antioxidant in the brain in both watery and fatty

Alpha-lipoic acid: This fatty acid is found inside every cell in the body, where it’s needed to produce the energy for the body’s normal functions. It crosses the blood-brain barrier and acts as a powerful antioxidant in the brain in both watery and fatty tissues. Scientists are now investigating it as a potential treatment for strokes and other brain conditions involving free radical damage, such as dementia. 14 Although the body can produce adequate supplies of this fatty acid, our modern lifestyles and inadequate diets often require supplementation. Vitamin D: It’s a misnomer to call vitamin D a “vitamin” because it’s actually a fat-soluble steroid hormone. Although most people associate it strictly with bone health and calcium levels—hence its addition to milk—vitamin D has far-reaching effects on the body and especially on the brain. We know there are receptors for vitamin D throughout the entire central nervous system; we also know that vitamin D helps regulate enzymes in the brain and cerebrospinal fluid that are involved in manufacturing neurotransmitters and stimulating nerve growth. Both animal and laboratory studies have indicated that vitamin D protects neurons from the damaging effects of free radicals and reduces inflammation. Let me state a few key findings: 15 Reports have shown a 25 percent risk reduction in cognitive decline in individuals with higher levels of vitamin D (severely deficient individuals in one such study were 60 percent more likely to undergo cognitive decline over the six-year follow-up). 16 A study done over seven years among 498 women showed that those with the highest intake of vitamin D had a 77 percent risk reduction for developing Alzheimer’s disease. 17 When the mental states of 858 adults were evaluated between 1998 and 2006, there was substantial decline in mental function in those individuals with severe vitamin D deficiency. 18 Multiple studies link low levels of vitamin D with risk for Parkinson’s and relapse in multiple sclerosis patients. (As an aside: Studies have shown that each 5 ng/mL increase in vitamin D levels in the blood correlates with a 16 percent reduction in relapses in MS.) 19 Low vitamin D levels have long been shown in medical literature to contribute to depression and even chronic fatigue. 20 Adequate vitamin D is needed by the adrenal glands to help regulate an enzyme necessary for the production of dopamine, epinephrine, and norepinephrine—critical brain hormones that play a role in mood, stress management, and energy. People with mild to severe depression have been known to experience turnarounds and improvements through supplementation alone. Correcting insufficient levels of vitamin D can take several months of supplementation, but doing so will significantly improve your entire body’s chemistry—from bone health to brain health—and even its insulin sensitivity. My dietary protocol will also provide good sources of natural vitamin D found in nature, such as cold-water fish and mushrooms. CHAPTER 8 Genetic Medicine Jog Your Genes to Build a Better Brain Old minds are like old horses; you must exercise them if you wish to keep them in working order. —JOHN ADAMS POP QUIZ! WHAT’S GOING TO MAKE YOU SMARTER and less prone to brain diseases? Is it A. solving a complex brainteaser, or B. taking a walk? If you guessed A, I won’t come down hard on you, but I will encourage you to go for a walk first (as fast as you can) and then sit down to work on a brainy puzzle. The answer, it turns out, is B. The simple act of moving your body will do more for your brain than any riddle, math equation, mystery book, or even thinking itself. Exercise has numerous pro-health effects on the body—especially on the brain. It’s a powerful player in the world of epigenetics. Put simply, when you exercise, you literally exercise your genetic makeup. Aerobic exercise not only turns on genes linked to longevity, but also targets the gene that codes for BDNF, the brain’s “growth hormone.” Aerobic exercise has been shown to reverse memory decline in the elderly and increase growth of new brain cells in the brain’s memory center. For a long time now, we’ve known that exercise is good for the brain, but only in the past decade have we really been able to quantify and qualify the extraordinary relationship between physical fitness and mental fitness. 1, 2 It has taken the collective force of many inquisitive researchers working from different camps, including neuroscientists, physiologists, bioengineers, psychologists, anthropologists, and doctors from various other fields of medicine. It has also taken the development of many advanced technologies for us to be able to analyze and understand the inner workings of brain matter itself, including its individual neurons. The newest findings make it undeniably clear that the link between exercise and brain health isn’t just a relationship. In the words of science writer Gretchen Reynolds for the New York Times, “It is the relationship.” 3 Exercise, according to the latest science, “appears to build a brain that resists physical shrinkage and enhances cognitive flexibility.” And this, my friends, may mean that there is no greater tool at our fingertips than physical movement. Take a look at the following two graphics, one showing the percentage difference in one’s risk for Alzheimer’s disease based on level of exercise, and another showing the difference based on intensity of exercise. I think these are quite telling: 4 Alzheimer’s risk compared to level of activity Alzheimer’s risk compared to intensity of activity THE MAGIC OF MOVEMENT As humans we have always been physically active until only quite recently. Modern technology has afforded us the privilege of a sedentary existence; virtually anything we need these days is available without having to exert much effort, much less get out of bed. But our genome, over millions of years, evolved in a state of constant challenge, from a physical perspective, in our quest to find food. In fact, our genome expects frequent exercise—it requires regular aerobic exercise to sustain life. But unfortunately, too few of us respect that requirement today. And we have the chronic illness and high mortality rates to show for it. The idea that exercise can make us smarter has intrigued not just traditional researchers in biomedical labs, but also anthropologists searching for clues to the shaping of humankind through millennia. In 2004, the journal Nature published an article by evolutionary biologists Daniel E. Lieberman of Harvard and Dennis M. Bramble of the University of Utah, who argue that we survived this long in history by virtue of our athletic prowess. 