Book Review: The Alzheimer's Antidote

Alzheimer’s Disease (AD) is generally viewed as an unstoppable disease with a cause that is too complex to understand or prevent. Amy Berger, author of The Alzheimer’s Antidote, counters that AD may not be as enigmatic as commonly believed. Medical literature often refers to AD as “Type 3 Diabetes” and like most chronic diseases, it is related to chronically elevated insulin. Berger is far too nuanced and too practical to claim bulletproof treatment or prevention of this dignity-robbing disease. However, her approach of using a ketogenic diet and other lifestyle modifications is an important step towards improving cognition in AD-afflicted people. Some of the same tactics can also mitigate the risk of developing AD in the first place.

This is the only way I could make the review any more glowing.

Berger postulates that the defining factor of AD is the brain’s inability to properly fuel itself via glucose. The good news is that brains unable to properly metabolize glucose can still metabolize ketones. Ketones are produced by the liver when one eats a very-low-carbohydrate diet, so Berger promotes this ketogenic way of eating (along with other ketone-boosting interventions) to improve cognition in a person suffering from AD.

The book highlights the work of Dr. Dale Bredesen. In contrast to the disappointing results from drug-based AD treatments, Bredesen’s work has been largely successful. His ketogenic approach has allowed many of his severely AD-impaired patients to go back to work and lead their normal lives. Berger shares his quote: “AD is not a mysterious, untreatable brain disease-- it is a reversible, metabolic/toxic, usually systemic illness with a relatively large window for treatment.”

Berger discusses brain health from many angles, and she spends lots of time underscoring the value of cholesterol for a healthy brain. She is highly critical of the idea of cholesterol-lowering medications (statins) and calls out the fact that people who take them have increased risk of brain fog, cognitive impairment, depression, hormonal imbalances, diabetes, low libido, infertility, and memory loss. Furthermore, antacids (e.g. Pepto-Bismol) and proton pump inhibitors (e.g. Prilosec) can lead to brain-atrophying vitamin B12 deficiency. With common usage of these drugs and with common diets being nutrient-poor and insulin-spiking, it is no wonder that we are seeing cognitive decline in people earlier than we used to.

The Alzheimer’s Antidote pushes back against a common idea that beta-amyloid plaques are a driving factor in Alzheimer’s. Rather than disease causes, these plaques are effects: the plaques build up when an enzyme that could degrade them instead is too busy degrading excessive insulin. Long before beta-amyloid plaques show up in the brain, decreased brain glucose metabolism can be detected in PET scans (including in people just in their 30s and 40s). Berger also downplays common concern about the APoE4 gene variant. While APoE4 carriers do have an increased AD risk, focusing on genetics distracts from the root cause of elevated insulin levels.

For AD sufferers, for AD caregivers, and for anyone who cares about maintaining cognitive health, this book is a terrific resource. In a a practical, compassionate, and realistic manner, it teaches the reader how to implement a low-carb diet to improve cognition. It also makes the case for lifestyle practices like exercise and intermittent fasting. Berger’s work gives plenty of “why” and lots of "how" but it ultimately provides something else even more important: hope.

If you want to see a heartwarming real-life example of Berger's approach, see here. That video is what inspired me to finally read this book.

While you will find Berger's name in several of my favorite podcasts, I think one of her best interviews is here on the Peak Human podcast.

The Power of Nutrition

For anyone wondering why someone would become interested in, fascinated by, or obsessed with nutrition, check out this Tweet:

7 months ago my Mom, who has #Alzheimers, could barely walk. Eating #keto, she lost 23 lbs, gained sharpness & mobility. Share this video of my Mom dancing, she'll smile knowing she can give others hope. Tx :- ) @TuitNutrition @DietDoctor1 @tednaiman @Nutradvance @bigfatsurprise pic.twitter.com/c5cYBSV3gq

— 50 Fitty (@50Fitty) January 14, 2019

Things like this are why people like me are so passionate about nutrition. And about the potential of keto. 😃😃😃

This is Your Health on Keto

A well-formulated ketogenic diet (WFKD) improves insulin resistance. Insulin resistance is the condition connected to nearly every chronic disease: from type 2 diabetes to cancer to heart disease to Alzheimer’s and more. Most American adults today are insulin resistant. About 9 out of 10. Therefore nearly everybody could benefit from eating a ketogenic diet. A full description of a WFKD is beyond the scope of this post, but at its essence, a WFKD is a low-carbohydrate diet consisting of whole foods (=/= 50 grams of carbohydrate or less per day, eat until full, no calorie counting).

