Source: Natashamam/123RF
Alzheimer’s Disease is a Brain Fuel Problem
Once someone has been diagnosed with Alzheimer’s, is continuing deterioration inevitable? We used to think so, but there is new science emerging that offers a more hopeful path for people who are willing to change their lifestyle—especially their diet.
The human brain is an energy hog, demanding a constant supply of fuel to feed hungry, hard-working brain cells. Unfortunately, the brains of people with dementia have great difficulty burning glucose (blood sugar), which can lead to sluggish brain activity, brain shrinkage and even death of precious brain cells over time.
Can Ketones Awaken the Sluggish Alzheimer’s Brain?
People with Alzheimer’s disease essentially have an energy crisis on their hands, so they are in desperate need of an alternative fuel source. Luckily, except in advanced cases of Alzheimer’s disease, the brain has no problem whatsoever burning ketones for fuel instead of glucose. This fact inspired researchers from the University of Kansas to explore whether ketone supplements and low-carbohydrate diets that switch on the body’s own ketone production could be the way forward for some people with Alzheimer’s disease. Their study, nicknamed KDRAFT (the Ketogenic Diet Retention and Feasibility Trial), is the first study in the world to test ketogenic diets in people with Alzheimer’s disease.
These scientists aimed to answer three main questions:
- Can people who already have mild to moderate Alzheimer’s follow a ketogenic diet?
- Are ketogenic diets safe and well-tolerated in people with Alzheimer’s disease?
- Do ketogenic diets have the potential to improve memory and cognition in people with Alzheimer’s disease?
Study Design
Fifteen men and women with mild to moderate Alzheimer’s disease participated in this 4-month study, each with a dedicated caregiver to help with dietary changes and monitoring.
Dietitians taught participants to eat a ketogenic diet of 10% carbohydrate, 20% protein, and 70% fat without lowering the number of calories they were accustomed to eating.
Participants were also given MCT oil supplements to take daily, beginning at 10% of calories during week 1 and gradually increasing to 40% of calories by week 4. [MCT oil is a type of fat that turns rapidly into ketones in the body].
Daily multivitamin, vitamin D, calcium, and phosphorus supplements were also provided. [It seems as if at least some participants were also taking cholinesterase inhibitor medications (medicines such as Aricept designed to try to slow the progression of Alzheimer’s). While details are not provided, it is inferred that these medications were not initiated or intentionally changed just prior to or during the study.]
Participants monitored urine ketones every evening at home and attended monthly visits to the research center for EKG, body weight/composition, and fasting blood tests (including glucose, insulin, electrolytes, cholesterol, liver/kidney function, and beta-hydroxybutyrate ketone level).
Cognitive tests were administered before the study began, after three months on a ketogenic diet, and again at four months (after participants had been back on their usual diet for a month). Two tests were used: the MMSE (Mini-Mental Status Examination) and the ADAS-cog (Alzheimer’s Disease Assessment Scale-cognitive subscale).
Results
People with mild Alzheimer’s were able to successfully manage a ketogenic diet with the help of a caregiver. Ten of 15 participants safely and successfully completed the 4-month study. All 10 had mild Alzheimer’s disease (due to caregiver burden, all four participants with moderate Alzheimer’s and one person with mild disease were unable to complete the study). All completers stayed in mild ketosis most days (on average 60.6% of the time) according to home urine testing. Blood ketone levels rose on average from 0.11 mmol/L before the diet to 0.52 mmol/L after one month on the diet, then dropped to 0.34 mmol/L after two months, and to 0.31 mmol/L after three months.
The ketogenic diet was safe and well-tolerated. The only side effects reported were gastrointestinal issues caused by MCT oil supplements. Nobody lost weight. The only blood test that changed significantly during the three-month ketogenic diet phase was blood ketone levels. Fasting blood glucose, insulin, and cholesterol levels and all other clinical markers measured during the study remained about the same throughout the study.
Cognitive test results improved significantly in 9 out of 10 participants.* The ADAS-cog is a 70-point test of memory, language, attention, and task completion (drawing shapes, mailing letters, etc.) On average, ADAS-cog test scores improved by more than 5 points; better than with any available Alzheimer’s medication. For example, in this 3-month study of Aricept (donepezil), ADAS-cog scores improved by only 3 to 4 points.
There was also a small but statistically significant increase of about one point (on a scale of 0 to 20) on the MMSE.
Interestingly, improvements in cognitive test scores disappeared when participants returned to their usual diets.
*Test results worsened throughout the study for one individual, who also happened to have stopped taking Alzheimer’s medication.
Limitations of the Research
This was a very small pilot study and there was no control group for comparison, so the authors caution that, although the cognitive improvements were clear and significant, we can’t say for sure whether the ketogenic diet + MCT oil was responsible for them. It could simply have been other aspects of the intervention—attention from a dietitian, participation in an exciting and hopeful research project, or other lifestyle changes that participants may have adopted to try to get better. However, the fact that the cognitive improvements went away during month four when people went back to their usual diets strongly suggests that the diet + MCT oil was doing something helpful.
Commentary
Ketone levels were modest and inconsistent. One wonders whether the results would have been any different had ketone levels been a little higher and more consistent. The authors reported that people were eating on average about 46 grams of carbohydrate per day, whereas most experts recommend lowering daily carbohydrate intake to 25 grams or less to achieve and maintain ketosis.
Diet composition is not described, so we don’t know what people were eating. Was this a whole foods diet or did it contain a significant amount of processed foods? Were sugar substitutes or dairy products included which have the potential to affect insulin and ketone levels?
MCT oil effectively serves as a source of “exogenous ketones” (ketones that come from outside the body, as opposed to ketones generated from inside the body through diet). MCT supplements raise blood ketone levels only briefly, and we don’t know how often or at what times of day MCT supplements were taken. MCT supplements may confuse the metabolic picture by artificially raising blood ketone levels. Exogenous ketones also increase insulin levels, which can ultimately drive down the body’s own ketone production.
Hope for the Future
Alzheimer’s disease is a devastating condition that is very difficult to treat, and all of the medications designed to try to help have been remarkably disappointing. This groundbreaking study suggests that, with some instruction and in-home support, people with mild Alzheimer’s disease may be able to improve their brain function by raising their blood ketone levels. This promising pilot project lays the foundation for larger, controlled trials with the potential to teach and inspire us about hopeful new possibilities for families grappling with Alzheimer’s disease.
If your family is coping with Alzheimer’s disease and you’re interested in learning more about how ketogenic diets may help, I highly recommend the excellent book The Alzheimer’s Antidote by Amy Berger, MS, CNS, NTP.
If you’re curious to learn more about how to reduce your risk for Alzheimer’s in the first place, please read Preventing Alzheimer’s May Be Easier Than You Think.
