High sodium intake is a significant risk factor for hypertension, overweight/obesity, and cardiovascular diseases. Previous research indicated a positive association between dietary sodium intake and NAFLD. NAFLD, hypertension, and obesity share chronic inflammation as a common pathophysiological mechanism. C-reactive protein (CRP) and red cell distribution width (RDW) are considered biomarkers of systemic inflammation. β-carotene, an antioxidant with anti-inflammatory effects, was hypothesized to potentially attenuate the effects of high sodium intake on NAFLD. This study aimed to investigate these hypotheses using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010, employing mediation analyses to assess the mediating effects of CRP and RDW on the relationship between dietary sodium and NAFLD, defined by the hepatic steatosis index (HSI) and fatty liver index (FLI). The study also examined the modifying effect of β-carotene intake on this relationship. Understanding the role of inflammation and the potential protective effect of β-carotene is crucial for developing strategies to prevent or manage NAFLD.

Numerous studies have established the link between high sodium intake and various health problems, including hypertension and cardiovascular disease. Several studies have also reported an association between high sodium intake and NAFLD, using different assessment methods for NAFLD and varying measures of sodium intake. The mechanisms underlying this association remain uncertain, but chronic inflammation is suspected to play a critical role. CRP and RDW have emerged as potential markers of this inflammation. Conversely, β-carotene, a widely studied antioxidant, exhibits anti-inflammatory properties and has shown potential benefits in various health conditions. Existing literature suggests a potential inverse relationship between β-carotene and NAFLD. This study aimed to build upon this existing research by directly investigating the mediating role of inflammation (CRP and RDW) and the modifying effect of β-carotene in the relationship between dietary sodium and NAFLD risk.

Data were obtained from two cycles (2007-2008 and 2009-2010) of the NHANES. After excluding participants based on age (<20 years), unreliable dietary data, pregnancy, heavy alcohol consumption, positive HBsAg or anti-HCV, and missing covariates, a total of 6725 participants were included in the HSI-defined NAFLD analysis, and 3237 in the FLI-defined analysis. Dietary sodium and β-carotene intake were assessed using two 24-h dietary recalls. NAFLD was defined using both HSI and FLI. Other relevant variables including demographics, lifestyle factors, and inflammatory markers (CRP, RDW) were collected. The data were analyzed using several statistical methods: one-way ANOVA and Chi-square tests for comparing baseline characteristics, unconditional binary logistic regression for estimating odds ratios (ORs) of NAFLD, restricted cubic spline models for dose-response analyses, and mediation analyses (using the R mediation package) to assess the mediating effects of CRP and RDW. The mediation analyses followed the AGREMA statement guidelines. The analyses were performed with and without adjustment for β-carotene intake to determine the potential moderating effect of β-carotene.

A total of 6725 participants were included. Compared to the high sodium-low β-carotene group, the high sodium-high β-carotene group showed a 16% and 26% lower odds of HSI- and FLI-defined NAFLD, respectively. Mediation analyses revealed positive indirect effects of dietary sodium intake on both HSI-defined NAFLD (indirect effect: 0.0057, 95% CI: 0.0021–0.0091, *P* < 0.0001) and FLI-defined NAFLD (indirect effect: 0.0081, 95% CI: 0.0024–0.0162, *P* < 0.0001) when CRP was the mediator. These mediating effects were somewhat attenuated after adjusting for β-carotene intake. Similar results were observed with RDW as a mediator in the HSI-defined NAFLD analysis. Dose-response analyses showed a positive association between sodium intake and NAFLD and an inverse association between β-carotene intake and NAFLD.

The findings support the hypothesis that higher sodium intake increases the risk of NAFLD, at least partially through upregulation of inflammation (as indicated by CRP and RDW). The significant attenuation of the mediating effects after adjusting for β-carotene suggests a protective role for β-carotene against the pro-inflammatory effects of sodium, potentially by reducing inflammation and thereby lowering the risk of NAFLD. The results align with previous studies demonstrating associations between dietary sodium intake and NAFLD, as well as the anti-inflammatory effects of β-carotene. The study contributes novel evidence by explicitly demonstrating the mediating role of inflammation and the moderating effect of β-carotene using a robust analytical approach.

This study provides evidence that high sodium intake increases NAFLD risk via inflammation, and β-carotene may mitigate this association. Future research should utilize more reliable sodium intake measurements, consider additional inflammatory biomarkers, and employ longitudinal study designs to confirm causality and further investigate the complex interplay between sodium, β-carotene, inflammation, and NAFLD pathogenesis.

The study's limitations include using 24-h dietary recalls instead of 24-h urinary sodium excretion for sodium intake assessment, using HSI and FLI rather than liver biopsies for NAFLD diagnosis, and considering only a limited set of inflammatory markers. The cross-sectional design also precludes establishing causality. Future research should address these limitations to strengthen the evidence base.