Single-meal challenges produce distinct acute proteomic responses in healthy volunteers

Diet can influence cardiometabolic health, but the immediate molecular responses to different meals are not fully characterized. In this prospective crossover study, 20 healthy volunteers completed five single-meal challenges: a high-glucose oral glucose tolerance test, ketogenic meal, high-fat high-calorie meal, normal-fat normal-calorie meal, and low-fat low-calorie meal. Researchers collected 500 plasma and 500 urine samples for high-throughput proteomic profiling and used Mendelian randomization to examine the genetic relevance of diet-responsive proteins to cardiometabolic outcomes. The study was registered as NCT04984642.

Each meal was associated with a distinct protein response. Compared with the low-fat, low-calorie meal, the ketogenic meal increased PPBP, SRGN, GSTO1, BLVRB, MIF, and S100A4, proteins linked to platelet activation, inflammation, and oxidative stress. Compared with the high-glucose challenge, the high-fat, high-calorie meal altered proteins including JUP, DSP, APOA5, TAGLN2, RAP1B, and TMSB4X. The high-glucose challenge was associated with reductions in PRDX1, CAT, and SOD1, which are involved in redox defense. Urine analyses showed complementary meal-specific responses.

These results provide mechanistic observations rather than evidence that particular meals change clinical outcomes. The study involved only 20 healthy volunteers and assessed acute responses to single meals; the findings do not establish long-term health effects or support changes to dietary advice. The authors report that the proteomics dataset is publicly available.