Alpha-lipoic acid

Educational overview

Oral dietary supplement; compounded IV use remains under FDA evaluation and evidence is condition- and formulation-specific.

Alpha-lipoic acid (ALA, also called thioctic acid) is a naturally occurring dithiol compound that serves as a cofactor for mitochondrial dehydrogenase enzymes, including the pyruvate dehydrogenase complex. Small amounts are synthesized in the body and are present in foods such as organ meats and spinach. As a supplement it is studied for antioxidant properties: the reduced form, dihydrolipoic acid, scavenges reactive oxygen species and regenerates other antioxidants such as glutathione and vitamins C and E. Commercial products contain either the racemic mixture of R- and S-enantiomers or the R-enantiomer alone, and the two forms differ in bioavailability. Pharmacologically it is grouped with antioxidant and metabolic supplements rather than with hormones or peptides.

The strongest human evidence concerns symptomatic diabetic polyneuropathy. Several randomized, placebo-controlled trials conducted mainly in Germany and Russia, including the SYDNEY 2 trial published in Diabetes Care in 2006, reported reductions in neuropathic symptom scores with oral treatment over a few weeks. The four-year NATHAN 1 trial found improvements in some neuropathic impairment measures but did not meet its primary composite endpoint. A 2012 meta-analysis of randomized trials concluded that intravenous administration produced clinically relevant symptom improvement, while the oral evidence was less consistent. Evidence for other uses, such as glycemic control, body weight, or skin aging, is limited to small or short trials, and no large outcome studies exist.

Regulatory status differs sharply by jurisdiction and route. In Germany, alpha-lipoic acid has been a prescription medicine for diabetic polyneuropathy for decades, marketed as thioctic acid in oral and intravenous forms. In the United States it is sold as a dietary supplement under the Dietary Supplement Health and Education Act and is not an FDA-approved drug for any indication; supplement labels cannot claim to treat neuropathy. Injectable alpha-lipoic acid in the United States comes only from compounding pharmacies. FDA's Pharmacy Compounding Advisory Committee has reviewed the substance for the section 503A bulk drug substances list, and its inclusion status remains a matter of agency rulemaking rather than product approval.

Oral capsules and tablets are stored at room temperature away from moisture and light according to the manufacturer's label. Compounded intravenous preparations are light-sensitive and carry a beyond-use date assigned by the compounding pharmacy, which is typically much shorter than the shelf life of a commercial supplement. For a dose log or inventory record, relevant details include the product's stated form (racemic or R-enantiomer), the amount per capsule or the concentration per milliliter, the route, the lot number, the source pharmacy for compounded products, and any concurrent diabetes medicines, since ALA has been reported to lower blood glucose and, rarely, to trigger insulin autoimmune syndrome in genetically susceptible individuals.

Category

Antioxidant / metabolic supplement

Routes represented

Oral / Other / unspecified

Storage context

Follow the product or pharmacy label; requirements vary by route and formulation.