What supplements are recommended for patients with Metabolic Associated Fatty Liver Disease (MAFLD)?

Supplements for Metabolic Associated Fatty Liver Disease (MAFLD)

Based on current guidelines, nutraceuticals cannot be recommended for MAFLD treatment as there is insufficient evidence of their effectiveness in reducing liver damage/fibrosis and liver-related outcomes, as well as concerns about their safety. 1

Current Evidence on Supplements for MAFLD

Mediterranean Diet Rather Than Supplements

The primary approach to MAFLD management should focus on dietary patterns rather than specific supplements:

• Mediterranean diet should be advised to improve steatosis and insulin sensitivity 1
• Diet quality (similar to Mediterranean pattern) and limiting ultra-processed foods rich in sugars and saturated fat is strongly recommended 1
• Avoid fructose-containing beverages and foods 1

Coffee Consumption

• Coffee consumption has been associated with improvements in liver damage and reduced liver-related clinical outcomes in observational studies 1
• No liver-related limitations for coffee consumption 1
• Coffee is more likely to benefit health than harm in MAFLD patients 1

Vitamin E

• Given the lack of robust demonstration of histological efficacy on steatohepatitis and liver fibrosis from large phase III trials and potential long-term risks, vitamin E cannot be recommended as a MASH-targeted therapy 1
• While vitamin E has shown some benefits in decreasing transaminase levels, liver lobular inflammation, and steatosis, it could have different side effects including increased risk of certain types of cancer or hemorrhagic stroke 1

Vitamin D

• MAFLD patients have been shown to have decreased levels of serum vitamin D 1
• While epidemiological data support a relationship between hypovitaminosis D and NAFLD/NASH, results from vitamin D supplementation trials on liver outcomes are controversial 2
• Potential benefits may exist for selected populations with shorter disease duration and mild to moderate liver damage 2

Other Micronutrients

• MAFLD patients often show decreased levels of zinc, copper, vitamins A, C, and carotenoids 1
• Iron and selenium excess have been reported to play a role in the severity of MAFLD 1
• Despite these associations, there is insufficient evidence to recommend specific micronutrient supplementation 1

Dietary Components More Important Than Supplements

Macronutrient Composition

• Cholesterol and saturated fatty acid intake is independently associated with the presence of advanced fibrosis 3
• Cholesterol/saturated fatty acid-restricted dietary regimens (like Mediterranean diet) may reduce risk of advanced fibrosis 3
• Low-to-moderate fat and moderate-to-high carbohydrate intake is recommended 1

Fiber and Prebiotics

• Low fiber intake is thought to be related to MAFLD development 1
• The rationale is that low fiber intake induces dysbiosis, modifies the microbiota causing endotoxemia, systemic inflammation, insulin resistance, and liver damage 1
• Prebiotic intake has been shown to improve liver phenotype in MAFLD patients 1

Omega-3 Fatty Acids

• Cross-sectional studies demonstrate higher rates of MAFLD with lower intakes of oily fish rich in omega-3 fatty acids 1
• Increasing dietary marine omega-3 fatty acids may be beneficial, as supplement trials indicate that increased dose is associated with reduced hepatic steatosis 1
• Traditional diets have an omega-6 to omega-3 ratio close to 2:1, whereas Western diets have a ratio closer to 20:1 1

Lifestyle Modifications More Important Than Supplements

• Weight loss of 7-10% is the target of most lifestyle interventions and results in improvement of liver enzymes and histology 1
• Both aerobic exercise and resistance training effectively reduce liver fat 1
• Physical activity (150-200 min/week of moderate intensity) should be tailored based on patient preferences for long-term adherence 1
• In normal weight MAFLD patients, increased physical activity to improve insulin resistance and fibrosis is recommended 1

Clinical Algorithm for MAFLD Management

1. First-line approach: Focus on weight loss (7-10%) through diet and exercise

   • Mediterranean diet pattern
   • Limit ultra-processed foods, added sugars, and saturated fats
   • Physical activity (150+ minutes/week)

2. Diet quality optimization:

   • Increase consumption of whole grains, fruits, vegetables, fatty fish, and extra virgin olive oil
   • Reduce red meat, processed meats, sodas, and processed foods
   • Consider coffee consumption (no limitations)

3. Consider pharmacotherapy (if approved locally):

   • For non-cirrhotic MASH with significant liver fibrosis (stage >2): resmetirom 1
   • For obesity or diabetes: GLP-1 receptor agonists (e.g., semaglutide) 1

4. Avoid supplements without strong evidence:

   • Current guidelines do not support the use of nutraceuticals for MAFLD 1
   • Vitamin E is not recommended due to potential long-term risks 1

Pitfalls and Caveats

• Do not rely on supplements as primary treatment for MAFLD when diet and lifestyle modifications have stronger evidence
• Avoid high-cholesterol and saturated fat diets which are associated with advanced fibrosis
• Be cautious with vitamin E supplementation due to potential increased risk of certain cancers and hemorrhagic stroke
• Remember that the quality of the overall diet pattern is more important than individual supplements
• Recognize that inactive individuals with MAFLD require even greater attention to diet quality 4