In Switzerland, tens of thousands of people follow a vegan diet, which excludes all animal-derived products. Although a plant-based diet is recommended, notably for its environmental benefits, the health consequences of such a diet – in which protein intake is exclusively plant-based – are not yet fully understood. Scientists at the University of Geneva (UNIGE) have studied, in mice, the effects of switching from a diet containing both animal and plant proteins to one containing only plant proteins. Within just a few days, liver metabolism changes and the willingness to engage in physical exercise decreases significantly. At the heart of these changes lies a liver enzyme, glutamate dehydrogenase (GDH). The findings are published in Molecular Metabolism.

The proteins we eat, whether animal or plant-based, are made up of amino acids, small molecules linked together like the links in a chain. Their nature and proportions vary depending on the food source. Plant-based proteins naturally contain fewer branched-chain amino acids than animal proteins. However, these specific amino acids serve more than just building our proteins. They also provide the liver with some of the raw material needed to produce and maintain sufficient levels of glucose in the blood during fasting.

What impact does switching from a mixed diet (animal and plant proteins) to an exclusively plant-based diet have on the body, and on liver metabolism in particular? This is what Pierre Maechler, full professor in the Department of Cell Physiology and Metabolism and at the Diabetes Centre of the UNIGE Faculty of Medicine, set out to investigate by comparing two groups of mice: one on a lacto-vegetarian diet comprising both plant-based and animal proteins, and the other on a vegan diet.

“In just two days, the mice fed an exclusively vegan diet showed less efficient glucose production,” explains Pierre Maechler. “Furthermore, their livers were less effective at eliminating ammonia, a toxic substance released during the breakdown of amino acids. A significant reduction in physical activity also suggests effects on the body as a whole.”

The pivotal role of the GDH enzyme

This impaired regulation of glucose and ammonia suggests the involvement of a specific molecular player: the enzyme glutamate dehydrogenase (GDH). Located in the mitochondria of liver cells, GDH acts as a bridge between protein metabolism and sugar metabolism. By comparing their two groups of mice lacking GDH in the liver, one group on a lacto-vegetarian diet and the other on a strict vegan diet, the team confirmed the essential role of this enzyme in the metabolic changes induced by a strict vegan diet.

In mice fed exclusively on plant proteins, the absence of GDH led to a severe build-up of ammonia and impaired blood glucose regulation, compared to mice that were also fed animal proteins. “Overall, a change in diet alters liver metabolism very quickly, but this effect is just as rapidly reversible,” emphasises Pierre Maechler. “The body adapts within one to two days to even subtle changes in dietary composition and returns to normal upon the reintroduction of animal proteins.”

Diversifying your diet to maintain balance

While this ability to adapt illustrates the liver’s remarkable plasticity, it also has practical implications for our everyday diet. “In addition to the ethical and environmental considerations that often motivate a switch to a plant-based diet, there are also scientific factors relating to the physiological functioning of our metabolism that are worth being aware of,” notes Pierre Maechler.

This research serves as a reminder that a change in diet is not without significance for the body. In the case of a strict vegan diet, in addition to ensuring an adequate intake of specific vitamins, it is important to prioritise protein sources rich in branched-chain amino acids, such as nuts, tofu or lentils, in order to best support the liver’s metabolic functions.