# Immune modulation in response to coffee intake: a pilot study

## TL;DR

This study explores how coffee and caffeine affect immune responses in healthy people, finding that pure caffeine has a stronger anti-inflammatory effect than coffee.

## Contribution

The study is the first to directly compare immune modulation by coffee versus caffeine alone in humans.

## Key findings

- Pure caffeine significantly reduced pro-inflammatory cytokines like IL-17A, IL-12p70, and IL-2.
- Coffee and caffeine both modulate immune homeostasis but with distinct cytokine responses.
- Bioactive compounds in coffee beyond caffeine contribute to its immunological effects.

## Abstract

Coffee consumption has been associated with various health benefits; however, the underlying biological mechanisms remain poorly understood. In particular, the acute effects of coffee on circulating cytokines and the specific role of caffeine compared with the whole coffee matrix are still insufficiently characterised in humans. To our knowledge, no previous human study has directly compared immune modulation by coffee versus caffeine alone. We therefore aimed to elucidate the effect of a usual caffeine dose of 130 mg on postprandial cytokine secretion, and whether responses differ between coffee and pure caffeine.

In a randomized pilot trial, ten healthy volunteers completed three test days receiving either a coffee brew, an aqueous caffeine solution (each 130 mg caffeine/100 ml), or water. Quantitative analysis of caffeine was performed with UHPLC-MS/MS, immune markers were measured by a multiplex immunoassay.

Our study demonstrates that both caffeine and coffee consumption influence the immune homeostasis, albeit with notable differences on cytokine secretion. Pure caffeine induced a higher anti-inflammatory response, as evidenced by the significant decrease in pro-inflammatory cytokines such as IL-17 A, IL-12p70, and IL-2 compared to coffee and water. The integrated response on the immune system is exemplified by the decrease of the pro-inflammatory IFN-γ (0.649 ± 0.068) and the anti-inflammatory IL-10 (0.478 ± 0.043), vs. baseline, respectively.

These findings provide novel in vivo evidence that usual coffee and caffeine acutely affects cytokine responses differently in healthy individuals. In conclusion, our study addresses an important gap regarding the immune properties of coffee and suggests that bioactive compounds beyond caffeine contribute substantially to its immunological effects.

The online version contains supplementary material available at 10.1007/s00394-026-03913-z.