A recent study has found that caffeine may exacerbate the negative effects of chronic sleep deprivation on the brain’s gray matter. Researchers found that people who consumed caffeine during periods of sleep deprivation experienced a greater decrease in gray matter volume compared to those who did not. The findings were published recently in Scientific Reports.
Caffeine is the most widely used psychoactive substance in the world and is known for its ability to increase alertness and reduce cognitive impairment caused by sleep deprivation. However, acute sleep deprivation and daily caffeine intake are associated with reduced volume of grey matter, a key component of the brain involved in processing information and regulating various cognitive functions.
By examining the interaction between chronic sleep deprivation and daily caffeine intake, the researchers aimed to determine whether consuming caffeine during periods of sleep deprivation would further reduce gray matter volume. Additionally, the study aimed to investigate the role of the adenosine system, specifically adenosine A1 receptor availability, in mediating the brain’s response to caffeine and sleep deprivation.
Adenosine A1 receptors are a type of receptor in the brain that play an important role in regulating neuronal activity and promoting sleep. They are part of the adenosine system, which helps balance energy expenditure and maintain homeostasis. Caffeine acts as an antagonist of these receptors, inhibiting their action and thereby increasing alertness and reducing sleepiness.
The study was conducted in part by lead author Yu-Shuang Lin of the Psychiatry Clinic of the University of Basel in Switzerland, and senior author David Elmenhorst of the Institute of Neuroscience and Medicine at the Jülich Research Center in Germany.
“The concept for this work was conceived by Dr. Previous research in Center for Chronobiology“Therefore, we observed a caffeine concentration-dependent decrease in gray matter after 10 days of caffeine restriction, which was independent of caffeine-induced vasoconstriction and was only partially mitigated after 36 hours,” the two researchers told PsyPost in a joint statement.
“This effect of caffeine on grey matter plasticity adds to the wealth of evidence from animal studies implicating adenosine receptors, the main property through which caffeine binds and exerts its effects in modulating synaptic plasticity in the central nervous system. To understand the potential role of adenosine in grey matter plasticity, Yu Shuan contacted Professor David Elmenhorst from the Jülich Research Centre for a collaborative project.”
“At the time, David was conducting a PET-MRI study in collaboration with the German Aerospace Center to investigate the effects of chronic sleep deprivation and daily caffeine intake on adenosine A1 receptor (A1R) availability. In addition to A1R measurements, In vivoThis study was very exciting as it may provide insight into adenosine regulation of brain plasticity through sleep disruption.”
“Adenosine metabolism and signaling play a key role in sleep homeostatic mechanisms,” explain Lin and Elmenhorst. “Disrupted sleep, in turn, alters adenosine signaling and is frequently associated with impaired brain structure in both animal models and humans. Sleep deprivation intensifies caffeine-consuming behavior, and both are often prevalent simultaneously in modern society.”
“We therefore repurposed our arterial spin labeling data, as well as PET and T1-weighted MR imaging, to consider the effects of caffeine on cerebral perfusion and to examine gray matter plasticity following chronic sleep restriction with or without concomitant caffeine, and the potential mediation of A1R in these gray matter responses.”
The study was conducted at the German Aerospace Center’s research facility in Cologne on 36 healthy adults, including 15 women and 21 men, all around 29 years old. The participants were selected based on their low habitual caffeine intake (<450 mg per day) and non-smoking status. The participants were divided into two groups, one of which was given caffeinated coffee (CAFF group) and the other decaffeinated coffee (DECAF group).
The study took place over nine days in a controlled laboratory environment. It began with an adaptation day, followed by two baseline days, where participants slept eight hours per night. This was followed by five days of chronic sleep restriction, where participants slept only five hours per night, followed by a recovery day where they slept eight hours. During the chronic sleep restriction period, the CAFF group consumed 200 mg of caffeine in the morning and 100 mg in the afternoon, while the DECAF group consumed the same amount of decaffeinated coffee.
To measure the effects on grey matter volume, participants underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) scans at three time points: after a baseline day, after the chronic sleep restriction period, and after a recovery day. Saliva samples were taken periodically to monitor caffeine levels, allowing for precise tracking of caffeine intake and its physiological effects.
