Fatty Liver: Causes, Diagnosis, Risk Factors, and Integrative Treatments That Work

Nonalcoholic fatty liver disease (NAFLD) is one of the most common and underdiagnosed chronic conditions worldwide, now affecting nearly 1 in 3 adults in the U.S. It represents a spectrum of liver disorders characterized by excessive fat accumulation in liver cells, in the absence of significant alcohol intake. While once considered benign, we now know that fatty liver can progress to more serious conditions, including nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even liver cancer.

Fortunately, fatty liver disease is both preventable and reversible, especially when caught early. In this post, we'll explore what causes fatty liver, how it's diagnosed, who is most at risk, and how functional and integrative medicine provide powerful tools to treat it—including cutting-edge therapies like the GLP-1/GIP/glucagon receptor agonists retatrutide and survodutide, which have shown stunning results in clinical trials.

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What Is Fatty Liver Disease?

Fatty liver disease refers to the abnormal accumulation of fat (mainly triglycerides) in the liver. There are two major types:

• Alcoholic fatty liver disease (AFLD): Caused by excessive alcohol intake.

• Nonalcoholic fatty liver disease (NAFLD): Occurs in people who drink little or no alcohol.

NAFLD itself is divided into two categories:

• Simple steatosis: Fat accumulation without inflammation.

• Nonalcoholic steatohepatitis (NASH): Fat accumulation with inflammation and liver cell injury, which can lead to scarring (fibrosis).

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What Causes Fatty Liver?

NAFLD is driven primarily by insulin resistance, which leads to:

• Increased lipolysis in adipose tissue (fat breakdown), flooding the liver with free fatty acids.

• Elevated de novo lipogenesis (DNL): The liver converts excess carbohydrates (especially fructose) into fat.

• Impaired fat oxidation and export, resulting in fat storage in liver cells.

Additional contributing factors include:

• High intake of refined carbs and fructose (e.g., soda, processed foods)

• Sedentary lifestyle

• Obesity, especially visceral fat

• Type 2 diabetes and prediabetes

• Gut dysbiosis and increased intestinal permeability ("leaky gut")

• Chronic inflammation

• Nutrient deficiencies (e.g., choline, vitamin E, omega-3s)

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How Is Fatty Liver Diagnosed?

Fatty liver is often silent in its early stages, which makes proactive screening important for at-risk individuals.

Diagnostic tools include:

1. Liver enzymes: ALT and AST may be elevated but can also be normal.

2. Imaging:

   • Ultrasound: Most common, but subjective.

   • FibroScan (transient elastography): Measures liver stiffness and fat.

   • MRI-PDFF: Gold standard for measuring liver fat.

3. Liver biopsy: Most definitive, but invasive.

4. Serologic scoring systems:

   • NAFLD Fibrosis Score

   • FIB-4 Index

Functional medicine may also test for:

• Fasting insulin and glucose

• HOMA-IR

• Lipid panel (especially triglycerides and small-dense LDL)

• hs-CRP and ferritin (inflammatory markers)

• Organic acid and stool testing (to evaluate gut health and dysbiosis)

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Who Is at Risk for Fatty Liver?

NAFLD is strongly linked to metabolic syndrome, a cluster of conditions that includes:

• Abdominal obesity

• Elevated fasting blood sugar

• High blood pressure

• High triglycerides

• Low HDL cholesterol

High-risk groups include:

• People with type 2 diabetes (up to 70% have NAFLD)

• Those with obesity or central (visceral) fat

• Patients with polycystic ovary syndrome (PCOS)

• Individuals with sleep apnea

• Those with a family history of fatty liver

NAFLD is also becoming alarmingly common in children and teens, primarily due to ultra-processed diets, sedentary behavior, and rising childhood obesity rates.

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Why Fatty Liver Matters

Fatty liver is more than a liver condition—it's a systemic disease with wide-reaching consequences. It increases the risk for:

• Type 2 diabetes

• Cardiovascular disease (the leading cause of death in NAFLD patients)

• Chronic kidney disease

• Liver fibrosis and cirrhosis

• Hepatocellular carcinoma (liver cancer)

Even "simple" steatosis is not entirely benign; it still represents metabolic dysfunction and should be addressed aggressively.

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Functional Medicine Approach to Fatty Liver

Unlike conventional medicine, which often takes a "watch and wait" approach, functional medicine aims to reverse fatty liver by treating the root causes.

1. Nutrition

The first step is reversing insulin resistance and eliminating liver stressors.

Key dietary strategies:

• Low-glycemic, anti-inflammatory diet (e.g., Mediterranean or Paleo)

• Eliminate refined sugar, fructose, and processed carbs

• Prioritize high-fiber vegetables, lean protein, and healthy fats

• Intermittent fasting or time-restricted eating to improve insulin sensitivity

• Increase choline-rich foods (eggs, liver, salmon) to support fat export from liver

2. Exercise

• Resistance training + aerobic exercise = best combo for reducing liver fat

• Goal: At least 150 minutes/week of moderate activity

3. Gut Health Support

Gut dysbiosis and endotoxemia can worsen NAFLD.

