Ketosis and Cognition

by Amylee Amos MS, RDN

Contrary to popular belief, you can eat a pro-longevity, plant based diet and achieve a state of mild ketosis. The ketogenic diet does not require the sacrifice of vegetables nor does it require piles of saturated fats and animal products. The question isn’t can it be done, but should it be done? Should you be checking your ketones and tracking your beta hydroxybutyrate levels?

Not necessarily. As with any diet trend, the ketogenic diet is certainly over-hyped, but in some cases it’s also undervalued. There are certain groups of people who benefit from spending the majority of their day in mild ketosis. People with Alzheimer’s disease or those at high risk for Alzheimer’s disease certainly fall into that category. If you have or are at risk for Alzheimer’s disease, achieving a state of mild ketosis (which does not mean the stereotypical ketogenic diet) is definitely something to discuss with a nutrition or health professional. Here is the science that explains why.

Individuals with Alzheimer’s disease and some other types of cognitive decline exhibit what’s called decreased cerebral glucose utilization. Basically that means that the brains of people with Alzheimer’s disease are unable to efficiently use carbohydrate (glucose) as fuel (1). When carbohydrate is available, the body breaks it down and uses that glucose as its primary energy source. In a healthy and optimally functioning individual, the brain, along with the rest of the body, is able to use that glucose as energy. The brain alone, which is about 2% of our body weight, uses about 20% of the body’s total energy, more than any other human organ (2). It needs that energy to carry out its basic functions from creation of new neurons, to fueling synapses so the neurons can communicate, to cellular maintenance. However in Alzheimer’s patients, the utilization of available glucose as energy is ineffective, meaning that even when glucose is present, the brain is unable to use it for energy. This leaves the brain starving for energy (1).

The story becomes more complicated when we add genetics into the mix. The gene best known for its correlation with Alzheimer’s disease is ApoE. We all have two copies of ApoE, one from our mother and one from our father. There are three different variants or alleles of ApoE, known as ApoE2, ApoE3, and ApoE4. We can have any combination of the two, depending on the genes of our parents. ApoE4 is a genetic allele that is known to be the strongest genetic risk factor for Alzheimer’s disease. In fact, research shows that just simply carrying this genetic variant results in some of the same cognitive abnormalities as people with diagnosed Alzheimer’s disease. More specifically, cognitively healthy ApoE4 carriers as young as age thirty, also exhibit the decreased cerebral glucose utilization that we see in Alzheimer’s patients (1). Basically, in your 30’s your brain can be starving for energy because of your diet and your genetics.

Luckily, unlike impaired glucose utilization, ketone utilization is not impaired in individuals with Alzheimer’s disease or carriers of the ApoE4 allele (3). A lipid based metabolism in the form of ketones bypasses the impaired functioning of the glucose metabolism systems (4). Basically, when adequate carbohydrate is unavailable through the diet or in body stores, the body flips into a lipid based metabolism through ketosis. The ketone bodies are able to bypass the damaged glucose metabolism pathways and be utilized as energy by the brain, feeding it the fuel it needs. It is for this reason that achieving a state of mild ketosis is so beneficial for individuals with Alzheimer’s disease and cognitive decline.

In other words, in this population of people, glucose or carbohydrate may not be an adequate fuel source for the brain, but ketones are an efficient fuel source. So achieving a state of mild ketosis can adequately fuel the brain, which can suppress symptoms of cognitive decline in the Alzheimer’s population and reduce the risk of cognitive decline in ApoE4 carriers, and even contribute to the regeneration of neurons. This is incredibly hopeful. It means that we can account for damage caused by our genetics and bypass the issues that damage causes, all by modifying our diet. It also demonstrates that ‘the perfect diet’ probably doesn’t exist. We are all different. We have different genes, in different environments. Maybe this is why nutrition science is so muddy. We can’t simplify it down the way we might like.

In my opinion, research such as this is the reason to get genetic testing to determine ApoE status. What was once just an indicator of high risk is now actionable information. While metabolic flexibility, the ability to transition seamlessly between glucose and lipid metabolism,  is a good goal for everyone, actively pursuing mild ketosis is not necessarily something you should work to achieve if you’re cognitively healthy and unsure of your genetic makeup. However, if you have Alzheimer’s disease or know that you have one or two copies of ApoE4, contact a nutrition professional who is trained to help you target the nutrition plan that will optimize your genetics and lifestyle to help you prevent or reverse cognitive decline, without sacrificing your overall health.

References:

  1. Nielsen, H. M., Chen, K., Lee, W., Chen, Y., Bauer, R. J., Reiman, E., … Bu, G. (2017). Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism. Alzheimer’s Research & Therapy, 9(5).
  2. Raichle, M.E. & Gusnard, D. A. (2002). Appraising the brain’s energy budget. Proceedings of the National Academy of Sciences, 99 (16) 10237-10239.
  3. Cunnane, S., Courchesne-Loyer A., St-Pierre V., Vandenberghe C., Pierotti T., Fortier M., Croteau E., Castellano C. (2016). Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease. A_nnals of the New York Academy of Sciences, 1367_; 12-20.
  4. Cunnane, S., Nugent, S., Roy, M., Courchesne-Loyer, A., Croteau, E., Tremblay, S., … Rapoport, S. (2011). BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE. Nutrition, 27(1), 3–20.