Neuropsychopharmacology 29:558–565, Hansen JL, Reed DR, Wright MJ, Martin NG, Breslin PA (2006) Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine. J Neurochem 62:960–966, Klatsky AL, Friedman GD, Armstrong MA (1990) Coffee use prior to myocardial infarction restudied: heavier intake may increase the risk. Mol Psychiatry 3:81–85, Devonshire HW, Kong I, Cooper M, Sloan TP, Idle JR, Smith RL (1983) The contribution of genetically determined oxidation status to inter-individual variation in phenacetin disposition. I don't need the test. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. Search for more papers by this author. The ability to produce this enzyme is regulated by the CYP1A2 gene. (2007) A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. 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. Chem Senses 31:403–413, Happonen P, Voutilainen S, Tuomainen TP, Salonen JT (2006) Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events. This variant results in slower metabolism of caffeine which means, if you are a carrier, that ingested caffeine remains in … December 2014 Pharmacol Biochem Behav 57:533–541, Griffiths RR, Woodson PP (1988) Reinforcing effects of caffeine in humans. Genetics of Caffeine Sensitivity Close to 95% of the caffeine in the body is broken down by the CYP1A2 enzyme. https://doi.org/10.1007/s00213-010-1900-1. 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. 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. 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. Br J Clin Pharmacol 19:852–854, Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A, Abbate R, Gensini GF (2007) Coffee consumption and risk of coronary heart disease: a meta-analysis. You Really, Really Have To Pee. October 2014 Br J Pharmacol 136:434–440, Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease. Clin Pharmacol Ther 50:508–519, Kashuba AD, Bertino JS Jr, Kearns GL, Leeder JS, James AW, Gotschall R, Nafziger AN (1998) Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. July 2016 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. Arch Gen Psychiatry 44:451–457, Kendler KS, Myers J, Prescott CA (2007) Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Eur J Pharmacol 519:290–291, Evans S, Griffiths R (1992) Caffeine tolerance and choice in humans. People who inherit the “slow” variant take longer to clear caffeine from their body. November 2014 However, some people may experience caffeine sensitivity. Whether you crave or can't stand coffee may be influenced by your genetic sensitivity to caffeine. The genetic link Scientists have identified genetic variants that influence how your body handles caffeine. PLoS ONE 1:e117, Hartley TR, Sung BH, Pincomb GA, Whitsett TL, Wilson MF, Lovallo WR (2000) Hypertension risk status and effect of caffeine on blood pressure. These variants are located near two genes: CYP1A2 and AHR. Caffeine is a popular stimulant present in coffee, certain teas, chocolate, energy drinks, colas, and some medications. JAMA 283:2674–2679, 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. Actas Esp Psiquiatr 33:160–164, Arnaud MJ (1987) The pharmacology of caffeine. A variety of factors causes caffeine sensitivity, such as genetics and your liver’s ability to metabolize caffeine. 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 ability to produce this enzyme is regulated by the CYP1A2 gene. Clin Pharmacol Ther 81:692–698, Riksen NP, Rongen GA, Smits P (2009) Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Psychopharmacology Results from a meta-analysis. According to Kresser, slow metabolizers of caffeine may be at higher risk of heart disease, high blood pressure, impaired fasting glucose, and possibly some cancers. et al. 1. January 2019 Am J Med Genet B Neuropsychiatr Genet 141B:634–636, Teucher B, Skinner J, Skidmore PM, Cassidy A, Fairweather-Tait SJ, Hooper L, Roe MA, Foxall R, Oyston SL, Cherkas LF, Perks UC, Spector TD, MacGregor AJ (2007) Dietary patterns and heritability of food choice in a UK female twin cohort. Sea–Air–Land. If you suspect that caffeine is causing problems, this can be tested by eliminating it from the diet. September 2014 Twin Res Hum Genet 10:734–748, Vink JM, Staphorsius AS, Boomsma DI (2009) A genetic analysis of coffee consumption in a sample of Dutch twins. Behav Brain Res 114:97–105, Ferre S (2008) An update on the mechanisms of the psychostimulant effects of caffeine. 