NR Doubles Liver Repair Efficiency!
When discussing liver health, one fundamental question arises: how can we effectively support this “biochemical factory of the human body” in its complex repair processes when faced with metabolic stress, fat accumulation, or even injury?
In recent years, scientific attention has increasingly focused on a crucial intracellular coenzyme—nicotinamide adenine dinucleotide (NAD⁺). NAD⁺ levels decline with aging and metabolic disorders, which is closely associated with various liver dysfunctions. Emerging research suggests that supplementing its precursor, nicotinamide riboside (NR), combined with a key participant in energy metabolism—malate, may offer a multi-target, synergistic strategy for maintaining liver health.
While earlier studies have outlined the complexity of hepatic energy metabolism, a study published in Hepatology Communications directly demonstrated the practical benefits of increasing NAD⁺ levels for repairing damaged liver tissue.
This research addressed a significant clinical challenge: obesity impairs liver regeneration, especially after portal vein embolization (PVE)—a procedure used to induce liver hypertrophy before major liver resection. In obese patients, liver regeneration efficiency is often markedly reduced.
The researchers established a high-fat diet-induced obese rat model and performed PVE surgery. One group received NR supplementation (3 mg/mL in drinking water), while the control group did not. The results were striking:
Figure: After NR supplementation (PVE+NR group), the liver-to-body weight ratio was significantly higher in the early postoperative period (days 1 and 3), indicating accelerated liver regeneration.
Mechanistic analysis suggests that NR exerts its effects through modulation of the MCART1/ASB3 axis:
Another study published in the American Journal of Physiology – Gastrointestinal and Liver Physiology highlighted the importance of malate as a key metabolic substrate.
Malate is a core intermediate of the tricarboxylic acid (TCA) cycle, playing a pivotal role in cellular ATP production. When combined with:
Notably, the study found that:
This suggests that, in the liver, malate combined with specific amino acids (such as glutamate) may represent a more favorable energy-producing pathway. Adequate malate availability is therefore critical for maintaining efficient mitochondrial function and meeting the liver’s high demands for biosynthesis and detoxification.
Additionally, the study revealed sex differences in mitochondrial function:
Based on these findings, a combined supplementation strategy—Nicotinamide Riboside Hydrogen Malate (NRHM)—has emerged with a clear scientific rationale:
In summary, recent scientific advances provide important insights into liver health from two perspectives:
While further clinical studies are needed to confirm its effects in humans, current scientific evidence provides a strong theoretical foundation for this promising approach.
References：
[1] Dave, D. D., et al. (2025). Sex dimorphism and substrate dependency of liver mitochondrial bioenergetics and H₂O₂ production. American Journal of Physiology-Gastrointestinal and Liver Physiology, 329(6): G664-G679.
[2] Wang, H., et al. (2026). Nicotinamide riboside enhances liver regeneration via the MCART1/ASB3 axis in obesity-compromised rats. Hepatology Communications, 10: e0866.
In recent years, scientific attention has increasingly focused on a crucial intracellular coenzyme—nicotinamide adenine dinucleotide (NAD⁺). NAD⁺ levels decline with aging and metabolic disorders, which is closely associated with various liver dysfunctions. Emerging research suggests that supplementing its precursor, nicotinamide riboside (NR), combined with a key participant in energy metabolism—malate, may offer a multi-target, synergistic strategy for maintaining liver health.
PART 01
Direct Evidence of NR: Promoting Regeneration in Obesity-Damaged LiverWhile earlier studies have outlined the complexity of hepatic energy metabolism, a study published in Hepatology Communications directly demonstrated the practical benefits of increasing NAD⁺ levels for repairing damaged liver tissue.
This research addressed a significant clinical challenge: obesity impairs liver regeneration, especially after portal vein embolization (PVE)—a procedure used to induce liver hypertrophy before major liver resection. In obese patients, liver regeneration efficiency is often markedly reduced.