5 It was our cavemen ancestors who were able to outpace predators and hunt down valuable prey for food that allowed for survival—producing meals and energy for mating. And those early endurance athletes passed on their genes. It’s a beautiful hypothesis: We are designed to be athletes so that we can live long enough to procreate. Which is to say that natural selection drove early humans to evolve into supremely agile beings—developing longer legs, stubbier toes, and intricate inner ears to help us maintain better balance and coordination while standing and walking on just two feet as opposed to four. For a long time, science couldn’t explain why our brains had gotten so big—disproportionately so, when you consider our body’s size in comparison to other animals’. Evolutionary scientists in the past liked to talk about our carnivore behaviors and need for social interaction, both of which demanded complicated thinking patterns (to hunt and kill, and to engage in relationships with others). But now science has another ingredient to add to the mix: physical activity. According to the latest research, we owe our tremendous brains to the need to think… and the need to run. To arrive at this conclusion, anthropologists examined patterns between the brain size and endurance capacity of many animals, from guinea pigs and mice to wolves and sheep. 6 They noted that the species with the highest innate endurance capacity also had the highest brain volumes relative to their body size. Then the researchers took their experiment further by looking at mice and rats that were intentionally bred to be marathon runners. They created a line of lab animals that excelled at running by interbreeding those that ran the most in their cage’s wheels. And then the truth began to emerge: Levels of BDNF and other substances that promote tissue growth and health began to increase in these newly bred animals. BDNF is also known to drive brain growth, which is why the new thinking is that physical activity may have helped us to evolve into clever, quick-witted beings. David A. Raichlen, an anthropologist at the University of Arizona and leading scientist in the evolution of the human brain, summed up the concept brilliantly in his explanation to the New York Times, as reported and paraphrased by Gretchen Reynolds: “The more athletic and active survived and, as with the lab mice, passed along physiological characteristics that improved their endurance, including elevated levels of BDNF. Eventually, these early athletes had enough BDNF coursing through their bodies that some could migrate from the muscles to the brain, where it nudged the growth of brain tissue.” 7, 8 With an enhanced ability to think, reason, and plan, early humans could then sharpen the skills that they needed to survive, such as hunting and killing prey. They benefited from a positive feedback loop: Being in motion made them smarter, and sharper minds further allowed them to stay in motion and move more effectively. Over time, humans would come to engage in complex thinking and invent things like math, microscopes, and MacBooks. The bottom line is that if physical activity helped us develop the brains we use today, then it’s safe to say we need exercise to maintain those brains (not to mention to continue to evolve into a smarter, faster, more clever species). BE NIMBLE AND QUICK 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. 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 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. We know that exercise spurs the generation of new brain cells. Scientists have actually measured this effect by comparing mice and rats that ran for a few weeks versus those that were sedentary. The running animals had about twice as many new neurons in their hippocampi as the couch potatoes. Other studies have looked at which types of exercise are the most effective. In 2011, when a group of 120 older men and women were split into two groups—one assigned to a walking program and the other to a stretching regimen—the walkers won over the stretchers. 11 They were the ones who showed larger hippocampi after a year and higher levels of BDNF in their bloodstreams. The stretchers, on the other hand, lost brain volume to normal atrophy and didn’t perform as well on cognitive tests. Take a look at the results: Change in size of the hippocampus over 1 year comparing aerobic exercisers to those doing stretching program Whatever the activity, we have enough proof to confidently say that exercise needn’t be exhausting to be effective for the brain. GROW NEW NETWORKS 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. With an understanding of the relationship of BDNF to exercise, researchers have been examining the effect of physical exercise in people at risk for or already suffering from brain disorder and disease. In a recent report in the Journal of the American Medical Association, Professor Nicola Lautenschlager of the University of Western Australia found that elderly individuals engaged in regular physical exercise for a twenty-four-week period had an 1,800 percent improvement on measures of memory, language ability, attention, and other important cognitive functions compared to a control group. 