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Grain Brain by David Perlmutter

Updated: Feb 5, 2023

This is was one of the books that really sparked my interest in taking deeper dives into health related topics. This book also reminded me that books are a source of immense and concentrated knowledge. Cover to cover, I was completely absorbed. My keto journey lead me to read Grain Brain because I wanted to understand exactly how come my health improved so much by simply changing my diet.

In a single sentence, Grain Brain by Dr. David Perlmutter(2013) is about how grains and gluten are destroying your health...whether you realize it or not. This article consists of all the notes that I made as I was reading along. I've read this book many times and I've pulled the key concepts and put them all in one place!



One of the biggest fears people have with aging is falling victim to dementia. Many people fear dementia over death and cancer. It is commonly believed that declining mental faculties are a natural consequence of aging and that it is an inevitability. Some believe that it is part of your genes. It's not just dementia...we also suffer from other types of brain disorders like chronic headaches, depression and extreme mood fluctuations. David Perlmutter says that the culprit might not be in your DNA.... It might be the food that you're eating. Modern grains are destroying your brain. This includes ALL grains... even the ones we've embraced as being healthy like whole wheat, whole grain, multigrain, seven grain, live grain, stone ground...etc. Fruits and other carbohydrates have far reaching consequences as well. They wreak havoc on your brain and accelerate the body's aging process from the inside out.

Our genes determine how we process food but they also determine how we respond to the foods that we eat. One of the most prominent causes of decline in brain health in modern society was the introduction of wheat grain into the human diet. Ancient people did eat miniscule amounts of grain however the wheat that we are eating today bears little resemblance to the wild variety that they consumed. With genetic modification and hybridization the stuff we consume today shares no genetic, chemical, or structural likeness to what ancient people would have encountered. We are increasingly challenging our physiology with ingredients that we are not genetically prepared to deal with.

This book isn't about celiac disease. It's for all of us...even if, as far as you know, you have no known issue with gluten. Gluten is a silent germ. It inflicts damage without you even knowing. Food is a powerful epigenetic modulator and it goes far beyond as serving as a source of calories, fat, protein and micronutrients. The things you eat can change your DNA for better or worse. Food regulates the expression of many of our genes. Looking at wheat from this perspective is a very scary thing.

Key Topics:


It Doesn't Happen by Chance

Brain disease doesn't strike out of the blue because of genetic predisposition. It doesn't befall us by chance. Brain dysfunction is no different than heart dysfunction. It develops over time according to our behaviors and habits. So the good thing is that you can consciously prevent disorders of your nervous system and cognitive decline by eating right and getting exercise. Many things from dementia to depression are related to our nutritional and lifestyle choices.

The Truth About Whole Grains

You likely already know that carbohydrates and processed sugars are bad for your health but it might be hard to imagine that your brain would be suffering over a piece of toast or a bowl of pasta. What about whole grains and natural sugars? Those must be good right? When the brain is bombarded with carbohydrates, many of them are loaded with inflammatory ingredients like gluten which can irritate your nervous system. The damage begins with daily nuisances like headaches and unexplained anxiety and eventually progress to more sinister things like depression and dementia.

The origin of brain disease is predominantly dietary. There are a lot of different factors that kick off brain disorders. There are many neurological afflictions that are the result of consuming too many carbs and too few healthy fats. The most dreaded neurological affliction is Alzheimer's and it should be looked at as a type of diabetes that is triggered by diet alone. It is known that poor diet can lead to obesity and diabetes... But it can also mess your brain up.

Ponder this:

Our ancestors probably spent a lot of time searching for food and when they came across food it would have likely been animal fats or small amounts of sugars from berries and plants if the season is right. They didn't have breads, processed foods and an endless supply of fresh fruits all year round!

Alzheimer's as Type 3 Diabetes

You can prevent Alzheimer's just by changing the things you eat.

What the heck does diabetes and the brain have to do with the brain?! For most of our existence glucose was scarce. This is the body's main source of energy for most cells so we developed ways to store glucose and convert other things into it. The body can generate glucose from fat and protein...which is called gluconeogenesis. This process requires a lot of energy as opposed to converting dietary starches and sugar into glucose... Which is a more straightforward reaction. The process by which our cells accept and utilize glucose is elaborate. Cells just don't suck up glucose floating by them. They are allowed into the cell by the hormone insulin which is created by pancreas. Insulin is one of the most important substances for cellular metabolism. Its job is to shuttle glucose from the bloodstream into muscle, fat and liver cells so that it can be used as fuel. Normal cells have a high sensitivity to insulin. When cells are persistently exposed to high levels of insulin due to constant intake of glucose, which is caused by hyper processed foods filled with refined sugars, which causes spikes in insulin..... The cells react by reducing the number of receptors on their surfaces that respond to insulin. They basically desensitize themselves to insulin which causes insulin resistance. They ignore the insulin and then they are not able to retrieve the glucose from their blood. The pancreas responds by pumping out more insulin. Higher levels of insulin is needed to get the sugar out of the blood and into the cells. It creates a cyclical problem which culminates in type 2 diabetes. People with diabetes have high blood sugar because the body cannot get sugar into the cells where it can be safely stored for energy. The sugar in the blood is like shards of glass which causes many serious health problems.


Insulin is an anabolic hormone. Stimulates growth and promotes fat formation and retention and encourages inflammation. When insulin levels are high other hormone levels can be affected adversely. It plunges the body into chaos.

Type 1 diabetes is a while different beast. People with type 1 diabetes make little or no insulin because their immune system attacks and destroys the cells in the pancreas that produce insulin. That's why they need injections of insulin to keep their blood sugars in balance.

There is no cure for type 1. Even though genes influence type 1 diabetes, environment plays an important role too.

Insulin Resistance

Insulin resistance sparks the formation of plaques that are often present in diseased brains. These plaques are a build up of a strange protein in the brain and hijacks the brain and takes the place of normal brain cells. The fact that we can associate low levels of insulin with brain disease is why it is being considered type 3 diabetes.

