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.

Keywords: aging; endothelium-dependent dilation; large elastic artery stiffness; oxidative stress; trehalose.

Figure 1

Study flow diagram

Figure 2

Forearm blood flow responses to acetylcholine (ACh) at baseline (closed circles) and following 12 weeks (open circles) of maltose and trehalose supplementation in all subjects (A) and in the subset of subjects who maintained body mass within 2.3 kg (B). FAV, forearm volume. Values are mean ± SE; *P<0.05 vs. baseline.

Figure 3

Forearm blood flow responses to acetylcholine (ACh) in the absence (dark grey bars) vs. presence (light grey bars) of the endothelial NO synthase inhibitor, NG-monomethyl-l-arginine (L-NMMA) at baseline (base) and following 12 weeks of maltose and trehalose supplementation in the subset of subjects who maintai-ned body mass within 2.3 kg. AUC, area under the dose response curve. Values are mean ± SE; *P<0.05 vs. baseline FBF_ACh in the absence of L-NMMA.

Figure 4

Forearm blood flow responses to acetylcholine (ACh) in the absence (dark grey bars) vs. presence (light grey bars) of the antioxidant, vitamin C, at baseline (base) and following 12 weeks of trehalose and maltose supplementation in the subset of subjects who maintained body mass within 2.3 kg. AUC, area under the dose response curve. Values are mean ± SE; *P<0.05 vs. baseline of same group; ‡P<0.05 vs. forearm blood flow to ACh in the absence of vitamin C at the same time point.

Figure 5

Forearm blood flow responses to sodium nitroprusside (SNP) at baseline (closed circles) and following 12 weeks (open circles) of maltose and trehalose supplementation in all subjects (A) and in the subset of subjects who maintained body weight within 2.3 kg (B). FAV, forearm volume. Values are mean ± SE; *P<0.05 vs. baseline.

Figure 6

Brachial artery flow-mediated dilation (FMD) expressed as percent (left) and absolute (right) change at baseline (base) and following 4 and 12 weeks of maltose and trehalose supplementation. Values are mean ± SE.

Figure 7

Aortic pulse wave velocity (aPWV) at baseline (base) and following 12 weeks of maltose and trehalose supplementation. Values are mean ± SE.

Figure 8

Carotid compliance (left) and β-stiffness index (right) at baseline (base) and following 12 weeks of maltose and trehalose supplementation. Values are mean ± SE. *P<0.05 vs. baseline of same group.