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Ketogenic Diet Improves Symptoms of Alzheimer’s Disease in Randomized Controlled Trial (February 2021)

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Quick Summary tl;dr

This randomized controlled crossover trial was a strong research study because each participant served as her/his own control, the dietary interventions were conducted for a long period of time, and the assessors were blinded to the intervention.

A ketogenic diet improves symptoms of Alzheimer’s disease, including daily functioning and quality of life, as compared to a low-fat diet.

At the that I’m writing this, it’s been less than four hours since an exciting research paper went live in the journal Alzheimer’s Research & Therapy entitled, “Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease.” ( Matthew C. L. Phillips, 2021) This research has several strengths that have been absent in prior human studies and shows convincingly that a ketogenic diet improves symptoms of Alzheimer’s disease.

Background

A decrease in brain’s ability to use glucose as a fuel is thought to be one of the early steps in the development of cognitive decline and Alzheimer’s disease. Therefore, it makes sense that providing ketone bodies, an alternate source of fuel for the brain that also boosts mitochondrial biogenesis and protects against amyloid toxicity, would improve cognition in those with Alzheimer’s disease.

Ketone bodies are a fuel for the brain that boost mitochondrial biogenesis and protect against Alzheimer’s amyloid toxicity.

Study Design and Strengths

This study was a two-period randomized controlled crossover trial comparing a ketogenic diet with a low-fat diet. This jargon means that each of the participants underwent both dietary protocols in a random order so that each person could serve as her/his own control, eliminating between-person variability. Such randomized crossover trials are the gold standard for clinical research.

The diets themselves both appeared relatively healthy, with the low-fat diet being based on the New Zealand healthy eating guidelines. The ketogenic diet was 58% calories from fat, which was sufficient to help participants achieve nutritional ketosis, and the low-fat diet was 11% calories from fat. Each dietary intervention was conducted for 12 weeks with a 10-week washout period between the diets. This is presumably enough time for adaptation to occur.

Not only did each participant undergo each diet, but both diets were presented to participants as healthy options and the assessors who examined participants’ symptoms before and after the intervention were blinded to the participants’ groups. This suggests that any differences observed between the diets were a result of the diet and not participant or assessor bias.

Symptoms were measured before and after the interventions using three assessments.

  • Activities of Daily Living (ADCS-ADL) inventory was used to assess individuals’ abilities to function in daily life.
  • Quality of Life in AD (QOL-AD) questionnaire was used to determine quality of life.
  • Addenbrookes Cognitive Examination — III (ACE-III) scale was used to assess cognition (attention, memory, fluency, language, and visuospatial ability).

On all tests, higher scores represent better performance.

Results and Conclusions

Average blood 𝛽-hydroxybutyrate levels in the ketogenic diet group were 0.95 mM, confirming that the patients did adhere to the diet overall. Only one of the twenty-six participants abandoned the ketogenic diet because of an adverse outcome, which was diarrhea as the result of consuming more coconut oil than instructed. Whoops! In a word, the diet was “sustainable,” even for those with dementia.

Ketogenic diets are sustainable, even if you have dementia.

Ketogenic Diet Improves Symptoms of Alzheimer’s Disease in Randomized Controlled Trial (February 2021)

Most importantly, symptoms significantly improved in individuals who sustained even mild nutritional ketosis, as compared to the low-fat group. On the ADCS-ADL inventory for daily functioning, scores improved +2.95 points in the ketogenic group as compared to low-fat (p = 0.04). On the QOL-AD questionnaire for quality of life, scores improved +4.28 points in the ketogenic group as compared to low-fat (p = 0.03). On the ACE-III scale for cognition, scores were trending towards an improvement, +2.56 (p = 0.12). Thus, as compared to the low-fat diet, daily functioning and quality of life improved significantly on the ketogenic diet, and cognition appeared to improve, although the difference was just shy of significance likely because of the small sample size and relatively light degree of ketosis.

Ketogenic diets are better than low-fat diets for improvement Alzheimer’s disease symptoms.

Cardiovascular risk also improved on the ketogenic diet as compared to the low-fat diet, as measured by improvements in weight, BMI, HDL, HbA1c and a trend towards improved triglycerides. LDL also increased, but given the improvements in other metrics (in particular HDL and trending triglycerides), this was unlikely to constitue a meaningful increase in risk. An LDL subfractionation would likely have revealed an increase in big, fluffy healthy LDL, not small dense LDL.

Ketogenic Diet Improves Symptoms of Alzheimer’s Disease in Randomized Controlled Trial (February 2021)

Ketogenic Diet Improves Symptoms of Alzheimer’s Disease in Randomized Controlled Trial (February 2021)

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Dr. Nicholas Norwitz
PhD in Ketogenics and Metabolism, Oxford University

Nicholas Notwitz

Dr. Nicholas Norwitz is a new shining star in nutrition science. This 25-year-old Ivy League Valedictorian obtained his PhD at Oxford University in just two years and is now pursing his MD at Harvard Medical School. His research expertise is ketosis and brain aging; however, he has published scientific papers on topics ranging from neuroscience to heart disease to gastrointestinal health to genetics to bone health to diabetes.

