The Effects of Ketogenic Diet on the Heart and Brain

NCT05012748 | Completed DMC

• 1 other identifier: 1-10-72-232-18
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

A ketogenic diet consists of a high intake of fats and a limited intake of carbohydrates, which causes an increased level of ketone bodies in the body. In recent years, it has been shown that the diet has cardiovascular protective effects. The investigators have also shown that ketone bodies act as super-gasoline for the heart. In addition, an increased level of ketone bodies will improve memory and comprehension in humans, possibly due to increased blood flow in the brain. The purpose of the experiment is to investigate how a ketogenic diet affects the heart and brain. The theory is that an increased level of ketone bodies will improve energy utilization in the heart by reducing oxygen deficiency in the heart as well as increasing blood flow in the brain. The study participants must go through two periods of 3 weeks, during which they must eat an ordinary Danish diet and a ketogenic diet, respectively. The periods end with an examination day, where blood samples and samples from muscle and fat tissue are taken. They will also be scanned with CT, PET and MRI scans to determine their body's ability to absorb sugar, fat and ketone bodies. The investigators expect the results to be of crucial importance for dietary recommendations for people at risk for cardiovascular disease and type 2 diabetes.

Conditions

Ketogenic Dieting

Keywords

Ketogenic dieting; Heart metabolism; Brain perfusion

Outcome Measures

Primary Outcomes (1)

• Cardiac substrate metabolism and in perfusion in the brain

  The change in substrate metabolism and perfusion after a ketogenic diet compared to a standard western diet, will be measured with photon emission tomography (PET) combined with computed tomography (CT) and magnetic resonance (MR) scans. The values/units will be measured as radiation defined as radiation over time (becquerel/time). With specific PET-tracers we are able to measure absolute free fatty acid (palmitate tracer), perfusion (water tracer), energy (acetate tracer) and ketone bodies (beta-hydroxybutyrate tracer).

  Measurements will be made after 3 weeks on each diet with a washout period in between

Secondary Outcomes (7)

• Differences in circulating concentrations of free fatty acids, total cholesterol, glucose, andhemoglobine measured in mmol/l

  Measurements will be made on a screening day and after 3 weeks on each diet with a washout period in between

• Differences in circulating concentrations of lactate dehydrogenase, glucagon, hydroxybutyrate, gastric inhibitory peptide, and glucagon-like peptide-1, alanintransaminase, alkaline phosphatase, and erythropoietin measured in units/l

  Measurements will be made on a screening day and after 3 weeks on each diet with a washout period in between

• Differences in circulating concentrations c-reactive protein measured in mg/l

  Measurements will be made on a screening day and after 3 weeks on each diet with a washout period in between

• Changes in signaling in muscle and adipose tissue

  Measurements will be made after 3 weeks on each diet with a washout period in between

• Differences in body composition and fat distribution

  Measurements will be made on a screening day and after 3 weeks on each diet with a washout period in between

Study Arms (2)

Ketogenic diet

EXPERIMENTAL

The participants are instructed to follow a ketogenic diet consisting of 75% fat, 20% protein and 5% carbohydrates. The diet will be standardised and matched to the energy consumption of each participant.

Other: Ketogenic diet

Normal western diet

NO INTERVENTION

The participants are instructed to follow a normal western diet without emphasising any particular macronutrient.

Interventions

Ketogenic diet OTHER

The ketogenic diet will consist of 75% fat, 20% protein and 5% carbohydrates. The diet will be standardised and matched to the energy consumption of each participant. The diet does not dictate time of consumptions. The food regime will be strictly followed every day for 3 weeks, where the investigator will contact the participants every day to secure adherence.

Ketogenic diet

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 50-70-years old
• BMI: 28-40

You may not qualify if:

• All drugs that could affect the outcome
• HbA1c \> 48 mmol/mol
• Known heart failure og episodes of acute myocardial infarction
• Liver disease ALAT \> higher than 3 times of the normal level
• Kidney disease eGFR \< 60 ml/min
• Participation in other studies with radiation in the last 6 months
• Alcohol addiction

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus N, Jutland, 8200, Denmark

Location

Related Publications (1)

• Svart M, Rittig N, Luong TV, Gopalasingam N, Vestergaard ET, Gormsen L, Sondergaard E, Thomsen HH, Gravholt CH. Three Weeks on a Ketogenic Diet Reduces Free Testosterone and Free Estradiol in Middle-Aged Obese Men and Women. J Nutr Metab. 2024 Aug 6;2024:9301369. doi: 10.1155/2024/9301369. eCollection 2024.

  PMID: 39139216 DERIVED

MeSH Terms

Interventions

Diet, Ketogenic

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will be performed as a randomized, placebo-controlled crossover study in 12 healthy obese patients (BMI: 28-40 kg/m2) in the age group 50-70 years. Each participant will undergo two periods of three weeks, during which they must follow a ketogenic diet or a standard diet in random order with one week of wash out between periods. At the end of each period, a study day with Metabolic and PET examinations will be performed.

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: August 19, 2021
• Study Start: June 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 31, 2022
• Last Updated: November 2, 2022

Record last verified: 2021-06

Locations

DK (1)