Alpha-Lipoic Acid (ALA): What It Is, Uses, Evidence, and Safety

Alpha-lipoic acid (ALA) is a sulfur-containing antioxidant with a chemical formula C8H14O2S2 and molecular weight ≈206.3 g/mol. The R-enantiomer is biologically active; most supplements are racemic. ALA regenerates other antioxidants, crosses the blood-brain barrier, and has the strongest clinical support for reducing symptoms of diabetic peripheral neuropathy (typical trial doses 300-600 mg/day). Evidence for use in neurodegenerative disorders and heavy-metal detoxification is limited or inconclusive. ALA can lower blood glucose and may cause gastrointestinal side effects or rare autoimmune hypoglycemia; consult a clinician before use.

What is alpha-lipoic acid?

Alpha-lipoic acid (ALA) is a sulfur-containing compound that acts as a metabolic cofactor and antioxidant. Its chemical formula is C8H14O2S2 and its molecular weight is about 206.3 g/mol. At physiological pH it exists mainly as the lipoate anion rather than a neutral acid.

ALA occurs in two mirror-image forms, R-ALA and S-ALA. R-ALA is the naturally occurring, biologically active enantiomer. Most over-the-counter supplements are a racemic mixture (R+S), though R-ALA preparations are also sold.

> Historically ALA was isolated in the 1950s and has been referred to as thioctic acid. It was reportedly called a "pyruvate activation factor" in early work .

How ALA works

ALA is both water- and fat-soluble, which allows it to act across cellular compartments. It can neutralize reactive oxygen species directly and helps regenerate other antioxidants such as vitamin C, vitamin E, and glutathione. ALA also crosses the blood-brain barrier, which is one reason researchers have studied it for neurodegenerative conditions.

Clinical uses and evidence

• Diabetic neuropathy: ALA has the strongest clinical support for reducing symptoms of diabetic peripheral neuropathy. Clinical trials - often using 600 mg/day oral dosing or intravenous regimens - have shown symptomatic improvement in some patients.

• Neurodegenerative disease: ALA has been investigated for Alzheimer's and Parkinson's disease because of its antioxidant and metabolic roles. Clinical evidence remains limited and inconclusive.

• Metal chelation/heavy-metal toxicity: ALA can bind metal ions in biochemical studies and animal models; clinical evidence for treating mercury or other heavy-metal poisoning in humans is limited and inconsistent ¹.

Typical doses and sources

Supplements commonly contain 100-600 mg per capsule. Clinical trials often use 300-600 mg daily; some protocols use 600 mg once daily. R-ALA formulations are available but costlier. Dietary sources of small amounts of lipoic acid include organ meats (liver, heart), spinach, broccoli, and yeast.

Safety and precautions

ALA is generally well tolerated. Common side effects include gastrointestinal upset and skin rash. Because ALA can lower blood glucose, people with diabetes should use it under medical supervision and monitor glucose closely. Rare case reports link ALA to autoimmune-mediated hypoglycemia (insulin autoimmune syndrome) in susceptible individuals ².

If you are pregnant, breastfeeding, on glucose-lowering medications, or considering ALA for a specific medical condition, talk with a healthcare provider before starting supplements.

Bottom line

Alpha-lipoic acid is a biologically active antioxidant with clinically supported benefit for diabetic neuropathy and plausible mechanisms for broader neuroprotective roles. Evidence for heavy-metal detoxification and neurodegenerative disease treatment remains limited. Typical supplement doses are 300-600 mg/day, and safety monitoring is advisable for people with diabetes or those on interacting medications.

1. Confirm historical reference that alpha-lipoic acid was called 'pyruvate activation factor' in early literature.
2. Verify clinical evidence strength for ALA as a chelator in mercury or other heavy-metal poisoning in humans.
3. Verify frequency and causal evidence for insulin autoimmune syndrome (autoimmune-mediated hypoglycemia) linked to ALA use.