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 how great we were feeling. A few of us remarked on having improved mental clarity — a benefit some people have reported from the ketogenic lifestyle.1
So they wondered, could drastically cutting carbs 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 parents’ 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 meter 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 a validated cognitive assessment test to help chart and document any changes 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 neither for weight loss nor 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 provide an alternative fuel for their brains? 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 Western societies.
Currently an estimated 50 million cases of Alzheimer’s and dementia exist globally, including 7.5 million in Western Europe and 5 million in North America. Those numbers are expected to increase by more than 200% over the next 30 years, reaching 150 million cases worldwide by 2050.2
Modifiable risk factors for Alzheimer’s include type 2 diabetes, obesity, metabolic syndrome, and high blood pressure.3 Research has shown that these risk factors may be controlled or improved with a low-carb or ketogenic lifestyle.4
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 lives. 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. And with each passing year after entering the late 80s the incidence of dementias increases exponentially, reaching upwards of 40% by age 100.5
At this time there is neither a cure nor an effective treatment. Research for the last two decades has been burgeoning and more than 3,200 clinical trials for various interventions are currently underway around the world, including studies in various phases on more than 100 new drugs.6 Yet the track record for drug effectiveness has been dismal.7
Because rates of Alzheimer’s have increased so dramatically, many people in middle to older age report being concerned that they may develop it or other forms of dementia.8
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 the brain can use ketones to meet a large portion of its fuel needs.9 Your liver creates ketones from fatty acids, either from fat in your diet or fat stored in your body.
Although carbs break down to glucose in your digestive tract, you don’t have to eat carbs to supply your brain with the small amount of glucose it requires. This is because your liver can make all the glucose your brain needs through a process known as gluconeogenesis (literally “making new glucose”).10 Evidence that certain impaired brain functions can improve by increasing the use of ketones for brain fuel has existed for almost a century.
For instance, several high-quality trials have shown that in some but not all cases, the ketogenic diet can reduce the frequency and severity of seizures in children with epilepsy.11 And a number of researchers have hypothesized that tapping into ketone metabolism may have powerful applications to many other areas of brain health.12
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, including anxiety, depression and bipolar illness.13Yet the research base, while promising, is slim by some accounts.14
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 2018 review suggests that ketones may enhance energy production, increase nerve cell growth factors, strengthen the signal sent between nerve synapses, and reduce brain inflammation.15 And a 2020 study suggested ketones “stabilize” the brain’s nerve connections while glucose destabalizes them.16
“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.17 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.18
Scientific evidence: Alzheimer’s brains show reduced uptake of glucose
In Alzheimer’s disease, insulin resistance (IR) in the brain may hamper the uptake of glucose for fuel, Dr. Ede notes in her 2017 video. She also delves into the issue 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.”19
This brain IR, which limits the brain’s use of glucose no matter how high blood sugar rises, may help explain the higher rates of Alzheimer’s among those with type 2 diabetes.20 For example, in a 2004 study, autopsy data revealed that 81% of people with Alzheimer’s had either type 2 diabetes or prediabetes.21 In another autopsy study, people who died with Alzheimer’s disease had evidence of brain glucose dysregulation.22
However, brain IR may even impact the uptake of glucose in people with diabetes or prediabetes who are years away from any cognitive symptoms.23 In addition, it may affect young women with polycystic ovarian syndrome (PCOS).24 PCOS is a reproductive metabolic disorder in which insulin resistance is a factor — and for which a low-carb or keto diet may be beneficial.
“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.25
“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, including several 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 is not.26
In a February 2018 presentation, 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.27
Early clinical trials: promising preliminary results
While the scientific rationale for using ketones in Alzheimer’s is solid, it is still seen as a very novel, unorthodox approach by many Alzheimer’s researchers and clinicians. While a number of rodent studies have been done, only a handful of ketogenic human interventions have occurred amidst thousands of other clinical trials for Alzheimer’s. In addition, there are only a few new trials in the active or recruiting stage.
