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书籍: Grain Brain 作者: Perlmutter, David ======================================== *** 高亮 2016/8/7 Maintaining order rather than correcting disorder is the ultimate principle of wisdom. To cure disease after it has appeared is like digging a well when one feels thirsty, or forging weapons after the war has already begun. —NEI JING, 2ND CENTURY BC ======================================== *** 高亮 2016/8/7 I’m here to tell you that the fate of your brain is not in your genes. It’s not inevitable. And if you’re someone who suffers from another type of brain disorder, such as chronic headaches, depression, epilepsy, or extreme moodiness, the culprit may not be encoded in your DNA. It’s in the food you eat. ======================================== *** 高亮 2016/8/7 Yes, you read that right: Brain dysfunction starts in your daily bread, and I’m going to prove it. I’ll state it again because I realize it sounds absurd: Modern grains are silently destroying your brain. By “modern,” I’m not just referring to the refined white flours, pastas, and rice that have already been demonized by the anti-obesity folks; I’m referring to all the grains that so many of us have embraced as being healthful—whole wheat, whole grain, multigrain, seven-grain, live grain, stone-ground, and so on. Basically, I am calling what is arguably our most beloved dietary staple a terrorist group that bullies our most precious organ, the brain. I will demonstrate how fruit and other carbohydrates could be health hazards with far-reaching consequences that not only will wreak physical havoc on your brain, but also will accelerate your body’s aging process from the inside out. This isn’t science fiction; it’s now documented fact. ======================================== *** 高亮 2016/8/7 It is my objective in writing Grain Brain to provide information that is sound and based on evolutionary, modern scientific and physiological perspectives. This book goes outside the box of the layman’s accepted dogma—and away from vested corporate interests. It proposes a new way of understanding the root cause of brain disease and offers a promising message of hope: Brain disease can be largely prevented through the choices you make in life. So if you haven’t figured it out by now, I’ll be crystal clear: This is not just another diet book or generic how-to guide to all things preventive health. This is a game-changer. ======================================== *** 高亮 2016/8/7 . I believe that the shift in our diet that has occurred over the past century—from high-fat, low-carb to today’s low-fat, high-carb diet, fundamentally consisting of grains and other damaging carbohydrates—is the origin of many of our modern scourges linked to the brain, including chronic headaches, insomnia, anxiety, depression, epilepsy, movement disorders, schizophrenia, attention deficit hyperactivity disorder (ADHD), and those senior moments that quite likely herald serious cognitive decline and full-blown, irreversible, untreatable, and incurable brain disease. I’ll reveal to you the profound effect that grains could be having on your brain right now without your even sensing it. ======================================== *** 高亮 2016/8/7 For starters, diabetes and brain disease are this country’s costliest and most pernicious diseases, yet they are largely preventable and are uniquely tied together: Having diabetes doubles your risk for Alzheimer’s disease. In fact, if there’s one thing this book clearly demonstrates, it’s that many of our illnesses that involve the brain share common denominators. Diabetes and dementia may not seem related at all, but I’m going to show you just how close every one of our potential brain dysfunctions is to conditions that we rarely attribute to the brain. I’m also going to draw surprising connections between vastly different brain disorders, such as Parkinson’s and a propensity to engage in violent behavior, that point to root causes of an array of afflictions that involve the brain. ======================================== *** 高亮 2016/8/7 . It’s pretty straightforward: Our genes determine not just how we process food but, more important, how we respond to the foods we eat. ======================================== *** 高亮 2016/8/7 The information that I will reveal to you is not just breathtaking; it’s undeniably conclusive. You’ll be shifting how you eat immediately. And you’ll be looking at yourself in a whole new light. Right about now, you might be asking, Is the damage already done? Have you doomed your brain from all those years of having your cake and eating it too? Don’t panic. More than anything, I intend this book to be empowering, equipping you with a remote control to your future brain. It’s all about what you do from this day forward. ======================================== *** 高亮 2016/8/7 Drawing on decades of clinical and laboratory studies (including my own), as well as extraordinary results I’ve seen over the past thirty-odd years in my practices, I’ll tell you what we know and how we can take advantage of this knowledge. I’ll also offer a comprehensive action plan to transform your cognitive health and add more vibrant years to your life. And the benefits don’t stop at brain health. I can promise that this program can help any of the following: ======================================== *** 高亮 2016/8/7 ADHD anxiety and chronic stress ======================================== *** 高亮 2016/8/7 The chief function of the body is to carry the brain around. —THOMAS A. EDISON ======================================== *** 高亮 2016/8/9 . Cholesterol is a critical brain nutrient essential for the function of neurons, and it plays a fundamental role as a building block of the cell membrane. It acts as an antioxidant and a precursor to important brain-supporting elements like vitamin D, as well as the steroid-related hormones (e.g., sex hormones such as testosterone and estrogen). Most important, cholesterol is looked upon as an essential fuel for the neurons. Neurons themselves are unable to generate significant cholesterol; instead, ======================================== *** 高亮 2016/8/9 Most Americans consume gluten through wheat, but gluten is found in a variety of grains including rye, barley, spelt, kamut, and bulgur. It’s one of the most common food additives on the planet and is used not only in processed foods, but also in personal care products ======================================== *** 高亮 2016/8/10 Of all the lessons in this book, the one I hope you take seriously is the following: Respect your genome. Fat—not carbohydrate—is the preferred fuel of human metabolism and has been for all of human evolution. We have consumed a high-fat diet for the past two million years, and it is only since the advent of agriculture about ten thousand years ago that carbohydrates have become abundant in our food supply. We still have a hunter-gatherer genome; it’s thrifty in the sense that it’s programmed to make us fat during times of abundance. ======================================== *** 高亮 2016/8/10 Perhaps one of the most extraordinary studies performed on the positive impact of cholesterol on the entire neurological system is a 2008 report published in the journal Neurology, which describes high cholesterol as a protective factor in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease ======================================== *** 高亮 2016/8/10 14 The study was a retrospective evaluation of twenty-one previous medical reports involving more than three hundred forty thousand subjects followed from periods of five to twenty-three years. It concluded that “intake of saturated fat was not associated with an increased risk of coronary heart disease, stroke, or cardiovascular disease.” In comparing the lowest to the highest consumption of saturated fat, the actual risk for coronary heart disease was 19 percent lower in the group consuming the highest amount of saturated fat. The authors also stated: “Our results suggested a publication bias, such that studies with significant associations tended to be received more favorably for publication.” What the authors are implying is that when other studies presented conclusions that were more familiar to the mainstream (i.e., fat causes heart disease), not to mention more attractive to Big Pharma, they were more likely to get published. The truth is we thrive on saturated fats. In the words of Michael Gurr, PhD, author of Lipid Biochemistry: An Introduction, “Whatever causes coronary heart disease, it is not primarily a high intake of saturated fatty acids.”15 In a subsequent report from the American Journal of Clinical Nutrition, a panel of leading researchers in the field of nutrition from around the globe clearly stated: “At present there is no clear relation of saturated fatty acid intake to these outcomes [of obesity, cardiovascular disease, incidence of cancer and osteoporosis].” The researchers went on to say that research should be directed at “biological interactions between insulin resistance, reflected by obesity and physical inactivity, and carbohydrate quality and quantity.”16 ======================================== *** 高亮 2016/8/11 To fully grasp the bane of carbs and the benefits of fats, it helps to understand some basic biology. In the body, dietary carbohydrates, including sugars and starches, are converted to glucose, which you know by now tells the pancreas to release insulin into the blood. Insulin shuffles glucose into cells and stores glucose as glycogen in the liver and muscles. It’s also the body’s chief fat-building catalyst, converting glucose to body fat when the liver and muscles have no more room for glycogen. Carbohydrates—not dietary fats—are the primary cause of weight gain. (Think about it: Many farmers fatten animals destined for the butcher block with carbohydrates like corn and grain, not fats and proteins. You can see the difference just by comparing, for example, a cut of grain-fed New York strip steak and a grass-fed one: the grain-fed cut will contain a lot more fat.) This partly explains why one of the major health effects of a low-carbohydrate diet is weight loss. Moreover, a low-carb diet decreases ======================================== *** 高亮 2016/8/11 blood sugar in diabetics and improves insulin sensitivity. In fact, replacing carbohydrates with fat is increasingly becoming the preferred method for treating type 2 diabetes. ======================================== *** 高亮 2016/8/11 When your diet is continuously rich in carbohydrates, which in effect keep your insulin pumps on, you severely limit (if not completely halt) the breakdown of your body fat for fuel. Your body gets addicted to that glucose. You may even use up your glucose but still suffer from a lockdown of available fat for fuel due to high volumes of