The ketogenic diet for Alzheimer’s prevention and treatment: can it help?
Anne and parents
“Let’s do it,” said my father, 92. “What have we got to lose?”
My elderly parents, fiercely independent, living on their own, and aging relatively well, are highly motivated to keep their brains functioning at an optimal level. A significant loss of cognitive skills in either one of them would seriously threaten their cherished freedoms and greatly reduce their quality of life.
Over the last three years their daughters, sons-in-law, and some grandchildren had embraced the ketogenic diet and they’d heard us extol about how great we were feeling. Some of us remarked on our feelings of improved mental clarity — an unexpected bonus from the ketogenic lifestyle.
So they wondered: could drastically cutting carbohydrates and eating more fat benefit their brains? My Mom was having some memory problems that frustrated and scared her, such as having difficulty writing down items on a shopping list: she knew what she needed but the names or spellings sometimes would not come. She had voluntarily given up driving last year as she knew that at random times, especially under stress, she would have moments of confusion. Dad was still very sharp, but he felt his memory was not as strong as he would like. Could a ketogenic diet help slow or halt more cognitive decline at their late stage of life?
They were intellectually curious and eager to find out. So was I.
So in mid February I left my home on the West Coast of Canada and flew five hours back to my parent’s home north of Toronto. I moved in with them for a month to coach them on keto eating and to help them shop, meal plan, and cook.
I had ketostix and a blood ketone metre to monitor their ketone levels. I had a tape measure and weight/body fat scale to make sure they did not lose too much weight. I also had validated cognitive assessment tests to help chart and document any changes to their cognitive skills during our month-long experiment.
They are, perhaps, the oldest couple yet to publicly try Diet Doctor’s low-carb challenge. They are doing it not for weight loss, nor for diabetes reversal, but in the hope it might benefit their brains.
Would they be able to easily get into ketosis — and feel good doing so? Would they produce enough ketones to act as an alternate fuel to glucose for their brains’ energy needs? Would their cognitive skills measurably improve?
My parental guinea pigs and I were keen to find out.
Alzheimer’s and other dementias — the growing scourge
Alzheimer’s disease and other related neurodegenerative conditions, which impact memory, behavior and decision-making, are now an epidemic hitting all Western societies.
Currently an estimated 50 million cases of Alzheimer’s and dementia exist globally, which are growing by 10 million people every year. In Western Europe, 7.5 million people are now affected and in North America, 5 million people. Those numbers are expected to increase by more than 200% over the next 30 years, reaching 150 million cases worldwide by 2050.
Modifiable risk factors for Alzheimer’s include type 2 diabetes, obesity, metabolic syndrome, and high blood pressure — all factors that here at Diet Doctor we know can be improved by a low-carb ketogenic diet.
My parents fit the demographic of those most protected from Alzheimer’s. They are highly educated: he was a general surgeon and professor of surgery at three Canadian medical schools; she, before raising her family, was a scholarship student to university and worked post-grad as a research assistant in the lab of the Nobel-prize winning discoverers of insulin. They are financially secure, socially engaged and have been physically active all their life. They gave up weekly skiing at 83 but Dad still enjoys snow-blowing the driveway in Canada’s harsh winters (and he won’t let anyone help!)
One risk factor that is impossible to change is increasing age. The older you grow, the higher your risk of dementia. One third of those over age 85 have some form of cognitive impairment. With each passing year as we enter our late 80s the incidence of dementias increases exponentially, reaching upwards of 70% by the late 90s.
For unknown reasons, women’s aging brains are more vulnerable to Alzheimer’s then men’s, with triple the incidence of dementia and double the speed of decline.
There is still no cure nor effective treatment. Research for the last two decades has been burgeoning and more than 2200 clinical trials for various interventions are currently underway around the world, including studies in various phases on more than 100 new drugs. But the track record for drug effectiveness has been dismal. In fact, since 2003, more than 240 drugs have failed clinical trials, with 2017 being a particularly disappointing year.
My parents share that fear. If a ketogenic diet has even the slimmest chance of offering a positive impact, they want to try it.
The brain likes ketones
It has long been known that the brain can use two fuels for its energy needs: 1) glucose or 2) ketones. Glucose is the product of the breakdown of carbohydrates that we eat or is made via our liver by a process called gluconeogenesis (which literally means “new glucose making.”) Ketones are the product of the breakdown of fat to fatty acids, either from fat in our diet or fat stored in our adipose tissue.Evidence that certain impaired brain functions can improve by increasing the use of ketones for brain fuel has existed for almost a century. Since the 1920s the ketogenic diet has been known to reduce the frequency and severity of seizures in children with epilepsy . Since then, a number of researchers have hypothesized that tapping into ketone metabolism may have powerful applications to many other areas of brain health.
