Does Sugar Really Rot Your Brain?

Halloween Hangover.

A few years ago, my son came home from a Halloween party with a growling tummy ache and jitters. There was nothing I needed to say. He had made an important discovery all on his own: sugar was not the sweet and innocent thing he had expected it to be.

He lay there in bed, one hand on his stomach and the other on his forehead, wondering aloud if he would be able to go to school in the morning. He even moaned periodically, like an adult with a hangover. It was touching. And a little pathetic.

And yet, how often do we adults suffer from too much sugar and fail to make any connection whatsoever? How often do we feel crummy from eating sugar only to reach for more sugar to fix how we feel, starting a cycle that may go on for days, months, or even years?

Sound familiar?

I've certainly been there. But before you beat yourself up too much, consider this: functional MRI scans of your brain on sugar look similar to scans of your brain on drugs, like alcohol and cocaine. Yes, cocaine. So I'd say you have every right to feel whipped by that "other white powder", especially since it has been added by the cupful to nearly every processed food you’ve ever learned to love.

In a master stroke of marketing, modern food has been engineered to keep you hooked on sugar—forever. It's a gimmick that plays on your natural design. Your genes know the gambit well. You were designed to seek out sweet and starchy things so you could pack away as many fattening carbohydrates as you possibly could during their brief seasonal availability, just before winter.

But now, with the birth of modern agriculture, extracted sugars, shelf-stable breads, cookies, crackers, pastas, and fresh fruit flown in from around the world 24/7, we have turned that brief season into one endless summer of sweet, starchy, glutinous delights. And disease. It's another case of the ever-growing mismatch between our ancient genome and our modern food culture.

Coping With Modern Food Culture.

You didn't singlehandedly make today's food environment and you won't singlehandedly change it. But there are many simple things you can do to reduce your exposure. For example, I once had a patient lose an astonishing amount of weight, simply by eliminating soft drinks from his diet and switching to crisp, clean water. Not too complicated, that. (For the record, diet soda is not water. In fact, consuming artificially-sweetened drinks poses an even higher risk of developing type II diabetes than consuming sugar-sweetened drinks. Am J Clin Ntr 2013;97:517-23. Who knew!

Delighting Ourselves Into Dementia.

But how serious is the problem, really? How ill could we possibly be making ourselves with a little sugar? In his bombshell book, Grain Brain, neurologist Dr. David Perlmutter explained to us—all the way back in 2013—just how deep the sugar-brain connection goes.

But who can remember 2013, right? So, let's review:

In his book, Perlmutter demonstrates convincingly how sugar doesn't just make you fat and contribute to diabetes and heart disease; it drills all the way down (or up) to the organ that makes you, you. The brain.

Modern doses of sugar—which are really pharmacological doses of sugar—may be the most underrated contributor to a disease that is erasing the lives of otherwise healthy people all across this country: Alzheimer's.

Paradoxically, this is good news, because it means dementia and Alzheimer's may be more under our control than we thought.

Could it really boil down to food? If so, how exactly does sugar go about pickling your brain?

Here’s the sugar-brain premise in a nutshell:

  • We can certainly burn sugar for fuel. But sugar is toxic if it hangs around the body unattended. When your blood sugar rises (even transiently) above what your insulin can efficiently handle, the left-over, loitering sugar gets into trouble. It undergoes a spontaneous chemical reaction that binds it firmly to nearby proteins. Such “cross-linking” between proteins and sugar is not governed by enzymes. It's unintentional and haphazard—a crusty affair with ugly consequences. We call this process “glycation”. Ultimately, it leads to Advanced Glycation End-products, or AGEs, which are clunky structures that must be cleared by the immune system. AGE is a remarkably fitting acronym because all this sugary flotsam and jetsam accelerates aging—everywhere—including your brain (perhaps by as much as 50 fold).

