Recent research shows that coffee drinkers come in two flavors: “fast” metabolizers and “slow” metabolizers. People with a particular gene variant are more vulnerable to it’s effects. The gene in question controls the production of a key enzyme, known as CYP1A2, responsible for metabolizing coffee in the liver. People who inherit the slow version face a greater risk of non-fatal heart attacks at high levels of caffeine intake.
“The association between coffee and myocardial infarction [heart attack] was found only among individuals with the slow CYP1A2 allele [gene variant], which impairs caffeine metabolismm, suggesting that caffeine plays a role in the association,” the authors wrote in the Journal of the American Medical Association (JAMA).
The University of Toronto’s Ahmed El-Sohemy, a co-author of the published study, told the Associated Press that metabolic differences might help to explain why previous studies of caffeine’s cardiovascular effects have proven to be contradictory and inconclusive.*
Unfortunately, at present only an expensive lab test will reveal which variant a given coffee drinker has inherited.
Sources:
--Cornelis, Marilyn, C., et al. “Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction.” Journal of the American Medical Association. 295 10: 1135 March 8, 2006.
--”Coffee May Spell Heart Trouble for Some.” Associated Press. March 7, 2006.
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*Drugs are broken down into their constituent waste products by specific sets of enzymes. A subset of the human population, variously estimated at 3% to 7%, are categorized as “poor metabolizers.” For them, a drug’s recommended dosage is often far too high.
The culprit is a genetic variant that codes for a liver enzyme called cytochrome P450 isoenzyme 2D6, known in shorthand as CYP2D6. Poor metabolizers produce less of this crucial enzyme, which means that drugs are broken down and excreted at a much slower pace. In these people, the recommended dose results in higher drug concentrations. This obviously can make a crucial difference in how a person reacts to the drugs.
About one out of 20 people has a mutation in the 2D6 gene that causes a lack of the enzyme, according to UC-San Francisco biochemist Ira Herskowitz. “Those people are really getting a whopping dose.” In addition, if a person with normal CYP2D6 levels is taking several drugs that are broken down by CYP2D6, then the enzyme’s ability to degrade one drug can greatly inhibit its ability to degrade the others. This increases the possibility of adverse drug interactions, particularly among the elderly, who may already be suffering from liver disease or impaired renal function. Drugs of abuse severely complicate these enzymatic issues, since addicts and alcoholics are not known for volunteering information about their condition to medical or hospital personnel. Poor metabolizers often have little or no reaction to codeine-based medications. Screening tests for CYP2D6 variations are becoming cheaper and more widely available.
Enzyme interactions can work the other way, too. St. John’s Wort, for example, is suspected of activating another drug breakdown enzyme, CPY3A, thereby accelerating, rather than retarding, the destruction of other drugs. The herb can alter the metabolization of Phenobarbital, tamoxifen, oral contraceptives, and antiviral medications. Drugs must be combined with caution, and people need to monitor dosages, because of the tremendous degree of metabolic variation that exists.
“Start low and go slow” is still the best advice.
--The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.
