of the neurotransmitters

of the neurotransmitters serotonin, epinephrine, norepinephrine, GABA, and dopamine. At the same time, B-complex vitamins, which are needed to make those neurotransmitters (and a few hundred other things), get used up. Magnesium levels also diminish, and this handicaps both your nervous system and liver. In addition, high blood sugar triggers a reaction called “glycation,” which we’ll explore in detail in the next chapter. In simplest terms, glycation is the biological process whereby glucose, proteins, and certain fats become tangled together, causing tissues and cells to become stiff and inflexible, including those in the brain. More specifically, sugar molecules and brain proteins combine to create deadly new structures that contribute more than any other factor to the degeneration of the brain and its functioning. The brain is tremendously vulnerable to the glycating ravages of glucose, and this is made worse when powerful antigens like gluten accelerate the damage. In neurological terms, glycation can contribute to the shrinking of critical brain tissue. Aside from sweetened beverages, grain-based foods are responsible for the bulk of carbohydrate calories in the American diet. Whether from pasta, cookies, cakes, bagels, or the seemingly healthful “whole-grain bread,” the carbohydrate load induced by our food choices ultimately doesn’t serve us well when trying to optimize brain health and function. When you add to this list the potpourri of other high-carbohydrate foods like potatoes, corn, fruit, and rice, it’s no wonder that Americans are now rightly called “carboholics.” It’s also not surprising that we have an epidemic of metabolic dysfunction and diabetes in our culture. The data confirming the relationship between high carbohydrate consumption and diabetes is clear and profound, and it’s compelling to note that in 1994, when the American Diabetes Association recommended that Americans should consume 60 to 70 percent of their calories from carbohydrates, rates of diabetes exploded. In fact, the number of cases of diabetes in this country actually doubled between 1997 and 2007. 21 Take a look at the rapid upward slope from 1980 through 2011, during which the number of Americans diagnosed with diabetes more than tripled: In 1992, the U.S. government endorsed a high-carb, low-fat diet. The American Diabetes Association and the American Heart Association followed suit with similar recommendations in 1994. Notice the sharp incline thereafter as more people became diabetic (and obese). This is significant since, as you already know, becoming a diabetic doubles your risk of Alzheimer’s disease. Even being “pre-diabetic,” when blood sugar issues are just beginning, is associated with a decline in brain function and shrinkage of the brain’s memory center; it is also an independent risk factor for full-blown Alzheimer’s disease. It’s hard to believe that we couldn’t have known about this connection between diabetes and dementia sooner, but it’s taken us a long time to connect the dots and conduct the kind of longitudinal studies that such a conclusion requires. It’s also taken us time to figure out the obvious question that stems from this link: How does diabetes contribute to dementia? First, if you’re insulin resistant, your body may not be able to break down a protein (amyloid) that forms brain plaques associated with brain disease. Second, high blood sugar provokes menacing biological reactions that injure the body, by producing certain oxygen-containing molecules that damage cells and causing inflammation that can result in hardening and narrowing of the arteries in the brain (not to mention elsewhere in the body). This condition, known as atherosclerosis, can lead to vascular dementia, which occurs when blockages and strokes kill brain tissue. We tend to think about atherosclerosis in terms of the heart, but the brain can be equally affected by changes in its arteries’ walls. Back in 2004, Australian researchers boldly stated in a review paper that “there is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall.” 22 They also pointed out that such oxidation is a response to inflammation. A most disturbing finding was made by Japanese researchers in 2011 when they looked at 1,000 men and women over age sixty and found that “people with diabetes were twice as likely as the other study participants to develop Alzheimer’s disease within fifteen years. They were also 1.75 times more likely to develop dementia of any kind.” 23 This link remained true even after they took into account several factors associated with both diabetes and dementia risk, such as age, sex, blood pressure, and body mass index. Now they and other researchers are documenting how controlling blood sugar and reducing risk factors for type 2 diabetes also reduces dementia risk. GET THE FACTS ON FAT: YOUR BRAIN’S BEST FRIEND 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 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. 