Alpha-lipoic acid
IV alpha-lipoic acid improved nerve conduction in diabetic neuropathy, in mostly poor-quality trials. Pooled oral trials eased symptoms, though a 4-year trial missed its main endpoint. Weight fell 0.6 to 1.3 kg more than placebo. One review found lower fasting glucose and HbA1c, another found no change in overweight adults. Case reports link it to autoimmune low blood sugar.
Add to Bio HackChecked 2026-11-09
- Status
- Dietary supplement in the US.
- Also called
- ALA, lipoic acid, thioctic acid, R-lipoic acid, R-ALA, R,S-lipoic acid, alpha lipoic acid
- Taken for
- diabetic neuropathy, nerve pain, blood sugar, weight loss, antioxidant, multiple sclerosis, skin aging, energy
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help3
- StrongShown to add about 0.6 to 1.3 kg of weight loss over placebo across trials. The analyses disagree on waist size.
- ModerateShown to raise nerve conduction speed in people with diabetic neuropathy when given by IV for 2 to 4 weeks. Most trials were poor quality.
- ModerateShown to lower nerve symptom scores in people with diabetic neuropathy over 5 weeks. Over 4 years, the main combined measure did not change.
Reported risks4
- LimitedOne 4-year trial had serious adverse events in 38% on 600 mg a day against 28% on placebo, with no difference in tolerability.Very common
- LimitedCase reports: six adults had episodes of low blood sugar 30 to 120 days after starting 600 mg a day, which eased after stopping.How often is not known
- LimitedOne trial found nausea, vomiting and vertigo rose with dose from 600 to 1,800 mg a day over 5 weeks.How often is not known
- LimitedOne trial found protein in the urine more often on 1,200 mg a day than on placebo over 24 months in people with progressive MS.How often is not known
What people take it for, and what was found
Shown to help3
Diabetic nerve damage, IV treatment
Shown to raise nerve conduction speed in people with diabetic neuropathy when given by IV for 2 to 4 weeks. Most trials were poor quality.
The numbers and sources
- Effect
- IV alpha-lipoic acid at 300 to 600 mg a day for 2 to 4 weeks raised nerve conduction velocity by 3.2 to 4.6 m/s across four nerves, and overall improvement was 4 times as likely as on control (OR 4.03, 95% CI 2.73 to 5.94) [1].
- Population
- 15 randomized trials in diabetic peripheral neuropathy [1].
- Sources
- [1]
- Caveats
- The authors note most trials were of poor quality [1].
Diabetic nerve symptoms, oral treatment
Shown to lower nerve symptom scores in people with diabetic neuropathy over 5 weeks. Over 4 years, the main combined measure did not change.
The numbers and sources
- Effect
- Over 5 weeks, total symptom scores fell 51% on 600 mg a day, 48% on 1,200 mg and 52% on 1,800 mg, against 32% on placebo (all P < 0.05) [2]. Over 4 years, 600 mg a day did not change the primary composite of impairment and nerve tests (P = 0.105). Impairment scores improved on secondary measures (NIS, P = 0.028) [3]. A 2026 network meta-analysis ranked oral alpha-lipoic acid first for lower-limb impairment scores (NIS-LL, SUCRA 97.4%, I² 0%). IV ranked first for symptom scores, and both routes raised global satisfaction [4]. A 2026 meta-analysis found lower paresthesia (SMD -1.04, 95% CI -1.24 to -0.84) and numbness (SMD -0.23, 95% CI -0.44 to -0.01) scores, mostly at 600 mg a day. HbA1c and two nerve conduction measures did not change [5].
- Population
- 181 people with diabetic polyneuropathy in Russia and Israel [2]; 460 people with mild to moderate diabetic polyneuropathy [3]; 9 randomized trials of 600 to 1,800 mg a day for 3 to 208 weeks [4]; 15 studies in diabetic neuropathy [5].
- Sources
- [2], [3], [4], [5]
- Caveats
- In the 4-year trial, the placebo group did not worsen, so the trial could not test prevention of decline as designed [3]. The abstract of [5] does not separate oral from IV use, and some comparisons were against other treatments.
Weight loss
Shown to add about 0.6 to 1.3 kg of weight loss over placebo across trials. The analyses disagree on waist size.
The numbers and sources
- Effect
- Weight loss was 1.27 kg greater on alpha-lipoic acid than placebo (95% CI 0.25 to 2.29) and BMI 0.43 lower [6]. A second analysis found weight -0.69 kg (95% CI -1.27 to -0.10) and BMI -0.38. Waist circumference did not change [7]. A 2026 analysis of 63 trials found weight -0.64 kg (95% CI -1.04 to -0.24), fat mass -1.42 kg (95% CI -2.53 to -0.31) and waist circumference -1.10 cm (95% CI -1.66 to -0.54) against control [8].
- Population
- 10 trials [6]; 12 trials [7]; 63 randomized trials [8].
- Sources
- [6], [7], [8]
- Caveats
- Dose did not predict effect [6]. Trials were short. The two analyses that measured waist size disagree [7][8].
Mixed results1
Blood sugar
Mixed results: one large review found lower fasting glucose and HbA1c, while a review of overweight adults and neuropathy trials found no change.
The numbers and sources
- Effect
- Across 63 trials, fasting glucose fell 5.28 mg/dL (95% CI -7.21 to -3.35), HbA1c 0.40% (95% CI -0.66 to -0.14), fasting insulin 1.70 mU/mL and HOMA-IR 0.74 against control [8]. In 11 trials of 704 overweight or obese adults, fasting glucose (SMD 0.13, 95% CI -0.16 to 0.41) and HOMA-IR (SMD -0.23, 95% CI -0.60 to 0.15) did not differ from control [9]. In diabetic neuropathy trials, HbA1c did not change [5].
