No More Average Coffee Drinking People
Jacob Schor, ND
August 20, 2007
The premise that, “All men are created Equal” makes sense if you are founding a democracy or establishing a religion. It makes little sense biologically or as an unspoken assumption in medical research.
We have approached medical research seeking answers for the average person, the one we are all, more or less, equal to. This does not always give clear answers. The reason is that people are not the same and an ‘average person' can be the mean between two extremes.
These ruminations are triggered by several articles on coffee consumption and the effect it has on health. I've written in the past on coffee and whether it is a risk or benefit to a person's health. The scientific view on coffee has shifted over time, taking a slow pendulum swing from evil poison to ambrosial panacea.
Early reports that coffee consumption increased blood pressure and increased risk of myocardial infarction are now discounted. Protective effects against liver cancer are now in the headlines. Starbucks locations are multiplying exponentially; who can doubt that coffee is good?
A paper published in the March 2006 issue of JAMA brings all our assumptions into question. Researchers from the University of Toronto asked, what in retrospect seems to be, a reasonable question. We all know that coffee does not affect all people the same. Some people are very sensitive to coffee, a cup in the morning will leave them sleepless all night. Others drink coffee with dinner and at bedtime with no ill effect. This variation is due to genetics. The enzyme that breaks down caffeine is coded for by the CYP1A2 gene. Individuals with one version of this gene are “rapid” caffeine metabolizers. Those who carry another variation are “slow metabolizers.”
In this study, drinking coffee had a very different effect on risk for myocardial infarction depending on whether people were fast of slow metabolizers. For slow metabolizers, drinking coffee increased their risk of having a heart attack. For fast metabolizers, coffee lowered their risk: [i]
Risk of MI and coffee consumption:
Number of cups per day fast metabolizers slow metabolizers
<1 cup 1.00 1.00
1 0.48 1.24
2-3 0.57 1.67
4 0.83 2.60
For people who metabolize coffee quickly due to their genes, drinking a cup of coffee a day, cuts their risk of a heart attack by a little more than half. On the other hand, that same cup of coffee will increase a slow metabolizers risk by about 25%.
There may be as much as a 15-fold difference in rate of caffeine detoxification between the fast and slow metabolizers. The same enzyme responsible for detoxifying caffeine also breaks down many other chemicals, including 20 commonly prescribed drugs.
A May 2007 paper brought this same concern about genetic variations into questions about coffee and breast cancer risk. In women, the BRCA-1 gene mutation increases their risk of developing breast cancer. In these particular women, coffee consumption decreased their risk of developing breast cancer. When these women were segregated by variations of the CYP1A2 gene, the numbers shifted. The basic CYP1A2 genotype did not affect breast cancer risk. However, for women with a particular variation of the gene, those who consumed coffee had a 64% reduction in breast cancer risk. No significant protective effect was seen for other variations of the gene. In this particular genetic sub-group drinking coffee looks very protective against breast cancer. [ii]
We are a long way from understanding all of this in detail. It is starting to look as if randomized controlled studies looking at ‘average' people do not always provide useful data. In the future, we will see more and more studies that shift data along factors of genetic variation. Simple answers to simple questions like, “Is coffee good for me?” may no longer work. Coffee is good for you if you are a fast detoxifier and especially if you are a female with a BRCA-1 mutation and a specific CYP1A2 variant. If you are a slow detoxifier, coffee may increase your risk of a heart attack. There is no longer an average person nor a simple answer.
Past Newsletters on Coffee:
[i] JAMA. 2006 Mar 8;295(10):1135-41.
JAMA. 2006 Aug 16;296(7):764-5; author reply 765-6.
Coffee, CYP1A2 genotype, and risk of myocardial infarction.
Cornelis MC , El-Sohemy A , Kabagambe EK , Campos H .
Department of Nutritional Sciences, University of Toronto , Toronto , Ontario , Canada .
CONTEXT: The association between coffee intake and risk of myocardial infarction (MI) remains controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. OBJECTIVE: To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI. DESIGN, SETTING, AND PARTICIPANTS: Cases (n = 2014) with a first acute nonfatal MI and population-based controls (n = 2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence, were genotyped by restriction fragment-length polymorphism polymerase chain reaction. A food frequency questionnaire was used to assess the intake of caffeinated coffee. MAIN OUTCOME MEASURE: Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional logistic regression. RESULTS: Fifty-five percent of cases (n = 1114) and 54% of controls (n = 1082) were carriers of the slow *1F allele. For carriers of the slow *1F allele, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of nonfatal MI associated with consuming less than 1, 1, 2 to 3, and 4 or more cups of coffee per day were 1.00 (reference), 0.99 (0.69-1.44), 1.36 (1.01-1.83), and 1.64 (1.14-2.34), respectively. Corresponding ORs (95% CIs) for individuals with the rapid *1A/*1A genotype were 1.00, 0.75 (0.51-1.12), 0.78 (0.56-1.09), and 0.99 (0.66-1.48) (P = .04 for gene x coffee interaction). For individuals younger than the median age of 59 years, the ORs (95% CIs) associated with consuming less than 1, 1, 2 to 3, or 4 or more cups of coffee per day were 1.00, 1.24 (0.71-2.18), 1.67 (1.08-2.60), and 2.33 (1.39-3.89), respectively, among carriers of the *1F allele. The corresponding ORs (95% CIs) for those with the *1A/*1A genotype were 1.00, 0.48 (0.26-0.87), 0.57 (0.35-0.95), and 0.83 (0.46-1.51). CONCLUSION: Intake of coffee was associated with an increased risk of nonfatal MI only among individuals with slow caffeine metabolism, suggesting that caffeine plays a role in this association.
PMID: 16522833 [PubMed - indexed for MEDLINE]
[ii] Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):912-6.
The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers.
Kotsopoulos J , Ghadirian P , El-Sohemy A , Lynch HT , Snyder C , Daly M , Domchek S , Randall S , Karlan B , Zhang P , Zhang S , Sun P , Narod SA .
Centre for Research in Women's Health, Women's College Hospital , University of Toronto , Canada .
We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations.
PMID: 17507615 [PubMed - in process]