RESEARCH REVIEW: KETOGENIC DIET THERAPY AND ALZHEIMER’S DISEASE
Alzheimer's disease affects around 6 million people in the United States, which is projected to increase nearly 3-fold in the next 40 years, with estimates of 14 million people being impacted by Alzheimer's by the year 2060.
We know that risk factors such as aging and genetics may play a role in the progression of Alzheimer's disease, but effective preventative strategies and treatment protocols have yet to be defined. For this reason, scientists are turning to metabolic and nutritional approaches to slow or even prevent the onset of Alzheimer's and other forms of dementia.
The ketogenic diet is of particular interest as this high-fat diet plan was originally developed back in the 1920s to help calm the nervous systems of people with epilepsy. Since then, ketones have been studied for various potential therapeutic outcomes, with neurological health being one of the most promising.
In a recent article published in the journal Advances in Gerontology, investigators conducted a research review of clinical trials focusing on ketogenic diet therapy for Alzheimer's disease. The review focuses on the potential therapeutic effect of ketones on Alzheimer's symptoms and pathology, as well as the clinical outcomes of this dietary pattern.
Let's take a closer look at what they've uncovered.
Study Design And Methods
The authors of the study conducted a literature search in the following databases to gather all relevant human studies related to Alzheimer's disease or mild cognitive impairment and the ketogenic diet:
- CENTRAL databases for clinical trials
Their review noted trends in outcomes, along with common threads in the mechanisms by which ketones may help protect the brain. The studies focused primarily on cognitive assessments and brain energy metabolism.
How Do Ketones Protect The Brain?
Neurological diseases like Alzheimer's and other dementias are associated with a range of abnormalities in the brain, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired glucose metabolism.
Ketones, due to their unique structure and function, impart valuable therapeutic effects on brain tissue by combating potential damage to brain cells and providing neuroprotection against future damage.
Ketones, Mitochondria, and Oxidative Stress
While oxidation is a natural physiological process, and small amounts of oxidative stress are normal, brain tissue is especially vulnerable to oxidative damage.
Research shows that oxidative stress plays a role in the functional changes accompanying Alzheimer's disease due to increased production of reactive oxygen species (ROS), outpacing antioxidant defenses.
This is partially due to mitochondrial dysfunction, which can be affected by amyloid peptides that are common in Alzheimer's disease. Your mitochondria are the powerhouse of your cells; they are the organelle in which all energy production occurs.
When the amyloid peptides interact with mitochondria, they can interfere with their proper function and create an upsurge of ROS. In fact, mitochondrial dysfunction and the resulting increase in ROS are thought to be one of the instigating factors that set the stage for Alzheimer's disease.
Ketones are known to enhance antioxidant forces while decreasing oxidative stress. Furthermore, the generation and use of ketones for fuel may enhance cellular metabolism and improve mitochondrial function as well as mitochondrial biogenesis.
Put simply; ketones may relieve some of the oxidative burden that happens when mitochondria are damaged.
Along with oxidative stress, neuroinflammation also appears to have a prominent role in the pathogenesis of Alzheimer's disease. There is still debate as to whether the inflammatory response is the result of Alzheimer's pathology or a part of the initiating cause. Either way, reducing inflammation in the brain may help to slow some of the damage caused by the disease.[5,6]
Studies show that the ketogenic diet provides broad anti-inflammatory benefits, including targeting inflammation in the brain. Specifically, the ketone body beta-hydroxybutyrate has been shown to down-regulate several inflammatory pathways that are associated with Alzheimer's disease.[7,8]
Impaired Brain Glucose Metabolism
Brain scans of people with Alzheimer's and other dementia's show that there are specific areas of the brain that exhibit a reduced glucose uptake, impairing glucose utilization. Glucose is the primary source of fuel for neurons (brain cells(, which makes its impairment a contributing factor to the decline in neurological health that's exhibited in dementia.
Although the pathology isn't clear, clinical studies show that impaired glucose metabolism is likely due to functional issues in the blood-brain barrier, which inhibits glucose from reaching the brain tissue[9,10].
Issues can be further exacerbated for people that already have some form of insulin resistance or type 2 diabetes.
Ketones, which offer an alternative energy source, don't exhibit the same inhibition as glucose. In fact, studies show that ketone metabolism in people with dementia is comparable to that of healthy individuals.
Research Review Outcomes and Conclusions
From their research review, the study authors found significant evidence for the following positive outcomes in the use of the ketogenic diet in Alzheimer's disease:
- Increased cognitive function scores
- Improved verbal and episodic memory
- Improved attention
- Increased cerebral blood flow
- Enhanced cognitive performance in logical memory
- 230% enhanced brain metabolism of ketones
- Improved language skills
- Improved executive function
The authors conclude that in the absence of effective treatment for Alzheimer's disease, the ketogenic diet holds promise to not only slow but potentially stop the progression of early-stage Alzheimer's disease and mild cognitive impairment (MCI).
In addition to several areas of cognitive improvement, low-carbohydrate diets also improve energy metabolism in the brain.
The authors did not cite any adverse effects on biomarkers in AD patients.
With that being said, more research is needed to follow up on what we've learned here and assess the clinical effects of ketosis beyond six months.
Neurodegenerative diseases like Alzheimer's and Parkinson's disease are becoming more prevalent in older adults, instigating cognitive decline and impairing quality of life.
Although the authors note that more clinical studies are needed to assess the long-term effects of keto, it appears that following a ketogenic diet may be both a safe and effective option for halting the progression of Alzheimer's.
If you’re interested in learning more about the ketogenic diet, check out the BioCoach App Membership.
Research Review: Şimşek, H., and A. Uçar. "Is Ketogenic Diet Therapy a Remedy for Alzheimer’s Disease or Mild Cognitive Impairments?: A Narrative Review of Randomized Controlled Trials." Advances in Gerontology 12.2 (2022): 200-208.
- Huang, Wen‑Juan, X. I. A. Zhang, and Wei‑Wei Chen. "Role of oxidative stress in Alzheimer's disease." Biomedical reports 4.5 (2016): 519-522.
- Picone, Pasquale, et al. "Mitochondrial dysfunction: different routes to Alzheimer’s disease therapy." Oxidative medicine and cellular longevity 2014 (2014).
- Gano, Lindsey B., Manisha Patel, and Jong M. Rho. "Ketogenic diets, mitochondria, and neurological diseases." Journal of lipid research 55.11 (2014): 2211-2228.
- Kinney, Jefferson W., et al. "Inflammation as a central mechanism in Alzheimer's disease." Alzheimer's & Dementia: Translational Research & Clinical Interventions 4 (2018): 575-590.
- Leng, Fangda, and Paul Edison. "Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?." Nature Reviews Neurology 17.3 (2021): 157-172.
- Pinto, Alessandro, et al. "Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease." Antioxidants 7.5 (2018): 63.
- Koh, Sookyong, Nina Dupuis, and Stéphane Auvin. "Ketogenic diet and neuroinflammation." Epilepsy Research 167 (2020): 106454.
- Kuehn, Bridget M. "In Alzheimer research, glucose metabolism moves to center stage." Jama 323.4 (2020): 297-299.
- Cunnane, Stephen C., et al. "Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease." Annals of the New York Academy of Sciences 1367.1 (2016): 12-20.