Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar--Your Brain's Silent Killers




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.


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 sleep is so normal to them that they forget what it’s like to have a good night’s sleep until they experience it again. Samuel may have thought that sleeping through the night was just a side benefit to the relief he found from going gluten-free. But it was more than that. The moment Samuel began to have refreshing sleep night after night was the moment he began to deeply “re-plumb” his body—hormonally, emotionally, physically, and even spiritually. Casting aside all of his issues with gluten and even his thyroid disorder, I can say without a doubt that achieving regular, restful sleep played a huge role in reversing his conditions and bringing him to exactly where he wanted to be: a place of optimal health.

Most of us undervalue the benefits of sleep, but it’s one of the few assets in our lives that’s totally free and absolutely essential to well-being. It’s also, as you’re about to find out, a fundamental tool in preventing brain decay.


In the last ten years, the science of sleep has been a media darling. And for good reason: We understand the value of sleep from a scientific perspective as we never have before. Both laboratory and clinical studies have shown that virtually every system in the body is affected by the quality and amount of sleep we get, especially the brain.1 Among the proven benefits: Sleep can dictate how much we eat, how fast our metabolism runs, how fat or thin we get, whether we can fight off infections, how creative and insightful we can be, how well we can cope with stress, how quickly we can process information and learn new things, and how well we can organize and store memories.2 Adequate sleep, which for the vast majority of us means at least seven solid hours, also influences our genes. In early 2013, scientists in England found that a week of sleep deprivation altered the function of 711 genes, including some involved in stress, inflammation, immunity, and metabolism.3 Anything that negatively affects these important functions in the body impacts the brain. We depend on those genes to produce a constant supply of proteins for replacing or repairing damaged tissue, and if they stop working after just a week of poor sleep, that says a lot about the power of sleep. 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. All of these conditions are uniquely tied to the brain.

We’ve also recently come to understand that few of us get enough sleep to support our bodies’ true needs. About 10 percent of Americans suffer from chronic insomnia, while fully 25 percent of us report not getting enough sleep at least on occasion.4 And beyond getting enough sleep, experts are now focused on the quality of sleep in terms of its ability to restore the brain. Is it better to sleep solidly for six hours or terribly for eight? One would think that questions like that are easy to answer, and that we’d know everything there is to know about something all of us do for a large portion of our lives. But science is still trying to unravel the mystery of sleep and even how it affects men and women differently. Just as I was writing this chapter, a new study emerged about sleep’s “surprising effects on hunger”; apparently, the hormones influenced by sleep deprivation are different for men and women.5 Although the outcome is the same for both sexes—an inclination to overeat—the underlying spark for that hunger is not the same for both sexes. In men, lack of sufficient sleep leads to elevated levels of ghrelin, a hormone that stimulates appetite. In women, on the other hand, ghrelin levels aren’t influenced by lack of sleep, but levels of GLP-1, an appetite-suppressing hormone, are. Granted, such a subtle difference may seem insignificant since the overall result of eating more occurs either way, but it goes to show how little we know about the entire biochemistry of the human body in response to sleep.

If there’s one thing we do know about sleep, it’s that it increasingly becomes a challenge the older we get. This is true for a variety of reasons, many of them stemming from medical conditions that can put a dent in sound sleep. As many as 40 percent of older adults can’t get a good night’s sleep due to chronic problems like sleep apnea and insomnia. We even have evidence now for the relationship between disrupted sleep and cognitive decline. Kristine Yaffe is a psychiatrist at the University of California, San Francisco, who studies people who have a higher risk of developing cognitive impairment and dementia. At her memory disorders clinic she sees a common thread in patients’ complaints: difficulty falling asleep and staying asleep. They report being tired throughout the day and resorting to naps. When Yaffe led a series of studies analyzing more than thirteen hundred adults older than seventy-five over a five-year period, she noted that those with disrupted sleep, such as sleep-disordered breathing or sleep apnea, were more than twice as likely to develop dementia years later. Those who experienced breaks in their natural circadian rhythm or who awoke throughout the night were also at increased risk.6

