# Vitamin D Deficiency Mediates the Link Between Dietary Patterns, Inflammatory Biomarkers, and Iron Status Indicators (Ferritin and Hemoglobin) in Metabolic Syndrome

## TL;DR

This study shows that vitamin D deficiency connects poor diet, inflammation, and iron levels in people with metabolic syndrome, suggesting vitamin D-rich foods could help reduce inflammation.

## Contribution

The study identifies vitamin D deficiency as a mediator between dietary patterns, inflammation, and iron status in metabolic syndrome patients.

## Key findings

- Vitamin D deficiency was strongly linked to higher inflammation (CRP) and elevated ferritin levels in metabolic syndrome patients.
- Dietary intake of vitamin D-rich foods was associated with lower inflammation, and vitamin D deficiency mediated this relationship.
- Hyperferritinemia was more closely tied to inflammation than iron overload, with vitamin D deficiency as a key predictor.

## Abstract

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.