Introduction
Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition characterised by excessive fat accumulation in the liver, affecting up to 25% of the global population. Risk factors for NAFLD include obesity, type 2 diabetes, and metabolic syndrome. While lifestyle changes like diet, exercise, and weight loss are the cornerstone of NAFLD management, certain supplements have shown promise in improving liver health. Supplements for fatty liver, such as vitamin E, milk thistle, omega-3 fatty acids, probiotics, and others, have been studied for their potential to reduce liver fat, inflammation, and fibrosis through various mechanisms. However, more research is needed to firmly establish the efficacy and optimal use of these supplements in the context of a comprehensive NAFLD treatment plan under medical supervision.
Vitamin E
Vitamin E, particularly the alpha-tocopherol form, is a potent antioxidant that has been widely studied for its potential benefits in NAFLD and nonalcoholic steatohepatitis (NASH) (Sanyal et al., 2010; Abdelmaoud et al., 2020). Meta-analyses have found that vitamin E supplementation improves liver pathology, reduces liver enzyme levels, and lowers LDL-cholesterol and fasting blood glucose in adults with NAFLD (Amanullah et al., 2019; Xu et al., 2015).
The PIVENS trial, a key study, showed that vitamin E at a dose of 800 IU/day for 96 weeks led to a significant reduction in steatosis and inflammation and improvement in liver histology compared to placebo in patients with NASH. However, vitamin E did not significantly improve fibrosis scores (Sanyal et al., 2010).
Tocotrienols, other members of the vitamin E family, have also shown promise in NAFLD management. In a randomised controlled trial, 200 mg mixed tocotrienols twice daily for one year resulted in significant reductions in fatty liver index scores (Pervez et al., 2018). Another study found that 200 mg tocotrienols twice daily for 12 weeks decreased insulin resistance, liver enzymes, inflammatory markers, and oxidative stress in NAFLD patients (Magosso et al., 2013).
While these findings are encouraging, more research is needed to determine the optimal dose and duration of vitamin E supplementation for NAFLD. Additionally, concerns have been raised about the long-term safety of high-dose vitamin E, particularly in regards to prostate cancer risk (Klein et al., 2011).
Milk Thistle (Silybum marianum)
Milk thistle and its active complex silymarin have a long history of use as liver tonics and detoxicants (Gillessen & Schmidt, 2020). Silymarin, a mixture of flavonolignans, has antioxidant, anti-inflammatory, and antifibrotic properties that may benefit NAFLD (Zhong et al., 2017).
Meta-analyses have found that silymarin supplementation reduces liver enzyme levels in individuals with NAFLD. One analysis of 8 randomised controlled trials found that silymarin lowered alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to placebo or no treatment (Zhong et al., 2017). Another meta-analysis of 6 studies reported similar reductions in ALT and AST with silymarin in NAFLD patients (Cacciapuoti et al., 2017).
In a randomised, double-blind, placebo-controlled trial, 700 mg silymarin three times daily for 48 weeks led to a significant reduction in fibrosis in patients with biopsy-confirmed NASH. Fibrosis improved by at least one stage in 22.4% of silymarin-treated patients versus only 6% who received placebo (Wah Kheong et al., 2017).
Silymarin has also shown benefits in NAFLD when combined with other nutrients. A clinical trial found that silymarin plus vitamin E and vitamin C for 12 months improved insulin resistance and liver enzymes in NAFLD patients (Aller et al., 2015). Another study reported reduced liver enzymes and improved liver ultrasound with silymarin, vitamin E, and phospholipids for 12 months in NAFLD (Loguercio et al., 2012). Silymarin combined with vitamin E and L-carnitine for 3 months also decreased ALT, AST, and gamma-glutamyl transferase (GGT) in NAFLD patients (Aller et al., 2011).
While milk thistle appears to be a promising therapy for NAFLD, more high-quality trials are needed to confirm its efficacy and determine the optimal silymarin formulation and dosage. Standardisation of silymarin products is also important to ensure consistent potency and effects.
Omega-3 Fatty Acids
Omega-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundant in fatty fish and fish oil supplements, have anti-inflammatory and metabolic benefits that may ameliorate NAFLD. Omega-3s can synthesise specialised pro-resolving mediators that resolve inflammatory activity and may improve liver lipid and glucose metabolism (Hodson et al., 2018; Scorletti & Byrne, 2018).
Multiple meta-analyses have found that omega-3 fatty acid supplementation decreases liver fat content, liver enzyme levels, body mass index (BMI), triglyceride and glucose levels, and insulin resistance in NAFLD patients (Yan et al., 2015; Lu et al., 2016; Musa-Veloso et al., 2018). A meta-analysis of 10 randomised controlled trials concluded that omega-3 supplementation reduced liver fat, AST, ALT, GGT, triglycerides, and TNF-alpha compared to placebo in NAFLD (Yan et al., 2015).
