Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become prevalent worldwide, affecting 32% of adults globally. The prevalence of this condition, which coincides with the obesity and diabetes epidemics, exceeds 40% in North and South America and Southeast Asia, and it is higher among males.¹ The initially asymptomatic nature of the problem can make diagnosis difficult, delaying treatment.
In addition to addressing the dietary and lifestyle factors for cardiometabolic health, supplements may be an important adjunct for the clinician’s toolbox. Pharmacologic treatments specifically for fatty liver are limited. Certain nutrients and herbs may reduce steatosis abnormal accumulation of excess fat within cells and organs), expedite hepatic repair and healing, and ultimately reverse fatty liver disease.
How Fatty Liver Develops
Fatty liver disease is the pathological accumulation of triglycerides inside hepatocytes, also known as hepatic steatosis. Oxidative stress and inflammation contribute to the pathological process. It’s a spectrum of disease, including simple fatty liver and, as it progresses, hepatitis, fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma.²
Depending on the cause, fatty liver may be mostly benign or may progress to more serious problems. Alcohol use and cardiometabolic risk factors are the leading causes. Various medications and diseases are also risk factors for fatty liver. These include chronic kidney disease, genetic factors, Polyendocrine Metabolic Ovarian Syndrome (PMOS), previously Polycystic Ovarian Syndrome (PCOS), and use of amiodarone, aspirin, tamoxifen, steroids, and several other medications.¹,³
MASLD, NAFLD, MASH, NASH, ALD – What Do the Acronyms Mean?
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) or fatty liver disease (MAFLD)
This condition is formerly known as non-alcoholic fatty liver disease (NAFLD), although the terminology is used interchangeably. Excess visceral fat contributes to atherogenic dyslipidemia and insulin resistance, increasing the risk of type 2 diabetes and promoting the onset and progression of fatty liver disease.¹,³ Alcohol is not the main contributor. Histologically, this condition is defined as ≥5% fat content in the absence of hepatocellular injury.³
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Formerly known as non-alcoholic steatohepatitis (NASH), although NASH is still widely referred to. MASH occurs when MASLD progresses to inflammation (hepatitis), causing tissue damage and fibrosis. Technically, MASH is distinguished from MASLD histologically with findings of ≥5% fat content, evidence of hepatocellular inflammation and cell death, and varying degrees of fibrosis. Continued progression can lead to cirrhosis, hepatocellular carcinoma, and liver failure.³
Alcoholic liver disease (ALD) or alcohol-related liver disease (ARLD)
Excessive alcohol consumption can cause hepatic steatosis when alcohol metabolism disrupts normal lipid metabolism in the liver, leading to the accumulation of fat within liver cells.³
How is Fatty Liver Diagnosed?
According to the American Heart Association, most patients with MASLD are undiagnosed.³ Most clinicians first become aware that the patient’s liver is affected when elevated liver enzymes are found on routine testing. Free online algorithms incorporate validated serological markers and include the Fatty Liver Index (FLI), NAFLD Fat Score, and Hepatic Steatosis Index (HIS). These scores have been validated in clinical studies and can be used to predict fatty liver.² In patients with metabolic risk factors, this may be enough information to begin addressing fatty liver.
However, to properly diagnose MASLD, imaging or histology is required for confirmation. Many patients with MASLD have normal liver function tests, resulting in poor sensitivity and specificity of these tests.³
An ultrasound may be ordered to visualize fat buildup in the liver. A FibroScan, a specialized ultrasound called transient elastography, detects the amount of fat, scar tissue, and liver stiffness, and may help with the diagnosis. CT or MRI may also be used. A liver biopsy distinguishes between simple fatty liver and progressive disease.4
Diet and Lifestyle Changes Are Fundamental for Reversing Fatty Liver
Cardiovascular disease (CVD) is the most common cause of death in MASLD patients.²,³,5,6 Therefore, the focus on CVD prevention and treatment with diet and lifestyle is key. Physical exercise, healthy nutrition, weight reduction, and improved insulin sensitivity are goals. The Mediterranean diet is recommended by several expert organizations for MASLD. It has been shown to reduce the risk of type 2 diabetes, obesity, and CVD, all of which are related to MASLD.7
Obesity is common among patients with MASLD; however, approximately 10% to 20% of Americans and Europeans with MASLD are lean. Weight loss reduces liver fat content, and as little as 5% weight loss in obese individuals can histologically resolve MASLD and some with NASH/MASH.²,4
Supplements Considerations for Fatty Liver
While lifestyle changes are important, compliance can be challenging, and other strategies like targeted supplements can help manage oxidative stress, inflammation, and insulin resistance. Notably, this article includes several meta-analyses of randomized controlled trials (RCTs) examining the effects of various nutrients on MASLD, providing a robust synthesis of the available evidence. Enhanced efficacy is seen when these therapies are paired with a Mediterranean diet and other healthy lifestyle changes.8
In addition to the following supplements and herbs, other notable considerations with strong clinical evidence include artichoke leaf extract, higher dose CoQ10, vitamin D, phosphatidylcholine, and coffee.6,8,9