insulin. In essence, the body becomes physically starved due to your carb-based diet. This is why many obese individuals cannot lose weight while continuing to eat carbs. Their insulin levels hold those fat stores hostage. ======================================== *** 高亮 2016/8/11 Now let’s turn to dietary fat. Fat is and always has been a fundamental pillar of our nutrition. Beyond the fact that the human brain consists of more than 70 percent fat, fat plays a pivotal role in regulating the immune system. Simply stated, good fats like omega-3s and monounsaturated fats reduce inflammation, while modified hydrogenated fats, so common in commercially prepared foods, dramatically increase inflammation. Certain vitamins, notably A, D, E, and K, require fat to get absorbed properly in the body, which is why dietary fat is necessary to transport these “fat-soluble” vitamins. Because these vitamins do not dissolve in water, they can only be absorbed from your small intestine in combination with fat. Deficiencies due to incomplete absorption of these vitally important vitamins are always serious, and any such deficiency can be linked to brain illness, among many other conditions. Without enough vitamin K, for instance, you won’t be able to form blood clots upon injury and can even suffer from spontaneous bleeding (imagine that problem in the brain). Vitamin K also contributes to both brain and eye health, helping reduce the risk of age-related dementia and macular degeneration (and dietary fat is good for macular degeneration). Without adequate vitamin A, your brain won’t develop properly; you will go blind and become exceptionally vulnerable to infections. A lack of vitamin D is known to be associated with increased susceptibility to several chronic diseases, including schizophrenia, Alzheimer’s, Parkinson’s, depression, seasonal affective disorders, and a number of autoimmune diseases such as type 1 diabetes. ======================================== *** 高亮 2016/8/11 If you follow today’s conventional wisdom, you know that you’re supposed to limit your total fat intake to no more than 20 percent of your calories (and when it comes to saturated fat, that percentage goes down to less than 10). You also know that this is difficult to achieve. (You can breathe a sigh of relief: It’s misguided advice, and on my program you won’t have to worry about counting fat grams or overall percentages.) However, while the synthetic trans fats found in margarine and processed foods are poisonous, we know now that monounsaturated fats—such as the fat found in avocados, olives, and nuts—are healthy. We also know that the polyunsaturated omega-3 fatty acids in cold-water fish (e.g., salmon) and some plants (e.g., flaxseed oil) are deemed “good.” But what about natural saturated fats such as those found in meat, egg yolks, cheese, and butter? As I’ve been detailing, saturated fat has gotten a bad rap. Most of us don’t even question why these particular fats are unhealthy anymore; we just assume that the purported science is true. Or we erroneously place these fats in the same category as trans fats. But we need saturated fat, and our body has long been designed to handle the consumption of natural sources of it—even in high amounts. ======================================== *** 高亮 2016/8/11 Few people understand that saturated fat plays a pivotal role in a lot of biochemical equations that keep us healthy. If you were breast-fed as a baby, ======================================== *** 高亮 2016/8/11 One of the most pervasive myths I’m constantly debunking is the notion that the brain prefers glucose for fuel. This also couldn’t be further from the truth. The brain uses fat exceptionally well; it is considered a brain “superfuel.” This is why we use a fat-based diet as therapy for all manner of neurodegenerative diseases (in chapter 7, I describe in detail how the brain accesses fat for fuel and what this means for health and for tailoring the perfect diet ======================================== *** 高亮 2016/8/11 Part of the reason I am focusing on fats, and cholesterol in particular, is not only because these ingredients have everything to do with brain health, but also because we live in a society that continues to demonize them, and the huge pharmaceutical industry preys on the public’s misinformation and perpetuates falsehoods, many of which could physically destroy us. To really understand where I’m going with this, let’s look at one problematic area: the statin epidemic. ======================================== *** 高亮 2016/8/11 In 2009, an updated review of two major studies completed in 2001 of statin medications used by more than twenty-six thousand individuals at risk for dementia and Alzheimer’s disease showed that statins are not protective against Alzheimer’s, which contradicted previous thinking. The lead author of the study, Bernadette McGuinness, was quoted by ScienceDaily as saying, “From these trials, which contained very large numbers and were the gold standard—it appears that statins given in late life to individuals at risk of vascular disease do not prevent against dementia.”29 When asked to comment on the results, UCLA researcher Beatrice Golomb said, “Regarding statins as preventive medicines, there are a number of individual cases in case reports and case series where cognition is clearly and reproducibly adversely affected by statins.”30 Golomb further added that various studies have demonstrated that statins either negatively affected cognition or were neutral, and that no trial has ever shown a positive outcome. ======================================== *** 高亮 2016/8/11 Okay. So cholesterol is a good thing. But it’s not just about your brain’s wit, physical health, and future longevity. It’s also about a very important part of your lifestyle that typically gets shoved under the carpet in serious health books. I’m talking about your sex life. How sparky is it? Although I’m a neurologist, I treat a fair share of people who suffer from sexual dysfunction and are either impotent and avoid sex altogether or who hoard bottles of pills to help them out. You know about these pills—the ones that get advertised like candy on the evening news and promise to transform your sex life. My patients with sexual health woes obviously don’t come to me for that specifically, but it’s a noted problem when I ask them about that part of their life in addition to any neurological issues I am addressing. A quick anecdote. A seventy-five-year-old retired engineer came to see me with a variety of complaints, including insomnia and depression. He had been taking sleeping pills for the past forty years, and his depression had worsened in the two to three months prior to his appointment. At the time I saw him, he was actually taking a few drugs: an antidepressant, a medication for anxiety, and Viagra for erectile dysfunction. I first checked him for gluten sensitivity and discovered, to his surprise, a positive panel. He agreed to adopt a gluten-free, high-fat diet, and we next communicated by telephone after about one month. That’s when he had magnificent news: His depression had improved, and he no longer needed to take Viagra in order to have sex with his wife. He thanked me very much. ======================================== *** 高亮 2016/8/11 Most everyone can agree that sex has everything to do with what’s going on in the brain. It’s an act that’s deeply tied to emotions, impulses, and thoughts. But it’s also inexorably connected to hormones and blood chemistry. Without question, if you’re depressed and not sleeping well, like my engineer patient, sex is the last thing on your mind. But one of the most common reasons for impotence is actually neither of these two conditions. It’s what I’ve been talking about through much of this chapter: abysmally low cholesterol levels. And the studies to date have achieved proof of concept: Unless you have healthy testosterone levels (this goes for both men and women), you’re not going to have a hot sex life, if any at all. And what makes testosterone? Cholesterol. What are millions of Americans doing today? Lowering their cholesterol levels through diet and/or taking statins. In the meanwhile, they are lowering their libido and ability to perform. Is it any wonder there’s an epidemic of erectile dysfunction (ED) and demand for ED drugs today, not to mention (perhaps ironically) testosterone replacement therapy? Plenty of studies have confirmed these connections.36 Decreased libido is one of the most common complaints among those taking statins, and lab reports ======================================== *** 高亮 2016/8/11 have repeatedly demonstrated low testosterone in statin consumers.37 Those on statins are twice as likely to have low testosterone levels. Luckily, this condition is reversible by stopping the statin and increasing cholesterol intake. There are actually 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. One study that came out in the United Kingdom in 2010 looked at 930 men with coronary heart disease and measured their testosterone levels.38 Low testosterone was found in 24 percent of the patients, and the risk of dying was 12 percent in those with normal testosterone but 21 percent in those with low testosterone. The conclusion was staring them in the face: If you have coronary disease and low testosterone, you’re at much greater risk of dying. So again we are giving statin medications to lower cholesterol, which lowers testosterone… and lower testosterone increases the risk of dying. Is this crazy or what? I rest my case. THE SWEET TRUTH I’ve covered a lot of ground in this chapter, mostly dealing with the role of fats on the brain. But we now have to ask ourselves the following: What happens when you inundate the brain with sugar instead? I started this chapter by addressing the ills of carbohydrates on our bodies, but I’ve saved the conversation about this particularly devastating carbohydrate for its own chapter. Unfortunately, this is a subject area that’s gotten remarkably little attention in the press. We increasingly hear about the relationship between sugar and “diabesity,” sugar and heart disease, sugar and fatty livers, sugar and metabolic syndrome, sugar and risk for cancer, etc…. but sugar and brain dysfunction? It’s time you got up close and personal with your brain on sugar. ======================================== *** 高亮 2016/8/12 Your liver takes care of the fructose component of sugar. Glucose from other carbs and starches, on the other hand, is 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. And your liver will also be taxed if it’s hit with liquid forms of these sugars, those found in soda or fruit juices. Drinking liquid sugar is not the same as eating, say, an equivalent dose of sugar in whole apples. Fructose, by the way, is the sweetest of all naturally