Your DNA on Caffeine

In this episode of Daily Value, we look at the relationship between genetics, habitual caffeine intake, and cognitive performance, using insights from a recent study (PMID: 39648354) in the Journal of Psychopharmacology. Whether you’re a "fast" or "slow" caffeine metabolizer could significantly influence how caffeine impacts your brain.

Discussion Points:

• Gene-Caffeine Interactions: how variants in CYP1A2 and ADORA2A genes modulate caffeine metabolism and sensitivity, leading to differential effects on executive function and social cognition.
• Cognitive Domains: Why slow metabolizers consuming high caffeine outperform fast metabolizers in emotion recognition tasks, and why moderate caffeine enhances executive function in fast metabolizers.
• Practical Applications: Tailoring caffeine intake based on genetic predisposition to optimize focus, decision-making, and cognitive flexibility.

https://pubmed.ncbi.nlm.nih.gov/39648354/

Chapters

• 0:00 Genetics and Caffeine's Cognitive Effects
• 8:46 Unlocking Caffeine's Cognitive Complexities

Transcript

Speaker 1: 0:00

Caffeine, the world's most consumed psychoactive substance, is famous for its ability to increase alertness and ward off fatigue, but have you ever wondered why its effects can vary so widely from person to person? Why, well, the answer may lie in genetics. In this episode, we'll look at new research that sheds light on how your genetic makeup influences your body's response to caffeine, and how this interplay affects different areas of cognition, such as attention, memory and executive function. Hello everyone, and welcome back to Daily Value. I'm William Wallace, and today we're diving into a topic that blends neuroscience, genetics and nutrition, that is, the interaction between caffeine in your genes and cognitive performance.

Speaker 1: 0:50

It's probably not surprising for you to hear that the effects of caffeine are not uniform. Studies show that, while acute caffeine intake consistently improves simple cognitive tasks like attention and reaction time, that its impact on more complex cognitive functions like decision making or memory is inconsistent Again, that's with acute intake. On the other hand, there is data that shows the opposite when looking at habitual or chronic caffeine use, that being better high-level cognitive functioning, like executive functioning and memory performance, but no association with improved lower-order function like attention or reaction time and again, that's with chronic or habitual use. Now there are studies that have been replicated, showing variability in different brain regions related to vision and emotional processing between low and high caffeine consumers. That reflects changes in functional connectivity of the brain, along with brain metabolism of caffeine and the levels of the expression of adenosine receptors in the brain. There's a good deal of variability in outcomes in many studies looking at caffeine consumption and cognitive outcomes, and a lot of that variation has been attributed to genetic differences between individuals.

Speaker 1: 2:10

To understand how genetics influence caffeine's effects, let's start with caffeine metabolism. Two key genes, cytochrome P4501A2, also called CYP1A2 for short, and the aryl hydrocarbon receptor, also called ARH, encode enzymes responsible for breaking down caffeine in the liver. The latter actually affects the expression of the former. Depending on your genetic variance, you may fall into one of two categories fast metabolizers or slow metabolizers. Fast metabolizers process caffeine quickly, clearing it from the body very efficiently, while slow metabolizers take longer, resulting in prolonged exposure to the effects of caffeine. Another gene, adenosine receptor A2A, also called ADORA2A, affects how sensitive your brain is to caffeine. Variants in this gene influence adenosine receptor activity, which can either amplify or reduce caffeine's impact. For example, individuals with certain EDORA2A variants may experience heightened anxiety or insomnia after consuming caffeine, while others may feel nothing but enhanced focus. Variations to these three genes, known as single nucleotide polymorphisms, or SNPs for short, that make someone more likely to be a high caffeine consumer due to faster caffeine metabolism, have been shown to be associated with habitual caffeine consumption, which supports the hypothesis that individuals self-regulate when it comes to caffeine. In other words, fast caffeine metabolizers may have more caffeine to avoid symptoms of abstinence or withdrawal. The issue with many studies on caffeine and how it affects cognition is that they focus usually on a single genetic variant related to caffeine metabolism or response. So one or the other.

