J Transl Med. 2025 Dec 17;23(1):1403. doi: 10.1186/s12967-025-07295-4.

ABSTRACT

BACKGROUND: Chronic inflammation, oxidative stress, and high CRP are linked to metabolic dysfunction-associated steatotic liver disease (MASLD); Very low energy ketogenic therapy (VLEKT) shows anti-inflammatory effects in obesity. The primary aim was to evaluate the effects of ketogenic phase of VLEKT on MASLD and the secondary aim was to identify the underlying mechanisms in women with obesity.

METHODS: This prospective outpatient study included 80 women with obesity (mean age 39.25 ± 4.89 years; BMI 37.27 ± 4.58 kg/m2) and MASLD (FLI ≥ 60) who followed ketogenic phase of VLEKT (< 800 kcal/day, with macronutrient composition comprising 13% carbohydrates, 43% proteins and 44% fats at the University Hospital Federico II of Naples. Assessments at baseline and after ketogenic phase of VLEKT included anthropometric measurements, body composition (via bioelectrical impedance analysis), biochemical analyses, high-sensitivity C-reactive protein (hs-CRP) levels and the Fatty Liver Index (FLI).

RESULTS: After ketogenic phase, significant reductions were observed in BMI, waist circumference, fat mass, total and LDL cholesterol, triglycerides, gamma-glutamyl transferase (γGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting plasma glucose and Hs-CRP levels (p < 0.001, for all). Weight loss (%Δ weight) showed significant positive correlations with %Δ fat mass (p < 0.001), %Δ total cholesterol (p < 0.001), %Δ LDL cholesterol (p < 0.001), and %Δ γGT (p < 0.001), while %Δ HDL cholesterol showed a significant negative correlation (p < 0.001). Multiple regression analysis identified %Δ hs-CRP as the main predictor of MASLD improvement, explaining 65.9% of the variance (p < 0.001).

CONCLUSIONS: MASLD improved post-ketogenic-phase of VLEKT in women with obesity, primarily via reduced chronic inflammation.

PMID:41408292 | DOI:10.1186/s12967-025-07295-4

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