Obese people are at a much greater risk of impaired brain function. Those with diabetes are more than twice likely to develop Alzheimer's disease. Dr. Perlmutter is not saying that diabetes causes Alzheimer's disease but he is saying that they both share the same origin. They both rise from food that force the body to develop biological pathways that lead to dysfunction and illness.

How Did This Happen?!

Most people wonder "How this this happen?!" when they, or a loved one, is diagnosed with brain disease. The truth is, it didn't come out of nowhere. The reality is that the person was likely:

  • Living with chronic high blood sugar levels even in the absence of diabetes.

  • Eating too many carbohydrates over the course of life.

  • Opted for a low fat diet that minimized cholesterol.

  • Had undiagnosed gluten sensitivity... which is the protein that is found in wheat, rye and barley.

Gluten: The Biggest Threat to Humanity

Gluten sensitivity represents the biggest threat to humanity.

When most people think of gluten, they think in the context of intestinal health not neurological wellness... So the concept of being profoundly impacted by gluten is not in a lot of people's awareness. Gluten doesn't just affect people with celiac disease, which is a really small amount of people. Ponder this though....what if we're all sensitive to gluten from the perspective of the brain? There is a link between gluten sensitivity and neurological dysfunction. This is true for even people that test negative for gluten sensitivity and have no problem digesting gluten.

The cornerstone of all degenerative conditions is inflammation.

Gluten and a high carbohydrate diet are one of the primary instigators of inflammatory pathways. The worst part is that we don't know when we are being affected by it. It's not like there are digestive symptoms like gas, bloating and pain which emerge quickly. The brain is different... It could be enduring assaults at a molecular level and you won't feel it.

Oxidation and Antioxidants

Free radicals are molecules that have lost an electron. Normally electrons spin around in pairs. T such as stress, pollution, chemical exposures, toxic dietary triggers, ultraviolet light and ordinary body activities can make one of them break off. It then starts to steal electrons from other molecules. This is the oxidization process. It kicks off inflammation and creates more free radicals. Oxidized tissues and cells tissues and cells do not function normally so it sets you up for health challenges. Anything that reduces oxidation reduces inflammation. Anything that reduces inflammation reduces oxidation. That's partly why antioxidants are so important. Vitamins a c and e donate electrons to these free radicals.... And this interrupts the chain reaction and prevents damage. Historically we used to eat foods that were rich in antioxidants. The food industry today processes out a lot of these essential nutrients.

Free radicals are molecules that have lost an electron. Normally electrons spin around in pairs. Things such as stress, pollution, chemical exposures, toxic dietary triggers, ultraviolet light and ordinary body activities can make one of them break off. It then starts to steal electrons from other molecules. This is the oxidization process. It kicks off inflammation and creates more free radicals. Oxidized tissues and cells tissues and cells do not function normally... so it sets you up for health challenges. Anything that reduces oxidation, reduces inflammation. Anything that reduces inflammation, reduces oxidation. That's partly why antioxidants are so important. Vitamins A, C and E donate electrons to these free radicals which interrupts the chain reaction and prevents damage. Historically, we used to eat foods that were rich in antioxidants. The food industry today processes out a lot of these essential nutrients.


Statins, a cholesterol lowering drug, are sometimes touted as a way to lower overall inflammation. BUT new research says that statins may decrease brain function and increase risk for heart disease. The brain needs cholesterol to thrive. Cholesterol is an essential brain nutrient. It is essential for the function of neurons. Cholesterol plays a fundamental role as a building block of the cell membrane. It also acts as an antioxidant and is a precursor to Vitamin D. Cholesterol is a essential fuel for neurons.

Neurons rely on delivery of cholesterol from the bloodstream via a specific carrier protein called LDL. People call this bad cholesterol. The function of LDL in the brain is to capture cholesterol and transport it to the neuron where it performs critically important functions. When cholesterol levels are low the brain doesn't work well. Individuals with low cholesterol are at risk for dementia and other neurological problems. What about coronary artery disease and LDL? That has to do with oxidized LDL. How does LDL become so damaged that it is no longer able to deliver cholesterol to the brain? By physical modification caused by glucose. Sugar molecules attach themselves to LDL and change the molecule shape rendering it less useful while increasing free radical production.

You might have the following skeptical questions:

Can we accelerate our brains decline by adopting a low fat high carb diet with fruit on the side?

Can we really control the fate of our brains through lifestyle alone despite inherited DNA?

Is there too much invested interest in big pharma to consider the fact that we can naturally prevent and treat and sometimes cure without drugs a spectrum of bring-based ailments?

The answer is yes .

Brain Health to Total Health

We have evolved into a species that requires fat for life and health. The massive amounts of carbs we eat today are fueling a silent shitstorm in our bodies and brains.

We need to look the role of the stick protein, glutens role in brain inflammation

We all get headaches and stuff like that. We mostly shrug it off to a long day at work or some sort of bug that's going around. But what if it doesn't go away and it plagues you regularly. That's not normal. It's not just headaches...some people have mental health issues and abnormal body movements. Sometimes a simple dietary change can have a life-transforming impact. People may have vastly different medical complaints, but they share a common thread: gluten sensitivity


What does the scientific community have to say about gluten sensitivity? What does it mean to be “gluten sensitive”? How does it differ from celiac disease? What’s so bad about gluten? Hasn’t it always been around? And just what exactly do I mean by “modern grains”?

Gluten is a protein composite that acts as an adhesive material, holding flour together to make bread products, including crackers, baked goods, and pizza dough.

Gluten is not a single molecule; it’s actually made up of two main groups of proteins, the glutenins and the gliadins. A person may be sensitive to either of these proteins or to one of the twelve different smaller units that make up gliadin. Any of these could cause a sensitivity reaction leading to inflammation.

There’s a huge difference between celiac disease and gluten sensitivity. Celiac disease is an extreme manifestation of gluten sensitivity. Celiac disease is what happens when an allergic reaction to gluten causes damage to the small intestine. There is a wide spectrum of gluten sensitivity because people can carry genes that code for mild versions of gluten intolerance. Celiac disease doesn’t just harm the gut. Once the genes for this disease are triggered, sensitivity to gluten is a lifelong condition that can affect the skin, mucous membranes, and cause blisters in the mouth.

