Treatment of alcohol-related liver disease with thioctic acid: a six month randomised double-blind trial.
ABSTRACT A randomised double-blind trial of thioctic acid (alpha-lipoic acid), 300 mg/day versus placebo was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a six month period. Twenty patients received the active drug and 20 placebo. Twenty-two of the 40 patients (55%) abstained from alcohol and showed significant improvements (p less than 0.01) in mean values for serum aspartate transaminase, serum glutamyl transpeptidase, and mean corpuscular volume. Seventeen of the 22 (77%) showed overall histological improvement on liver biopsy. The remaining 18 patients (45%) continued to drink but significantly reduced their mean daily alcohol intake (p less than 0.001). No significant changes occurred in their laboratory indices, but five of the 18 (28%) showed overall histological improvement. Changes occurred irrespective of treatment with thioctic acid, which suggested that, over six months, this drug did not influence the course of alcohol-related liver disease.
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ABSTRACT: An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed "mitochondrial nutrients" (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with "classical" antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed.International Journal of Molecular Sciences 11/2014; 15(11):20169-20208. DOI:10.3390/ijms151120169 · 2.34 Impact Factor
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ABSTRACT: A new and efficient process was developed by lipase-catalyzed transacylation to resolve ethyl 8-chloro-6-hydroxy octanoate (ECHO) to produce an important chiral precursor for the synthesis of (R)-α-lipoic acid. After optimization of biocatalyst, solvent, acyl donor, temperature and enzyme loading, (S)-O-acetylated ECHO was achieved in 94% ee, 35% isolated yield and 38 g L−1 d−1 space-time yield using Novozym 435 as biocatalyst. Subsequently, the enzymatic resolution reaction was successfully repeated for 7 batches, retaining over 40% conversions.Journal of Molecular Catalysis B Enzymatic 01/2014; 99:102–107. DOI:10.1016/j.molcatb.2013.11.005 · 2.75 Impact Factor