Why does coffee affect me more than others?

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Dr J W Langer, medical doctor, lecturer and science journalist

“Why does coffee affect me more than others?” is a commonly-asked question. The short answer to the question is that research has shown that, if a group of people drink the same standardised amount of coffee, their reactions are determined by their genetic make-up, which defines to what degree a given amount of caffeine will affect the individual1. Some will metabolise caffeine quickly, while others will metabolise it more slowly; some will show greater sensitivity to the stimulating effects of caffeine, while others needs higher amounts to feel an effect1.

In my report, which was authored for ISIC, I explored the current research on genetic variability and individual responses to caffeine as well as stressing the importance of taking individual responses into consideration when advising patients and consumers.

Coffee is one of the world’s most popular and widely consumed natural stimulants in daily life. A typical cup of coffee contains 75-100mg of caffeine2. Caffeine does not accumulate in our body, but is broken down in the liver. The liver enzymes responsible for metabolising caffeine are called cytochrome P450 enzymes. One of these is a key enzyme called CYP1A2, which is responsible for inactivating 95% of all ingested caffeine. The ability to produce this enzyme is coded for by the CYP1A2-gene – different people have different versions of this gene, and these genetic variations determines how active the CYP1A2-enzyme is in each person. This polymorphism divides people into one of two groups1,3,4:

  • Fast-metabolisers metabolise caffeine quickly. The stimulating effects of caffeine in the body are short in duration. A fast-metaboliser may drink multiple cups of coffee a day
  • Slow-metabolisers metabolise caffeine more slowly, so caffeine will be present in the body and brain for a longer period of time. The physiological effects of caffeine will generally last longer and be more pronounced

In my view, it makes sense to propose three descriptive levels of overall caffeine sensitivity depending on both the genetic variability in liver metabolism and central nervous system:

  • High sensitivity to caffeine – Slow-metabolism in the liver and high binding in the central nervous system. Even small amounts of caffeine will cause a stimulating effect and higher doses may cause sleep problems, as seen in a minority of people
  • Regular sensitivity to caffeine – The balance between caffeine inactivation in the liver and binding in the central nervous system means that the individual can typically drink 2–5 cups of coffee during the day but without adverse reactions or sleep disturbances. Caffeine is normally not recommended in the evening, but individual differences prevail, as seen in most people.
  • Low sensitivity to caffeine – Fast-metabolisers of caffeine. Higher intakes can be consumed, (although healthcare professionals should advise that they still stay within the EFSA guidelines of no more than 5 cups of coffee per day13). Coffee drinking before bedtime does not typically disturb sleep.

Generally speaking, most individuals tend to consume the amount of caffeine that they feel comfortable with. This can be considered a sort of self-regulating mechanism rooted in the individual’s genetic make-up and driven by their own experiences and reactions to caffeine. Because individuals respond differently to caffeine depending on a number of factors, individual advice regarding coffee and caffeine intake is the most appropriate cause of action. Those with particular queries should seek medical advice.

The research into the role of genetics in habitual caffeine intake and its physiological effects is still in its infancy. There is a lot more to be learned and further research into caffeine could categorise populations further by gene types and investigate what this could mean for various physiological functions during caffeine consumption.

References

  1. Nehlig A. (2018) Inter-individual differences in caffeine metabolism and factors driving caffeine consumption. Pharmacol Rev. 70(2):384–41.
  2. Heckman M.A. et al. (2010) Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci, 75:R77–87.
  3. 7 Sachse C. et al. (1999) Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol, 47(4):445–9.
  4. 8 Denden S. et al (2016) Gender and ethnicity modify the association between the CYP1A2 rs 762551 polymorphism and habitual coffee intake: evidence from a meta-analysis. Genet Mol Res, 15(2).

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