The stickiness of gluten interferes with the breakdown and absorption of nutrients. Poorly digested food leads to a pasty residue in your gut which puts the immune system on alert which eventually results in an assault on the lining of the small intestine.

Inflammation kicks off many brain disorders. Inflammation can be initiated when the immune system reacts to a substance in a person’s body.

It goes like this:

  1. Antibodies from your immune system come into contact with proteins to which you are allergic.

  2. Inflammatory cascade starts (a bunch of damaging chemicals known as cytokines) are released.

Someone that is gluten sensitive has elevated levels of antibodies against the gliadin component of gluten. So when these antibodies combine with gliadin they turn specific genes in a special type of immune cell in the body.

Once these genes are turned on inflammatory cytokine chemicals collect and can attack the brain. Cytokines can damage brain tissue and leave the brain vulnerable to dysfunction and disease. If you keep consuming gluten then this assault continues.

The antibodies against gliadin can directly combine with specific proteins found in the brain that structurally look similar to the gliadin protein found in gluten-containing foods. The antibodies don't know the difference and your brain endures an assault.

“Gluten sensitivity can be primarily, and at times, exclusively, a neurological disease.” -Dr. Hadjivassiliou

Essentially, people with gluten sensitivity can have issues with brain function without having any gastrointestinal problems whatsoever

Also, just to drive this point home, Dr. Rodney Ford of the Children’s Gastroenterology and Allergy Clinic in New Zealand stated in his 2009 article titled “The Gluten Syndrome: A Neurological Disease”: The fundamental problem with gluten is its “interference with the body’s neural networks… gluten is linked to neurological harm in patients, both with and without evidence of celiac disease.”


Celiac reflects one extreme. Understanding how celiac does it thing can have implications for anyone who consumes gluten. Studies have shown that people with celiac have significantly increased production of free radicals and they have free radical damage to their fat, protein, and DNA.

They also lose their ability to produce antioxidant substances in the body as a result of the immune system’s response to gluten. Specifically, they have reduced levels of glutathione(antioxidant in the brain), vitamin E, retinol, and vitamin C in their blood—all of these things help regulate the body’s free radicals. It seems like gluten disables the immune system such that it cannot fully support the body’s natural defenses

The immune system’s reaction to gluten activates signaling molecules that basically turn on inflammation and induce what’s called the COX-2 enzyme, which leads to increased production of inflammatory chemicals. This is what ibuprofens and aspirin block.

High levels of another inflammatory molecule called tumor necrosis factor α (TNFα) have also been seen in celiac patients. Elevations of this cytokine are among the hallmarks of Alzheimer’s disease and virtually every other neurodegenerative condition.

Bottom line: Gluten sensitivity, whether celiac or not, increases the production of inflammatory cytokines... these inflammatory cytokines play a key role in neurodegenerative disorders. Also, the brain is the most susceptible organ to this inflammation.

Modern Food The gluten that are are currently consuming is not the same stuff our ancestors were exposed to when they figured out how to farm and mill wheat. The grains we eat today bear little resemblance to the grains that entered our diet about ten thousand years ago. Our genetic makeup and physiology haven’t changed much since the time of our ancestors BUT our food chain has had a rapid makeover during the past fifty years. Modern food manufacturing, including genetic bioengineering, have allowed us to grow grains that contain up to forty times the gluten of grains cultivated just a few decades ago.


Gluten-containing grains are gives you a pleasant feeling. Gluten breaks down in the stomach to become a mix of polypeptides. These polypeptides cross the blood-brain barrier. Once they are in there they bind to the brain’s morphine receptor to produce a sensorial high.

This is the same receptor to which opiate drugs bind, creating their pleasurable and addicting effect. These polypeptides are called exorphins(exogenous morphine-like compounds). Gluten can change our biochemistry down to our brain’s pleasure and addiction center ....that's nuts.

Insulin Resistance Consuming lots of grains and carbs can be so harmful because they raise blood sugar in ways other foods(meat, fish, poultry, and vegetables) do not. High blood sugar causes the pancrease to increase the production of insulin produces because the body is trying to move the sugar into the body’s cells. The higher the blood sugar, the more insulin. As the insulin increases, cells become less and less sensitive to the insulin signal. Cells become desensitized to insulin’s message. The pancreas thus increases its insulin output. Higher levels of insulin cause the cells to become even less responsive to the insulin signal. Its a dysfunctional cycle and the body is still trying to deal with lowering the blood sugar. The pancreas works overtime. This is called insulin resistance because the cells are resistant to the insulin signal. As this process worsens, the pancreas reached a point where it's making as much insulin as it could possibly make, but it’s still not enough. At this stage cells stop responding to insulin and then blood sugar begins to rise which leads to type 2 diabetes. The system breaks down and this is when diabetes drugs are used to keep the body’s blood sugars balanced. You don’t have to be diabetic to suffer from chronic high blood sugar.

Consider a tablespoon of sugar, a chocolate bar, and a slice of whole wheat bread...which one produces the highest surge in blood sugar? The glycemic index (GI) is rating that reflects a measure of how quickly blood sugar levels rise after eating a particular type of food. The glycemic index encompasses a scale of 0 to 100. The higher the value the more rapid the rise in blood sugar. The reference point is pure glucose, which has a GI of 100.

It’s not the sugar (GI = 68) or the the candy bar (GI = 55).It’s the whole-wheat bread with a GI of 71

...thats pretty messed up.

Carbs vs Fat It's more than just gluten, carbohydrates in general have a big impact on brain health. Consuming excess carbohydrates—even those that don’t contain gluten—can be just as harmful as eating a gluten-laden diet.

To shift your body’s biochemistry to one that burns fat, tames inflammation, and prevents illness and mental dysfunction, you need to consider another big piece of the equation: carbs versus fats. An extremely low-carb and high-fat diet is what your body fundamentally craves and needs.

