The aim of this project is to provide information on the potential cause-and-effect relationship of ketosis and disease risk.

Ketosis is broadly defined as a process that happens when your body doesn't have enough carbohydrates to burn for energy and instead burns fat. This process creates ketones, which it can use for energy.

We want to identify any differences between ketosis achieved by restricting carbohydrate intake or by taking a ketone supplement on disease risk.

We hope that this will provide the justification to advise for or against the use of such nutritional approaches to prevent the risk of developing diseases like heart disease, type 2 diabetes, cancer and kidney disease. In addition, this project will provide a template to determine the cause and effect of various nutritional approaches on disease risk.

Background information

Understanding the cause and effect for diet and disease is extremely challenging.

The gold-standard method of establishing cause and effect is the randomised controlled trial (RCT). Using RCTs to determine cause and effect of diet and disease, however, is limited by the ethical and practical constraints of asking people to follow a diet they have been assigned to at random for decades.

An approach based on our genetics (known as Mendelian randomisation) can be used to estimate cause and effect of biological factors, such as cholesterol levels, on disease risk. Mendelian randomisation is, however, limited in the ability to establish cause and effect of complex behaviours such as diet.

In this project, we will combine a RCT with Mendelian randomisation to overcome the limitations of each approach in isolation. We will use this unique combination to understand how a very-low carbohydrate (ketogenic) diet may influence disease risk, and whether the potential benefits of a ketogenic diet can be achieved without the need to restrict dietary carbohydrates (via simple supplementation with a ketone supplement).

Our research study

We will ask volunteers with a body mass index (BMI: weight in kilograms divided by height in metres squared) between 25-45 kg/m2 to participate in our research.

Participants will be provided all their required food for four weeks of a ketogenic diet. This will either be provided during the main testing phase, or for people assigned to one of the control groups, as an optional extra after the main study period.

In addition, people will be provided with either a ketone supplement or a placebo supplement to take during a four-week period. They will visit the Centre for Nutrition, Exercise and Metabolism’s laboratories for two main testing days, plus an optional third visit.

On these days, measures of metabolism from breath samples and blood samples will be taken, alongside some biopsies (small samples) of fat tissue and a whole-body body scan to determine body composition. We will measure people’s responses to a meal by taking blood samples for four hours after ingesting a beverage.

On the third optional visit, we will take a single blood sample and perform a whole-body scan to determine changes in metabolism and body composition.

Find out more about how you can take part in our research study

Team members

This project benefits from the skills and expertise of researchers from the University of Bath, the University of Bristol and Imperial College London.

• Professor Javier Gonzalez, University of Bath
• Emma Hazelwood, Cambridge University
• Dr Francoise Koumanov, University of Bath
• Dr Jennifer Maher, University of Bath
• Dr Sophie Russell, University of Bath
• Bruno Spellanzon, University of Bath
• Dr Emma Vincent, University of Bristol
• Dr James Yarmowlinsky, Imperial College London
• Harry Yuen, University of Bath