A new study, published in BMJ Medicine, has looked at the effect of higher blood caffeine levels on body weight and the long-term risks of type 2 diabetes and major cardiovascular diseases, such as coronary artery disease, stroke, heart failure, and irregular heart rhythm (atrial fibrillation).

Researchers used a statistical technique called Mendelian randomization, which uses genetic variants as a tool to investigate the causal relationship between a trait and an outcome.

"These findings offer important insight into the potential causal effect of caffeine on adiposity [obesity] and diabetes risk."Dr Dipender GillSchool of Public Health

The results of their analysis showed that higher genetically predicted blood caffeine levels were associated with lower body weight (BMI). Higher genetically predicted blood caffeine levels were also associated with a lower risk of type 2 diabetes.

The findings suggest that it may be worth exploring the potential for calorie-free caffeinated drinks to play a role in lowering the risk of obesity and type 2 diabetes.

Dr Dipender Gill, senior author for the study, from Imperial College London’s School of Public Health, said: “These findings offer important insight into the potential causal effect of caffeine on adiposity [obesity] and diabetes risk. However, further clinical study is warranted before individuals should use these results to guide their dietary preferences.”

The study was a collaboration between researchers from Imperial College London, the University of Bristol, the London School of Hygiene and Tropical Medicine, and Uppsala University in Sweden.

Previous research has indicated that drinking 3-5 cups of coffee a day is associated with a lower risk of type 2 diabetes and cardiovascular disease. An average cup of coffee contains around 70–150 mg of caffeine.

However, the researchers note that most of the published research to date has come from observational studies, which cannot reliably establish causal effects, because of the other potentially influential factors involved. It is also difficult to disentangle any specific effects of caffeine from other compounds included in caffeinated drinks and foods.

Using Mendelian randomization, the researchers looked at the role of two common genetic variants of the CYP1A2 and AHR genes in nearly 10,000 people of predominantly European ancestry, who were taking part in six long-term studies. The CYP1A2 and AHR genes are associated with the speed of caffeine metabolism in the body.

People who carry genetic variants associated with slower caffeine metabolism drink, on average, less coffee, yet have higher levels of caffeine in their blood than people who metabolise it quickly to reach or retain the levels required for its stimulant effects. 

The researchers also studied the extent to which any effect of caffeine on type 2 diabetes risk might principally be driven by concurrent weight loss. The results showed that weight loss drove nearly half (43%) of the effect of caffeine on type 2 diabetes risk.

No strong associations emerged between genetically predicted blood caffeine levels and the risk of any of the studied cardiovascular disease outcomes.

The researchers acknowledge that there are limitations to the study, including the use of only two genetic variants, and the inclusion of only people of European ancestry.

‘Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study’ by Susanna C Larsson et al. is published in BMJ Medicine.