You don't have to avoid eating fat and cholesterol ... these are actually what you need to preserve the highest functioning of your brain. Its a curious thing that advertisements, weight-loss companies, grocery stores, and popular books are touting the idea that we should be on a low-fat or as close to a no-fat, low cholesterol diet. There ARE certain types of fat that are associated with health issues like commercially modified fats and oils. Also these is scientific support that “trans fats” are toxic and are linked to a number of chronic diseases.

But the missing message is simple: Our bodies thrive when given “good fats,” and cholesterol is one of these. We don’t function optimally with copious amounts of carbohydrates, even if those carbs are gluten-free, whole grain, and high in fiber. The human dietary requirement for carbohydrate is virtually zero; we can survive on a minimal amount of carbohydrate, which can be produced by the liver. But we can’t go long without fat. We equate the idea of eating fat to being fat. Obesity has almost nothing to do with dietary fat consumption and everything to do with carbohydrate addiction. Same thing with cholesterol: Eating high cholesterol foods has no impact on our actual cholesterol levels. Also, the alleged correlation between higher cholesterol and higher cardiac risk is an absolute fallacy.

Our Genes Favor Fat

Respect yo' genome. Fat (not carbohydrate) is the preferred fuel of human metabolism and it has been like this for all of human evolution. For TWO MILLION YEARS, we have consumed a high-fat diet... it is only since the development of agriculture about ten thousand years ago that carbohydrates have become abundant in our food supply. We still have a hunter-gatherer genome. We are still programmed to store fat during times of abundance

It takes 40,000 to 70,000 years for any significant changes to take place in the genome that might allow us to adapt to such a drastic change in our diet . Humans invented agriculture between 7,000 and 10,000 years best case scenario...we'll be okay in 33000 years.

I'm just kidding but you see the point.


Basically, there are omega-3 and omega-6 fats. omega-6 fats are generally called the “bad fat” because they are a bit pro-inflammatory. There is evidence that higher consumption of these fats is related to brain disorders. The typical diet in North America is extremely high in omega-6 fats. When people thing of omegas they probably think of eggs or supplements but for people that eat meat it is important to know what your "meat" was eating. If animals are fed grains, then they will not have adequate omega-3 in their diets and their meat will be deficient in these vital nutrients. This is why grass-fed beef and wild fish is recommended. Dr. Gundry’s The Plant Paradox explains this point so well.


LDL is a carrier protein which is not necessarily bad. The role of LDL in the brain is to capture cholesterol and transport it to the neuron where it performs critically important functions. When cholesterol levels are low...the brain just doesn't work well. This increases the risk for neurological problems. Once free radicals damage the LDL molecule it is much less capable of delivering cholesterol to the brain. Sugar also renders LDL much less effective as binds to it and accelerates oxidization. So the goal should be to reduce LDL oxidation, not LDL levels.

Glucose is a big it changes the shape of the molecule. A high carbohydrate diet yields oxidized LDL and an increased risk of atherosclerosis. When LDL becomes a glycosylated molecule it cannot present cholesterol to brain cells.

We have been led to believe that dietary fat will raise our cholesterol, which increases our risk for heart attack and strokes. This is proven not to be true.

"The diet-heart hypothesis has been repeatedly shown to be wrong, and yet, for complicated reasons of pride, profit and prejudice, the hypothesis continues to be exploited by scientists, fund-raising enterprises, food companies and even governmental agencies. The public is being deceived by the greatest health scam of the century." --George Mann, ScD, MD, Former Co-Director, The Framingham Study

Brain on Fire (Carbs, Diabetes and Brain Diseases)

Grains and carbs set fire to the brain by causing surges in blood sugar. Surges in blood sugar negatively impact the brain and kicks off the inflammatory cascade. It has everything to do with neurotransmitters. These things are your main mood and brain regulators, and when your blood sugar increases, there’s an immediate depletion of the neurotransmitters serotonin, epinephrine, norepinephrine, GABA, and dopamine. At the same time, B-complex vitamins, which are needed to make those neurotransmitters (and a few hundred other things), get used up. Magnesium levels also go down, and this impairs both your nervous system and liver. High blood sugar triggers a reaction called glycation. Glycation is the biological process where glucose, proteins, and certain fats become tangled together. This process causes tissues and cells to become stiff and inflexible, including those in the brain. Sugar molecules and brain proteins combine to create deadly new structures that are the main contributing factor to the degeneration of the brain and its functioning.

How Does Diabetes Contribute to Dementia? If you’re insulin resistant, your body may not be able to break down a protein (amyloid) that forms brain plaques associated with brain disease. Also, high blood sugar provokes biological reactions that injure the body. Your body starts producing certain oxygen-containing molecules that damage cells and cause inflammation that contribute to the hardening and narrowing of the arteries in the brain. This condition is called atherosclerosis can cause blockages and stroke which kill brain tissue and lead to vascular dementia. Usually when you hear atherosclerosis you think about the heart but the brain is equally affected by changes in its arteries’ walls.

Carbs Cause High Cholesterol....Not Cholesterol

It’s important to understand that when you have a blood cholesterol test, the number that is represented is actually 75 to 80 percent derived from what your body manufactures and not necessarily what you’ve eaten. Foods that are high in cholesterol actually decrease the body’s production of cholesterol.

So what happens if you restrict your cholesterol intake?

The body sends out a signal that there is famine.

Your liver senses this signal and begins to produce an enzyme called HMG-CoA reductase

This enzyme helps make up for the deficit by using carbohydrates in the diet to produce an excess supply of cholesterol. Interestingly, this is the same enzyme that statins target.

As you eat excessive carbohydrates while lowering your cholesterol intake, you trigger the overproduction of cholesterol in the body. The only way to stop this mess is to consume an adequate amount of dietary cholesterol and back way off on carbs.

Sexual Disfunction

If you’re depressed and not sleeping well, sex is the last thing on your mind. One of the most common reasons for impotence is abysmally low cholesterol levels. Unless you have healthy testosterone levels (this goes for both men and women), your sexual health will suffer. What makes testosterone? Cholesterol. Millions of people are lowering their cholesterol levels through diet and by taking statins. This lowers you libido and ability to perform.

