Naturopathic Treatment For Non-Alcoholic Fatty Liver Disease

Non-Alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic fat in people who do not consume alcohol. NAFLD is now the most common cause of abnormal liver biochemistry in North America and likely in the United Kingdom. While the cause is not always identified, it is known to be associated with some drugs, genetic defects, obesity, insulin resistance, and type 2 diabetes.¹

Prevalence Of NAFLD

NAFLD may progress to cirrhosis and is likely an important cause of cryptogenic cirrhosis.^{2 3}

In the United States, prevalence of NAFLD is 10% to 46% of the population.⁴ Worldwide prevalence is 6% to 35%, with a median of 20%.⁵

Given the ethnic diversity of individuals in the US population, the prevalence varies among different ethnic groups. For example, in a 2004 study in the journal Hepatology, the authors concluded that:

The frequency of hepatic steatosis varied significantly with ethnicity (45% in Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white women). The higher prevalence of hepatic steatosis in Hispanics was due to the higher prevalence of obesity and insulin resistance in this ethnic group.⁶

Types of NAFLD

NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The former is present without significant liver inflammation, while the latter is consistent with hepatic inflammation that may not be distinguishable histologically from alcoholic steatohepatitis.⁷

Need For  Understanding Liver Disease

Currently, there is a perception that most liver diseases are due to alcohol or hepatitis⁸; yet in medicine today, NAFLD is considered as the hepatic manifestation of one of several major risk factors. These include central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome.⁹

Besides the aforementioned risk factors, patients with NAFLD (particularly those with NASH) often have one or more of the following co-morbidities:^{10 11}

• Obesity,
• Systemic Hypertension, and
• Type 1 Diabetes.

Causes Of Non-Alcoholic Fatty Liver Disease

The pathogenesis of nonalcoholic fatty liver disease is not fully understood. One of the leading theories involves insulin resistance as a key mechanism leading to hepatic steatosis and perhaps also steatohepatitis.

Another theory postulates that NAFLD is caused by oxidative stress secondary to steatohepatitis.

Hepatic iron,¹² leptin,¹³ antioxidant deficiencies,¹⁴ and intestinal bacteria¹⁵ have all been noted to be part of the pathogenesis of NAFLD.

Most individuals with NAFLD are asymptomatic, although some with NASH may complain of vague right upper abdominal discomfort, fatigue, and/or malaise.¹⁶ In clinical reality, NAFLD typically comes to the attention of the healthcare practitioner because laboratory testing reveals elevated liver aminotransferases.

On physical exam, some patients may have hepatomegaly due to the fatty infiltration.¹⁷ Hepatic steatosis can also be detected incidentally on abdominal imaging.

In clinical reality, nonalcoholic fatty liver disease typically comes to the attention of the healthcare practitioner because laboratory testing reveals elevated liver aminotransferases.

Normal aminotransferase enzymes do not exclude those with NAFLD, but they present with mild to moderate elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT).¹⁸

When elevated, these aminotransferases may be 2 to 5 times the upper limit of normal with a ratio of less than 1, whereas in alcoholic fatty liver disease, the ratio is typically greater than 2.

It should be noted that the degree of aminotransferase elevation does not predict the degree of hepatic inflammation or fibrosis.

Furthermore a normal ALT does not exclude histological injury.¹⁹ Other laboratory findings that may be found are an abnormal or high end of normal gamma γ-glutamyl transferase (GGT).^{20 21}

Treatment Consideration

Numerous therapies have been investigated for the NAFLD treatment. Weight loss is the only therapy with reasonable evidence suggesting it is beneficial and safe, although emerging data supports nutritional interventions.

Conventionally, the following strategies are typically employed:

• Weight loss for patients who are overweight or obese;
• Hepatitis A and B vaccinations, except in those with serologic evidence of immunity;²²
• Treatment of risk factors for cardiovascular disease; and
• Abstention from alcohol.

Pharmacological agents, such as pioglitazone, are not recommended. Numerous other drugs have been examined for the treatment of NASH. While some have shown initial promise, none have been sufficiently studied.

I have routinely screened my patients with high normal GGT levels, in isolation or in conjunction with high normal or elevated AST and/or ALT levels, with a liver ultrasound and have frequently seen evidence of NAFLD on the radiology report.