13 The exercise group spent about 142 minutes in physical activity weekly, which averages about 20 minutes a day. The researchers attributed these improvements to better blood flow, the growth of new blood vessels, growth of new brain cells, and improved brain “plasticity.” In a similar study, Harvard researchers identified a strong association between exercise and cognitive function in elderly women, concluding: In this large, prospective study of older women, higher levels of long-term regular physical activity were strongly associated with higher levels of cognitive function and less cognitive decline. Specifically, the apparent cognitive benefits of greater physical activity were similar to being about three years younger in age and associated with a 20 percent lower risk of cognitive impairment. 14 Multiple effects coalesce when the body is engaged in physical activity. Exercise is a potent antiinflammatory. By activating the Nrf2 pathway I described earlier, physical exercise turns on the genes that suppress inflammation. And this can be measured in the laboratory. Scientists have documented time and time again that C-reactive protein—a commonly used laboratory marker of inflammation— is lower among people who keep an exercise routine. Exercise also improves insulin sensitivity. It helps manage blood sugar balance and reduce the glycation of proteins. We know this to be true from studies done on the effects of exercise on hemoglobin A1C. In one notable study, researchers told thirty participants to make no lifestyle changes while putting thirty-five others on an exercise program three days a week. 15 The control group did not participate in any form of exercise. After the sixteenth week, hemoglobin A1C decreased by 0.73 in the exercise group but increased by 0.28 in the non- exercise group. To put these numbers in context, if your hemoglobin A1C was 6.0, a reduction of 0.73 brought on by exercise represents a 12 percent reduction of hemoglobin A1C, and this rivals diabetes medications. IT DOESN’T TAKE MUCH TO MAKE AN IMPACT 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 eightytwo 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. PICK A PLAY Clearly, you don’t need to set your sights on climbing Mt. Everest. Nor do you need to train for an endurance event. But regular exercise that gets your heart pumping is a must. Although a small number of studies have found cognitive benefits among older people who just lifted weights for a year, most studies to date, and all animal experiments, have involved running or other aerobic activities such as swimming, bicycling, hiking, and brisk walking at least five days a week for at least twenty minutes per session. I realize that exercise is not on most people’s list of top priorities, but I hope the evidence I’ve provided in this chapter will encourage you to rethink your to-dos if you don’t already maintain an exercise routine. I’ll ask that you devote one week during the program to focus on this important area of your life and commence a regular workout if you don’t already have one. And if you do, then you can use the week to increase the duration and intensity of your workouts, or try something new. CHAPTER 9 Good Night, Brain Leverage Your Leptin to Rule Your Hormonal Kingdom Finish each day before you begin the next, and interpose a solid wall of sleep between the two. —RALPH WALDO EMERSON WHEN SAMUEL, A FORTY-EIGHT-YEAR-OLD STOCKBROKER, came to see me on a late-November day, he asked me to “optimize his health.” This wasn’t the first time someone had made such a blanket, somewhat vague request, but I knew what he really wanted: He wanted me to get to the bottom of his misery and deliver him to a place of vibrant health like he’d never felt before. A tall order for any doctor to fill, but something in his bloated face instantly clued me in to what could have been the problem. I started by getting to know his medical history and chief complaints. He had a history of low thyroid function, for which he was taking medication. He said his life was quite stressful, but rated his overall health as “good.” There wasn’t much to report as far as past medical problems, but interestingly enough, he mentioned that his son had been “sensitive” to solid foods during his infancy and was diagnosed as having gluten sensitivity. We discussed his thyroid issue further, and it turned out that he had an autoimmune disease called Hashimoto’s thyroiditis, which is caused by abnormal activation of the immune system that causes it to attack the thyroid gland. I went ahead and ordered a gluten sensitivity test, which produced compelling results. He was indeed highly sensitive to gluten; only one of the twenty-four antibodies tested was in the normal range. He desperately needed to try a gluten-free diet. His response to the diet was quite remarkable and, frankly, somewhat predictable in light of both his son’s experience and his off-the-charts test. Four months after he started the diet, I received a letter from him that made me smile. He admitted in writing just how bad his life had gotten by the time he made his appointment to come see me. Evidently, he’d fibbed when he told me that his health was “good.” It was far from that. He wrote: Prior to diagnosing me as gluten sensitive, my health was in a downward spiral…. Even though I was in my early forties and worked out daily, I was lethargic and struggled to make it through the day…. I was becoming more moody and would easily snap at the smallest things…. Depression set in, as I couldn’t shake negative thoughts. I was convinced that I was dying… [Today] I am a new person. I am once again happy-go-lucky, and I have energy throughout the day. I’m sleeping through the night regularly, and my joint pain is gone. I'm able to think clearly and not get side-tracked on my tasks. The best part is that the stubborn fat around my midsection virtually melted off in two weeks. I thank you for helping me get my life back. Even though Samuel didn’t mention his sleep problems when I first examined him, I had a hunch that restful sleep had evaded him for some time. He looked exhausted and had all the trademark signs of long-term, unfathomable sleep deprivation. For many of my patients prior to being treated, lack of