No wonder why so many suffer from erectile dysfunction (ED) and end up taking ED drugs, and consider testosterone replacement therapy. Decreased libido and low testosterone is one of the most common complaints among those taking statins. Thankfully you can reverse this by stopping the statin and increasing cholesterol intake. There are two ways that statins can lower testosterone. The first is by directly lowering levels of cholesterol. The second is by interfering with the enzymes that create active testosterone.

Brain Disfunction and Sugar

Evolutionarily, sugar was available to our ancestors as fruit for only a few months a year (at harvest time), or as honey, which was guarded by bees. But in recent years, sugar has been added to nearly all processed foods, limiting consumer choice. Nature made sugar hard to get; man made it easy. —Dr. Robert Lustig ET AL.

Glucose Fructose

The various kinds of sugar are metabolized by the human body in different ways. Pure glucose is the simplest form of sugar.

Table sugar is a combination of glucose and fructose.

Fructose is a type of naturally occurring sugar found only in fruit and honey.

If you eat 100 calories of glucose from a potato, for instance, you metabolize it differently—and experience different effects—than if you were to eat 100 calories of sugar comprising half glucose and half fructose.

Here’s why:

Your liver takes care of the fructose component of sugar.

Glucose from other carbs and starches, are processed by every cell in the body. So consuming both types of sugar (fructose and glucose) at the same time means your liver has to work harder than if you ate the same number of calories from glucose alone.

Your liver gets hit harder when you consume liquid forms of these sugars, those found in soda or fruit juices. Drinking liquid sugar is not the same as eating an equivalent dose of sugar in, for instance, whole oranges.

Fructose is the sweetest of all naturally occurring carbohydrates. Contrary to what you might think, it has the lowest glycemic index of all the natural sugars. This is because the liver metabolizes most of the fructose so it has no immediate effect on our blood sugar and insulin levels, unlike sugar or high-fructose corn syrup, whose glucose ends up in general circulation and raises blood sugar levels.

Fructose may not have an immediate effect but it has a long-term effects when it’s consumed in sufficient quantities from unnatural sources. Consuming fructose is associated with impaired glucose tolerance, insulin resistance, high blood fats, and hypertension. Also, fructose does not trigger the production of insulin and leptin which are two key hormones in regulating our metabolism so diets high in fructose lead to obesity and its metabolic repercussions.

You can still eat fruit. The quantity of fructose in most whole fruit pales in comparison to the levels of fructose in processed foods.

What the Heck Is Sugar?

What is the difference between table sugar, fruit sugar, high-fructose corn syrup?

Fructose is a type of sugar naturally found in fruit and honey. It’s a monosaccharide just like glucose.

Table sugar (sucrose)—the white granulated stuff—is a combination of glucose and fructose, thus making it a disaccharide (two molecules linked together).

High-fructose corn syrup(the stuff found in sodas, juices, and many processed foods) is yet another combination of molecules dominated by fructose—it it 55 percent fructose, 42 percent glucose, and 3 percent other carbohydrates.

Carbohydrates are simply long chains of sugar molecules, as distinguished from fat (chains of fatty acids), proteins (chains of amino acids), and DNA. Not all carbohydrates are equal and not all carbohydrates are treated equally by the body. The feature that differentiates them is how much each type of carbohydrate raises blood sugar...and then insulin.

Meals that are higher in carbohydrate...especially ones higher in simple glucose cause the pancreas to increase its insulin output in order to store the blood sugar in cells. During digestion carbohydrates are broken down and sugar is liberated into the bloodstream which again causes the pancreas to increase its output of insulin so glucose can penetrate cells.

The carbs that trigger the biggest surge in blood sugar are typically the most fattening. This includes anything made with refined flour (breads, cereals, pastas); starches such as rice, potatoes, and corn; and liquid carbs like soda, beer, and fruit juice. These things get digested quickly because they flood the bloodstream with glucose and spike insulin, which then packs away the excess calories as fat.

What about the carbs in a vegetable? Stuff like leafy green vegetables( broccoli and spinach) are tied up with fiber which is indigestible so it takes longer to break down. The fiber slows things down...causing a slower funneling of glucose into the bloodstream. P

Does how long one has diabetes play into the severity of cognitive decline?

Absolutely. If diabetes begins before 65 years old, the risk for mild cognitive impairment was increased by 220 percent. The risk of mild cognitive impairment in individuals who had diabetes for 10 years or longer was increased by 176 percent. If people are taking insulin, their risk of cognitive impairment is increased by 200 percent.

Hemoglobin A1C

Hemoglobin A1C is the protein found in the red blood cell that carries oxygen and binds to blood sugar. Naturally, this binding is increased when blood sugar is elevated. By now, if you've read a few of my book notes, you know that hemoglobin A1C isn't a moment-to-moment indication of what the blood sugar is rather an “average” of what your blood sugar has been over the previous 90 days. Also, glycated hemoglobin is a powerful risk factor for diabetes, but it’s also been correlated with risk for stroke, coronary heart disease, and death from other illnesses. Any measurement of hemoglobin A1C above 6.0 not good. Elevated hemoglobin A1C is associated with changes in brain size. A study, published in the journal Neurology, researchers looking at MRIs to determine which lab test correlated best with brain atrophy found that the hemoglobin A1C demonstrated the most powerful relationship. When comparing the degree of brain tissue loss in those individuals with the lowest hemoglobin A1C (4.4 to 5.2) to those having the highest hemoglobin A1C (5.9 to 9.0), the brain loss in those individuals with the highest hemoglobin A1C was almost doubled during a six-year period. So hemoglobin A1C is far more than just a marker of blood sugar balance...the great thing is that it is all within your control.

Fasting Insulin

It's also important to test fasting insulin. Just because your blood sugar levels are all good it doesn't mean that you're in the clear.

