High Fat Diet for Cardiac Metabolic Reprogramming

Summary

Heart failure (HF) continues to be a leading cause of morbidity and mortality worldwide, despite advances in treatment. HF is often characterized by an altered metabolism in the heart, where glucose is favored over fatty acids as the primary energy substrate. This metabolic shift has been hypothesized to contribute to disease progression. Previous studies using animal models have demonstrated that restoring fatty acid metabolism through dietary intervention can reverse the adverse metabolic effects and improve heart function. A transgenic murine model with mitochondrial defects, for instance, exhibited improved cardiac function after an HFD intervention. These findings were reinforced by a translational pig model of non-ischemic DCM, where a high-fat diet significantly improved LVEF compared to a standard diet.

Building upon these promising preclinical results, a small-scale human study showed that lipid infusion, rather than glucose, improved cardiac function in HF patients. However, the long-term benefits of a HFD in heart failure patients have yet to be thoroughly explored. The HF4HF trial aims to fill this gap by evaluating the effects of an HFD over a two-month period in patients with non-ischemic DCM and reduced LVEF.

The "High Fat Diet for Heart Failure" (HF4HF) study is a proof-of-concept randomized controlled trial designed to investigate the efficacy of a high-fat diet (HFD) as a therapeutic intervention in patients with non-ischemic dilated cardiomyopathy (DCM) and reduced left ventricular ejection fraction (LVEF). The study hypothesizes that cardiac metabolic reprogramming, achieved through a controlled nutritional intervention involving an HFD, can enhance systolic function, myocardial energetics, and overall heart function in heart failure (HF) patients. Cofunded by the European Commission and national entities, the trial is spearheaded by a consortium of cardiovascular research centers across four countries: Spain, Italy, France, and Romania.

Conditions

• Non-ischemic Dilated Cardiomyopathy
• Heart Failure With Reduced Ejection Fraction

Interventions

OTHER

High fat diet

Weekly isocaloric dietary profile, with total daily energy intake distributed as follows: 70% from fats, primarily sourced from nuts, extra virgin olive oil, avocados, and animal fats from fish and cheese; protein intake of 0.8-1.2 g per kg body weight (10-20%); and the remaining calories from carbohydrates (10-20%).

OTHER

Standard diet

Weekly isocaloric dietary profile, with total daily energy intake distributed as follows: 30% from fats, primarily sourced from nuts, extra virgin olive oil, avocados, and animal fats from fish and cheese; protein intake of 0.8-1.2 g per kg body weight (10-20%); and 50-60% from carbohydrates.

Sponsors & Collaborators

• Puerta de Hierro University Hospital

  collaborator OTHER

• European Georges Pompidou Hospital

  collaborator OTHER

• Carol Davila University of Medicine and Pharmacy

  collaborator OTHER

• University of Florence

  collaborator OTHER

• Hospital Universitario Fundación Jiménez Díaz

  collaborator OTHER

• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

  lead OTHER

Principal Investigators

• Francesco Sofi, MD PhD · University of Florence, Clinical and Experimental Medicine, Unit of Clinical Nutrition, Florence,

• Pablo García Pavía,, MD PhD · Fundación Investigación Biomédica Hospital Universitario Puerta de Hierro (IIS), Hospital Universitario Puerta de Hierro Majadahonda

• Ruxandra Jurcut, MD PhD · University of Medicine and Pharmacy "Carol Davila", Bucharest,

• Jean-Sébastian Hulot, MD PhD · Hôpital Européen Georges Pompidou, INSERM, Paris,

• Mikel Taibo Urquía, MD · Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

• Borja Ibánez,, MD PhD · Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-15

Primary Completion

2026-06-30

Completion

2026-12-31

Countries

• France
• Italy
• Romania
• Spain

Study Locations