A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease

Published: Neurobiology of Aging, 2014
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619192/ 

Background: Alzheimer’s disease – the most common form of dementia and cognitive decline – is characterized by two key pathologies: “amyloid plaques” and “tau tangles.” It is these plaques and tangles, along with dysfunctional carbohydrate metabolism in the brain, that are thought to contribute to Alzheimer’s disease.

Results: Adult mice were given either a control diet or a diet containing the same number of calories but supplemented with ketone ester. As they aged, the mice that received the ketone supplement exhibited less amyloid and tau in the regions of their brain associated with anxiety (amygdala) and memory (hippocampus). Importantly, the mice that received the ketones were also less anxieties and cognitively sharper in old age, providing both pathological and functional support for the notion that ketones are good for the aging brain. 

 

Further Reading

Over time, the human body undergoes wear and tear at the cellular level. This is called “biological aging” and it is, more or less, inevitable. However, while the rate at which you chronologically age is fixed, the rate at which you biologically age is not. Just like you can prolong the life of your car by maintaining it, you can likely slow biological aging and prolong life by properly fueling and maintaining your metabolic engine. 

Because ketones are a cleaner cellular fuel than carbohydrates, it would make sense that a body running on ketones would biologically age at a slower rate than a body running on mostly carbohydrates. Evidence from mice suggests this may be the case. In a study in which normal healthy adult mice ate either a control diet of standard mouse chow or a ketogenic diet containing the same number of calories, the ketogenic mice lived 13% longer. They also were cognitively shaper and physical stronger later into old age, suggesting that the ketogenic mice aged more slowly [1].

Direct human evidence that ketones slow aging is lacking and, therefore, no claims can be made regarding the potential anti-aging properties of ketones in human. However, it’s well established that ketones are a particularly clean and efficient cellular fuel, which means your body generates less damage when burning them as compared to other fuels [2]. Ketones also block oxidative stress and inflammation, which you can think of as the pathological foundations of biological aging [3, 4]. 

Until more research is conducted on humans, we cannot know for certain whether or not ketone molecules actually slow aging. However, multiple expert opinions published in the peer-reviewed scientific literature seem to imply that by increasing your ketone levels you stand the best chance of being around to find out [5, 6].  

1. Roberts, M.N., et al., A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab, 2017. 26(3): p. 539-546 e5.

2. Sato, K., et al., Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J, 1995. 9(8): p. 651-8.

3. Norwitz, N.G., M.T. Hu, and K. Clarke, The Mechanisms by Which the Ketone Body D-beta-Hydroxybutyrate May Improve the Multiple Cellular Pathologies of Parkinson's Disease. Front Nutr, 2019. 6: p. 63.

4. Curtis, W., et al., Mitigation of damage from reactive oxygen species and ionizing radiation by ketone body esters.  In: Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. Oxford Medicine, 2016.

5. Veech, R.L., et al., Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life, 2017. 69(5): p. 305-314.

6. Han, Y.M., T. Ramprasath, and M.H. Zou, beta-hydroxybutyrate and its metabolic effects on age-associated pathology. Exp Mol Med, 2020. 52(4): p. 548-555.