mitochondrial folds, with missing or broken parts.
Conversely, the mitochondria in the EtOH+NAM group were greatly improved compared to the EtOH group, suggesting the ability of NAM to rescue energy metabolism disorder and prevent liver injury from alcohol.
"By contrast, mitochondrial damage was well improved in the EtOH+NAM group. The mitochondrial density was slightly increased and mitochondrial swelling was reduced."
NAM was shown to upregulate enzymes essential to ATP synthesis, both of which saw a reduction in the EtOH group.
"Results revealed that SDH and CS were expressed significantly lower in the EtOH group than in the CTRL group, yet were shown as a normal level in EtOH+NAM group."
Similarly, uncoupling protein 2 (UCP2), important for efficient mitochondrial energy production, was lowered by NAM when elevated by EtOH.
"[UCP2] was lowered in the EtOH+NAM group, suggesting that the NAM supplement protects against EtOH‐induced UCP2 dysregulation."
NAM addressed the low production of ATP in the liver resulting from alcohol consumption, suggesting the potential to restore mitochondrial energy production and enhance liver cellular function.
Comprehensive research on mitochondrial health helps explain why restoring NAD+ availability is central to reversing alcohol-related energy deficits and supporting organ recovery.
Liver Damage Reversed With Boosted Liver Cell Regeneration
Undoubtedly, the EtOH group saw more serious liver damage and fat buildup than the other groups, while NAM specifically worked to mitigate the damage.
"Following 4 and 7 days post‐PH, the basic structure of liver cells in the ETOH+NAM group recovered faster than that in the ETOH group."
As well, there was a boost in liver repair cell growth in the EtOH+NAM group to enhance regeneration, likely due to an increase in ATP production.
"We observed more increased active proliferation hepatocytes in the EtOH+NAM group than that in the EtOH group. These results suggested that NAM may accelerate ATP generation to support liver regeneration after PH."
When testing specific liver injury biomarkers, NAM reduced liver damage after alcohol and helped restore NAD+ levels to enhance the healing process.
Conclusion
Alcohol is known to cause dysfunction in energy metabolism, contributing to alcoholic liver disease (ALD). This study found NAM restored energy metabolism balance and shows promise as a therapeutic for ALD.
"Our results showed that NAM supplements not only protected the liver from alcohol‐induced injury and improved alcohol‐induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content."
"These findings suggested that NAM… can promote liver regeneration and improves liver function by alleviating alcohol‐induced energy metabolism disorder."
