How Can Alpha Lipoic Acid Help Prevent the Progression of Fatty Liver Disease?

Clinical Evidence
Recommended Dosage

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The progression of non-alcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) begins with the activation of hepatic stellate cells (HSCs) in the liver. These cells produce fibrotic changes in the liver in an attempt to wall off inflammation. Research suggests that Nrf2, a protein found in the cells, stimulates genes that produce other antioxidants and beneficial proteins. These protective effects help block HSC activation and fibrosis. ^(iv.145)

Animal and human clinical studies indicates alpha lipoic acid may help protect the liver from damage caused by a high-fat diet and NAFLD. Studies show that alpha lipoic acid also significantly stimulates Nrf2, which may help explain some of its antifibrotic effects in the liver. ^{(iv.100, 146-147)}

Beneficial effects include:

Table IV.17: Alpha Lipoic Acid's Effects on Fatty Liver Risks
Effect	↑ Proteins (e.g., AMPK, SIRT1, and adiponectin) that regulate energy metabolism	↑ Natural Antioxidants (e.g., glutathione) and/or ↓ Free Radicals	↓ Insulin Resistance	↓ Elevated Triglyceride Cholesterol Levels	↑ Phase I and II Detoxifying Enzymes	Anti-Inflammatory	↓ HSCs
↓ Fat deposits in the liver (steatosis)	♦ ^{(iv.100, 147-148)}	♦ ^{(iv.78, 149)}	♦ ^{(iv.47, 149)}	♦ ^(iv.100)		♦ ^(iv.100)
Improved carbohydrate metabolism & glucose regulation	♦ ^{(iv.100, 130, 147)}	♦ ^{(iv.78, 149)}	♦ ^{(iv.47, 149)}	♦ ^(iv.100)		♦ ^(iv.100)
↓ Abnormal liver enzyme levels	♦ ^(iv.100)	♦ ^(iv.150)				♦ ^(iv.150)	♦ ^(iv.150)
↓ Inflammation	♦ ^(iv.147)	♦ ^(iv.150)			♦ ^(iv.130)		♦ ^(iv.150)
↓ Fibrosis (liver damage)		♦ ^{(iv.78, 145, 147, 150-151)}				♦ ^(iv.151)	♦ ^{(iv.146-147, 150)}
↓ Liver cell death		♦ ^{(iv.78, 146, 150)}					♦ ^(iv.150)
Improved liver function		♦ ^{(iv.78, 130)}

Clinical Evidence of Benefit

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Results of a controlled clinical study suggest that taking 300 mg/day of alpha lipoic acid could help treat fatty liver disease and NASH. The 6-month study included 155 patients with NAFLD or NASH who also had a BMI of between 28 and 33. None of the participants had diabetes, insulin resistance, hepatitis, or thyroid conditions. ^(iv.100)

Benefits were found when alpha lipoic acid was taken alone or in combination with vitamin E supplements. Each supplement performed better than placebo to reduce most clinical markers of the liver conditions. However, the combination of the two together worked much better than either alone. ^(iv.100)

Alpha lipoic acid also showed benefit in another randomized, placebo-controlled clinical trial involving 120 patients with NAFLD. The study combined alpha lipoic acid with a low calorie diet and another antioxidant (UDCA). Results indicated: ^(iv.152)

Significantly reduced fibrosis.
Moderately reduced abnormal enzyme levels.

Doses used were 400 mg/day of alpha lipoic acid with 300 mg/day of UDCA. ^(iv.152)

Recommended Dosage and Helpful Combinations

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People with liver disease may also have reduced levels of alpha lipoic acid. Nutritional experts suggest 300-600 mg/day of alpha lipoic acid supplements may help NAFLD. Studies indicate alpha lipoic acid may be helpful with metabolic syndrome conditions linked to NAFLD as well. ^{(iv.70, 100, 130)}

Research suggests that combining alpha lipoic acid with other supplements or dietary factors may be especially beneficial for liver health. These include:

Table IV.18: Natural Combinations for Liver Health
Substance Used With Alpha Lipoic Acid	Benefit/Purpose
Acetyl-l-carnitine	Lower unhealthy liver enzyme levels and improve cell mitochondria. ^(iv.153)
Flax seed oil	Increase natural antioxidants, reduce stress from free radicals, and block fat deposits in liver. ^(iv.154)
Ursodeoxycholic acid and low-calorie diet	Reduce fibrotic damage and abnormal liver enzyme levels. ^(iv.152)
Vitamin E	Improve liver function. ^(iv.100)

At lower doses (100 mg/kg of body weight. Higher doses (200 mg/kg) increased inflammation. ^(iv.147)

The one exception for alpha lipoic acid was that it did not reduce levels of the liver enzyme alanine aminotransferase. ^(iv.100)

Ursodeoxycholic acid. ^(iv.152)

Such as obesity, diabetes, and heart disease. ^{(iv.70, 100, 130)}

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