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.

Don't Resist. Be (Insulin) Sensitive

Overview

Just take me to the bullet points. . .

Basics About Insulin

Insulin is a protein and hormone produced by the pancreas and released into the bloodstream; one of its primary functions is to reduce elevated blood glucose levels.

• Insulin resistance: cells in the body are resistant to the effects of insulin. This is metabolically unhealthy.
• Insulin sensitivity: cells in the body are sensitive to the effects of insulin. This is metabolically healthy. 

Insulin resistance is tightly coupled with hyperinsulinemia, a condition in which excess levels of insulin are in the bloodstream relative to the levels of blood glucose. Because the insulin-resistant cells do not properly process insulin, the pancreas is forced to secrete additional insulin in order to stabilize blood glucose levels. And those cells may have become insulin-resistant because of chronically elevated insulin. The cause-and-effect relationship between insulin resistance and hyperinsulinemia is a difficult puzzle to piece together, but as a general rule: where there's insulin resistance, there's hyperinsulinemia. And vice versa. And they're both very bad news.

Why are Insulin Resistance and Hyperinsulinemia Relevant?

Insulin resistance and hyperinsulinemia are connected to most of the major health problems that plague modern humanity: type 2 diabetes, cardiovascular disease, polycystic ovary syndrome, erectile dysfunction, Alzheimer's, certain cancers, osteoarthritis, atherosclerosis. . . the list goes on and on.

In general, the higher your fasting insulin is, the higher likelihood you have of getting a chronic disease.

Most people today are on the path to a chronic disease. That is harsh, but likely accurate. A 2015 JAMA study found that in 2012, 49 - 52% of American adults have either prediabetes or diabetes. And that number undersells the true scale of the metabolic problem, as the measurements used in the study are plasma glucose or HbA1c levels. Elevated insulin levels precede elevated glucose levels by up to 24 years. If half of American adults have elevated glucose levels, significantly more than half of American adults have elevated insulin levels and are therefore headed towards chronic disease.

How to Know if You Are Insulin Resistant

There are several ways to test out how insulin resistant you are.

Two Hour Insulin Glucose Challenge Test

You can ask your doctor if he/she will prescribe the test for you. Otherwise, you can order it without a doctor's orders from WalkInLab. Fasting insulin levels are checked at fasting, then one hour after ingesting 75 or 100 grams of glucose, then two hours after the glucose.

The lower your insulin levels are, the better, at all three measurements.

HOMA-IR Score (Fasting Insulin and Fasting Glucose Levels)

HOMA-IR stands for Homeostatic Model Assessment of Insulin Resistance. It is composed of two tests: fasting glucose and fasting insulin. You can ask your doctor if he/she will prescribe these tests for you. Otherwise, you can order them without a doctor's orders from WalkInLab (fasting glucose and fasting insulin). It is relatively inexpensive. You can then plug your fasting glucose and fasting insulin numbers into this calculator to figure out your HOMA-IR score. Or calculate it yourself: HOMA-IR = (insulin uIU/mL * glucose mg/dL) / 405

Generally speaking, the lower your HOMA-IR score is, the more insulin sensitive you are. Definitions for insulin resistance are slippery, so different groups define insulin resistance at different levels. It is likely wise to use the ranges from The Blood Code: 0.5 - 1.4 is optimal, 1.9 - 2.89 is early insulin resistance, and 2.9+ represents significant insulin resistance.

LP-IR Score

LP-IR stands for Lipid Profile Insulin Resistance. You can get it tested without doctor's orders from WalkInLab. The lower your score, the more insulin sensitive you are. The lab report should provide decent reference ranges so you know how your insulin sensitivity compares to other people's.

Triglyceride : HDL Ratio

You may be able to get an idea of what your insulin sensitivity is through a standard lipid test. A lipid panel can be ordered inexpensively without a doctor's orders here. Lipid panels return basic information about your cholesterol (total, HDL, and LDL) and your triglycerides.

A high ratio of triglycerides to HDL cholesterol (>= 3.5) has been found to be a straightforward way to identify insulin resistant people. Triglyceride-to-HDL ratio is not a perfect measure of insulin resistance. But if all you have are results from a standard lipid test, the results are useful. You want a low ratio-- the lower, the better.

How to Improve Your Insulin Sensitivity

Now you know how crucial it is to be insulin sensitive and how to measure whether or not you are insulin sensitive. With that in mind, how can you improve (or maintain) your insulin sensitivity?

Six ways to improve insulin sensitivity are nutrition, exercise, sleep, reducing stress, not smoking, and sunshine.

Nutrition

There are multiple ways to improve your insulin sensitivity via diet. Whichever dietary approach you follow, make sure you avoid processed foods that were never eaten by healthy traditional peoples studied by Weston A. Price. Exclude white flour, sugary products, and vegetable oils!

