Higher plasma caffeine levels may reduce obesity and the risk of developing type 2 diabetes

suggests research published in the Open Access Journal BMJ Medicine.

In light of their findings, the potential role of no-calorie caffeinated beverages in reducing the risk of obesity and type 2 diabetes is probably now worth exploring, the researchers say.

The researchers note that previously published research indicates that drinking 3-5 cups of coffee per day, which is a rich source of caffeine, is associated with a lower risk of type 2 diabetes and cardiovascular disease. An average cup of coffee contains about 70-150 mg of caffeine.

But most of the research published to date has been of observational studies, which cannot reliably establish causal effects, due to other potentially confounding factors, the researchers note.

Furthermore, it is difficult to separate any specific effects of caffeine from other compounds included in caffeinated beverages and foods, they add.

To try to work around these issues, the researchers used the randomized Mendelian method to investigate the effect of higher blood levels of caffeine on body fat and long-term risks for type 2 diabetes and major cardiovascular disease-; Coronary artery disease, stroke, heart failure, and an irregular heartbeat (atrial fibrillation).

Mendelian randomization is a technique that uses genetic variants as proxies for a particular risk factor- ; In this case the levels of caffeine in the blood-; To obtain genetic evidence to support a particular outcome- ; In this study, weight (body mass index) 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 descent who participated in 6 long-term studies. The CYP1A2 and AHR genes are related to how quickly caffeine is metabolized in the body.

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

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

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

The researchers then used Mendelian randomization to investigate the effect of caffeine on the risk of developing type 2 diabetes, which could be primarily driven by concurrent weight loss.

The results showed that weight loss offset nearly half (43%) of the effect of caffeine on type 2 diabetes risk.

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

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. It is estimated that taking 100 mg per day increases energy intake by about 100 calories per day, which may therefore reduce the risk of obesity.

“Our Mendelian randomized findings suggest that caffeine may explain, at least in part, the inverse association between coffee consumption and the risk of developing type 2 diabetes,” the researchers write.

They concluded that “randomized controlled trials are warranted to evaluate whether no-calorie beverages may play a role in reducing the risk of obesity and type 2 diabetes.”


Journal reference:

Larson, South Carolina, et al. (2023) Evaluation of the causal effect of plasma caffeine on obesity, type 2 diabetes, and cardiovascular disease: a randomized, two-sample Mendel study. BMJ Medicine. doi.org/10.1136/bmjmed-2022-000335.

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