Silymarin from Milk Thistle
Silymarin is one of the most studied plant constituents for hepatic disease. Its hepatoprotective actions include anti-inflammatory, antioxidant, anti-apoptotic, antifibrotic, choleretic, insulin-sensitizing, and metabolic effects.6 It can help maintain the integrity of hepatocyte membranes and regulate membrane permeability during toxic exposure.5
Several meta-analyses have found that silymarin significantly reduced liver enzymes AST (aspartate aminotransferase) and ALT (alanine aminotransferase) in MASLD patients compared with the control group.5,10 A 2023 meta-analysis also found improvements in lipid profiles, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fatty liver index and fatty liver scores, and histological evidence of reduced hepatic steatosis.10 Optimal dosing ranges from 420 to 600 mg divided daily.8 Its bioavailability is increased when taken with phosphatidylcholine.6
Vitamin E
Vitamin E is an extensively studied lipid-soluble antioxidant that inhibits lipid peroxidation, protecting hepatocytes from oxidative damage. It also inhibits lipogenesis, decreasing hepatic triglyceride accumulation.8
A meta-analysis of 12 randomized trials involving 794 patients with MASLD showed a significant reduction in ALT levels and a moderate reduction in AST levels using vitamin E compared with placebo.11 A systematic review also showed reduced hepatic steatosis and lobular inflammation.12 Doses 400-800 IU/day are most effective for MASLD patients; however, doses higher than 400 IU daily may present safety concerns. There is a slightly increased risk of hemorrhagic stroke and prostate cancer in specific population studies.8
Omega-3 Fatty Acids
Excess omega-6 and decreased omega-3 fat intake, common in Western diets, are linked to MASLD pathogenesis. Omega-3 fats inhibit sterol regulatory element-binding protein 1 (SREBP-1), preventing de novo lipogenesis and triglyceride synthesis in hepatocytes. They increase Peroxisome Proliferator-Activated Receptor alpha (PPARα) expression, which activates fatty acid metabolism and insulin sensitivity. Omega-3s are anti-inflammatory and reduce oxidative stress and lipid peroxidation, preventing MASLD progression.8
A meta-analysis of patients with MASLD found that omega-3 supplementation significantly reduced liver fat content and improved lipid profiles and BMI compared to placebo.13 Another systematic review and meta-analysis found significant improvements in liver fat content, steatosis score, and AST and ALT levels.14 Study doses ranged from 2 to 4 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily for MASLD.8
Berberine
Berberine’s use has become popular for its microbiome-modulating and insulin-sensitizing properties, both of which benefit MASLD patients. Berberine also directly addresses liver fat accumulation through AMP-activated protein kinase (AMPK) activation.15
A meta-analysis of 10 RCTs involving 811 MASLD patients showed significant reductions in ALT, AST, GGT, lipids, HOMA-IR, and BMI.16 A review of 9 clinical studies showed a measurable reduction of liver fat via imaging, and improved lipids and hepatic enzymes.17 Efficacious doses for MASLD range from 500-1500 mg/day, divided.8
Curcumin
Curcumin, the primary compound in turmeric (Curcuma longa), has a long history of use for inflammatory conditions. In MASLD, curcumin targets several pathways. It downregulates NF-κB, a major driver of inflammation, and reduces pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It has antioxidant properties and helps increase glutathione levels. It also activates AMPK, which inhibits lipogenesis and helps break down fat into usable energy.8
A meta-analysis assessing the ultrasound effects of curcumin on MASLD patients showed reduced or resolved steatosis compared to placebo groups.18 Although there was some discrepancy, several meta-analyses and systematic reviews also found that curcumin improves AST, ALT, lipids, fasting blood sugar, waist circumference, and BMI in patients with MASLD.18-20 Effective curcumin doses for MASLD range from 250 mg to 3000 mg daily, with the phytosomal form showing a better therapeutic effect.8
Green Tea (EGCG)
Green tea’s main active compound, epigallocatechin gallate (EGCG), has antioxidant and anti-inflammatory properties to protect the body and liver from oxidative damage. Two meta-analyses of MASLD patients found that green tea significantly reduced ALT and AST levels.21,22 It also had favorable effects on BMI, lipid levels, and HOMA-IR.21 Drinking 3-5 cups of green tea daily delivers approximately 200-400 mg EGCG, which is the recommended dose for MASLD. Decaffeinated tea provides the same benefits for those sensitive to caffeine. Green tea may cause nausea or vomiting if consumed on an empty stomach.8
Probiotics and Treating the Gut
A dysfunctional gut-liver axis contributes to MASLD via dysbiosis, small intestinal bacterial overgrowth (SIBO), increased intestinal permeability, imbalanced microbiome metabolites, and increased bacterial toxins like lipopolysaccharides (LPS).8,23 Endotoxicity from bacteria and LPS can cause long-term damage to hepatocytes. Probiotics can improve intestinal barrier integrity, correct dysbiosis, and reduce liver inflammation.24
Several meta-analyses have been conducted in MASLD patients showing that pre- and probiotics improve various metabolic parameters. Studies showed improved AST, ALT, lipid profiles, fasting glucose, insulin, HOMA-IR, TNF-α, and waist circumference. Treatments varied widely, making translation to clinical practice difficult.24-27 Most studies used capsules containing Lactobacillus, Bifidobacterium, or Streptococcus species for 12 to 24 weeks at doses of 109 to 1011 CFU daily.8
Will A Liver Cleanse or Liver Detox Help?