It may simply mean that your pancreas is working hard to keep blood sugar normal. Elevated insulin levels happens long before blood sugar rises and a person becomes diabetic. This is why you need to test both fasting blood sugar and your fasting insulin level. If your fasting insulin level is high then it is an indicator that your pancreas is trying hard to normalize your blood sugar. It’s also a sign that you are consuming too much carbohydrate.


“How can the body live on fat and never get fat?”

It sounds absurd to think we can live on virtually zero carbs but copious amounts of fat and cholesterol in our diet. But we can, and we should if we’re going to protect our genome. Despite what food marketers / government make you believe, we’ve had a fat-based diet shaping our genome for the past 2.6 million years. Look at what happened when we tried to deviate from that...we got fat.


Epigenetics is the study of particular sections of your DNA, called “marks”, that essentially tell your genes when and how strongly to express themselves. Epigenetic marks are the remote control to your health, longevity and also to how you pass your genes on to future generations. Our day-to-day lifestyle choices have a big effect on the activity of our genes.

"The food choices we make, the stress we experience or avoid, the exercise we get or avoid, the quality of our sleep, and even the relationships we choose actually choreograph to a significant degree which of our genes are active and which remain suppressed."

We can change the expression of more than 70 percent of the genes that have a direct bearing on our health and longevity.


You're not stuck with the number of neurons we’re born with.

  • We can grow new neurons throughout our entire lives.

  • We can also fortify existing brain circuits and create entirely new and elaborate connections, too, with new brain cells.

In 1998, the journal Nature Medicine published a report by Swedish neurologist Peter Eriksson in which he claimed that within our brains exists a population of neural stem cells that are continually replenished and can differentiate into brain neurons. He was right. This has led to a new science called neuroplasticity.

How can we grow new brain neurons?

What influences neurogenesis?

And what can we do to enhance this natural process?

The process is controlled by our DNA. Specifically, a gene located on chromosome 11 codes for the production of a protein called “brain-derived neurotrophic factor,” or BDNF. BDNF plays a key role in creating new neurons. Beyond its role in neurogenesis, BDNF protects existing neurons and encourages synapse formation(the connection of one neuron to another). This process is vital for thinking, learning, and higher levels of brain function. Studies have demonstrated decreased levels of BDNF in Alzheimer’s patients. BDNF is also associated with with a variety of neurological conditions, including epilepsy, anorexia nervosa, depression, schizophrenia, and obsessive-compulsive disorder.

Factors that influence our DNA to produce BDNF are mostly under our direct control. "The gene that turns on BDNF is activated by a variety of lifestyle habits, including physical exercise, caloric restriction, following a ketogenic diet, and the addition of certain nutrients like curcumin and the omega-3 fat DHA. "

This is good news because these are factors within our control....they are choice we can easily make today that helps the growth of new brain cells.

Calorie Restriction:

One epigenetic factor that turns on the gene for BDNF production is calorie restriction. Many studies have demonstrated that when animals are on a reduced calorie diet (30 percent reduction), their brain production of BDNF shoots up and they show dramatic improvements in memory and other cognitive functions.

It might seem hard to reduce your caloric intake by 30 percent but consider the following:

People are already eating over 500 more calories per day than they did 50 years ago.

The book says that any average adult is now consuming 3770 calories per day, according to data from the Food and Agriculture Organization of the United Nations. I find this hard to believe the heck could people be consuming this much calories? The point is that normal calorie consumption is accepted to be 2,000 calories daily for women and 2,550 for men.

If you just still to that're pretty much already there. The average person

consumes at least 100lbs of refined sugar per year. This is 25 percent more than was consumed 30 years ago. All this to say, if you just cut back on sugar, you will reduce your calorie intake and it will help you lose weight.

It seems like a no brainer to me because we know:

  • Blood sugar is associated with reduced levels of BDNF

  • Obesity is associated with reduced levels of BDNF

Quick recap:

Calorie restriction:

  • Confers profound neuroprotection

  • Increases the growth of new brain cells

  • Allows existing neural networks to expand their sphere of influence (neuroplasticity)

The mechanism by which calorie restriction works:

The mechanism by which calorie restriction works is:

  1. via improved mitochondrial function

  2. controlling gene expression.

Consuming fewer calories decreases the generation of free radicals and enhances energy production from the mitochondria. Mitochondria are the tiny things in our cells that generate chemical energy in the form of ATP (adenosine triphosphate).

Mitochondria have their own DNA, and they play a key role in degenerative diseases such as Alzheimer’s and cancer.

Caloric restriction:

  • Triggers a decrease in inflammatory factors

  • Increase in neuroprotective factors, specifically BDNF.

  • Increase the body’s natural antioxidant defenses by boosting enzymes and molecules that deal with excessive free radicals.

There is a molecule associated with caloric restriction and the growth of new brain cells... sirtuin-1 (SIRT1). It is an enzyme that regulates gene expression. In monkeys, increased SIRT1 activation enhances an enzyme that degrades amyloid...which is the stuff that is present in Alzheimer's brains. SIRT1 activation changes certain receptors on cells, leading to reactions that have the overall effect of reducing inflammation. Activation of the sirtuin pathway by caloric restriction also enhances BDNF.

The Benefits of a ketogenic diet

Caloric restriction activates diverse pathways, which are protective of the brain and enhance the growth of new neuronal networks....but the same pathway can be activated by the consumption of special fats called ketones. The most important fat for brain energy utilization is beta-hydroxybutyrate (beta-HBA).

A ketogenic diet:

  • Reduces amyloid in the brain

  • Increases glutathione, the body’s natural brain-protective antioxidant, in the hippocampus.

  • Stimulates the growth of mitochondria and thus increases metabolic efficiency.

  • Produce ketones in special cells called astrocytes. (Usually the liver is seen as the main source of ketone production in human physiology but the brain does it too.)

Ketone Bodies:

  • Very neuroprotective.

  • decrease free radical production in the brain,

  • increase mitochondrial creation,

  • stimulate production of brain-related antioxidants.

  • Block the apoptotic pathway that would otherwise lead to self-destruction of brain cells.