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. 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. 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. 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, then saturated fats were your staple, as they make up 54 percent of the fat in breast milk. Every cell in your body requires saturated fats; they comprise 50 percent of the cellular membrane. They also contribute to the structure and function of your lungs, heart, bones, liver, and immune system. In your lungs, one particular saturated fat—16-palmitic acid —creates lung surfactant, reducing surface tension so that your alveoli—the tiny air sacs that capture oxygen from your inhalations and allow it to be absorbed into your bloodstream—are able to expand. Without surfactant, you would not be able to breathe because the wet surfaces of your lungs’ alveoli would stick together and prevent your lungs from expanding. Having healthy lung surfactant prevents asthma and other breathing disorders. Heart muscle cells prefer a type of saturated fat for nourishment, and bones require saturated fats to assimilate calcium effectively. With the help of saturated fats, your liver clears out fat and protects you from the adverse effects of toxins, including alcohol and compounds in medications. The white blood cells of your immune system partly owe their ability to recognize and destroy invading germs, as well as to fight tumors, to the fats found in butter and coconut oil. Even your endocrine system relies on saturated fatty acids to communicate the need to manufacture certain hormones, including insulin. And they help tell your brain when you are full so you can pull away from the table. I don’t expect you to remember all this biology. I mention it as a way of emphatically expressing to you the biological necessity of saturated fat. For a complete list of where these good fats can be found (and where the bad fats lurk), here. THE CASE FOR CHOLESTEROL If you’ve had your cholesterol levels tested, you’ve probably lumped HDL (high-density lipoprotein) and LDL (low-density lipoprotein) into two different categories—one “good” and one “bad.” I’ve already mentioned these two labels for cholesterol in passing. But contrary to what you might think, they are not two different kinds of cholesterol. HDL and LDL reflect two different containers for cholesterol and fats, each of which serves a different role in the body. Several other lipoproteins also exist, such as VLDL (very low) and IDL (intermediate). And as I’ve already begun to outline, cholesterol—no matter which “kind”—is not as terrible as you’ve been taught to believe. Some of the most remarkable studies of late on the biological value of cholesterol—and for brain health in particular—clue us in on how the pieces to this puzzle fit together and tell a coherent story. As we’ve seen, science is only recently discovering that both fat and cholesterol are severely deficient in diseased brains and that high total cholesterol levels in late life are associated with increased longevity. 24 The brain holds only 2 percent of the body’s mass but contains 25 percent of the total cholesterol, which supports brain function and development. One-fifth of the brain by weight is cholesterol! Cholesterol forms membranes surrounding cells, keeps cell membranes permeable, and maintains cellular “waterproofing” so different chemical reactions can take place inside and outside the cell. We’ve actually determined that the ability to grow new synapses in the brain depends on the availability of cholesterol, which latches cell membranes together so that signals can easily jump across the synapse. It’s also a crucial component in the myelin coating around the neuron, allowing quick transmission of information. A neuron that can’t transmit messages is useless, and it only makes sense to cast it aside like junk—the debris of which is the hallmark of brain disease. In essence, cholesterol acts as a facilitator for the brain to communicate and function properly. Moreover, cholesterol in the brain serves as a powerful antioxidant. It protects the brain against the damaging effects of free radicals. Cholesterol is a precursor for the steroid hormones like estrogen and the androgens, as well as for vitamin D, a critically important fat-soluble antioxidant. Vitamin D is also a powerful anti-inflammatory, helping to rid the body of infectious agents that can lead to lifethreatening diseases. Vitamin D is not really a vitamin; it acts more like a steroid in the body or a hormone. Given that vitamin D is directly formed from cholesterol, you won’t be surprised to hear that vitamin D levels are low in