Description of included studies.
| Sl. No. | Author name | Dose, route, duration (number of subjects) | Sample size (number of subjects) | Intervention | Parameters | Safety | Outcomes and conclusions |
|---|---|---|---|---|---|---|---|
| 1 | Ziegler et al., 2011 [29] | 600 mg, oral route, 4 years | Control = 224ALA = 230 | ALA, once daily | HbA1C, NIS-LL, NIS, MNCV, NSC, VPT, TSS | Adverse effects were more common with ALA, yet the placebo group had a higher incidence of deaths. | ALA shows improvement in NIS and NIS-LL, but MNCV and SNAP are seen. ALA slows the progression of DSPN but doesn’t improve the condition. |
| 2 | Ziegler et al., 2006 [26] | 600 mg, 1,200 mg, 1,800 mg, oral route, 5 weeks | Control = 43ALA 600 = 45ALA 1,200 = 47ALA 1,800 = 46 | ALA, once daily | HbA1C, NIS, NIS-LL, NSC, TSS, global satisfaction | Adverse events in the treatment group were dose-dependent, with the highest incidence observed in the 1,800 mg group. | ALA shows improvement in TSS, NSC, NIS, and NIS-LL parameters when compared with the placebo group. |
| 3 | Reljanovic et al., 1999 [12] | 600 mg, 1,200 mg, oral route, 24 months | Control = 20ALA 600 = 27ALA 1,200 = 18 | ALA | HbA1C, MNCV | Treatment-related adverse effects were noted. But the overall tolerability assessment was rated as very good or good. | Improvement in MNCV is seen in the ALA 1,200 mg group. |
| 4 | El-Nahas et al., 2020 [30] | 600 mg, two times daily (1,200 mg/day) oral route for 6 months | Control = 100ALA = 100 | ALA | HbA1C, NSS, NDS, VPT, VAS | Nausea. | ALA is effective, safe, and tolerable for the treatment of DPN. |
| 5 | Ruhnau et al., 1999 [31] | 600 mg, three times daily, oral route (1,800 mg/day) for 3 weeks | Control = 12ALA = 12 | Thioctic acid (ALA) | HbA1C, TSS, NDS | No adverse effects seen. | Short-term treatment with oral ALA ameliorates neuropathic symptoms. |
| 6 | Vijayakumar et al., 2014 [18] | 600 mg, oral route, 3 months | Control = 10ALA = 10 | ALA | HbA1C, MNCV | No data available. | Oral ALA improves MNCV in DN patients. |
| 7 | Siddique et al., 2021 [28] | 600 mg, oral route, 6 months | Control = 55ALA = 55 | ALA | HbA1C, TSS | No data available. | Significant improvement in TSS was seen. ALA improved symptoms of neuropathy pain and enhanced QOL. |
| 8 | Millan-Guerrero et al., 2018 [37] | 1,200 mg, oral route, 4 weeks | Control = 49ALA = 51 | ALA | MNCV | No adverse effects seen. | No clinically significant improvement was seen. |
| 9 | Tang et al., 2007 [27] | 600 mg, 1,200 mg, 1,800 mg, oral route, 5 weeks | Control = 43ALA 600 = 45ALA 1,200 = 47ALA 1,800 = 56 | ALA | Global satisfaction | Nausea, vomiting, and vertigo. | ALA is effective in reducing neuropathic symptoms in DSPN. |
ALA: alpha lipoic acid; HbA1C: glycated hemoglobin; NIS: neuropathy impairment score; NIS-LL: NIS-low limb; MNCV: motor nerve conduction velocity; NSC: neuropathy symptoms and change; TSS: total severity score; SNAP: sensory nerve action potential; VPT: vibration perception threshold; NDS: neurological disability score; NSS: neurological symptom scale; VAS: visual analogue scale; DSPN: diabetic distal symmetric polyneuropathy; DPN: diabetic peripheral neuropathy; DN: diabetic neuropathy; QOL: quality of life.