Circadian rhythms are at the heart and soul of our well-being. By about six weeks old, all of us establish this pattern of repeated activity associated with the cycles of day and night that remains for the rest of our lives. As with sunrises and sunsets, these rhythms rerun roughly every twenty-four hours. We have many cycles that coincide with the twenty-four-hour solar day, from our sleep-wake cycle to the established patterns in our biological beats—the rise and fall of hormones, the fluctuations in body temperature, and the ebb and flow of certain molecules that feed into our health and wellness. When our rhythm is not in sync with the twenty-four-hour solar day, we can feel ill or tired, which is what happens, for instance, when we travel across time zones and force the body to adapt quickly to a new cycle.

I find that most people don’t appreciate how much of their body’s inherent rhythm is grounded in their sleep habits and controlled by their brain. Our body’s natural day/night cycles pretty much command everything about us, when you consider that our hormonal secretion patterns are tethered to this cycle. A prime example is our body temperature, which, as a consequence of a dance of certain hormones in the body, rises during the day, takes a little dip in the afternoon (hence that late-day lull), peaks in the evening, then begins to decrease during the night. In the early morning hours, it reaches its nadir just as another pattern begins to peak, as cortisol levels reach their height in the morning and thereafter decrease throughout the day. Shift workers, who are notorious for keeping irregular sleep patterns due to their job responsibilities, live with a higher risk for a host of potentially serious illnesses as a result. Indeed, they don’t call it the graveyard shift for nothing.

So the next time you’re feeling uncharacteristically tired, moody, thirsty, hungry, mentally slow, forgetful, or even alert, aggressive, or horny, you can examine your recent sleep habits to glean insights. Suffice it to say we require a regular, reliable pattern of wakefulness and refreshing sleep to regulate our hormones. Volumes could be written on the body’s hormones, but for purposes of this discussion and, in particular, the link between sleep and brain health, we’re going to focus on one of the body’s most underrated, unsung hormones: leptin. Because it essentially coordinates our body’s inflammatory responses and helps determine whether or not we crave carbs, no conversation about brain health can exclude this important hormone. And it’s powerfully impacted by sleep. If you can gain control of this biological master of ceremonies, you can rule your hormonal kingdom for the benefit of your brain and body.


The year was 1994. It was a discovery that startled the medical community and forever changed how we view not only the human body and its complex hormonal system, but also sleep and its true value in orchestrating the empire. Just when we thought we had discovered all the hormones and their functions, we found a new hormone that we didn’t previously know existed.7, 8 It’s called leptin, and it turns out that this isn’t just your average hormone; like insulin, leptin is a major one that ultimately influences all other hormones and controls virtually all the functions of the hypothalamus in the brain. Your hypothalamus is where your inner dinosaur lives; this ancient structure that pre-dates humans sits in the middle of your head and is responsible for your body’s rhythmic activities and a vast array of physiological functions, from hunger to sex. But perhaps this finding came so late because leptin was identified in an unlikely place: fat cells.

Earlier I mentioned how we used to think that fat cells were just holding cells packed with unnecessary calories for a rainy day. But now we know that adipose tissue participates in our physiology as much as other “vital” organs, thanks to resident hormones like leptin that control whether or not we will end up with bulging bellies and small brains. First, a quick disclaimer: Leptin’s function in the body, like most every hormone’s, is extremely complex. The entire hormonal system, in fact, is extraordinarily intricate. There are untold numbers of interrelationships, and describing them all is beyond the scope of this book. I am going to keep it simple and reveal only what you need to know to take control of your hormones for the benefit of the brain.

Leptin is, at a most basic level, a primitive survival tool. It’s uniquely tied to the coordination of our metabolic, hormonal, and behavioral response to starvation. As such, it has a powerful effect on our emotions and behavior. Leptin is a gatekeeper of sorts, and once you have an understanding of this hormone you’ll know how to regulate the rest of your hormonal system and, in doing so, manage your health in unimaginable ways.