Low Carbohydrate Diet

A low-carbohydrate diet is a terrific way to improve your insulin sensitivity. In a controlled study, Type 2 Diabetes patients treated with a low-carbohydrate ketogenic diet improved their HOMA-IR scores by an average of 55% (measured by insulin levels, 29% measured by C-peptide). Fasting insulin levels themselves dropped by 43% in the same study. [Note: That study is groundbreaking and amazing. 60% of the patients reversed their diabetes in the first year. (!!!!!!!!!!!!!) Check out more about it here.]

Results from a continuous glucose monitoring device before and after adopting a low-carb diet. Notice how there is no blood sugar "rollercoaster" in the "After Low Carb" section. This is one reason low-carb diets are effective for treating insulin resistance. This image comes from the Twitter account of RD Dikeman, who is a prominent partner of Dr. Richard Bernstein.

One of the driving ideas behind a low-carb diet is that it keeps your blood sugar levels relatively stable. When your blood glucose levels stay stable, your pancreas does not have to produce much insulin in order to lower your blood glucose. Keeping the insulin levels consistently low helps avoid insulin resistance and hyperinsulinemia.

General idea: Low blood sugar -> low insulin levels -> better insulin sensitivity

Intermittent Fasting

Intermittent fasting involves deliberately shrinking the window of time during the day in which you eat. Some people consider it intermittent fasting to eat within 12 hours (e.g. eating occurs between 7 AM and 7 PM), while others do things such as One Meal A Day (OMAD). No matter what eating window an intermittent faster uses, their general idea is to spend more time in the "fasted" state as opposed to the "fed" state.

There is a lot of research on intermittent fasting in animals, and slightly less in humans (but there is some). But anecdotal and clinical experience shows terrific results. Intermittent fasting leads to improved insulin sensitivity. This may be partially because shrinking your daily eating window leads to a shrunken window of time during the day where insulin is elevated.

General idea: Shrink your eating window -> shrink number of blood sugar spikes -> shrink number of insulin spikes -> better insulin sensitivity

Caloric Restriction

Caloric restriction involves consistently eating significantly less than what you would eat naturally. Caloric restriction can also improve your insulin sensitivity. The mechanism by which it does this is not clear, but it is consistent with the idea that losing weight leads to improved insulin sensitivity.

Caloric restriction is difficult to sustain, especially for the long term. However, it can be a viable option for improving insulin sensitivity. Some research even shows that it can be very beneficial for quality of life.

General idea: Caloric restriction works for improving insulin sensitivity, but it may be tough to deal with the rather consistent hunger.

Exercise

Exercise to improve your insulin sensitivity!

Sleep

Not getting enough sleep increases insulin resistance in as little as two days! Get plenty of sleep to improve your insulin sensitivity!

Reducing Stress

Stress hormone cortisol is negatively associated with insulin sensitivity. Stress reduction is beneficial for improving insulin sensitivity. Find something that brings you joy. Have meaningful social interactions, meditate, hug a puppy... whatever it takes, reduce that stress!

Not Smoking

Smoking is bad for you. It's bad for insulin resistance. Don't smoke.

Sunshine

Low Vitamin D is associated with increased insulin resistance. The sun is the most natural source of Vitamin D there is. Get adequate sunlight to improve your insulin sensitivity!

Summary

• You want to be insulin sensitive. You don't want to be insulin resistant. You don't want hyperinsulinemia.
• Insulin resistance and hyperinsulinemia are intertwined; they are associated with diseases such as type 2 diabetes, cardiovascular disease, male and female reproductive problems, Alzheimer's, certain cancers, atherosclerosis, and many more.
• Insulin levels are better markers of disease than blood glucose levels; elevated fasting insulin levels can be detected years or decades before elevated fasting glucose levels.
• If you aren't already being intentional about your nutrition, there is a good chance that you have elevated fasting insulin levels and are on your way to developing a metabolic disease.
• You can easily and inexpensively get your insulin resistance tested. Everyone should do this; generally speaking, learning your insulin resistance levels lets you know your disease risk years or decades before it will be detected by mainstream medical checkups.
• There is good news; you can do something about your insulin resistance! Diet and lifestyle play a huge role. Dietary approaches effective in improving insulin sensitivity are low carbohydrate diets, intermittent fasting, and caloric restriction. Other interventions effective at improving insulin sensitivity are exercise, getting sunshine, getting enough sleep, and stress reduction.

References that Dig Deeper

It's the Insulin, Stupid - blog series by Amy Berger
Hyperinsulinemia: A Unifying Theory of Chronic Disease? by Catherine Crofts et. al. - narrative review of hyperinsulinemia and chronic disease
Hyperinsulinemia: Best Management Practice by Catherine Crofts et. al. - narrative review of best ways to manage hpyerinsulinemia
Hyperinsulinemia and Insulin Resistance: Scope of the Problem - editorial by Jason Fung, Amy Berger
The One Test Your Doctor Isn't Doing That Could Save Your Life by Mark Hyman
Why a Low Insulin Lifestyle is Essential for Health by P.D. Magnan
Low Carb Cardiologist Podcast Episode 27 - Bret Scher and Jason Fung
BioHackers Lab Podcast Episode 42 - Gary Kirwan and Ben Bikman
A Guide to Intermittent Fasting - Ted Naiman