The form of omega-3 used may influence its effects on NAFLD. Some evidence suggests that omega-3 phospholipids may have a more pronounced ability to combat liver fat accumulation than omega-3 triglycerides. A 2022 randomised controlled trial found that krill oil, rich in omega-3 phospholipids, led to greater reductions in liver fat and liver enzymes than fish oil in individuals with NAFLD (Murru et al., 2022).
However, not all trials have found significant benefits with omega-3 supplementation in NAFLD. The WELCOME trial, which used an omega-3 supplement providing 4 grams EPA+DHA daily for 15-18 months in NAFLD patients, did not find a significant reduction in liver fat compared to placebo, although there were improvements in liver enzymes, serum triglycerides, and insulin sensitivity (Scorletti et al., 2014).
More research is needed to clarify the optimal omega-3 dosage, duration, and form for NAFLD management. Omega-3 supplements can cause digestive side effects and may interact with anticoagulant medications. Therefore, their use should be monitored by a healthcare professional.
Probiotics
The gut microbiome plays a key role in NAFLD development and progression. Dysbiosis, an imbalance in gut bacteria, can increase intestinal permeability, allowing bacterial endotoxins to enter the portal circulation and promote liver inflammation and injury (Lavekar et al., 2017). Probiotics are beneficial bacteria that may help restore a healthy gut microbiome and have shown promise in NAFLD management.
Probiotics may benefit NAFLD through multiple mechanisms, including repairing gut barrier function, reducing endotoxin-induced liver injury, and supporting healthy lipid and glucose metabolism and immune function (Lavekar et al., 2017). Numerous clinical trials using various strains of Lactobacillus, Bifidobacterium, and other genera have shown that probiotics can reduce liver fat, fibrosis, liver enzymes, and markers of inflammation and metabolic dysfunction in NAFLD patients.
A randomised, double-blind, placebo-controlled trial found that a multi-strain probiotic containing Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei, Pediococcus pentosaceus, Bifidobacterium lactis, and Bifidobacterium breve for 12 weeks significantly reduced liver fat, fibrosis scores, and inflammatory markers in NAFLD patients (Duseja et al., 2019). Another trial using a probiotic mixture of Bifidobacterium, Lactobacillus, Lactococcus, and Propionibacterium strains for 8 weeks led to significant reductions in fatty liver index scores, ALT, AST, GGT, and TNF-alpha in NAFLD patients (Kobyliak et al., 2018).
A 2019 randomised controlled trial reported that a multi-species probiotic containing Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei, Pediococcus pentosaceus, Bifidobacterium lactis, and Bifidobacterium breve for 12 weeks improved liver steatosis, triglycerides, total cholesterol, and LDL-cholesterol in patients with NAFLD (Ahn et al., 2019). In obese children with NAFLD, supplementation with Lactobacillus rhamnosus GG for 12 weeks reduced liver enzymes and liver steatosis compared to placebo (Famouri et al., 2017).
Other trials have found benefits with Lactobacillus casei (Nabavi et al., 2014), Lactobacillus bulgaricus and Streptococcus thermophilus (Asgharian et al., 2016), and Bifidobacterium longum (Malaguarnera et al., 2012) in improving liver health markers in NAFLD.
While the research on probiotics for NAFLD is promising, more studies are needed to identify the most effective strains and dosages. Probiotics are generally well-tolerated but can cause mild digestive side effects. Individuals with compromised immune function should use probiotics cautiously.
Vitamin D
Vitamin D insufficiency is common in NAFLD patients and correlates with disease severity. A meta-analysis found that NAFLD patients had 26% higher rates of vitamin D deficiency compared to healthy controls, and lower vitamin D levels were associated with greater severity of liver steatosis and fibrosis (Eliades et al., 2013). Another meta-analysis reported that the prevalence of vitamin D deficiency was 57% higher in NAFLD patients than controls (Patel et al., 2016).
Vitamin D and its receptors participate in liver, adipose tissue, and gut homeostasis through its anti-inflammatory, insulin-sensitising, antifibrotic, and antimicrobial effects (Pacifico et al., 2019). Vitamin D may benefit NAFLD by reducing hepatic stellate cell activation and collagen production, suppressing proinflammatory cytokines, enhancing insulin signalling, and modulating the gut microbiome (Pacifico et al., 2019).