To highlight what happens to real people when they go on a ketogenic diet, it is helpful to look at a couple interesting cases: (1) the Virta Health study, and (2) dual lab values between twins: one eats the standard American diet, one eats a ketogenic diet.

Virta Health Study

In one year, using the ketogenic diet, the Virta Health program reversed Type 2 Diabetes in 60% of its patients. Yes, that’s right: type 2 diabetes, commonly thought to be chronic and progressive, can be reversed. In the same peer-reviewed study, 94% of patients reduced or eliminated their usage of injected insulin.

Nearly all health markers improved for the patients treated with the ketogenic diet. This includes reduced inflammation, weight loss, improved blood pressure, improved liver function, and improved cardiovascular health markers. (Despite the common belief that saturated fat is unhealthy, it turns out that a low-carbohydrate diet with a significant amount of saturated fats is likely very good for heart health.)

That all sounds abstract, but the Virta ketogenic intervention was performed on 218 real people who greatly improved their health by modifying their diet. Many of these people reversed their diabetes and greatly improved their quality of life. That is the power of nutrition; and specifically, that is the potential of a well-formulated ketogenic diet. You can read some of their testimonials here.

Lab Values of Twins (One Keto, One Standard American Diet)

This video details the lab value differences between two 16-year-old twin sisters. One twin eats a ketogenic diet. The other eats something akin to the standard American diet (some meals are ketogenic because the meals eaten with her family are low-carb). They share the same genetics but different diets.

The twins have remarkably similar lab values for most health biomarkers. Even their blood glucose levels were nearly identical. However, the standard American diet twin is significantly more insulin resistant. The keto twin’s fasting insulin is significantly lower than the other twin’s. Likewise, the keto twin’s C-peptide measurement (a proxy for insulin resistance) is significantly lower. As discussed in this post on insulin resistance, elevated insulin levels are an indicator of impending health problems. These elevated insulin levels may appear decades before blood glucose levels rise to prediabetic or diabetic levels.

Measurement	Standard American Diet Twin	Keto Diet Twin	Note
LDL Cholesterol (mg/dL)	61	98	For more on proper context for interpreting LDL-C results on keto diet, visit www.cholesterolcode.com
HDL Cholesterol (mg/dL)	53	57
Triglycerides (mg/dL)	38	42	Both excellent
Glucose (mg/dL)	87	88
Hemoglobin A1C	4.90%	4.80%
hsCRP (mg/L)	0.25	0.17	This is a marker of inflammation. Both have excellent results, extremely low inflammation.
C-peptide (ng/mL)	2.6	1.3	Significant difference-- and generally, the higher the C-peptide, the greater the insulin resistance.
Insulin (uIU/mL)	13.4	4.6	Wow, what a difference. And in the (arguably) most important health marker measurement of the lab results.

Summary

• Most modern people are insulin resistant, which is likely at the heart of most chronic diseases.
• A well-formulated ketogenic diet improves insulin resistance.
• Therefore, eating a WFKD is likely a good way for most people to improve existing conditions related to insulin resistance and to reduce the risk of developing such conditions.
• On a related note, eating a WKFD is likely to lower an individual's inflammation, improve cardiovascular health, and improve liver function.

This post looks at lab values to utilize common objective measurements. However, in real life, subjective experiences are what count. In other words, I don't care if my triglycerides look great on a lab sheet if I feel like crap. For the keto dieters with improved insulin resistance markers, what do you think happened to their moods and energy levels? (If you want a hint, try Googling "keto mood")

The results listed here are a small sample size; they are just from one study and one twin vs. twin comparison. The sample size is small but meaningful. (And remember, you yourself are a small but damn important sample size.) The Virta info is peer-reviewed science carried out in the real world. The twin comparison is a look at two teenagers sharing common genetics but different diets in the real world. I showcase them because they reflect broader truths about what typically happens when people in the real world adopt ketogenic diets. Ketogenic diets improve insulin resistance and therefore they improve people's health, often to an incredible degree.


*Disclaimer: I am not guaranteeing that a ketogenic diet is appropriate for every person, nor that it is the only way to improve insulin resistance. However, the ketogenic diet is so reliable at improving health for the vast majority of the population that it is more appropriate to get that message across as opposed to discussing every rare exception. Focusing on rare exceptions would be missing the forest for the trees. For what it’s worth, Virta Health medical director Dr. Sarah Hallberg says the only type of person she has found that is not a good candidate for a ketogenic diet is someone who has hyperchylomicronemia (1 in 1-2 million people). Regardless, if considering a change, do your own research and always consult a medical professional where appropriate.

