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Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men

Departments of Cardiovascular Medicine (H.K., N.H., T.Y., H.S., S.M., H.O.) and Pharmacy (A.K.), Kumamoto University School of Medicine, Kumamoto Aging Research Institute (H.Y.), Kumamoto 860-8556, Japan; and Department of Clinical Pharmacy Graduate School of Pharmaceutical Sciences, University of Shizuoka (M.N.), Shizuoka 422-8529, Japan

Address all correspondence and requests for reprints to: Hiroaki Kawano, M.D., Ph.D., Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City 860-8556, Japan. E-mail: koumei{at}gpo.kumamoto-u.ac.jp.

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.

This work was supported by a grant from the Kanae Foundation for Life and Socio-Medical Science; the Japan Cardiovascular Research Foundation; a grant-in-aid from the Smoking Research Foundation (Tokyo, Japan); a research grant (141719019) from the Ministry of Health, Labor, and Welfare; and a grant-in-aid for scientific research (14770318) from the Ministry of Education, Science; and Culture, Japan.

Abbreviations: DHEA, Dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; PAI-1, plasminogen activator inhibitor type 1; SSPG, steady state plasma glucose; SSPI, steady state plasma insulin.

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