We evolved to handle ketones in the blood and it is probably due to our large brain to body weight ratio and the high energy requirements of our brain. At rest, 20 percent of our oxygen consumption is used by the brain, which only represents 2 percent of the human body.

The ability to use ketones as fuel when blood sugar and liver glycogen was completely depleted. became essential for our survival. Ketosis is something that help us survive and evolve as a species during times of food scarcity.

“In fact, we can define this mild ketosis as the normal state of human metabolism when we’re not eating the carbohydrates that didn’t exist in our diets for 99.9 percent of human history. As such, ketosis is arguably not just a natural condition but even a particularly healthful one.” -Gary Taubes

Curcumin and DHA

Curcumin is known for its antioxidant, anti-inflammatory, anti-fungal, and antibacterial properties.

It also has the ability to increase BDNF.

Docosahexaenoic acid (DHA).

Scientists have been studying this critical brain fat for at least three reasons:

  1. More than two-thirds of the dry weight of the human brain is fat, and of that fat, one quarter is DHA. So 16.5% of the dry weight of your brain is DHA. DHA is an important building block for the membranes surrounding brain cells, particularly the synapses, which lie at the heart of efficient brain function.

  2. DHA is a regulator of inflammation. It reduces the activity of the COX-2 enzyme. This enzyme is responsible for turning on the production of damaging inflammatory chemicals.

  3. DHA has a role in regulating gene expression for the production of BDNF.

Intellectual Stimulation Bolsters New Networks

We know that keeping the brain intellectually stimulated is a good thing for brain health.

Challenging the mind strengthens new neural networks. It's just like muscles and weightlifting except the weight is intellectual stimulation. The brain becomes faster and more efficient in its processing capacity and is also better able to store more information.

The Antioxidant Hoax

Antioxidants help control free radicals. The brain generates tremendous amounts of free radicals but lacks the level of antioxidant protection found everywhere else in the body.

There is something we can do about it and its NOT by consuming antioxidants themselves. Our DNA can turn on the production of antioxidants in the presence of specific signals and this internal antioxidant system is far more powerful than any nutritional supplement

So how do we turn on our internal antioxidant system?

We need to turn our attention towards our mitochondria. In the normal process of producing energy, each mitochondrion produces hundreds ...possibly thousands of free radical molecules each day. Now multiply that by ten million how much free radicles we are dealing with.

Most antioxidants work by sacrificing themselves to become oxidized when faced with free radicals. So if we're talking about vitamin molecule of vitamin C is oxidized by one free radical. Can you imagine how much vitamin C or other oral antioxidant it would take to neutralize the unimaginable number of free radicals generated by the body on a daily basis?

During times of high oxidative stress our body uses its own biochemistry to create more protective antioxidants . Our cells have their own innate ability to generate antioxidant enzymes on demand. We are not entirely dependent on external food sources of antioxidants.

High levels of free radicals turn on a protein in the nucleus called Nrf2, which essentially opens the door for the production of a vast array of our body’s most important antioxidants and also detoxification enzymes. The next logical question is... what else activates Nrf2?

When the omega-3 fats EPA and DHA are oxidized, they significantly activate the Nrf2 pathway. For years researchers have noted decreased levels of free radical damage in individuals who consume fish oil...which is the source of EPA and DHA.


The human body produces many enzymes that help deal with the large number of toxins that we are exposed in our external environments and those that are generated internally through the course of metabolism. Your body produces these enzymes under the direction of your DNA.

Glutathione is one of the most important detoxification agents in the human brain.

It serves as a major antioxidant in cellular physiology, not only helping to protect the cell from free radical damage but also protecting your mitochondria.

Scientists often measure cellular glutathione levels as an overall indicator of cellular health.

Glutathione aids in detoxification as well by binding to various toxins to render them less noxious.

Glutathione serves as a substrate for the enzyme glutathione S-transferase. This enzyme is involved in transforming many toxins making them more water soluble and thus more easily excreted.

Basically glutathione is both an antioxidant and a major factor in detoxification. We need to do everything possible to maintain and even enhance glutathione levels.

Several natural compounds that turn on antioxidant and detoxification pathways through activation of the Nrf2 system have been identified.

  • Curcumin from turmeric

  • Green tea extract

  • Silymarin (milk thistle)

  • Bacopa extract

  • DHA

  • Sulforaphane (contained in broccoli)

  • Ashwagandha

The “Alzheimer’s Gene”

Scientists have not identified a specific gene that causes Alzheimer’s disease. One genetic risk factor that appears to increase one’s risk of developing the disease is associated with the apolipoprotein E (ApoE) gene on chromosome 19.

It encodes the instructions for making a protein that helps transport cholesterol and other types of fat in the bloodstream. It comes in several different forms... or alleles.

The three main forms are:

  • ApoE ε2

  • ApoE ε3

  • ApoE ε4

ApoE ε2 is pretty rare. If you inherit this allele, you’re more likely to develop Alzheimer’s disease later in life.

ApoE ε3 is the most common allele. It’s believed to neither increase nor decrease your risk. ApoE ε4 is the one that is feared the most. 25 to 30 percent of people have it.

About 40 percent of all people with Alzheimer’s carry this allele.

You won’t necessarily get Alzheimer’s if you have this ApoE ε4 allele. Some people whose DNA contains the ApoE ε4 allele never suffer from any cognitive decline. There are many people who develop Alzheimer’s but who lack any of these genetic risk factors. It's poorly understood but I left it in here because these are my book notes and I may return to this later.

Baby Inoculation

I first read Grain Brain in 2019 and I was really intrigued by this section of the book. This book doesn't go into too much detail about the microbiome and gut flora but Dr. Perlmutter's next book, Brain Maker, is a deeper dive on this topic.

Babies who are born via Cesarean section have a higher risk of developing ADHD..... but why? This is an example of the importance of healthy gut bacteria to sustain intestinal health and overall wellness. When a baby passes through the birth canal naturally...billions of healthy bacteria wash over the child, inoculating the newborn with appropriate probiotics whose pro-health effects remain for life. If a child is born via C-section... they miss out on this inoculation which sets the stage for bowel inflammation and in turn, an increased risk of sensitivity to gluten and ADHD later in life.