Interventions:

• Probiotics (e.g., Lactobacillus, Bifidobacterium)

• Immunoglobulins (e.g., Immuno-30)

• Prebiotic fiber

• Digestive enzymes for better nutrient absorption

4. Targeted Supplements

Several nutrients and botanicals can support liver fat reduction and inflammation control:

• Omega-3s (EPA/DHA) – Anti-inflammatory and reduces liver triglycerides

• Vitamin E (mixed tocopherols/tocotrienols) – Shown to improve NASH

• Berberine – Improves insulin sensitivity, lowers liver fat

• Curcumin (e.g., Curcumin Complex) – Reduces inflammation and fibrosis

• Resveratrol – Supports mitochondrial health

• Choline – Helps export fat from the liver

• Inositol (especially in PCOS patients)

5. Hormonal Optimization

Low testosterone, estrogen dominance, and thyroid dysfunction can worsen NAFLD. Bioidentical hormone therapy may be appropriate when indicated.

6. Peptide and GLP-1 Agonist Therapies

Here’s where functional and regenerative medicine is transforming fatty liver care.

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Retatrutide: A Game-Changer for Fatty Liver

Retatrutide is a novel triple agonist that targets the GLP-1, GIP, and glucagon receptors, amplifying weight loss, insulin sensitivity, and fat oxidation.

Clinical Trial Highlights:

• In a 2023 phase 2 trial, retatrutide caused up to 24% body weight loss in people with obesity.

• Imaging showed dramatic reductions in liver fat content across all dose groups.

• One of the highest rates of NAFLD resolution seen to date in a drug trial.

Mechanism of Action:

• GLP-1 and GIP improve insulin secretion and appetite regulation.

• Glucagon receptor activation increases energy expenditure and fat burning, particularly visceral and liver fat.

This makes retatrutide particularly exciting for patients with NASH + obesity and metabolic syndrome.

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Survodutide: The Dual Agonist Targeting NASH

Survodutide (also called BI 456906) is a GLP-1/glucagon receptor dual agonist being studied for obesity and NASH.

Clinical Findings:

• In a 2024 phase 2 trial in patients with biopsy-confirmed NASH:

  • Survodutide led to significant liver fat reduction.

  • A high percentage achieved resolution of NASH without worsening of fibrosis.

  • Substantial weight loss (10–16%) was seen over 48 weeks.

Why It Matters:

• Glucagon receptor activation promotes lipolysis and hepatic fat clearance.

• GLP-1 activity reduces appetite and improves insulin sensitivity.

Survodutide is one of the most promising agents specifically being tested in patients with biopsy-proven NASH, offering hope for halting and reversing fibrosis progression.

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Summary: An Integrative Roadmap to Reverse Fatty Liver

Fatty liver is not a hopeless diagnosis—it's a warning sign and an opportunity to transform metabolic health.

Functional medicine focuses on:

• Addressing root causes like insulin resistance, gut dysbiosis, inflammation, and nutrient deficiencies

• Using targeted lifestyle changes to normalize liver fat metabolism

• Supporting healing with supplements, probiotics, and when appropriate, hormone therapy

• Integrating the latest breakthroughs like retatrutide and survodutide for patients with advanced disease or difficulty losing weight

If you or someone you love has fatty liver, now is the time to act. With the right personalized plan, it is possible to completely reverse this condition and protect long-term health.

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References

1. Jastreboff AM, et al. (2023). Retatrutide, a novel triple hormone receptor agonist, for the treatment of obesity. NEJM.

2. Lofton D, et al. (2024). Survodutide in patients with NASH: Phase 2 trial results. The Lancet Gastroenterology & Hepatology.

3. Younossi Z, et al. (2019). Global epidemiology of NAFLD. Hepatology.

4. Sanyal AJ, et al. (2015). Challenges and opportunities in drug development for NASH. Gastroenterology.

5. Zelber-Sagi S, et al. (2017). Lifestyle intervention and fatty liver: A review. Journal of Hepatology.

6. Lavine JE, et al. (2010). Vitamin E and metformin in pediatric NAFLD. JAMA.

7. Eslam M, et al. (2020). A new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Lancet Gastroenterol Hepatol.

8. Musso G, et al. (2012). Probiotics and NAFLD. Hepatology.

9. Friedman SL, et al. (2018). Mechanisms of NAFLD/NASH progression. Nature Medicine.

10. Armstrong MJ, et al. (2015). GLP-1 receptor agonists in NAFLD/NASH. Hepatology.