occurring carbohydrates, which probably explains why we love it so much. But contrary to what you might think, it has the lowest glycemic index of all the natural sugars. The reason is simple: Because the liver metabolizes most of the fructose, 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. Don’t let that fact fool you, however. While fructose may not have an immediate effect, it has more long-term effects when it’s consumed in sufficient quantities from unnatural sources. And the science is well documented: Consuming fructose is associated with impaired glucose tolerance, insulin resistance, high blood fats, and hypertension. And because it does not trigger the production of insulin and leptin, two key hormones in regulating our metabolism, diets high in fructose lead to obesity and its metabolic repercussions. (I will clarify later what this means for those who enjoy eating lots of fruit. Fortunately, for the most part, you can have your fruit and eat it, too. The quantity of fructose in most whole fruit pales in comparison to the levels of fructose in processed foods.) ======================================== *** 高亮 2016/8/12 We hear about sugar and its effects on virtually every other part of the body except for the brain. This, again, is a subject area that’s gotten remarkably little attention in the press. The questions to ask, and which I’ll answer in this chapter, are: What does excess sugar consumption do to the brain? ======================================== *** 高亮 2016/8/12 Can the brain distinguish between different types of sugar? Does it “metabolize” sugar differently depending on where it’s coming from? If I were you, I’d put down that biscuit or biscotti you’re having with your coffee and buckle up. After reading this chapter, you’ll never look at a piece of fruit or sugary treat in quite the same way. ======================================== *** 高亮 2016/8/12 SUGAR AND CARBS 101 Let me begin by defining a few terms. What, exactly, is the difference between table sugar, fruit sugar, high-fructose corn syrup, and the like? Good question. As I’ve said, fructose is a type of sugar naturally found in fruit and honey. It’s a monosaccharide just like glucose, whereas table sugar (sucrose)—the white granulated stuff we sprinkle in coffee or dump into a bowl of cookie batter—is a combination of glucose and fructose, thus making it a disaccharide (two molecules linked together). High-fructose corn syrup, which is what we find in our sodas, juices, and many processed foods, is yet another combination of molecules dominated by fructose—it’s 55 percent fructose, 42 percent glucose, and 3 percent other carbohydrates. ======================================== *** 高亮 2016/8/12 . But you already know that not all carbohydrates are created equal. And not all carbohydrates are treated equally by the body. The differentiating feature is how much a certain carbohydrate will raise blood sugar and, in effect, insulin. Meals that are higher in carbohydrate, and especially those that are higher in simple glucose, cause the pancreas to increase its insulin output in order to store the blood sugar in cells. During the course of digestion, carbohydrates are broken down and sugar is liberated into the bloodstream, again causing the pancreas to increase its output of insulin so glucose can penetrate cells. Over time, higher levels of blood sugar will cause increased production of insulin output from the pancreas. ======================================== *** 高亮 2016/8/12 The carbs that trigger the biggest surge in blood sugar are typically the most fattening for that very reason. They include anything made with refined flour (breads, cereals, pastas); starches such as rice, potatoes, and corn; and liquid carbs like soda, beer, and fruit juice. They all get digested quickly because they flood the bloodstream with glucose and stimulate a surge in insulin, which then packs away the excess calories as fat. What about the carbs in a vegetable? Those carbs, especially the ones in leafy green vegetables such as broccoli and spinach, are tied up with indigestible fiber, so they take longer to break down. The fiber essentially slows down the process, causing a slower funneling of glucose into the bloodstream. Plus, vegetables contain more water relative to their weight than starches, and this further dampens the blood sugar response. When we eat whole fruits, which obviously contain fruit sugar, the water and fiber will also “dilute” the blood sugar effect. If you take, for instance, a peach and a baked potato of equal weight, the potato will have a much bigger effect ======================================== *** 高亮 2016/8/12 on blood sugar than the watery, fibrous peach. That’s not to say the peach, or any other fruit for that matter, won’t cause problems. ======================================== *** 高亮 2016/8/12 Our caveman ancestors did in fact eat fruit, but not every day of the year. We haven’t yet evolved to be able to handle the copious amounts of fructose we consume today—especially when we get our fructose from manufactured sources. Natural fruit has relatively little sugar, when compared to, say, a can of regular soda, which has a massive amount. A medium-sized apple contains about 44 calories of sugar in a fiber-rich blend thanks to the pectin; conversely, a 12-ounce can of Coke or Pepsi contains nearly twice that—80 calories of sugar. If you juice several apples and concentrate the liquid down to a 12-ounce beverage (thereby losing the fiber), lo and behold you get a blast of 85 sugar calories that could just as well have come from a soda. When that fructose hits the liver, most of it gets converted to fat and sent to our fat cells. No wonder fructose was called the most fattening carbohydrate more than forty years ago by biochemists. And when our bodies get used to performing this simple conversion with every meal, we can fall into a trap in which even our muscle tissue becomes resistant to insulin. Gary Taubes describes this domino effect brilliantly in Why We Get Fat: “So, even though fructose has no immediate effect on blood sugar and insulin, over time—maybe a few years—it is a likely cause of insulin resistance and thus the increased storage of calories as fat. The needle on our fuel-partitioning gauge will point toward fat storage, even if it didn’t start out that way.” ======================================== *** 高亮 2016/8/12 The most disturbing fact about our addiction to sugar is that when we combine fructose and glucose (which we often do when we eat foods made with table sugar), the fructose might not do much to our blood sugar right away, but the accompanying glucose takes care of that—stimulating insulin secretion and alerting the fat cells to prepare for more storage. The more sugars we eat, the more we tell our bodies to transfer them to fat. This happens not only in the liver, leading to a condition called fatty liver disease, but elsewhere in the body as well. Hello, love handles, muffin tops, beer bellies, and the worse kind of fat of all—invisible visceral fat that hugs our vital organs. I love how Taubes draws a parallel between the cause-and-effect relationship uniting carbohydrates and obesity, and the link between smoking and cancer: If the world had never invented cigarettes, lung cancer would be a rare disease. Likewise, if we didn’t eat such high-carb diets, obesity would be a rare condition.6 I’d bet that other related conditions would be uncommon as well, including diabetes, heart disease, dementia, and cancer. And if I had to name the kingpin here in terms of avoiding all manner of disease, I’d say “diabetes.” That is to say, don’t become diabetic. ======================================== *** 高亮 2016/8/12 THE DEATH KNELL IN DIABETES I cannot reiterate enough the importance of avoiding the path to diabetes, and if diabetes is already a card you’re playing with, then keeping blood sugars balanced is key. In the United States there are close to 11 million adults sixty-five years or older with type 2 diabetes, which speaks volumes to the magnitude of the potential catastrophe on our hands if all of these individuals—plus the ones who haven’t been officially diagnosed yet—develop Alzheimer’s. The data that supports the relationship between diabetes and Alzheimer’s disease is profound, but it’s important to understand that diabetes is a powerful risk factor for simple cognitive decline. This is especially true in individuals whose diabetes is under poor control. Case in point: In June 2012, the Archives of Neurology published an analysis of 3,069 elderly adults to determine if diabetes increased the risk of cognitive decline and if poor blood sugar control was related to worse cognitive performance.7 When first evaluated, about 23 percent of the participants actually had diabetes, while the remaining 77 percent did not (the researchers intentionally chose a “diverse group of well-functioning older adults”). A small percentage, however, of that 77 percent went on to develop diabetes during the nine-year study. At the beginning of the study a panel of cognitive tests was performed, and over the next nine years these tests were repeated. The conclusion stated the following: “Among well-functioning older adults, DM [diabetes mellitus] and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.” The researchers demonstrated a fairly dramatic difference in the rate of mental decline among those with diabetes as compared to the non-diabetics. More interesting still, they also noted that even at the start of the study, baseline cognitive scores of the diabetics were already lower than the controls.’ The study also found a direct relationship between the rate of cognitive decline and higher levels of hemoglobin A1C, a marker of blood glucose control. The authors stated, “Hyperglycemia (elevated blood sugar) has been proposed as a mechanism that may contribute to the association between diabetes and reduced cognitive function.” They went on to state that “hyperglycemia may contribute to cognitive impairment through such mechanisms as the formation of advanced glycation end products, inflammation, and microvascular disease.” ======================================== *** 高亮 2016/8/12 Before I get to explaining what advanced glycation end products are and how they are formed, let’s turn to one more study done earlier, in 2008. This one, from the Mayo Clinic and published in the Archives of Neurology, looked at the effects of the duration of diabetes. In other words, does how long one has diabetes play into the severity of cognitive decline? You bet. The numbers are eye-popping: According to the Mayo’s findings, if diabetes began before a person was sixty-five years old, the risk for mild cognitive impairment was increased by a whopping 220 percent. And the risk of mild cognitive impairment in individuals who had diabetes for ten years or longer was increased by 176 percent. If people were taking insulin, their risk was increased by 200 percent. The authors described a proposed mechanism to explain the connection between persistent high blood sugar and Alzheimer’s disease: “increased production of advanced glycation end products.”8 Just what are these glycation end products cropping up in the medical literature in reference to cognitive decline and accelerated aging? I mentioned them briefly in the previous chapter, and I will explain their significance in the next section. ======================================== *** 高亮 2016/8/12 While mad cow disease isn’t usually classified with classic neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease, all the conditions have a similar deformation in the structure of proteins needed for normal, healthy functioning. Granted, Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease are not transmissible to people like mad cow is, but they nevertheless result in similar features that scientists are just beginning to understand. And it all boils down to deformed proteins. ======================================== *** 高亮 2016/8/12 Much in the way we now know that dozens of degenerative diseases are linked by inflammation, we also know that dozens of those same diseases—including type 2 diabetes, cataracts, atherosclerosis, emphysema, and dementia—are linked to deformed proteins. What makes prion diseases so unique is the ability of those abnormal proteins to confiscate the health of other cells, turning normal cells into misfits that lead to brain damage and dementia. It’s similar to cancer in that one cell hijacks the normal regulation of another cell and creates a new tribe of cells that don’t act like healthy ones. Working in laboratories with mice, scientists are finally collecting evidence to show that major neurodegenerative conditions follow parallel patterns.9 ======================================== *** 高亮 2016/8/13 Most doctors employ a measurement of one glycated protein routinely in their medical practice. I’ve already mentioned it: hemoglobin A1C. This is the same standard laboratory measurement used to measure blood sugar control in diabetics. So, while your doctor may be measuring your hemoglobin A1C from time to time to get an understanding of your blood sugar control, the fact that it’s glycated protein has vast and extremely important implications for your brain health. But hemoglobin A1C represents more than just a simple measurement of average blood sugar control over a 90-to 120-day period. Hemoglobin A1C is the protein found in the red blood cell that carries oxygen and binds to blood sugar, and this binding is increased when blood sugar is elevated. While hemoglobin A1C doesn’t give a moment-to-moment indication of what the blood sugar is, it is extremely useful in that it shows what the “average” blood sugar has been over the previous ninety days. This is why hemoglobin A1C is frequently used in studies that try to correlate blood sugar control to various disease processes like Alzheimer’s, mild cognitive impairment, and coronary artery disease. It’s well documented that 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. These correlations have been shown to be strongest with any measurement of hemoglobin A1C above 6.0 percent. ======================================== *** 高亮 2016/8/13 As I’ve already described, having normal blood sugar levels may mean that the pancreas is working overtime to keep that blood sugar normal. Based upon this understanding, you can see that high insulin levels will happen long before blood sugar rises and a person becomes diabetic. That’s why it’s so important to check not only your fasting blood sugar, but also your fasting insulin level. ======================================== *** 高亮 2016/8/13 An elevated fasting insulin level is an indicator that your pancreas is trying hard to normalize your blood sugar. It’s also a clear signal that you are consuming too much carbohydrate. And make no mistake about it: Even being insulin resistant is a powerful risk factor for brain degeneration and cognitive impairment. It’s not good enough to look at the diabetes data as it relates to brain disease and be confident that your risk has been ameliorated because you are not diabetic. And if your blood sugar happens to be normal, the only way you will know if you are insulin resistant is to have your fasting blood insulin level checked. Period. ======================================== *** 高亮 2016/8/13 . Overall, the lower the insulin level, the better. The average insulin level in the United States is about 8.8 micro international units per milliliter (µIU/mL) for adult men and 8.4 for women. But with the degree of obesity and carbohydrate abuse in America, it’s safe to say that these “average” values are likely much higher than what should be considered ideal. Patients who are being very careful about their carbohydrate intake might have insulin levels indicated on their lab report as less than 2.0. This is an ideal situation—a sign that the individual’s pancreas is not being overworked, blood sugars are under excellent control, there is very low risk for diabetes, and there is no evidence of insulin resistance. The important point is that if your fasting insulin level is elevated—anything over five should be considered elevated—it can improve, and I will show you how to do that in chapter 10. ======================================== *** 高亮 2016/8/13 Most everyone has a pretty good idea that carrying around extra weight is unhealthy. But if you needed just one more reason to drop the excess pounds, perhaps the fear of losing your mind—physically and literally—will help motivate you. ======================================== *** 高亮 2016/8/13 When I was studying to be a doctor, the prevailing wisdom was that fat cells were primarily storage bins where unwanted masses of excess could hang out silently on the sidelines. ======================================== *** 高亮 2016/8/13 hang out silently on the sidelines. But that was a grossly misguided perspective. Today we know that fat cells do more than simply store calories; they are far more involved in human physiology. Masses of body fat form complex, sophisticated hormonal organs that are anything but passive. You read that right: Fat is an organ.18 And it could very well be one of the body’s most industrious organs, serving a lot of functions beyond keeping us warm and insulated. This is especially true of visceral fat—the fat wrapped around our internal, “visceral” organs such as the liver, kidneys, pancreas, heart, and intestines. Visceral fat has also gotten a lot of press lately: We know now that this type of fat is the most devastating to our health. We may lament our thunder thighs, under-arm curtains, love handles, cellulite, and big butts, but the worst kind of fat is the kind many of us cannot even see, feel, or touch. In extreme cases we do see it in the bulging bellies and muffin tops that are the outward signs of fat-enveloped internal organs belowdecks. (For this very reason, waist circumference is often a measurement of “health,” as it predicts future health challenges and mortality; the higher your waist circumference, the higher your risk for disease and death.19) ======================================== *** 高亮 2016/8/13 The dots connecting excessive body fat, obesity, and brain dysfunction are not hard to follow given the information you’ve already learned in this book. Excessive body fat increases not only insulin resistance, but also the production of inflammatory chemicals that play directly into brain degeneration. ======================================== *** 高亮 2016/8/13 In a 2005 study, the waist-to-hip ratios of more than 100 individuals were compared to structural changes in their brains.21 The study also looked at brain changes in relation to fasting blood sugar and insulin levels. What the authors wanted to determine was whether or not a relationship existed between the brain’s structure and the size of a person’s belly. And the results were striking. Essentially, the larger a person’s waist-to-hip ratio (i.e., the bigger the belly), the smaller the brain’s memory center, the hippocampus. The hippocampus plays a critical role in memory, and its function is absolutely dependent upon its size. As your hippocampus shrinks, your memory declines. More striking still, the researchers found that the higher the waist-to-hip ratio, the higher the risk for small strokes in the brain, also known to be associated with declining brain function. The authors stated: “These results are consistent with a growing body of evidence that links obesity, vascular disease, and inflammation to cognitive decline and dementia.” Other studies since then have confirmed the finding: For every excess pound put on the body, the brain gets a little smaller. How ironic that the bigger the body gets, the smaller the brain gets. ======================================== *** 高亮 2016/8/13 In a joint research project between UCLA and the University of Pittsburgh, neuroscientists examined brain images of ninety-four people in their seventies who had participated in an earlier study of cardiovascular health and cognition.22 None of the participants had dementia or other cognitive impairments, and they were followed for five years. What these researchers found was that the brains of obese people—defined by having a body mass index above 30—looked sixteen years older than their healthy counterparts of normal weight. And those who were overweight—defined by having a body mass index between 25 and 30—looked eight years older than their leaner counterparts. More specifically, the clinically obese people had 8 percent less brain tissue, while the overweight had 4 percent less brain tissue compared to normal-weight individuals. Much of the tissue was lost in the frontal and temporal lobe regions of the brain, the place from which we make decisions and store memories, among other things. The authors of the study rightfully pointed out that their findings could have serious implications for aging, overweight, or obese individuals, including a heightened risk for Alzheimer’s disease. Without a doubt, vicious cycles are at play here, each of which is contributing to the other. Genetics could affect one’s propensity to overeat and gain weight, and this then factors into activity levels, insulin resistance, and risk for diabetes. Diabetes then affects weight control and blood sugar balance. Once a person becomes diabetic and sedentary, it’s inevitable that a breakdown in tissues and organs occurs, and not just in the brain. What’s more, once the brain begins to degenerate and physically shrink, it begins to lose its ability to ======================================== *** 高亮 2016/8/13 function