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Higher plasma caffeine levels linked to reduced body fat and type 2 diabetes risk according to genetic study

23rd March 2023

Increased plasma caffeine levels may help reduce body mass index as well as fat mass and the risk of developing type 2 diabetes

A higher plasma caffeine (PC) concentration may produce a lower body mass index (BMI) as well as reducing body fat and the risk of type 2 diabetes according to the findings of a genetic study by Swedish and UK researchers.

Caffeinated beverages such as coffee, tea and soda drinks are widely consumed across the world. Given that caffeine has a known thermogenic effect and which might help lower body weight, there is the potential that caffeine-containing beverages may have a role in lowering the risk of disease related to adiposity. In fact, there is already some data to suggest that caffeine-containing drinks such as coffee are inversely associated with risk of type 2 diabetes.

It is recognised the caffeine metabolism occurs mainly in the liver by the cytochrome P450 isoform 1A2 (CYP1A2) and how genetic variations near two genes, CYP1A2 and AHR (which regulates the expression of CYP1A2) are linked to PC concentrations. In fact, individuals with genetic variants linked to slower caffeine metabolism, although generally consuming less caffeine-related beverages, do have higher plasma caffeine levels. Using Mendelian randomisation, researchers sought to investigate the effects of long-term exposure to higher plasma caffeine concentrations on adiposity, type 2 diabetes and major cardiovascular diseases. They used data from a genome-wide association meta-analysis of 9876 individuals of European ancestry from six population-based studies and which identified genome-wide significant associations of single nucleotide polymorphisms near CYP1A2 and AHR loci with plasma caffeine concentrations.

Plasma caffeine and adiposity-related outcomes

Researchers identified that genetically predicted higher PC concentrations in those carrying the two gene variants, were in fact, associated with a lower BMI, with one standard deviation (SD) increase in predicted PC equal to about 4.8 kg/m2 in BMI (p < .001). Similarly, for whole-body fat mass, one SD increase in PC equated to a reduction of about 9.5 kg (p < .001), although interestingly, there was no association with fat-free body mass (p= 0.17).

Again among genetically predicted higher PC concentrations, there were also significant and lower associations with the risk of developing type 2 diabetes, with the combined odds ratio of type 2 diabetes per SD increase in PC concentration being 0.81 (95% CI 0.74 – 0.89, p < 0.001).

The authors concluded that while their study found evidence of a causal association between a higher plasma caffeine concentration and lower levels of adiposity and a reduced risk of type 2 diabetes, they called for randomised trials to further examine the role of caffeine in reducing the risk of obesity and diabetes.

Larrson SC et al. Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study. BMJ 2023