Introduction
Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide and is closely linked with obesity, type 2 diabetes, hypertension, and dyslipidemia. The disease spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which may progress to advanced fibrosis, cirrhosis, and end-stage liver disease.
MAFLD is now defined by hepatic steatosis in association with metabolic dysfunction such as overweight/obesity, insulin resistance, or type 2 diabetes. Its pathogenesis is multifactorial, involving excess free fatty acid influx, de novo lipogenesis, oxidative stress, mitochondrial dysfunction, inflammatory signaling, hepatic stellate cell activation, and gut dysbiosis. Liver fibrosis assessment relies on invasive biopsy, while noninvasive modalities such as transient elastography and magnetic resonance elastography are increasingly used for disease staging.
Despite its rising global burden, no approved pharmacological therapy exists for MAFLD. Curcumin, a bioactive polyphenol derived from Curcuma longa, has shown hepatoprotective, antioxidant, anti-inflammatory, and metabolic regulatory effects in preclinical and clinical studies. However, clinical evidence remains inconsistent, particularly regarding liver enzyme modulation, and data on liver fat content and fibrosis are still limited.1
Mechanisms of action
Curcumin exerts multi-targeted actions in metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating key pathways involved in lipid accumulation, inflammation, and oxidative stress. It downregulates lipogenic transcription factors such as sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase, thereby reducing hepatic de novo lipogenesis. Simultaneously, it enhances fatty acid β-oxidation through activation of peroxisome proliferator-activated receptor-α (PPAR-α), contributing to decreased hepatic lipid deposition.
- Anti-inflammatory and antioxidant effects:
Chronic hepatic inflammation is a central driver of MAFLD progression. Curcumin inhibits nuclear factor kappa B (NF-κB) signaling and suppresses pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). In parallel, it reduces oxidative stress by scavenging reactive oxygen species and enhancing endogenous antioxidant defense systems such as superoxide dismutase, catalase, and glutathione peroxidase, thereby limiting lipid peroxidation and hepatocellular injury.2
- Effects on insulin resistance and metabolic regulation:
Curcumin improves insulin sensitivity by modulating insulin signaling pathways and reducing systemic metabolic inflammation.3 It has been shown to regulate glucose homeostasis, decrease hyperinsulinemia, and improve lipid profiles by lowering triglycerides, low-density lipoprotein cholesterol, and total cholesterol while increasing high-density lipoprotein cholesterol. These effects collectively contribute to improved metabolic balance in MAFLD patients.
- Antifibrotic potential:
Progression of MAFLD to fibrosis involves activation of hepatic stellate cells and excessive extracellular matrix deposition. Curcumin inhibits hepatic stellate cell activation and downregulates profibrotic mediators such as transforming growth factor-β (TGF-β) and connective tissue growth factor. This helps attenuate fibrogenesis and may slow or prevent progression to cirrhosis.
- Gut–liver axis modulation:
Emerging evidence suggests that curcumin positively influences gut microbiota composition, restoring intestinal barrier integrity and reducing endotoxin translocation.4 By decreasing lipopolysaccharide-mediated inflammatory signaling, it further alleviates hepatic inflammation and metabolic dysregulation associated with MAFLD.
Clinical evidence
Clinical studies evaluating curcumin supplementation in MAFLD patients have demonstrated improvements in liver enzymes, particularly alanine aminotransferase and aspartate aminotransferase, along with reductions in hepatic steatosis in some trials. However, heterogeneity in dosage, formulation, and treatment duration has resulted in variable outcomes across studies, and consistent effects on liver stiffness and fibrosis remain insufficiently established.
Limitations and challenges
Despite promising therapeutic potential, curcumin’s clinical utility is limited by poor bioavailability, rapid metabolism, and low systemic absorption. These pharmacokinetic constraints necessitate high doses or specialized formulations, which may affect consistency of clinical outcomes.
Conclusion
Curcumin demonstrates multi-dimensional therapeutic effects in MAFLD through lipid regulation, anti-inflammatory, antioxidant, insulin-sensitizing, and antifibrotic mechanisms. Although preclinical evidence is strong, further large-scale, standardized clinical trials using optimized formulations are required to confirm its efficacy and establish its role as a therapeutic adjunct in MAFLD management.
References:
- Lukkunaprasit T, Tansawet A, Boonmanunt S, et al. An updated meta-analysis of effects of curcumin on metabolic dysfunction-associated fatty liver disease based on available evidence from Iran and Thailand. Sci Rep. 2023;13(1):5824. Published 2023 Apr 10. doi:10.1038/s41598-023-33023-3. https://pmc.ncbi.nlm.nih.gov/articles/PMC10086025/
- Cheng M, Ding F, Li L, et al. Exploring the role of curcumin in mitigating oxidative stress to alleviate lipid metabolism disorders. Front Pharmacol. 2025;16:1517174. Published 2025 Jan 30. doi:10.3389/fphar.2025.1517174. https://pmc.ncbi.nlm.nih.gov/articles/PMC11822302/
- Li X, Wang Y, Xiong M, Xie C, Yang D. The therapeutic effect of curcumin in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of animal studies. Front Pharmacol. 2025;16:1714245. Published 2025 Nov 24. doi:10.3389/fphar.2025.1714245. https://pmc.ncbi.nlm.nih.gov/articles/PMC12682766/
- Konaktchieva M, Stojchevski R, Hadzi-Petrushev N, et al. Curcumin and Tetrahydrocurcumin as Multi-Organ Modulators of the Adipose Tissue-Gut-Liver Axis: Mechanistic Insights, Therapeutic Potential, and Translational Challenges. Pharmaceuticals (Basel). 2025;18(12):1791. Published 2025 Nov 25. doi:10.3390/ph18121791. https://pmc.ncbi.nlm.nih.gov/articles/PMC12735883/