I have blogged before about “Losing my Marbles”, a traumatic brain injury and the Paleo diet. Researchers discovered that a traumatic brain injury can lead to Altzheimers, and the Paleo diet appears to help reduce cognitive decline. Below is an exerpt from an interview with neurologist Dr Perlmutter, author of the New York Times bestseller “Grain Brain”. It is an eye opening look into how the brain uses high glycemic foods and you may be interested in changing your diet after reading this.
In his new book Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar — Your Brain’s Silent Killers, Dr. David Perlmutter, Associate Professor at the University of Miami School of Medicine, advocates that lifestyle modifications, starting with a high-fat, nearly carbohydrate-free diet, can prevent or greatly lower dementia risk and progression — and he’s armed with plenty of data to back up the claim. But detractors say the evidence isn’t quite there. With Grain Brain about to hit its 15th straight week on the New York Times best-seller list (including a stint at the top spot) Medscape spoke with Dr. Perlmutter about his thoughts on the impact of carbohydrates and gluten on the brain.
Medscape: For those unfamiliar with your ideas, can you summarize the thesis behind your new book and how you arrived at it?
Dr. Perlmutter: Certainly. I’m a board-certified neurologist and a fellow of the American College of Nutrition. I’ve been very frustrated with neurology over the past 20 years, because we’re trained in residency and practice to basically treat symptoms of neurologic disorders. I found that not to be satisfying and thought it was important to delve into causality as opposed to just focus on treating the smoke and ignoring the fire.
That said, with time we began seeing wonderful research citations that were drawing a link between risk for dementia, for example, and blood sugar levels appearing in our most well-respected journals. For example, a study published in Neurology in 2005  pointed a finger squarely at the most powerful metric being glycated hemoglobin. Even back then, it was becoming clearer that there was something going on with blood sugar correlating with rate of brain atrophy, specifically hippocampal atrophy, and cognitive decline. When you now retrospectively evaluate that study, you begin to appreciate that glycated hemoglobin is more than just a metric of average blood sugar, which is typically how it’s looked upon even today.
Glycated hemoglobin is a glycated protein. This is a marker not just of average blood sugar, but more important, it’s a marker of the degree of glycation that’s going on in human physiology — a process that increases inflammation and dramatically increases the production of free radicals and oxidative stress. So the idea that even subtle elevations of sugar, which is a dietary lifestyle choice, are related to risk for brain degeneration really began to crystallize.
This notion has gained traction and, I think, is profoundly supported by a couple of more recent studies. A study published in August 2013 in the New England Journal of Medicine (NEJM)  was very supportive, indicating that even subtle elevations of fasting blood sugar translates to dramatically increased risk for dementia. This was a prospective analysis that measured fasting blood sugar and followed 839 men and 1228 women for a mean of 6.8 years. I’ll quote the conclusion: “Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes.”
Why? These are levels of 105 and 110 mg/dL — levels that most doctors are going to be satisfied with. However, according to the study, these numbers translated into a significantly increased risk for dementia in individuals who were not demented.
Medscape: That is striking. However, I think it’s important to point out that many of the studies you cite report associations between glucose and risk for dementia and don’t necessarily prove causality, correct?
Dr. Perlmutter: You are 100% correct. I’ll stand and take my lumps from those individuals who want to make the argument that there’s no smoking gun here. But when a prestigious journal like NEJM calls our attention to this relationship effect in glucose and cognitive decline, we’ve got to take notice, especially at a time when we have no other choice. It’s the best thing that we have going.
We know that a lower-carbohydrate diet is the right choice for the heart and the immune system. There’s no downside to it. I offer it up as being supported by the current peer-reviewed literature. If that’s as good as it gets, that’s the best we have right now.
You can wage criticism that the NEJM study was not interventional. It wasn’t a double-blind study testing some sort of pharmaceutical intervention. It was a prospective study that basically asked who’s going to get dementia on the basis of fasting blood sugar levels.
Some people criticize prospective or even retrospective studies because they’re not interventional. I tend to think that they can provide very, very valuable information. There’s never been an interventional trial that’s demonstrated that seatbelts are effective in reducing injuries in a car accident.
Medscape: What type of diet or interventions do you recommend to prevent or slow dementia?
Dr. Perlmutter: The data show that individuals with lower blood sugar levels have a lower risk for dementia. Therefore, we’ve got to keep blood sugar low. We do so by using the time-honored dietary intervention of a lower-carbohydrate, higher-fat diet.
This is what the scientists have told us for years is the best way to lower blood sugar. If you look at the A TO Z trial,which was published in JAMA in 2007,  dramatic reductions in blood sugar were seen in participants on a lower-carb, higher-fat diet.
A similar article was published in NEJM in 2008.  This was an interventional trial demonstrating both weight loss and reduction of fasting blood sugar in individuals eating a higher-fat, lower-carbohydrate diet.
