Ketosis Controversy

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The ketogenic diet is a high-fat, low-carbohydrate and normal-protein diet that has been used for the treatment of clinically refractory childhood epilepsy since the 1920s. During a low carbohydrate intake, the controlled and regulated production of ketone bodies causes a physiological state known as dietary ketosis.

Although beneficial effects of the ketogenic diet have been proven, there is still controversy surrounding some of the issues. Proponents of the ketogenic diet proclaim it as a magical diet that can even cure cancer, while opponents denounce the diet due to misconceptions about the underlying physiology. As with so many issues of controversy, the reality lies somewhere in between.

Image Credit: Oleksandra Naumenko / Shutterstock
Image Credit: Oleksandra Naumenko / Shutterstock

A potential role in cancer

Carcinogenesis is a complex process in which normal cells turn into cancer cells via multiple sequential mutations occurring randomly in the DNA over many years. Hyperinsulinaemia, hyperglycemia and chronic inflammation may influence the neoplastic process through various pathways, and a majority of cancer cells express insulin and insulin-like growth factor 1 (IGF-1) receptors.

It has been demonstrated that insulin can stimulate mitogenesis (induction of mitosis), even in cells lacking IGF-1 receptors. Multiple cancer mechanisms can also be stimulated, including proliferation, protection from apoptosis (programmed cell death), invasion and metastasis.

Taking into account the tangible relationship between carbohydrates, insulin and IGF-1, a connection between carbohydrates and cancer is a potential consequence; hence certain links have been recognized since the 1920s when it was observed that glycosuria falls off strikingly in diabetic patients who developed cancer.

Even though randomized controlled trials of a ketogenic diet on patients are lacking and the bulk of evidence in relation to its influence on patient survival is still anecdotal, some recent studies suggest that the insulin inhibition caused by a ketogenic diet could be a viable adjunctive treatment for patients with cancer.

Still, the relative contributions of genetic mutations, immune cell dysfunction, metabolic disturbances and influences of the microenvironment are likely to differ depending on the type of tumor and thus necessitate different treatments. That is the reason why many experts believe that, as with many other hyped cancer cures, the ketogenic diet could be helpful for some tumors, but almost certainly not for others.

Side effects and drawbacks of the ketogenic diet

Like most dietary approaches, the ketogenic diet has certain benefits and drawbacks. Most of the side effects from this type of dieting are related to nutrient and energy deficiencies. Lack of carbohydrates, proteins and other nutrients can result in lack of weight gain and growth retardation – especially at a young age.

Rare side effects include cardiomyopathy, prolonged QT syndrome, mineral and vitamin deficiencies, pancreatitis, basal ganglia injury and bruising. The long-term results of the aforementioned side effects have not been properly studied; hence follow-up and monitoring of any adverse responses are necessary.

If ketogenic diets are equated with high-protein diets (which is not always a correct association), there are potentially hazardous implications for kidney function that can lead to its progressive impairment. Increased consumption of dietary protein results in high levels of nitrogen, subsequently causing an increase in glomerular pressure and hyperfiltration.

Another common criticism of epilepsy studies is that the live brain has not been studied as meticulously as in vitro preparations. In addition, rats treated with 2-3 weeks of a ketogenic diet did not show changes in tests of locomotor function or in a conditioned fear test. There were also no changes in electrophysiological estimates of long-term potentiation in vivo.

The extent of medical complications and their potential importance mandate a high level of expertise, practical knowledge and a high index of suspicion in children undertaking a ketogenic diet. The ketogenic diet has been proven beneficial for epilepsy and other health issues, but for a small group of patients (namely children) its complications can be severe and life-threatening.

Further Reading

Last Updated: Apr 8, 2021

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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