Department of Psychiatry & Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Ave, MC 3077, Chicago, IL, 60637, USA, Amy Yang, Abraham A. Palmer & Harriet de Wit, Department of Human Genetics, The University of Chicago, Chicago, IL, USA, You can also search for this author in Clin Sci (Lond) 109:55–60, Perlis ML, Merica H, Smith MT, Giles DE (2001) Beta EEG activity and insomnia. Arch Gen Psychiatry 42:233–243, Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD (2002) Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Drug Alcohol Depend 57:69–78, Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, de Wit H (2005) Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. These variants are located near two genes: CYP1A2 and AHR. J Neural Transm 108:837–848, Zahniser NR, Simosky JK, Mayfield RD, Negri CA, Hanania T, Larson GA, Kelly MA, Grandy DK, Rubinstein M, Low MJ, Fredholm BB (2000) Functional uncoupling of adenosine A2A receptors and reduced response to caffeine in mice lacking dopamine D2 receptors. Neurosci Lett 209:181–184, Laitala VS, Kaprio J, Silventoinen K (2008) Genetics of coffee consumption and its stability. Nutr Metab Cardiovasc Dis 17:209–223, Swan GE, Carmelli D, Cardon LR (1996) The consumption of tobacco, alcohol, and coffee in Caucasian male twins: a multivariate genetic analysis. Recipes With Caffeine Genetic testing has revealed three general categories of caffeine sensitivity related to our genetic makeup: Hypersensitivity to caffeine : These people have very low CYP1A2 activity. Am J Epidemiol 132:479–488, Kuribara H (1994) Modification by caffeine of the sensitization to methamphetamine and cocaine in terms of ambulation in mice. Am J Dis Child 113:81–82, Shi D, Nikodijević O, Jacobson KA, Daly JW (1993) Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Sea–Air–Land. February 2015 et al. Ann Neurol 63:295–302, Lieberman HR, Wurtman RJ, Emde GG, Roberts C, Coviella ILG (1987) The effects of low doses of caffeine on human performance and mood. Genetic Link to Caffeine Sensitivity Caffeine is metabolized by the liver using the enzyme CYP1A2. If you are a slower metabolizer, you will feel the effects of caffeine for a longer time. People who inherit the “slow” variant take longer to clear caffeine from their body. J Neurosci 20:5949–5957. Independent replication is essential for establishing a credible genotype-phenotype association. Am J Clin Nutr 83:1039–1046, Arias Horcajadas F, Sánchez Romero S, Padìn Calo J, Fernández-Rojo S, Fernández Martìn G (2005) Psychoactive drugs use in patients with panic disorder. April 2016 Andrew Zaeh for Bustle. Psychiatry Res 15:211–217, Lee M, Flegel P, Greden J, Cameron O (1988) Anxiogenic effects of caffeine on panic and depressed patients. As he describes in his Caffeine Sensitivity article (see link below): " Caffeine is metabolized in the liver using the enzyme CYP1A2. Prog Drug Res 31:273–313, Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Caffeine sensitivity depends on how long it stays around in our bodies. The longer caffeine stays in the circulation, the higher the risk of a heart attack or high blood pressure (hypertension). This research was supported by NIDA (DA021336 and DA02812). J Neurosci 26:2080–2087, Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. Clin Pharmacol Ther 63:540–551, Kawachi I, Colditz GA, Stone CB (1994) Does coffee drinking increase the risk of coronary heart disease? JAMA 295:1135–1141, Cornelis MC, El-Sohemy A, Campos H (2007) Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Neuropsychopharmacology 33:2791–2800, Ciruela F, Casado V, Rodrigues RJ, Lujan R, Burgueno J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortes A, Canela EI, Lopez-Gimenez JF, Milligan G, Lluis C, Cunha RA, Ferre S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. If I drink a cup of coffee even in the morning, I will lay awake all night. Pharmacol Ther 121:185–191, Robertson D, Wade D, Workman R, Woosley RL, Oates JA (1981) Tolerance to the humoral and hemodynamic effects of caffeine in man. Immediate online access to all issues from 2019. Please Subscribe for 3x Videos Per Week + Live Broadcasts https://www.youtube.com/user/TheTdelauer?sub_confirmation=1 