Speaker 1: 4:10

Well, a newly published study in the Journal of Psychopharmacology explored the interactions between habitual caffeine intake, genetics and cognitive performance across four domains memory, attention, executive function and social cognition. What they found were differences in social cognition between slow and fast metabolizers. This domain involves the ability to recognize and interpret emotions and social cues. That's an essential skill for effective communication and interaction. Obviously, the study found that slow metabolizers who consumed high levels of caffeine performed significantly better on emotion recognition tasks compared to fast metabolizers of caffeine. The researchers hypothesized that prolonged caffeine exposure in slow metabolizers might enhance the brain's ability to process social information by sustaining adenosine receptor blockade and dopamine activity. There were also differences in executive function. This cognitive domain encompasses skills like problem solving, decision making, multitasking and planning. Interestingly, fast metabolizers outperformed slow metabolizers on executive function tasks, but only when consuming moderate amounts of caffeine. High caffeine intake appeared to diminish their performance, thought to be due to overstimulation in this case. Memory and attention scores were also worth noting here. While no significant gene-caffeine interactions were observed in these domains, the study reaffirmed that factors like age and baseline cognitive capacity play a role in determining caffeine's impact on these functions.

Speaker 1: 5:59

Attention, for instance, is closely tied to dopamine signaling, which caffeine can enhance in certain individuals. Why do these genetic variations lead to such distinct outcomes? The answer lies in the biochemical pathways affected by caffeine and its metabolites, for instance adenosine receptor activity. Variants in the adenosine receptor A2A or the ADORA2A gene alter the sensitivity of adenosine receptors, modulating caffeine's ability to improve wakefulness and focus. In sensitive individuals, even small amounts of caffeine can trigger heightened anxiety or restlessness.

Speaker 1: 6:36

In CYP1A2 and the aryl hydrocarbon receptor AHR metabolism, fast metabolizers often consume more caffeine to achieve the same level of alertness as slow metabolizers. This self-regulation may explain why fast metabolizers perform better on tasks like decision-making and problem-solving when consuming moderate caffeine doses. Remember that's moderate intake, as high intake, even in fast metabolizers, seems to hurt performance. Here it's worth noting that high caffeine consumers often report greater daytime sleepiness, which may counteract some of caffeine's cognitive benefits. This is especially relevant for fast metabolizers, who experience rapid, rapid caffeine clearance, potentially leading to withdrawal symptoms that impair performance, which explains why they perform better when keeping a stream of moderate caffeine in their system to keep arousal levels high enough to perform. There are companies out there that provide genetic testing kits to healthcare practitioners to look at the gene variations we're talking about here. One such example is the company Neutrogenomics Incorporated.

Speaker 1: 7:49

If you enjoy caffeine in your routine, here are some practical tips For slow metabolizers. Lower doses of caffeine may suffice to enhance focus and social cognition without triggering side effects like jitteriness or anxiety. If you suspect you're a slow metabolizer, consider spreading smaller doses throughout the day to maintain a steady level of alertness. For fast metabolizers, moderate caffeine, which is approximately 200 to 300 milligrams of caffeine daily, appears most beneficial, particularly for tasks requiring executive function. Avoid consuming caffeine too late in the day to minimize sleep disturbances, but do be aware that typical overnight caffeine abstinence results in substantial elimination of systemic caffeine by early morning. So upon awakening, fast metabolizers have entered the early stages of caffeine withdrawal.

Speaker 1: 8:46

If you're curious about your metabolism, consider a nutrigenetic test or monitor your response to caffeine doses. Do you feel energized after one cup or does it take three? Paying attention to these patterns can guide your caffeine habits. It's certainly not a one-size-fits-all approach. Future research intends to examine how environmental factors like stress or diet, or even gene variants affecting other things that impact cognition, like genetic variants that affect sleep, interact with genetic predispositions to shape caffeine's cognitive effects. Caffeine's impact on cognition is far from straightforward. Your genetic makeup, habitual intake and even the time of day can all influence how your caffeine affects your brain. By understanding these nuances, you can make informed choices about your caffeine consumption to optimize focus, memory and decision making. Thank you for tuning in to Daily Value. If you found this episode enlightening, please share it with someone who's curious about their daily caffeine habits. Stay sharp, stay informed and stay healthy.