BACKGROUND AND PURPOSE:

• Coffee consumption has been linked with a lower risk of type 2 diabetes and cardiovascular disease in observational studies
• Larsson et al. (BMJ, 2023) investigate the potential causal effects of long-term plasma caffeine concentrations on adiposity, type 2 diabetes, and major cardiovascular diseases using mendelian randomization to determine causality

METHODS:

• Two sample mendelian randomization study
• Population
  • Primarily European ancestry
  • Participating in cohorts contributing to genome-wide association study consortia
• Exposures
  • Genome-wide association study summary data for associations of two single nucleotide polymorphisms associated with plasma caffeine at the genome-wide significance threshold
    • rs2472297 near the CYP1A2 gene
    • rs4410790 near the AHR gene
• Primary outcomes
  • BMI | Whole body fat mass | Whole body fat-free mass | Type 2 diabetes | Ischemic heart disease | Atrial fibrillation | Heart failure | Stroke

RESULTS:

• 9876 individuals
• Higher genetically predicted plasma caffeine concentrations were associated with lower
  • BMI
    • Beta −0.08 standard deviation (95% CI, −0.10 to −0.06)
    • 1 SD equals about 4.8 kg/m2 in BMI, for every standard deviation increase in plasma caffeine
  • Whole body fat mass
    • Beta −0.06 SD (95% CI, −0.08 to −0.04)
    • 1 SD equals about 9.5 kg | P<0.001
• There was no association with fat-free mass
  • Beta −0.01 SD (95% CI, −0.02 to −0.00)
  • 1 SD equals about 11.5 kg | P=0.17
• Higher genetically predicted plasma caffeine concentrations were associated with a lower risk of type 2 diabetes (two consortia: FinnGen and DIAMANTE)
  • Combined OR 0.81 (95% CI, 0.74 to 0.89) | P<0.001
• Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through BMI reduction
  • 43% (95% CI, 30 to 61)
• There were no strong associations between genetically predicted plasma caffeine concentrations and a risk of any of the studied cardiovascular diseases

CONCLUSION:

• A genetic prediction of lifelong, higher plasma caffeine concentrations was associated with a lower BMI and lower risk of type 2 diabetes
• The authors state

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index reduction 

Learn More – Primary Sources:

Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study