In light of their findings the potential role of calorie free caffeinated drinks for lowering the risks of obesity and type 2 diabetes is probably now worth exploring, say the researchers.

Previously published research indicates that drinking 3-5 daily cups of coffee, a rich source of caffeine, is associated with a lower risk of type 2 diabetes and cardiovascular disease, note the researchers. An average cup of coffee contains around 70–150 mg caffeine.

But most of the published research to date has concerned observational studies, which can’t reliably establish causal effects, because of the other potentially influential factors involved, point out the researchers.

What’s more, it’s difficult to disentangle any specific effects of caffeine from the other compounds included in caffeinated drinks and foods, they add.

To try and overcome these issues, the researchers used Mendelian randomisation to find out what effect higher blood caffeine levels have on body fat and the long term risks of type 2 diabetes and major cardiovascular diseases—coronary artery disease, stroke, heart failure, and irregular heart rhythm (atrial fibrillation).

Mendelian randomisation is a technique that uses genetic variants as proxies for a particular risk factor—in this case blood levels of caffeine—to obtain genetic evidence in support of a particular outcome—in this study, weight (BMI) and type 2 diabetes risk.

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 6 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 results of the analysis showed that higher genetically predicted blood caffeine levels were associated with lower weight (BMI) and body fat. 

Higher genetically predicted blood caffeine levels were also associated with a lower risk of type 2 diabetes.  

The researchers then used Mendelian randomisation to further explore the extent to which any effect of caffeine on type 2 diabetes risk might principally be driven by the 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 various limitations to their findings, including the use of only two genetic variants, and the inclusion of only people of European ancestry.

But caffeine is known to boost metabolism, increase fat burning, and reduce appetite, they explain. And a daily intake of 100 mg has been estimated to increase energy expenditure by around 100 calories a day, which could consequently lower the risk of developing obesity.

Dr Susanna Larsson, Associate Professor in the Institute of Environmental Medicine at the Karolinska Institute, and lead author of the paper, said: “Our mendelian randomisation finding suggests that caffeine might, at least in part, explain the inverse association between coffee consumption and risk of type 2 diabetes.”

Benjamin Woolf, PhD student in the Tobacco and Alcohol Research Group at the University of Bristol, co-author who led on the statistics for the paper, added: “Randomised controlled trials are warranted to assess whether non-caloric caffeine containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

Paper

‘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, Benjamin Woolf and Dipender Gill in BMJ Medicine [open access]

Further information

About Mendelian Randomisation 
Information on Mendelian Randomisation: a method of using variation in genes of known function between people to examine the causal effect of a modifiable exposure (i.e., diet) on disease (i.e. cancer) in observational studies. The use of genetics reduces any potential measurement or human, error associated with questionnaires and participant recall which are often used to record lifestyle factors such as level of physical activity. University of Bristol researchers have published guides in the BMJ and Nature Reviews Methods, contributed to bmj and freakonomics podcasts, and produced a two-minute video primer.   

About the Tobacco and Alcohol Research Group (TARG)
TARG conduct research into the psychological and biological factors underlying health behaviours. They are part of the MRC Integrative Epidemiology Unit (MRC IEU) at the University of Bristol.

About the MRC Integrative Epidemiology Unit
The MRC Integrative Epidemiology Unit (IEU) at the University of Bristol conducts some of the UK’s most advanced population health science research. It uses genetics, population data and experimental interventions to look for the underlying causes of chronic disease. The unit exploits the latest advances in genetic and epigenetic technologies. They develop new analytic methods to improve our understanding of how our family background behaviours and genes interact to influence health outcomes.