Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials
by
Giovanni Pagano 1,*, Annarita Aiello Talamanca 1, Giuseppe Castello 1, Mario D. Cordero 2, Marco D'Ischia 3
, Maria Nicola Gadaleta 4, Federico V. Pallardó 5, Sandra Petrović 6, Luca Tiano 7 and Adriana Zatterale 8
Giovanni Pagano 1,*, Annarita Aiello Talamanca 1, Giuseppe Castello 1, Mario D. Cordero 2, Marco D'Ischia 3, Maria Nicola Gadaleta 4, Federico V. Pallardó 5, Sandra Petrović 6, Luca Tiano 7 and Adriana Zatterale 8
1
Istituto Nazionale Tumori Fondazione G. Pascale—Cancer Research Center at Mercogliano (CROM)—IRCCS, Naples I-80131, Italy
2
Research Laboratory, Dental School, Universidad de Sevilla, Sevilla 41009, Spain
3
Department of Chemical Sciences, University of Naples "Federico II", Naples I-80126, Italy
4
National Research Council, Institute of Biomembranes and Bioenergetics, Bari I-70126, Italy
5
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), University of Valencia—INCLIVA, Valencia 46010, Spain
6
Vinca" Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia
7
Biochemistry Unit, Department of Clinical and Dental Sciences, Polytechnical University of Marche, Ancona I-60131, Italy
8
Genetics Unit, Azienda Sanitaria Locale (ASL) Napoli 1 Centro, Naples I-80136, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(11), 20169-20208; https://doi.org/10.3390/ijms151120169
Received: 7 October 2014 / Revised: 29 October 2014 / Accepted: 30 October 2014 / Published: 5 November 2014
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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.
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Keywords:
mitochondrial nutrients; mitochondrial dysfunction; oxidative stress; oxidative phosphorylation; Krebs cycle
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MDPI and ACS Style
Pagano, G.; Aiello Talamanca, A.; Castello, G.; Cordero, M.D.; D'Ischia, M.; Gadaleta, M.N.; Pallardó, F.V.; Petrović, S.; Tiano, L.; Zatterale, A. Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials. Int. J. Mol. Sci. 2014, 15, 20169-20208.
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