Ketogenic diet delays the early stages of Alzheimer's-related memory loss in mice

A new study from researchers at the University of California, Davis, shows a ketogenic diet significantly delays the early stages of Alzheimer's-related memory loss in mice. This early memory loss is comparable to mild cognitive impairment in humans that precedes full-blown Alzheimer's disease. The study was published in the Nature Group journal Communications Biology.

The ketogenic diet is a low-carbohydrate, high fat and moderate protein diet, which shifts the body's metabolism from using glucose as the main fuel source to burning fat and producing ketones for energy. UC Davis researchers previously found that mice lived 13% longer on ketogenic diets.

Slowing Alzheimer's

The new study, which follows up on that research, found that the molecule beta-hydroxybutyrate, or BHB, plays a pivotal role in preventing early memory decline. It increases almost seven-fold on the ketogenic diet.

The data support the idea that the ketogenic diet in general, and BHB specifically, delays mild cognitive impairment and it may delay full blown Alzheimer's disease. The data clearly don't support the idea that this is eliminating Alzheimer's disease entirely."

Gino Cortopassi, co-corresponding author, biochemist and pharmacologist with the UC Davis School of Veterinary Medicine

Scientists gave mice enough BHB to simulate the benefits of being on the keto diet for seven months.

"We observed amazing abilities of BHB to improve the function of synapses, small structures that connect all nerve cells in the brain. When nerve cells are better connected, the memory problems in mild cognitive impairment are improved," said co-corresponding author Izumi Maezawa, professor of pathology in the UC Davis School of Medicine.

Cortopassi noted that BHB is also available as a supplement for humans. He said a BHB supplement could likely support memory in mice, but that hasn't yet been shown.

Other cognitive improvements

Researchers found that the ketogenic diet mice exhibited significant increases in the biochemical pathways related to memory formation. The keto diet also seemed to benefit females more than males and resulted in a higher levels of BHB in females.

"If these results translated to humans, that could be interesting since females, especially those bearing the ApoE4 gene variant, are at significantly higher risk for Alzheimer's," Cortopassi said.

The research team is optimistic about the potential impact on healthy aging and plans to delve further into the subject with future studies.

The study was funded by the National Institute on Aging, a unit of the National Institutes of Health.

Other authors include Jacopo Di Lucente and Lee-Way Jin with the Department of Pathology and the MIND Institute at UC Davis Health; John Ramsey, Zeyu Zhou, Jennifer Rutkowsky, Claire Montgomery and Alexi Tomilov with the School of Veterinary Medicine; Kyoungmi Kim with the Department of Public Health Sciences at UC Davis Health; Giuseppe Persico with the European Institute of Oncology, IRCCS; and Marco Giorgio with the University of Padova.