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Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis

Veronese, Nicola, MD; Stubbs, Brendon, PhD; Solmi, Marco, MD; Ajnakina, Olesya, PhD; Carvalho, Andre, F., MD; Maggi, Stefania, MD

doi: 10.1097/PSY.0000000000000537

Objective Deficiency of acetyl-L-carnitine (ALC) seems to play a role in the risk of developing depression, indicating a dysregulation of fatty acid transport across the inner membrane of mitochondria. However, data about ALC supplementation in humans are limited. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs).

Methods A literature search in major databases, without language restriction, was undertaken from inception until 30 December 2016. Eligible studies were RCTs of ALC alone or in combination with antidepressant medications, with a control group taking placebo/no intervention or antidepressants. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for summarizing outcomes with a random-effect model.

Results Twelve RCTs (11 of which were ALC monotherapy) with a total of 791 participants (mean age = 54 years, % female = 65%) were included. Pooled data across nine RCTs (231 treated with ALC versus 216 treated with placebo and 20 no intervention) showed that ALC significantly reduced depressive symptoms (SMD = −1.10, 95% CI = −1.65 to −0.56, I2 = 86%). In three RCTs comparing ALC versus antidepressants (162 for each group), ALC demonstrated similar effectiveness compared with established antidepressants in reducing depressive symptoms (SMD = 0.06, 95% CI = −0.22 to 0.34, I2 = 31%). In these latter RCTs, the incidence of adverse effects was significantly lower in the ALC group than in the antidepressant group. Subgroup analyses suggested that ALC was most efficacious in older adults.

Conclusions ALC supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects. Future large scale trials are required to confirm/refute these findings.

From the National Research Council, Neuroscience Institute (Veronese, Maggi), Aging Branch, Padova, Italy; South London and Maudsley NHS FoundationTrust (Stubbs), Denmark Hill; Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London (Stubbs, Ajnakina), De Crespigny Park, London; Faculty of Health, Social Care and Education, Anglia Ruskin University (Stubbs), Chelmsford, United Kingdom; Department of Neurosciences, University of Padova (Solmi), Padova, Italy; and Translational Psychiatry Research Group, Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara (Carvalho), Fortaleza, CE, Brazil.

Supplemental Content

Address correspondence to Nicola Veronese, MD, National Research Council, Neuroscience Institute, Aging Branch, Via Giustiniani, 2-35128 Padova, Italy. E-mail:

Received for publication May 6, 2017; revision received September 11, 2017.

Copyright © 2018 by American Psychosomatic Society
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