Ketogenic Diets Are Associated with an Elevated Risk for All Cancers: Insights from a Cross-Sectional Analysis of the NHANES 2001–2018

Ketogenic diet (KD) has increasingly been applied in anti-cancer therapy in recent years; however, its effect on cancer development risk remains controversial. We examined the association between dietary ketogenic ratio (DKR) and cancer incidence using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018. Dietary intake information was collected via a detailed 24-h dietary recall survey, and DKR values were calculated using a specialized formula. Multivariate logistic regression analysis was performed to evaluate the correlation between DKR and tumor occurrence, with restricted cubic splines (RCS) utilized to assess potential nonlinear relationships. Furthermore, a two-stage linear regression analysis was carried out to determine the inflection point. Furthermore, subgroup analyses were conducted stratified by demographic variables, including age, gender, race, body mass index (BMI), smoking status, and diabetes mellitus. A significant association was observed between DKR and cancer risk in multivariate logistic regression models fully adjusted for all potential confounding factors (OR, 1.58; 95%CI: 1.08, 1.54; p = 0.049). Moreover, individuals in the highest quartile of DKR exhibited a significantly increased risk for all cancers compared to those in the lowest quartile (Q4: OR, 1.29; 95%CI: 1.08, 1.34; p = 0.005). The RCS analysis revealed a non-linear relationship between DKR and cancer risk (p < 0.001, P for nonlinear trend = 0.003), with a turning point identified at 0.44 units on the scale used in this study. Piecewise regression analysis based on this threshold indicated that DKR values below 0.44 (DKR < 0.44) were significantly associated with an increased risk for all cancers within the context of this investigation (OR, 1.08; 95%CI: 1.04, 1.12; p < 0.001), while no significant correlation was observed for DKR values above this threshold (DKR ≥ 0.44) (OR, 1.01; 95%CI: 0.95, 1.07; p = 0.77). Furthermore, the findings from the subgroup analyses were consistent with the overall results. Therefore, we conclude that a KD might elevate the risk for all cancers, and further studies are warranted to validate this hypothesis.