Alpha-lipoic acid
Also sold as: ALA · Thioctic acid · Lipoic acid · R,S-alpha-lipoic acid
A metabolic enzyme cofactor and antioxidant studied mainly for diabetic neuropathy and cardiometabolic outcomes. Oral supplements and clinical intravenous treatment have different evidence.
Longevity
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Research
- Longevity: Human lifespan or healthy-longevity benefit is not established. Glycemic and inflammatory biomarker changes are not longevity outcomes.
REALITY CHECK // ALA has its clearest research context in symptomatic diabetic neuropathy, with stronger short-term symptom evidence for intravenous treatment than for an oral supplement. Oral trials and reviews disagree on durable neurological benefit; the four-year trial did not meet its composite primary endpoint. Small weight or glucose changes do not demonstrate nerve repair or longer life.
Levels: how we grade evidence. Grey = evidence of no benefit; amber = evidence it makes this goal worse.
Ratings are self-reported by a self-selected group of users: how it felt, not proof that it works.
Check your bottle
Compare what your label says with what was used in trials. This is a trial range, not a personal prescription.
Enter the amount from your label to see the result.
How it was studied
01 // STUDIED_DOSE_RANGE
600–1,800 mg oral in trials
600 mg/day racemic ALA is a common reference. Intravenous 600 mg/day evidence must remain separate from oral supplements.
02 // TIMING_&_MATRIX
Food changes the tradeoff
Empty-stomach absorption and gastrointestinal tolerability differ; the source does not establish one timing schedule for every patient.
03 // EVALUATION_WINDOW
Weeks to years; different endpoints
Three-week intravenous symptom trials and four-year oral progression trials answer different questions.
04 // SAFETY_&_QUALITY_GATE
Hypoglycemia and overdose
No official numerical UL is established here. Insulin autoimmune syndrome and severe overdose toxicity preclude an unlimited-safety claim.
UPPER LIMIT // No numerical EFSA or NIH/IOM ALA UL is established in the supplied dossier. A review discussing tolerability up to about 1,200 mg/day is not an official safe ceiling. The current EFSA position on insulin autoimmune syndrome was not verified in the source.
Summary
ALA has its clearest research context in symptomatic diabetic neuropathy, with stronger short-term symptom evidence for intravenous treatment than for an oral supplement. Oral trials and reviews disagree on durable neurological benefit; the four-year trial did not meet its composite primary endpoint. Small weight or glucose changes do not demonstrate nerve repair or longer life.
Mechanism
Lipoic acid participates in mitochondrial oxidative decarboxylation and redox recycling. Antioxidant and metal-binding mechanisms do not establish a clinical detoxification or longevity benefit.
Typical studied dose
Human oral trials used 600–1,800 mg/day, with 600 mg/day a common racemic-ALA reference. The intravenous meta-analysis used 600 mg/day for three weeks under clinical supervision. The R/S mixture is the trial compound: 600 mg racemate must not be relabeled as a 300 mg trial dose by counting only its R fraction.
Upper limit
No numerical EFSA or NIH/IOM ALA UL is established in the supplied dossier. A review discussing tolerability up to about 1,200 mg/day is not an official safe ceiling. The current EFSA position on insulin autoimmune syndrome was not verified in the source.
Popular stacks with Alpha-lipoic acid
Not enough stack data yet. A combination with Alpha-lipoic acid appears here once 5 people rate the same set.