References that Dig Deeper

The Ketogenic Diet as a Treatment for Metabolic Syndrome

Complete Guide to Ketogenic Diet for Beginners
Diet Doctor Podcast with Guest Dr. Sarah Hallberg
BioHackers Lab Podcast with Dr. James McCarter
Virta Health
HEAL Clinics (treats Type 2 Diabetes with keto, claims 98% success at eliminating injected insulin)
My Notes (Part 1) on August 2018 Keto Science Conference
My Notes (Part 2) on August 2018 Keto Science Conference
My Notes (Part 3) on August 2018 Keto Science Conference
My Notes (Part 4) on August 2018 Keto Science Conference

OSU Keto Conference, Day 2 (Part 2)

continued from Day 2, part 1

Day 2, part 2

During this part of the day, the speakers were discussing the effect of ketosis on the brain-- specifically, the effects of ketosis on Alzheimer's and epilepsy.

Stephen Cunnane, PhD: Brain Glucose and Ketone Metabolism (Alzheimer's)

Cunnane talks about how ketones are an essential fuel for infant development. Breast-fed babies spend time in ketosis. There are medium chain triglycerides (MCTs) in mammalian milk.

Glucose is pulled into the brain, while ketones are pushed into the brain.

Alzheimer's sufferers have inhibited glucose uptake into the brain. And glucose uptake deficiency precedes cognitive decline. However, the ketogenic diet shows promise as an Alzheimer's treatment because when brain glucose uptake is impaired, brain ketone uptake is fine.

Cunnane mentioned cerebral metabolic rate. Interestingly, the ketone uptake rate into the brain is not as variable as blood ketone levels. People with Alzheimer's can still uptake ketones!

Cunnane talked about the BENEFIC trial (n=39) where cognitive performance was improved with MCT supplementation (MCTs are easily converted into ketones in the body) ("Conclusion: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.")

The more MCT consumed, the less the brain energy gap there was (glucose was still low, but ketones make up the difference). Also, exercise helps get both glucose and ketones to the brain in Alzheimer's patients. Cunnane noted the difficulty of doing such trials; it took 7 years to get 5 Alzheimer's patients through this protocol.

Summary bullet points (from Cunnane's slides):

• Pre-symptomatic, glucose-specific brain energy deficit.
• Brain energy rescue by ketones is feasible in MCI [Mild Cognitive Impairment] and AD [Alzheimer's Disease].
• Recapitulates role of ketones in infant brain.
• Cognitive benefits and mechanism of action need further evaluation.

Eric Kossoff, MD: Ketogenic Diet and Seizure Management (Epilepsy)

Kossoff is the Director of the Child Neurology Residency Program and a Professor of Neurology at Johns Hopkins. He covered the ketogenic diet's (KD) history in its use as a treatment for epilepsy. We are beyond the tipping point using KD for epilepsy. It is now a mainstream-accepted treatment.

Kossoff noted that in Mark 9:14-29, Jesus recommended prayer and fasting for seizure cure.

In 1921, Dr. Wilder at the Mayo Clinic learned that Low-Carb, High-Fat (LCHF) mimics fasting.

Fasting and ketosis work for epilepsy via different mechanisms.

There was an anticonvulsant drug explosion in 1938, then in the 50s, 70s, and 90s, all of which led to decreased usage of the KD for epilepsy; drugs were now an option, seems easier.

Kossoff mentioned that medical marijuana is now an alternative to the KD (he says it probably won't work).

In the early 1990s, the KD was rarely used. It was a last resport. There was no interest in it at the American Epilepsy Society. Then, in 1993, enter the Charlie Foundation (side note: The Charlie Foundation was started by one of the creators of the best movie of all time [Airplane!] when he went outside the mainstream to use the KD to cure his son's epilepsy. He actually teamed up with Meryl Streep for a related movie titled ...First Do No Harm.)

The number of KD studies has gone up exponentially since the late 1990s.

The Cochrane Collaboration, published in 2012, stated that the KD shows good results for epilepsy.

Today, the KD is usually used after 2 drugs have failed. It is one of the 4 major treatments. Mainstream!

Now, in 2018, the Charlie Foundation has been around for 25 years. 2018 will mark the 6th Ketogenic Diet symposium in South Korea. There is something called KetoCollege and KetoUniversity. The American Epilepsy Society, which showed no interest in the KD in 1993, is holding a symposium on the KD in 2018. Furthermore, the international guidelines are being revised!

