Mild Ketosis for Alzheimer’s Disease and Cognitive Decline

by Eva Coles MS, RDNNutrition
the word, keto, spelled with foods

The keto diet and modified versions of it are increasingly being explored as a potential treatment for cognitive decline and to optimize brain health [1]. So how exactly can ketosis promote cognitive function? What does some of the latest research show on Alzheimer’s disease?

What is the Ketogenic Diet?

To provide a brief overview, the keto diet is a low carbohydrate (<10% total energy), high fat (80-90% total energy), moderate protein (~10% total energy) food plan intended to put you in ketosis, a state during which your liver breaks down fat to produce chemical compounds called ketones [1]. Restricting carbohydrates to such an extent causes the body to go through a metabolic switch, from using carbohydrates (glucose) to using fat (lipids) as its main source of energy [2]. This ability to switch between the two fuel types is known as metabolic flexibility, which you can learn more about in a previous blog post where we also discussed some misconceptions about the ketogenic diet. When you achieve a state of metabolic ketosis, your liver will break fat down through a process called beta-oxidation into a few different ketone bodies or ketones, including acetoacetate (ACA), beta-hydroxybutyrate (BHB), and acetone (yes, the nail polish remover) [2]. 

In our practice we focus on a predominantly Mediterranean-style  plant-based keto diet, which you may be surprised can still be modified to achieve ketosis. If you want to delve a little deeper, we have covered how you can achieve mild ketosis with a plant-based diet and its cognitive benefits 

Why is the Keto Diet Good for Cognition?

Research has shown that a mild state of ketosis is optimal for cognition [3], which means you would not have to adhere to the draconian-like restrictions you may associate to a ketogenic diet. Interestingly, most of the benefits from this food plan are attributed to ketone bodies, notably BHB and ACA, which work in a number of ways: 

  • Ketones bypass the imparied glucose metabolism associated with cognitive decline and Alzheimer’s and serve as an alternative fuel source for the brain [4]. Read more about glycotoxic Alzheimer’s here. 
  • ACA can reduce the levels of glutamate, a neurotransmitter that can become overactivated causing cell death and neurodegeneration [4,5].
  • BHB can boost the production of brain-derived neurotrophic factor (BDNF), which promotes ther growth of new neurons [6]
  • Ketone bodies can reduce inflammation and oxidative stress in the brain [4,8]

What the Latest Science Says

In this section, we will summarize some key findings from recent studies investigating a ketogenic diet and ketogenic supplements (MCT oil, BHB) in subjects with Alzheimer’s disease, mild cognitive decline, and mice models. 

Mice Models

  • Reduced B amyloid in mice given either a keto diet or BHB for 8-35 weeks in four separate studies [7]
  • Reduced Tau protein and inflammation in mice given BHB supplementation for 8 weeks [7]. 
  • Increased neurotransmitter levels in mice given a ketogenic diet for 35 weeks. 

Human Studies [7,8,9,10] 

  • Improved memory in adults with MCI given a ketogenic diet for 6 weeks. 
  • Improved cognition in adults with MCI or mild Alzheimer’s given MCT oil (17g-30g) for 4-26 weeks
  • Improved quality of life in adults with mild Alzheimer’s given a keto diet for 12 weeks

Some Limitations

While ketogenic diets offer a number of health benefits, it is important to note some significant limitations and challenges with the existing research: 

  • Some patients experienced mild digestive discomfort, especially after longer periods of being under a ketogenic diet. So it is important to be mindful of how you may react to a dietary change and always communicate with your dietitian or healthcare professional.
  • Most of the research includes small scale studies with short-term follow-up, which implies we have limited information of long-term efficacy for congition. 
  • There is no standardized ketogenic diet intervention and each study varied greatly in the foods and macronutrient distributions they used. This makes it difficult to confirm findings. 

What if You are an ApoE4 Carrier?