Forms and label traps
| Form on label | Active content | Studied range / day | Absorption & GI tolerance | Verdict |
|---|---|---|---|---|
| Racemic ALA: 50% R and 50% S, full compound mass Best for: Comparing oral racemic-ALA trial mass. |
Extract weight · ~100% marker | 600–1800 mg | Oral exposure is variable; the source reports R-enantiomer Cmax 36–43% and AUC 64–79% relative to a reference solution. Reflux, burning or nausea may limit use. |
Studied standard [REFERENCE // TRIAL_CONTEXT] Trials count the entire R/S compound. The R fraction is 50%, but no division by two belongs in the trial-dose comparison; active_pct 100 denotes total ALA mass. |
| Pure R-alpha-lipoic acid Best for: Understanding enantiomer claims. |
Extract weight · ~100% marker | 600–1800 mg | Enantiomer-specific pharmacokinetic differences exist; free R-ALA stability can be problematic. Comparative GI superiority is unproven. |
Avoid / not comparable [AVOID // SAFETY_OR_COMPARABILITY] The displayed 600–1,800 mg comparator belongs to racemic trials, not a validated R-ALA efficacy range. No clinical equivalence factor is established. |
| Sodium R-lipoate Best for: Identifying salt versus declared R-ALA mass. |
Unstandardized: active content unknown | 600–1800 mg | Stabilization may improve formulation handling; clinical superiority is not demonstrated here. Comparative clinical data are limited. |
Avoid / not comparable [AVOID // SAFETY_OR_COMPARABILITY] No reliable salt-to-trial efficacy conversion is supplied. The displayed range is racemic context only, not a sodium-R-lipoate target. |
Common label traps
- TRAP_01 // R-ALA is clinically far stronger
Pharmacokinetics and the endogenous R enantiomer do not establish superior neuropathy outcomes; most efficacy trials used racemate. - TRAP_02 // Repairs damaged nerves
Symptom-score improvements are not structural nerve regeneration, and the long-term composite primary endpoint was not met. - TRAP_03 // A fat burner or liver detox
Weight effects averaged roughly 0.6–0.7 kg; the dedicated NAFLD meta-analysis found no significant benefit. - TRAP_04 // A home mercury-chelation protocol
Metal binding is not evidence of a safe self-directed treatment; suspected poisoning needs clinical toxicology assessment.
Other outcomes studied
Outside the five leaderboard goals. Same evidence levels as above.
- DIABETIC NEUROPATHY: INTRAVENOUS Moderate · benefit
A four-trial meta-analysis (n=1,258) of 600 mg/day IV for three weeks reported relative TSS improvement 24.1% (95% CI 13.5–33.4), NIS-LL 16.0% (5.7–25.2), and at least 50% TSS response in 52.7% versus 36.9%. These are clinician-delivered IV data.
PMID 14984445 PMID 22837391 - DIABETIC NEUROPATHY: ORAL Limited · benefit
The 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates.
PMID 37630823 PMID 38205823 PMID 42643396 PMID 10480774 PMID 10499773 - GLYCEMIC MARKERS Moderate · benefit
The supplied 63-RCT dose-response review reports HOMA-IR WMD -0.74 (95% CI -1.17 to -0.31), fasting glucose -5.28 mg/dL (-7.21 to -3.35), HbA1c -0.40 percentage points (-0.66 to -0.14), and insulin -1.70 mU/mL. These are adjunctive biomarkers in metabolic disease.
PMID 41077538 PMID 29990473 PMID 35304727 - WEIGHT AND BMI Moderate · benefit
A 12-RCT review reported -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38 kg/m² (-0.53 to -0.24), both I²=0%. Overall waist change was not significant. A newer review reports weight -0.64 kg, BMI -0.27 kg/m², fat mass -1.42 kg and waist -1.10 cm; practical weight effects are small.
PMID 28629898 PMID 32091656 PMID 28295905 PMID 41077538 - INFLAMMATORY BIOMARKERS Limited · benefit
The 19-study review reports lower CRP, IL-6 and TNF-alpha, but extreme heterogeneity (I² 97.6–99.7%) makes magnitude uncertain; these are surrogate markers, not clinical-event prevention.
PMID 30721699 PMID 29753588 PMID 33827267 - NAFLD Moderate · no benefit
A seven-RCT meta-analysis (n=414) found no significant benefit for liver enzymes, lipids, glycemic indices, adipocytokines or obesity measures.
PMID 41917882 - BURNING MOUTH SYNDROME Limited · benefit
Reviews identify a possible pain or burning benefit but small inconsistent trials do not establish a proven treatment.
PMID 36246031 PMID 34787861 PMID 35026405
Reader questions
Is R-ALA better than ordinary ALA?
The dossier documents pharmacokinetic differences but no convincing head-to-head superiority on clinical outcomes. The racemate supplies most efficacy evidence.
Can ALA cause low glucose even without diabetes?
Rare insulin autoimmune syndrome can cause recurrent severe hypoglycemia. Ordinary additive glucose lowering is also relevant with diabetes treatments or supplement stacks; symptoms require assessment rather than another supplement.
Should reflux be ignored to maximize absorption?
No. Food may alter exposure, but persistent burning, nausea or other symptoms require reassessment; the dossier does not establish that maximizing absorption improves outcomes.
Stack interactions
- Caution Diabetes medicines or glucose-lowering supplement stacks [CAUTION // CLINICAL_REVIEW]
Potential additive glucose lowering warrants clinical review; medication changes require the treating clinician. Glycemic meta-analyses support the glucose effect, not a quantified interaction rate.