Detox programs generally involve a healthy diet and detox supplements aimed at improving phase 1 and phase 2 detoxification, restoring microbiome balance, and gut elimination of toxins. Most cleanses are intended for shorter timeframes such as 2-4 weeks. Clinical studies using the nutrients mentioned generally lasted months to see effects. A temporary cleanse/detox may be a nice catalyst to jumpstart healthier habits for the long term, but there is no evidence that they effectively treat fatty liver.
Key Takeaways
- Addressing the cause of fatty liver disease is foundational, whether it be alcohol reduction, weight loss, or incorporation of healthy lifestyle habits.
- Nutraceuticals can help reduce steatosis and recover liver function. Extensive human data exists for silymarin, vitamin E, curcumin, berberine, omega-3 fats, and others.
- Depending on the extent of damage, fatty liver and tissue damage can be reversed.
References
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- Duell PB, Welty FK, Miller M, et al. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology. Jun 2022;42(6):e168–e185. doi:10.1161/atv.0000000000000153
- Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md). Jan 2018;67(1):328–357. doi:10.1002/hep.29367
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- Vrentzos E, Pavlidis G, Korakas E, et al. Nutraceutical Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Path to Liver Health. Nutrients. May 13 2025;17(10)doi:10.3390/nu17101657
- Maev IV, Samsonov AA, Palgova LK, et al. Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study). BMJ Open Gastroenterol. 2020;7(1):e000341. doi:10.1136/bmjgast-2019-000341
- Li S, Duan F, Li S, Lu B. Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis. Annals of Hepatology. Mar–Apr 2024;29(2):101174. doi:10.1016/j.aohep.2023.101174
- Vogli S, Naska A, Marinos G, Kasdagli MI, Orfanos P. The Effect of Vitamin E Supplementation on Serum Aminotransferases in Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review and Meta-Analysis. Nutrients. Aug 25 2023;15(17)doi:10.3390/nu15173733
- Usman M, Bakhtawar N. Vitamin E as an Adjuvant Treatment for Non-alcoholic Fatty Liver Disease in Adults: A Systematic Review of Randomized Controlled Trials. Cureus. Jul 6 2020;12(7):e9018. doi:10.7759/cureus.9018
- Lee CH, Fu Y, Yang SJ, Chi CC. Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis. Nutrients. Sep 11 2020;12(9)doi:10.3390/nu12092769
- Musa-Veloso K, Venditti C, Lee HY, et al. Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease. Nutrition Reviews. Aug 1 2018;76(8):581–602. doi:10.1093/nutrit/nuy022
- Koperska A, Wesołek A, Moszak M, Szulińska M. Berberine in Non-Alcoholic Fatty Liver Disease-A Review. Nutrients. Aug 23 2022;14(17)doi:10.3390/nu14173459
- Nie Q, Li M, Huang C, et al. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. Journal of Translational Medicine. Mar 1 2024;22(1):225. doi:10.1186/s12967-024-05011-2
- Ionita-Radu F, Patoni C, Nancoff AS, et al. Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease-Clinical and Pre-Clinical Overview and Systematic Review of the Literature. International Journal of Molecular Sciences. Apr 10 2024;25(8)doi:10.3390/ijms25084201
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- Mahmoodi M, Hosseini R, Kazemi A, Ofori-Asenso R, Mazidi M, Mazloomi SM. Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials. Phytotherapy Research: PTR. Jul 2020;34(7):1587–1598. doi:10.1002/ptr.6637
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