Could a ketogenic diet improve cognitive function in Alzheimer’s disease?

By Lauren Wheeler

Ketogenic diets, which are characterised by high levels of dietary fat, moderate levels of protein and very low levels of carbohydrates, have been popularised recently by the mainstream media as a weight loss solution, promising rapid and pronounced results. This is not, however, the first time that the diet has been used with the aim of improving health; for almost half a century doctors have been using the regime to treat sufferers of epilepsy, with patients who achieve ketosis experiencing significant reductions in seizures (Peterman, 1925). 

New evidence is beginning to emerge which suggests that the ketogenic diet also has potential in the treatment of another neurological disorder, Alzheimer’s disease. The condition, a form of dementia which currently affects around 50 million people worldwide, causes significant deterioration in patients’ cognitive function and ultimately results in a complete loss of ability to carry out everyday activities independently (WHO, 2019). There are currently no viable ways to cure Alzheimer’s disease, only a handful of medications to temporarily improve symptoms which show limited success.

Before exploring the therapeutic potential of the ketogenic diet for Alzheimer’s, it is important to define what is meant by the term ketosis. Ketosis refers to the metabolic state in which the body uses fat, rather than carbohydrates in the form of glucose, to provide the energy required for cell function. This state is characterised by the production of molecules known as ketone bodies which are produced by the liver when products from the breakdown of fatty acids exceed what the body can use for respiration^{^}. This occurs predominantly when a person consumes a diet very high in fat or low in carbohydrate (Gasior et al., 2006).

By now you may be wondering what role ketones could play in treating Alzheimer’s disease. Typically, glucose is the brain’s preferred fuel source, with the organ, which accounts for up to 20% of the body’s overall energy use, requiring an estimated 110-145 grams of glucose each day (Owen et al., 1967). In Alzheimer’s disease, however, glucose uptake by neurons^{^^} has been shown to be impaired, with dysfunctional glucose metabolism having become recognised as a hallmark of the condition’s pathophysiology (Butterfield and Halliwell, 2019). 

This is where ketones come in. 

It turns out that ketone bodies can be used as an alternative fuel source by cells, not only in the body but also by neurons in the brain. Ketones are in fact a principal source of energy during early mental development. This has led researchers to investigate whether they could be effective in providing supplementary energy in the brains of Alzheimer’s patients, in lieu of ATP generated from the respiration of glucose. Early research in this area is encouraging, with studies demonstrating that whilst glucose metabolism decreases in patients with the condition, ketone metabolism does not (Castellano et al, 2014). A recent study into the feasibility of the diet for people with Alzheimer’s disease also found improvements in the cognition of patients with a mild form of the disease, which diminished when the diet was discontinued (Taylor et al, 2018).

It is critical to note, however, that following a ketogenic diet as a therapeutic approach has its limitations. Patients with Alzheimer’s often suffer from lack of appetite and subsequent weight loss, especially in the later stages of the disease. They also appear to show a preference for sweet, high-carbohydrate foods such as puddings, sweets etc. Since the ketogenic diet is both quite restrictive and, being so high in fat, also more satiating than a diet high in carbohydrates, there are worries about both patients’ ability to adhere to the diet and to maintain their weight whilst following it. In the aforementioned study on the feasibility of a ketogenic diet for Alzheimer’s disease, researchers found that a handful of patients in the more advanced stages of the disease were unable to comply with the diet, withdrawing from the study. This was hypothesised to be due to the fact that caregivers of these patients were already under increased burden due to the severity of the disease and unable to assume the additional responsibility of implementing a strict food routine. 

Luckily there may be another solution for those who are unable to tolerate a ketogenic diet. Exogenous ketones, which are not produced in the body but administered as a dietary supplement, in the form of Medium Chain Triglycerides (MCTs), have also been found to be effective in ameliorating cognitive function in Alzheimer’s disease (Reger et al, 2004). This therapy negates the need for sufferers to follow a strict regime, providing ketone bodies in addition to the patient’s standard diet, which may be preferential both in terms of weight maintenance and practicality.

Whilst further studies on the efficacy of the ketogenic diet and/or exogenous ketone supplementation to improve cognitive symptoms in Alzheimer’s patients are required, initial evidence shows promise. Until the exact causes of this debilitating neurological disorder have been elucidated and an effective treatment found, any approach which can slow patients’ deterioration or improve quality of life seems a worthy cause for consideration.

Footnotes:

^The process by which energy is released from the oxidation of glucose, producing ATP

^^Specialised cells of the nervous system found primarily in the brain and spinal cord 

References:

Peterman, M.G. (1925) THE KETOGENIC DIET IN EPILEPSY. JAMA: The Journal of the American Medical Association. [Online] 84 (26), 1979. Available from: doi:10.1001/jama.1925.02660520007003.

World Health Organisation (2019) Dementia. [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia.

Gasior, M., Rogawski, M.A. & Hartman, A.L. (2006) Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural Pharmacology. [Online] 17 (5–6), 431–439. Available from: doi:10.1097/00008877-200609000-00009.

Owen, O.E., Morgan, A.P., Kemp, H.G., Sullivan, J.M., et al. (1967) Brain metabolism during fasting. The Journal of Clinical Investigation. [Online] 46 (10), 1589–1595. Available from: doi:10.1172/JCI105650. 

Butterfield, D.A. & Halliwell, B. (2019) Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nature Reviews Neuroscience. [Online] 20 (3), 148–160. Available from: doi:10.1038/s41583-019-0132-6.

Castellano, C.-A., Nugent, S., Paquet, N., Tremblay, S., et al. (2014) Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer’s Disease Dementia. Journal of Alzheimer’s Disease. [Online] 43 (4), 1343–1353. Available from: doi:10.3233/JAD-141074.

Taylor, M.K., Sullivan, D.K., Mahnken, J.D., Burns, J.M., et al. (2018) Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. [Online] 4 (1), 28–36. Available from: doi:10.1016/j.trci.2017.11.002.

Reger, M.A., Henderson, S.T., Hale, C., Cholerton, B., et al. (2004) Effects of β-hydroxybutyrate on cognition in memory-impaired adults. Neurobiology of Aging. [Online] 25 (3), 311–314. Available from: doi:10.1016/S0197-4580(03)00087-3.