Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men.
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.
Kawano
Hiroaki
H
Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan. koumei@gpo.kumamoto-u.ac.jp
Yasue
Hirofumi
H
Kitagawa
Akira
A
Hirai
Nobutaka
N
Yoshida
Toshiaki
T
Soejima
Hirofumi
H
Miyamoto
Shinzo
S
Nakano
Masahiro
M
Ogawa
Hisao
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D001916:Brachial Artery / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D017395:Plasminogen Activator Inhibitor 1; D003687:Dehydroepiandrosterone