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High Caffeine Levels May Reduce Body Fat and Diabetes Risk

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A new study has found that high levels of caffeine in the blood may reduce a person’s risk of developing Type 2 diabetes, as well as the amount of body fat they carry. The research is published in BMJ Medicine.

The benefits of caffeine

Coffee, one of the most widely consumed beverages in the world, is rich in the stimulant molecule caffeine, with the average cup containing 70–150 mg.

Aside from increasing our alertness and cognitive performance, previous research has suggested that caffeine from coffee consumption is also associated with reducing the risk of Type 2 diabetes and cardiovascular disease.

Nevertheless, most published research to date has been in the form of observational studies – these studies only measure certain variables without looking at the effect of an intervention on an outcome. Therefore, they do not reliably establish cause-and-effect because of other variables that may be involved. For example, it is difficult to rule out the specific effects of caffeine from other compounds also found in caffeinated food and beverages.

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To overcome these difficulties, the researchers in the current study used a technique called Mendelian randomization. This involves using information on different genetic variants instead of the risk factor being investigated – i.e., levels of caffeine in the blood – to determine if these are associated with weight, diabetes risk and cardiovascular disease.

Effects on body fat and diabetes?

As a proxy for blood caffeine levels, the researchers selected two variants of the cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AHR) genes, both of which are linked to the speed of the body’s metabolism of caffeine. They investigated the role of these genes in a group of almost 10,000 people (mainly of European ancestry) taking part in long-term studies.

The findings revealed that people with genetic variants linked to slow caffeine metabolism consumed less coffee on average, though they still had higher blood caffeine levels than people with genes linked to faster caffeine metabolism.

Additionally, those who were – according to their genetics – predicted to have higher caffeine levels were associated with having a lower bodyweight (BMI), body fat and also a lower risk of developing Type 2 diabetes.

But to what extent was the influence of caffeine on the risk of developing diabetes actually driven by weight loss? Mendelian randomization analysis suggested that weight loss facilitated almost half (43%) of the effect of caffeine on Type 2 diabetes.

However, genetically predicted caffeine levels were not significantly associated with cardiovascular disease outcomes, such as coronary artery disease, stroke, heart failure and irregular heart rhythm (atrial fibrillation).

Additional investigation warranted

Overall, the researchers suggest that a high blood caffeine level may curb body fat and the risk of developing Type 2 diabetes.

The researchers also acknowledge some of the limitations of the study, stating that only two genetic variants were used, which may weaken the analysis. Furthermore, genetic predictors of blood caffeine levels have not been established in individuals not of European ancestry, and it may not be possible to generalize these findings to non-European ancestry populations.

However, the researchers explain that these promising results suggest that caffeine may indeed contribute towards the association between coffee consumption and lower diabetes risk, calling for further investigation. “Randomized 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,” they write in the paper.

Reference: Larsson SC, Woolf B, Gill D. Appraisal of the causal effect of plasma caffeine on adiposity, Type 2 diabetes, and cardiovascular disease: two sample mendelian randomization study. BMJ Medicine. 2023;2. doi: 10.1136/bmjmed-2022-000335

This article is a rework of a press release issued by The British Medical Journal. Material has been edited for length and content.