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Key Points
- NMN restored NAD+ balance and activated SIRT1
- Markers of oxidative damage decreased
- Damaged liver structure improved
- NMN reduced inflammatory proteins
- Stronger results seen at higher doses
Study Overview
40 eight-week-old mice were divided into four groups:
- Control (CTRL): 10 mice were given a standard liquid diet for 10 days
- Ethanol (EtOH): 10 mice were given 5% ethanol liquid diet for 10 days
- Ethanol + low dose NMN (EtOH + NMNL): 10 mice were given 300 mg/kg NMN + 5% ethanol liquid diet for 10 days
- Ethanol + high dose NMN (EtOH + NMNH): 10 mice were given 500 mg/kg NMN + 5% ethanol liquid diet for 10 days
All of the mice started with a standard liquid diet for five days to adjust and create a baseline. NMN was administered daily by intraperitoneal injection.
Oxidative Stress and Alcohol-Driven Inflammation Improved
Oxidative stress is a major driver of liver aging and degeneration. NMN reversed changes in oxidative stress markers.
"NMN supplementation significantly reduced hepatic MDA [malondialdehyde] levels, with the high-dose NMN group showing a more pronounced effect."
Further, antioxidant markers increased for enhanced antioxidant defense.
"NMN treatment increased SOD activity and GSH content compared to the ethanol group."
Inflammaging provides context for why reducing oxidative stress and inflammatory cytokines is so impactful for liver resilience and tissue repair.
*Here, superoxide dismutase (SOD), a natural antioxidant, was significantly down-regulated in the EtOH group (yellow) and restored in both NMN-supplemented groups (red & green).*
Sharp increases in inflammatory proteins were lowered back to control levels.
"NMN-treated mice showed significantly lower levels of TNF-Ξ±, IL-6, and IL-1Ξ² compared to the ethanol group."
Interestingly, the high-dose NMN saw more favorable results, suggesting a strong link between NMN and liver repair processes.
"NMN effectively mitigates alcohol-induced liver injury by suppressing oxidative stress and inflammation, with higher doses yielding more pronounced benefits."
NAD+ Levels & Energy Balance Restored
In addition to restored NAD+ levels, improvements in the NAD+/NADH ratio and normalization of NAMPT levels suggest enhanced cellular repair cycling.
"NMN supplementation effectively restored the protein expression levels of NAMPT and NMNAT, which were diminished due to ethanol exposure, and reversed the ethanol-induced decline in NAD+ levels and the NAD+/NADH ratio."
*This figure demonstrates the dramatic decrease in NAD+/NADH ratio from the control mice (blue) to the ethanol group (yellow). The high-dose (green) showed the greatest improvement towards control levels.*
SIRT1, key for supporting antioxidant defenses and enhancing cellular resilience, also saw increased activity.
"NMN provides a protective effect against alcohol-induced liver injury in mice, primarily through the activation of SIRT1."
NMN also significantly suppressed CYP2E1, an enzyme that generates ROS during alcohol metabolism, reducing a major source of oxidative injury.
"NMN treatment downregulated CYP2E1 expression⦠NMN may decrease ROS production and enhance antioxidant defense by inhibiting CYP2E1 expression."
NMN Preserved Gut Barrier Integrity & Function
NMN restored intestinal energy levels by improving ATP/ADP ratios. The effect was most potent in the high-dose (EtOH+NMNH) group.
"Ethanol exposure also significantly decreased ileal ATP levels and the ATP/ADP ratio, whereas high-dose NMN supplementation effectively restored energy balance."
Similarly, NMN also preserved key proteins and expression of genes essential for maintaining a healthy gut barrier.
"Levels of ZO-1, Claudin-1, and Occludin were reduced in the EtOH group⦠NMN supplementation effectively reversed the ethanol-induced decrease in the expression of these proteins."
Conclusion
NMN improved liver architecture and reduced histological signs of inflammation caused by alcohol exposure.
"Basic architecture of liver cells in the ethanol group was disrupted, with evident steatosis, enlargement of liver cells, and infiltration of inflammatory cells⦠NMN supplementation significantly mitigated the ethanol-induced histopathological changes in the liver."
This study shows that NMN protects against alcohol-induced liver injury in mice by restoring NAD+ metabolism, activating SIRT1 signaling, reducing oxidative stress and inflammation, and maintaining gut barrier integrity.
"NMN protects against alcoholic liver injury in a mouse model, primarily through mechanisms involving reduced oxidative stress, suppression of the inflammatory response, and enhancement of intestinal permeability, all of which are mediated by modulation of the NAD+/SIRT1 signaling pathways."
Mitochondrial energy production is central to protecting metabolically active organs like the liver.
While conducted in an animal model, the findings reinforce NMN's role as a metabolic and cellular resilience compound with relevance to liver health, gut integrity, and aging biology.
"NMN may influence the onset and progression of alcoholic liver disease, offering new perspectives for treatment strategies. Therefore, NMN presents as a promising health product warranting further investigation."