properly. That is to say, the brain’s appetite and weight-control centers won’t be firing on all cylinders and could actually be misfiring, and this again feeds the vicious cycle. ======================================== *** 高亮 2016/8/13 As study after study has proven, weight loss through dieting can have a dramatic effect on insulin signaling and insulin sensitivity. In one report, doctors evaluated 107 obese individuals at least sixty-five years of age over a ======================================== *** 高亮 2016/8/13 So the take-home lesson is clear: You can improve insulin sensitivity and reduce your risk of diabetes (not to mention all manner of brain diseases) simply by making lifestyle changes that melt that fat away. And if you add exercise to the dieting, you’ll stand to gain even bigger benefits. By now you should know that I’m going to prescribe a low-carb diet rich in healthy fats, including cholesterol. And don’t take my word for it. Just turn to the latest studies proving the power of this type of diet. Last year the Journal of the American Medical Association published the effects of three popular diets on a group of overweight or obese young adults.25 Each of the participants tried each of the diets for a month—one was low-fat (60 percent of the calories came from carbohydrate, 20 percent from fat, and 20 percent from protein), one was low-glycemic (40 percent of the calories came from carbohydrate, 40 percent from fat, and 20 percent from protein), and the third was a very low carbohydrate diet (10 percent of the calories came from carbohydrates, 60 percent from fat, and 30 percent from protein). All of the diets provided the same number of calories, but those on the low-carb, high-fat diet burned the most calories. The study also looked at insulin sensitivity during the four-week period on each diet, finding that the low-carb diet triggered the biggest improvement in insulin sensitivity—almost twice that of the low-fat diet. Triglycerides, a powerful cardiovascular risk marker, averaged 66 in the low-carb group and 107 in the low-fat group. (As an aside, elevated triglyceride levels are also a hallmark of too many carbs in the diet.) The authors pointed out that the lab results they measured in the low-fat diet showed changes in people’s blood chemistry that left them vulnerable to weight gain. Clearly, the best diet for maintaining weight loss is a low-carbohydrate, high-fat one. ======================================== *** 高亮 2016/8/13 Many other studies have arrived at the same conclusion: A low-carb, high-fat diet will outperform a low-fat, high-carb diet any day, and by virtually every measure in the body, from its internal chemistry to its external waistline. And when we consider all of the parameters that affect health, and specifically brain health, such as weight loss, insulin sensitivity, blood sugar control, and even C-reactive protein, a low-carbohydrate diet is substantially more effective than any other diet. Those other diets will result in outcomes that heighten your risk for a multitude of brain dysfunctions, from daily nuisances like headaches to chronic migraines, anxiety disorders, ADHD, and depression. And if the thought of being as sharp as a whip until your last breath on earth isn’t enough to motivate you, then consider all the benefits that your heart (and virtually every organ in your body) will gain by ditching a low-fat diet. In March 2013, the New England Journal of Medicine published a large landmark study showing that ======================================== *** 高亮 2016/8/13 people age fifty-five to eighty who ate a Mediterranean diet were at lower risk of heart disease and stroke—by as much as 30 percent—than those on a typical low-fat diet.26 The results were so profound that scientists halted the study early because the low-fat diet proved too damaging for the people eating lots of commercially baked goods rather than sources of healthy fats. The Mediterranean diet is famous for being rich in olive oil, nuts, beans, fish, fruits and vegetables, and even wine with meals. Although it does allow room for grains, it’s very similar to my dietary protocol. In fact, if you modify the traditional Mediterranean diet by removing all gluten-containing foods and limiting sugary fruits and non-gluten carbs, you have yourself the perfect grain-brain-free diet. ======================================== *** 高亮 2016/8/13 Does every cocktail you drink really kill thousands of brain cells? As it turns out, we are not stuck with the number of neurons we’re born with, or even those that develop in early childhood. 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. I’ve been lucky enough to participate in this discovery that has overturned generations of conventional wisdom in neuroscience, though many people still believe otherwise. During my college years I was given the opportunity to explore the brain using technology that was just in its infancy. It was in the early 1970s, and the Swiss had begun developing microscopes that could be used by neurosurgeons performing delicate brain procedures. While this technology was evolving and surgeons in the United States were eager to adopt this new approach to brain surgery, a problem soon became evident. While learning to actually use the operating microscope was relatively easy, the neurosurgeons found that they were becoming somewhat lost in terms of understanding the anatomy of the brain from this new microscopic perspective. I was nineteen years old and just starting my junior year in college when I received a phone call from Dr. Albert Rhoton, chairman of the Department of Neurological Surgery at Shands Teaching Hospital in Gainesville, Florida. Dr. Rhoton was leading the way for expansion of the use of the operating ======================================== *** 高亮 2016/8/13 microscope in the United States and wanted to create the first anatomy text of the brain as seen through the microscope. He invited me to spend the following summer studying and mapping the brain, and it was from this research that we eventually published a series of research papers and book chapters that gave neurosurgeons the needed roadmap to more carefully operate on the brain. ======================================== *** 高亮 2016/8/13 In addition to anatomy, we also had the opportunity to explore and develop other aspects of microneurosurgery, including innovative instruments and procedures. Spending so much time behind the microscope, I had become quite adept at manipulating and repairing extremely small blood vessels that, prior to the use of the microscope, would have been destroyed during brain operations, often with dire consequences. Our lab had gained international recognition for its achievements in this new and exciting field and often attracted visiting professors from around the world. And it was soon after a delegation of Spanish neurosurgeons had visited that I found myself accepting an invitation to continue my research at the prestigious Centro Ramón y Cajal in Madrid, Spain. Their microneurosurgery program was in its infancy, but their team was dedicated, and I felt honored to be assisting them in their groundwork efforts, especially those dealing with understanding the brain’s blood supply. The hospital was named in honor of Dr. Santiago Ramón y Cajal, a Spanish pathologist and neuroscientist working at the turn of the twentieth century, who is still regarded as the father of modern neurology; images of him on the walls were numerous and there was clearly a deep sense of pride among my Spanish colleagues that they could claim such an influential scientist as their own. In 1906 he won the Nobel Prize in medicine for his pioneering investigations of the microscopic structure of the brain. Today, hundreds of his handmade drawings are still used for educational purposes. During my visit to Madrid I was compelled to learn more about Dr. Cajal and came to deeply respect his explorations of human brain anatomy and function. One of his major tenets held that brain neurons were unique compared to other cells of the body, not only because of their function, but also because they lacked the ability to regenerate. The liver, for example, perpetually regenerates by growing new liver cells, and similar regeneration of cells occurs in virtually all other tissues, including skin, blood, bone, and intestines. ======================================== *** 高亮 2016/8/13 admit that I was pretty well sold on this theory that brain cells do not regenerate, but I did wonder back then why it wouldn’t make sense for the brain to retain the ability to regenerate—to have the ability to grow new brain neurons. After all, researchers at the Massachusetts Institute of Technology had shown previously that neurogenesis, the growth of new brain neurons, occurred throughout the entire lifetime in rats. And so much about the human body is regeneration; it relies on continuous self-renewal to survive. For example, certain blood cells turn over every few hours, taste receptor cells get replaced every ten days, skin cells turn over every month, and muscle cells take about fifteen years to completely renew themselves. In the last decade, scientists have determined that the heart muscle—an organ that we long thought was “fixed” since birth—does in fact experience cellular turnover as well.1 When we’re twenty-five years old, about 1 percent of our heart muscle cells are replaced every year; but by the age of seventy-five, that rate has fallen to less than half a percent per year. Hard to believe that we’ve only recently come to identify and understand this phenomenon in the body’s blood-pumping machine. And now we’ve finally decoded the brain and discovered its self-renewing qualities. ======================================== *** 高亮 2016/8/14 . In his seminal 1928 book Degeneration and Regeneration of the Nervous System, Cajal stated: “In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated.”2 If I could change his statement to reflect what we know today, I’d swap out the words fixed, ended, and immutable for the absolute opposite: pliable, open-ended, and alterable. I’d also say that brain cells may die, but they most certainly can be regenerated. Indeed, Cajal made great contributions to our knowledge of the brain and how neurons work; he was even ahead of his time in trying to understand the pathology of inflammation. But his belief that the brain was somehow stuck with its bill of goods is one that pervaded for most of human history—until modern science in the late twentieth century proved just how flexible the brain could be. ======================================== *** 高亮 2016/8/14 In my previous book, Power Up Your Brain: The Neuroscience of Enlightenment, Dr. Alberto Villoldo and I told the story of how science has come to understand the gift of neurogenesis