Analysis of more than 200 studies found that drinking three to four cups of coffee a day (400 mg/day) was associated with a reduced risk of all cause mortality (relative risk 0.83, 95% CI 0.83-0.88), cardiovascular mortality (0.81, 95% CI 0.72-0.90), and cardiovascular disease (0.85, 95% CI 0.80-0.90), reported Robin Poole, MD, of the University of Southampton in England, and colleagues.
Increasing consumption to more than three cups a day was not linked to harmful effects, but the benefit was less pronounced, they wrote online in BMJ.
Poole's group searched PubMed, Embase, CINAHL, and the Cochrane Database of Systematic Reviews for meta-analyses of observational or interventional studies that investigated the link between coffee consumption and any health outcome. Searching for "coffee OR caffeine" and "systematic review OR meta-analysis," they found 201 meta-analyses of observational research with 67 unique outcomes and 17 meta-analyses of randomized controlled trials with nine unique outcomes.
A meta-analysis of 40 cohort studies showed a lower incidence of cancer for high versus low coffee consumption (relative risk 0.82, 95% CI 0.74 to 0.89), any versus no consumption (RR 0.87, 95% CI 0.82-0.92), and one additional cup per day (RR 0.97, 95% CI 0.96-0.98), they reported.
Any versus no coffee consumption was associated with a 29% lower risk of non-alcoholic fatty liver disease (relative risk 0.71, 95% CI 0.60-0.85), a 27% lower risk for liver fibrosis (odds ratio 0.73, 95% CI 0.56-0.94), and a 39% lower risk for liver cirrhosis (OR 0.61, 95% CI 0.45-0.84), as well as a lower risk of cirrhosis with high versus low consumption (OR 0.69, 95% CI 0.44-1.07).
Additionally, coffee consumption was consistently associated with a lower risk of type 2 diabetes for high versus low consumption (RR 0.70, 95% CI 0.65-0.75) and Alzheimer's disease (RR 0.73, 95% CI 0.55-0.97).
Poole's group didn't find any consistent evidence of harmful associations between coffee consumption and health outcomes except for those related to pregnancy and risk of fracture in women.
After adjustment for smoking, consumption in pregnancy was associated with harmful outcomes related to low birth weight (OR 1.31, 95% CI 1.03-1.67), preterm birth in the first trimester (OR 1.22, 95% CI 1.00-1.49), and second trimester (OR 1.12, 95% CI 1.02-1.22), and pregnancy loss (OR 1.46, 95% CI 1.06-1.99).
A research limitation was that much of the evidence was low quality and came from observational studies which may include residual confounding. However, the researchers noted that "the analysis indicates that future randomised controlled trials in which the intervention is increasing coffee consumption, within usual levels of intake, possibly optimised at three to four cups a day, would be unlikely to result in significant harm to participants."
In an accompanying editorial, Eliseo Guallar, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, agreed but cited several suggestions regarding future research. "Poole and colleagues argue that randomised clinical trials are needed, although the complexity of long term trials of behavioural interventions, the large sample size required, and the high cost complicate the feasibility of trials prospectively testing the effect of coffee on clinical endpoints."
"Mendelian randomisation analyses may also help, but their power is limited if genetic traits explain only a small fraction of coffee intake patterns, and their interpretation is complicated by the pleiotropic effects of the genes involved in metabolising caffeine," Guallar noted.
Poole and co-authors disclosed no relevant relationships with industry.