Diet Doctor has a number of videos and posts about positive impacts of the ketogenic diet for migraines, brain cancer, and traumatic brain injury. Anecdotally many people who adopt the ketogenic diet report improvements in their mental health, such as for anxiety, depression and bipolar illness, but the research base, while promising, is slim by some accounts. Psychiatrist Dr. Georgia Ede takes a more hopeful view. “My mantra is that the most powerful way to change your brain chemistry is by food, because that’s where brain chemicals come from in the first place,” she says.
While the exact mechanisms of ketones on brain health are still unclear, a 2017 paper in the journal Neurochemistry summarized what is known: ketones as fuel in the brain have been shown to enhance mitochondrial respiration (energy production), increase neuronal growth factors, strengthen the signal sent between synapses, reduce brain inflammation, and reduce oxidative stress. These effects, the paper noted, then seem to have downstream implications for a wide range of brain functional pathways.
“A ketogenic diet to prevent or even treat Alzheimer’s makes perfect sense to me. There is nothing to lose by trying it,” says Dr. Ede. “It is an area of huge potential.”
A popular recent book promoting the ketogenic diet for Alzheimer’s prevention is Amy Berger’s The Alzheimer’s Antidote.1 Another 2015 book, written by Dr. Mary Newport, details how she slowed her husband’s Alzheimer’s by feeding him plenty of coconut oil, MCT oil (medium chain triglycerides – derived from coconut oil, palm kernel oil and dairy products) and ketone supplements.
Scientific evidence: Alzheimer’s brains show reduced uptake of glucose
In Alzheimer’s disease there is documented insulin resistance in the brain that hampers the uptake of glucose for fuel, Dr. Ede notes in her 2017 video about reducing insulin resistance to prevent Alzheimer’s. She delves into the issue, too, in a related column for Psychology Today, “Preventing Alzheimer’s may be easier than you think.”Insulin resistance of the brain as a factor associated with Alzheimer’s is so well documented that some researchers have called Alzheimer’s “type 3 diabetes.” This brain IR, which prevents the brain’s use of glucose no matter how high blood sugar rises, helps explain the higher rates of Alzheimer’s among those with diabetes.
However, IR of the brain even impacts the uptake of glucose in those without diabetes who are years away from any cognitive symptoms, such as in the brains of those with prediabetes and in the brains of young women with polycystic ovarian syndrome, a reproductive metabolic disorder in which insulin resistance is a factor — and for which a low-carb high-fat (LCHF)/ketogenic diet is known to help.
“We know that in Alzheimer’s disease, the brain loses its ability to use glucose,” said Dr. Stephen Cunnane, PhD, of the University of Sherbrooke, in Quebec. Cunnane and his team are one of the world leaders using Positron Emission Tomography (PET scan) imaging which uses glucose molecules with radioactive tags to visualize how brain cells take up the sugar.
Says Cunnane, it has been known since the early 1980s, through the use of PET scanning, that brain glucose metabolism is impaired in individuals with Alzheimer’s. The problem with the aging brain’s ability to take up glucose for energy shows up on imaging studies of the brain many years before cognitive problems begin to show.
“In Alzheimer’s disease, some areas of the brain are down by 40% in terms of glucose metabolism. We believe this energy gap increases the risk of neuronal dysfunction and cognitive decline,” Cunnane says.
Cunnane has been an author on more than 60 papers, examining brain energy metabolism using PET imaging, especially in Alzheimer’s disease and other dementias. His team’s studies have found that while glucose uptake is impaired in early Alzheimer’s, the brain’s use of ketones for energy is not.
In a February 2018 presentation “Can Ketones Slow Down Alzheimer’s,” Cunnane likens our brains to a hybrid car that can run on glucose or ketones. If it is no longer running well on glucose, it is very reasonable for people to switch the fuel to ketones, either by a ketogenic diet or by adding ketone supplements. “Attempting to treat the cognitive deficit early in Alzheimer’s using ketogenic interventions in clinical trials is safe, ethical and scientifically well-founded,” Cunnane noted in a 2016 paper entitled: “Can Ketones Help Rescue Brain Fuel Supply in Later Life?”
Early clinical trials: promising preliminary results
While the scientific rationale for using ketones in Alzheimer’s is very solid, it is still seen as a very novel, unorthodox approach by the vast majority of Alzheimer’s researchers and clinicians. While a number of mice and rat interventions have been undertaken, only a handful of clinical trials in humans have occurred amidst the thousands of other clinical trials for Alzheimer’s. Here is a summary of notable studies:
- One of the first human trials occurred in 2004 when Japanese researchers took 19 healthy, cognitively normal adults over the age of 60. They fed them a ketogenic meal with MCT oil, measured elevations of blood ketones, then ran them through cognitive tests 90 and 180 minutes after the meal. Those with the worst cognitive scores prior to receiving ketones showed the most improvement in working memory, visual attention and task-switching after receiving ketones.