people with a variety of neurodegenerative diseases like Parkinson’s, Alzheimer’s, and multiple sclerosis. As we age, natural cholesterol levels generally increase in the body. This is good because as we age our production of free radicals increases. Cholesterol can offer a level of protection against these free radicals. And beyond the brain, cholesterol plays other vital roles in human health and physiology. The bile salts secreted by the gallbladder, which are needed for the digestion of fat and, therefore, the absorption of fat-soluble vitamins like A, D, and K, are made of cholesterol. Having a low cholesterol level in the body would therefore compromise a person’s ability to digest fat. It would also jeopardize your body’s electrolyte balance since cholesterol helps manage that delicate equilibrium. In fact, cholesterol is regarded by the body as such an important collaborator that every cell has a way to make its own supply. So what does this mean for dietary recommendations? For years we have been told to focus on “low-cholesterol” foods, but foods rich in cholesterol, such as eggs, are very helpful and should be considered “brain food.” We have eaten cholesterol-rich foods for more than two million years. As you now know, the real culprits when it comes to decreased brain function and health are foods that are high on the glycemic index—basically, high in carbohydrate. 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). 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. THE STATIN EPIDEMIC AND THE LINK TO BRAIN DYSFUNCTION Our understanding of how cholesterol is critical for brain health has brought me and many others in my field to believe that statins—the blockbuster drugs prescribed to millions of Americans to lower cholesterol—may cause or exacerbate brain disorders and disease. Memory dysfunction is a known side effect of statins. Dr. Duane Graveline, a former doctor to NASA astronauts who earned the nickname “Spacedoc,” has been a strong opponent of statins. Ever since he experienced total memory loss that he believed was caused by the statins he was taking at the time, he has been collecting evidence of their side effects from people around the world. Today he has written three books on the matter, the most famous of which is Lipitor, Thief of Memory. 25 In February 2012, the FDA released a statement indicating that statin drugs could cause cognitive side effects such as memory lapses and confusion. One recent study performed by the American Medical Association and published in the Archives of Internal Medicine in January 2012 demonstrated an astounding 48 percent increased risk of diabetes among women taking statin medications. 26 Risk of type 2 diabetes in women using statin drugs This study involved big numbers—more than one hundred sixty thousand postmenopausal women —making it hard to ignore its significance and gravity. Recognizing that type 2 diabetes is a powerful risk factor for Alzheimer’s disease, a relationship between statin drugs and cognitive decline or cognitive dysfunction is certainly understandable. In 2009, Stephanie Seneff, a senior research scientist in the Computer Science and Artificial Intelligence Laboratory at MIT who recently became interested in the effects of drugs and diet on health and nutrition, wrote a compelling essay explaining why low-fat diets and statins may cause Alzheimer’s. 27 In it, she chronicles our knowledge of statins’ side effects and paints a stunning portrait of how the brain suffers in their presence. She also synthesizes the latest science and input from other experts in the field. As Dr. Seneff explains, one of the main reasons statins promote brain disorder is that they handicap the liver’s ability to make cholesterol. Consequently, the level of LDL in the blood drops significantly. As I’ve just detailed, cholesterol plays a vital role in the brain, enabling communication between neurons and encouraging the growth of new brain cells. In an ironic twist, the statin industry advertises its products by saying that they interfere with cholesterol production in the brain as well as in the liver. Professor of Biophysics at Iowa State University Dr. Yeon-Kyun Shin is a noted authority on how cholesterol functions within neural networks to transmit messages. He put it bluntly in an interview for a ScienceDaily reporter: 28 If you deprive cholesterol from the brain, then you directly affect the machinery that triggers the release of neurotransmitters. Neurotransmitters affect the data-processing and memory functions. In other words—how smart you are and how well you remember things. If you try to lower the cholesterol by taking medication that is attacking the machinery of cholesterol synthesis in the liver, that medicine goes to the brain too. And then it reduces the synthesis of cholesterol, which is necessary in the brain. Our study shows there is a direct link between cholesterol and the neurotransmitter release, and we know exactly the molecular mechanics of what happens in the cells. Cholesterol changes the shape of the proteins to stimulate thinking and memory. 