However, clinical trials examining vitamin D supplementation in NAFLD have shown mixed results. A meta-analysis of 6 randomised controlled trials found no significant improvements in liver enzymes, liver fat, or fibrosis with vitamin D supplementation in NAFLD patients (Tabrizi et al., 2018).
One trial found that 50,000 IU vitamin D3 every 14 days for 4 months improved serum ALT and ultrasound findings in NAFLD patients (Sharifi et al., 2014). However, another trial using 2000 IU vitamin D3 daily for 24 weeks in patients with type 2 diabetes and NAFLD did not find significant changes in liver fat, liver enzymes, or CK-18 (a marker of NASH) compared to placebo (Barchetta et al., 2016).
Differences in study populations, vitamin D dosages, and outcome measures may account for the inconsistent findings. More research is needed to clarify the effects of vitamin D on NAFLD and determine the optimal supplementation protocol. Vitamin D deficiency should be corrected in NAFLD patients, but whether supplementation provides additional therapeutic benefits remains uncertain.
Other Promising Supplements
Berberine
Berberine, a plant compound used in traditional Chinese medicine, has shown potential for improving NAFLD through its metabolic and anti-inflammatory effects. A meta-analysis of 6 randomised controlled trials found that berberine supplementation significantly reduced liver fat content, ALT, AST, GGT, total cholesterol, triglycerides, LDL-cholesterol, fasting blood glucose, and insulin resistance compared to placebo in NAFLD patients (Wei et al., 2016).
However, some preclinical research raises concerns about the long-term safety of berberine. Animal studies suggest that chronic berberine intake may promote insulin resistance, hepatic steatosis, and gut microbiome alterations (Ashraf et al., 2021; Zhao et al., 2020). More human trials are needed to assess the efficacy and safety of berberine for NAFLD.
Curcumin
Curcumin, the active component of turmeric, has potent anti-inflammatory and antioxidant properties that may benefit NAFLD. Multiple meta-analyses have indicated that curcumin supplementation reduces liver enzymes, lipid levels, glucose, and insulin resistance in NAFLD patients (Jalali et al., 2020; Baziar et al., 2020; Saadati et al., 2019).
Randomised controlled trials suggest that 500-1500 mg daily curcumin supplementation, particularly formulations with enhanced bioavailability, may be most effective for improving NAFLD. One trial found that 1000 mg curcumin daily for 8 weeks reduced liver fat, ALT, AST, and GGT in NAFLD patients (Rahmani et al., 2016). Another study using 500 mg curcumin with piperine daily for 12 weeks led to significant reductions in liver enzymes, glucose, and inflammatory markers in NAFLD (Panahi et al., 2017). A trial of 1500 mg nano-curcumin daily for 12 weeks in obese NAFLD patients found significant improvements in liver fat, liver enzymes, lipids, glucose, insulin resistance, and inflammatory markers (Jazayeri-Tehrani et al., 2019).
While curcumin appears promising for NAFLD, more research is needed to determine the optimal dosage and formulation. Curcumin is generally well-tolerated but can cause digestive side effects and may interact with certain medications.
Green Tea Extract
Green tea extract, rich in polyphenols like epigallocatechin gallate (EGCG), may improve NAFLD through its antioxidant, anti-inflammatory, and lipid-lowering effects. A meta-analysis of 4 randomised controlled trials found that green tea supplementation significantly reduced ALT, AST, and liver fat in NAFLD patients (Mansour-Ghanaei et al., 2018).
One trial found that 500 mg green tea extract daily for 90 days significantly decreased ALT, AST, insulin resistance, and liver steatosis in NAFLD patients (Pezeshki et al., 2016). Another study using 1000 mg green tea extract with 70% EGCG daily for 12 weeks reported significant reductions in liver enzymes, total cholesterol, LDL-cholesterol, and triglycerides in patients with NAFLD (Hussain et al., 2017).
Green tea extract is generally safe but can cause digestive symptoms and may interact with certain drugs. Excessive intake of green tea extract has been linked to rare cases of liver injury (Mazzanti et al., 2015). Therefore, green tea supplements should be used cautiously and under medical supervision.
Conclusion
Conclusion
Nonalcoholic fatty liver disease (NAFLD) is a complex condition influenced by multiple factors, including diet, lifestyle, genetics, and gut health. While there is no single magic bullet for treating NAFLD, certain supplements have shown promise in improving liver health markers and supporting the body’s natural mechanisms for reducing liver fat and inflammation.
The supplements with the most evidence for potential benefits in NAFLD include vitamin E, silymarin (milk thistle extract), omega-3 fatty acids, probiotics, berberine, curcumin, and green tea extract. These supplements may help improve NAFLD through various mechanisms, such as reducing oxidative stress and inflammation, improving insulin sensitivity and glucose metabolism, modulating the gut microbiome, and supporting healthy liver fat metabolism and detoxification pathways.
