Ketogenic diets in the prevention and treatment of Alzheimer's disease

We now know that Alzheimer’s dementia is a multifactorial metabolic disease, and that one possible cause is the disturbance of sugar and insulin metabolism. The connection between these diseases, i.e., between diabetes mellitus and Alzheimer’s disease, is already well established in the field of Alzheimer’s research. Accordingly, Alzheimer’s disease has also been termed type-3 diabetes. A characteristic feature of this clinical picture is that, despite the blood being flooded with sugar (glucose), there is a consequent lack of energy and thus an energetic undersupply in the brain.

But the good news is: there are other potential energy sources besides glucose that the brain could use and thus get out of the energy crisis. These alternative fuels include the monosaccaride galactose as well as the so-called keto(n)bodies or ketones.

Ketones as an alternative energy source to glucose

Ketones are formed in the mitochondria of liver cells from fats, more precisely from fatty acids, via the process of ß-oxidation. This process produces the three ketone compounds acetoacetate, ß-hydroxybutyrate and acetone. Their production starts when the blood glucose level drops and all sugar deposits (glycogen) are depleted. This is the case in starvation metabolism (e.g., during periods of fasting, low carbohydrate intake, intense physical training, and in untreated type-1 diabetes). The body is now in physiological ketosis, which is an alternative supply program for the body to provide energy during periods of carbohydrate shortage to keep it alive. However, this is not to be confused with ketoacidosis, a condition that can only occur in cases of absolute insulin deficiency, such as type-1 diabetes. In ketoacidosis, up to 10 times more ketone bodies are produced and the blood becomes overacidified, a life-threatening condition! In contrast, the state of physiological ketosis is characterized by ketone concentrations of 0.5-3 mmol/l in the blood, which are harmless.

Ketogenic diet and Alzheimer’s dementia

A therapeutic benefit of a low-carbohydrate diet seems reasonable because the brain of Alzheimer’s patients is still able to metabolize ketones as an energy source without restriction despite its pathological disorder of glucose utilization ^[1]. Thus, energy deficiency, the causative risk factor of AD, could be eliminated in these patients. This type of diet has long been used in the treatment of epilepsy ^[2].

The body of studies on the effects of ketogenic diets in Alzheimer’s patients is still quite thin, but promising.

The pilot studies published to date in AD patients report positive effects of a ketogenic diet on the disease ^{[3][4] [5]}. In particular, the results of a first randomized crossover trial from the beginning of 2021 are more than promising ^[6]:

In this new study, early-stage Alzheimer’s patients were able to perform everyday activities better after being for only 12 weeks on a ketogenic diet (in direct comparison to a conventional low-fat diet), and that their quality of life was also significantly improved. Precisely these two parameters are of enormous importance for people with dementia. Cognitive abilities also improved in patients following the ketogenic diet. It was also important that no significant adverse effects occurred in all studies. The authors were further particularly pleased with the fact that the switch to the ketogenic diet was smooth and very well accepted and adhered to ^[6].

An important advantage of the ketogenic diet is the stabilization of blood glucose levels. Unfortunately, our typical Western diet is overloaded with (empty) carbohydrates such as white bread, French fries, pasta, pizza and such, and also characterized by an excess of sugary foods, sweets and highly sweetened drinks, which leads to a constant flooding of the blood with sugar. This is encouraged by the fact that even nutritional societies still make outdated and incorrect dietary recommendations.

We have long known that too much sugar in the blood is not good for our brains in the long run. As early as 2013, a study in healthy non-diabetics showed that a higher blood glucose level, measured by the long-term blood glucose level HBA1c, correlates directly with poorer learning and memory performance ^[7].

A carbohydrate-balanced diet MUST be a milestone in the prevention of neurodegenerative diseases such as Alzheimer’s dementia.

