Dropping Acid and Reversing Dementia

Healthy lifestyle choices for better Alzheimer’s and dementia outcomes

Neurologist David Perlmutter, MD on dropping acid, keto diet and dementia

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Life would be a lot easier (and longer!) if there was a magic pill to universally fix chronic diseases like Alzheimer’s and dementia. But humans are complex systems living in complicated environments. Instead, says Dr. David Perlmutter, MD, FACN, ABIHM, neurologist and author of bestselling book, The Grain Brain, optimal health means individual lifestyle choices over a lifetime.

“We’re inculcated with the notion that we should live our lives, come what may, and then once things start to happen, there’ll be a magic fix, no matter what it is. You can get a new hip or a knee. But you can’t really get a new brain.”

When it comes to Alzheimer’s disease and dementia, there is nothing in the Pharmacopeia to treat this incredibly pervasive disease, now affecting some 6 million Americans. However, says Dr. Perlmutter, data shows that lifestyle choices are exceedingly valuable in choosing a better destiny for cognitive function. 

He considers it his mission to spread the message that each person controls their own health destiny. 

Ways to optimize brain health for Alzheimer’s prevention

According to Dr. Perlmutter there are so many areas to explore when it comes to a healthier lifestyle for optimal brain health. Some broad categories include the following:

• Physical exercise 
• Keeping blood sugar under control
• Reducing inflammation
• Reducing stress
• Getting enough sleep
• A ketogenic diet periodically

The problem, though, is that most people ask themselves, why bother? It’s not until a patient or family is faced with Alzheimer’s or cognitive dysfunction that people wish they had heard this information before. 

A small percent of Alzheimer’s may be genetic or have a strong genetic component. Certain genes, such as the presenilin gene and the APOE array have a role to play in a person’s risk for developing Alzheimer’s disease and dementia. They predispose, but they’re not determinants, says Dr. Perlmutter. 

A challenge for genetic makeup, though, says Dr. Perlmutter, is the current lifestyle that is so contrary to the way humans evolved over millions of years. 

Evolutionary causes of high uric acid

When it comes to Alzheimer’s, diabetes, obesity or any of the chronic metabolic issues, there’s a contradiction between our current environment and our evolution, according to Dr. Perlmutter. “What our genome wants to see or should see, is not what it’s actually seeing based upon our lifestyle choices.”

Dr. Perlmutter explains that early humans were under heavy environmental pressure when there wasn’t as much food available. There was an evolutionary advantage to being able to make a little more body fat, raise blood sugar and have slightly more inflammation to help protect them against infection. 

Those genetic changes were passed on. “One of the gene mutations that happened some 14 to 17 million years ago in our primate ancestors was the gene array that deals with the formation of an enzyme called uricase that breaks down uric acid. These ancestors had higher levels of uric acid,” says Dr. Perlmutter.

How uric acid can contribute to chronic disease

Uric acid is a waste product found in blood created when the body breaks down chemicals called purines. Most uric acid dissolves in the blood, passes through the kidneys and leaves the body in urine.

High uric acid is most well known for causing gout. Iit can also cause other diseases. Uric acid plays a major role in the following: 

• Blood pressure control
• Lipogenesis
• How much fat a person produces
• How much fat they burn
• Metabolic state
• Production of new blood sugar called gluconeogenesis
• Insulin resistance

Dr. Perlmutter says this makes humans today predisposed to make more fat and have high blood sugar and high blood pressure when consuming certain foods like fructose, which is fruit sugar. The consumption of fructose millions of years ago, and continuing on to paleolithic ancestors, allowed them to survive. 

Risk factors of elevated plasma uric acid concentration include some of the following:

• Gout
• Insulin resistance 
• Type 2 diabetes
• Cardiovascular disease
• Alzheimer’s disease

“In a very real sense then, these metabolic diseases like cardiovascular disease and

Alzheimer’s and some forms of cancer, and certainly type 2 diabetes represent a genetic issue going back to these changes in the human genome that were once important survival

mechanisms,” says Dr. Perlmutter. 

Now high uric acid is instead contributing to these metabolic issues and chronic degenerative conditions. The good news, says Dr. Perlmutter, is that lifestyle choices can reign them in.

What is the ideal range for uric acid? 

“You can reverse your uric acid or begin to institute change within days,” says Dr. Perlmutter. One study in England looked at 22 young men who had slight elevation of uric acid (but still within a healthy range) and put them on either quercetin 500 milligrams a day or a placebo. In two weeks their uric acid levels came down significantly.

Coupling that treatment with reducing fructose consumption, as well as other dietary changes, can have an impact on uric acid quickly. 

