Cochrane Systematic Review of Acetyl-L-Carnitine for the Treatment of Diabetic Polyneuropathy

Abstract

Introduction - Painful diabetic polyneuropathy (DPN) occurs in 20% of people with diabetes; a complete and comprehensive management strategy for the prevention and treatment of painful DPN has not yet been defined. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation and induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation could have clinical therapeutic potential. We undertook a Cochrane Review to assess the effects of acetyl-L-carnitine for the treatment of diabetic polyneuropathy1. This abstract is based on a draft pre-peer review version of a Cochrane Review. Upon completion and approval, the final version is expected to be published in the Cochrane Database of Systematic Reviews (www.cochranelibrary.com). Methods - On 10 February 2017, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and two clinical trials registries without any language filter. We checked references, searched citations, and contacted study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs. Participants could have any severity and either type of DPN, and we accepted any definition of minimum criteria for DPN: probable, confirmed, or subclinical, in accordance with the Toronto Consensus2. The intervention was ALC compared with placebo, other therapy, or no intervention. Pain was the primary outcome, measured as the proportion of participants with a 30%>50% decrease in pain and on a visual analogue scale (VAS) or Likert scale3. We used standard methodological procedures expected by Cochrane4. Results - Searches of the literature revealed 74 potentially eligible records from which we identified three studies (906 participants) fitting inclusion criteria and suitable for analysis. These studies provided data for two comparisons: ALC versus placebo (two trials) and ALC versus methylcobalamin (MC) (one trial). One placebo-controlled trial investigated ALC at a dose of 2000 mg/day; the other compared two doses of ALC (1500 mg/day and 3000 mg/day) and placebo. The latter trial was at high risk of bias; the other two trials were at low risk of bias. For the primary outcome (pain measured on a 0 to 100 mm VAS), the result favoured ALC over placebo, but moderate heterogeneity was present (mean difference (MD) -9.87, 95% confidence interval (CI) -18.95 to -0.79; two studies; N = 540; P < 0.03; I2 = 75%; random-effects). Subgroup analysis indicated that VAS scores were little different from placebo with ALC at a dose of 1500 mg/day or less (MD -0.21, 95% CI: -10.03 to 9.61; one study; N = 159; P = 0.97) but at doses greater than 1500 mg/day there was very low-quality evidence of an effect in favour of ALC (MD -14.94, 95% CI: -19.15 to -10.72; two studies; N = 381; P < 0.00001; I2 = 0%). See the figure. The third included study compared ALC with MC in 232 participants, but did not report effects on pain. Conclusion - Low to very low quality evidence suggests that ALC may reduce pain after 6 to 12 months in people with DPN when compared with placebo; this effect may not be present at doses under 1500 mg/day. A trial comparing ALC and MC provided no data on pain relief. Further high quality studies are needed to clarify the findings.