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Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels

Lovallo, William R. PhD; Whitsett, Thomas L. MD; al’Absi, Mustafa PhD; Sung, Bong Hee PhD; Vincent, Andrea S. PhD; Wilson, Michael F. MD

doi: 10.1097/01.psy.0000181270.20036.06
Original Articles

Objective: Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake.

Methods: Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM.

Results: After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period.

Conclusion: Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis.

ANOVA = analysis of variance; C = caffeine; HPAC = hypothalamic-pituitary-adrenocortical axis; P = placebo; ACTH = adrenocorticotropin.

From the Veterans Affairs Medical Center (W.R.L., A.S.V., B.S.M., T.L.W.), Department of Psychiatry and Behavioral Sciences (W.R.L., A.S.V.), and Department of Medicine (T.L.W.), University of Oklahoma Health Sciences Center, Oklahoma City, OK; Department of Behavioral Sciences (M.A.), University of Minnesota Medical School, Duluth, MN; Cardiology (M.F.W., B.H.S.), Kaleida, Millard Fillmore Division, Buffalo, NY.

Address correspondence and reprint requests to William R. Lovallo, PhD, VA Medical Center (151A), 921 NE 13th Street, Oklahoma City, OK 73104. E-mail:

Received for publication January 31, 2005; revision received April 28, 2005.

Supported by NHLBI grant HL32050, NIRR grant M01-RR14467, and the Department of Veterans Affairs Medical Research Service.

Copyright © 2005 by American Psychosomatic Society
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