As you likely already know, being a carrier of the ApoE4 allele increases your risk for developing Alzheimer’s. Having one copy is associated with about a 30% increased risk, and two copies with 90%. Specifically, this mutation can lead to impaired clearance of amyloid plaque, hyperphosphorylation of tau protein, heightened inflammatory response in the brain, impaired cholesterol synthesis and secretion in the brain, impaired cerebral glucose metabolism [11]. All things considered, these statistics generally apply to individuals who have not made changes in their lifestyle to address their predisposition and reduce their risk.

ApoE4 carriers can greatly benefit from a ketogenic for several reasons [11]:

  • A low glycemic diet can optimize insulin sensitivity: ApoE4 and insulin resistance work synergistically to increase your risk for Alzheimer’s.
  • A low-carbohydrate diet can prevent glycation of ApoE: ApoE4 is three times more likely to bind to AGEs and glycation of ApoE reduces its uptake and activity in the brain, promoting disease progression
  • A keto diet could protect against inflammation-induced toxicity in the brain: ApoE4 brains tend to have stronger inflammatory responses. (Fun fact: this is thought to be a protective adaptation that helped us fight off pathogens in the past). 
  • Ketone bodies can reduce oxidative stress

In summary, ApoE4 carriers may benefit the most from a ketogenic or low-carbohydrate diet. The physiological effects of these food plans act directly on oxidative stress, inflammation and insulin resistance, factors that are more likely to worsen carriers’ health outcomes. As always, more research is needed to reach conclusive findings. 

Tips and Considerations 

Tips for Optimizing Cognition with Keto

  • Buy a ketone meter: you can purchase a blood meter (most accurate), urine strips, or a ketone breathalyzer online. 
  • Your diet should be mostly whole food and plant-based
    • Non-starchy vegetables
    • High quality protein
    • Healthy Fats
  • Treat poultry and meat as a condiment, not a main dish
  • Exercise at least 150 minutes per week
  • Avoid eating 3 hours before bed
  • Fast 12 hours overnight: if you stop eating at 8PM, wait until 8AM to have any food or drink (water, tea, black coffee are acceptable)
  • Avoid processed foods, simple carbohydrates, alcohol

Some Safety Considerations

If you have been diagnosed with insulin resistance (Type II diabetes) or cardiovascular disease, or have elevated markers for either, I advise against going on a ketogenic diet on your own. We have had patients try to modify their diet without the help of a professional. Although they have reached the correct macronutrient ratio, they continue to consume processed foods, refined carbohydrates, and a lot of meat, which can be harmful to their health. Speaking with a licensed professional is crucial because the way you eat to achieve ketosis will determine if it can help or hurt you. 

Takeaways

All in all, switching your metabolism into a state of ketosis shows immense promise not only for optimizing brain health and function, but also for preventing and potentially treating cognitive decline and Alzheimer’s disease. More research is desperately needed to reveal the long-term efficacy and adherence to ketogenic diets in the context of cognitive decline and Alzheimer’s. If you are interested in trying a ketogenic diet to improve your brain function or if are an ApoE4 carrier and want to learn more about how you can reduce your risk, contact the Amos Institute today! You can speak to a qualified dietitian nutritionist who specializes in functional medicine and the Bredesen Protocol. 

References: 

  1. Bredesen, D.E. The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline. New York: Avery, 2017
  2. Goodpaster & Sparks, 2017: https://doi.org/10.1016/j.cmet.2017.04.015 
  3. Altayyar et al., 2022: https://doi.org/10.3390%2Fnu14030513 
  4. Lilamand et al., 2020: http://dx.doi.org.libproxy2.usc.edu/10.1186/s13195-020-00615-4
  5. Wang & Reddy 2017: https://doi.org/10.3233%2FJAD-160763
  6. Walsh et al., 2021: https://doi.org/10.1113/jp281988 
  7. Lilamand et al., 2022: https://doi.org/10.3389/fnut.2021.807970 
  8. Gough et al., 2021: https://doi.org/10.3389/fnut.2021.782657
  9. Lilamand et al., 2021: https://doi.org/10.1097/mco.0000000000000759 
  10. Myette-Cote et al., 2020: https://doi.org/10.1016/j.plefa.2020.102236 
  11. Norwitz et al., 2021: https://doi.org/10.3390/nu13041362