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

by Dr Geoffrey Modest

2 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)

— Dietary intake was assessed through different validated instruments, baseline biomarkers were assessed (albumin, alkaline phosphatase, ALT, AST, GGT, CRP, A1c, HDL, lipoprotein(a))

— analysis was based on the number of cups of coffee drunk daily: 0, <1, 1 to 2, 2 to 3, and >3 cups per day, where a cup was defined as 237 mL

— Mean coffee consumption was 300 mL per day in quartile 2 and 855 per day in quartile 4 for men; 253 for quartile 2 and 684 for quartile for in women

— mean age 50, BMI 25, 23% university educated

— 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

— there was no evidence of heterogeneity by countries, and overall similar trends were found for caffeinated vs decaffeinated coffee, though the association was somewhat more pronounced for decaffeinated

— 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

— for cardiovascular disease mortality (multivariate analysis):

— for women, 22% decrease, HR 0.78 (0.68-0.90), p<0.001 for trend

— for cancer mortality (multivariate analysis):

— 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.

–one advantage of this study is that it covers many different countries where coffee is made in different ways (some older studies have found differences depending on how the coffee was brewed)

–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 for 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​)



–185,855 participants in the MEC (Multiethnic Cohort) prospective population-based cohort study between 1993 and 1996, with evaluation of mortality until 2012, average follow-up of 16.2 years

–this co​hort included African-Americans, Japanese, Native Hawaiians, Latinos and whites

–coffee intake was assessed at baseline

–58,397 people died during 3,195,484 person-years of follow-up



–adjusting for smoking, 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)

​–the trend for increasing coffee consumption and decreasing mortality was highly statistically significant, with p<0.001

–similar trends for caffeinated and decaffeinated coffee, though benefit more pronounced in those drinking caffeinated coffee, and were similar for men and women.

–benefit was found for all of the different race/ethnic groups,  though did not reach significance for Native Hawaiians (there were many fewer Native Hawaiians in the study group)

–inverse relationships (ie benefits) were found in never-smokers, those <55yo, and those without reporting a chronic disease

–and inverse associations were found for deaths from heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease



–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

–For suicides (also found in other studies): not sure what to make of this. Some studies have found that coffee has antidepressant effects, also it turns out that mice in stressful situations given caffeine have fewer stress-induced changes in their brains and behavior, but this doesn’t really answer the question about coffee or especially about decaffeinated coffee in humans (of note, the number of suicides in the first study was pretty small and therefore more likely related to statistical aberration)


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


Here are links to some relevant prior blogs:

–see a Korean study finding that moderate coffee consumption is associated with lower coronary artery calcium scores

— see an analysis of the Nurse’s Health Study and the Health Professionals Follow-up Study, finding decreased all-cause mortality, both in smokers and non-smokers

–see the Molecular Epidemiology of Colorectal Cancer study, finding that there was a dose-response curve with increasing intakes of coffee being associated with lower odds of colorectal cancer

— see the International Agency for Research on Cancer of the World Health Organization study, finding that consuming hot drinks in general (greater than 65°C) was “probably carcinogenic to humans”, but for caffeine, there seems to be decreased incidence of bladder cancer, liver cancer, endometrial cancer and possibly breast cancer, with a comment “overall coffee drinking was evaluated as unclassifiable as to its carcinogenicity to  humans “. So, hot liquids are bad, but caffeine is probably okay-to-good