Natural Activators of Autophagy Increase Maximal Walking Distance and Reduce Oxidative Stress in Patients with Peripheral Artery Disease: A Pilot Study

• Published in: Antioxidants 2022-09, Vol.11 (9), p.1836
• Main Authors: Martinelli, Ombretta, Peruzzi, Mariangela, Bartimoccia, Simona, D'Amico, Alessandra, Marchitti, Simona, Rubattu, Speranza, Chiariello, Giovanni Alfonso, D'Ambrosio, Luca, Schiavon, Sonia, Miraldi, Fabio, Saade, Wael, D'Abramo, Mizar, Pingitore, Annachiara, Loffredo, Lorenzo, Nocella, Cristina, Forte, Maurizio, Pignatelli, Pasquale
• Format: Article
• Language: English
• Subjects: Anticoagulants; Antioxidants; Atherosclerosis; Autophagy; Autophagy (Cytology); CYBB protein; Diabetes; Disease; Endothelin 1; Endothelins; Hydrogen peroxide; Intermittent claudication; Ischemia; Kinases; Nicotinamide; Nitrates; Nitric oxide; Observations; Oxidative stress; Patients; peripheral artery disease; Peripheral vascular diseases; Physiological aspects; Polyphenols; Proteins; Risk factors; Spermidine; Trehalose; Ultrasonic imaging; Values; Vascular diseases; Walking
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11091836

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 < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H2O2 (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, 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.