- Population
- 63 randomized trials [8]; adults with a BMI of 25 or more [9]; people with diabetic neuropathy [5].
- Sources
- [8], [9], [5]
- Caveats
- The reviews disagree. The overweight review rated 8 of its 11 trials at low risk of bias [9].
Not shown to help1
Progressive multiple sclerosis
One trial found 1,200 mg a day did not slow walking decline over 24 months in progressive MS. Brain volume looked steadier than on placebo.
The numbers and sources
- Effect
- Over 24 months, 1,200 mg a day did not slow the decline in walking speed (-0.39 against -0.30 ft/s, difference -0.08, 95% CI -0.33 to 0.17). Mobility and patient-reported outcomes did not differ. Whole-brain and deep gray matter volume appeared stable on lipoic acid and declined on placebo [10].
- Population
- 115 people with primary or secondary progressive MS at 11 sites in the US and Canada [10].
- Sources
- [10]
- Caveats
- 37% on lipoic acid and 17% on placebo left the study [10].
Doses studied
IV trials used 300 to 600 mg a day for 2 to 4 weeks [1]. Oral trials used 600, 1,200 and 1,800 mg once a day for 5 weeks [2] and 600 mg a day for 4 years [3]. The MS trial used 1,200 mg a day [10].
Risks
Reported risks4
Serious adverse events in long-term use
One 4-year trial had serious adverse events in 38% on 600 mg a day against 28% on placebo, with no difference in tolerability.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Over 4 years, serious adverse events occurred in 38.1% on 600 mg a day and 28.0% on placebo. Overall tolerability and dropouts for tolerability did not differ [3].
- Population
- 460 people with diabetic polyneuropathy [3].
- Sources
- [3]
- Caveats
- The abstract does not list the events.
Low blood sugar from insulin autoantibodies (insulin autoimmune syndrome)
Case reports: six adults had episodes of low blood sugar 30 to 120 days after starting 600 mg a day, which eased after stopping.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Six patients developed episodes of fasting and post-meal hypoglycemia 30 to 120 days after starting 600 mg a day. Hypoglycemic episodes fell after stopping lipoic acid. Five carried the HLA-DRB1*04:03 allele [11].
- Population
- Case series of 6 European adults, median age 63 [11].
- Sources
- [11]
- Caveats
- Case reports without controls. The authors note the syndrome is linked to sulfhydryl compounds, and in Japanese patients to the HLA-DRB1*04:06 allele [11].
Nausea, vomiting and dizziness
One trial found nausea, vomiting and vertigo rose with dose from 600 to 1,800 mg a day over 5 weeks.
Protein in the urine
One trial found protein in the urine more often on 1,200 mg a day than on placebo over 24 months in people with progressive MS.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- On 1,200 mg a day for 24 months, proteinuria was more common than on placebo, and lab monitoring was increased to every 3 months because of it [10].
- Population
- 115 people with progressive MS [10].
- Sources
- [10]
- Caveats
- One trial. The authors describe it as a newly described adverse event [10].
Claims tested and not found
- That lipoic acid slows disability in progressive multiple sclerosis. Walking speed and other clinical outcomes did not differ from placebo over 24 months [10].
Sources
- Han T, Bai J, Liu W, et al. A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. European Journal of Endocrinology. 2012. https://doi.org/10.1530/EJE-12-0555
- Ziegler D, Ametov A, Barinov A, et al. Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 trial. Diabetes Care. 2006. https://doi.org/10.2337/dc06-1216
- Ziegler D, Low PA, Litchy WJ, et al. Efficacy and Safety of Antioxidant Treatment With α-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy. Diabetes Care. 2011. https://doi.org/10.2337/dc11-0503
- Shen J, Zheng Y, Yu M, Wang X. Oral, intravenous, or sequential alpha-lipoic acid for diabetic peripheral neuropathy? A Bayesian network meta-analysis of randomized controlled trials. Frontiers in Neurology. 2026. https://doi.org/10.3389/fneur.2026.1904967
- Salinas AV, Caroca TM, Santibáñez FP, et al. Effectiveness of alpha lipoic acid supplementation on biochemical, clinical, and inflammatory parameters in patients with diabetic polyneuropathy: A systematic review and meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2026. https://doi.org/10.1016/j.dsx.2026.103374
- Kucukgoncu S, Zhou E, Lucas KB, et al. Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. Obesity Reviews. 2017. https://doi.org/10.1111/obr.12528
- Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials. Clinical Nutrition. 2018. https://doi.org/10.1016/j.clnu.2017.06.002
- Mohammadi S, Ashtary-Larky D, Alaghemand N, et al. Effects of alpha-lipoic acid supplementation on cardiometabolic risk factors: A systematic review and dose-response meta-analysis. Nutrition, Metabolism and Cardiovascular Diseases. 2026. https://doi.org/10.1016/j.numecd.2025.104370
- Luo Y, Zhang J, Guo H. Alpha-lipoic acid on intermediate disease markers in overweight or obese adults: a systematic review and meta-analysis. BMJ Open. 2025. https://doi.org/10.1136/bmjopen-2024-088363
- Spain RI, Paz Soldán MM, Freedman MS, et al. Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. Neurology. 2026. https://doi.org/10.1212/WNL.0000000000214454
- Gullo D, Evans JL, Sortino G, et al. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid. Clinical Endocrinology. 2014. https://doi.org/10.1111/cen.12334