- In 2012, US researchers led by Dr. Robert Krikorian randomly assigned 23 older adults with mild cognitive impairment (MCI) to six weeks on either a very low-carb ketogenic diet or a high-carb low-fat diet. Those on the ketogenic diet lost weight and inches around their waist, and also saw improvements in fasting blood sugar and fasting insulin levels. Most importantly, performance on memory tests measurably improved in the low-carb group, with the greatest improvements among those who achieved the highest levels of blood ketones.
- In December 2017, a team of Kansas researchers published the results of “The Ketogenic Diet Retention and Feasibility Trial (KDRAFT)” that enrolled 15 participants with mild and moderate Alzheimer’s. The study put all 15 on a ketogenic diet for three months and added MCT oil to achieve higher levels of ketones in the blood. A family member was required to cook for them for four months. All four of the subjects with moderate Alzheimer’s dropped out — the intervention was too burdensome for their caregivers. But 10 of 11 with mild Alzheimer’s disease kept to the diet and saw an average 4.1 point improvement on cognitive tests, a significant improvement. (A clinical improvement of 3 to 4 points is considered “clinically meaningful” in tests of Alzheimer’s drugs.) A month after stopping the diet, the subjects’ cognitive performance improvements were lost.
“While more studies are needed, this suggests that the diet performed as well or better in people with mild Alzheimer’s disease than any of the currently available Alzheimer’s medicines. If a new drug intervention had achieved that degree of improvement, people would be jumping up and down with excitement,” said Dr. Ede of the Kansas trial.
Cunnane announced his group’s results of a six-month randomized-controlled trial of ketone supplementation (30 g of MCT a day) in mild cognitive impairment at the Alzheimer Association International Congress in London in July 2017. The full paper will be published later in 2018. “The cognitive results were quite encouraging. With what we’ve learned from that study, we would recommend 40-45 g a day of MCT instead of 30g,” he said.
Currently two more US clinical trials are underway examining the effect of a ketogenic diet on elderly patients with mild or moderate Alzheimer’s:
- One study, out of Wake Forest University in North Carolina, is in the process of examining the impact of low-carb high-fat diets and low-fat high-carb diets on the memory, biomarkers and neuroimaging of two groups of adults — a group with prediabetes but no symptoms yet of any cognitive impairment, and a second group with symptoms of mild cognitive impairment. A third group of healthy older adults will be the control, and have their memory and biomarkers tested but not have either dietary intervention. This study is expected to report out in late 2019.
- The second study, out of Johns Hopkins University in Baltimore, is still actively recruiting 60 community living adults older than 65, with either mild cognitive impairment or early Alzheimer’s. They and a caregiver will be coached how to eat a ketogenic diet of less than 20 g of carbs a day. They will be followed for 12 weeks with food logs, measurements and cognitive tests. The study requires an adult who is not cognitively impaired to live with the study subject full time to help him or her adhere to the ketogenic diet.
That Johns Hopkins protocol sounded almost exactly like what I planned to do with my parents
A small family study of N=3
On Sunday February 19, 2018, we started our experiment. I weighed my parents and measured their height, waist, leg, hip and arm circumferences. Neither one has ever been overweight in their long life; losing too much weight, and becoming too frail, was a concern. Mom was 5’2″ (157 cm) and 111 lbs (50 kg), with a BMI of 21. Dad was 5’9” (175 cm) and 160 lbs (73 kg) for a BMI of 23.6. We would be doing no fasting and I would be sure to keep their calories high to try to prevent weight loss.
Fortunately Mom is not on a single prescription medication — a rarity for a senior — so we did not need to worry about drug impacts for her. Dad is on five medications: a diuretic and beta blocker for blood pressure and mild heart failure (he had a small silent heart attack about 15 years ago), a drug for a hypoactive thyroid, and warfarin and a baby aspirin for atrial fibrillation and for stroke prevention. As a doctor he felt confident his medications levels would be fine.
That afternoon, before starting the keto diet, I gave them each separately the Montreal Cognitive Assessment (MoCA) test. It is a validated 30 point, 15 minute test which family doctors can do in their office to identify patients with cognitive impairment. The test has a number of tasks including drawing a clock face with the hands at a specific time, drawing a geometric shape, naming pictures of four exotic animals, remembering five words without prompting, subtracting 7s in a sequence from a starting number, and doing other visual, verbal, executive, reasoning, and memory tests.
Dad, who still reads the medical journal The Lancet every week and devours almost a book every two days, only had trouble with the delayed recall of four out of five words. He got a normal score of 26/30.
Mom struggled with a number of sections: putting the hands on the clock face for the right time, drawing the 3D geometric shape, naming the exotic animals, and subtracting 7s, listing all words she knew starting with F. But she had no problem with the attention and delayed recall of words. She scored lower than we expected in the high teens.
