Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline.

3rd Department of Internal Medicine 1st Medical Faculty Charles University 128 08 Prague 2 Czech Republic

Amsterdam UMC University of Amsterdam 1100 DD Amsterdam The Netherlands

CIBER Fisiopatología de la Obesidad y Nutrición 28007 Madrid Spain

Department of Cardiology Cliniques Universitaires Saint Luc Université Catholique de Louvain 1200 Brussels Belgium

Department of Endocrinology Aarhus University Hospital DK 8200 Aarhus N Denmark

Department of Health Promotion Sciences Maternal and Infantile Care Internal Medicine and Medical Specialities School of Medicine University of Palermo 90127 Palermo Italy

Department of Medicine University of Cordoba 14004 Cordoba Spain

Department of Nephrology Hypertension Dialysis and Transplantation University Hospital Centre Zagreb 10 000 Zagreb Croatia

Department of Pharmacology and Therapeutics Trinity College Dublin and St James Hospital Dublin 8 Ireland

Diagnosis and Therapeutic Center Hôtel Dieu Hospital Paris Descartes University 75004 Paris France

Faculty of Medicine Vilnius University LT 03101 Vilnius Lithuania

Hypertension and Cardiovascular Risk Factors Research Group Medical and Surgical Sciences Department Sant'Orsola Malpighi University Hospital 40138 Bologna Italy

Lipids and Atherosclerosis Unit Department of Internal Medicine Reina Sofia University Hospital 14004 Cordoba Spain

Maimonides Biomedical Research Institute of Cordoba 14004 Cordoba Spain

School of Health Sciences Faculty of Medicine University of Ioannina 451 10 Ioannina Greece

Vilnius University Hospital Santariškių Klinikos LT 08661 Vilnius Lithuania

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