However, it is important to recognise that the research on supplements for NAFLD is still evolving, and more high-quality, long-term studies are needed to fully understand their efficacy, optimal dosing, and potential risks. The existing evidence, while promising, has some limitations, such as small sample sizes, short durations, and inconsistent formulations of supplements used.
Additionally, supplements should not be viewed as a standalone solution for NAFLD. The most effective approach for managing NAFLD is a comprehensive one that addresses the root causes and risk factors through sustainable diet and lifestyle changes, such as adopting a whole-foods, plant-focused eating pattern, increasing physical activity, achieving and maintaining a healthy weight, and supporting gut health.
Individuals with NAFLD should work closely with a healthcare practitioner who can help guide supplement use based on their unique needs and medical history. Supplements can interact with medications and may not be appropriate for everyone. A personalised, integrative approach that combines evidence-based supplements with diet, lifestyle, and medical interventions is the best way to support liver health and prevent the progression of NAFLD.
In conclusion, while supplements like vitamin E, silymarin, omega-3s, probiotics, berberine, curcumin, and green tea extract have shown potential benefits for liver health in NAFLD, they should be used judiciously and as part of a holistic treatment plan under the guidance of a qualified healthcare professional. More research is needed to refine our understanding of the role of supplements in NAFLD management and to develop targeted, personalised approaches that address the multifactorial nature of this complex condition.
Key Highlights and Actionable Tips
- Nonalcoholic fatty liver disease (NAFLD) is characterized by excess fat buildup in the liver, often caused by overeating, especially too much sugar and saturated fat
- Adopting a healthy diet low in added sugars, saturated fat, and calories, along with regular exercise and maintaining a healthy weight, are the cornerstone of NAFLD prevention and treatment
- Weight loss of more than 5% of body weight can reduce liver fat, and 7% or more can reverse inflammation and fibrosis in NAFLD patients who are overweight or obese
- Probiotics, vitamin E, milk thistle, berberine, curcumin, omega-3 fatty acids, green tea, and French oak wood extract have shown promise in clinical trials for improving liver health markers in NAFLD
- Screening for NAFLD is recommended for those with metabolic syndrome, type 2 diabetes, obesity, or other risk factors, and involves blood tests, imaging, and possibly liver biopsy
What lifestyle changes are most important for reversing NAFLD?
The most important lifestyle changes for reversing NAFLD are adopting a healthy diet low in added sugars, saturated fat, and calories, and engaging in regular physical activity. A weight loss of 5-7% of body weight through diet and exercise can significantly reduce liver fat and inflammation. Avoiding alcohol and eating a diet rich in fiber, healthy fats, and antioxidants from vegetables, fruits, whole grains, nuts, seeds, and legumes is also beneficial.
Are there any supplements that can help improve liver health in NAFLD?
Several supplements have shown promise in clinical trials for improving markers of liver health in NAFLD. These include probiotics, vitamin E, silymarin from milk thistle, berberine, curcumin, omega-3 fatty acids (especially DHA and EPA), green tea extract, and French oak wood extract. However, it’s important to talk to your doctor before starting any new supplement regimen, as some may interact with medications or have side effects.
How is NAFLD diagnosed?
NAFLD is often first suspected based on elevated liver enzymes on a routine blood test or an enlarged liver on physical exam or imaging. Further testing may include additional blood work to rule out other causes of liver disease, imaging such as ultrasound or MRI to assess liver fat, and possibly liver biopsy to determine the severity of inflammation and fibrosis. Noninvasive scoring tools that incorporate blood test results and other patient data are also used to predict the likelihood of NAFLD and advanced fibrosis.
Can NAFLD be reversed?
Yes, NAFLD can often be reversed, especially in its early stages, through lifestyle changes such as adopting a healthy diet, losing weight, and exercising regularly. The liver has a remarkable ability to repair and regenerate itself when damaging conditions are corrected. Even in more advanced cases with inflammation and fibrosis, progression can be halted and scar tissue can be reduced over time with dedicated lifestyle changes and weight loss.
What are the potential complications of NAFLD?
If NAFLD progresses, it can lead to a more severe form called nonalcoholic steatohepatitis (NASH), which is characterized by significant liver inflammation. NASH, in turn, can lead to fibrosis (scarring), cirrhosis (advanced scarring), liver failure, and hepatocellular carcinoma (liver cancer). NAFLD is also associated with increased risks of cardiovascular disease and type 2 diabetes. Early identification and lifestyle intervention are critical for preventing these serious complications.
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Sanyal, A
