Natural Activators of Autophagy Increase Maximal Walking Distance and Reduce Oxidative Stress in Patients with Peripheral Artery Disease: A Pilot Study
Ombretta Martinelli,
Mariangela Peruzzi,
Simona Bartimoccia,
Alessandra D’Amico,
Simona Marchitti,
Speranza Rubattu,
Giovanni Alfonso Chiariello,
Luca D’Ambrosio,
Sonia Schiavon,
Fabio Miraldi,
Wael Saade,
Mizar D’Abramo,
Annachiara Pingitore,
Lorenzo Loffredo,
Cristina Nocella,
Maurizio Forte,
Pasquale Pignatelli
Affiliations
Ombretta Martinelli
Department of General and Specialistic Surgery “Paride Stefanini”, Sapienza University of Rome, 00161 Rome, Italy
Mariangela Peruzzi
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Simona Bartimoccia
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Alessandra D’Amico
Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, Italy
Simona Marchitti
IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy
Speranza Rubattu
IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy
Giovanni Alfonso Chiariello
Cardiovascular Sciences Department, Agostino Gemelli Foundation Polyclinic IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
Luca D’Ambrosio
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy
Sonia Schiavon
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy
Fabio Miraldi
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Wael Saade
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Mizar D’Abramo
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Annachiara Pingitore
Department of General and Specialistic Surgery “Paride Stefanini”, Sapienza University of Rome, 00161 Rome, Italy
Lorenzo Loffredo
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Cristina Nocella
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Maurizio Forte
IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy
Pasquale Pignatelli
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H2O2 production, H2O2 break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p p p p 2O2 (−40%, p p p p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070.
