Obesity, diabetes and cardiovascular diseases can be treated with a ketogenic diet, consisting mainly of… fat.

The observations of dieticians and clinical practitioners are confirmed by molecular-level research carried out at the French institute Inserm (French National Institute for Health and Medical Research) by Prof. Aneta Balcerczyk. Prof. Balcerczyk carried out her research during a fellowship financed by NAWA scholarship under the Bekker Programme. The results indicate that fat metabolism products have a beneficial effect on blood vessels. The condition is to reduce carbohydrate intake to an absolute minimum.

NAWA: What prompted you to undertake this research?

Prof. Aneta Balcerczyk, University of Lodz: Our knowledge of the role of diet in treating and supporting the treatment and prevention of various types of pathologies has increased greatly in recent years. Yet I think we can still do more on this subject. The ketogenic diet, on which we focused in our study, is a special type of high-fat diet. It is characterized by a very high fat content, oscillating between 80 and 90%. Carbohydrates represent less than 5% of the nutrients taken in this diet, and the rest are proteins. Such a high fat content makes the body start to treat fat as the primary source of energy for all metabolic processes. We started research on the ketogenic diet and the function of ketone bodies, which are metabolic products of the diet, including beta-hydroxybutyrate (3HB), because we know fairly much about the effects of this model of nutrition, but rather little about the underlying molecular mechanisms.

When is the ketogenic diet used?

The ketogenic diet is successfully used in the treatment of drug-resistant epilepsy in children, also in people with congenital lack of protein responsible for glucose transport (GLUT-1). The results are promising in the treatment of obesity and diabetes. The use of ketogenic diet as a factor supporting the treatment of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and autism is taken into consideration as well. As I mentioned, the molecular consequences of the presence of ketone bodies are underresearched. The reports, e.g. on the potential inhibition of histone deacetylases (HDACs), which are targeted by anticancer therapies, are often contradictory.

What is the focus of the research project you participate in?

In our project, we focus on the vascular endothelium. It is a layer of cells lining the inside of blood vessels. Their abnormalities may affect the progression of cancer and the formation of cardiovascular pathologies such as atherosclerosis or hypertension. In addition, they can intensify complications resulting from diabetes or obesity.

Why are you testing the vascular endothelium?

The vascular endothelium is not only a layer of cells. It is basically an endocrine organ that produces substances responsible for regulating a range of processes that determine the work of the cardiovascular system, such as vascular tension, osmotic blood pressure, adhesion of morphotic blood elements to the endothelium, the process of wound healing, the creation of new blood vessels, or blood clotting. A disturbance of normal endothelial function leads to its activation and changes in secretion profile, including from anti-inflammatory to pro-inflammatory, and to the secretion of mediators that intensify endothelial dysfunction, which in consequence and long-term perspective leads to serious cardiovascular diseases.

What are the most important findings of the study?

We are only just beginning a series of experiments on the mouse model, so it is difficult for me to extrapolate based on the data obtained from cell cultures, i.e. on the endothelial cells of the microvascular endothelium. Still, the results so far are promising and give reason to believe that 3HB has an anti-inflammatory potential against the endothelium, at least in vitro, i.e. under conditions that only partially mimic those of the body.

What effect can the results of this study have on dietary recommendations?

I would like to postpone the final answer to this question until we have more data. The current ‘healthy eating pyramid’ places fats on top of it, suggesting low fat intake. However, it should be stressed that the ketogenic diet strictly defines the ratio of fats to carbohydrates, limiting the intake of the latter to a minimum (no more than 5% of all products). The idea is to change the metabolism, i.e. to change the metabolic fuel from carbohydrates (which are the source of energy in a balanced diet based on the current ‘healthy eating pyramid’) to fats. It is very important not to exceed the recommended carbohydrate dose. It seems that with such a high fat content as is present in the ketogenic diet, carbohydrates may in the long run act as a catalyst to induce pathological states within the cardiovascular system, but also systemically lead to obesity.

How did the NAWA scholarship help you to carry out your research plans?

I was awarded a NAWA scholarship under the Bekker Programme, which involved fellowship at one of the best scientific centres in the world – INSERM in France. My stay at the CarMeN Institute in Lyon was very valuable from the point of view of strengthening international cooperation. It allowed me to carry out a HARMONIA research project (NCN 2019/30/M/NZ3/00682) in cooperation with Prof. L. Pirola and Prof. M. Strigini. It resulted in two scientific articles, which were published in the International Journal of Molecular Sciences and World Journal of Diabetes. And that is not the end of it: we continue our cooperation, which we hope will enable us to explore the phenomenon of the ketogenic diet.  

How would you encourage other scientists to apply for a NAWA scholarship?

The mobility of researchers and the experience gained during a research fellowship involving working abroad are extremely important and valuable, not only scientifically, but also culturally. Research stays allow us to develop our research workshop and exchange scientific ideas. Very often, they result in establishing long-term cooperation and joint research projects. In addition, by deciding to stay at a foreign research institution, away from our home university or centre, we go somewhat beyond our daily comfort zone. We have to adapt to new conditions, which makes us more tolerant and open to a new culture. All this enriches us not only as scientists, but also simply as people. It allows us to broaden our horizons and open our minds. And this is what should characterise a scientist – an open mind, a desire to know the unknown.  

Thank you for your time.

Dr. Aneta Balcerczyk, professor of the University of Lodz, is a graduate of the Faculty of Biology and Environmental Protection of the University of Lodz, and currently professor at the Department of Molecular Biophysics of the University of Lodz. Her scientific interests are mainly: the search for epigenetic mechanisms of angiogenesis regulation determined by posttranslational modifications of histone proteins; the influence of hyperglycaemia on cell functions, mainly of the vascular endothelium; and issues concerning the role of diet in endothelial cell metabolism and cardiovascular functioning. She was a winner in the ‘Start’ Programme of the Foundation for Polish Science (FNP) twice. As part of the Human Frontier Science Program Organization (HFSPO) scholarship, and later the FNP’s Columbus Program, she completed a three-year fellowship at the Baker Heart&Diabetes Research Institute in Melbourne, where she was mainly involved in the study of mechanisms of epigenetic metabolic memory. Moreover, she won a ĽOreal postdoctoral fellowship and a foreign visit scholarship from the Polish National Agency for Academic Exchange (NAWA) under the Bekker Programme. It entailed her stay at INSERM U1060, CarMeN Laboratory in Lyon, where she carried out a project on the influence of the ketogenic diet on vascular endothelial function in cooperation with other scientists.

Professor Balcerczyk is the author of numerous research and review publications in journals listed in the Journal Citation Reports. She has directed or participated in several research projects financed, among others, by the National Science Centre (NCN), the Ministry of Science and Higher Education, and the Scientific Research Committee. Moreover, she has been a reviewer of research projects submitted under the EU ‘Horizon 2020’ programme and the NCN competition as well as scientific articles in Polish and foreign journals. (Photo: Prof. Aneta Balcerczyk’s archive)

How to become a NAWA scholarship holder under the Bekker Programme? 

For detailed information about NAWA, click HERE

Photo on home page: ©doucefleur stock.adobe.com.