in humans. Although scientists have long proven neurogenesis in various other animals, it wasn’t until the 1990s that scientists began focusing exclusively on trying to demonstrate neurogenesis in humans.3 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.4 And indeed, he was right: We all experience brain “stem cell therapy” every minute of our lives. This has led to a new science called neuroplasticity. ======================================== *** 高亮 2016/8/14 I’m going to save the bulk of this conversation for chapter 8, which explores in great depth the role of exercise in preventing cognitive decline. The science is stunning. Physical exercise is one of the most potent ways of changing your genes; put simply, when you exercise, you literally exercise your genes. Aerobic exercise in particular not only turns on genes linked to longevity, but also targets the BDNF gene, the brain’s “growth hormone.” More specifically, aerobic exercise has been shown to increase BDNF, reverse memory decline in elderly humans, and actually increase growth of new brain cells in the brain’s memory center. Exercise isn’t just for trim looks and a strong heart; perhaps its most powerful effects are going on silently in the upstairs room where our brains reside. The emerging scientific view of human evolution and role of physical activity gives a whole new meaning to the phrase “jog your memory.” A million years ago, we triumphed over long distances because we could outrun and outwalk most other animals. This ultimately helped make us the clever human beings we are today. The more we moved, the fitter our brain became. And even today our brain’s healthy functioning requires regular physical activity despite the passage of time and ills of the aging process ======================================== *** 高亮 2016/8/14 In 2008, Dr. Veronica Araya from the University of Chile in Santiago reported on a study she performed during which she placed overweight and obese subjects on a three-month calorie-restricted diet, with a total reduction of 25 percent of calories.15 She and her colleagues measured an exceptional increase in BDNF production, which led to notable reductions in appetite. It’s also been shown that the opposite occurs: BDNF production is decreased in animals on a diet high in sugar.16 One of the most well-studied molecules associated with caloric restriction and the growth of new brain cells is sirtuin-1 (SIRT1), an enzyme that regulates gene expression. In monkeys, increased SIRT1 activation enhances an enzyme that degrades amyloid—the starch-like protein whose accumulation is the hallmark of diseases like Alzheimer’s.17 In addition, SIRT1 activation changes certain receptors on cells, leading to reactions that have the overall effect of reducing inflammation. Perhaps most important, activation of the sirtuin pathway by caloric restriction enhances BDNF. BDNF not only increases the number of brain cells, but also enhances their differentiation into functional neurons (again, because of caloric restriction). For this reason, we say that BDNF enhances learning and memory. ======================================== *** 高亮 2016/8/14 Now this is where the story gets really exciting. New research has identified a variety of modifiable factors that can turn on the Nrf2 switch, activating genes that can produce powerful antioxidants and detoxification enzymes. Vanderbilt University’s Dr. Ling Gao has found that 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 (the source of EPA and DHA), but with this new research, the relationship between fish oil and antioxidant protection is now clear. As Dr. Gao reported, “Our data support the hypothesis that the formation of… compounds generated from oxidation of EPA and DHA in vivo can reach concentrations high enough to induce Nrf2-based antioxidant and… detoxification defense systems.”38 ======================================== *** 高亮 2016/8/15 IF SUGARS AND GLUTEN-FILLED CARBS, including your daily whole-grain breads and favorite comfort foods, are slowly impinging on your brain’s long-term health and functionality, what else can these ingredients do on a more short-term basis? Can they trigger changes in behavior, seize control of focus and concentration, and underlie some tic disorders and mood conditions like depression? Can they be the culprit in chronic headaches and even migraines? Yes, they can. The facts of “grain brain” go far beyond just hampering neurogenesis and increasing your risk for cognitive challenges that will progress stealthily over time. As I’ve already hinted at throughout the previous chapters, a diet heavy in inflammatory carbs and low in healthy fats messes with the mind in more ways than one—affecting risk not just for dementia but for common neurological ailments such as ADHD, anxiety disorder, Tourette’s syndrome, mental illness, migraines, and even autism. Up until now, I’ve focused primarily on cognitive decline and dementia. Now, let’s turn to gluten’s destructive effects on the brain from the perspective of these common behavioral and psychological disorders. I’ll start with the afflictions that are often diagnosed in young children, and then move on to cover a wider array of issues that are found in people of every age. One thing will be clear: The removal of gluten from the diet and the adoption of a grain-brain-free way of life is often the surest ticket to relief for these brain ailments that plague millions, and this simple “prescription” can often trump drug therapy. ======================================== *** 高亮 2016/8/15 Attention deficit hyperactivity disorder (ADHD) is one of the most frequent diagnoses offered in the pediatrician’s office. Parents of hyperactive children are led to believe that their children have some form of a disease that will limit their ability to learn. The medical establishment too often convinces parents that medication is the best “quick fix.” The whole notion that ADHD is a specific ======================================== *** 高亮 2016/8/15 disease easily remedied by a pill is convenient but alarming. In several schools throughout the United States as many as 25 percent of students are routinely receiving powerful, mind-altering medications, the long-term consequences of which have never been studied! ======================================== *** 高亮 2016/8/15 It’s a heartbreaking fact: Depression is the leading cause of disability worldwide. It’s also the fourth leading contributor to the global burden of disease. The World Health Organization has estimated that by the year 2020, depression will become the second largest cause of suffering—next only to heart disease. In many developed countries, such as the United States, depression is already among the top causes of mortality.19 ======================================== *** 高亮 2016/8/16 An untold number of things can trigger a headache, from a bad night’s sleep or changes in the weather to chemicals in foods, sinus congestion, head trauma, brain tumors, or too much alcohol. The exact biochemistry of headaches, especially migraines, is under active study. But we know a lot more today than we ever did before. And for those sufferers who can’t nail down a reason (and thus a likely solution) for their headaches, my bet is that nine times out of ten that reason could be undiagnosed gluten sensitivity. ======================================== *** 高亮 2016/8/16 Numerous things can trigger a headache. I cannot possibly list all of the potential offenders, but I can offer a few tips to end the suffering: Keep a very strict sleep-wake cycle. This is key to regulating your body’s hormones and maintaining homeostasis—the body’s preferred state of being, where its physiology is balanced. Lose the fat. The more you weigh, the more likely it is that you’ll suffer from headaches. Stay active. Remaining sedentary breeds inflammation. Watch caffeine and alcohol use. Each of these in excess can stimulate a headache. Don’t skip meals or keep erratic eating habits. As with sleep, your eating patterns control many hormonal processes that can affect your risk for a headache. ======================================== *** 高亮 2016/8/16 Manage emotional stress, anxiety, worry, and even excitement. These emotions are among the most common triggers of headaches. Migraine sufferers are generally sensitive to stressful events, which prompt the release of certain chemicals in the brain that can provoke vascular changes and cause a migraine. Adding insult to injury, emotions such as anxiety and worry can increase muscle tension and dilate blood vessels, intensifying the severity of the migraine. Go gluten-, preservative-, additive-, and processed-free. The low-glycemic, low-carb, high–healthy-fat diet outlined in chapter 11 will go a long way to reducing your risk for headaches. Be especially careful about aged cheese, cured meats, and sources of monosodium glutamate (MSG, commonly found in Chinese food), as these ingredients may be responsible for triggering up to 30 percent of migraines. Track the patterns in your headache experience. It helps to know when you’re at a greater risk of getting one so you can pay extra attention during those times. Women, for example, can often trace patterns around their menstrual cycle. If you can define your patterns, you can better understand your unique headache and act accordingly. ======================================== *** 高亮 2016/8/16 . Remember, if you do nothing else recommended in this book but eliminate gluten and refined carbohydrates, you will experience profound positive effects beyond those described in this chapter. In addition to watching your mood brighten up, you’ll watch your weight go down and your energy soar in just a few weeks. Your body’s innate healing capacities will be in high gear, as will your brain’s functionality. ======================================== *** 高亮 2016/8/16 . In this section of the book, we examine three key habits: diet, exercise, and sleep. Each of these plays a significant role in whether or not your brain thrives or begins to falter. And with the lessons gleaned in this part, you’ll be fully prepared to execute the four-week protocol outlined in part 3. ======================================== *** 高亮 2016/8/16 What happens when you substantially reduce your carbohydrate intake and derive more of your calories from fat? I just finished explaining the benefits of fasting, which stimulates the brain to turn to fat for fuel in the form of ketones. A similar reaction takes place when you follow a diet low in carbohydrates and rich in healthy fats and proteins. This is the foundation of the Grain Brain dietary protocol. ======================================== *** 高亮 2016/8/16 lean and served us well in our hunter-gatherer days. As you already know, eating carbohydrates stimulates insulin production, which