Caffeine is the world’s most widely consumed psychoactive substance, found in coffee, tea, chocolate, some energy drinks, and medications. It enhances alertness and focus, making it a staple in many daily routines. However, not everyone responds to caffeine in the same way. This variance can largely be attributed to genetic differences, specifically involving the CYP1A2 and ADORA2A genes. This blog explores caffeine’s global presence, its metabolism, and the impact of genetics on individual responses to caffeine.


What is Caffeine?

Caffeine is a stimulant that acts on the central nervous system to prevent tiredness and improve concentration. It’s naturally present in several plants and is consumed worldwide, predominantly through beverages like coffee and tea. Global consumption figures highlight the extensive use of caffeine, with an estimated two billion cups of coffee consumed daily. This underscores caffeine’s integral role in various cultures and societies.


The Genetic Basis of Caffeine Metabolism

Individual differences in caffeine sensitivity and metabolism can be traced back to genetics. The CYP1A2 and ADORA2A genes are particularly influential in determining how the body processes and responds to caffeine.


CYP1A2 Gene and Caffeine Metabolism

The CYP1A2 gene codes for an enzyme that metabolises about 95% of ingested caffeine. Genetic variations can classify individuals as either fast or slow metabolisers. Fast metabolisers break down caffeine quickly, reducing its duration in the body and lessening the risk of negative health effects. Conversely, slow metabolisers process caffeine at a slower rate, leading to prolonged exposure and potentially increasing the risk of conditions such as hypertension and heart disease with high levels of caffeine consumption.

Studies have highlighted the importance of the CYP1A2 gene in caffeine metabolism. For instance, research published in the “Journal of the American Medical Association” found that individuals with the slow-metabolising variant of the CYP1A2 gene who consumed large amounts of coffee (more than 4 cups per day) had a higher risk of heart disease compared to those with the fast-metabolizing variant.


ADORA2A Gene and the Effects of Caffeine

While CYP1A2 affects the metabolism of caffeine, the ADORA2A gene influences an individual’s sensitivity to the stimulant’s effects. Variations in this gene can affect how a person experiences caffeine, impacting aspects like sleep and anxiety. Some people with specific ADORA2A gene variants may experience increased anxiety and difficulty sleeping after consuming caffeine.


Findings from our systematic review

Results highlight the significant role of genetic variability in the relationship between caffeine and cardiometabolic health outcomes. This review explored how genetic differences, particularly in genes like CYP1A2 and ADORA2A, influence our body’s response to caffeine. This could have important implications for personalised nutrition strategies. 


Key insights: 

  • Genetic Variability in Caffeine Metabolism: The CYP1A2 rs762551 gene variant is linked to how caffeine affects glucose levels, especially when consumed with carbohydrates.
  • Caffeine, Hypertension, and Genetics: The same CYP1A2 rs762551 variant also influences the relationship between coffee consumption and hypertension.
  • Blood Pressure Regulation: The ADORA2A rs5751876 and ADRA2B I gene variants are important in moderating how caffeine affects blood pressure.
  • Mixed Findings on Cardiovascular Disease: Research shows mixed results regarding the impact of genetic variations, like CYP1A2, COMT, ADORA, and TRIB1, on the relationship between caffeine and cardiovascular diseases.
  • Implications for Personalised Nutrition: Understanding these genetic interactions can lead to tailored advice on caffeine consumption for optimising individual cardiometabolic health.


Practical Implications

The knowledge of how genetics affects caffeine metabolism and sensitivity has practical applications for personalised nutrition and health. Genetic testing can reveal an individual’s CYP1A2 and ADORA2A gene variants, providing a basis for informed decisions on caffeine intake. This approach allows for the optimisation of caffeine’s benefits while minimising its risks, tailoring consumption to suit individual genetic profiles.



The interaction between genetics and caffeine highlights the complexity of dietary influences and the importance of considering individual genetic makeup when making dietary choices. The study of genes like CYP1A2 and ADORA2A illustrates the critical role genetics play in how we respond to caffeine. As genetic testing becomes more accessible, it offers a pathway to personalised nutrition strategies, enabling individuals to align their caffeine consumption with their genetic predispositions.


📖 For a deeper dive into the systematic review click here: