Could a keto diet boost brain health?

The ketogenic diet, more commonly referred to as the keto diet, has been around for over a century now. This may surprise many, as it only really gained traction in popular culture in the mid-1990s. The term ‘ketogenic’ was first coined by Dr Russell Wilder of the Mayo Clinic in the United States in 1921 in his works to find a nutritional treatment for epilepsy. Since then, scientists and health professionals have been looking at the potential benefits of the ketogenic diet on other health issues and on general health. FoodNavigator previously reported on a study by the University of California, Davis, which looked at the potential for the ketogenic diet to combat the early signs of Alzheimer’s​. Now, researchers are looking at the ketogenic diet as a way to improve brain health.

How can the keto diet boost brain health?​

A new study, conducted by scientists at the Buck Institute and the University of Chile, has found that the high-fat, low-carbohydrate content of the ketogenic diet enhances memory in older mice. The team identified a novel molecular signalling pathway that improves synapse function, when consuming the ketogenic diet, shedding light on the diet’s benefits for brain health and aging. “Our work indicates that the effects of the ketogenic diet benefit brain function broadly, and we provide a mechanism of action that offers a strategy for the maintenance and improvement of this function during aging,” says Dr Christian González-Billault, Professor at the University of Chile. The study follows on from previous research carried out by the team, looking at the impact of the ketogenic diet on memory. “Building off our previous work showing that a ketogenic diet improves healthspan and memory in aging mice, this new work indicates that we can start with older animals and still improve the health of the aging brain, and that the changes begin to happen relatively quickly,” said Dr John Newman, at the Buck Institute. “It is the most detailed study to date of the ketogenic diet and aging brain in mice. The current study aimed to understand what part of the ketogenic diet was having the memory-saving effect and how it was affecting the brain on a molecular level to improve memory.

How was the study conducted?​

The study involved one group of mice fed a ketogenic diet of 90% calories from fat and 10% from protein, and another group of mice on a control diet fed the same amount of protein but only 13% fat. The team explained that the benefits of the ketogenic diet were demonstrated through neurophysiological and behavioural experiments. The mice were tested on memory generation, storage, and retrieval function. The test results showed that the ketogenic diet appeared to benefit how well the synapses, responsible for memory, worked. “Surprisingly, we saw that the ketogenic diet caused dramatic changes in the proteins of the synapse,” explains Dr Birgit Schilling, Professor at the Buck Institute. Dr Birgit Schilling further explained that the changes started after a relatively brief exposure to the diet, with the mice showing positive results after only one week on the diet. The effects were also shown to become more pronounced over time. Further testing indicated that in synapses, a particular signalling pathway (protein kinase A, which is critical to synapse activity) was activated by the ketogenic diet. In isolated cells, the team then showed that it appears that BHB, the main ketone body produced in a ketogenic diet, is activating this pathway. “BHB is almost certainly not the only molecule in play, but we think this is an important part of understanding how the ketogenic diet and ketone bodies work,” said Newman “This is the first study to really connect deep molecular mechanisms of ketone bodies all the way through to improving the aging brain.”

Health concerns linked to a ketogenic diet​

The ketogenic diet has received some criticism in recent years following links to a range of health concerns including an increased risk of kidney stones, liver disease and micronutrient deficiencies. There are further long-term concerns relating to the impact of the high-fat levels, maintained in the ketogenic diet, on cardiovascular health. Source: Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signalling pathway in aging mice
Published online: 5 June 2024
DOI: https://doi.org/10.1016/j.xcrm.2024.101593
Authors: Diego Acuña-Catalán, Samah Shah, Cameron Wehrfritz, Mitsunori Nomura et al.