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. Besides statins’ direct impact on cholesterol, they have an indirect effect on the supply of fatty acids and antioxidants. They not only reduce the amount of cholesterol contained in LDL particles, but also diminish the actual number of LDL particles. So in addition to depleting cholesterol, they limit the stash available to the brain of both fatty acids and antioxidants, which are also carried in the LDL particles. Proper brain functioning depends on all three of these substances 31 (and later on, you’ll read about the importance of boosting the body’s own natural production of antioxidants). Another way in which statins may contribute to Alzheimer’s, beautifully described by Dr. Seneff, 32 is by paralyzing cells’ ability to make coenzyme Q10, a vitamin-like substance found throughout the body, where it serves an important role as an antioxidant and in producing energy for cells. Because coenzyme Q10 shares the same metabolic pathway as cholesterol, its synthesis is disrupted by statins, and the body and brain are deprived of it. Some of the side effects listed for statins, such as fatigue, shortness of breath, problems with mobility and balance, and muscular pain, weakness, and atrophy, are related to the loss of coQ10 in muscles and a reduced capacity for energy production. At the extreme, people who experience severe reactions to statins suffer from serious damage to their skeletal muscles. A deficiency in coQ10 also has been linked to heart failure, hypertension, and Parkinson’s disease. Given all these effects, it’s logical to see why coQ10 has been proposed as an actual treatment for Alzheimer’s disease. Finally, statins could have an indirect effect on vitamin D. The body makes vitamin D from cholesterol in the skin upon exposure to UV rays from the sun. If you were to look at the chemical formula for vitamin D, you’d have a hard time distinguishing it from cholesterol’s formula; they look virtually identical. “If LDL levels are kept artificially low,” writes Dr. Seneff, “then the body will be unable to resupply adequate amounts of cholesterol to replenish the stores in the skin once they have been depleted. This would lead to vitamin D deficiency, which is a widespread problem in America.” 33 Vitamin D deficiency is not just about an increased risk for weak, soft bones and, at the extreme end, rickets; it’s associated with many conditions that heighten one’s risk for dementia, such as diabetes, depression, and cardiovascular disease. If the brain didn’t demand vitamin D for proper development and function, then it wouldn’t have widespread receptors for it. The benefits of statins are questionable, and major studies have failed to show how they protect the body from illness. Although numerous studies do point to the positive effects statins have on reducing mortality rates in people with coronary artery disease, new research reveals that these outcomes have little to do with the cholesterol-lowering activity of these drugs and more likely reflect the fact that they reduce inflammation, a mainspring of the disease. But that doesn’t mean that the trade-offs for taking a statin merit their seal of approval. For some, the risk of negative side effects is just too great. People with a low risk of heart disease but a high risk for other ailments would be putting themselves in harm’s way if they chose to take a statin. Studies dating back to the mid-1990s reveal a link between statin use and an increased risk of certain cancers, not to mention a long list of side effects from digestive challenges to asthma, impotence, inflammation of the pancreas, and liver damage. 34 A trial published in January 2010 in the American Journal of Cardiology found that statin medications actually increased the risk of death. Researchers in Israel followed nearly 300 adults diagnosed with heart failure for an average of 3.7 years, and in some cases up to 11.5 years. Those who were taking statin drugs and had the lowest levels of low-density lipoprotein (LDL) were found to have the highest rates of mortality. Conversely, people with higher levels of cholesterol had a lower risk of death. 35 HOW CARBS—NOT CHOLESTEROL—CAUSE HIGH CHOLESTEROL If you can limit carb intake to a range that is absolutely necessary (the details of which are in chapter 10) and make up the difference with delicious fats and protein, you can literally reprogram your genes back to the factory setting you had at birth. This is the setting that affords you the ability to be a mentally sharp, fat-burning machine.