Dr. Perlmutter recommends asking your physician to order a lab test to check your uric acid level. The normal range according to a lab is seven or below. Dr. Perlmutter instead likes an “optimal” range for his patients of 5.5 milligrams per deciliter. The number 7.0 was derived based on the risk for gout. 

Psychedelics has a ‘huge’ potential for treating inflammation

There are huge potential health benefits for the safe and appropriate use of psychedelics, and research is just getting started, says Dr. Perlmutter.

A lot of people suffer from inflammation caused by various metabolic issues. “Inflammation tends to segregate the brain away from being able to tap into the prefrontal cortex and kind of locks us into more primitive, impulsive thinking, as opposed to being able to use the prefrontal cortex and bring the adult back in the room,” says Dr. Perlmutter.

One thing we see with meditation is that it tends to light up that prefrontal cortex, and psychedelics can do this as well. “I think that moving forward, we’re going to see that there’ll be a lot of empowerment derived from the appropriate, judicious use of specific psychedelics in certain circumstances. We’re right at the very beginning of understanding where clinically that can go, but I think it’s going to be a huge, positive way of really unwinding a lot of issues that people have with respect to brain functionality.”

Ketamine for major depression

Ketamine became the first new medication that the FDA has approved for major depression in decades back in March 2019. The drug is a nasal spray called esketamine, derived from ketamine—an anesthetic that has made waves for its surprising antidepressant effect.  

Dr. Perlmutter says, “The data coming out with major depressive disorder is really profound. I am very excited about the role that ketamine might have in that regard.” 

Whether it’s depression, dementia or anxiety, one unifying symptom is inflammation, says Dr. Perlmutter. Reigning in inflammation may prove effective as part of the solution. Diet, elevated blood sugar, obesity and changes in the gut bacteria all play a role in the inflammatory cascade that underlies many chronic problems. 

Referring to his book, Brain Wash, Dr. Perlmutter says lifestyle choices can help the brain’s prefrontal cortex have more influence over the more impulsive, shortsighted amygdala. “We are given this notion that, just do whatever you want and we’ll fix it. And we really need to bring that prefrontal cortex online and embrace the fact that the future is coming, and there is no treatment for Alzheimer’s from the pharmaceutical industry. It’s really up to us.”

Each of us is responsible, choosing our cognitive destiny in a very real way, says Dr. Perlmutter.

What’s normal cognitive decline as we age versus dementia? 

There’s nothing good about dementia. Instead, says Dr. Perlmutter, it’s pathology. “It’s just not old timer’s disease.” 

There is no such thing as a senior moment where suddenly you don’t remember your grandchildren’s names. And while it’s true we are living longer than ever, our bodies and brains manifest the accumulation of a lifetime of input that isn’t always supportive of structural or functional continued activity compared to during younger, reproductive years.

Dr. Perlmutter explains an idea that dementia is characterized by shortsighted risk-taking. When the brain activates what’s called the polyol pathway, it’s converting glucose into fructose. Ultimately that can lead to compromising functionality of various parts of the brain and reverting the brain to what is called foraging activity, whereby we act impulsively. “We’re not thinking about the future, we’re just looking for food right now because the brain thinks the body is starving by virtue of the fact that the fructose level is higher,” says Dr. Perlmutter.

That could have been a survival mechanism obviously to be in that foraging behavior. It’s more characteristic of rodents in the laboratory setting when you give them higher levels of fructose, for example. 

New research shows that the Alzheimer’s brain is characterized by much higher levels of fructose. Glucose to fructose has an intermediary called sorbitol, which is high in the Alzheimer’s brain as well. 

According to Dr. Perlmutter, it may be that Alzheimer’s was designed as a way of enhancing foraging activity, by limiting thinking as a survival mechanism. However in today’s world, higher levels of fructose in the brain can lead to insulin resistance, even higher levels of glucose, upregulation of uric acid production and inflammation. 

Higher levels of uric acid and fructose can disrupt the mitochondria in the brain. When mitochondria dysfunction, they replicate and they trigger caspase enzymes that ultimately lead to pre-programmed cell death. “That defective mitochondria ultimately leads to neuronal death,” says Dr. Perlmutter.

This is why the brains of Alzheimer’s patients show areas where glucose can’t be used on PET scans that look at glucose utilization. Those neurons have dysfunctional mitochondria, and insulin isn’t working as well as it should. 

How a ketogenic diet supports cognitive care

When fructose and sorbitol build up in the brain of a patient with Alzheimer’s, the ketogenic diet can be an effective option. A recent study by Dr. Matthew Phillips demonstrated cognitive improvement in patients with mild to moderate stage Alzheimer’s patients on a ketogenic diet. 

