# Mediation of Systemic Inflammation and Oxidative Stress Markers in the Association of Life’s Crucial 9 with Periodontitis: Evidence from NHANES 2009–2014

**Authors:** Ruoyao Zhang, Chong Han, Dijia Hu, Qiukai Chen, Jinguo Zheng, Toshinori Okinaga

PMC · DOI: 10.3290/j.ohpd.c_2469 · 2026-01-28

## TL;DR

Higher levels of Life’s Crucial 9 are linked to lower odds of periodontitis, with systemic inflammation and oxidative stress markers partially explaining this relationship.

## Contribution

This study identifies systemic inflammation and oxidative stress as potential mediators linking Life’s Crucial 9 to periodontitis.

## Key findings

- LC9 was inversely associated with periodontitis odds, with a 16% reduction per 10-point increase.
- Systemic inflammation markers like white blood cell count and neutrophil count explained up to 32.53% of the association.
- Age, race, and marital status were found to moderate the relationship between LC9 and periodontitis.

## Abstract

To examine the cross-sectional association between LC9 and periodontitis using NHANES 2009-2014 data, while also investigating the roles of systemic inflammation and oxidative stress in this relationship.

LC9 was calculated based on the 8 components of LE8 and the depression score assessed by the Patient Health Questionnaire-9. Periodontitis was assessed according to the CDC-AAP definition. Multivariable logistic regression and restricted cubic spline (RCS) analyses were used to explore the relationship between LC9 and periodontitis. Exploratory mediation analyses were performed to examine the roles of systemic inflammation and oxidative stress markers.

A total of 7191 participants were enrolled, and 3540 had periodontitis. In the fully adjusted model, LC9 was inversely associated with the odds of periodontitis (OR per 10-point increase 0.85, 95% CI 0.80-0.90, p < 0.0001). Compared to Q1, participants with LC9 at Q2, Q3, and Q4 had statistically significantly lower periodontitis prevalence (OR 0.78, 0.64, and 0.62, respectively; p for trend = 0.0001). Most LC9 component scores were inversely associated with periodontitis. RCS analysis showed that LC9 was linearly associated with the odds of periodontitis. Exploratory mediation analyses suggested that white blood cell count, neutrophil count, systemic immune-inflammation index, serum albumin, and uric acid may explain 32.53%, 24.05%, 3.64%, 10.70%, and 6.64% of this association, respectively. Stratified analysis showed that age, race, and marital status moderate the relationship between LC9 and periodontitis.

LC9 was linearly and negatively associated with the odds of periodontitis; systemic inflammation and oxidative stress markers may partially explain this association. These findings suggest that LC9 may serve as a valuable, comprehensive tool for assessing the likelihood of developing periodontitis, emphasizing that improving overall cardiovascular and mental health may be associated with lower prevalence of periodontitis.

## Linked entities

- **Diseases:** periodontitis (MONDO:0005076)

## Full-text entities

- **Genes:** GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}
- **Diseases:** immune (MESH:D007154), GR (MESH:D005889), Disease (MESH:D004194), LC9 (MESH:D003643), periodontal disease (MESH:D010510), CVD (MESH:D002318), Depression (MESH:D003866), bone loss (MESH:D001847), Alzheimer's disease (MESH:D000544), diabetes (MESH:D003920), Chronic systemic inflammation (MESH:D007249), anxiety (MESH:D001007), oral diseases (MESH:D009059), Periodontitis (MESH:D010518), obesity (MESH:D009765), Stage I HTN (MESH:D062706), tooth loss (MESH:D016388)
- **Chemicals:** Alcohol (MESH:D000438), tianeptine (MESH:C050504), Blood glucose (MESH:D001786), cholesterol (MESH:D002784), glucose (MESH:D005947), lipids (MESH:D008055), UA (MESH:D014527), nicotine (MESH:D009538), ACKNOWLEDGMENTS (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12852985/full.md

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Source: https://tomesphere.com/paper/PMC12852985