leads to fat production, fat retention, and a reduced ability to burn fat. What’s more, as we consume carbohydrates we stimulate an enzyme called lipoprotein lipase that tends to drive fat into the cell; the insulin secreted when we consume carbohydrates makes matters worse by triggering enzymes that lock fat tightly into our fat cells. As I’ve also described, when we burn fat as opposed to carbohydrate, we enter ketosis. There’s nothing inherently bad about it, and our bodies have been equipped for this activity for as long as we’ve roamed Earth. Being in a mild ketosis state is actually healthy. We are mildly ketotic when we first wake up in the morning, as our liver is mobilizing body fat to use as fuel. Both the heart and the brain run more efficiently on ketones than on blood sugar, by as much as 25 percent. Healthy, normal brain cells thrive when fueled by ketones. Certain brain tumor cells, however, can only use glucose as fuel. Standard treatment for glioblastoma, one of the most aggressive types of brain tumor, is surgery, radiation therapy, and chemotherapy. But quite honestly, results from these approaches are fairly dismal. Taking advantage of the fact that glioblastoma cells can only use glucose, and not ketones, Dr. Giulio Zuccoli of the University of Pittsburgh School of Medicine reasoned that a ketogenic diet might actually prove effective in treating glioblastoma along with traditional treatments.4 And, in fact, he published a case report of treating a glioblastoma patient using a ketogenic diet with impressive results. If a ketogenic diet can prolong the life of a cancer patient, what can it do in a healthy individual? ======================================== *** 高亮 2016/8/16 The high-carb diet I put you on twenty years ago gave you diabetes, high blood pressure, and heart disease. Oops.” I love a cartoon that offers a nugget of wisdom in a matter of eyebrow-raising seconds, the time it takes to absorb the image and caption. The one above caught my eye years ago; I only wish more doctors were as smart as cartoonist Randy Glasbergen. Given all the science we’ve accumulated since this cartoon was first published in 2004, we can add “and set you up for brain disease” to this caption. ======================================== *** 高亮 2016/8/16 . Suffice it to say, DHA is one of the most well-documented darlings in protecting the brain. I often ask doctors in my lectures what they think the richest source of DHA is in nature. I hear all kinds of answers—cod-liver oil, salmon oil, anchovy oil. Some guess flaxseed oil or avocados, but those don’t contain adequate DHA. The richest source of DHA in nature is human breast milk. Which explains why breast-feeding is continually touted as important for the neurologic health and long-term performance of a child. ======================================== *** 高亮 2016/8/16 Plenty of high-quality DHA supplements are available today, and there are more than 500 food products that are enriched with DHA. It doesn’t really matter whether you buy DHA that’s derived from fish oil or from algae. Opt for the algae-derived variety if you’re a strict vegetarian ======================================== *** 高亮 2016/8/16 Resveratrol: The magic behind the health benefits of drinking a glass of red wine a day has a lot to do with this natural compound found in grapes, which not only slows down the aging process, boosts blood flow to the brain, and promotes heart health, but also curbs fat cells by inhibiting their development. You can’t get enough resveratrol in that glass of wine, though. Hence the need to supplement with higher doses to reap the benefits. ======================================== *** 高亮 2016/8/16 Because this so-called miracle molecule protects cells against a remarkable range of diseases, it’s frequently touted as an assistant in the body’s immune and defense system. Within the last decade we’ve come to learn just how this is possible, thanks largely to the work of Harvard’s Dr. David Sinclair, who discovered the supplement’s ability to activate certain genes called sirtuins, which affect longevity.5 In 2010, scientists at Northumbria University in the United Kingdom published a study in the American Journal of Clinical Nutrition that discussed exactly why resveratrol can be so effective in optimizing brain function.6 In it, they explained that they gave twenty-four students resveratrol and recorded marked increases in blood flow in the brain while they were performing mental tasks. And the harder the tasks, the greater resveratrol’s effect. ======================================== *** 高亮 2016/8/16 Turmeric: Turmeric (Curcuma longa), a member of the ginger family, is the subject of intense scientific research, much of it evaluating the anti-inflammatory and antioxidant activities that stem from its active ingredient, curcumin. Turmeric is the seasoning that gives curry powder its yellow color, and as I mentioned earlier, it has been used for thousands of years in Chinese and Indian medicine as a natural remedy for a variety of ailments. In a report for the American Journal of Epidemiology, researchers investigated the association between curry consumption level and cognitive function in elderly Asians.7 Those who ate curry “occasionally” and “often or very often” scored much better on specific tests designed to measure cognitive function than did people who “never or rarely” consumed curry. ======================================== *** 高亮 2016/8/16 One of curcumin’s secret weapons is its ability to activate genes to produce a vast array of antioxidants that serve to protect our precious mitochondria. It also improves glucose metabolism. All of these properties help reduce risk for brain disease. Unless you make lots of curry dishes at home, you probably don’t get a lot of turmeric in your diet on a regular basis. ======================================== *** 高亮 2016/8/16 The biology of how exercise can be so beneficial to brain health goes far beyond the argument that it promotes blood flow to the brain and thus delivers nutrients for cell growth and maintenance. Indeed, cerebral blood flow is a good thing. But that’s old news. The latest science behind the magic of movement in protecting and preserving brain function is stunning. It boils down to five benefits: controlling inflammation, increasing insulin sensitivity, influencing better blood sugar control, expanding the size of the memory center, and, as I’ve already mentioned, boosting levels of BDNF. ======================================== *** 高亮 2016/8/16 Some of the most compelling science has been performed in just the last couple of years.9 In 2011, Dr. Justin S. Rhodes and his team at the Beckman ======================================== *** 高亮 2016/8/16 Institute for Advanced Science and Technology at the University of Illinois made discoveries using four groups of mice in four different living arrangements.10 One group lived in the lap of luxury in a setting that included lavish, mice-friendly meals (nuts, fruits and cheeses, and flavored waters) and lots of playful toys to explore, such as mirrors, balls, and tunnels. The second group of mice had access to the same treats and toys, but their living quarters included running wheels. A third group’s cages resembled a Motel 6; they contained nothing extraordinary and the mice ate standard kibble. The fourth group of mice similarly lacked access to fancy amenities and food, but their home included running wheels. At the start of the study, the mice underwent a series of cognitive tests and were injected with a substance that allowed the researchers to track changes in their brain structures. Over the next several months, the scientists let the mice do whatever they wanted in their respective homes, after which the researchers re-tested the mice’s cognitive functions and examined their brain tissues. The one variable that clearly stood out above all others was whether or not the mice had a running wheel. It didn’t matter if they had things to play with in their cages. The animals that exercised were the ones who had healthier brains and outperformed on the cognitive tests. Those that didn’t run, even if their world was otherwise stimulating, didn’t improve cognitively. The researchers were specifically looking for cognitive improvements that implied a boost in complex thinking and problem solving. Only exercise proved key to that improvement. ======================================== *** 高亮 2016/8/16 Exercise has been proven to induce growth of new neurons in the brain, but the real miracle is that it also has been shown to help build novel networks in the brain. It’s one thing to give birth to brain cells, but another to organize those cells into a network that functions in harmony. We don’t get “smarter” just by making new brain cells. We have to be able to interconnect those cells into the existing neural network, otherwise they will roam around aimlessly and eventually die. One way to do this is to learn something new. In a 2007 study, newborn neurons in mice became integrated into the animals’ brain networks if the mice learned to navigate a water maze.12 This is a task that requires more cognitive power than physical ability. The researchers also noted that the newbie cells were limited in what they could do; they couldn’t, for example, help the mice perform other cognitive tasks beyond the maze. To do that, the mice would need to exert themselves physically, which would encourage those new cells to become spry and cognitively limber. And therein lies the secret benefit of exercise: It makes neurons nimble and able to multitask. We don’t know how exercise facilitates mental makeovers on a molecular level, but we do know that BDNF plays a role by strengthening cells and axons, fortifying the connections among neurons, and sparking neurogenesis. Neurogenesis increases the brain’s ability to learn new things, which in turn strengthens those new brain cells and further fortifies the neural network. Remember, too, that higher levels of BDNF are associated with a decrease in appetite. So for those individuals who have trouble controlling their appetite, this provides yet another impetus to exercise. ======================================== *** 高亮 2016/8/16 Okay, so exercise does a body and brain good. But how much? How rigorous? Do household chores and customary daily activities like gardening and taking out the trash count? To answer this, let’s turn to a study from Rush University’s Memory and Aging Project—the study that led to the graphics I showcased here. When Dr. Aron S. Buchman examined the effects of daily physical exercise on one’s risk for Alzheimer’s disease, he found dramatic differences between relatively sedentary people and those performing various types of activities, including simple acts like cooking, washing the dishes, playing