The researchers established a high-fat diet-induced obese rat model and performed PVE surgery. One group received NR supplementation (3 mg/mL in drinking water), while the control group did not. The results were striking:
- Increased NAD⁺ Levels
NR supplementation significantly elevated NAD⁺ levels in liver tissue, confirming its effectiveness. - Improved Liver Injury and Steatosis
Compared to obese rats receiving PVE alone, the NR-treated group showed significantly reduced serum ALT and AST levels, indicating improved liver function. Histological analysis also revealed reduced inflammatory infiltration and lipid accumulation. - Accelerated Hepatocyte Proliferation and Liver Regeneration
EdU labeling and Ki67 staining demonstrated significantly enhanced hepatocyte proliferation in the NR group. Macroscopically, the liver-to-body weight ratio was significantly higher on postoperative days 1 and 3, clearly indicating accelerated liver regeneration.
Figure: After NR supplementation (PVE+NR group), the liver-to-body weight ratio was significantly higher in the early postoperative period (days 1 and 3), indicating accelerated liver regeneration.
Mechanistic analysis suggests that NR exerts its effects through modulation of the MCART1/ASB3 axis:
- MCART1 (mitochondrial carrier triple repeat protein 1), associated with energy metabolism
- ASB3 (ankyrin repeat and SOCS box-containing protein 3), associated with lipid metabolism
PART 02
The Role of Malate: A Central Node in Energy MetabolismAnother study published in the American Journal of Physiology – Gastrointestinal and Liver Physiology highlighted the importance of malate as a key metabolic substrate.
Malate is a core intermediate of the tricarboxylic acid (TCA) cycle, playing a pivotal role in cellular ATP production. When combined with:
- Pyruvate (PM combination), or Glutamate (GM combination)
Notably, the study found that:
- The glutamate + malate (GM) combination supports a higher mitochondrial respiration rate than pyruvate + malate (PM)
This suggests that, in the liver, malate combined with specific amino acids (such as glutamate) may represent a more favorable energy-producing pathway. Adequate malate availability is therefore critical for maintaining efficient mitochondrial function and meeting the liver’s high demands for biosynthesis and detoxification.
Additionally, the study revealed sex differences in mitochondrial function:
- Female rats showed higher respiration rates and H₂O₂ production than males
- However, their energy coupling efficiency was lower
PART 03
Synergistic Enhancement: The Liver-Protective Logic of NRHMBased on these findings, a combined supplementation strategy—Nicotinamide Riboside Hydrogen Malate (NRHM)—has emerged with a clear scientific rationale:
(1) NR Boosts the “Energy Currency” NAD⁺
As an efficient NAD⁺ precursor, NR directly elevates intracellular NAD⁺ levels. Increased NAD⁺ activates deacetylases such as SIRT1 and SIRT3, leading to:- Improved mitochondrial function
Promotes mitochondrial biogenesis and fatty acid oxidation - Reduced oxidative stress and inflammation
Enhances antioxidant defenses and inhibits inflammatory pathways such as the NLRP3 inflammasome - Enhanced DNA repair
Provides substrate for PARP enzymes to maintain genomic stability
(2) Malate Supplies Metabolic “Fuel”
Hydrogen malate provides malate that directly enters the TCA cycle:- Optimizes energy production
Ensures efficient TCA cycle operation, supporting NADH and ATP generation - Supports liver-specific metabolism
Malate-based pathways (e.g., with glutamate) may have unique advantages in hepatic metabolism - Potential synergistic effect
Adequate TCA intermediates may help meet increased metabolic flux demands induced by elevated NAD⁺ levels
PART 04
Conclusion and OutlookIn summary, recent scientific advances provide important insights into liver health from two perspectives:
- Fundamental level
Revealing the complexity and individual variability of liver mitochondrial metabolism, highlighting the central role of malate - Applied level
Demonstrating that increasing NAD⁺ levels (via NR supplementation) can significantly improve obesity-related liver injury and promote liver regeneration
- Enhancing core coenzyme (NAD⁺)
to - Optimizing energy metabolism pathways (TCA cycle)
- Its globally leading full-enzyme production technology
- The world’s first patented NRHM crystal form
While further clinical studies are needed to confirm its effects in humans, current scientific evidence provides a strong theoretical foundation for this promising approach.
References：
[1] Dave, D. D., et al. (2025). Sex dimorphism and substrate dependency of liver mitochondrial bioenergetics and H₂O₂ production. American Journal of Physiology-Gastrointestinal and Liver Physiology, 329(6): G664-G679.
[2] Wang, H., et al. (2026). Nicotinamide riboside enhances liver regeneration via the MCART1/ASB3 axis in obesity-compromised rats. Hepatology Communications, 10: e0866.
