David Perlmutter, MD, FACN, ABIHM discusses new edition of “Grain Brain”

Integrative Practitioner: One the focuses of the new edition is the ketogenic diet. Why has this become a central part of your work?

Perlmutter: The ketogenic diet, keto terms in general, is one of the most rapidly searched on Google, and with good reason. It’s a very exciting way that clinicians can enhance brain function.

We’re now seeing research that indicates actual cognitive improvement in individuals on a ketogenic program, and really while we’re seeing all this new excitement, one study that demonstrates the effects of the ketogenic diet has been going on for about 2.5 million years—in other words, for almost the entire time that we have walked this planet, humans have primarily been eating in a way that has increased ketones in our bodies. It allowed us to survive, it allowed us to flourish, it protected our brains.

Over the past couple of million years, we have experienced a three-fold increase in the size of our brains. But interestingly, about 12,000 years ago, the size of the human brain began to decline. We now understand, looking at fossils, our brains are about 10 percent smaller than they were 10-12,000 years ago. Interestingly, that is when agriculture was developed and when we started to cultivate grains. Grains came in to the diet, humans began eating grains, eating higher levels of gluten, and dramatically higher levels of carbohydrates, and our brains have shrunk, and our health has declined overall.

But why is the ketogenic diet so good for the brain? There are multiple reasons. One, we have learned since the 1960s, that ketones are a brain super fuel, that when the brain cells are powered with ketones, they are able to produce energy, ATP molecules, much more efficiently gram for gram in comparing using ketones for fuel versus carbohydrates, but also do so with less production of damaging free radicals, which are kind of like the exhaust of brain metabolism. So, less exhaust, less damaging free radicals, and higher levels of these ATP molecules.

We know that a ketogenic diet that reduces inflammation in the human body, and as such it is reducing that fundamental mechanism that underlies Alzheimer’s and Parkinson’s, and diabetes, and coronary artery disease and, really, across the board all the chronic degenerative conditions. We also know that ketones specifically one ketone, beta-hydroxybutyrate, amplifies the gene transcription to make BDNF. Again, that’s key to increasing the growth of new brain cells, increasing the connection of brain cells which we could call neuroplasticity or synaptogenesis, but also BDNF is important in protecting brain cells against trauma.

A ketogenic diet helps increase insulin sensitivity. [Insulin] plays a very important role in keeping the brain functional. We need insulin functionality in the brain not only because of how it delivers glucose to the brain. Insulin in the brain also acts as a trophic hormone and improves the functionality of brain cells.

Finally, we know that beta-hydroxybutyrate acts to stimulate guanine nucleotide-binding proteins (g proteins), and these g proteins regulate immune function, regulate inflammation, regulate really the vitality and functionality of brain cells.

There are really a lot of reasons that going on a ketogenic diet directly is beneficial, and slightly indirect is that a ketogenic diet helps people lose weight. Really, well beyond the cosmetic part of that statement, being thinner, having a small abdomen, is associated with decreased risk for developing dementia. A study was done 30 years prior to determining risk for dementia, and all it did was measured how big a person’s belly was. That’s it. They followed this group of individuals for 30 years and what did they find? Those individuals who, 30 years ago, had a bigger belly, had a bigger risk for dementia. That’s really very important because it says that our outreach, our messaging, should be targeting people in their adolescents, in their teens, when they are setting themselves up for a bigger belly, for obesity. This study reveals that people in their 30s and 40s who had lots of abdominal fat, had a dramatic increased risk for becoming demented, a situation for which there is no medical treatment. That’s why this becomes important.

Integrative Practitioner: How do you incorporate fasting in to your recommendations?

Perlmutter: Fasting can take any number of forms. It might simply mean that each day you put off having your first meal until noon or later in the afternoon, and that meal is when your fast is over, we call that meal “breaking fast” or breakfast, that’s what that meal is all about. If you decide that you’re going to have your breakfast later in the day, that you’ve extended the time between your evening meal the night before, that may be 14-16 hours, and during that time, your body is creating ketones, and those ketones are doing all the great things for your brain that you want them to do. And believe me, it’s not just in the brain, but this improvement of insulin sensitivity is something your entire body will benefit from. That is fasting that can be done daily.

