Coffee Drinking, Genetic Variation, and Mortality

July 07, 2018 – A very recent paper by Loftfield E. et al., published online in JAMA Intern. Med. on July 02, looked at the association of coffee drinking with mortality by genetic variation in caffeine metabolism. In contrast to the often prevalent feeling in the general population that coffee drinking may be unhealthy, the study found that coffee drinking was inversely associated with mortality, including among those drinking 8 or more cups per day and those with genetic polymorphisms indicating slower or faster caffeine metabolism. These findings suggest the importance of noncaffeine constituents in the coffee-mortality association and provide further reassurance that coffee drinking can be a part of a healthy diet and lifestyle. This certainly is very good news for many of us, and as heavy coffee drinkers we may hope for a long life.

This was a large prospective cohort study of a half million people (whose records were selected from the UK Biobank) revealing the inverse associations for coffee drinking with mortality, including participants drinking 1 up to 8 or more cups per day. No differences were observed in analyses that were stratified by genetic polymorphisms affecting caffeine metabolism.

Prospective cohorts in North America, Europe, and Asia show consistent inverse associations between coffee drinking and mortality, including deaths from cardiovascular disease and some cancers. However, concerns about coffee, particularly among people with common genetic polymorphisms affecting caffeine metabolism and among those drinking more than 5 cups per day, remained and have now been further elucidated. Among other parameters, the study investigated potential effect modification by caffeine metabolism, defined by a genetic score of previously identified polymorphisms in the AHR, CYP1A2, CYP2A6, and POR genes that have an effect on caffeine metabolism. Of the 502’ 641 participants who consented with baseline data  those who were not pregnant and had complete data on coffee intake and smoking status (n = 498’ 134) were included.

Overall, in the study, scientifically seen, the data are very impressive and show that coffee drinking was inversely associated with all-cause mortality. Using non–coffee drinkers as the reference group, HRs for drinking less than 1, 1, 2 to 3, 4 to 5, 6 to 7, and 8 or more cups per day were 0.94 (95% CI, 0.88-1.01), 0.92 (95% CI, 0.87-0.97), 0.88 (95% CI, 0.84-0.93), 0.88 (95% CI, 0.83-0.93), 0.84 (95% CI, 0.77-0.92), and 0.86 (95% CI, 0.77-0.95), respectively. Similar associations were observed for instant, ground, and decaffeinated coffee, across common causes of death, and regardless of genetic caffeine metabolism score. For example, the HRs for 6 or more cups per day ranged from 0.70 (95% CI, 0.53-0.94) to 0.92 (95% CI, 0.78-1.10), with no evidence of effect modification across strata of caffeine metabolism score (P = .17 for heterogeneity).

In conclusion, we may well continue to enjoy a cup of coffee (or even quite many of them) a day without worrying about a shortening of your life span, or,  more precisely, the risk of mortality from any cause.  It seems that in real life, there exist much more important traits we may have to worry about than coffee and caffeine. It also seems that our personal genetic outfit with respect of our body’s handling of coffee and caffeine has not a major or even any impact at all.

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About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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