A 32-week, 30%-energy-deficit Mediterranean-style intervention in 190 overweight adults revealed that ferritin trajectories diverged markedly by clinical subgroup. Participants with metabolic syndrome (MS) entered with the highest baseline ferritin — median 149.5 ng/mL — and experienced the largest decline, averaging −22.0 ng/mL, while healthy-overweight and long-COVID groups showed minimal change (+8.0 and +3.3 ng/mL, respectively). Sex and muscle mass emerged as independent correlates of the multivariate inflammatory profile, and changes in muscle mass, Mediterranean diet adherence score, and Fatty Liver Index each associated with ferritin change. However, the model explained only 16% of variance (adjusted R² = 0.16), underscoring how much inflammatory heterogeneity remains unexplained.
Ferritin is increasingly recognized as a dual-purpose biomarker — reflecting both iron status and systemic inflammation — and elevated levels in MS likely capture both iron overload and inflammasome activation linked to visceral adiposity. The meaningful ferritin drop in the MS group aligns with prior evidence that caloric restriction and Mediterranean eating patterns reduce hepatic fat and low-grade inflammation together. Yet the weak R² and observational design are sobering: without randomization or comprehensive iron-panel data (transferrin saturation, hepcidin), causality cannot be inferred. The inclusion of a long-COVID subgroup is novel and timely but underpowered for subgroup conclusions. Overall, this is a hypothesis-generating, incremental contribution — useful for framing future controlled trials that pair dietary interventions with full iron-status phenotyping.