Background Carnitine deficiency is common in patients with chronic kidney disease (CKD) who require dialysis. Several clinical studies have suggested that carnitine supplementation is beneficial for dialysis-related symptoms. However, the clinical effectiveness and potential adverse effects of carnitine supplementation in dialysis patients have not been determined. Objectives This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 16 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria We included all randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) that compared carnitine supplements with placebo or standard care in people with CKD requiring dialysis. Data collection and analysis Two authors independently extracted study data and assessed study quality. We used a random-effects model to perform a quantitative synthesis of the data. We used the I-2 statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with 95% confidence intervals (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Main results We included 52 studies (47 parallel RCTs and five cross-over RCTs) (3398 randomised participants). All studies compared L-carnitine with a placebo, other treatment, or no treatment. Standard care was continued as co-interventions in each group. Most studies were judged to have an unclear or high risk of bias. L-carnitine may have little or no effect on the quality of life (QoL) SF-36 physical component score (PCS) (4 studies, 134 participants: SMD 0.57, 95% CI -0.15 to 1.28; I-2 = 73%; low certainty of evidence), and the total QoL score (Kidney Disease Quality of Life (KDQOL), VAS (general well-being), or PedsQL) (3 studies, 230 participants: SMD -0.02, 95% CI -0.29 to 0.25; I-2 = 0%; low certainty of evidence). L-carnitine may improve SF-36 mental component score (MCS) (4 studies, 134 participants: SMD 0.70, 95% CI 0.22 to 1.18; I2 = 42%; low certainty of evidence). L-carnitine may have little or no effect on fatigue score (2 studies, 353 participants: SMD 0.01, 95% CI -0.20 to 0.23; I-2 = 0%; low certainty of evidence), adverse events (12 studies, 1041 participants: RR, 1.14, 95% CI 0.86 to 1.51; I-2 = 0%; low certainty of evidence), muscle cramps (2 studies, 102 participants: RR, 0.44, 95% CI 0.18 to 1.09; I-2 = 23%; low certainty of evidence), and intradialytic hypotension (3 studies, 128 participants: RR, 0.76, 95% CI 0.34 to 1.69; I-2 = 0%; low certainty of evidence). L-carnitine may improve haemoglobin levels (26 studies, 1795 participants: MD 0.46 g/dL, 95% CI 0.18 to 0.74; I-2 = 86%; low certainty of evidence) and haematocrit values (14 studies, 950 participants: MD 1.78%, 95% CI 0.38 to 3.18; I-2 = 84%; low certainty of evidence). Authors' conclusions The available evidence does not currently support the use of carnitine supplementation in the treatment of dialysis-related carnitine deficiency. Although carnitine supplementation may slightly improve anaemia-related markers, carnitine supplementation makes little or no difference to adverse events. However, these conclusions are based on limited data and, therefore, should be interpreted with caution. PLAIN LANGUAGE SUMMARY Carnitine supplements for people with chronic kidney disease requiring dialysis What is the issue? Carnitine deficiency is an important problem in chronic kidney disease (CKD) patients requiring dialysis. Dialysis-related carnitine deficiency can exacerbate intradialytic symptoms (e.g. muscle symptoms including muscle cramps and weakness, and hypotension) and chronic complications of kidney failure (e.g. anaemia). However, it is unknown whether carnitine supplementation can improve the symptoms of dialysis-related carnitine deficiency. What did we do? We searched the medical literature for all randomised trials conducted on carnitine supplementation in CKD patients requiring dialysis. Our aim was to determine whether supplementation improves quality of life (QoL) and symptoms due to carnitine deficiency. We also assessed whether carnitine supplementation is safe in terms of adverse events. Evidence certainty was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). What did we find? We identified 52 studies with a total of 3398 CKD patients undergoing dialysis. We could not determine the impact of L-carnitine on quality of life (QoL) and symptoms due to dialysis-related carnitine deficiency. L-carnitine may improve anaemia in these patients. Additionally, evidence for the adverse effects of L-carnitine supplementation in this patient population is very limited. Conclusions We found that the effects of carnitine supplementation with respect to QoL, fatigue score, muscle cramps, and intradialytic hypotension remain unclear. L-carnitine may improve anaemia-related markers (haemoglobin level and haematocrit values) in CKD patients requiring dialysis. More studies are needed to assess the effectiveness and safety of carnitine supplements in this patient population.
