Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men

Abstract

The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 +/- 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 +/- 0.5%; 4 wk, 6.9 +/- 0.7%; 8 wk, 7.9 +/- 0.6%; 12 wk, 8.4 +/- 0.7% (P < 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 +/- 0.6%, 4.5 +/- 0.5%, 3.9 +/- 0.5%, and 4.4 +/- 0.6% (P < 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 +/- 2.2, 6.4 +/- 2.3, 5.5 +/- 2.8, and 5.1 +/- 2.0 IU/ml (P < 0.01 vs. baseline, by ANOVA); placebo: 9.0 +/- 2.1, 10.4 +/- 2.2, 9.5 +/- 2.2, and 9.6 +/- 2.1 IU/ml (P < 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 +/- 12.2; 12 wk, 132.0 +/- 12.8 mg/dl (P < 0.01, by ANOVA); placebo: 181.0 +/- 13.8 and 179.6 +/- 12.4 mg/dl (P < 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease.

Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies

“…The selection of patients with low values of DHEA may have been an important factor for the finding of significant effects on body composition and fat distribution in that study, although other studies performed in men with low DHEA-S or women with adrenal insufficiency found no effects of DHEA on body composition (130,139). Finally, in the study by Kawano et al (127), although no effect on the lipid profile or body fatness were observed, other cardiovascular disease-related outcomes such as endothelial function and insulin sensitivity were significantly improved in response to DHEA supplementation in this sample of 24 hypercholesterolemic men, which may be considered as a cardioprotective effect of DHEA (127).…”

“…These studies were performed with dosage ranging from 25 to 1600 mg/day oral DHEA and durations from 4 to 36 weeks (127, 129 -131, 134 -137). Examining the effects of DHEA replacement in subjects with previously documented hypercholesterolemia did not lead to the finding of significant effects of the treatment in a 12-week randomized placebo-controlled study using 25 mg/day oral DHEA (127). On the other hand, some studies reported significant effects of DHEA on blood lipids (6, 11, 125,126,128,132,133).…”

Association of Plasma Dehydroepiandrosterone-Sulfate Levels with Endothelial Function in Postmenopausal Women with Coronary Risk Factors

“…Williams et al (12) showed a significant increase in FMD after the 12-week administration of DHEA (50 mg/day) in healthy postmenopausal women, while Silvestri et al (22) observed no effect using the same dose of DHEA for 4 weeks in postmenopausal women with increased cardiovascular risk. In middle-aged men, it has been reported that low-dose DHEA supplementation (25 mg/day) for 12 weeks improved FMD (23). Experimental studies have also demonstrated the effects of DHEA on endothelial proliferation (12) and endothelial nitric oxide synthase (24), further supporting the notion that DHEA(-S) has a protective effect on the endothelium.…”

Serum Dehydroepiandrosterone Sulphate Levels in Patients with Non-Alcoholic Fatty Liver Disease

“…These are also supported by our results in that the insulin sensitivity index HOMA-%S was inversely associated with serum ALT. DHEA is known to have potential to improve insulin sensitivity in vivo (21)(22)(23)(24). It also has properties to increase insulin sensitivity in hepatocytes (25).…”