Kossoff said we need to know how to make the KD easier and safer.

The traditional KD started with a 24-hour fast. 4:1 ratio of fat to other macronutrients. Kids seen every 3-6 months. After 2 years, they try to wean the kids off the KD.

Now. . . they don't need the 24-hour fast to initiate. Kids often don't need admission to the hospital for treatment. Kids can be gradualized in to the KD.

Kossoff detailed 4 ketogenic diets and said they are all equally valid (slight differences in macronutrient ratios-- Ketogenic Diet vs. Medium Chain Triglyceride Diet vs. Modified Atkins Diet vs. Low Glycemic Index Treatment).

Can the KD be replaced with a pill? People are trying. Certainly not definitive. Maybe as a supplement.

History of: "Can KD help infants?"

1963: No. Not helpful.

2002: Yes. Safe and effective.

2015: Yes. Kids under 2 do even better than older kids.

Johns Hopkins started an Adult Epilepsy Diet Center in August 2010 (previously there had been issues where it was tough to get treatment after turning 18 and no longer being eligible for pediatric care). There are now over 300 adults in the clinic. About 20% were already on the KD. 80% were not doing keto; they get put on the Modified Atkins diet (10-20 g carbohydrate per day, approximately 25% protein, 70% fat).

Outstanding questions to look into: How to improve compliance? What are the implications when patients see elevated lipids? Is the diet safe in pregnancy? (He says he thinks it probably is. In the Q&A below, he touches on this further)

Q&A Session, Cunnane and Kossoff

Is there any research on ketosis for Multiple Sclerosis since it may be an inflammatory brain disease like Alzheimer's? Kossoff said there is not much, although he noted there is some work looking at intermittent fasting for MS.

Dr. Scheck asked about people going off the KD. . . why wouldn't the epilepsy symptoms come back after going off the diet? Kossoff said the mechanism is debated. Said there is some evidence that the KD can alter underlying brain. Cunnane said that with AD patients, going off the KD leads to immediately diminished cognition.

Could the effects of ketones partially be an autophagy effect? Cunnane said they are trying to get funding to study just this.

Someone asked about the APOE4 gene allele-- that tends to lead to problems with saturated fat. . . my notes are slightly confused here. What I jotted down was that the APOE4 gene dampened cognitive benefit and metabolic benefit. But his study saw no difference between APOE4 and non-APOE4. So maybe the dampened benefits are what is typically thought, but his results did not support those.

Is there trouble getting trials for kids? Kossoff said institutional review boards (IRBs) are definitely keto-friendly for epilepsy now. But there are pregnancy exclusions for trials (hence, why he listed "Is it safe for pregnancy?" as an outstanding question in his speech). Just can't do pregnancy trials. Cunnane said the problem is that IRBs are scared of ketoacidosis (toxically high ketone levels) in those cases.

A sports medicine physician from Georgia asked about brain blood flow. Cunnane said you can get the acute effect with exogenous ketones. Cunnane then asked whether it is a desirable effect to get increased blood flow. He answered his own question by saying he's not sure that is a requirement.

A health coach from Detroit asked what the mechanism from exercise is for getting increased glucose and increased ketones to the brain in AD patients. Cunnane said he was not sure. Increased ketones because of increased capacity. Increased glucose: open question.

Someone asked abot children with autism (as approximately 30% of autistic children experience seizures). Is there any research of the KD for autism? Kossoff said the autism community is desperate for answers and treatments. He said a 2003 Greece study showed a very modest benefit. A 2017 Hawaii gluten free modified Atkins beneft also showed a very modest benefit. The mechanism is a hot topic. He said there is some work being done in animal models.

A functional registered dietician asked what may change after long-term KD adherence. Kossoff said only 5% of patients use the KD for > 2 years. He said there are very few long-termers. He said the results of long-termers have been "not great but not bad". He referenced that bone density and bone fractures have been issues. Growth has been an issue. He has seen good lipids and good GI results.

A family doctor from Canada asked about Alzheimer's studies with Metformin, as it can sometimes be helpful with insulin resistance. Cunnane said there are two schools of thought with Metformin. One says it is beneficial because it decreases insulin resistance. The other says it increases the risk.

A neuroscientist asked about nasal insulin as an AD treatment. And about nasal ketones. Cunnane said getting ketones to the brain is the goal. Unknown for both, but I thought Cunnane seemed skeptical.