Vitamin D Deficiency Mediates the Link Between Dietary Patterns, Inflammatory Biomarkers, and Iron Status Indicators...

Background/Objectives: Chronic low-grade inflammation and nutritional deficiencies, particularly vitamin D deficiency, have emerged as important contributors to Metabolic syndrome (MetS) pathogenesis but remain underexplored. This study aimed to comprehensively evaluate the associations between dietary intake, vitamin D status, and inflammatory biomarkers (high-sensitivity C-reactive protein -CRP- and ferritin) in patients with MetS. Methods: A cross-sectional observational study was conducted on 141 adult MetS patients at a Mexican hospital. Clinical, anthropometric, dietary (using a validated food frequency questionnaire), and biochemical data including serum 25-hydroxyvitamin D, CRP, ferritin, and neutrophil-to-lymphocyte ratio (NLR) were collected. Vitamin D deficiency was defined as serum 25(OH)D < 20 ng/mL, and high inflammation as CRP ≥ 3 mg/L. Logistic regression models adjusted for confounders were used to analyze associations. Mediation analysis assessed whether vitamin D deficiency mediated the link between dietary intake and high CRP or ferritin. Results: Patients with elevated CRP had significantly lower serum vitamin D levels (14.0 ± 5.1 vs. 22.1 ± 7.0 ng/mL; p < 0.001). Multivariable analysis showed vitamin D deficiency (adjusted OR 7.1; 95% CI 2.5-19.4; p < 0.001) and hyperferritinemia (ferritin ≥ 200 μg/L; aOR 8.0, 95% CI 3.5-18.2, p < 0.001) as predictors of high CRP. Conversely, hyperferritinemia was predicted by vitamin D deficiency (aOR 24.69; 95% CI 3.76-162.16; p = 0.001), elevated CRP (aOR 5.06; p = 0.014), Hb (aOR 63.23; p < 0.001), and inversely by grade 2 obesity (aOR 0.11; 95% CI 0.02-0.60; p = 0.03), confirming bidirectional CRP-ferritin associations and hyperferritinemia as an inflammation marker rather than iron overload indicator. Although Hb > 14.3 g/dL associated with hyperferritinemia, it did not independently predict CRP in multivariate analyses. Frequent consumption of vitamin D-rich foods (milk, fish, Manchego and Oaxaca cheese) was associated with lower inflammation. Mediation analysis confirmed that vitamin D deficiency mediated dietary intake-CRP and dietary intake-ferritin links (Sobel test p < 0.05). Conclusions: Vitamin D deficiency is a key mediator linking inadequate dietary vitamin D intake to systemic inflammation in MetS. Nutritional strategies emphasizing vitamin D repletion and consumption of vitamin D fortified foods may effectively reduce chronic inflammation and improve metabolic outcomes.