Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial

Abstract

Caffeine is commonly used to combat high sleep pressure on a daily basis. However, interference with sleep–wake regulation could disturb neural homeostasis and insufficient sleep could lead to alterations in human gray matter. Hence, in this double-blind, randomized, cross-over study, we examined the impact of 10-day caffeine (3 × 150 mg/day) on human gray matter volumes (GMVs) and cerebral blood flow (CBF) by fMRI MP-RAGE and arterial spin-labeling sequences in 20 habitual caffeine consumers, compared with 10-day placebo (3 × 150 mg/day). Sleep pressure was quantified by electroencephalographic slow-wave activity (SWA) in the previous nighttime sleep. Nonparametric voxel-based analyses revealed a significant reduction in GMV in the medial temporal lobe (mTL) after 10 days of caffeine intake compared with 10 days of placebo, voxel-wisely adjusted for CBF considering the decreased perfusion after caffeine intake compared with placebo. Larger GMV reductions were associated with higher individual concentrations of caffeine and paraxanthine. Sleep SWA was, however, neither different between conditions nor associated with caffeine-induced GMV reductions. Therefore, the data do not suggest a link between sleep depth during daily caffeine intake and changes in brain morphology. In conclusion, daily caffeine intake might induce neural plasticity in the mTL depending on individual metabolic processes.

Metabo-tip: a metabolomics platform for lifestyle monitoring supporting the development of novel strategies in predictive, preventive and personalised medicine

“…To overcome some of these obstacles, we investigated sweat collected from clean fingertips via metabo-tip. This procedure is fast, non-invasive and easy to use, thereby supporting multiple measurements within a short timeframe, and ensuring good compliance by the test subjects [31]. A determination of individual enzymatic activities and a management strategy to cope with normalisation issues, related to the total amount of sweat collected per sample, has already been demonstrated [32].…”

“…A comprehensive analysis of endogenous processes related to the uptake and individual metabolism of xenobiotics requires sensitive analytical techniques in addition to noninvasive and fast sampling methods, allowing short interval sampling and therefore enabling kinetic time-course measurements in humans [31,32]. The analysis of sweat from the fingertips fulfils these requirements and supports compliance of test subjects.…”

Time to recover from daily caffeine intake

“…The magnitude, however, was reduced in withdrawal compared to the caffeine condition (tW-C = 3.2, pW-C = 0.003). On the other hand, CBF in precuneus, thalamus, and basal ganglia, which was reduced during daily caffeine intake (21), was elevated at 36.5-h in the withdrawal compared to the placebo condition (tW-P = 2.1, pW-P = 0.039).…”

“…Cerebral blood flow (CBF) was measured by 2D Echo-Planar Imaging (EPI) pulsed arterial spin labeling (ASL) sequence (4x4x4mm 3 , TR=3000ms, TE=12ms, FA=90). For the detailed pipeline of preprocessing and the whole-brain analyses (WBAs), please find the methods in (21). The current analysis adopted a region-of-interest (ROI) approach based on the previously reported caffeine-induced results in a whole-brain analysis (21).…”

“…For the present report, we leveraged salivary samples of a previous study with three within-subject conditions (21): caffeine (150 mg caffeine x 3/day x 10 days), placebo (150 mg mannitol x 3/day x 10 days), and withdrawal (caffeine x 9 days + placebo x 1 day). We report a 43-h profile of caffeine and paraxanthine levels, the kinetics of each compound and their association with habitual caffeine intake.…”