Primary Care Corner with Geoffrey Modest MD: Coffee and decreased mortality

by Dr Geoffrey Modest

Two articles just came out finding that coffee drinkers had decreased all-cause mortality. One study was from 10 European countries (see doi:10.7326/M16-2945).


521,333 people enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition) from 10 European countries, followed 16.4 years. 41,693 deaths occurred (18,003 were from cancer, 9106 were from circulatory diseases, 2380 were from cerebrovascular diseases, 3536 from ischemic heart disease, 1213 from digestive disease, 1589 respiratory, 1571 external causes, and 418 from suicide). The analysis was based on the number of cups of coffee drunk daily:

There were significant increases in coffee consumption as smoking increased, less physical activity by men but increasing activity by women increased consumption of red and processed meats and fewer fruits and vegetables and alcohol consumption


Compared with coffee non-consumers, those in the highest quartile of consumption had significantly lower all-cause mortality by multivariate analysis:

Men, 12% decrease, HR 0.88 (0.82-0.95), p<0.001 for trend, and lowest incidence was in quartile 3, 16% decrease

Women, 7% decrease, HR 0.93 (0.87-0.98), p=0.009 for trend, and lowest incidence in quartiles 2 and 3, 10% decrease

For digestive disease mortality (one-third of which was from liver disease, and the results were largely from the mortality benefit from liver disease, including from cirrhosis), (multivariate analysis):men, 59% decrease, HR 0.41 (0.32-0.54), p<0.001 for trend  women, 40% decrease HR 0.60 (0.46-0.78), p<0.001 for trend

No  statistically significant difference in overall cancer incidence in men, though in general lower coffee consumptions seem to be somewhat better

Statistically significant inverse association (ie benefit) between medium to low coffee consumption and lung cancer mortality in men, and liver cancer mortality and men and women. No difference in respiratory disease mortality

For women, 31% increase In ovarian cancer, HR 1.31 (1.07-1.61), p=0.015 for trend

Higher coffee consumption also associated with lower serum alkaline phosphatase, ALT, AST, GGT. And in women, lower CRP, lipoprotein (a), and A1c levels



2.25 billion cups of coffee are consumed worldwide daily. Several US studies (see prior blogs listed at the end) all suggested decreases in all-cause mortality with coffee consumption, though large studies have not been done in the European population.

Overall, reviewing the breakdown of their data, moderate coffee consumption seemed to have the most significant benefit

Probably the most important confounder in this study was the association between coffee consumption and smoking. Controlling for smoking showed some strengthening of the association between coffee drinking and the reduced risk of death. Coffee consumption was also associated with reduced risk of all-cause mortality among ever-smokers as well as other subgroups at higher risk. And limiting the analysis to never-smokers also demonstrated an inverse relationship with cancer, circulatory, digestive, and respiratory diseases.

This was still an observational study, so it is difficult to assess causality given the possibility of unexpected/unmeasured confounders. The results were similar when the analysis was limited to those reporting “excellent” or “good” health, probably making reverse causality less likely, where sicker people more likely to die might drink less coffee.

And, a US study found a lower risk of death in non-white coffee consumers (see doi:10.7326/M16-2472 )

Details:185,855 participants in the MEC (Multiethnic Cohort) prospective population-based cohort study between 1993 and 1996, with evaluation of mortality until 2012, an average follow-up of 16.2 years. This cohort included African-Americans, Japanese, Native Hawaiians, Latinos and whites. 58,397 people died during 3,195,484 person-years of follow-up


Adjusting for smoking, the number of cigarettes smoked, age, sex, BMI, education, physical activity, alcohol consumption, total energy intake, energy  from fat, and pre-existing illnesses, compared to non-drinkers:

1 cup coffee/day was associated with 12% decreased total mortality, HR 0.88 (0.85-0.91); 2-3 cups coffee/day was associated with 18% decreased total mortality, HR 0.82 (0.79-0.86); 3 cups coffee/day was associated with 18% decreased total mortality, HR 0.82 (0.78-0.87)


–these results were similar to the findings in the PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening trial) finding an 18% reduction in coffee drinkers, and the National Institutes of Health-AARP Diet and Health Study, finding a 10% reduction in men and 13% in women, though these studies were largely in white populations

This study was limited by the assessment of coffee consumption since it was self-reported and only assessed at baseline

–Why does this relationship make sense? it is not just the caffeine since there were pretty similar benefits to caffeinated and decaffeinated coffee

–For cardiovascular disease: chlorogenic acid, lignans, quinides, trigonelline, and magnesium in coffee reduce insulin resistance and systemic inflammation. And, the improvement in inflammatory markers in the above study supports the finding of cardiovascular benefit (and also lower risk of diabetes in some studies)

–For hepatic disease (one of the strongest findings above): there is experimental evidence that caffeine has antifibrotic effects on hepatocytes, and also reduces fat accumulation, oxidative stress, and liver inflammation in mice

–For neurological diseases (other studies have also found coffee consumption was associated with lower risk of Parkinson’s): for MPTP-induced Parkinson’s, there is loss of striatal dopamine transporter binding sites, and dopaminergic neurons, which is attenuated by caffeine

Overall these studies add to many others finding health benefits to coffee consumption. which is really good news for many of us.


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