You wish to follow a "Paleolithic" diet? Here is what you can expect

High-protein diets, also known as "Paleolithic diets," are currently in vogue.

Using mouse models, scientists from the University of Geneva (UNIGE) have studied their impact. While effective for weight regulation and diabetes stabilization, they are not without risks.


Excess protein significantly increases the production of ammonium, and the liver, responsible for its elimination, becomes overwhelmed. Excess ammonium can cause neurological disorders, including coma in the most severe cases. These findings, published in the Journal of Biological Chemistry, urge caution when considering these diets.

Type 2 diabetes is a metabolic disease that is on the rise. In Switzerland, it is estimated that over 400,000 people are affected. Due to a sedentary lifestyle and a diet that is too rich, the damaged pancreas struggles to regulate blood sugar levels. While current treatments allow those affected to control the progression of the disease, they do not cure it. A significant part of its management involves weight loss.

"Diets rich in animal and/or plant proteins, known as Paleolithic diets, can be used to stabilize type 2 diabetes and regulate weight," explains Pierre Maechler, professor in the Department of Cellular Physiology and Metabolism at the Faculty of Medicine of UNIGE, who led this research. These diets are inspired by the meat-based diet that prevailed during prehistoric times. "But what are their effects on the body? Are they really harmless? That's what we aimed to find out."

The liver under pressure

Ammonium is a normal waste product from the breakdown of proteins, which is largely eliminated in the liver as non-toxic urea by an enzyme, glutamate dehydrogenase, or GDH. In case of protein overload, the GDH enzyme is put under pressure. To study the impact of high-protein diets, Pierre Maechler's team fed healthy mice and mice lacking the GDH enzyme in the liver with protein-rich foods, mimicking so-called Paleolithic diets.

The scientists observed that in healthy mice, although excess protein increases ammonium production, the liver manages to handle this surplus via the action of the GDH enzyme, which detoxifies ammonium before it can cause damage. "Conversely, in mice lacking the GDH enzyme, the liver cannot get rid of the toxic excess ammonium from proteins. No need for weeks or months, a change in diet for just a few days is enough to observe significant consequences," explains Karolina Luczkowska, former doctoral student in the Department of Cellular Physiology and Metabolism at the Faculty of Medicine of UNIGE, and first author of the study.

Caution is advised

These results suggest that in case of GDH enzyme dysfunction, high-protein diets would cause a harmful excess of ammonium. Ammonium, not eliminated by the liver, can lead to severe disorders, notably neurological ones.

Based on a blood test, it would be possible to assess GDH activity and avoid overloading the metabolism with proteins in individuals where the GDH enzyme does not permit it. "It is therefore important to be well-informed before following a high-protein diet," concludes Pierre Maechler.