Alpha-lipoic acid
(R)-lipoic acid
Also known as: ALA, Thioctic acid, Lipoic acid, R-lipoic acid, RLA
Alpha-lipoic acid is a powerful antioxidant that is both water- and fat-soluble, allowing it to work throughout the body. It is approved in Germany for diabetic neuropathy treatment.
Introduction
Alpha-lipoic acid (ALA), also known as thioctic acid, is a naturally occurring compound that functions as a cofactor for several mitochondrial enzymes involved in energy metabolism. It was first isolated in 1951 and has been extensively studied for its antioxidant properties and therapeutic potential.
What makes ALA unique among antioxidants is its ability to function in both aqueous (water) and lipid (fat) environments, earning it the nickname "universal antioxidant." This allows it to protect virtually all parts of cells from oxidative damage.
ALA also has the ability to regenerate other antioxidants including glutathione, vitamin C, and vitamin E, effectively recycling them back to their active forms. This antioxidant network effect amplifies its protective capabilities.
In Germany, ALA is an approved drug for the treatment of diabetic neuropathy at doses of 600 mg/day. It has been shown to reduce neuropathic pain, burning, and numbness in diabetic patients.
Beyond neuropathy, ALA has been studied for blood sugar control, metabolic syndrome, cognitive decline, and various other conditions. The R-enantiomer (R-lipoic acid) is the naturally occurring form and may be more bioactive than the synthetic racemic mixture.
Main Benefits
Clinically proven to reduce symptoms of diabetic peripheral neuropathy including pain, burning, and numbness.
May improve insulin sensitivity and blood sugar control in type 2 diabetes.
Universal antioxidant that works in both water and fat environments; regenerates other antioxidants.
May reduce symptoms of metabolic syndrome including blood pressure and lipid abnormalities.
Shows potential neuroprotective effects and may slow cognitive decline.
Mechanism of Action
Alpha-lipoic acid exerts its effects through multiple mechanisms:
Mitochondrial Cofactor: ALA is an essential cofactor for several mitochondrial enzyme complexes including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, critical for energy metabolism.
Direct Antioxidant: ALA scavenges various free radicals including superoxide, hydroxyl radicals, and singlet oxygen. Its disulfide bond allows it to neutralize oxidants and be regenerated by cellular reducing systems.
Antioxidant Regeneration: ALA can regenerate other antioxidants including glutathione, vitamin C, and vitamin E back to their reduced (active) forms, amplifying cellular antioxidant capacity.
Metal Chelation: ALA can chelate transition metals like iron and copper, preventing them from catalyzing free radical formation through Fenton reactions.
Glucose Uptake: ALA appears to enhance glucose uptake into cells through recruitment of glucose transporters (GLUT4) to the cell membrane, independent of insulin.
Nerve Blood Flow: In diabetic neuropathy, ALA may improve nerve blood flow through its antioxidant effects on blood vessels and nitric oxide preservation.
Natural Sources
ALA is found in small amounts in many foods but not in therapeutically significant quantities.
Examples:
Red meat (especially organ meats)
Spinach
Broccoli
Tomatoes
Yeast (brewer's and nutritional)
Present in small amounts in foods; therapeutic doses require supplementation; dietary sources insufficient for clinical effects.
Recommended Daily Intake
No established RDA (body synthesizes it). Therapeutic doses: 300-600 mg for general antioxidant support; 600-1200 mg for diabetic neuropathy.
Reference Values:
| General antioxidant | 300-600 mg/day |
| Diabetic neuropathy | 600-1200 mg/day |
| R-lipoic acid (bioactive form) | 100-300 mg/day (equivalent to higher racemic doses) |
Sources for RDI/AI:
Take on an empty stomach for best absorption. R-lipoic acid form more bioactive but more expensive. Effects may take weeks to months for neuropathy.
Effectiveness for Specific Focuses
Universal antioxidant; regenerates other antioxidants; both water and fat soluble; strong antioxidant network effects.
Improves insulin sensitivity; enhances glucose uptake; supports metabolic health; approved for diabetic neuropathy.
Clinically proven effects on diabetic neuropathy; reduces nerve pain; improves nerve conduction; neuroprotective and cognitive support.
Antioxidant and mitochondrial support may benefit aging; limited direct longevity evidence.
Safety Information
Potential Side Effects
Nausea
Rashes
Headache
Low blood sugar (hypoglycemia)
Contraindications
Thiamine (vitamin B1) deficiency (should be corrected first)
Hypothyroidism (may affect thyroid hormones)
Overdose Information
Very safe; no serious toxicity reported; excellent safety profile even at high doses.
Excellent safety profile. Approved drug in Germany with decades of safe use.
Interactions
Drug Interactions:
Diabetes medications (may enhance glucose-lowering effects)
Thyroid medications (may affect thyroid hormone levels)
Chemotherapy (antioxidant effects may interfere - discuss with oncologist)
Monitor blood sugar with diabetes medications; may affect thyroid medications; discuss with oncologist during chemotherapy.
Other Supplement Interactions:
Biotin - high doses may compete for absorption
Other antioxidants - synergistic effects
High doses may compete with biotin; synergistic with other antioxidants.
Take on empty stomach (30 min before meals) for best absorption. May lower blood sugar - monitor if diabetic. Ensure adequate thiamine (B1) intake.
Forms and Bioavailability
Racemic ALA contains both R and S forms; R-lipoic acid is the naturally occurring bioactive form with potentially better activity.
R-lipoic Acid (stabilized)
Pure bioactive R-enantiomer; better bioactivity than racemic mixture; requires stabilization.
Naturally occurring form; better bioactivity; may be effective at lower doses than racemic ALA.
Preferred form if available. R-ALA polymerizes easily and requires stabilization (often as sodium salt). More expensive but potentially more effective.
Racemic ALA (R/S mixture)
Standard synthetic form containing both R and S enantiomers; S form may compete with R form.
Well-studied; S-enantiomer may compete with R-enantiomer but still effective; lower cost.
Standard form in most supplements. Less expensive than R-ALA. Still effective; just requires slightly higher doses.
Warnings & Suitability
Did You Know...?
Alpha-lipoic acid is approved as a prescription drug in Germany specifically for the treatment of diabetic neuropathy.
ALA is both water and fat soluble, making it one of the few antioxidants that can work throughout the entire cell.
The R-enantiomer of ALA is the only form naturally produced by the body; the S-enantiomer in racemic supplements is synthetic.
ALA can regenerate "used up" vitamin C and vitamin E, restoring them to their active antioxidant forms.
General Scientific Sources
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Content Verification
Last Medical Review: 2/13/2026
Reviewed by: Editorial Team