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

Aging. 2016;8:1167-1183.

Rachelle E. Kaplon, Sierra D. Hill, Nina Z. Bispham, Jessica R. Santos-Parker, Molly J. Nowlan, Laura L. Snyder, Michel Chonchol, Thomas J. LaRocca, Matthew B. McQueen, Douglas R. Seals


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<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.

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