The study results showed that chronic sleep deprivation led to changes in gray matter volume, with caffeine intake having a significant effect on gray matter volume. Participants who did not consume caffeine during the sleep deprivation period (decaf group) showed increased gray matter volume in several brain regions, including the prefrontal cortex, temporo-occipital cortex, and thalamus. These regions are associated with a variety of cognitive and sensory functions, indicating a potential compensatory response to sleep deprivation.
“We were somewhat surprised to see that participants who did not consume caffeine (the decaf group) had an increase, rather than a decrease, in gray matter after chronic sleep restriction,” Lin and Elmenhorst told PsyPost. “However, we found that previous studies (Dai et al. (2018)) shed light on a potential explanation for this finding. In this study, they looked at changes in grey matter over a 20- to 36-h wakefulness period and found that multiple brain regions actually showed increases in the early phase (20 hours) that then reversed to decreases in the later phase (36 hours).”
“Although the effects of complete sleep deprivation cannot be generalized to chronic sleep deprivation, we speculated that gray matter responses to increasing duration or intensity of sleep deprivation may not follow a linear trajectory. More studies are needed to systematically investigate gray matter changes during different patterns of sleep deprivation.”
In contrast, participants who consumed caffeine during the sleep restriction period (CAFF group) experienced reduced grey matter volume in the same regions, suggesting that caffeine may inhibit the brain’s compensatory mechanisms during periods of sleep deprivation, exacerbating the deleterious effects of sleep deprivation on brain structure.
The researchers also found that individual differences in adenosine receptor availability played an important role in the extent of gray matter changes: participants with lower baseline availability of subcortical adenosine receptors experienced greater declines in gray matter volume when consuming caffeine during sleep restriction. This finding highlights the importance of adenosine receptor activity in mediating the effects of sleep deprivation and caffeine on brain structure.
“Individuals with higher A1R availability appear to be more resistant to the effects of caffeine on gray matter,” the researchers explain. “After recovery sleep and approximately 30 hours of caffeine abstinence, most of the gray matter changes were reversed, except for increases in the dorsolateral prefrontal cortex associated with chronic sleep restriction and decreases in the thalamus associated with caffeine intake.”
“It is well known that caffeine intake suppresses sleepiness. Our data further show that caffeine intake also influences brain plasticity induced by sleep deprivation. However, caffeine does not simply inhibit or normalize grey matter changes, it also has an opposite effect on grey matter. It is unclear how this effect of brain plasticity manifests at a cognitive-behavioral level, but we know that it is likely indicative of adenosine regulation in neural homeostasis.”
Despite its rigorous methodology, the study has some limitations to consider: The sample size was relatively small and participants were selected based on a specific genetic profile related to caffeine metabolism, which may limit how applicable the findings are to the broader population.
Additionally, while the MRI scans showed changes in gray matter, it’s not clear exactly what causes these changes. It could be an increase or decrease in neurons, changes in synapse density, or changes in the number of supporting cells such as microglia. To pinpoint these specific changes, future studies may use PET scans with special markers to measure synapses, mitochondria, or microglia, the researchers explain.
“Synaptic Homeostasis Hypothesis (SHY) He said: “Sleep is the price we pay for brain plasticity,” the researchers said. “Although it has been a decade since SHY was published, this intriguing hypothesis has yet to be tested in humans. In vivoDavid has therefore devoted himself to studying the molecular mechanisms of sleep-wake regulation using biomedical imaging, while Yu Shuan continues to focus on pharmacological PET-MR imaging to investigate adenosine regulation and its role in the effects of caffeine. We hope that future achievements in this direction will bring insight into the findings of this current study.”
the study, “Repeated caffeine ingestion suppresses the gray matter response to chronic sleep deprivation in an A1 adenosine receptor-dependent manner: a double-blind randomized controlled study using PET-MRI” was written by Yu-Shiuan Lin, Denise Lange, Diego Manuel Baur, Anna Foerges, Congying Chu, Changhong Li, Eva-Maria Elmenhorst, Bernd Neumaier, Andreas Bauer, Daniel Aeschbach, Hans-Peter Landolt, and David Elmenhorst.
