SNP Highlight - Caffeine & CYP1A2

85% of Americans consume a caffeinated beverage daily, averaging about 165 mg per day. An 8oz cup of brewed coffee can contain anywhere from 95-165 mg of caffeine. And while coffee is the most common and well-known caffeine contributor, there are many other drinks that contain hidden caffeine. For example, a can of Diet Coke has 46 mg of caffeine, while a Monster Energy drink has 160 mg per can. Drinking all of these different caffeinated drinks can add up and become harder for the body to breakdown, depending on a individual's caffeine metabolism.

Caffeine acts to block adenosine receptors which in turn stimulate the central nervous system. It has many actions on the body, including increasing the need to urinate, increasing the intensity of cardiac muscle contractions, and relaxing smooth muscle. The effects of caffeine are seen within 30-60 minutes and and its effects last in the body for an average of 5 hours, although eating a meal can slow its absorption into the bloodstream. This that have a history of anxiety, heart or liver issues should consider drinking less or avoiding caffeine completely (1-5).

The Science Behind Caffeine

Caffeine is used to treat headaches, improve mental alertness and enhance physical performance. Studies have shown improvements in vigilance and attention. Doses ranging from 40-300 mg can improve cognition, as well as mental alertness due to lack of sleep. It should be noted that the increased cognitive benefits are seen more in those who are tired or who are not caffeine adapted. Additionally, consuming more than 200 mg of caffeine within 1 hour of physical exercise has been shown to improve physical performance. Studies have shown improvement in muscle strength and endurance, high intensity interval training and endurance exercise (5).

Caffeine & cytochrome P450? 

Cytochrome P450 (CYP450) is a group of genes that code for enzymes that make and metabolize endogenous and xenobiotic substances. They are generally found in liver cells, but can be found throughout the body. Currently, there are around 60 types of CYPs that are responsible for metabolizing bile, drugs and toxins in the human body. Certain drugs can induce or inhibit the enzymes, affecting the metabolism of drugs that use the same pathway. CYP1A2 is an enzyme found primarily in the liver that affects the metabolism of substrates such as estradiol (estrogen), propranolol (heart medication), caffeine and antidepressant medications. Smoking and certain cruciferous vegetables such as broccoli are common triggers that can induce the enzyme, which speeds up metabolism, while drugs such as amiodarone (heart medication) and ciprofloxacin (antibiotic) inhibit the enzyme, or slow it down. For example, smoking will induce CYP1A2, which will speed up the metabolism of caffeine. Therefore, caffeine will be metabolized (broken down) faster in a smoker than a non-smoker, which can lead the person to feel that the caffeine did not have much of an effect on their body (7-9). 

I have the results of my client's CYP1A2 test. Now what? 

As of 2010, over 40 haplotypes have been identified, affecting the expression of the gene and its enzyme activity. The wild type (or the most common variant) CYP1A2 polymorphism is CYP1A2*1A. The major allele variant is *1F.

%: more than 3 cups of coffee daily

The *1F variant is well-studied, but is not the only gene that affects caffeine metabolism. Other CYP1A2 variants like *1C and *1K, as well as genes like ADORA, AHR and BDNF play into how long caffeine remains in the body (10-12).

Lifestyle Considerations

It’s important to think about caffeine habits in relationship to genetics. Individuals with the AA genotype who drink 3 or more cups of coffee per day may have the opposite effect of what was intended. Consuming more caffeinated beverages will activate the enzyme, causing them to metabolize their caffeine even faster. These individuals would benefit from drinking no more than 2 cups per day to get the full effects from the caffeine.

Conversely, research has found people with the C allele are slow caffeine metabolizers, meaning it takes their body longer to break down caffeine, which can lead to a stronger response to caffeine. Individuals with this variant should be mindful of drinking their last caffeinated drink in the afternoon. It is possible that the effects will last more than 5 hours, which could make it harder to fall asleep.

In conclusion, knowing your client's genetics can help you gain a better understanding of how your client's behaviors may be affecting their health at an individual level. You will be able to provide an explanation for why they may be able to only drink 1 cup of coffee before noon or drink coffee right up until bed. If they are struggling with focus or sleep quality, taking a look at their caffeine genes in their Health Action Plan will help to guide the creation of an appropriate treatment protocol for the individual. 

Have additional questions? Contact us at info@toolboxgenomics.com

References

1. Mitchell DC, et al. Beverage caffeine intakes in the U.S. Food Chem Toxicol. 2014 Jan; 63:136-42. Accessed at https://www.ncbi.nlm.nih.gov/pubmed/24189158

2. Caffeine content for coffee, tea, soda and more [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2017. Available from: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/caffeine/art-20049372. Accessed May 1, 2018

3. https://www.coca-colaproductfacts.com/en/faq/caffeine/caffeine-in-coke-and-diet-coke/

4. https://www.monsterenergy.com/products/monster-energy

5. Caffeine. Lexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; Accessed May 1,2018.

6. McLellan TM, et al. A review of caffeine’s effects on cognitive, physical and occupational performance. Neurosci Biobehav Rev. 2016 Dec;71:294-312. Accessed at https://www.sciencedirect.com/science/article/pii/S01497634163 00690?via%3Dihub

7. Cytochrome p450 - Genetics Home Reference [Internet]. U.S. National Library of Medicine. National Institutes of Health; Available from: https://ghr.nlm.nih.gov/primer/genefamily/cytochromep450. Accessed May 1, 2018

8. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). "/clinpharm/ddis/clinical-table/" Accessed April 29, 2018

9. Thorn CF, et al. PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenet Genomics. 2012 Jan; 22(1): 73–77. Accessed at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346273/

10. https://www.pharmvar.org/gene/CYP1A2

11. Djordjevic, N., Ghotbi, R., Jankovic, S. et al. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C>A polymorphism. Eur J Clin Pharmacol (2010) 66: 697.

12. Sachse, C., Brockmöller, J., Bauer, S., & Roots, I. (1999). Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. British Journal of Clinical Pharmacology, 47(4), 445–449. Accessed May 1, 2018