A prospective cohort study of nearly 500,000 people in the United Kingdom found that drinking 1 to 8 or more cups of coffee per day was inversely associated with all-cause mortality. The inverse association held for both ground and instant coffee, as well as decaffeinated coffee.

“There has been concern about the health effects of heavy coffee drinking [>5 cups per day], particularly in participants with common genetic polymorphisms that affect caffeine metabolism,” said study authors led by Erikka Loftfield, PhD, MPH, a postdoctoral fellow at the National Cancer Institute in Rockville, Maryland. “These results provide further evidence that coffee drinking can be part of a healthy diet and may provide reassurance to those who drink coffee and enjoy it.”

Researchers accessed genetic data for 403,816 of the 498,134 study participants to create 2 genetic “caffeine metabolism” scores (CMS G ) by “adding the number of alleles of single base changes, or single nucleotide polymorphisms (SNPs), previously associated with blood caffeine metabolite levels, and the map near genes with plausible roles in caffeine metabolism.”

The scores were calculated using 2 or 4 known caffeine-related SNPs. The CMS G2 scores were calibrated to range from 0 to 4 and the CMS G4 scores from 0 to 8, with higher scores indicating faster caffeine metabolism.

Over the 10 years of follow up (median, 7 years) the study found that participants with lower CMS G scores had similar associations between coffee drinking levels and mortality as participants with higher scores, “indicating no modification of the association between coffee drinking and all-cause mortality by these common polymorphisms related to caffeine metabolism.”

With non-coffee drinkers as a reference group, hazard ratios for coffee intake and all-cause mortality generally decreased with increasing coffee intake:

Less than 1 cup: 0.94 (95% CI, 0.88-1.01)

1 cup: 0.92 (95% CI, 0.87-0.97)

2-3 cups: 0.88 (95% CI, 0.84-0.93)

4-5 cups: 0.88 (95% CI, 0.83-0.93)

6-7 cups: 0.84 (95% CI, 0.77-0.92)

8 or more cups: 0.86 (95% CI, 0.77-0.95)

Additionally, the study found that cancer, cardiovascular disease, and respiratory disease accounted for approximately 8294 (58%), 2833 (20%), and 553 (4%) deaths in the cohort, respectively. The authors noted inverse associations for coffee drinking with cancer and cardiovascular diseases of all kinds. There were potential, but not statistically significant, inverse associations for stroke, colorectal cancer, and female breast cancer.

An interesting result was that the consumption of each type of coffee—ground, instant, and decaffeinated—was inversely associated with all-cause mortality, with ground coffee showing a stronger association.

The authors noted that the stronger association between ground coffee and all-cause mortality might be explained by confounding factors, such as education level. They found that participants without a college degree more commonly drank instant coffee compared to college graduates. “Alternatively,” they suggested, “instant coffees have been shown to have lower amounts of bioactive compounds, including polyphenols, than ground coffees, which may have an effect on observed associations.”

Mechanisms to explain the protective effect of coffee consumption include reduced inflammation, improved insulin sensitivity, and effects on liver enzyme levels and endothelial function, according to the study. The authors called for future studies with more detailed data collection on coffee type and preparation to provide further insights.

The study, “Association of Coffee Drinking With Mortality by Genetic Variation in Caffeine Metabolism,” was published in JAMA Internal Medicine.