Inverse association between dietary potassium-to-sodium ratio and systemic inflammatory markers: A cross-sectional analysis of the NHANES 2021–2023 data

Systemic chronic inflammation (SCI) is associated with a range of noncommunicable diseases. Emerging evidence indicates that the dietary potassium-to-sodium (K/Na) ratio may predict cardiovascular and inflammatory health more accurately than potassium or sodium alone. However, its relationship with established systemic chronic inflammation markers (SCI markers) has not yet been thoroughly investigated. This study was conducted to examine the association between dietary K/Na ratio and serum concentrations of alpha-1-acid glycoprotein (AGP) and C-reactive protein (CRP), and to explore the shape of these dose-response relationships. We performed a cross-sectional analysis of 892 adults aged ≥ 20 years using data from the National Health and Nutrition Examination Survey (NHANES) 2021 to 2023. Dietary intake was assessed via two 24-hour recalls, from which individual potassium and sodium intakes were used to calculate the K/Na ratio. Serum alpha-1-acid glycoprotein (AGP) and high-sensitivity C-reactive protein (hs-CRP) were measured using standardized immunoturbidimetric assays. We applied survey-weighted multivariable linear regression models to examine adjusted associations between the continuous K/Na ratio and each inflammatory marker, controlling for age, sex, race/ethnicity, education, income, smoking, physical activity, body mass index, hypertension, diabetes, and lipid profiles. Generalized additive models (GAMs) with penalized splines were used to assess potential nonlinear dose-response relationships. Sensitivity analyses excluded participants with CRP > 10 mg/L and explored subgroup effects by sex and race/ethnicity. After full adjustment, each 1-unit increase in dietary K/Na ratio was associated with a 0.068 mg/dL decrease in AGP (SE = 0.021; P = .001) and a 0.248 decrease in ln-transformed hs-CRP (SE = 0.095; P = .009). GAM analyses revealed a significant nonlinear inverse relationship between K/Na ratio and AGP (effective degrees of freedom = 1.49; P = .007), whereas the association with ln-CRP remained linear (edf = 1.33; P = .499). Findings were consistent across sensitivity and subgroup analyses. In this nationally representative US sample, a higher dietary K/Na ratio is independently associated with lower systemic inflammation, supporting public health strategies that promote improved potassium-to-sodium balance to mitigate chronic disease risk.