To learn more, visit … Enjoyed this interesting, accessible summary. January 2015 I don't need the test. Psychopharmacology (Berl) 179:813–825, Hettema JM, Corey LA, Kendler KS (1999) A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins. Regular sensitivity to caffeine Ann Epidemiol 15:460–466, Gunes A, Dahl ML (2008) Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Thats because while coffee is a readily available source of caffeine, its also a common culprit for unwanted side effects that go beyond the jitters. Cell Mol Neurobiol 3:69–80, Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, Maier W, Beckmann H, Propping P (1998) Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Am J Cardiol 95:1389–1392, Fenu S, Cauli O, Morelli M (2000) Cross-sensitization between the motor activating effects of bromocriptine and caffeine: role of adenosine A2A receptors. J Exp Anal Behav 57:91–107, Smits P, Thien T, Van ’t Laar A (1985) The cardiovascular effects of regular and decaffeinated coffee. The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 +/- 3.1 years), including 62 monozygotic and 131 dizygotic twin pa … July 2014 Subscription will auto renew annually. Genetics of Caffeine Sensitivity Close to 95% of the caffeine in the body is broken down by the CYP1A2 enzyme. Eur J Neurosci 10:1826–1834, Migliardi JR, Armellino JJ, Friedman M, Gillings DB, Beaver WT (1994) Caffeine as an analgesic adjuvant in tension headache. M Adam. Acta Genet Med Gemellol (Roma) 39:91–98, Carter AJ, O’Connor WT, Carter MJ, Ungerstedt U (1995) Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors. https://doi.org/10.1007/s00213-010-1900-1, DOI: https://doi.org/10.1007/s00213-010-1900-1, Over 10 million scientific documents at your fingertips, Not logged in October 2014 Neurobiol Dis 35:474–476, Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Psychopharmacology 92:308–312, Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R (2002) Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Ann Neurol 50:56–63, Bchir F, Dogui M, Ben Fradj R, Arnaud MJ, Saguem S (2006) Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects. A Genetic Variation in the Adenosine A 2A Receptor Gene (ADORA2A) Contributes to Individual Sensitivity to Caffeine Effects on Sleep J V Rétey. There are two common genetic variants of this enzyme – a “fast” metabolizer variant and a “slow” metabolizer variant. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. Br J Clin Pharmacol 22:177–182, LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM (2008) Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Caffeine sensitivity depends on how long it stays around in our bodies. DNA the key to caffeine sensitivity SCIENCE now has the answer to whether you can enjoy that espresso after dinner — or whether you should steer clear of having energy drinks. J Neurochem 105:1067–1079, Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Addict Behav 19:229–256, Tan EK, Lu ZY, Fook-Chong SMC, Tan E, Shen H, Chua E, Yih Y, Teo YY, Zhao Y (2006) Exploring an interaction of adenosine A2A receptor variability with coffee and tea intake in Parkinson’s disease. However, some people may experience caffeine sensitivity. Based on these genetic factors, Dr Langer has proposed three descriptive levels of overall caffeine sensitivity: High sensitivity to caffeine; Slow-metabolism in the liver and high binding in the central nervous system. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine. Hormone imbalances might be a sign that you don’t process caffeine efficiently. Caffeine is a popular stimulant present in coffee, certain teas, chocolate, energy drinks, colas, and some medications. How caffeine works. 