Alpha-Lipoic Acid (ALA / R-ALA)
A unique antioxidant — works in both water and fat compartments, regenerates other antioxidants, and improves insulin sensitivity. Best evidence is in diabetic neuropathy.
Strong for diabetic peripheral neuropathy (SYDNEY-2 and other RCTs — symptom reduction with both oral and IV forms). Strong for insulin sensitivity improvement. Moderate for metabolic syndrome markers. Effects: 4–8 weeks for blood sugar and neuropathy.
Alpha-lipoic acid is a small sulfur-containing molecule the body makes in small amounts and uses inside mitochondria to help generate energy. As a supplement it crosses both water- and fat-soluble barriers — unusual for an antioxidant — letting it work in blood, cell membranes, and intracellular compartments. It also regenerates oxidised forms of vitamins C and E and glutathione. The most established clinical use is diabetic peripheral neuropathy (approved as a drug in Germany), with secondary uses in metabolic syndrome, insulin resistance, and brain fog. Two forms exist: R-ALA (the natural, bioactive isomer) and synthetic 50:50 R/S-ALA — the R form is more potent.
- Form
- R-ALA (R-alpha-lipoic acid) or Na-R-ALA (stabilised sodium R-lipoate) — the active form, more bioavailable. R/S-ALA (cheaper, racemic) works but at higher doses.
- Dose
- R-ALA: 100–300 mg/day. R/S-ALA: 300–600 mg/day (1–2x daily). Therapeutic for neuropathy: 600 mg twice daily of R/S-ALA.
- Timing
- Empty stomach for best absorption (food reduces it ~30%). 30–60 min before meals. AM or pre-meal.
- Schedule
- Daily. Some users cycle (3 months on, 1 off) for sustained sensitivity.
- Side effects
- Mild GI upset, rash, hypoglycemia (especially if diabetic), skin reactions. Rarely insulin autoimmune syndrome (in genetically predisposed individuals — mostly Japanese / Korean populations).
- Interactions
- Diabetes medications — additive glucose lowering, watch for hypoglycemia. Thyroid medications — may bind and reduce absorption (separate by 4 hours). Chemotherapy — interaction debated.
- Contraindications
- Thiamine deficiency / chronic alcohol use (can precipitate Wernicke's — supplement thiamine first). Insulin autoimmune syndrome history.
- Lab markers
- Fasting insulin, HbA1c, fasting glucose for metabolic tracking.
- Food sources
- Spinach, broccoli, red meat, organ meats (liver, heart, kidney), brewer's yeast. Food sources provide micrograms — therapeutic effect requires supplementation.
Pairs with
Biotin — ALA can deplete biotin at high chronic doses; co-supplementation prevents this. Acetyl-L-carnitine — synergistic mitochondrial pair, esp. for brain. CoQ10 (mitochondrial network). Vitamin C and E.
Where to buy
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within Polyphenols & antioxidants