Key points
Drips reduce symptoms. A 3-week course of 600 mg of alpha-lipoic acid (ALA) given intravenously reduced pain, burning and numbness in the feet more than placebo: in a pooled analysis of 4 studies (1258 people), the Total Symptom Score (TSS) was 24% better, and the difference became noticeable from day 8 (Ziegler D Diabet Med 2004. PMID 14984445).
Tablets helped too. In the 600 mg group (45 people versus 43 on placebo), oral ALA once a day for 5 weeks lowered the symptom score by 51% versus 32% on placebo (Ziegler D Diabetes Care 2006. PMID 17065669).
Slowing the disease is not proven. Short courses of ALA reduced symptoms, but it has not been shown that ALA stops nerve damage: in a 4-year study the main goal was not met (Ziegler D Diabetes Care 2011. PMID 21775755).
What alpha-lipoic acid is
Alpha-lipoic (thioctic) acid works in mitochondria, the cell’s “power stations”: it is needed by the enzymes pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which take part in getting energy from food. It is also an antioxidant that acts both in membranes and in the fluids of the cell and serves as a “go-between” for vitamins E and C (Burgerstein, Handbuch Nährstoffe 2015, p. 170–171). Nerve damage in diabetes is linked, among other things, to oxidative stress — hence the idea of using an antioxidant for neuropathy.
Drips: 600 mg for 3 weeks
ALADIN. In the ALADIN study (Alpha-Lipoic Acid in Diabetic Neuropathy), 328 people with type 2 diabetes received drips of 1200, 600 or 100 mg of ALA or placebo for 3 weeks. At 600 mg the foot symptom score fell by 63.5%, on placebo by 38.4%. Adverse events occurred in 18.2% at 600 mg, in 20.7% on placebo and in 32.6% at 1200 mg (Ziegler D Diabetologia 1995. PMID 8786016).
SYDNEY. In the SYDNEY study of 120 people, after 14 drips of 600 mg the symptom score fell by an average of 5.7 points versus 1.8 on placebo, and each of the symptoms decreased (Ametov AS Diabetes Care 2003. PMID 12610036).
Pooled data. In a meta-analysis — a pooling of results — of 4 drip studies, symptoms decreased at least by half in 52.7% on ALA versus 36.9% on placebo (Ziegler D Diabet Med 2004. PMID 14984445). A meta-analysis by another group of authors also called this course a clinically significant way to reduce neuropathic pain; both meta-analyses pooled largely the same studies (Mijnhout GS Int J Endocrinol 2012. PMID 22331979).
Tablets: 600 mg a day
In the SYDNEY 2 study, 181 people took 600, 1200 or 1800 mg of ALA once a day or placebo for 5 weeks. The symptom score fell by 51, 48 and 52% versus 32% on placebo. Nausea, vomiting and dizziness became more frequent with dose, so the authors consider 600 mg the optimal dose (Ziegler D Diabetes Care 2006. PMID 17065669). The authors of a meta-analysis by another group considered it unclear whether improvements after 3–5 weeks of oral intake at doses above 600 mg a day are clinically significant (Mijnhout GS Int J Endocrinol 2012. PMID 22331979).
Long-term use: what is not yet proven
ALADIN III. 509 people with type 2 diabetes received 3 weeks of drips, then 600 mg three times a day by mouth for 6 months — or placebo. Already by the end of the drips (day 19) the symptom score did not differ from placebo, and at 7 months it did not either; the authors attribute this partly to differences in how symptoms were assessed at different centres (Ziegler D Diabetes Care 1999. PMID 10480774).
NATHAN 1. In the NATHAN 1 study, 460 people with mild to moderate neuropathy took 600 mg of ALA once a day or placebo for 4 years. The main goal was not met: the composite score — a foot examination and 7 nerve function tests — did not differ from placebo, and on placebo it did not worsen significantly over 4 years. On secondary measures, on the Neuropathy Impairment Score (NIS), results on ALA were better: more people had a clear improvement and fewer had a worsening (Ziegler D Diabetes Care 2011. PMID 21775755).
Cochrane review. The review included 3 studies lasting 6 months or longer (816 people). In the only study with an assessment at 6 months (330 people), ALA probably had little or no effect on symptoms; on examination, possibly the same (low certainty), although a noticeable benefit cannot be ruled out (Baicus C Cochrane Database Syst Rev 2024. PMID 38205823).
