Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

• Published in: Aging (Albany, NY.) Vol. 8; no. 6; pp. 1167 - 1183
• Main Authors: Kaplon, Rachelle E, Hill, Sierra D, Bispham, Nina Z, Santos-Parker, Jessica R, Nowlan, Molly J, Snyder, Laura L, Chonchol, Michel, LaRocca, Thomas J, McQueen, Matthew B, Seals, Douglas R
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 01.06.2016
• Subjects: Acetylcholine - pharmacology; Aged; Aging - physiology; Brachial Artery - drug effects; Brachial Artery - physiology; Double-Blind Method; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Female; Forearm - blood supply; Humans; Male; Middle Aged; Oxidative Stress - drug effects; Oxidative Stress - physiology; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Research Paper; Trehalose - pharmacology; Vascular Stiffness - drug effects; Vascular Stiffness - physiology; endothelium-dependent dilation; trehalose; aging; large elastic artery stiffness; oxidative stress
• ISSN: 1945-4589
• DOI: 10.18632/aging.100962

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass less than 2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ~30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ~30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass ≥ 2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO.