Dietary caffeine consumption and withdrawal: confounding variables in quantitative cerebral perfusion studies?

PURPOSE To evaluate the effects of dietary caffeine intake and withdrawal on cerebral blood flow (CBF), as determined from a randomized, blinded, placebo-controlled study. MATERIALS AND METHODS Twenty adults (16 men, four women; age range, 24-64 years) categorized as low (mean, 41 mg/d) or high (mean, 648 mg/d) caffeine users underwent quantitative flow-sensitive alternating inversion-recovery perfusion magnetic resonance (MR) imaging twice: 90 minutes after a dose of caffeine (250 mg) on one day and after a dose of placebo on another day (randomized counterbalanced design). Doses were preceded by 30 hours of caffeine abstinence to induce withdrawal in high caffeine users. Quantitative CBF maps were gray matter (GM)-white matter (WM) segmented and subjected to region-of-interest analysis to obtain mean CBF in WM, anterior circulation GM (AGM), and posterior circulation GM (PGM). By using two-way repeated-measures analysis of variance, regional CBF data were tested for within-subject differences between caffeine and placebo and for between-subject differences related to dietary caffeine habits. Linear regression was used to determine whether dietary caffeine use predicts CBF or CBF response to caffeine. RESULTS Caffeine reduced CBF (P < or =.05) by 23% (AGM, PGM) and 18% (WM) in all subjects. Postplacebo (withdrawal) CBF in high caffeine users exceeded that in low users (P < or =.05) by 31% (AGM) and 32% (WM) (PGM, not significant). Mean postcaffeine CBF reduction in AGM was 26% in high users versus 19% in low users (P < or =.05; PGM and WM, not significant). Increasing caffeine consumption predicted higher CBF (P < or =.05) in all regions: r = 0.79 (AGM), 0.57 (PGM), and 0.76 (WM). Dietary caffeine use did not predict CBF response to caffeine. CONCLUSION Dietary caffeine consumption and withdrawal are potential confounding variables in cerebral perfusion and functional MR imaging.

[1]  F. Gibbs,et al.  The cerebral blood flow in man as influenced by adrenalin, caffein, amyl nitrite and histamine , 1935 .

[2]  H. Shenkin,et al.  Effects of various drugs upon cerebral circulation and metabolism of man. , 1951, Journal of applied physiology.

[3]  L. Edvinsson,et al.  Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study , 1976, Brain Research.

[4]  M. L. Bunker,et al.  Caffeine content of common beverages. , 1979, Journal of the American Dietetic Association.

[5]  R. Mathew,et al.  Caffeine and Cerebral Blood Flow , 1983, British Journal of Psychiatry.

[6]  W H Wilson,et al.  Caffeine Consumption, Withdrawal and Cerebral Blood Flow , 1985, Headache.

[7]  J. Fastbom,et al.  Adenosine A1-receptors in human brain: Characterization and autoradiographic visualization , 1986, Neuroscience Letters.

[8]  M. Arnaud.  The pharmacology of caffeine. , 1987, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[9]  R R Watson,et al.  The effects of caffeine on various body systems: a review. , 1987, Journal of the American Dietetic Association.

[10]  P. Smits,et al.  Caffeine reduces dipyridamole-induced myocardial ischemia. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  Phillis Jw,et al.  Adenosine in the control of the cerebral circulation. , 1989 .

[12]  S. Ogawa,et al.  Oxygenation‐sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields , 1990, Magnetic resonance in medicine.

[13]  O. Cameron,et al.  Caffeine and human cerebral blood flow: a positron emission tomography study. , 1990, Life sciences.

[14]  J W Belliveau,et al.  Functional cerebral imaging by susceptibility‐contrast NMR , 1990, Magnetic resonance in medicine.

[15]  R. Griffiths,et al.  Low-dose caffeine physical dependence in humans. , 1990, The Journal of pharmacology and experimental therapeutics.

[16]  U. Traversa,et al.  Effects of chronic administration of adenosine antagonists on adenosine A1 and A2a receptors in mouse brain. , 1994, In vivo.

[17]  Egm Couturier,et al.  Influence of Caffeine and Caffeine Withdrawal on Headache and Cerebral Blood Flow Velocities , 1997, Cephalalgia : an international journal of headache.

[18]  B. Fredholm,et al.  A1 and A2A adenosine receptors and A1 mRNA in mouse brain: effect of long-term caffeine treatment , 1997, Brain Research.

[19]  B B Fredholm,et al.  Distribution of adenosine receptors in the postmortem human brain: An extended autoradiographic study , 1997, Synapse.

[20]  Jeff H. Duyn,et al.  Multislice Imaging of Quantitative Cerebral Perfusion with Pulsed Arterial Spin-Labeling , 1998, NeuroImage.

[21]  Astrid Nehlig,et al.  Are we dependent upon coffee and caffeine? A review on human and animal data , 1999, Neuroscience & Biobehavioral Reviews.

[22]  R. Herning,et al.  Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity , 2000, Psychopharmacology.

[23]  S. Dager,et al.  Brain imaging and the effects of caffeine and nicotine , 2000, Annals of medicine.

[24]  C. Cass,et al.  Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system , 2001, Neuropharmacology.

[25]  Paul J. Laurienti,et al.  Dietary Caffeine Consumption Modulates fMRI Measures , 2002, NeuroImage.

[26]  Narter Ari,et al.  Test‐retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge , 2002, Magnetic resonance in medicine.

[27]  D. Gitelman,et al.  On the Use of Caffeine as a Contrast Booster for BOLD fMRI Studies , 2002, NeuroImage.

[28]  Joseph A Maldjian,et al.  Relationship between caffeine-induced changes in resting cerebral perfusion and blood oxygenation level-dependent signal. , 2003, AJNR. American journal of neuroradiology.

[29]  R. Griffiths,et al.  Caffeine physical dependence: a review of human and laboratory animal studies , 2004, Psychopharmacology.