Very Low Energy Ketogenic Therapy Effects on Fibrosis-Dependent Metabolic Reprogramming: A Serum NMR Pilot Study

Area of Science:

• Metabolomics
• Biochemistry
• Hepatic Fibrosis Research

Background:

• Ketogenic diets cause significant metabolic changes.
• Impact on patients with hepatic fibrosis is not well understood.
• Very Low Energy Ketogenic Therapy (VLEKT) is a specific dietary intervention.

Purpose of the Study:

• Investigate serum metabolic alterations induced by VLEKT.
• Assess how hepatic fibrosis influences metabolic adaptations to VLEKT.
• Correlate metabolic changes with fibrosis risk.

Main Methods:

• 1D 1H CPMG NMR spectroscopy on serum samples from obese patients.
• Analysis at baseline (T0) and after 8 weeks of VLEKT (T1).
• Stratification based on FIB-E fibrosis index into low-risk (LR) and intermediate-high-risk (IHR) groups.

Main Results:

• VLEKT induced significant metabolic shifts, increasing ketone bodies (e.g., acetone, β-hydroxybutyric acid).
• LR patients showed better modulation of TCA cycle metabolites; IHR patients had persistent alterations in aromatic amino acids and lipids.
• Tyrosine and β-alanine levels correlated with clinical markers, indicating a fibrosis-dependent metabolic signature.

Conclusions:

• Circulating metabolites can indicate hepatic vulnerability and metabolic adaptability to VLEKT.
• NMR-based metabolomics is a valuable tool for non-invasive assessment of metabolic and hepatic health.
• Fibrosis stage influences metabolic response to VLEKT.