Think of it this way, glycation bonds are dysfunctional bonds that change the shape or texture of a target protein. They are like the sugar-coating on a frosted flake, or the caramelized crust on Crème brûlée. Such “frosted” or “caramelized” proteins are immediately marked for destruction and clearance by your ever-vigilant immune system. Basically, before you can say, “Trix are for kids”, you have an inflammatory response on your hands. And unfortunately, inflammation causes a lot of collateral damage wherever it goes. In the brain, inflammation causes atrophy, memory loss, tangles, and plaques—in a word, dementia.

Ok, now that you've got the basic idea, I’ll summarize Grain Brain simply by bullet-pointing some of the research you’ll find in it. Grain Brain is engaging, practical, and remarkably easy to understand, (and delicious too; yes, there are recipes!). I have heard Dr. Perlmutter speak in person several times and his book is every bit as personable as he is. So I would encourage you to read it. But for brevity’s sake, I’m just going to give you some scannable content here. I think the studies speak for themselves:

  • A Japanese study of 1,000 men and women over age 60 showed that those with diabetes were twice as likely to develop Alzheimer’s within 15 years, and 1.75 times more likely to develop any form of dementia. Kiyohara Y. Rinsho Shinkeigaku. 2011:51(11):906-909.

  • A European study found that glycated proteins (sugar-damaged proteins) produced nearly 50 times more free radicals and oxidative stress on the brain than non-glycated proteins. European Archives of Psychiatry and Clinical Neuroscience 249(3):S68-S73: 1999.

  • Impaired glucose tolerance during the 6th decade of life doubles the risk of developing Alzheimer’s later on.

  • Hippocampal atrophy is directly correlated with blood sugar levels. (The hippocamus is the memory center of the brain.) I don't have permission to publish the incredible shrinking brain photos from this study, but trust me, the fMRI images are arresting. The scans show non-diabetic individuals with elevated blood sugar and loss of brain volume in two key structures: the hippocampus and the amygdala. Brain shrinkage occurs even at glucose levels heretofore considered to be in the normal range. (See my comment about the pitfalls of normal ranges in the "What to do now" section.) Cherbuin N, et al. Neurology. 2012; 79:1019-1026.

  • A Mayo Clinic study showed that people eating the most carbs had four times the risk of mild cognitive impairment compared with those eating the least carbs. Note: the carb eaters in this study sourced their carbs mainly from sugar, flour, and fruit—not veggies. In other words, they were eating the usual carbs. Roberts RO, et al. J Alz Dis. 2012;32(2):329-339.

  • And finally, a recent study published in the New England Journal of Medicine shows that higher blood glucose levels are associated with an increased risk of dementia even among persons without diabetes. The authors demonstrate with 95% confidence, that over a 5-year period of time, there was a significant difference in the rate of dementia between those individuals with an average blood sugar of 100 mg/dl and those with an average of only 115 mg/dl. Think about that. That's almost a razor's edge between staying sharp in your old age and going senile. Current ADA guidelines do not even begin to help clinicians with this kind of nuance. So, for the time being, you'll want to be your own advocate. Glucose Levels and Risk of Dementia, NEJM 369;6 August 8,2013.

What About Gluten and Wheat?

Not Your Great-Grandma's Grain.

Grain-derived starches and sugars provide the bulk of carbs in our Standard American Diet (SAD diet). Much of it comes from corn in the form of high-fructose corn syrup. But a good deal of it also comes from wheat, spelt, kumut, rye, triticale, malt, and barely. And when carbohydrates come from these grains, they travel with a little something extra, a hitch-hiker called gluten.

We all like the texture of gluten, whether we know anything about it or not. Gluten is that gooey, chewy, elastic protein that allows fine flour to swell into something as light and airy as a croissant. Sounds wonderful, doesn't it? A baker’s dream. But for a growing number of people, it’s become a nightmare.