Ketone formation through coconut oil or MCT oil

It is now also known that a diet that is not quite so drastically carbohydrate-reduced, but instead is supplemented with coconut oil or MCT oil (MCT = Middle Chain Triglycerides), also leads to ketone formation under certain conditions. These medium-chain fatty acids contain 6 to 12 carbon atoms and, due to their shorter structure, do not take the detour via the lymph but, after being absorbed in the intestine, reach the liver directly with the portal blood, independently of bile acids and fat-splitting enzymes, where they are rapidly converted into ketones via ß-oxidation. Coconut oil contains about 16% ketogenic medium-chain fatty acids, whereas MCT oil consists entirely of fats containing medium-chain fatty acids. It should be noted, however, that food fats are never composed solely of these fats and their consumption levels are also individualized, preferably by an experienced nutritional therapist, as both coconut oil and MCT oil are saturated fats.

A therapeutic effect of these medium-chain fats on Alzheimer’s disease was first impressively demonstrated by the American physician Dr. Mary Newport ^[8]: she initially treated her husband Steve, who was suffering from an early form of Alzheimer’s disease, with coconut oil (35 ml daily). After this showed positive effects in the clock test after a short time (see Figure 2), she gradually increased the dose with MCT oil to a 4:3 mixture (MCT to coconut oil) until finally 165 ml/day, divided into 3 to 4 servings, was reached. The surprising result was that after 2.5 months, there was a tremendous improvement in cognitive abilities. In addition, Steve Newport gradually improved his memory, word-finding ability, social participation, and gait. Magnetic resonance imaging also showed no further brain atrophy over a long period of time ^[8].

Figure 2: Clock test according to Shulman, drawn by Steve Newport ^[8]. 1: Before coconut oil intake, 2: After 14 days intake, 3: After 37 days intake. The clock test is a common psychometric test in Alzheimer’s diagnosis. The patient has to draw a clock, i.e. a circle with 12 digits, and enter a time according to the instructions with the hour and minute hands. This task is only successful if the patient still possesses the necessary mental abilities (memory, retentiveness, visual orientation, etc.) to a sufficient degree.

That this is not an isolated case is also shown by several other studies on Alzheimer’s patients in early and advanced stages: in almost all studies, an increase in the cognitive functions, processing speed and/or memory performance was detectable already a short time after the administration of ketogenic oils or ketone preparations ^[9].

In short, scientific findings for ketone-producing diets, although still in their infancy due to small patient numbers and short intervention periods, are already leading the way for many affected individuals and their families: ketogenic diets, whether through carbohydrate restriction and/or supplementation with coconut or MCT oils, appear to be extremely effective prevention and treatment strategies for Alzheimer’s that are both feasible and, above all, free of side effects, and thus represent another important weapon in the fight against this relentless disease.

Conclusion:

We now know that the damaged brains of insulin-resistant Alzheimer’s patients are in an energy crisis despite the flood of sugar in their bodies. However, despite their impaired glucose utilization, the brain cells are still fully capable of utilizing alternative fuels such as ketones as an energy source. Therefore, these substances are thought to have great therapeutic potential in Alzheimer’s disease. The liver forms ketones from fats as soon as the body runs out of glucose as fuel. This state, known as ketosis, occurs physiologically in starvation metabolism, but also during severely carbohydrate-reduced (ketogenic) diets. However, the production of ketones can also be stimulated by consuming oils containing medium-chain fatty acids (e.g., MCT oils and coconut oil).

The therapeutic potential of ketones was impressively demonstrated in a recent study: In this randomized crossover study, already after a 12-week ketogenic diet, the performance of daily activities, cognitive performance and quality of life improved in Alzheimer’s patients, compared to a usual low-fat diet. And all this without side effects! The results of other studies are also more than promising: ketone-forming diets, whether through carbohydrate restriction and/or supplementation with coconut or MCT oils, have proved to be effective, viable and, most importantly, side-effect-free prevention and treatment strategies for Alzheimer’s, thus representing another important weapon in the fight against this relentless disease.

Therefore, our tip to you: reduce your excessive sugar and sweets consumption today, avoid highly sweetened beverages, avoid excessive consumption of starchy (highly processed) foods in the form of white flour, pasta, chips, etc., and integrate coconut oil or MCT oils into your diet – it’s worth it, and not just for your brain health!