Coffee, Caffeine , CYP1A2 and rs762551
By Dr. Emily Brown Reeves, PhD, CNS
Caffeine is a psychoactive molecule that boosts energy, creates mental alertness, causes vasoconstriction, and elevates mood. Caffeine is found naturally in coffee, chocolate, and tea, but many common foods and drugs also add synthetic caffeine to enhance the properties of the product. Caffeine is usually ingested in a liquid form and is readily absorbed in the small intestine being both water and lipid soluble.
Caffeine passes the blood brain barrier easily and is also detectable in the cerebrospinal fluid. In both pregnancy and lactation, caffeine ingestion by the mother will affect the neonate via the umbilical cord and breast milk respectively.
Caffeine exerts its psychoactive effects by binding to adenosine the building block of ATP (adenosine triphosphate). In addition to its role in energy metabolism adenosine is a neuromodulator molecule that can control memory, learning and influence sleep. Adenosine modulates these behaviors by activating receptors that modulate neurotransmitter release. To see a video description of this click here.
Caffeine has a long half life of 5-7 hours and is metabolized primarily by the cytochrome P450 enzyme system in the liver. The CYP1A2 gene encodes the major enzyme responsible for caffeine metabolism. The CYP1A2 enzyme also processes hormones (melatonin, estrone, estradiol), drugs (Tylenol, some antipsychotics), and other toxins (exhaust, pollution, charcoaled meat) so that they can be removed from the body. Transcription of this gene (mRNA levels) has been reported to have as much as a 40-fold difference between individuals. This variability is attributable to polymorphisms and environmental induction.
Smoking for example is a very strong environmental inducer that can upregulate this enzyme. Exercise, cruciferous vegetables, and chargrilled meat also have been reported to upregulate CYP1A2 activity while contraceptives and fluoroquinolones downregulate CYP1A2.
A key polymorphism (genetic variant) in CYP1A2 that has been shown to affect its activity is rs762551 or -163C>A. The position rs762551 is usually either an ‘A’ or ‘C’. The ‘A’ allele potentiates the inducibility of CYP1A2 resulting in higher activity following an inducing action such as drinking coffee. This results in faster metabolism of caffeine. Individuals homozygous for ‘A’ at rs762551 usually enjoy caffeine freely.
To read a similar article we recommend SelfDecode’s blog on the CYP1A2 Enzyme.
References
Temple JL, Bernard C, Lipshultz SE, Czachor JD, Westphal JA, Mestre MA. The Safety of Ingested Caffeine: A Comprehensive Review. Front Psychiatry. 2017;8:80
Gunes A, Dahl M-L. Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics. 2008;9(5):625-637. doi:10.2217/14622416.9.5.625
Koonrungsesomboon N, Khatsri R, Wongchompoo P, Teekachunhatean S. The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. Pharmacogenomics J. 2018;18(6):760-768.
My brother suggested I might like this website. He was totally right. This post actually made my day. You cann’t imagine just how much time I had spent for this information! Thanks!