A recent study conducted on a mouse model has revealed promising results regarding the potential of a ketogenic (keto) diet in delaying the onset of Alzheimer’s disease (AD).
The study, conducted by researchers at the University of California, Davis (UC Davis), found that a ketogenic diet led to a sevenfold increase in the levels of the beta-hydroxybutyrate (BHB) molecule in mice, effectively postponing the onset of Alzheimer’s disease.
BHB, a molecule associated with delays in the onset of mild cognitive dementia typical of early-stage Alzheimer’s, is naturally produced in humans when the body burns fat for energy to fuel the body’s mitochondria. This molecule aids in the transfer of energy from the liver to the rest of the body when glucose levels are insufficient.
According to the authors of the study, their previous research has demonstrated that BHB exhibits anti-inflammatory properties for human brain cells inflamed by beta-amyloid plaques, which were once considered the primary cause of Alzheimer’s. However, foundational research identifying these plaques as the cause of Alzheimer’s has since been discredited, as many individuals with the plaques never develop the disease.
The study involved genetically modified APP/PS1 mice, which express both a mouse/human amyloid precursor protein and a mutant human presenilin 1 gene targeting central nervous system neurons. These mice were bred at UC Davis and raised in controlled environments, with a 12-hour light and 12-hour dark cycle and a standard mouse chow diet for the initial six months. Following this period, they were divided into weight-balanced groups and provided with either a ketogenic diet or a carbohydrate-rich standard diet, both of which contained the same number of calories.
Results of the study revealed that female mice exhibited higher levels of BHB in their bodies than males, along with increased brain enzymes known to support memory. Additionally, male mice switched to a ketogenic diet in late-midlife showed improvements in spatial memory.
Published in Nature Communications Biology, the study sheds light on the potential benefits of a ketogenic diet in delaying Alzheimer’s onset.
Understanding the Impact of Ketogenic Diet on Neuroinflammation
Michelle Routhenstein, who was not involved in the study, explained that a ketogenic diet induces ketosis, a metabolic state where the body primarily burns fat for fuel instead of carbohydrates, resulting in the production of ketone bodies as an alternative energy source.
While concerns regarding the higher fat content of a ketogenic diet may promote neuroinflammation, Routhenstein emphasized that certain fats, such as omega-3 fatty acids, fat-soluble carotenoids, and vitamins, possess neuroprotective properties that can mitigate inflammation and oxidative stress. However, excessive intake of saturated fats may elevate cholesterol levels and cardiovascular risk.
Routhenstein cautioned against strict adherence to a ketogenic diet due to potential long-term adverse effects on heart and gut health, as well as the risk of nutrient deficiencies, emphasizing the importance of balanced nutrition and consultation with a healthcare provider.
Elevating BHB Levels in Humans
Dr. Gino A. Cortopassi, the lead author of the study, highlighted the mechanisms through which BHB levels increase in humans. Fasting for approximately 12 hours leads to a rise in BHB levels as carbohydrate stores become depleted. Individuals following a ketogenic diet exhibit significantly higher BHB levels compared to those on a standard carbohydrate-rich diet.
Dr. Cortopassi outlined three methods to increase human BHB levels: adopting a ketogenic diet, taking BHB supplements, or following a one-meal-a-day carbohydrate diet, albeit less effectively, as BHB levels drop rapidly after consuming carbohydrates.
Limitations and Future Directions
While the study presents intriguing findings, Dr. Stefania Forner, Ph.D., director of medical and scientific relations at the Alzheimer’s Association, cautioned against extrapolating conclusions to humans based on animal studies alone. More research is warranted to comprehensively understand the impacts and outcomes of a ketogenic diet on individuals at risk for or living with Alzheimer’s.
Dr. Forner underscored the importance of conducting human studies, such as the U.S. POINTER clinical trial, scheduled for publication by the Alzheimer’s Association in 2025. This trial aims to assess whether lifestyle interventions targeting various risk factors, including diet, can protect cognitive function in older adults at increased risk for cognitive decline.
In conclusion, while the study offers promising insights into the potential benefits of a ketogenic diet in delaying Alzheimer’s onset, further research is essential to validate these findings and elucidate the complex interplay between diet and cognitive health in humans. Individuals considering dietary modifications for Alzheimer’s prevention or treatment should consult healthcare professionals for personalized guidance and recommendations.