Burgerstein’s handbook gives the usual dose of 0.2–1.0 g a day, and for neuropathy a course of at least 4 months (Burgerstein, Handbuch Nährstoffe 2015, p. 171). Current data are more cautious: benefit has been shown for short courses, but not for long ones.
What the studies showed
| What was tested | Who took part | Result |
|---|---|---|
| ALADIN, drips for 3 weeks, 1995 | 328 people with type 2 diabetes | 600 mg: symptoms −63.5% versus −38.4% on placebo |
| SYDNEY, 14 drips of 600 mg, 2003 | 120 people | Symptom score −5.7 versus −1.8 points |
| Meta-analysis of drips, 2004 | 4 studies, 1258 people | Symptoms decreased at least by half in 52.7% versus 36.9% |
| SYDNEY 2, tablets for 5 weeks, 2006 | 181 people | 600 mg: symptoms −51% versus −32% |
| ALADIN III, drips and tablets, 7 months, 1999 | 509 people with type 2 diabetes | At 7 months symptoms did not differ from placebo |
| NATHAN 1, 600 mg by mouth for 4 years, 2011 | 460 people | Main measure did not differ; some doctor assessments were better |
| Cochrane review, courses of 6 months or longer, 2024 | 3 studies, 816 people; assessment at 6 months — 1 study, 330 people | Symptoms: probably little or no effect; examination: possibly the same (low certainty), benefit cannot be ruled out |
For symptoms at 6 months, a clinically noticeable effect is probably absent; slowing of nerve damage has not been shown: in the NATHAN 1 study the main composite score did not worsen significantly on placebo, so there was nothing to test slowing against (Ziegler D Diabetes Care 2011. PMID 21775755), and in the Cochrane review all studies lost many participants (Baicus C Cochrane Database Syst Rev 2024. PMID 38205823).
Safety and Hirata disease
Short courses were well tolerated: in the meta-analysis of drips, adverse events were no more frequent than on placebo (Ziegler D Diabet Med 2004. PMID 14984445). The handbook says no side effects are expected even at large amounts (Burgerstein, Handbuch Nährstoffe 2015, p. 172). Studies are more cautious: with oral intake, nausea and vomiting became more frequent with dose (Ziegler D Diabetes Care 2006. PMID 17065669), and over 4 years serious adverse events — any severe health events, not necessarily caused by the drug — occurred in 38.1% on ALA versus 28.0% on placebo, with similar tolerability (Ziegler D Diabetes Care 2011. PMID 21775755).
Hirata disease. Insulin autoimmune syndrome (Hirata disease) is rare: the immune system makes antibodies to the person’s own insulin, and blood sugar falls in someone who has never injected insulin. Six Europeans (median age 63) have been described in whom episodes of low blood sugar began 30–120 days into taking 600 mg of ALA a day; after ALA was stopped, the episodes became fewer (Gullo D Clin Endocrinol 2014. PMID 24111525).
Who is prone to it. Susceptibility is linked to the genes for human leukocyte antigens (HLA) — tissue-compatibility proteins used to match donors. In a review of 68 cases with genetic testing, the HLA-DRB104:06 variant predominated in people of East Asian origin and DRB104:03 in Europeans, and in Europeans lipoic acid was a common trigger (Yao D Diabetes Metab Syndr Obes 2024. PMID 39309309).
Who should be more careful
- If you develop weakness, sweating, trembling or confusion while taking ALA, check your glucose. Repeated readings below 3.0 mmol/L (54 mg/dL) or above 8.9 mmol/L (160 mg/dL) are a reason to see a doctor and mention that you take ALA.
- If you are on insulin or glucose-lowering tablets, low blood sugar is easy to blame on them — tell your doctor about the supplement.
- Hirata disease has been described in Europeans and in people of East Asian origin; in Europeans, ALA is a common trigger (Yao D Diabetes Metab Syndr Obes 2024. PMID 39309309). Anyone taking ALA should know about it.
- If ALA makes you nauseous, do not increase the dose: 1200 and 1800 mg a day gave no more benefit than 600 mg.
Bottom line
Short courses of alpha-lipoic acid — 600 mg drips for 3 weeks and 600 mg tablets for 5 weeks — reduced burning, pain and numbness in the feet in diabetes. Slowing of neuropathy has not been proven, and there is a rare risk — Hirata disease with episodes of low blood sugar. How to avoid glucose dips is covered in the article No Sugar Swings. Whether ALA is right for you can be decided at a consultation.
This material is for information only and does not replace a doctor’s consultation. The decision on taking alpha-lipoic acid, the dose and the form is made by a doctor.
