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

To evaluate the effects of dietary caffeine intake and withdrawal on cerebral blood flow (CBF), as determined from a randomized, blinded, placebo-controlled study.

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.

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.

Dietary caffeine consumption and withdrawal are potential confounding variables in cerebral perfusion and functional MR imaging.