This is kind of a big topic that was lightly grazed in this book but he does an excellent job covering the microbiome in Brain Maker.


Depression is the leading cause of disability worldwide.

What’s messed up many depressed people have bottles of "antidepressants."

Drugs like Prozac, Paxil, Zoloft, and countless others are by far the most common treatments for depression, despite the fact that they have been shown in many cases to be no more effective than a placebo and in some cases can be exceedingly dangerous and even lead to suicides.

SSRIs are typically used as antidepressants but they are sometimes prescribed to treat anxiety

disorders and some personality disorders. They work by preventing the brain from reabsorbing the neurotransmitter serotonin. By changing the balance of serotonin.

If you’ve got low cholesterol, you’ve got a much higher risk of developing depression.

The lower your cholesterol, the closer you are to harboring thoughts of suicide

Depression and a Damaged Intestine

How does depression relate to a damaged intestine?

The gut gets injured by celiac disease causing it to become ineffective at absorbing essential nutrients. Nutrients such as zinc, tryptophan, and the B vitamins are important for brain health and their absorption is hindered when your gut lining is damaged.

These nutrients are key ingredients in the production of neurological chemicals such as serotonin. The nerve cells in your gut regulate muscles, immune cells, hormones, and also manufacture 80 to 90 percent of your body’s serotonin. Your gut makes more serotonin than the brain. Other nutritional deficiencies that have been linked to depression include vitamin D and zinc. Zinc plays an important role in the immune system and keeping memory sharp it is also required in the production neurotransmitters.

Vitamin D is discussed here and is also mentioned in the section about statins.


If you're experiencing daily headaches, you might not need to be taking medication for it every day, or seek high tech brain scans to figure out what the heck is going might just have a gluten sensitivity. You might as well try a gluten free diet...there's legit nothing to lose.

When the focus is on drugs rather than dietary choices and nutritional supplementation it doesn't address the underlying cause of the headache.

Dr. Dimitrova from Columbia University Medical Center conducted a yearlong study that documented chronic headaches in people that were gluten sensitive and also people that were diagnosed with celiac disease.

Dr. Dimitrova says:

It’s possible the patients with [inflammatory bowel disease] have a generalized inflammatory response, and this may be similar in celiac disease patients, where the whole body, including the brain, is affected by inflammation…. The other possibility is that there are antibodies in celiac disease that may… attack the brain cells and membranes covering the nervous system and somehow cause headaches. What we know for sure is that there is a higher prevalence of headache of any kind, including migraine headaches, compared to healthy controls.

She went on to say that many of her patients report major improvements in the frequency and

severity of their headaches once they adopt a gluten-free diet. For some people, headaches completely stop.



Docosahexaenoic acid (DHA) is a really important supplement and Dr. Perlmutter mentioned numerous times in this book. Further up in these book notes there is more information on why DHA is so important for brain health. To sum it all up, DHA helps orchestrate the production, connectivity and viability of brain cells while at the same time enhancing function.

DHA is an omega-3 fatty acid when you're at a health /nutrition store looking for DHA and the person brings you an omega supplement, don't worry...just read the back label and it will tell you how much DHA is in there. DHA represents more than 90 percent of the omega-3 fats in the brain. 50% of the weight of a neuron’s plasma membrane is composed of DHA. It is also a key component in heart tissue.

Resveratrol Resveratrol is a natural compound found in grapes, which slows down the aging process, boosts blood flow to the brain, promotes heart health, and also inhibits the development of fat cells. This is why people say a glass of red wine is healthy...because of this compound. This molecule protects cells against a range of diseases and it is an assistant in the body’s immune and defense system. Harvard’s Dr. David Sinclair discovered resveratrol's ability to activate certain genes called sirtuins, which affect longevity.

Curcumin Turmeric (Curcuma longa) is a member of the ginger family. Research is currently evaluating the anti-inflammatory and antioxidant activities that come from its active ingredient, curcumin.

Curcumin has the ability to activate genes to produce a vast array of antioxidants that serve to protect our precious mitochondria. It essentially boosts our our body's innate defense system.

Vitamin D Vitamin D isn't really a vitamin's a fat-soluble steroid hormone. There are receptors for vitamin D throughout the entire central nervous system. Vitamin D helps regulate enzymes in the brain and cerebrospinal fluid that are involved in manufacturing neurotransmitters and stimulating nerve growth. Vitamin D protects neurons from the damaging effects of free radicals and reduces inflammation.

Correcting low levels of vitamin D can take several months of supplementation. If you supplement consistently you can significantly improve your entire body’s chemistry...everything from from bone health to brain health and even its insulin sensitivity.


The last important concept that this book discusses is a hormone called leptin.

Leptin is one of those really important hormones like insulin. Leptin influences all other hormones and controls virtually all the functions of the hypothalamus in the brain. Your hypothalamus is your inner dinosaur. The hypothalamus is an ancient structure in your brain that even pre-dates humans. It is responsible for your body’s rhythmic activities and many physiological functions, from hunger to sex. Leptin was identified in an unlikely place: fat cells

Leptin is a primitive survival tool. It’s uniquely tied to the coordination of our metabolic, hormonal and behavioral response to starvation. It has a powerful effect on our emotions and behavior.

The more sensitive you are to leptin the healthier you will be. "Sensitivity” means how your body’s receptors for this hormone recognize and use leptin to carry out various operations. It's the same concept of insulin sensitivity in regards to insulin resistance. Actually, leptin and insulin have a lot in common. Both are proinflammatory molecules. Leptin is an inflammatory cytokine in addition to playing a big part in the body’s inflammatory processes. It controls the creation of other inflammatory molecules in your fat tissue throughout your body. Both hormones are directly impacted by carbohydrate consumption. The more refined/processed the carbohydrate... the more wonky healthy levels of leptin and insulin become.

There is no drug or supplement on the planet can balance leptin levels. The only thing you can do is sleep better and make better dietary choices.

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El Guanto
El Guanto
Aug 05, 2021

Thank you for this.

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