title: Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults.
abstract: 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.
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Rachelle E
authors.initials: RE
authors.lastname: Kaplon
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Sierra D
authors.initials: SD
authors.lastname: Hill
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Nina Z
authors.initials: NZ
authors.lastname: Bispham
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Santos-Parker
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Molly J
authors.initials: MJ
authors.lastname: Nowlan
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Snyder
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: LaRocca
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000375:Aging / Q000502:physiology*; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D014199:Trehalose / Q000494:pharmacology*; D059289:Vascular Stiffness / Q000187:drug effects / Q000502:physiology
chemical_list: D014199:Trehalose; D000109:Acetylcholine
keywords: aging; endothelium-dependent dilation; large elastic artery stiffness; oxidative stress; trehalose