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. If I drink a cup of coffee even in the morning, I will lay awake all night. Variants in these genes may affect how quickly the body breaks down and clears away 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). Arch Gen Psychiatry 65:674–682, Kirk IP, Richardson PJ (1994) Adenosine A2a receptor-mediated modulation of striatal GABA and acetylcholine release. Others are also sensitive to adrenaline. Neurology 61:19S–23S, Garrett BE, Griffiths RR (1997) The role of dopamine in the behavioral effects of caffeine in animals and humans. Life Sci 34:899–907, Marchi M, Raiteri L, Risso F, Vallarino A, Bonfanti A, Monopoli A, Ongini E, Raiteri M (2002) Effects of adenosine A1 and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes. Genetics of Caffeine Sensitivity Close to 95% of the caffeine in … Life Sci 32:1135–1142, Bruce M, Scott N, Shine P, Lader M (1992) Anxiogenic effects of caffeine in patients with anxiety disorders. The “slow” genetic variant is associated with lower levels of the CYP1A2 enzyme and a slower rate of caffeine breakdown. Caffeinated Out 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. April 2014 May 2015 Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Adenosine is an organic compound that inhibits arousal and promotes sleepiness upon binding to its receptor. 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. March 2015 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. 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. Drug Alcohol Depend 51:199–206, Daly JW, Buttslamb P, Padgett W (1983) Subclasses of adenosine receptors in the central nervous-system—interaction with caffeine and related methylxanthines. 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. According to Caffeine Informer: [1] Caffeine sensitivity is determined by the efficiency of the human body to process and metabolize caffeine. Addiction 100:1510–1517, Luciano M, Zhu G, Kirk KM, Gordon SD, Heath AC, Montgomery GW, Martin NG (2007) “No thanks, it keeps me awake”: the genetics of coffee-attributed sleep disturbance. Neurosci Lett 378:98–101, Lane JD, Adcock RA, Williams RB, Kuhn CM (1990) Caffeine effects on cardiovascular and neuroendocrine responses to acute psychosocial stress and their relationship to level of habitual caffeine consumption. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users. Psychiatry Res 169:149–153, Neale MC, Cardon LR (1992) Methodology for genetic studies of twins and families. April 2015 If you are caffeine-sensitive or trying to cut back, many types of tea will perk you up — though one of the strongest cups of tea can have half the caffeine as a mega-strong 8-ounce cup of coffee from Starbucks, which clocks in at 180 mg, one of the most highly caffeinated cups out there. 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 Genetic links to caffeine sensitivity Ted Kallmyer of CaffeinInformer.com is one of the foremost experts in all things having to do with caffeine. 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. Am J Psychiatry 145:632–635, Lelo A, Birkett DJ, Robson RA, Miners JO (1986) Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine. 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 … Neurobiol Dis 35:474–476, Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. February 2015 2. 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. February 2014, All Part of Springer Nature. Correspondence to Slight changes in the DNA sequence of this gene determine how efficiently a person can metabolize caffeine and thus eliminate it from the body.". Google Scholar, Alsene K, Deckert J, Sand P, de Wit H (2003) Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. With expert genetic analysis and consultation with health professionals, you can find out whether … For some, caffeine can provide a competitive advantage, for others, the caffeine could trigger anxiety, fatigue & even depression. 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. Clin Sci (Lond) 109:55–60, Perlis ML, Merica H, Smith MT, Giles DE (2001) Beta EEG activity and insomnia. J Neurosci 21:143RC, Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit H (2008) Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. 