Caffeine in coffee and tea has thermogenic and psychostimulant effects. Several short-term randomized controlled trials (RCTs) have found that caffeine (even in trivial amounts) helps decrease weight, fat mass, and body mass index (BMI). Hence, it is highly likely that more caffeine consumption (by tea and coffee drinking) might also lower the risk of adipose-related diseases, such as diabetes and cardiovascular disease. Observational studies have shown an inverse correlation between coffee consumption and diabetes risk. However, observational findings on its correlation with cardiovascular diseases are inconsistent, showing positive and inverse correlations. Thus, these studies did not reliably infer causality, potentially resulting in confounded associations. Furthermore, other compounds in caffeinated drinks and foods make delineating the specific caffeine effects on the risk of cardiometabolic diseases challenging.
In a recent study published in the BMJ Medicine, researchers performed two sample-mendelian randomizations studies to investigate the effects of long-term exposure to higher plasma caffeine concentrations on type 2 diabetes, adiposity and cardiovascular diseases, such as ischaemic heart disease, stroke and atrial fibrillation. The team obtained estimates of the correlations of the caffeine SNPs for BMI, whole body fat-free mass, and corresponding summary genetic data for diabetes and cardiovascular disease subtypes and atrial fibrillation. It helped them investigate the potential causal effects of long-term exposure to higher plasma caffeine concentrations on adiposity, T2D and major cardiovascular diseases. In the present study, researchers screened six european population-based studies to identify genome-wide associations (GWA) of single nucleotide polymorphisms (SNPs) near cytochrome P450 isoform 1A2 (CYP1A2) and AHR loci.
Genetic variations near CYP1A2, which metabolizes caffeine in the liver, and AHR, which regulates the expression of CYP1A2, are associated with plasma concentrations of caffeine. The researchers assumed that genetic variants used as instrumental variables in MR analysis fulfill three assumptions, relevance assumption, independence assumption, and exclusion restriction assumption. The authors noted an association between genetically predicted higher plasma caffeine concentrations and lower BMI and whole body fat mass, where one standard deviation (SD) was equal to 4.8 kg/m2 in BMI and 9.5 kg in fat mass, respectively. Per study estimates, BMI reduction mediated 43% of the effect of caffeine on T2D liability. However, for every SD increase in plasma caffeine, genetically predicted higher plasma caffeine was not associated with fat-free body mass.
Furthermore, higher plasma caffeine concentrations were correlated to a lower diabetes risk in FinnGen and DIAMANTE consortia. Previous observational findings could not set a clear association between genetically predicted coffee consumption and T2D in MR analyses. This MR study suggested that caffeine, at least in part, explains the inverse association between coffee consumption and T2D risk. Though study findings for plasma caffeine might superficially appear inconsistent and contradictory to previous MR analyses, the authors expected such discrepancy because the genetic variants in the two genomic regions associated with higher plasma caffeine concentrations are also associated with lower coffee and caffeine consumption. Moreover, the genetic method of this study only used SNPs located in genes encoding enzymes with an established role in caffeine metabolism.
This investigation, overall, found robust evidence to support causal associations of higher plasma caffeine concentrations with lower adiposity and risk of diabetes. The investigation speculates that caffeine itself, through a game of gene induction and enzyme regulation, may affect the adipose tissue turnover. Coffee, on the other hand, is known to have chemicals that positively affect the gut microbiota, whose unbalance is recognized to be linked to metabolic disturbances, the onset of diabetes, coronaropathies, autoimmunity and other medical issues. If caffeine helps in the process, why not?
- A cura del Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Larsson S, Woolf B, Gill D. BMJ Med 2023; 2(1):1-8.
Yuan S et al. Eur J Epidemiol. 2022; 37(7):723-733.
Yuan S, Larsson SC. Am J Kidney Dis. 2022; 79(1):9-14.