When fuel isn’t being used efficiently in the brain, you can switch the fuel.

In a ketogenic state, many people actually have more mental clarity, they stop feeling so hungry and they’re not as desperate to find that sugar rush. They think more clearly, have less anxiety and start to sleep better. 

However, says Dr. Perlmutter, “I wouldn’t argue that people should be in ketosis forever. Probably just as bad as burning sugar for fuel would be always burning fat for fuel. But some mix of going back and forth and accessing the brain healing benefits. When I think about ancestral diets, what was consistent about them was inconsistency.”

What is the best diet for our brains?

The best diet for the brain depends on each individual, says Dr. Perlmutter. “It’s more important to know the patient who has the disease rather than the disease the patient has. So I think we are now in the time of personalized medicine. It’s not appropriate to be very specific about a dietary recommendation for any specific individual.”

Dr. Perlmutter does recommend broad dietary goals. Some of the key goals for a healthy diet are as follows: 

• Keep blood sugar normalized. 
• Keep inflammation down.
• Provide the suite of micronutrients that we know are important.
• Nurture the gut bacteria and reduce gut permeability.
• Improve and maintain insulin sensitivity.

The mix of foods will vary based upon each person’s genetic makeup and environment. This, says Dr. Perlmutter is why wearable devices and gadgets such as continuous glucose monitoring can be helpful.

The role of gut bacteria and healthy fats in our health

Over the years, Dr. Perlmutter has continued to be fascinated by how food affects the brain and body. 

The role of our gut bacteria in our overall health and in brain health was a revelation to Dr. Perlmutter, he says. Learning more about that led him to consider gluten as a cause for some people’s neurological manifestations, based primarily on research by Marios Hadjivassiliou. 

“I started getting results in my practice by reducing gluten in patient’s diets, and their headaches

would improve, as well as other symptoms. But no one was talking about the microbiome relationship.” 

People have started to realize that changes in the gut bacteria could predispose people to type 2 diabetes. When Dr. Perlmutter heard fecal microbiota transplants could help with type 2 diabetes, he thought, “If it’ll help with type 2 diabetes, then there may well be something going on in the gut that relates to the brain.”

Over the years, one of the things that changed for Dr. Perlmutter was the adoption of recommending higher levels of fat in the diet. “Twenty five years ago, I was parroting the standard discussion that a low fat diet was a good diet. We all realized what a disservice that was. That was a big shift for me,” says Dr. Perlmutter.

His diet recommendations moving forward is that while there’s still room for meat, diet should be much more plant-based. 

He’s also realized how underrepresented dietary fiber is in the modern diet. Yet, it’s fundamental to nurturing gut bacteria that will help resolve inflammation. “There are so many different things that our gut bacteria do,” says Dr. Perlmutter.

What is the gut brain connection? 

The gut and the brain are all part of the same system, responding to the same influences, says Dr. Perlmutter. The gut has a powerful way of informing the brain to the external environment, including food and water availability and even threats.

Immunologically, there are chemical connections that we’re just beginning to understand when it comes to how the gut influences brain functionality, says Dr. Perlmutter.

“Now time to really recognize that our entire bodies are functioning with continuity between all seemingly disparate parts.”

What drugs do you recommend for Alzheimer’s?

Research shows that neither aricept or amiodarone drug options are the best choice for Alzheimer’s disease or dementia. These drugs don’t work, and they’re associated with side effects, according to Dr. Perlmutter. 

In a study of 2714 participants published in JAMA network in 2018, Richard Kennedy studied that those individuals taking at least the cholinesterase inhibitors aricept actually demonstrated a more rapid cognitive decline than those who did not. 

“Here’s a drug being given to Alzheimer’s patients to slow down their cognitive decline, and low and behold, they decline more rapidly. And yet it’s still okay to write prescriptions for this drug,” says Dr. Perlmutter.

Alzheimer’s affects 6 million Americans for which there is no treatment, yet we know that lifestyle choices are powerful levers to pull that will reduce a person’s risk for an incurable situation. “We need to let people know this is a one way street. But you don’t have to go down that street,” says Dr. Perlmutter.

There is no pharmaceutical fix. “We need to recognize that in each individual we can identify areas that may be contributing to brain decline and remedy those,” says Dr. Perlmutter.

We are each involved in choosing our brain’s destiny. It’s not something we can outsource.

David Perlmutter, MD, FACN, ABIHM is a Board-Certified Neurologist and Fellow of the American College of Nutrition. He’s a five time New York Times bestselling author. His books have been published in 32 languages, and include the number one New York Times bestseller Grain Brain. He’s host of the podcast “The Empowering Neurologist.”