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Randomized Controlled Trial (Single-blind)
JAMA Internal Medicine

Mediterranean Diet Reverses NAFLD: Randomized Controlled Trial Evidence

This landmark RCT demonstrated that a Mediterranean diet rich in extra-virgin olive oil significantly reduces liver fat content and improves metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD).

June 1, 2021

Core Finding

After 12 months, participants following a Mediterranean diet supplemented with extra-virgin olive oil (EVOO) achieved a 29% relative reduction in liver fat compared to 6% in the control low-fat diet. Liver fat normalization (<5%) occurred in 35% of the Mediterranean group vs. 8% of controls.

Research Background

Non-alcoholic fatty liver disease (NAFLD) affects ~25% of adults globally and has no approved pharmacotherapy. While weight loss is known to reduce liver fat, the optimal dietary composition has been unclear. This trial compared two isocaloric diets differing in fat composition.

Study at a Glance

Study Overview

Source: JAMA Internal Medicine (2021)

Duration: 12 months (with 6-month extension)

Intervention: Mediterranean diet + 50ml EVOO daily

Control: Low-fat diet (<25% total fat)

Primary endpoint: Change in liver fat by MRI-PDFF

Mediterranean Diet (EVOO group):

  • Total fat: 40-45% of calories (vs. control: <25%)
  • Monounsaturated fat: 22% of calories (primarily from EVOO)
  • Carbohydrates: 40-45% (emphasis on whole grains, legumes)
  • Protein: 15-20% (fish/seafood 3x/week, poultry moderate, red meat limited)
  • Key foods: EVOO (50ml/day), nuts (30g/day), vegetables (>2 servings/day), fruits (>2 servings/day)

Control Diet:

  • Total fat: <25% of calories
  • Carbohydrates: 55-60% (emphasis on grains, cereals)
  • Protein: 15-20%
  • Limited: Oils, nuts, avocado

Why EVOO Matters

Extra-virgin olive oil contains bioactive compounds beyond monounsaturated fats:

EVOO Bioactive Components

  • Polyphenols (oleocanthal, oleuropein): Potent anti-inflammatory and antioxidant effects
  • Vitamin E: Protects hepatocytes from oxidative stress
  • Squalene: Modulates lipid metabolism
  • Oleic acid: Improves insulin sensitivity and adiponectin secretion

Mechanisms of Action

  1. Reduced de novo lipogenesis: Lower insulin secretion decreases SREBP-1c activity
  2. Enhanced fatty acid oxidation: Polyphenols activate PPAR-α pathway
  3. Improved mitochondrial function: Reduced oxidative stress in hepatocytes
  4. Gut-liver axis modulation: EVOO polyphenols positively alter gut microbiota composition
  5. Adiponectin increase: Promotes fatty acid oxidation and inhibits hepatic glucose production

Clinical Implications

  1. First-line therapy: Mediterranean diet should be recommended as initial treatment for NAFLD
  2. Fat quality over quantity: Dietary fat composition matters more than absolute fat intake
  3. Sustainable approach: Higher palatability and adherence compared to low-fat diets
  4. Beyond liver: Concurrent improvements in cardiovascular risk factors

Important Considerations

  • Weight loss contributed to but did not fully explain liver fat reduction
  • EVOO is calorie-dense—portion control still matters
  • Participants were predominantly Mediterranean; results may vary by ethnicity
  • Alcohol excluded during study; NAFLD patients should minimize alcohol

Practical Implementation

  • Start with: 2-3 tablespoons EVOO daily (for cooking and dressings)
  • Replace: Butter with EVOO, processed meats with fish/legumes
  • Add: Nuts as snacks (30g/day)
  • Reduce: Red meat to <2 servings/week, sugary beverages to zero
  • Pattern: Daily fruit, vegetables, and whole grains at every meal

FAQ

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Mediterranean Diet Reverses NAFLD: Randomized Controlled Trial Evidence | Paper Interpretation