Beyond that, deciding not to eat for a day once a week or once a month is certainly well within reach for anyone. If you have any ongoing medical illness, it’s certainly reasonable to check with your healthcare practitioner prior to engaging in what would be nothing more than a water fast for 24 hours, nothing wrong with that.

We are seeing individuals use what is called a fasting-mimicking diet, developed by Valter Longo, PhD. Longo’s program does supply some food, but he believes he is able to mimic in terms of the biochemistry that happens, what would happen in your body if you were engaged in a complete fast. He’s done a lot of research in terms of Alzheimer’s and even cancer using his fasting-mimicking diet.

Some people use programs for three to five days of fasting, or even longer.

The idea of fasting is not well-defined, and yet the notion of fasting certainly provides us with an extremely valuable tool in terms of enhancing brain function and protecting the brain as well.

Integrative Practitioner: How do supplements factor in to the "Grain Brain" discussion?

Perlmutter: One of the supplements that is getting a lot of attention right now is something called medium-chain triglyceride (MCT) oil. It’s a type of fat that is very easily transformed in the liver into ketones. Normally, long chain fatty acids, like the types of fat that we store, or long chain fatty acids that may be part of our diet, require a little more effort on the part of the liver to be transformed in to ketones. Not only that, long chain fatty acids have to be absorbed in a more complicated way; they have to be transformed in what are called chylomicrons that have to be selectively absorbed through the gut lining. Then, these long chain fatty acids have to be coupled or activated by carnitine before they can be utilized by the liver to make these ketones.

MCTs, on the other hand, readily form ketones in the human body. Breast milk is the reason why breastfed infants have high levels of ketones in their blood, which is certainly good for brain development. But adults can take MCT oil and enhance the production of ketones immediately as well. That’s something we’re really very excited about.

Another new supplement on the scene is whole coffee fruit concentrate, which is a health food store item as well, and has been shown to dramatically increase the production of BDNF in humans, and that is certainly a plus for brain cells.

Beyond that, some tried-and-true supplements I think include vitamin D, a B-complex or, if a person has a problem with methylation [as determined through having their genome sequenced], a methylated form of B vitamins is worthwhile. Fish oil provides high levels of DHA is always a plus. I think providing a wide-spectrum probiotic is a reasonable idea as well.

Integrative Practitioner: Though the book focuses on brain health, how can these ideas be applied generally in patient practices?

Perlmutter: The first thing that practitioners need to recognize is that there is no treatment for Alzheimer’s. According to the Journal of the American Medical Association study mentioned earlier, the prescribed medications not only don’t work, but they worsen patients’ cognitive performance over time. That said, if we don’t’ have a treatment for the disease, it certainly makes the idea of prevention far more meaningful. What are the lifestyle choices that providers can recommend that are associated with decreased risk for Alzheimer’s disease? They include:

  • Regular physical aerobic exercise.
  • A diet that is associated with lowering blood sugar. In other words, a low-carbohydrate, low-sugar diet with higher levels of healthful fat.
  • Pay strict attention to the quality and quantity of your patient’s sleep. Every adult should have a formal sleep study.
  • Consider the use of certain supplements like MCT oil, vitamin D, methylated B vitamins, and a good dosage of DHA, 800-1,000 milligrams per day.
  • Talk to your patients about limiting stress. We know higher levels of cortisol brought on my constant stress are associated with degeneration of the very brain cells that we depend on for our memories located in the hippocampus.

We could go on and list many more. This list should not be overwhelming and doesn’t take that long. These are very powerful tools that any practitioner can incorporate in to her or his recommendations, not just for patients who are concerned by virtue of their family history that they may be at risk for Alzheimer’s disease, but any patient. We need to embrace the notion that if we live to be age 85 years old, our risk for this disease is 50-50. That means this is a discussion we should have with all of our patients.

Editor’s note: This interview has been edited and condensed.