Very low energy ketogenic therapy: an anti-inflammatory medical nutritional approach for MASLD in obesity

Dec 17, 2025Journal of translational medicine

Very low energy ketogenic diet as an anti-inflammatory treatment for fatty liver disease in obesity

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Abstract

Significant reductions were observed in BMI, waist circumference, and hs-CRP levels after the ketogenic phase of in women with obesity and .

Chronic inflammation, oxidative stress, and high CRP are linked to metabolic dysfunction-associated steatotic liver disease (MASLD).
The ketogenic phase of very low energy ketogenic therapy (VLEKT) resulted in weight loss and improvements in various metabolic markers.
Weight loss during VLEKT showed positive correlations with reductions in fat mass, total cholesterol, LDL cholesterol, and γGT.
A significant negative correlation was found between weight loss and HDL cholesterol levels.
Changes in hs-CRP levels were identified as the main predictor of improvement in MASLD, explaining 65.9% of the variance.

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BACKGROUND: Chronic inflammation, oxidative stress, and high CRP are linked to (MASLD); (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.

Key numbers

7.12 kg

Weight Loss

Weight decreased from 99.65±14.43 kg to 92.53±13.71 kg

1.49 mg/L

hs-CRP Reduction

hs-CRP levels dropped from 3.72±2.66 mg/L to 2.23±1.99 mg/L

14.03

FLI Improvement

FLI decreased from 85.64±16.25 to 71.61±24.22

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Very low energy ketogenic therapy: an anti-inflammatory medical nutritional approach for MASLD in obesity

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