Summary: A ketogenic diet significantly postpones the onset of Alzheimer’s-related memory decline in mice, a phase akin to human mild cognitive impairment preceding Alzheimer’s disease. Key findings highlight the molecule beta-hydroxybutyrate (BHB) as instrumental in this protective effect, showing a nearly seven-fold increase in mice on the diet and improving synaptic function critical for memory.
While the study indicates that the diet, particularly BHB, doesn’t eliminate Alzheimer’s, it suggests potential for delaying its early stages. Additionally, the research noted more pronounced benefits in female mice, pointing to intriguing implications for human health, especially among women at higher risk for Alzheimer’s.
Key Facts:
- Ketogenic Diet’s Protective Role: The ketogenic diet boosts levels of BHB in the body, which is linked to delaying the early stages of Alzheimer’s-related memory loss in mice.
- Gender-Specific Benefits: The ketogenic diet was found to be more beneficial for female mice, indicating a potential for greater impact on women, particularly those with the ApoE4 gene variant linked to higher Alzheimer’s risk.
- Future Research Directions: The findings open new avenues for research into healthy aging and Alzheimer’s prevention, with an emphasis on further exploring the effects of BHB supplementation and the ketogenic diet’s neuroprotective mechanisms.
Source: UC Davis
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,” said co-corresponding author Gino Cortopassi, a biochemist and pharmacologist with the UC Davis School of Veterinary Medicine.
“The data clearly don’t support the idea that this is eliminating Alzheimer’s disease entirely.”
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.
Funding: 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.
About this diet and Alzheimer’s disease research news
Author: Amy Quinton
Source: UC Davis
Contact: Amy Quinton – UC Davis
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Ketogenic diet and BHB rescue the fall of long-term potentiation in an Alzheimer’s mouse model and stimulates synaptic plasticity pathway enzymes” by Gino Cortopassi et al. Communications Biology
Abstract
Ketogenic diet and BHB rescue the fall of long-term potentiation in an Alzheimer’s mouse model and stimulates synaptic plasticity pathway enzymes
The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer’s Disease (AD) model APP/PS1.
KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-β (Aβ) levels. KD’s ‘main actor’ is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD’s 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity.
KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females.
We suggest KD rescues LTP through BHB’s enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer’s Disease.
