Effects of Intermittent Fasting on Insulin Resistance, Cardiac Metabolism, and Cerebral Perfusion

Summary

The overall purpose of the study is to investigate whether three weeks of intermittent fasting (alternate-day fasting, (ADF)) result in a more pronounced "metabolic shift" towards the use of ketone bodies than three weeks of Western diet. The investigators will use state-of-the-art PET/CT tracer techniques and well-established steady state kinetics methods for glucose and fatty acids. The study results will provide new insights into the physiological basis of the potential cardio-protective effects of ketone bodies during ADF and will determine whether ADF can help prevent and treat heart failure.

Ketone bodies are produced in the liver as an alternative fuel when blood glucose levels are low, as can be seen with various types of diets or after strenuous exercise. The energy produced by breaking down ketone bodies has been shown to require less oxygen than breaking down glucose and fatty acids. In a previous study, the investigators observed that ketone bodies act as a kind of "super fuel" for the heart and improve the heart's energy utilization. It is still unknown how high ketone levels are needed to see these cardio-protective effects. As patients with insulin resistance and/or heart failure have a lower glucose uptake in cardiac tissue, and as energy production by the breakdown of fatty acids is oxygen-demanding, an elevated level of blood ketones can therefore potentially reduce the morbidity seen in patients with type 2 diabetes and ischemic heart disease.

PET/CT is a non-invasive well-established imaging modality suitable for tracking the fate of metabolites, as most substances or metabolites can be labeled by a suitable PET isotope. PET has sufficient spatial and temporal resolution to enable direct quantification of e.g. uptake and oxidation rates and has been successfully used by the investigators' department to assess heart efficiency, oxygen consumption, and fatty acid metabolism. Currently, the investigators are in the process of validating the PET tracer 11C-beta-hydroxybutyrate (11C-3-OHB) as a radio tracer for human studies. The tracer will be able to detect changes in biodistribution and kinetics of ketone bodies during both Western diets and ADF.

The subjects must go through two study periods of each 3 weeks in which the intervention is western diet (no restrictions) and intermittent fasting (fasting every other day), respectively. After both study periods, there will be an examination day with PET scans and various laboratory examinations.

Conditions

• Obesity
• Insulin Resistance

Interventions

DIETARY_SUPPLEMENT

Intermittent fasting

Subjects fast from after dinner and throughout the next day, i.e., 36 hours of fasting, after which they are allowed to eat as usual until dinner the same day. Then they fast again for 36 hours, and this regimen will continue for three entire weeks.

Sponsors & Collaborators

• University of Aarhus

  lead OTHER

Principal Investigators

• Mette LG Kjærulff, MD · Aarhus University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

55 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-04-05

Primary Completion

2024-04-18

Completion

2025-04-11

Countries

• Denmark

Study Locations