Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective: Acetyl-L-carnitine (ALC), a constructive molecule in fatty acid metabolism, is an agent potentially effective for treating peripheral neuropathic pain (PNP). Its effect, however, remains uncertain. We aimed to access the efficacy and safety of ALC for the treatment of patients with PNP.

Methods: We searched MEDLINE (1996-2014), EMBase (1974-2014), and CENTRAL (May 2014) up to June 27, 2014 for randomized controlled trials (RCTs) comparing ALC with placebo or other active medications in diabetic and non-diabetic PNP patients that reported the change of pain using visual analogue scale (VAS). Mean difference (MD) and 95% confidence interval (CI) were used for pooling continuous data.

Results: Four RCTs comparing ALC with placebo and reporting in three articles (n = 523) were included. Compared with placebo, ALC significantly reduced VAS scores of PNP patients (MD of VAS, 1.20; 95% CI, 0.68-1.72, P <0.00001). In the subgroup analysis, the effect of ALC on VAS was similar in different administration routes (intramuscular-oral sequential subgroup: MD, 1.19; 95% CI, 0.34-2.04, P = 0.006; oral only subgroup: pooled MD, 1.15; 95%CI, 0.33-1.96, P = 0.006), and ALC appeared more effective in diabetic PNP patients than non-diabetic PNP patients (diabetic subgroup: MD, 1.47; 95%CI, 1.06-1.87, P <0.00001; non-diabetic subgroup: MD, 0.71; 95% CI, -0.01-1.43, P = 0.05). No severe adverse events were reported related to ALC. The common adverse events were pain, headache, paraesthesia, hyperesthesia, retching, biliary colic, and gastrointestinal disorders. The rates of total adverse events were similar in ALC and control group.

Conclusion: The current evidence suggests that ALC has a moderate effect in reducing pain measured on VAS in PNP patients with acceptable safety. Larger trials with longer follow-up, however, are warranted to establish the effects.

Fig 1. PRISMA Flow Diagram of the Meta-analysis.

Fig 2. Overall Meta-analysis on the VAS Scores.

Patients receiving ALC showed significantly more reduction in VAS scores than those receiving placebo. The values presented referred to the change of VAS scores from baseline. VAS = Visual Analogue Scale; ALC = acetyl-l-carnitine; UCE = U.S.-Canadian-European Study; UC = U.S.-Canadian Study; SD = standard deviation; CI = confidence interval.

Fig 3. Subgroup-analysis on the VAS Scores of the Diabetic and Non-diabetic Patients.

Subgroup-analysis was performed by subdividing RCTs according to whether the peripheral neuropathy diagnosed in patients was diabetic or non-diabetic. Taking ALC decreased VAS scores significantly in diabetic patients. VAS = Visual Analogue Scale; ALC = acetyl-l-carnitine; UCE = U.S.-Canadian-European Study; UC = U.S.-Canadian Study; SD = standard deviation; CI = confidence interval.

Fig 4. Subgroup-analysis on the VAS Scores by Subdividing RCTs according to the Route of Administration.

Oral administration of ALC decreased VAS scores significantly. VAS = Visual Analogue Scale; ALC = acetyl-l-carnitine; UCE = U.S.-Canadian-European Study; UC = U.S.-Canadian Study; SD = standard deviation; CI = confidence interval.