Benefits
Antioxidant support: lower oxidative stress markers
In a study of 31 healthy adults, the 16 who took 600 mg a day for 2 months had lower urinary F2-isoprostanes, a marker of fat oxidation, and LDL cholesterol that was harder to oxidize in lab tests. In trained men, 600 mg a day for 8 days cut blood markers of fat and protein oxidation by over 30% after hard exercise. A 4-week trial in 20 adults with high blood sugar found no change.
Nerve comfort support
In people with diabetic nerve symptoms, oral ALA at 600 mg a day lowered a foot symptom score (stabbing and burning pain, tingling and numbness) more than placebo over 5 weeks. The clearest results come from short courses given by intravenous drip, a different route from a supplement, and a 4-year oral trial missed its main nerve endpoint. ALA is not a treatment for neuropathy.
Insulin sensitivity
Pooled data from 28 trials (1,016 people) show ALA lowers insulin and HOMA-IR, a measure of insulin resistance, but does not change fasting glucose or HbA1c. Results varied between trials with dose, duration and the health of the people studied.
Mechanism of action
Mitochondrial cofactor activity
Lipoic acid bound to protein is a cofactor for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, two steps in the pathway that turns carbohydrate into usable energy inside mitochondria.
Antioxidant recycling (laboratory finding)
DHLA, the reduced form of lipoic acid, can convert the used (oxidized) forms of coenzyme Q10, vitamin C and glutathione back to their active forms in the test tube. Whether it does this effectively in the body is unclear.
Nrf2 pathway activation
Lipoic acid can react with Keap1, a protein that holds the Nrf2 switch in check, releasing Nrf2 to turn on the cell's own antioxidant defense genes. This has been shown in cell and animal studies.
Metal binding
Both lipoic acid and DHLA bind copper and iron and limit the oxidative damage these metals cause in test-tube studies.
Clinical trials
Multicenter, randomized, double-blind, placebo-controlled trial of once-daily oral ALA at 600, 1,200 or 1,800 mg or placebo for 5 weeks; main outcome was the Total Symptom Score of the feet. (Ziegler et al. 2006, Diabetes Care)
181 people with diabetes and distal symmetric polyneuropathy in Russia and Israel.
Symptom scores fell by about 51% on 600 mg versus 32% on placebo, with similar gains at higher doses; stabbing and burning pain and global ratings also improved. The nerve impairment score was only numerically lower. Nausea, vomiting and vertigo rose with dose, and the authors judged 600 mg a day the best balance of benefit and risk.
Randomized, placebo-controlled trial of 300 mg a day for 8 weeks. (Ansar et al. 2011, Saudi Med J)
57 adults with type 2 diabetes at a clinic in Shiraz, Iran.
Fasting glucose and HOMA-IR insulin resistance improved more than with placebo. Within the ALA group, glucose 2 hours after breakfast also fell, and glutathione peroxidase, an antioxidant enzyme, fell rather than rose. A single small trial.
Multicenter, randomized, double-blind, placebo-controlled trial of 600 mg a day for 4 years; main outcome was a composite of a lower-limb nerve impairment score and nerve tests. (Ziegler et al. 2011, Diabetes Care)
460 people with diabetes and mild to moderate distal symmetric sensorimotor polyneuropathy.
The main composite outcome did not differ from placebo (P = 0.105). Some secondary nerve impairment scores were better with ALA. Serious adverse events were more frequent on ALA (38.1%) than on placebo (28.0%).