LiverTox: Clinical and Research Information on Drug - Induced Liver Injury

May 2023
Bethesda (MD)

 

OVERVIEW

 

Introduction

Alpha lipoic acid is a natural occurring essential fatty acid that is synthesized intracellularly, but is also in many foods and absorbed to a variable extent. Alpha lipoic acid is a common ingredient in multivitamin tablets and in dietary supplements and is even included in many pet foods. While purported to have antioxidant, antidiabetic, and antiaging effects, it has not been approved by the FDA as therapy for any medical disease or condition. Alpha lipoic acid has been evaluated in many clinical trials and has not been associated with serum aminotransferase elevations or in cases of clinically apparent liver injury.

 

Background

Alpha lipoic acid is a natural occurring fatty acid that serves as a necessary, covalently-bound cofactor in many enzymatic processes including the alpha ketoacid dehydrogenases that play a critical role in mitochondria in energy metabolism. Adequate amounts of alpha lipoic acid are synthesized in mitochondria from octanoic acid, but the natural dithiol fatty acid is also found in many foods and can be absorbed from the intestines and taken up in many organs and tissues including liver, kidney, and brain. Alpha lipoic acid has been purported to have antioxidant activity in scavenging free radicals and restoring glutathione levels, as well as antidiabetes activities in normalizing glucose and insulin activity, and as chelating metals. While these pharmacological actions have been found in vitro and in vivo, it is not clear whether alpha lipoic acid supplements have clinically meaningful actions in humans. Multiple studies of alpha lipoic acid in patients with diabetic polyneuropathy, arthritis, diabetes, fibromyalgia, multiple sclerosis, osteoarthritis and other conditions have yielded variable results, but almost invariably with minimal or no adverse side effects. While available in many forms over-the-counter, alpha lipoic acid has not been approved for use by the FDA for any medical disease or condition. In placebo controlled clinical trials in patients with diabetes and peripheral neuropathy, alpha lipoic acid was associated with mild improvements in surrogate markers of neuropathy but was not shown to ameliorate symptoms or progression of neuropathy. Currently, alpha lipoic acid is available in tablets and capsules of 50 to 600 mg and the recommended dosage has ranged from 100 to 600 mg once or twice daily. Alpha lipoic acid is usually well tolerated but side effects at higher doses can include abdominal discomfort, heartburn, constipation or diarrhea, nausea, dizziness, and headache. Rare, potentially severe adverse effects reported after single large overdoses include confusion, stupor, seizures, lactic acidosis, rhabdomyolysis, coma, and multiorgan failure that can be fatal.

 

Hepatotoxicity

In multiple, largely short term clinical studies of different preparations and concentrations of alpha lipoic acid, adverse side effects were usually described as uncommon and minimal with either no change or slight improvement in serum aminotransferase levels. Despite widespread use, there have been no published reports of serum enzyme elevations or clinically apparent liver injury attributable to alpha lipoic acid given in conventional doses. In cases of overdose of alpha lipoic acid, some patients have developed lactic acidosis, hemodynamic instability, rhabdomyolysis, renal dysfunction, and multiorgan failure, but symptoms of neurologic, cardiac and renal dysfunction generally predominate and liver injury may be the result of shock and ischemia.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

 

Mechanism of Injury

The mechanism by which alpha lipoic acid might cause liver injury is unknown. In cases of overdose with seizures and lactic acidosis, clinical features suggest that there is generalized mitochondrial failure predominantly affecting the central nervous system, heart, and muscle. The liver histology associated with alpha lipoic acid overdose has not been described but dogs given high doses develop hepatic abnormalities.

 

Outcome and Management

Hepatotoxicity from alpha lipoic acid has not been reported.

 

Drug Class: Herbal and Dietary Supplements

Other names: ALA, Thioctic acid.