A. Jawamis, H. Al-Domi and NA. Sarayreh (2026). Effects of the ketogenic-caloric restricted diet on metabolic endotoxemia and metabolic health in adults with prediabetes: A randomized controlled trial. Nutrition (Burbank, Los Angeles County, Calif.), 146, 113119. https://doi.org/10.1016/j.nut.2026.113119

PubMed 41747400

[Abstract]
OBJECTIVE: To investigate the effects of a ketogenic-caloric-restricted (KD+CR) diet on metabolic endotoxemia and related metabolic markers in adults with obesity and prediabetes.

METHODS: A randomized controlled trial was conducted among 90 adults with obesity and prediabetes. Participants were randomized to three groups: 1) KD+CR, 2) normal diet with caloric restriction (ND+CR), or 3) normal diet without caloric restriction (ND). Lipopolysaccharides (LPS), inflammatory biomarkers, fasting glucose, insulin, HOMA-IR, and anthropometric measures were assessed at baseline and week 12.

RESULTS: After 12 wk, serum LPS levels were significantly higher in KD+CR group compared with ND+CR and ND (158.6 ± 6.9 versus 129.6 ± 6.6, 126.7 ± 7.0; P = 0.004). Interleukin-6 (IL-6) significantly decreased in KD+CR versus ND (2.4 ± 0.2, 3.9 ± 0.2; P = 0.004). Insulin and HOMA-IR were significantly lower in KD+CR and ND+CR than in ND (insulin: 12.0 ± 1.1, 13.9 ± 1.0, 19.3 ± 1.1; P < 0.001) (HOMA-IR: 2.9 ± 0.28, 3.2 ± 0.27, and 4.7 ± 0.29; P < 0.001). Body weight and fat mass reductions were greater in the KD+CR group than in the ND+CR and ND groups (body weight: -10.5%, -3.9%, -4.5%; P < 0.001), (body-fat mass: -21.7%, -7.7%, -9.8%; P < 0.001).

CONCLUSIONS: A 12-wk KD+CR diet in adults with obesity and prediabetes improved inflammatory markers, insulin sensitivity, and body composition, alongside a significant increase in serum LPS levels and altered LPS-cytokine dynamics. The long-term metabolic consequences of LPS changes during prolonged ketogenic exposure warrant investigation in future studies.

TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT06911879).