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Association between ketogenic diet ratio and overactive bladder and nocturia among U.S. adults with hyperlipidemia: a multiple mediation analysis of metabolic, psychological, and frailty pathways

Year: 2026

Type: article

Abstract: The ketogenic diet is a high-fat, low-carbohydrate diet. Its role in metabolic regulation has been widely studied. However, its metabolic impact in individuals with hyperlipidemia remains debated, with inconsistent evidence regarding lipid profiles, glycemic control, and inflammatory status. Whether this diet is associated with lower urinary tract symptoms (LUTS) in hyperlipidemic individuals remains unclear. Therefore, this study investigated the association between the ketogenic ratio (KDR) and overactive bladder and nocturia. It also examined whether albumin-corrected anion gap, depressive symptoms, and frailty index mediate this relationship in individuals with hyperlipidemia. A total of 17,633 adults with hyperlipidemia were selected from the National Health and Nutrition Examination Survey (NHANES) database, spanning 2005–2018. The KDR was calculated as (0.9 × fat + 0.46 × protein) / (0.1 × fat + 0.58 × protein + carbohydrates). Weighted multivariable logistic regression models evaluated associations between KDR and overactive bladder (OAB) or nocturia. Restricted cubic spline (RCS) and threshold effect analyses assessed nonlinear relationships. Mediation analyses examined the roles of depressive symptoms, frailty index (FI), and albumin-corrected anion gap (ACAG). Subgroup and interaction analyses identified potential effect modifiers. Among 17,633 individuals with hyperlipidemia, higher KDR was inversely associated with the odds of both OAB and nocturia. When analyzed as a standardized continuous variable, each standard deviation increase in KDR was associated with lower odds of OAB (OR = 0.93, 95% CI: 0.88–0.98) and nocturia (OR = 0.92, 95% CI: 0.88–0.96) in the fully adjusted model. Quartile analysis showed that participants in the highest quartile (Q4) had a lower likelihood of OAB (OR = 0.76, 95% CI: 0.63–0.92) and nocturia (OR = 0.71, 95% CI: 0.62–0.83) compared with those in the lowest quartile (Q1). RCS analysis indicated a nonlinear inverse association between KDR and OAB, with a threshold identified at KDR = 0.215. A linear inverse association was observed for nocturia. Subgroup analyses showed no significant effect modification for OAB. Smoking status significantly modified the association with nocturia, with stronger inverse associations observed among former and current smokers. Mediation analyses showed that ACAG, depressive symptoms, and the frailty index partially mediated the associations between KDR and both outcomes. The mediation proportions were 15.48%, 12.17%, and 19.36% for OAB, and 13.10%, 8.52%, and 17.87% for nocturia, respectively. Among individuals with hyperlipidemia, KDR was inversely associated with the prevalence of OAB and nocturia. The identification of metabolic, psychological, and frailty-related pathways as potential mediators highlights the possible interplay between dietary patterns, systemic metabolic status, and functional health. These findings provide complementary evidence supporting the relevance of dietary composition in the broader context of LUTS in metabolically vulnerable populations. Further prospective studies are warranted to validate these observations. Not applicable.

Source: Nutrition & Metabolism

DOI: 10.1186/s12986-026-01210-4

Authors: Yang Sun, Min Yin, Libin Zhou

Institutions: Ningbo University, Ningbo Medical Center Lihuili Hospital

Language: English

Topic: Diet and metabolism studies

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,590