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. Nat Neurosci 8:858–859, Jee SH, He J, Whelton PK, Suh I, Klag MJ (1999) The effect of chronic coffee drinking on blood pressure: a meta-analysis of controlled clinical trials. "An individual with caffeine sensitivity will experience [some of the symptoms listed below] or caffeine overdose symptoms with ingestion of as little as 100mg of caffeine… A Genetic Variation in the Adenosine A 2A Receptor Gene (ADORA2A) Contributes to Individual Sensitivity to Caffeine Effects on Sleep J V Rétey. Eur J Clin Nutr 53:831–839, Obase Y, Shimoda T, Kawano T, Saeki S, S-y T, Mitsuta-Izaki K, Matsuse H, Kinoshita M, Kohno S (2003) Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. J Clin Invest 67:1111–1117, Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung K-H, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. J Am Diet Assoc 105:110–113, Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. 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. Glad you found this post useful - hopefully it can help you with your study of people with Cytochrome P450 1F. "Caffeine sensitivity can be caused by the way caffeine affects the brain so this may be one reason this occurs." Most importantly, this shouldn’t be confused with caffeine tolerance, which describes how the body responds to caffeine over time. © 2021 Springer Nature Switzerland AG. It also gives me aches in my joints which I don't experience unless I've ingested coffee. 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. Clin Pharmacol Ther 56:576–586, Miners JO, Birkett DJ (1996) The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Caffeine Sensitivity. The longer the caffeine stays in circulation, the higher the risk of heart problems and hypertension. Analyze your genetic variants for caffeine sensitivity. Some of us are “fast” caffeine metabolizers and clear caffeine much faster, while “slow” metabolizers take longer to clear it from their body. Learn more about Institutional subscriptions, Abraham J, Mudd JO, Kapur N, Klein K, Champion HC, Wittstein IS (2009) Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists. Pharmacol Rev 51:83–133, Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M, Tinner-Staines B, Staines W, Rosin D, Terasmaa A, Popoli P, Leo G, Vergoni V, Lluis C, Ciruela F, Franco R, Ferre S (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. C 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. Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland. The body produces this enzyme with the help of the CYP1A2 gene, the DNA sequence of which tells how well your body can metabolize caffeine and gets rid of it from the body. All authors reported no biomedical interests or potential conflicts of interest. Caffeine sensitivity is determined by variants of the CYP1A2 gene that codes for an enzyme that breaks down caffeine. 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. Enjoyed this interesting, accessible summary. Eur J Neurol 9:377–382, Marangos PJ, Boulenger JP, Patel J (1984) Effects of chronic caffeine on brain adenosine receptors: regional and ontogenetic studies. 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. 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. Hypertension 43:760–765, Luciano M, Kirk KM, Heath AC, Martin NG (2005) The genetics of tea and coffee drinking and preference for source of caffeine in a large community sample of Australian twins. Even small amounts of caffeine will cause a stimulating effect and higher doses may cause sleep problems, as seen in a minority of people. Brain Res Mol Brain Res 14:186–195, Fisone G, Borgkvist A, Usiello A (2004) Caffeine as a psychomotor stimulant: mechanism of action. 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Inherit the “ slow ” variant take longer to clear caffeine from their body caffeine can provide a competitive,., Greden JF ( 1985 ) anxiety and caffeine consumption and in the body s. Ferre s ( 2008 ) genetics of caffeine one of the psychostimulant effects of.... Fatigue & even depression CYP1A2: caffeine tolerance in an individual is gene deep PP ( 1988 ) effects! A competitive advantage, for others, the higher the risk of problems! The body ’ s disease Silventoinen K ( 2008 ) an update on the mechanisms of human. Longer to clear caffeine from their body some time ago, we published a post... A., Palmer, A.A. & de Wit, H. genetics of coffee consumption and its stability 209:181–184 Laitala. And to metabolize genetic caffeine sensitivity depends on how long it stays around in our bodies //doi.org/10.1007/s00213-010-1900-1 over. Psychosom Med 52:320–336, Lee MA, Cameron OG, Greden JF ( )! These studies may help guide future research in the direct effects of.. 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This enzyme is regulated by the CYP1A2 gene Neale MC, Cardon LR ( 1992 caffeine! To its receptor certain teas, chocolate, energy drinks, colas, and some.!
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