No 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.

Background By binding to negatively charged polysaccharides called glycosaminoglycans, sodium can be stored in the body—particularly in the skin—without concurrent water retention. Concordantly, individuals with changed glycosaminoglycan structure (e.g. type 1 diabetes (DM1) and hereditary multiple exostosis (HME) patients) may have altered sodium and water homeostasis. Methods We investigated responses to acute (30-min infusion) and chronic (1-week diet) sodium loading in 8 DM1 patients and 7 HME patients in comparison to 12 healthy controls. Blood samples, urine samples, and skin biopsies were taken to investigate glycosaminoglycan sulfation patterns and both systemic and cellular osmoregulatory responses. Results Hypertonic sodium infusion increased plasma sodium in all groups, but more in DM1 patients than in controls. High sodium diet increased expression of nuclear factor of activated t-cells 5 (NFAT5)—a transcription factor responsive to changes in osmolarity—and moderately sulfated heparan sulfate in skin of healthy controls. In HME patients, skin dermatan sulfate, rather than heparan sulfate, increased in response to high sodium diet, while in DM1 patients, no changes were observed. Conclusion DM1 and HME patients show distinct osmoregulatory responses to sodium loading when comparing to controls with indications for reduced sodium storage capacity in DM1 patients, suggesting that intact glycosaminoglycan biosynthesis is important in sodium and water homeostasis. Trial registration These trials were registered with the Netherlands trial register with registration numbers: NTR4095 (https://www.trialregister.nl/trial/3933 at 2013-07-29) and NTR4788 (https://www.trialregister.nl/trial/4645 at 2014-09-12).