PMID 29990473 PMID 35304727 - Caution Thyroid medication and anticoagulants [CAUTION // CLINICAL_REVIEW]
The dossier raises thyroid-signaling and bleeding precautions but supplies no strong direct human interaction evidence; treat these as uncertainties, not established drug interactions. - Caution Minerals, biotin and thiamine [CAUTION // CLINICAL_REVIEW]
Metal binding and shared transporter or metabolic pathways provide theoretical interaction concerns; clinical deficiency or absorption magnitudes are not established in this dossier.
Red flags: interactions and who should avoid it
Interactions
Glucose-lowering medicines or supplements may add to glucose lowering. Thyroid-drug, anticoagulant, biotin-transport and mineral-binding concerns are limited or theoretical in this dossier. Thiamine status matters particularly with alcohol misuse or poor nutrition.
Avoid or ask a doctor first if
Pregnancy, breastfeeding, children, thiamine deficiency, recurrent hypoglycemia or insulin-autoimmune-syndrome susceptibility require medical assessment. Rare insulin autoimmune syndrome can cause severe hypoglycemia. Large overdoses, especially in children, can produce seizures, lactic acidosis and fatal toxicity. Unsupervised heavy-metal chelation is not an established indication. Reflux, burning and nausea occur at ordinary research doses.
Sources (PubMed, 22)
- Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis.
PMID 14984445 · 2004 · Meta-analysisA four-trial meta-analysis (n=1,258) of 600 mg/day IV for three weeks reported relative TSS improvement 24.1% (95% CI 13.5–33.4), NIS-LL 16.0% (5.7–25.2), and at least 50% TSS response in 52.7% versus 36.9%. These are clinician-delivered IV data.
- A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy.
PMID 22837391 · 2012 · Meta-analysisA four-trial meta-analysis (n=1,258) of 600 mg/day IV for three weeks reported relative TSS improvement 24.1% (95% CI 13.5–33.4), NIS-LL 16.0% (5.7–25.2), and at least 50% TSS response in 52.7% versus 36.9%. These are clinician-delivered IV data.
- Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review.
PMID 37630823 · 2023 · Meta-analysisThe 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates. Form or pharmacokinetic context: Trials count the entire R/S compound. The R fraction is 50%, but no division by two belongs in the trial-dose comparison; active_pct 100 denotes total ALA mass.
- Alpha-lipoic acid for diabetic peripheral neuropathy.
PMID 38205823 · 2024 · Systematic reviewThe 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates.
- Oral, intravenous, or sequential alpha-lipoic acid for diabetic peripheral neuropathy? A Bayesian network meta-analysis of randomized controlled trials.
PMID 42643396 · 2026 · Meta-analysisThe 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates.
- Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy.
PMID 10480774 · 1999 · Randomized controlled trialThe 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates.
- Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy.
PMID 10499773 · 1999 · Randomized controlled trialThe 2023 review (10 RCTs; n=1,242) reported better TSS, NDS and global satisfaction but no significant VAS, vibration threshold, NIS-LL or nerve-conduction improvement. Cochrane is more cautious about durable benefit; the source reports conflicting newer network estimates.
- Effects of alpha-lipoic acid supplementation on cardiometabolic risk factors: A systematic review and dose-response meta-analysis.
PMID 41077538 · 2026 · Meta-analysisThe supplied 63-RCT dose-response review reports HOMA-IR WMD -0.74 (95% CI -1.17 to -0.31), fasting glucose -5.28 mg/dL (-7.21 to -3.35), HbA1c -0.40 percentage points (-0.66 to -0.14), and insulin -1.70 mU/mL. These are adjunctive biomarkers in metabolic disease. A 12-RCT review reported -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38 kg/m² (-0.53 to -0.24), both I²=0%. Overall waist change was not significant. A newer review reports weight -0.64 kg, BMI -0.27 kg/m², fat mass -1.42 kg and waist -1.10 cm; practical weight effects are small.
- The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.
PMID 29990473 · 2018 · Meta-analysisThe supplied 63-RCT dose-response review reports HOMA-IR WMD -0.74 (95% CI -1.17 to -0.31), fasting glucose -5.28 mg/dL (-7.21 to -3.35), HbA1c -0.40 percentage points (-0.66 to -0.14), and insulin -1.70 mU/mL. These are adjunctive biomarkers in metabolic disease. Potential additive glucose lowering warrants clinical review; medication changes require the treating clinician. Glycemic meta-analyses support the glucose effect, not a quantified interaction rate.
- Could nutrient supplements provide additional glycemic control in diabetes management? A systematic review and meta-analysis of randomized controlled trials of as an add-on nutritional supplementation therapy.