cards, pushing a wheelchair, and cleaning. He managed to track people’s activity levels using a novel device called an ActiGraph, which is worn on the wrist to detect and quantify movement. The average age of the individuals, who did not have dementia, was eighty-two years. Of the original 716, 71 participants developed full-blown Alzheimer’s disease over the course of approximately 3.5 years of follow-up.16 The results of the study revealed that those individuals in the lowest 10 percent of daily physical activity had a 230 percent increased risk of developing Alzheimer’s disease compared to those in the highest 10 percent of physical activity. When the data was evaluated in terms of intensity of physical activity, the results were even more compelling. Comparing the people in the bottom 10 percent of intensity of physical activity to the individuals in the top 10 percent, Dr. Buchman and his team found that the risk of Alzheimer’s was nearly tripled in those who exerted themselves the least. Dr. Buchman rightfully articulated in his conclusions that we cannot underestimate the power of low-cost, easily accessible, and side-effect-free activities that may not entail formal exercise. The mere actions of daily living can provide brain-protective benefits at any age. ======================================== *** 高亮 2016/8/16 . Although we may not notice the side effects of poor sleep on a genetic level, we can certainly experience the other signs of chronic sleep deprivation: confusion, memory loss, brain fog, low immunity, obesity, cardiovascular disease, diabetes, and depression. ======================================== *** 高亮 2016/8/16 immunity, obesity, cardiovascular disease, diabetes, and depression. All of these conditions are uniquely tied to the brain. ======================================== *** 高亮 2016/8/17 . Over the course of the next month, you will achieve four important goals: 1. Shift your body away from relying on carbs for fuel and add brain-boosting supplements to your daily regimen. ======================================== *** 高亮 2016/8/17 .Incorporate a fitness routine into your schedule if you don’t already have one. 3. Work on getting restful, routine sleep seven days a week. 4. Establish a new rhythm and maintain healthy habits for life. I’ve broken down the program into four weeks, with each week devoted to focusing on one of these specific goals. In the days leading up to the first week, you should see your doctor to have certain tests performed that will give you a baseline. You’ll also use this time to get your kitchen organized, start your supplements, begin to wean yourself from carbs, and consider a one-day fast to kick-start the program. During week 1, “Focus on Food,” you’ll start my menu plans and execute my dietary recommendations. During week 2, “Focus on Exercise,” I’ll encourage you to start a regular workout program and give you ideas for moving more throughout the day. In week 3, “Focus on Sleep,” you’ll turn your attention to your sleep habits and follow a few simple tips to ensure that you’re achieving the best sleep possible every single night, weekends included. ======================================== *** 高亮 2016/8/17 Incorporate a fitness routine into your schedule if you don’t already have one. 3. Work on getting restful, routine sleep seven days a week. 4. Establish a new rhythm and maintain healthy habits for life. ======================================== *** 高亮 2016/8/17 During week 4, “Put It All Together,” I’ll help you put all the elements of this program together and equip you with strategies for permanently establishing these new behaviors in your life. Don’t second-guess your ability to succeed at this; I’ve designed this program to be as practical and easy to follow as possible. ======================================== *** 高亮 2016/8/17 Clear Out Your Kitchen In the days leading up to your new way of eating, you’ll want to take an inventory of your kitchen and eliminate items that you’ll no longer be consuming. Start by removing the following: ======================================== *** 高亮 2016/8/17 All sources of gluten (here for the full list), including whole-grain and whole-wheat forms of bread, noodles, pastas, pastries, baked goods, and cereals. • All forms of processed carbs, sugar, and starch: corn, yams, potatoes, sweet potatoes, chips, crackers, cookies, pastries, muffins, pizza dough, cakes, doughnuts, sugary snacks, candy, energy bars, ice cream/frozen yogurt/sherbet, jams/jellies/preserves, ketchup, processed cheese spreads, juices, dried fruit, sports drinks, soft drinks/soda, fried foods, honey, agave, sugar (white and brown), corn syrup, and maple syrup. • Packaged foods labeled “fat-free” or “low-fat” (unless they are authentically “fat-free” or “low-fat” and within the protocol, such as water, mustard, and balsamic vinegar). • Margarine, vegetable shortening, and any commercial brand of cooking oil (soybean, corn, cottonseed, canola, peanut, safflower, grape seed, sunflower, rice bran, and wheat germ oils)—even if they are organic. • Non-fermented soy (e.g., tofu and soy milk) and processed foods made with soy (look for “soy protein isolate” in list of ingredients; avoid soy cheese, soy burgers, soy hot dogs, soy nuggets, soy ice cream, soy yogurt). Note: Although some naturally brewed soy sauces are technically gluten-free, many commercial brands have trace amounts of gluten. If you need to use soy sauce in your cooking, use tamari soy sauce made with 100 percent soybeans and no wheat. Watch out for foods marked (and marketed) “gluten-free.” Some of these foods are fine because they never contained gluten to begin with. But many are labeled as such because they have been processed—their gluten has been ======================================== *** 高亮 2016/8/17 replaced by another ingredient such as cornstarch, cornmeal, rice starch, potato starch, or tapioca starch, all of which can be equally as offensive, raising blood sugar enormously. Also, trace amounts of gluten can remain. The term “gluten-free” has no legal meaning at the moment; the FDA has proposed a definition but has not yet finalized it. Be extra cautious about gluten-free sauces, gravies, and cornmeal products (e.g., tacos, tortillas, cereals, and corn chips). Restock The following items can be consumed liberally (go organic and local with your whole-food choices wherever possible; flash-frozen is fine, too): •Healthy fat: extra-virgin olive oil, sesame oil, coconut oil, grass-fed tallow and organic or pasture-fed butter, ghee, almond milk, avocados, coconuts, olives, nuts and nut butters, cheese (except for blue cheeses), and seeds (flaxseed, sunflower seeds, pumpkin seeds, sesame seeds, chia seeds) •Herbs, seasonings, and condiments: You can go wild here as long as you watch labels. Kiss ketchup and chutney good-bye but enjoy mustard, horseradish, tapenade, and salsa if they are free of gluten, wheat, soy, and sugar. There are virtually no restrictions on herbs and seasonings; be mindful of packaged products, however, that were made at plants that process wheat and soy. •Low-sugar fruit: avocado, bell peppers, cucumber, tomato, zucchini, squash, pumpkin, eggplant, lemons, limes •Protein: whole eggs; wild fish (salmon, black cod, mahimahi, grouper, herring, trout, sardines); shellfish and mollusks (shrimp, crab, lobster, mussels, clams, oysters); grass-fed meat, fowl, poultry, and pork (beef, lamb, liver, bison, chicken, turkey, duck, ostrich, veal); wild game •Vegetables: leafy greens and lettuces, collards, spinach, broccoli, kale, chard, cabbage, onions, mushrooms, cauliflower, Brussels sprouts, sauerkraut, artichoke, alfalfa sprouts, green beans, celery, bok choy, radishes, watercress, turnip, asparagus, garlic, leek, fennel, shallots, scallions, ginger, jicama, parsley, water chestnuts The following can be used in moderation (“moderation” means eating small amounts of these ingredients once a day or, ideally, just a couple times weekly): • Carrots and parsnips. • Cottage cheese, yogurt, and kefir: Use sparingly in recipes or as a topping. • Cow’s milk and cream: Use sparingly in recipes, coffee, and tea. • Legumes (beans, lentils, peas). Exception: you can have hummus (made from chickpeas). • Non-gluten grains: amaranth, buckwheat, rice (brown, white, wild), millet, quinoa, sorghum, teff. (A note about oats: although oats do not naturally contain gluten, they are frequently contaminated with gluten because they are processed at mills that also handle wheat; avoid them unless they come with a guarantee that they are gluten-free.) When non-gluten grains are processed ======================================== *** 高亮 2016/8/17 for human consumption (e.g., milling whole oats and preparing rice for packaging), their physical structure changes, and this increases the risk of an inflammatory reaction. For this reason, we limit these foods. • Sweeteners: natural stevia and chocolate (choose dark chocolate that’s at least 70 percent or more cocoa). • Whole sweet fruit: Berries are best; be extra cautious of sugary fruits such as apricots, mangos, melons, papaya, prunes, and pineapple. • Wine: one glass a day if you so choose, preferably red. ======================================== *** 高亮 2016/8/17 Optional Fast Ideally, start week 1 after you have fasted for one full day. Fasting is an excellent way to set the foundation and speed up your body’s shift to burning fat for fuel and producing biochemicals that have astonishing pro-health effects on the body and brain. For many, it helps to do the fast on a Sunday (last meal is dinner Saturday night), and then begin the diet program on a Monday morning. The fasting protocol is simple: No food but lots of water for a twenty-four-hour period. Avoid caffeine, too. If you take any medications, by all means continue to take them (if you take diabetes medications, please consult your physician first). If the idea of fasting is too painful for you, simply wean yourself from carbs for a few days as you prepare your kitchen. The more addicted your body is to carbs, the harder this will be. I prefer that my patients go cold turkey when it comes to nixing gluten, so do your best to at least eliminate sources of gluten entirely and cut back on other carbs. People whose bodies are not dependent on carbs can fast for longer periods, sometimes for days. When you’ve established this diet for life and want to fast for further benefits, you can try a seventy-two-hour fast (assuming you’ve checked with your doctor if you have any medical conditions to consider). I recommend that people fast at least four times a year; fasting during the seasonal changes (e.g., the last week of September, December, March, and June) is an excellent practice to keep. ========================================
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