We are not exactly sure why the incidence of gluten sensitivity has increased in the last few decades, but the numbers are real and not merely a fad. It may have something to do with the fact that modern wheat contains more gluten than ancestral varieties and bears little genetic resemblance to wheat consumed even 60 years ago. Or it could just be that we have shifted our entire diet to include more grains than ever before, thanks to industry-sponsored advice from the USDA food guide pyramid and the explosion of shelf-stable convenience foods containing gluten.

At some point, I will do a post looking at the effect of gluten on the gut and other organs, but for now let’s just consider its impact on the brain.

In brief, it turns out that gluten sensitivity may be a potent risk factor for dementia all by itself, quite apart from the refined carbohydrate company it keeps:

  • A 2006 Mayo Clinic study documented a connection between celiac disease and progressive cognitive impairment, including ataxia and peripheral neuropathy (Hu WT, et al. Arch Neurol. 2006;63(10);1440-1446).

  • In the same study, several patients with advanced cognitive decline who went gluten-free showed significant improvements in function, suggesting that the condition is reversible with a gluten-free diet.

While gluten sensitivity and celiac disease are not the same thing, Grain Brain discusses other disquieting evidence of gluten sensitivity and neurologic dysfunction, which you can read on your own. Make up your own mind. And perhaps, save your mind.

What to Do Now?

Laboratory Testing.

If you need more motivation to ditch sugar and tone down the grains, then I would suggest getting some lab work done. Hard personal data can be just what the doctor ordered to help you make and keep commitments. Labs can also be useful for tracking progress. Dr. Perlmutter suggests the following labs as the most helpful in assessing your dementia risk and helping you actually do something about it:

  • Hemoglobin A1c (HbA1c):

  • Elevated Hemoglobin A1c is one of the strongest predictors of brain atrophy. It is an excellent indicator of your total body burden of glycation—the amount of sugar-damaged proteins you have floating around causing inflammation, oxidative stress, and brain-rot. But don’t be satisfied with a merely “normal” result. Our current range of “normals” includes the lowest common denominator: Homer Simpson. The middle range is nothing more or less than the new normal of our present glycation crisis. It has nothing to do with optimal levels. Strive for a HbA1c of less than 5.0%. Merely going from 5.2% to 5.9% doubles your annual rate of brain shrinkage. Yet, some docs won’t take you seriously until your HbA1c reaches 6.5%, at which point you will finally be considered abnormal enough to get a diagnosis (diabetes) and a prescription to go with it. Can your brain wait for that? Mine can’t. (Geberhiwot T, et al. Ann Clin Biochem. 2005;42 (Pt 3):193-195 and (Neurology 64: 1704-11; May 24, 2005)

  • Cyrex Array 3: This is one of the most comprehensive assessment tools for gluten sensitivity available.

  • Cyrex Array 4: Measures cross-reactivity to foods that gluten-sensitive people often find problematic.

  • Other labs that may be helpful include: Fasting Glucose, Fasting Insulin, Fructosamine, Homocysteine, Vitamin D, C-Reactive Protein, Genetic Testing (keep in mind that not everyone with crummy genes gets Alzheimer’s. That’s why focusing on modifiable risk factors like sugar and gluten may prove to be more predictive and productive than knowing whether or not you have the ApoE4 allele).

Yours in Health and Resilience,

Marc Wagner, MD, MPH, NTP

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Useful Links:

  • Check out Dr. Perlmutter's new book, The Grain Brain Whole Life Plan. Available now. Grain Brain told you why. The Grain Brain Whole Life Plan will tell you how.

  • Watch Dr. Gupta's eye-opening video, Sugar and Kids: The Toxic Truth.

  • Watch Robert H. Lustig, MD Endocrinology, UCSF - The average American consumes 130 pounds of sugar per year—a pharmacologic dose. “Nature made sugar hard to get; man made it easy”, says Lustig. We are not just eating more calories than our ancestors, but a different mix of calories. The old dogma that “a calorie is a calorie is a calorie” is simply false.