Alpha-Lipoic Acid
Also known as ALA · thioctic acid · lipoic acid · R-lipoic acid
Research profile
Clinically studied12 key studies reviewed
401 human trials & reviews
7,943 papers on PubMed
Clinical evidence
What the research shows
Alpha-lipoic acid is a cofactor in mitochondrial energy enzymes and an antioxidant. Its best-supported use is symptom relief in diabetic nerve damage at 600 mg/day, where several RCTs and meta-analyses show benefit, though the 4-year NATHAN 1 trial missed its main endpoint. For weight, blood sugar and cholesterol, meta-analyses disagree: a large one found small improvements, while a 2025 analysis in overweight adults and a 2026 analysis in fatty liver found none. Rarely, ALA can trigger insulin autoimmune syndrome (dangerous low blood sugar) in genetically susceptible people.
Evidence applies mainly to adults with diabetes and nerve symptoms taking 600 mg/day, ideally under medical supervision. Evidence for metabolic benefit is mixed and mostly in people with existing metabolic disease.
The research is clear: ingredients deliver most when your body actually needs them. That’s why AXEL maps your terrain first, then builds a regimen around you.
Discover your terrainSafety & good-to-know
- EFSA (2021) concluded ALA in supplements likely raises the risk of insulin autoimmune syndrome (episodes of severe low blood sugar) in people with certain HLA gene types, based on 49 case reports; a safe threshold dose could not be set. The condition resolved after stopping ALA. PubMed 34122657PubMed 40488315PubMed 42707574
- Nausea, vomiting and vertigo increase with dose (seen at 1,200-1,800 mg). In NATHAN 1, serious adverse events were numerically more frequent on ALA (38% vs 28%), though tolerability was similar. PubMed 17065669PubMed 21775755
- A 2025 case report linked insulin autoimmune syndrome to ALA combined with captopril (another thiol drug). Supplements should be reviewed when investigating unexplained low blood sugar. PubMed 42707574
Every AXEL regimen can be reviewed by a physician in a consultation.
The studies (12)
Effectiveness of alpha lipoic acid supplementation on biochemical, clinical, and inflammatory parameters in patients with diabetic polyneuropathy: A systematic review and meta-analysis.
Meta-analysis of RCTs · Adults with diabetic polyneuropathy · n = 15 studies (12 analysed) · Various, mostly 600 mg/day · Varied
Improved tingling, numbness and pain scores; no significant change in HbA1c or several nerve-conduction measures.
Oral, intravenous, or sequential alpha-lipoic acid for diabetic peripheral neuropathy? A Bayesian network meta-analysis of randomized controlled trials.
Network meta-analysis · Adults with diabetic peripheral neuropathy · n = 9 RCTs · 600-1,800 mg/day oral, IV or sequential · 3-208 weeks
After removing biased studies, IV ALA ranked best for symptoms and oral ALA for lower-limb impairment scores.
Effects of alpha-lipoic acid supplementation on cardiometabolic risk factors: A systematic review and dose-response meta-analysis.
Meta-analysis of RCTs · Adults (various health states) · n = 63 RCTs · Various · Varied
Small reductions in insulin resistance, waist (~1 cm), weight (~0.6 kg), fasting glucose (~5 mg/dL), HbA1c (~0.4%) and triglycerides; no effect on LDL, HDL or blood pressure.
Ranking Alpha Lipoic Acid and Gamma Linolenic Acid in Terms of Efficacy and Safety in the Management of Adults With Diabetic Peripheral Neuropathy: A Systematic Review and Network Meta-analysis.
Network meta-analysis · Adults with diabetic neuropathy · n = 11 studies · ALA 600 mg/day (and GLA) · Varied
ALA 600 mg/day lowered total symptom score by about 1 standardised unit versus control, with very high heterogeneity; main side effects gastrointestinal.
Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.
RCT · Adults with diabetic polyneuropathy (Russia/Israel) · n = 181 · 600, 1,200 or 1,800 mg/day vs placebo · 5 weeks
All ALA doses cut total symptom score by about half versus about one-third on placebo. 600 mg gave the best balance of benefit and side effects; nausea, vomiting and vertigo rose with dose.
Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial.
RCT · Adults with mild-moderate diabetic polyneuropathy · n = 460 · 600 mg/day · 4 years
Did not improve the primary composite endpoint versus placebo. Some secondary neuropathy-impairment scores were better with ALA. Serious adverse events 38% vs 28%.
Effects of alpha-lipoic acid supplementation on patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized clinical trials.
Meta-analysis of RCTs · Adults with NAFLD · n = 7 RCTs, 414 participants · Various · Varied
No improvement in liver enzymes, lipids, glucose markers, adipokines or body weight.
Alpha-lipoic acid on intermediate disease markers in overweight or obese adults: a systematic review and meta-analysis.
Meta-analysis of RCTs · Overweight/obese adults · n = 11 RCTs, 704 adults · Various · Varied
No significant effect on triglycerides, cholesterol, LDL, HDL, insulin resistance or fasting glucose.
Full research notesOverview, research in progress and study doses
Further research
- Nerve comfort in people with diabetic neuropathy. At 600 mg/day, RCTs (SYDNEY 2) and meta-analyses found less burning, tingling and numbness in people with diabetic neuropathy. The 4-year NATHAN 1 trial missed its main endpoint, and one 2023 analysis found no clear benefit. PubMed 17065669PubMed 21775755PubMed 38295879PubMed 41619689PubMed 37933068PubMed 42643396
- Blood sugar, weight and lipids. A 63-RCT meta-analysis reports small drops in fasting glucose (~5 mg/dL), HbA1c (0.4%) and weight (0.6 kg), but meta-analyses in overweight adults and in fatty liver found no significant effect. Mixed. PubMed 41077538PubMed 40180416PubMed 41917882
Where the research is still limited
- No evidence that 50 mg/day boosts energy or mitochondrial function in healthy people.
- In overweight/obese adults, ALA did not significantly change lipids, glucose or insulin resistance (11 RCTs).
- In NAFLD, ALA did not improve liver enzymes, lipids, glucose or weight (7 RCTs).
- Over 4 years in diabetic neuropathy (NATHAN 1), ALA did not improve the primary composite nerve endpoint.
Study doses
Neuropathy trials used 600 mg/day (SYDNEY 2 tested 600–1,800 mg, with 600 mg giving the best balance of benefit and side effects), and metabolic trials typically 300–1,200 mg/day. C300 Hepa Factor provides 50 mg per serving as labelled, about 12 times below the main studied dose, so the neuropathy findings do not transfer to it.