Recently, we reported that insulin resistance is an important cause of Alzheimer’s disease. The disturbance of glucose metabolism can cause a lack of energy and thus an undersupply in the brain. This is also known as cerebral insulin resistance or type 3 diabetes. In this state, the simple sugar glucose can only be insufficiently used by the brain as an energy carrier. This is even more surprising as the blood of insulin-resistant patients is flooded with sugar, but it still does not reach the brain cells.
But the good news is that the insulin-resistant brain is able to use other sources of energy instead of glucose. In addition to the simple sugar galactose, these alternative fuels include the so-called keto(n)bodies or ketones.
Ketosis as an alternative supply program for the body
The ketones are formed in the liver from fats, more precisely from fatty acids. Their production starts when glucose is not available to the organism as fuel. This is the case in starvation metabolism (e.g., during periods of fasting or low carbohydrate intake). The body is now in physiological ketosis, an alternative supply program of the body to provide it with energy during times of carbohydrate shortage. However, this is not to be confused with the life-threatening ketoacidosis, a condition that only occurs in cases of absolute insulin deficiency, such as in type-1 diabetes.
The principle of physiological ketosis is also used in the ketogenic diet: the consumption of carbohydrates is greatly reduced and in return the consumption of fat is significantly increased so that the body enters ketosis and the liver switches to fat burning. Then ketones are produced as an alternative energy source to glucose.
Therapeutic potential of ketosis
Interestingly, the brain of Alzheimer’s disease patients is still able to utilize ketones as an energy source without restriction, despite its pathological impairment of glucose utilization (1). This has given rise to the idea of using the ketones in these patients to restore energy to the brain, thus eliminating energy deficiency as a causative factor in AD.
To date, however, there have been few studies on the effect of ketogenic diets in Alzheimer’s patients:
- For example, a 2017 study examined the effects of a 12-week ketogenic diet in 15 Alzheimer’s patients (2). Cognitive scores improved in the 11 participants, but because there was no control group, the effect cannot be attributed solely to ketone utilization.
- A more recent 2019 study provided preliminary data on the effects of a 12-week modified Atkins diet (= specific form of ketogenic diet) compared with a diet recommended by nutrition societies in 14 patients with mild cognitive impairment or Alzheimer’s disease (3). Memory function improved in patients who adhered best to the dietary guidelines.
In light of this „thin“ data, a randomized crossover trial was recently conducted for the first time (4). The research group wanted to find out what impact a defined ketogenic diet (high fat and severely low carbohydrate) had on Alzheimer’s symptomatology, cardiovascular risk factors and quality of life in Alzheimer’s patients, and also how well it was tolerated. The results were published this year.
The study design
For this purpose, 26 patients with clinically confirmed early-stage Alzheimer’s disease diagnosis were randomly divided into 2 groups. One of them received a modified ketogenic diet for 12 weeks, while the second group followed a low-fat diet according to New Zealand healthy eating guidelines during this time. The ketogenic diet plan provided a low-carbohydrate, high-fat macronutrient ratio with an average of 58% fat (of which 26% was saturated and 32% was unsaturated), 29% protein, 7% fiber, and 6% carbohydrate. The main dietary components were green vegetables, meat, eggs, nuts, seeds, spreads, and natural oils. The non-ketogenic dietary protocol included low-fat recipes with an average ratio of 11% fat (of which 3% saturated and 8% unsaturated), 19% protein, 8% fiber, and 62% carbohydrate. The ingredients were mainly green and root vegetables, meat, legumes, whole grains, and fruit.
After a 10-week break, the groups were switched and now the first group of patients received the low-fat diet and the 2nd group received the ketogenic diet for 12 weeks. Because of this crossover in study design, studies of this type are also called „crossover“ studies.
Before and after the 12-week test phases, the patients“ cognitive functions, executive functions (the ability to perform daily actions), and quality of life were assessed and evaluated either by validated test procedures or questionnaires. Furthermore, changes in cardiovascular risk factors and adverse effects of the diets were also recorded. The ketogenic-fed patients were also all in ketosis, which was continuously monitored by analyzing ketones in the patients“ blood.
The result of the study
Despite the shortness of time, the ketogenic diet, improved executive functions, and also significantly increased quality of life, two factors that are of great importance for people with dementia. Cognition also improved in patients who followed the ketogenic diet, although not statistically significantly. Since these parameters were studied in direct comparison to a high-carbohydrate, low-fat diet (recommended by nutrition societies), and in addition were tested on both groups of patients in a crossover design, the observed positive effects on AD symptoms can be directly attributed to the ketogenic diet. Changes in cardiovascular risk factors were unremarkable in the ketosis groups, and no serious adverse effects occurred. The authors mentioned as particularly gratifying the fact that the switch to the ketogenic diet went smoothly in both groups and was very well accepted and adhered to. Only one dropout was attributed to the dietary change.
However, because this study involved only a small group of patients in fairly short test phases, larger and longer studies are needed to confirm the observed effects.
However, this promising pilot study is already leading the way for many patients and their families: Ketogenic diets could be viable and effective, and most importantly, side-effect-free prevention and treatment strategies for Alzheimer’s disease, providing another important weapon in the fight against this relentless disease.
For more background information on this exciting topic, please also check here at „Knowledge stops Dementia“.
The link between diabetes mellitus and Alzheimer’s dementia is well established by now. The damaged brain of insulin-resistant Alzheimer’s patients is in an energy crisis, despite the flood of sugar in the body, but would be fully capable of using alternative fuels such as ketones as an energy source. The liver forms ketones from fats as soon as the body is deprived of glucose. This state, known as ketosis, happens physiologically in starvation metabolism, but also through the ketogenic diet. This gave rise to the idea that ketosis could have major therapeutic benefits in Alzheimer’s patients.
This year, the results of the first randomized trial examining the effect of a ketone-forming diet in patients diagnosed with early-stage Alzheimer’s were published. The results are promising: already after a 12-week ketogenic diet, classic symptoms of Alzheimer’s pathology, such as executive functions, cognitive performance and quality of life, improved in direct comparison to a usual low-fat diet. Thus, a high-fat and low-carbohydrate diet could represent an effective, feasible and, above all, side-effect-free prevention and treatment strategy for Alzheimer’s disease, and thus this approach holds great hope for Alzheimer’s patients and their families, but also for people at increased risk of dementia, in the fight against this terrible 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 sensibly integrate coconut oil or MCT oils into your diet – it’s worth it, not only for your brain health!
- Castellano C, Nugent S, Paquet N, Tremblay S, Bocti C, Lacombe G, et al. (2015) Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer’s disease dementia. J Alzheimers Dis.43: 1343–53.
- Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. (2017) Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y)4: 28–36.
- Brandt J, Buchholz A, Henry-Barron B, Vizthum D, Avramopoulos D, Cervenka M. (2019) Preliminary report on the feasibility and efficacy of the modified Atkins diet for treatment of mild cognitive impairment and early Alzheimer’s disease. J Alzheimers Dis. 68: 969–81.
- Matthew C. L. Phillips, Laura M. Deprez, Grace M. N. Mortimer, Deborah K. J. Murtagh, Stacey McCoy, Ruth Mylchreest, Linda J. Gilbertson, Karen M. Clark, Patricia V. Simpson, Eileen J. McManus, Jee-Eun Oh, Satish Yadavaraj, Vanessa M. King, Avinesh Pillai, Beatriz Romero-Ferrando, Martijn Brinkhuis, Bronwyn M. Copeland, Shah Samad, Shenyang Liao & Jan A. C. Schepel (2021) Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy 13: 51. doi: 1186/s13195-021-00783-x