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.
Highlights
Alpha-lipoic acid (1, 2-dithiolane-3-pentanoic acid; ALA) or thioctic acid is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule, being largely used worldwide as a dietary supplement [1].Previous investigations revealed that ALA can affect central and peripheral modulation of 5 -adenosine-monophosphate-activated protein kinase
Additional 139 papers were excluded due to being pre-print papers (n = 2), study protocols (n = 6), reporting data from studies lacking of an appropriate placebo-controlled design for the supplementation (n = 64), lacking of randomisation (n = 5), testing the acute effect of ALA supplementation (n = 7), testing ALA supplementation combined in nutraceutical compounds (n = 27), testing intravenous treatment with ALA (n = 11), testing topical treatment with ALA (n = 4), lacking sufficient information about the nature of the adverse events (n = 9), or reporting data overlapped with other publications (n = 4) (Supplementary file B)
Meta-analysis of extracted data suggested that supplementation with ALA was not associated Awntiitohxidaanntsin20c2r0e,a9s, exdFOrRisPkEEoRf RgEaVstIrEoWintestinal adverse events (AEs) (OR = 1.32, 95% confidence interval (95% CI) 0.97 to 1.78; p = 0.073; I2 = 01%8) (Figure 2)
Summary
Previous investigations revealed that ALA can affect central and peripheral modulation of 5 -adenosine-monophosphate-activated protein kinase. It activates peroxisome proliferator-activated receptor (PPAR) alpha and gamma (PPAR-γ), modulates PPAR-regulated genes and upregulates the expression of PPAR-γ messenger ribonucleic acid (mRNA) and other proteins in the cardiac tissue and aorta smooth muscle [2,3]. In about 50% of cases, IAS development is associated with drugs or dietary supplement containing a sulphur or sulfhydryl group. These cases are closely related to certain specific antigens of the major histocompatibility complex (MHC), which are more common in populations where IAS incidence is higher [7]. It is hypothesised that ALA might cause the development of antibodies to insulin and lead to a hypoglycaemic syndrome in predisposed subjects, even though evidence are inconclusive [8]
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