Caffeine is one of the most widely consumed compounds in the world, used to improve focus, energy, physical performance, and cognitive function. However, in clinical practice, responses vary significantly: some individuals report clear performance and energy benefits, while others experience anxiety, tachycardia, insomnia, or no benefit at all.
This variability is not random. It is strongly influenced by genetics.
Why doesn’t caffeine work the same for everyone?
Caffeine’s effects are not determined solely by the dose consumed, but by how the body recognizes, responds to, and metabolizes this compound.
A key factor involves adenosine receptors, which regulate alertness, fatigue, hormonal response, and exercise performance.
Caffeine works by blocking these receptors, but not everyone has the same genetic mechanism regulating this interaction. Specific genetic variants modulate individual response to caffeine.
The role of genetics in caffeine response
Certain genetic variants influence how the body responds to caffeine, affecting:
Alertness and focus during exercise
Physical performance improvements
Hormonal response to training
Fatigue delay and perceived exertion
Risk of side effects such as anxiety, palpitations, and sleep disturbances
This explains why two individuals consuming the same dose can experience completely different outcomes.
Caffeine, genetics, and physical performance
In performance contexts, caffeine can affect:
Work capacity
Anabolic response to training
Fatigue perception
Recovery
However, individuals with certain genetic variants may experience stronger ergogenic benefits, while others may show minimal or even negative responses, including excessive physiological stress.
This reinforces a key point: caffeine is not universally beneficial.
When caffeine may be detrimental
In clinical practice, signs of poor caffeine tolerance include:
Anxiety or irritability after intake
Worsened sleep quality even at low doses
Tachycardia or a “racing heart” sensation
Reduced performance instead of improvement
In many of these cases, the cause is not excessive intake, but genetic sensitivity.
Clinical application: using genetics to personalize caffeine
Genetic testing enables clinicians to:
Identify patients who benefit from caffeine
Detect those at higher risk of adverse effects
Adjust dose, timing, and usage strategy
Avoid generic approaches that lead to poor outcomes
Instead of asking “what is the ideal caffeine dose?”, the question becomes:
“Is this patient a good candidate for caffeine use?”
Conclusion
Caffeine is a powerful tool, but it is not neutral or universally beneficial. Genetics explains much of the variability in response observed in both clinical and sports settings.
Integrating genetic information into prescription allows clinicians to move beyond trial-and-error toward a more precise, safe, and individualized approach—especially in performance, cognitive focus, and metabolic health contexts.
Scientific reference
Rahimi MR, Semenova EA, John G, Fallah F, Larin AK, Generozov EV, Ahmetov II.
Effect of ADORA2A gene polymorphism and acute caffeine supplementation on hormonal response to resistance exercise: a double-blind, crossover, placebo-controlled study. Nutrients. 2024;16(12):1803. doi:10.3390/nu16121803.