PMID 35304727 · 2022 · Meta-analysisThe supplied 63-RCT dose-response review reports HOMA-IR WMD -0.74 (95% CI -1.17 to -0.31), fasting glucose -5.28 mg/dL (-7.21 to -3.35), HbA1c -0.40 percentage points (-0.66 to -0.14), and insulin -1.70 mU/mL. These are adjunctive biomarkers in metabolic disease. Potential additive glucose lowering warrants clinical review; medication changes require the treating clinician. Glycemic meta-analyses support the glucose effect, not a quantified interaction rate.
- Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials.
PMID 28629898 · 2018 · Meta-analysisA 12-RCT review reported -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38 kg/m² (-0.53 to -0.24), both I²=0%. Overall waist change was not significant. A newer review reports weight -0.64 kg, BMI -0.27 kg/m², fat mass -1.42 kg and waist -1.10 cm; practical weight effects are small.
- Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomised placebo-controlled clinical trials.
PMID 32091656 · 2020 · Meta-analysisA 12-RCT review reported -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38 kg/m² (-0.53 to -0.24), both I²=0%. Overall waist change was not significant. A newer review reports weight -0.64 kg, BMI -0.27 kg/m², fat mass -1.42 kg and waist -1.10 cm; practical weight effects are small.
- Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials.
PMID 28295905 · 2017 · Meta-analysisA 12-RCT review reported -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38 kg/m² (-0.53 to -0.24), both I²=0%. Overall waist change was not significant. A newer review reports weight -0.64 kg, BMI -0.27 kg/m², fat mass -1.42 kg and waist -1.10 cm; practical weight effects are small.
- The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials.
PMID 30721699 · 2019 · Meta-analysisThe 19-study review reports lower CRP, IL-6 and TNF-alpha, but extreme heterogeneity (I² 97.6–99.7%) makes magnitude uncertain; these are surrogate markers, not clinical-event prevention.
- Effects of alpha-lipoic acid supplementation on C-reactive protein level: A systematic review and meta-analysis of randomized controlled clinical trials.
PMID 29753588 · 2018 · Meta-analysisThe 19-study review reports lower CRP, IL-6 and TNF-alpha, but extreme heterogeneity (I² 97.6–99.7%) makes magnitude uncertain; these are surrogate markers, not clinical-event prevention.
- An updated systematic review and dose-response meta-analysis of the randomized controlled trials on the effects of alpha-lipoic acid supplementation on inflammatory biomarkers.
PMID 33827267 · 2023 · Meta-analysisThe 19-study review reports lower CRP, IL-6 and TNF-alpha, but extreme heterogeneity (I² 97.6–99.7%) makes magnitude uncertain; these are surrogate markers, not clinical-event prevention.
- Effects of alpha-lipoic acid supplementation on patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized clinical trials.
PMID 41917882 · 2026 · Meta-analysisA seven-RCT meta-analysis (n=414) found no significant benefit for liver enzymes, lipids, glycemic indices, adipocytokines or obesity measures.
- Efficacy of alpha-lipoic acid in patients with burning mouth syndrome compared to that of placebo or other interventions: a systematic review with meta-analyses.
PMID 36246031 · 2022 · Clinical or pharmacokinetic reportReviews identify a possible pain or burning benefit but small inconsistent trials do not establish a proven treatment.
- The efficiency of alpha-lipoic acid in the treatment of burning mouth syndrome: a systematic review.
PMID 34787861 · 2021 · Systematic reviewReviews identify a possible pain or burning benefit but small inconsistent trials do not establish a proven treatment.
- Evaluation of the analgesic effect of ɑ-lipoic acid in treating pain disorders: A systematic review and meta-analysis of randomized controlled trials.
PMID 35026405 · 2022 · Meta-analysisReviews identify a possible pain or burning benefit but small inconsistent trials do not establish a proven treatment.
- Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms.
PMID 25506250 · 2014 · Clinical or pharmacokinetic reportForm or pharmacokinetic context: Trials count the entire R/S compound. The R fraction is 50%, but no division by two belongs in the trial-dose comparison; active_pct 100 denotes total ALA mass. Form or pharmacokinetic context: The displayed 600–1,800 mg comparator belongs to racemic trials, not a validated R-ALA efficacy range. No clinical equivalence factor is established.
- Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study.
PMID 22609537 · 2012 · Clinical or pharmacokinetic reportForm or pharmacokinetic context: The displayed 600–1,800 mg comparator belongs to racemic trials, not a validated R-ALA efficacy range. No clinical equivalence factor is established.
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