Drinking more coffee may reduce the risk for symptomatic gallstone disease, according to a study published in the Journal of Internal Medicine.

Researchers also found genetic evidence to support a causal relationship between drinking caffeinated products and symptomatic gallstone disease.

“Because of the current global epidemic of obesity and metabolic syndrome, the incidence of gallstone disease is likely to increase in the coming years, and a potential protective effect of coffee intake on gallstone disease could have considerable clinical and public health relevance,” A.T. Nordestgaard,of the department of clinical biochemistry at Frederiksberg and Bispebjerg Hospital in Copenhagen, Denmark, and colleagues wrote.

“We and others have recently shown that coffee intake is associated with multiple variables known to be associated with risk of gallstone disease,” researchers noted.

“These variables are potential confounders for the association between coffee intake and symptomatic GSD. In addition, symptoms of gallstones such as colicky pain could in theory reduce individual coffee intake, because coffee stimulates cholecystokinin release, increases gallbladder motility and possibly enhances large bowel motility. This phenomenon in observational epidemiology is known as ‘reverse causation’. It is therefore unclear whether the observed association between coffee intake and gallstone disease is causal,” Nordestgaard and colleagues added.

To fill in the research gaps, researchers first tested whether high coffee intake was associated with a low risk for symptomatic gallstone disease in more than 100,000 individuals in the general population. Then, the researchers tested whether genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790) were associated with higher coffee intake. Lastly, the researchers evaluated whether the genetic variants in another 114,220 individuals — who had a mean follow-up of 38 years — were associated with a lower risk for symptomatic gallstone disease. In the second cohort, there were a total of 7,294 gallstone events.

Nordestgaard and colleagues found that individuals in the first group who drank more than six cups of coffee a day had a 23% lower risk for symptomatic gallstone disease vs. those who did not drink coffee at all (HR = 0.77; 95% CI, 0.61-0.94).

Their genetic analysis found that individuals with certain genetic variants previously linked to increased coffee and other caffeinated beverage consumption had a lower risk for gallstones.

Each additional cup of coffee a person drank translated to a 3% lower risk for symptomatic gallstone disease, they said. The corresponding genetic risk for symptomatic gallstone disease was 11% lower.

The differences between the new findings and previous ones that explored the link between coffee and symptomatic gallstone disease is likely attributable to differences in sample sizes, designs and study populations, according to researchers. – by Janel Miller