# Associations of vitamin D with lipid metabolism, inflammation, and mortality vary by glycemic status and gender: a nationwide prospective study

**Authors:** Meizhi Cai, Xuan Jiang, Xinyi Xu, Sidi Zhao, Yue Sun, Yushuo Yang, Ying Gu, Yifan Huang

PMC · DOI: 10.3389/fnut.2025.1597527 · Frontiers in Nutrition · 2025-10-08

## TL;DR

This study shows that vitamin D's effects on lipids, inflammation, and mortality depend on a person's blood sugar levels and gender.

## Contribution

The study reveals gender- and glycemic status-specific associations of vitamin D with biomarkers and mortality.

## Key findings

- In females, higher vitamin D was linked to higher HDL-cholesterol across all glycemic groups.
- In prediabetic males, vitamin D was inversely linked to triglycerides and inflammation, which partially explained lower mortality.
- Lipid and injury biomarkers did not mediate vitamin D's mortality effects in any subgroup.

## Abstract

We aimed to investigate the associations of 25-hydroxyvitamin D (25OHD) with lipid, inflammatory, and injury biomarkers, and their potential mediating roles in vitamin D-related mortality.

We analyzed data from 4,144 participants in the 2015–2018 National Health and Nutrition Examination Survey (NHANES). Glycemic status was classified using fasting plasma glucose and hemoglobin A1c levels. Key biomarkers were assessed, including visceral adiposity index (VAI) and systemic inflammation response index (SIRI). Multivariate linear regression and restricted cubic spline models examined associations.

In females, 25OHD was positively associated with HDL-cholesterol across all glycemic subgroups, and with triglycerides and total cholesterol in the normal glycemic subgroup (all p < 0.05). In males, inverse associations of 25OHD with triglycerides and VAI were most pronounced in the prediabetes group (p < 0.05). 25OHD was inversely associated with SIRI in normoglycemic individuals and prediabetic males. Mediation analyses revealed that SIRI partially mediated the inverse association between 25OHD and mortality only in prediabetic males, while lipid and injury biomarkers showed no significant mediation effects in any subgroup.

Gender and glycemic status influence the associations between vitamin D and biomarkers, with inflammation potentially mediating the relationship between vitamin D and mortality in prediabetic males.

## Linked entities

- **Chemicals:** 25-hydroxyvitamin D (PubChem CID 5353325)
- **Diseases:** prediabetes (MONDO:0006920)

## Full-text entities

- **Diseases:** inflammation (MESH:D007249), prediabetes (MESH:D011236), visceral adiposity (MESH:D007418)
- **Chemicals:** triglycerides (MESH:D014280), lipid (MESH:D008055), 25OHD (-), vitamin D (MESH:D014807), 25-hydroxyvitamin D (MESH:C104450), glucose (MESH:D005947), cholesterol (MESH:D002784)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12540101/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12540101/full.md

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Source: https://tomesphere.com/paper/PMC12540101