Here is a summary of notable studies that have been completed so far:
- A 2021 randomized crossover study found subjects following a modified ketogenic diet (29% protein, 59% fat, and 6% net carbs) had significant improvements in quality of life and ability to perform daily activities compared to when they followed a low-fat diet.28 They also noticed excellent complaince and no increase in side effects with the ketogenic diet.
- In a 2012 study, 23 older adults with mild cognitive impairment (MCI) were randomly assigned to eat either a very low-carb ketogenic diet or a high-carb low-fat diet for six weeks. Those on the ketogenic diet lost weight and inches around their waist and also saw improvements in fasting blood sugar and 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.29
- In 2018, Cunnane published his group’s results of a six-month randomized-controlled trial of ketone supplementation (30 grams of MCT a day) in 17 patients with mild to moderate Alzheimer’s disease.30 “The cognitive results were quite encouraging. With what we’ve learned from that study, we would recommend 40-45 grams a day of MCT instead of 30 grams,” he said.
- In 2016 Japanese researchers conducted a trial in 19 healthy, cognitively normal adults over the age of 60. They fed the participants a ketogenic meal with MCT oil, measured their blood ketones, and ran cognitive tests 90 and 180 minutes after the meal. Those with the worst cognitive scores prior to the keto meal showed the most improvement in working memory, visual attention and task-switching after the intervention.31
- In 2017, Kansas researchers published results of a study in older adults with mild or moderate Alzheimer’s disease. The 15 participants were fed a ketogenic diet supplemented with MCT oil for three months. All four subjects with moderate Alzheimer’s dropped out; the intervention was too burdensome for their caregivers. But 10 of 11 with mild Alzheimer’s stayed on the diet and experienced significant improvement on cognitive tests. However, a month after stopping the diet, those improvements were lost.32
- A 2020 systematic review of randomized controlled trials concluded that being in ketosis, either through a kethogenic diet, ketone supplements, or MCT supplements, “appears promising in improving both acute and long-term cognition among patients with AD/MCI (Alzheimer’s Disease or mild cognitive impairment).” They also noted a greater beneficial effect in those without an ApoE4 gene.33
A small family study of N=3
On Sunday February 19, 2018, my parents and I started our experiment. I weighed them and measured their height, waist, leg, hip and arm circumferences. Neither one has ever been overweight; losing too much weight and becoming too frail were of 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), with 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 stroke prevention. As a doctor, he felt confident his medications levels would be fine.
Before starting the keto diet, I separately gave each of my parents 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. It includes tasks like drawing a clock face with the hands at a specific time, drawing a geometric shape, identifying four exotic animals in pictures, remembering five words without prompting, and subtracting sevens in a sequence from a starting number, among other verbal, 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, subtracting sevens, and 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 lemon) 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 a 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 cleanup — 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 and 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 my blood readings ranging from 1.9 mmol/L to as high as 3.3 mmol/L. Mom’s ketones ranged from 0.7 to 1.3 mmol/L. Dad’s ranged from 0.6 to 0.9 mmol/L, never higher.
Cunanne’s group has published findings showing there is no difference in the ability of younger vs. older adults to make ketones.34 “The different ketone response of different people is well-known and is hard to account for,” he told me.
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 eating keto 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.
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Although the brain always needs some glucose, researchers have shown that during extended fasting or strict ketogenic eating, ketones can be used to meet between 30-70% of the brain’s energy requirement:
Journal of Cerebral Blood flow and Metabolism 2017: Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study [nonrandomized study, weak evidence]↩
Epilepsy Research 2016: Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: a randomized controlled trial [moderate evidence] ↩
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Archives of Neurology 2011: Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes [observational study; weak evidence]
In fact, some scientists propose using glucose metabolism as a surrogate marker for Alzheimer’s disease
Experimental gerontology 2018: A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease [case-control study; very weak evidence] ↩
Annals of the New York Academy of Sciences 2016: Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease [overview article; ungraded] ↩
Regarding this trial, Dr. Ede said, “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.”
Advances in Nutrition 2020:
To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease [systematic review of randomized trials; strong evidence] ↩