J Affect Disord. 2025 Jun 9:119652. doi: 10.1016/j.jad.2025.119652. Online ahead of print.

ABSTRACT

BACKGROUND: Ketogenic diets may modulate mood disorders, but epidemiological evidence for the dietary ketogenic ratio (DKR)-a ketogenic adherence biomarker-remains limited. We investigated the association between DKR and depressive symptoms,while exploring potential mechanisms involving inflammation and body composition.

METHODS: Using NHANES 2007-2018 data (30,133 U.S. adults), depressive symptoms were defined by a Patient Health Questionnaire-9 (PHQ-9) score of ≥10. DKR was calculated using the formula: (0.9 × fat +0.46 × protein) / (0.1 × fat +0.58 × protein + carbohydrates). Multivariable logistic regression adjusted for 19 confounders (demographics, comorbidities, lifestyle), restricted cubic splines, and mediation analyses. Robustness was assessed via propensity score matching.

RESULTS: A higher DKR showed a linear dose-response reduction in depressive symptoms risk (OR = 0.13 per unit increase, 95 % CI:0.03-0.48, p = 0.003; Q4 vs. Q1 OR = 0.59, p = 0.012)… Mediation analyses revealed opposing effects: traditional obesity metrics (BMI, waist circumference, BRI) mediated adverse associations (-14.69 % to -11.43 %), while the body shape index (ABSI) displayed protective mediation (11.03 %, p < 0.001). None of the 12 inflammatory markers showed significant mediation, as indicated by p-values >0.05 or mediation proportions <5 %.

CONCLUSION: DKR inversely associates with depressive symptoms risk, potentially through body composition remodeling rather than anti-inflammatory pathways. ABSI served as a positive mediator in the inverse association between DKR and depressive symptoms. Longitudinal studies are required to confirm causality and clinical utility of DKR.

PMID:[40499821](https://pubmed.ncbi.nlm.nih.gov/40499821/?utm_source=Pondercat RSSBot&utm_medium=rss&utm_content=1xePBFBNvSIhgdpjj8g-0nszUbxcwlDLTO–SZXWRvpgBezs5Z&fc=20250128071610&ff=20250612181332&v=2.18.0.post9+e462414) | DOI:10.1016/j.jad.2025.119652


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