Exercise and IgG Glycosylation Show No Strong Link in Young Medical Students

IgG N-glycosylation is increasingly recognized as a sensitive molecular readout of systemic immune and inflammatory status. Specific glycan features — particularly low galactosylation and sialylation — track with aging, chronic disease, and pro-inflammatory states, while higher galactosylation and sialylation reflect a more anti-inflammatory phenotype. Because regular physical activity (PA) broadly reduces low-grade inflammation, researchers hypothesized that habitual PA might be detectable at the level of IgG glycan composition, even in young, healthy individuals.

This cross-sectional study enrolled 79 first- and second-year medical students (56 women; median age 20 years) at the University Josip Juraj Strossmayer in Osijek, Croatia. PA was assessed via the validated International Physical Activity Questionnaire – Short Form (IPAQ-SF), capturing walking, moderate, and vigorous activity, total MET-min/week, and sitting time. Participants were classified as HEPA-active (n=23) or non-HEPA-active (n=56). IgG was isolated from plasma and N-glycans profiled using capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF), quantifying 27 glycan peaks and 8 derived structural traits (G0, G1, G2, S0, S1, S2, bisecting GlcNAc, and core fucosylation).

The two PA groups showed no statistically significant differences across any of the 27 individual glycan peaks or 8 derived traits after Benjamini-Hochberg false discovery rate correction (all FDR-adjusted P = 0.893). In unadjusted correlation analyses, modest associations emerged: vigorous PA correlated weakly with G1 (ρ = 0.24, P = 0.034), and total PA correlated with G1 (ρ = 0.27, P = 0.017) and negatively with G2 (ρ = −0.34, P = 0.002). However, none of these passed multiple-testing correction. BMI-adjusted partial Spearman correlations and interaction analyses did not reveal meaningful effect modification.

The authors attribute the null findings to several factors: the population is young, relatively healthy, and metabolically homogeneous, which narrows the biological range over which PA-related glycan variation could manifest. The mandatory PA curriculum at the medical school also likely compressed inter-individual PA differences. Self-reported PA via IPAQ-SF introduces measurement error, and the cross-sectional design cannot capture cumulative or dose-dependent effects over time. The sample size of 79 also limits statistical power.

These results temper expectations that short-term or moderate differences in habitual PA are readily detectable in the IgG glycome of young adults. Prior research suggesting PA-glycan links has largely focused on older adults, clinical populations, or structured athletic training — contexts where physiological contrasts are much larger. The study provides a useful null-result benchmark, suggesting that glycan biomarkers of PA may only be detectable in more extreme or longitudinal exposure scenarios.