1. This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers. "Caffeine sensitivity can be caused by the way caffeine affects the brain so this may be one reason this occurs." February 2014, All Remember that caffeine sensitivity is influenced by genetics; it isn’t the same as caffeine tolerance, which is a decreased response to caffeine from regular use. June 2015 Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. December 2014 Search for more papers by this author. You Really, Really Have To Pee. Arch Gen Psychiatry 65:674–682, Kirk IP, Richardson PJ (1994) Adenosine A2a receptor-mediated modulation of striatal GABA and acetylcholine release. Hypertension 33:647–652, Kalow W, Tang BK (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Am J Psychiatry 156:223–228, Kendler KS, Heath AC, Martin NG, Eaves LJ (1987) Symptoms of anxiety and symptoms of depression: same genes, different environments? C Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. Glad you found this post useful - hopefully it can help you with your study of people with Cytochrome P450 1F. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine. Br J Clin Pharmacol 16:157–166, Dhaenens CM, Burnouf S, Simonin C, Van Brussel E, Duhamel A, Defebvre L, Duru C, Vuillaume I, Cazeneuve C, Charles P, Maison P, Debruxelles S, Verny C, Gervais H, Azulay JP, Tranchant C, Bachoud-Levi AC, Durr A, Buee L, Krystkowiak P, Sablonniere B, Blum D (2009) A genetic variation in the ADORA2A gene modifies age at onset in Huntington’s disease. Cell Mol Life Sci 61:857–872, Frary CD, Johnson RK, Wang MQ (2005) Food sources and intakes of caffeine in the diets of persons in the United States. Psychopharmacology After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end. Caffeine Problem #3: If you struggle with hormone imbalances (and if you’re reading this right now, you or someone you love probably does), it can be sign that your body has a hard time metabolizing caffeine. Yang, A., Palmer, A.A. & de Wit, H. Genetics of caffeine consumption and responses to caffeine. They have a strong response to even small amounts of caffeine, and will commonly experience jitters and insomnia. But it turns out there might also be a genetic component. Cell Mol Neurobiol 13:247–261, Silverman K, Griffiths RR (1992) Low-dose caffeine discrimination and self-reported mood effects in normal volunteers. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Psychosom Med 52:320–336, Lee MA, Cameron OG, Greden JF (1985) Anxiety and caffeine consumption in people with anxiety disorders. Gen Pharmacol 27:245–249, Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. We have all heard of co-workers who drink 6 cups of coffee, the recreational drink for nearly 60% of Americans, every day, and friends who guzzle a cup an hour before bedtime. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22-28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic … If you suspect that caffeine is causing problems, this can be tested by eliminating it from the diet. According to Caffeine Informer:  Caffeine sensitivity is determined by the efficiency of the human body to process and metabolize caffeine. Tax calculation will be finalised during checkout. We have an enormous amount of genetic information at our fingertips. Curr Pharm Des 14:1500–1511, Rasmussen BB, Brix TH, Kyvik KO, Brøsen K (2002) The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. J Stud Alcohol 58:182–190, Swanson JA, Lee JW, Hopp JW (1994) Caffeine and nicotine: a review of their joint use and possible interactive effects in tobacco withdrawal. Am J Med Genet B Neuropsychiatr Genet 139B:42–44, Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users. Arch Gen Psychiatry 49:867–869, Carmelli D, Swan GE, Robinette D, Fabsitz RR (1990) Heritability of substance use in the NAS-NRC Twin Registry. The longer the caffeine stays in circulation, the higher the risk of heart problems and hypertension. Life Sci 32:1135–1142, Bruce M, Scott N, Shine P, Lader M (1992) Anxiogenic effects of caffeine in patients with anxiety disorders. Addiction 103:2054–2061, Lam P, Hong CJ, Tsai SJ (2005) Association study of A2a adenosine receptor genetic polymorphism in panic disorder. The ability to produce this enzyme is regulated by the CYP1A2 gene. Some time ago, we published a short post about the possibility of allergic reactions to caffeine. Caffeine sensitivity these studies may help guide future research in the circulation, higher. Fast metabolizers because they inherited two copies of the human body to process and metabolize caffeine on. 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