The Mayo Clinic published a study  in the Journal of Alzheimer’s Disease in 2012 demonstrating that in individuals favoring a high-carb diet, risk for mild cognitive impairment was increased by 89%, contrasted to those who ate a high-fat diet, whose risk was decreased by 44%. Drs. Barnes and Yaffe from the University of California, San Francisco, published a study in Lancet Neurology in 2011  indicating that about 54% of cases of Alzheimer disease in the United States could have been prevented with attention to lifestyle changes, such as exercise, weight loss, and controlling hypertension.
This province of lifestyle modification in neurologic diseases has not been one of comfort for neurology in general. We neurologists are acting in an essentially reactionary manner. In other words, we are responding to illnesses by hoping that there are medications to treat symptoms, whereas we really ought to embrace the notion of preventive medicine, because the science is staring us in the face.
Medscape: One of the points in your book I found interesting is that you’re not just talking about processed carbohydrates or sugars here, right? You believe that whole grains — typically presumed healthy — also increase dementia risk?
Dr. Perlmutter: Yes, they do. There’s a lot of very good information provided on the glycemic index of these foods. That is a metric of not only just the elevation of blood sugar and the consequence of consuming a particular food, but actually it’s also a measurement of how long the blood sugar remains elevated.
The glycemic index measures what the blood sugar is between 90 and 120 minutes after consuming a particular food. When you look at the glycemic index of whole-grain bread, for example, it’s extremely high: 72-74. It’s higher than that of white bread. It’s much higher than that of many candy bars. It becomes a huge issue in terms of how long your blood sugar remains elevated — that is, how long you have increased risk for glycation of proteins. It becomes a big issue that we have to reconsider these recommendations about whole grains in terms of the simple fact of looking just at the glycemic index.
Medscape: Does the same go for other grains common in health foods these days, such as flax and quinoa?
Dr. Perlmutter: Flax and quinoa (which by definition is actually not a grain) are gluten-free foods rich in fiber and healthful fat. However, they do contain modest amounts of carbohydrate, and assessing these foods by evaluating their glycemic indices will help decide how healthful they really are.
Medscape: What do you say to the fact that many global diets proven to be healthy — particularly the Mediterranean diet, which is continually shown to be beneficial in numerous medical and mental conditions — include whole grains? And that many of the world’s so-called “blue zones” — regions in which residents have notably long lifespans — also include grains in their diets?
Dr. Perlmutter: I think people do tolerate some amount of grains, and that the classic Mediterranean diet is one that has added fat and lower carbs. Of note, an April 2013 article in NEJM compared a standard US diet with a Mediterranean diet supplemented with extra-virgin olive oil and a Mediterranean diet supplemented with mixed nuts. The investigators looked at 3 endpoints: myocardial infarction, stroke, and death. They had to stop the study halfway through it, at 4.6 years, because the individuals with the highest fat consumption had a 30% lower risk for the endpoints. It was unfair to the rest of the participants.
Can people get away with having some whole grain products? I suspect so. But you have to understand that wheat products represent 20% of our caloric intake in the United States. That’s not the way it is around the rest of the world. The Mediterranean diet, for example, does not pound people over the head with soda.
Medscape: How would you respond to your detractors that there just isn’t enough evidence to support would could be considered a somewhat extreme change in our country’s dietary habits?
Dr. Perlmutter: My response is that the “extreme change in dietary habits,” to quote you, is actually what has happened to human nutrition in only the past several centuries. In the early 19th century, Americans consumed just over 6 pounds of sugar each year. That figure now exceeds 100 pounds. And there has been a dramatic reduction in the consumption of healthful fat. Beyond the mechanism of protein glycation, as well as the powerfully detrimental downstream effects of uncontrolled insulin signaling, we haven’t even begun to understand the epigenetic consequences related to the effects of these new dietary challenges in terms of maladaptive genetic expression.
So in reality, I am not suggesting a change. I am recommending that we end this grand experiment and return to a diet that isn’t evolutionarily discordant.
Medscape: Do you have any final comments for Medscape’s audience of clinicians? How do you feel your ideas should be incorporated into patient care?
Dr. Perlmutter: Again, look at A1c in a different way. Rather than simply representing a metric of average blood sugar over a 3- to 4-month period, look at it as a way of modifying your pharmaceutical intervention; look upon it as a marker of what it really is, glycation of protein. That glycation of protein dramatically relates to inflammation and oxidative stress. That’s number one.
Second, begin to incorporate a fasting insulin metric as a way of anticipating who’s going to then develop elevations of fasting blood sugar and glycation of hemoglobin moving forward. The earliest sign of pancreatic stress is elevation of fasting insulin — which ideally should be less than 8, not up to 24, which is what is in the so-called normal range.
Third, recognize that vitamin D is a powerful player in terms of brain health. Beyond strong and healthy bones, vitamin D activates more than 900 genes in human physiology, most of which are important for brain health. Low levels of vitamin D correlate with increased risk for multiple sclerosis, dementia, and Parkinson disease. Those are my 3 take-home messages.