Typically, the patient’s medical doctor has dismissed this finding, as if there was nothing to be done about it besides weight loss (if indicated).

This is where nutritional and nutraceutical therapies have an enormous role to play. A diet rich in organic fruits and vegetables (the more varied the colors, the better) and avoidance of refined, processed, and charred foods are beneficial.²³

I also recommend that my patients avoid trans fats and saturated fats,²⁴ along with nitrates/nitrates and high fructose corn syrup.^{25 26 27 28}

I recommend that they consume green tea, fresh fish, and liver-supportive foods. (Note of caution in regards to fish: Be aware of the mercury and other contaminants present in some fresh fish. The US Environmental Protection Agency is an excellent resource on safe fish consumption.²⁹)

Liver-supportive foods include high sulfur foods like garlic and onions, as well as cruciferous vegetables^{30 31 32} like Brussels sprouts, cabbage, cauliflower, and broccoli. Other nutritious liver-supportive foods include artichokes, turmeric, beets, and green tea.^{33 34 35 36 37}

The following nutrients have shown the greatest clinical efficacy in addressing and even reversing the spectrum of NAFLD. In my practice, I have seen positive results in as little as 3 months, but typically it takes 9 to 12 months to see the most restoration and reversal of NAFLD.

Tocotrienols

200 mg twice daily with food.³⁸ Gamma-tocotrienol, but not alpha-tocopherol, attenuates triglycerides accumulation by regulating fatty acid synthase and carnitine palmitoyltransferase enzymes, leading to a reduction of hepatic inflammation and endoplasmic reticulum stress.³⁹

N-acetyl-cysteine (NAC)

600 mg twice daily, best taken on an empty stomach.⁴⁰ NAC blocks the propagation of lipid peroxidation.⁴¹

Omega 3 Essential Fatty Acids

2 g to 4 g daily.⁴² Omega 3 polyunsaturated fatty acids are known to downregulate sterol regulatory element binding protein 1c and upregulate peroxisome proliferator activated receptor α, which would favor fatty acid oxidation and reduce steatosis.⁴³

Silybum marianum (Milk Thistle)

280 mg to 360 mg daily.⁴⁴Phytosomes provide the greatest bioavailability.⁴⁵ Silymarin interferes with leukotriene formation in Kupffer cell cultures, thus inhibiting hepatic stellate cell activation.⁴⁶

L-carnitine

1 g twice daily.⁴⁷ L-carnitine plays a critical role in fatty acid oxidation of energy regulation. It serves as a carrier to facilitate the transport of long-chain fatty acids through the mitochondrial membrane and to undertake free fatty acid b-oxidation.⁴⁸

Choline

250 mg to 1,000 mg daily.⁴⁹ The precise mechanism of choline is unknown, except for its methyl donor properties and the observation that those with genetic polymorphisms involved in choline biosynthesis are associated with an increased risk of developing fatty liver.⁵⁰

Betaine

20 g daily (1-6 g/d may beneficial if used in conjunction with other therapies).⁵¹ Betaine, when used in rats with alcohol-induced steatohepatitis, led to an increase in S-adenosyl-l-methionine, which in turn led to a reduction in hepatic steatosis.⁵²

Vitamin E (as RRR-α-tocopherol)

400 IU twice daily with food.⁵³ Although well studied, I don’t utilize this treatment by itself due to increased risk for adverse cardiovascular events⁵⁴ and gamma-tocopherol depletion⁵⁵ at this dose. Mixed tocopherols have also shown efficacy in NAFL.35 Vitamin E is an effective defense mechanism against lipid peroxidation.⁵⁶ Lipid peroxidation is increased in NAFLD and can promote inflammation and tissue damage.⁵⁷

Other less-studied nutrients with potential benefits in the treatment of NAFLD include pantethine or pantothenic acid, taurine, magnesium, zinc with copper, vitamin B6, biotin, manganese, and lysine.⁵⁸

Conclusion

Given the relatively high US prevalence of non-alcoholic fatty liver disease, along with its strong correlation in conditions such as metabolic syndrome, types I and II diabetes, obesity and dyslipidemia, evidence-based naturopathic strategies and interventions lay the framework for these treatments to take center stage.