Delicious meals, no hunger, no keto flu
For the next two weeks we followed the Diet Doctor ketogenic recipes for breakfast, lunch and dinner. Eggs — fried, scrambled, poached, baked — and either bacon or sausage were typical breakfast items, usually with avocado and cherry tomatoes on the side. For variety, some days we tried the various recipes for keto pancakes, always served with whipping cream and blueberries. The pancake recipe using cottage cheese was the hands down favourite. Morning coffee and afternoon tea had full-fat cream and a spoonful of coconut oil.
A typical lunch was a salad with homemade soup (such as vegetables and meat in a bone broth base, or mushroom soup in a full-fat cream sauce), often with a cheese plate and keto seed crackers. Dinner was usually a simple protein — a piece of fish (adding capers to the yummy baked salmon with lemons) or meat (roast chicken, roast beef) — with a salad and vegetables (always with butter or a cheese sauce.) The “crack slaw” stuffed cabbage casserole and the sausage, cauliflower and broccoli casserole were also favourites — with plenty of leftovers for lunches. Berries and whipping cream, with square of 85% chocolate, was the typical evening dessert.
“The food was delicious, and we never felt hungry,” said my mother.
Mom and I enjoyed working in the kitchen together; it was a time of bonding and sharing as we planned meals, shopped, chopped and cooked together. Dad was always involved in the table setting and clean up — he loads a dishwasher like an efficient engineer.
We had removed their typical meal items such as bread, potatoes, rice and a nightly high-carb dessert. The only thing Dad missed was the occasional piece of Mom’s apple pie, but when we made the low-carb baked apple dessert that hankering was easily met. (“And it was much easier than making pie!” said Mom.)
Ketostix showed that they both entered light ketosis within two days, with no keto flu nor any other side effects. Every few days I would measure the more accurate blood ketones against the ketostix results.
While the three of us were eating exactly the same diet, even almost identical portion sizes, our ketone readings were quite different from each other. I’ve been eating keto for three years and my blood markers showed I was in optimal ketosis the whole time, with my blood readings ranging from 1.9 mmol/L to as high as 3.3 mmol. Mom’ ketones ranged between 0.7 and 1.3 mmol/L. Dad ranged between 0.6 and 0.9 mmol/L, never higher. I have no idea why — could it be different levels of liver function in breaking down fat and converting it to ketones? Cunanne’s group has published findings that there is no difference in the ability of younger vs. older adults to make ketones. “The different ketone response of different people is well-known and is hard to account for,” he told me.
Despite my optimal ketosis, however, my weight stayed stable the whole time at 136 lbs (62 kg). Mom dropped 3 lbs (1 kg) and Dad dropped 5 lbs (2 kg) in the first five days — and stayed at the lower weight. I was worried that if they continued to lose weight, we would have to stop the experiment. But after that first week, they lost no more. I added butter, whipping cream, and coconut oil to absolutely everything, which is maybe why my ketone readings were so high but my weight stayed steady. I wasn’t burning any of my own body fat and the ketones in my blood reflected all the fat I was eating.
What did the cognitive tests show?
After two weeks of ketosis, we did another version of the MoCA test (same basic style, different questions.) Dad’s score went up by 3 points to 29/30. (He admits to practicing memorizing a list of words in the interim but that mental motivation and stimulation is fair game.) Mom went up by five points to 22/30 —a significant improvement. We felt those were impressive results. They report, however, that physically they didn’t feel any different. Ketosis did not give them the energy spurt and subjective feelings of mental clarity, unlike their daughters. But they liked the food all the same.
Two weeks later — after a total of four weeks of keto eating — we did another version of the test one more time. Dad was still 29/30 — great for a man of 92. Mom for the first time felt anxious and scared of the test. I tried to make it comfortable and light for her, just an interesting family experiment. But we both knew that her results really mattered to her. She slipped two points to 20/30, still higher than her original score pre-keto, but not as high as we had hoped. Was it just a bad day? We weren’t sure. “I didn’t feel so good. I was really nervous and I think I froze a bit,” she told me.
The next day it was time for me to fly home to my husband and children. But my Mom and Dad have decided to keep keto eating on their own for as long as they can — at least until the early summer. They want to give it at least the 12 weeks, to align with what current clinical trials are mandating.
Will they then deny themselves the fresh fruit and sweet corn that are the lovely summer bounty of the local farms outside their small town? They are not sure. At 92, they know they don’t have that many more opportunities to eat fresh produce from the farmers’ stands.
But the ketogenic diet makes sense to them.
“I understand what it is all about now, and it is not that hard to do,” says Mom. “I think it could be helping.”
“We are going to stay the course,” said Dad.
It may be impossible to turn back the hands of time, but they feel a sense of control and comfort by trying to get more ketones to their brains for now. As Dad says, they have nothing to lose by trying.