300–600 mg/day (the R form is better absorbed), on an empty stomach.
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Alpha-lipoic acid is an endogenous sulfur-containing compound present in virtually all cells of the body, where it functions as an essential cofactor for several key mitochondrial enzymes of energy metabolism (especially pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase); its most peculiar pharmacological characteristic is its simultaneous solubility in water and fat (amphipathic), which allows it to act as an antioxidant in both hydrophilic and hydrophobic cellular compartments, regenerate other antioxidants (vitamin C, vitamin E, glutathione) after their oxidative use, and chelate heavy metals, a combination of properties that has made it one of the antioxidant supplements with the broadest and best-documented clinical profile.
Unlike many supplements with an interesting mechanistic basis but weak clinical evidence, alpha-lipoic acid has recognized clinical applications in European countries where it is approved as a medication for painful diabetic neuropathy (Germany, Italy, and others), with therapeutic doses of 600 milligrams daily orally or parenterally, an indication supported by solid meta-analyses and specific neurological clinical guidelines.
The indication with the strongest clinical support is painful diabetic neuropathy: several meta-analyses have confirmed significant improvements in pain scales, sensation, and nerve conduction velocity with doses of 600 milligrams daily orally for 3-5 weeks, with clinically relevant magnitudes and a favorable tolerability profile; the European trials (especially the ALADIN, NATHAN, and SYDNEY series) are the basis of ALA's regulatory approval in several European countries.
In type 2 diabetes and insulin resistance, several studies have documented modest improvements in insulin sensitivity, fasting glucose, and glycated hemoglobin with supplementation at 600-1,800 mg/day for 8-24 weeks, an indication consistent with its mitochondrial and antioxidant role.
In weight loss, several trials have shown modest reductions with doses of 1,800 mg/day for 16-20 weeks; the effects are quantitatively small (1-2 kg) and do not justify ALA as a primary weight-loss strategy.
The doses studied range from 300 to 1,800 milligrams daily, divided into 2-3 doses on an empty stomach for better absorption; R-ALA forms (the natural enantiomer) are significantly more bioavailable than the cheaper racemic commercial forms; typical commercial products contain 200-600 mg per capsule.
Generally well tolerated at the doses studied; the adverse effects described are rare and mild (mild digestive discomfort, occasionally skin rash); the most important clinical consideration is the risk of hypoglycemia, especially in people with diabetes treated with insulin or secretagogues: ALA potentiates the glucose-lowering effect of these drugs and can precipitate clinically relevant hypoglycemia, requiring dose adjustment of the antidiabetic treatment under medical supervision; people with thiamine deficiency (chronic alcoholism, severe malnutrition) should correct the deficiency before starting ALA because it can worsen the condition; in pregnancy and breastfeeding the data are limited and avoidance is recommended as a precaution; people taking thyroid hormones may experience interference with absorption, and doses should be taken at separate times.
Information, not medical advice. Scientific evidence reflects the quality of the studies.