How Is Caffeine Affecting Your BrainUsed by approximately 87% of the population, caffeine has become the most widely consumed neurostimulant in the world. Although intended to raise alertness in its users, researchers have found it can also affect the blood flow in our brains. Present in coffee, soft drinks, tea, chocolate, analgesics and dietary supplements, caffeine (1,3,7 ??“ trimethylxanthine) has become a part of our everyday lives. Its abundance raises many concerns in regards to its effects on our health and whether its benefits outweigh the consequences.Led by Merideth Addicott, researchers have discovered that caffeine acts as a competitive antagonist of adenosine A2A and A2B receptors found on cerebrovascular smooth muscle, leading to vasoconstriction of blood vessels. As a result, cerebral blood flow (CBF) is reduced. Adenosine, an essential cellular component involved with energy metabolism, acts as an extracellular signaling molecule through its binding to receptors found on nearly every cell in the body. Normally adenosine would bind to those receptors on vascular smooth muscle and cause vasodilation, but the presence of caffeine creates competition for binding sites, ultimately leading to vasoconstriction. The vasoconstrictive property of caffeine leads to a reduction of CBF.Caffeine users have also been known to experience symptoms of withdrawal proportional to their daily intake of the drug. These symptoms include headache, fatigue, and impaired concentration, emerging between 12 and 24 hours following caffeine termination. Symptoms may be present with consumption of as little as 100 mg/day of caffeine use. In their study, forty-five adult volunteers, aged 18-50 years, were selected based on a strict list of criteria and were organized into categories based on their daily caffeine consumption. Participants were defined as either ???low users??? (less than 200 mg/day), ???moderate users??? (between 200 and 600 mg/day), or ???high users??? (more than 600 mg/day). Users??™ CBF was then measured in two different states: a caffeinated state and a caffeine abstinent state to determine the relationship between CBF and chronic caffeine use. Caffeine abstention was defined as 30 hours of no caffeine use to ensure that caffeine concentrations were below the detection threshold (0.2 ?µg/ml) at the time of testing. The authors hypothesized that following a period of caffeine abstention, CBF would increase proportional to the daily caffeine use, and while in a native caffeinated state there would be no differences in CBF between caffeine use groups. In a randomized, double-blind study design, participants were chosen on four separate occasions to undergo quantitative perfusion imaging to measure their CBF in either the native or abstinent state. To ensure compliance with the study??™s requirements, saliva tests were issued prior to imaging to measure caffeine levels. After the saliva test, participants were either administered a placebo or 250 mg of caffeine. An hour later, a second saliva sample was taken as well as measurements of respiration rate, end-tidal CO2, oxygen saturation, heart rate, and blood pressure. The participants were then placed in a MRI scanner where functional, structural and perfusion imaging were completed. As the researchers had expected, post-drug caffeine concentrations had increased from the pre-drug concentrations only in caffeine conditions, but not in placebo conditions. Since there was no effect of drug conditions, concentrations of caffeine were averaged and salivary results showed significant differences between the three user groups. Following caffeine administration, users had also experienced a decrease in heart rate and an increase in blood pressure. MRI results showed that caffeine reduced gray matter CBF by 27% across all caffeine users. In the caffeine-abstained placebo condition, there was a positive correlation between daily caffeine use and CBF. To explain this increase, researchers suggested that the number of adenosine receptors were increased to adapt to increasing amounts of caffeine present. This upregulation would allow for more adenosine to bind despite the presence of caffeine and therefore counteract vasoconstriction and raise CBF to a level that would have existed had the user not consumed caffeine. Since the users were given a placebo, adenosine had no competition for receptor sites. High users had the greatest upregulation of receptors, therefore the most free receptors for adenosine to bind to. This condition exhibited the greatest CBF among all user groups when compared with other conditions. Participants who abstained from caffeine, but were administered a 250 mg dose of caffeine prior to imaging showed a similar correlation. Slightly greater CBF was found in high users than low users, which supports the researchers??™ hypothesis that high users have more adenosine receptors. The differences in CBF were much less in this condition due to the static 250 mg of caffeine present in each user group, therefore limiting the number of available adenosine receptors to increase CBF.Despite a step-wise increase in salivary concentration of caffeine among the three user groups, the native placebo condition showed similar CBF between users. The chronic intake of caffeine can lead to an increased number of A2A and A2B receptors (upregulation), therefore raising the user??™s tolerance. While this increase in tolerance may result in more receptors, it is offset by the proportional increase in caffeine concentration. Of the three user groups, high users showed a trend towards less CBF than the low and moderate users. This suggested that a withdrawal, or ???rebound???, effect on CBF is proportional to daily caffeine use.The participants in a native caffeine state who were administered an additional 250 mg of caffeine displayed results similar to the abstain-caffeine condition. This lack of difference in CBF is explained by a ceiling effect caused by maximum vasoconstriction. The researchers hypothesized that the 250 mg of caffeine given before imaging was enough for both conditions to have the most receptors occupied by caffeine.What do the results of these conditions mean As our intake of caffeine increases, we are raising our tolerance to the drug and subsequently lowering the amount of blood flow in our brains. Our bodies are adapting to this new environment we are creating by increasing the number of adenosine receptors present to offset the increased caffeine concentrations in our system. But just how much caffeine can our body tolerateDaily intake of caffeine ranges from 166 to 336 mg/day among adults 18 years and older. As shown by the difference in CBF between the abstained-caffeine and native-caffeine conditions, a single dose of 250 mg caffeine will produce maximum vasoconstriction by occupying the most adenosine receptors, leading to a peak tolerance. The fact that a single 250 mg dose of caffeine is enough for maximum vasoconstriction of blood vessels shows just how relevant this study is to our health.
The conclusions made in the study are sound. The strong correlation found between daily caffeine use and CBF indicates caffeine may have a larger effect on the body than initially intended. One aspect of caffeine use that the study does not cover is how withdrawal symptoms factor into CBF. An interesting direction for future research on caffeine??™s effects would be to examine the relationship between withdrawal symptoms reported by participants and CBF following the ingestion of caffeine.Reference:
1 Addicott, Merideth A. et al. 2009. Human Brain Mapping. 30(10): 3102-3114.