Y. Sun, M. Yin and L. Zhou (2026). U-shaped and linear associations of ketogenic diet with nocturia and overactive bladder: mediation roles of frailty and platelet-to-HDL-C ratio and the influence of physical activity. Journal of health, population, and nutrition, 45(1), 51. https://doi.org/10.1186/s41043-025-01220-7

PubMed 41521350

[Abstract]
BACKGROUND: Ketogenic diet (KD), characterized by low carbohydrate and high fat intake, has become an increasingly popular strategy for weight management and metabolic improvement in recent years. However, its potential influence on lower urinary tract symptoms (LUTS), particularly overactive bladder (OAB) and nocturia, remains unclear. This study aimed to investigate the associations between the ketogenic diet ratio (KDR) and OAB or nocturia, and to explore the mediation roles of the frailty index (FI) and platelet-to-HDL-C ratio (PHR).

METHODS: We analyzed data from 22,249 adults in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. KDR was calculated as (0.9 × fat + 0.46 × protein) / (0.1 × fat + 0.58 × protein + carbohydrates). Weighted multivariable logistic regression models were used to assess the associations between KDR and OAB or nocturia. Restricted cubic spline and threshold effect analyses explored nonlinear relationships, while mediation analyses examined the roles of FI and PHR. Subgroup and interaction analyses evaluated the modifying effect of physical activity.

RESULTS: KDR showed distinct associations with LUTS phenotypes. A nonlinear, U-shaped relationship was observed between nocturia and KDR, with an inflection point at approximately 0.342. Below this point, higher KDR was associated with a lower nocturia risk, while above it, the risk increased. In contrast, KDR displayed a linear inverse association with OAB (OR = 0.48, 95% CI = 0.30-0.79, P = 0.004). The KDR-nocturia relationship was significantly modified by physical activity (P for interaction < 0.05): the inverse association was more pronounced in individuals with low physical activity (< 500 MET-min/week), whereas a threshold effect persisted among highly active participants. Mediation analyses further revealed that FI and PHR partially mediated the association between KDR and OAB, with indirect effect proportions of 21.6% and 5.8%, respectively.

CONCLUSIONS: KDR was inversely associated with OAB and showed a threshold-dependent, U-shaped relationship with nocturia, with patterns potentially influenced by physical activity. These findings provide a novel metabolic perspective on LUTS management and suggest that variations in ketogenic dietary balance and activity level may be relevant to bladder health. However, given the cross-sectional design, these associations should be interpreted cautiously, and causal relationships cannot be inferred.