Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies

Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M G Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F E Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F G Cicero, Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M G Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F E Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F G Cicero

Abstract

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.

Keywords: dietary supplement; meta-analysis; safety; thioctic acid; α-lipoic acid.

Conflict of interest statement

MR is currently Chief Medical and Scientific Advisor, Novo Nordisk South East Europe, Middle East and Africa (SEEMEA). The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the number of studies identified and included in the systematic review.
Figure 2
Figure 2
Forest plot for the risk of gastrointestinal adverse events (AEs) following alpha-lipoic acid (ALA) supplementation versus placebo.
Figure 3
Figure 3
Forest plot for the risk of neurological AEs following ALA supplementation versus placebo.
Figure 4
Figure 4
Forest plot for the risk of psychiatric AEs following ALA supplementation versus placebo.
Figure 5
Figure 5
Forest plot for the risk of musculoskeletal AEs following ALA supplementation versus placebo.
Figure 6
Figure 6
Forest plot for the risk of skin AEs following ALA supplementation versus placebo.
Figure 7
Figure 7
Forest plot for the risk of infections following ALA supplementation versus placebo.
Figure 8
Figure 8
Forest plot for the risk of CV system AEs following ALA supplementation versus placebo.
Figure 9
Figure 9
Forest plot for the risk of hospitalisation following ALA supplementation versus placebo.
Figure 10
Figure 10
Forest plot for the risk of death following ALA supplementation versus placebo.

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Source: PubMed

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