You can find Nick on Twitter at @nicknorwitz.

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Comments (9)

Hi Nick
I’m 90% vegetarian (I have anemia at times) and I find most keto recipes have lots of animal protein. Why is this?
Where would I find nutritionally balanced recipes for veggies. I love the science but have yet to get into ketosis. I have a hypothyroidism as well.

Hi Lorraine, most keto recipes contain some form of animal protein because that is how this diet has been designed: Complete Keto Diet Food List: What to Eat and Avoid on a Low-Carb Diet
Having said that, you can follow a vegetarian (lacto-ovo) friendly keto diet - there are lots of veggie keto recipes here: KetoDiet Blog: Recipes (simply use the recipe filter to find what you are looking for). Also, I'll be sharing a very popular vegetarian recipe today so stay tuned. I hope this helps!

I always use butter (KerryGold) and MCT oil.
Eggs👍🏻Mushrooms
But I can’t justify eating so much meat or fish it feels wrong somehow.
Thank you

Lacto-ovo-veg protein list:
Pea protein, Soy/tempeh, Eggs, Sheep & goat's milk cheeses. The first two are completely vegetarian and are, more or less, complete proteins. This means that they contain all nine "essential" amino acid protein building blocks. Eggs are an incredible source of nutrition all around. Sheep and goat's milk cheeses are less inflammatory thank cow's milk cheeses.
As it seems you're vegetarian for ethical reasons, with a little bit of leeway for nutrition, what I would suggest you consider looking into is the environmental impact and animal treatment practices of certain regenerative agriculture farms versus standard factory farming. White Oak pastures is one to check out. I bring this up because I am similarly concerned about the climate and animal-welfare issue. I personally choose to minimize my intake of standard supermarket meat because factory farming is horrendous for the environment and the animals are treated terribly. However, this does not necessarily mean eating meat is bad for the ecosystem or animals, in my opinion. On the former, reiterative farms actually put less CO2 into the atmosphere per pound of beef than plant-based alternatives, like beyond burger or impossible burger. Yes, you do end up eating the animal, but if they were treated right throughout life that's something. Also consider that plant agriculture generates about as much, if not more, death and the plows and mowers chop up the field mice and rodents. It's unfortunate, but it's reality. No pressure of course to change, but just something to consider. (Also, I like to eat organs and odds and ends because they are the most-nutrient dense parts and the parts that might otherwise go to waste. E.g. I ask the monger at Whole Foods to save the large fish heads for me. Usually there is a lot of fish meat there and otherwise it's going in the garbage. I realize this might not sound appealing, but I throw it out there.)
Finally, on the nutritional completeness front, if you're primarily vegetarian you'll want an algae-based EPA/DHA supplement for your essential omega-3s. Plant-based sources of omega-3 (walnuts, chia, flax) aren't sufficient because they are only ALA. You'll also want B-vitamins, especially B12 in the methylcobalamin form. I'd get a supplement for this if needs be, but it is very rich in non-red meat animal protein. Alaskan sockeye salmon is incredible and always wild.
On the hypothyroidism front, Martina cured her Hashi with Keto so she can give the best advice. We have thyroid targeting recipes without meat in our upcoming book too, as a sidebar.

Thank you so much for taking the time to share this info.
I am a Buddhist nun so I live in a community where meat/fish is forbidden this is mainly because we set an example of loving kindness and right living.but being vegetarian/vegan is a personal choice for everyone and was not proscribed by Buddha per se.
So I can eat Alaskan Salmon when I go to parents and also as you said the offal such as liver, but purely for medicine and not often once a month.
We do unfortunately live high up the food chain so in order to have food of any kind another being suffers. (Samsara)
Once again thank you and I am very interested in Martina’s path to curing her Hadshi

If we have 1 acre of land say, are you saying that CO2 generated from animals alone grazing that land is lower than plant agriculture alone growing in that land?

Hello Hafeez, may I please ask that we keep all comments relevant to the topic discussed in this article? I do not expect Nick to respond as we need to keep comments relevant to AD. Thank you for understanding.

I wish I could have shown this to my granny when she was sick. If only we've known all this years ago she could still be here. Because AD runs in our family I am fully committed to keto. Excited to see even more research!

Feel your pain Helen and feel the same way. I have great confidence that in the next 10 years we will learn a lot more. I've giving a lecture on precision nutrition for people at high-risk for AD this weekend to the Society of Metabolic Health Practitioners and if we can make it available here or at our new book's website in future we will. Be well 😊