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

• Main Authors: Ombretta Martinelli (Author), Mariangela Peruzzi (Author), Simona Bartimoccia (Author), Alessandra D'Amico (Author), Simona Marchitti (Author), Speranza Rubattu (Author), Giovanni Alfonso Chiariello (Author), Luca D'Ambrosio (Author), Sonia Schiavon (Author), Fabio Miraldi (Author), Wael Saade (Author), Mizar D'Abramo (Author), Annachiara Pingitore (Author), Lorenzo Loffredo (Author), Cristina Nocella (Author), Maurizio Forte (Author), Pasquale Pignatelli (Author)
• Format: Book
• Published: MDPI AG, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox11091836; 2076-3921
• Keywords: autophagy; oxidative stress; peripheral artery disease; trehalose; polyphenols; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 11, Iss 9, p 1836 (2022)

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