A controlled human study reveals that coffee’s complex chemical matrix may shape immune responses differently than pure caffeine, highlighting how everyday dietary exposures can subtly influence physiology.

Study: Immune modulation in response to coffee intake: a pilot study. Image Credit: ZeiMomArt / Shutterstock
In a recent study published in the European Journal of Nutrition, researchers evaluated the acute immunological effects of coffee compared with an equivalent dose of caffeine in solution and water in healthy adults.
Coffee consumption and caffeine exposure are widely studied due to their potential metabolic and immunological effects, which affect quality of life and generate public health interest. Many individuals consume caffeine regularly, and understanding its physiological effects remains important, while recognizing that biomarker changes do not necessarily translate into clinical health outcomes.
Dietary bioactive compounds, including caffeine and coffee polyphenols, have attracted attention for possible immunomodulatory effects. Caffeine is a methylxanthine present in coffee, acting partly through adenosine receptor antagonism rather than serotonergic pathways. Unlike pharmaceutical interventions, coffee intake represents a common dietary exposure rather than a clinical treatment, making its physiological impact relevant for everyday health research but not indicative of therapeutic effects.
The study and findings
In the present study, researchers evaluated the acute effects of orally consumed coffee compared with an aqueous caffeine solution and water in healthy volunteers. This was a randomized crossover pilot study involving a small sample (n = 10). Participants were aged 20 to 40 years, healthy, non-smoking regular coffee consumers with normal body mass index.
Individuals with chronic disease, medication use, pregnancy, or other health conditions affecting metabolism or immunity were excluded. Subjects were administered coffee brew, a caffeine solution, or water containing an equivalent caffeine dose (130 mg/100 mL) after a standardized meal to control for postprandial metabolic effects.
In each study phase, participants received one of the three beverages in randomized order with washout periods between sessions. The dose, approximately 130 mg caffeine per serving, was consumed orally.
The primary outcome was the postprandial immune response, including circulating cytokines and caffeine pharmacokinetics. Secondary measures included comparisons of inflammatory cytokines such as interferon gamma and interleukins, as well as caffeine exposure assessed by area under the curve. Safety monitoring included standard clinical observations appropriate for nutritional research.
Statistical analyses involved repeated-measures comparisons of cytokine levels and caffeine pharmacokinetics between interventions.
Findings
The study randomized 10 healthy participants to coffee, caffeine solution, and water crossover conditions. Participants were, on average, young adults and habitual coffee drinkers, with comparable baseline characteristics across interventions.
Immune marker responses differed modestly between interventions. Pure caffeine produced more pronounced suppression of certain cytokines, including interferon gamma and selected interleukins, whereas coffee often elicited responses closer to the water control despite equivalent caffeine content.
Systemic caffeine exposure was higher after coffee consumption than after the caffeine solution, suggesting potential matrix effects from other coffee constituents that may influence absorption or metabolism, although the authors interpreted this cautiously, given the pilot-scale design.
Most physiological changes were acute and transient following beverage consumption, with no evidence of clinically significant adverse health effects and no indication of lasting immune alterations within the short observation period.
The intervention was well tolerated among participants who received coffee or other caffeine-containing beverages. No serious adverse events or clinically meaningful abnormalities were reported, although minor transient physiological responses typical of caffeine intake were observed.
Conclusions
Acute consumption of coffee, which delivers approximately 130 mg of caffeine, produced measurable but modest immunological effects in healthy adults, distinct from those observed with isolated caffeine, suggesting that non-caffeine coffee components may modify physiological responses. The intervention appeared safe and well-tolerated.
These findings should be considered preliminary due to the small sample size, short-term design, and healthy participant population. Larger, longer studies across diverse populations and habitual intake patterns are needed to further evaluate the health implications of coffee and caffeine consumption.