# Alpha-lipoic acid (ALA)

Alpha-lipoic acid (ALA) is a sulfur-containing fatty acid. It is an essential helper (cofactor) for two mitochondrial enzyme complexes (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) that connect sugar-burning to the citric-acid cycle. Only one mirror-image form (R-ALA) is protein-bound and active. Commercial supplements are a 50/50 R/S mix. R-ALA absorbs about 40 to 50% better than the S form. ALA and its reduced partner (DHLA) are both fat- and water-soluble. So they can scavenge free radicals in any cell compartment. They also regenerate your spent glutathione, vitamin C, and vitamin E. That recycling cascade sets ALA apart from single-compartment antioxidants. Mitochondrial function and glutathione both fall with age. ALA partly restored both in rodents, though direct human evidence is thin. The strongest clinical evidence is in diabetic nerve damage. The SYDNEY trial (Ametov et al., 2003, 120 patients) tested IV ALA at 600 mg/day for three weeks. It cut neuropathy symptom scores versus placebo (p<0.001). The four-year NATHAN 1 trial (Ziegler et al., 2011, 460 patients) tested oral ALA 600 mg/day. Its main composite endpoint missed significance (p=0.105), though some secondary scores favored ALA. In healthy aging, the evidence is preliminary, mostly from animal or small mechanistic studies. A long-term human longevity benefit is not established.

## Sources

- Ametov AS, Barinov A, Dyck PJ, et al.. (2003). The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid. Diabetes Care. https://doi.org/10.2337/diacare.26.3.770
- Ziegler D, Low PA, Litchy WJ, et al.. (2011). Efficacy and Safety of Antioxidant Treatment With α-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy: The NATHAN 1 Trial. Diabetes Care. https://doi.org/10.2337/dc11-0503
- Salehi B, Yılmaz YB, Antika G, et al.. (2019). Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules. https://doi.org/10.3390/biom9080356

---

_Canonical: https://longevity-switzerland.com/en/glossary/alpha-lipoic-acid · Part of Longevity Cities · Updated 2026-06-22_