Although leptin is found in fat cells, that doesn’t mean it’s “bad.” In excess it would indeed lead to problems, notably degenerative diseases and a shorter life. But healthy levels of leptin do the opposite—preventing most diseases of aging and supporting longevity. The more you can increase your sensitivity to this critical hormone, the healthier you will be. By “sensitivity,” I’m referring to how your body’s receptors to this hormone recognize and use leptin to carry out various operations. Nora T. Gedgaudas, an acclaimed nutritional therapist, defines leptin succinctly in her book Primal Body, Primal Mind:

Leptin essentially controls mammalian metabolism. Most people think that is the job of the thyroid, but leptin actually controls the thyroid, which regulates the rate of metabolism. Leptin oversees all energy stores. Leptin decides whether to make us hungry and store more fat or to burn fat. Leptin orchestrates our inflammatory response and can even control sympathetic versus parasympathetic arousal in the nervous system. If any part of your [hormonal] system is awry, including the adrenals or sex hormones, you will never have a prayer of truly resolving those issues until you have brought your leptin levels under control.9

Gedgaudas calls leptin the “new kid on the block who runs the whole neighborhood,” and I couldn’t agree with her more. The next time you put down your fork and pull away from the dinner table, you can thank your leptin. When your stomach is full, fat cells release leptin to tell your brain to stop eating. It’s your brake. And this explains why people with low levels of leptin are prone to overeating. A now seminal study published in 2004 showed how people with a 20 percent drop in leptin experienced a 24 percent increase in hunger and appetite, driving them toward calorie-dense, high-carbohydrate foods, especially sweets, salty snacks, and starchy foods.10 And what caused this leptin plunge? Sleep deprivation.11 We’ve learned a lot about our hormones just from sleep studies alone. These, in turn, have informed us about the value of sleep in regulating our hormones.

Leptin and insulin have a lot in common, though they tend to antagonize each other. Both are pro-inflammatory molecules. Leptin is an inflammatory cytokine in addition to playing a big part in the body’s inflammatory processes. It controls the creation of other inflammatory molecules in your fat tissue throughout your body. And it helps explain why overweight and obese people are susceptible to inflammatory problems, including those that substantially increase risk for brain disorders, mental health problems, and neurodegenerative disease. Both leptin and insulin are the higher-ups in the body’s chain of command, so imbalances tend to spiral downward and wreak havoc on virtually every system of the body beyond those directly controlled by these hormones. What’s more, leptin and insulin are negatively influenced by similar things, and their biggest transgressors are carbohydrates. The more refined and processed the carbohydrate, the more out of whack healthy levels of leptin and insulin become. Earlier I explained how continuous carbohydrate abuse on the body’s insulin pumping and blood-sugar balancing will eventually lead to insulin resistance. The same happens with leptin. When the body is overloaded and overwhelmed by substances that cause continuous surges in leptin, the receptors for leptin start to turn off and you become leptin resistant. They stop hearing leptin’s message. Put simply, they surrender the controls and you’re left with a body vulnerable to illness and further dysfunction. So even though leptin is now elevated, it doesn’t work—it won’t signal to your brain that you’re full so you can stop eating. And if you cannot control your appetite, then you’re at a much greater risk for weight gain and obesity, which puts you at risk for brain disorders. Studies have also shown that elevated triglyceride levels, also a hallmark of too many carbs in the diet, cause leptin resistance.12

Not a single drug or supplement on the planet can balance leptin levels. But better sleep, as well as better dietary choices, will do the trick.

Are You Leptin Resistant?

It’s a question we all have to ask ourselves. Unfortunately, millions of Americans qualify as bona fide members of the leptin-resistant club. It’s practically a given if you’ve been eating a high-carb diet and don’t sleep well. In Ron Rosedale and Carol Colman’s The Rosedale Diet, a book that takes a sweeping look at leptin in weight control, they enumerate the signs, many of which are common with insulin resistance, too:13

·   being overweight

·   being unable to change how your body looks, no matter how much you exercise

·   being unable to lose weight or keep weight off

·   constantly craving “comfort foods”

·   fatigue after meals

·   feeling consistently anxious or stressed-out

·   feeling hungry all the time or at odd hours of the night

·   having a tendency to snack after meals

·   having high fasting triglycerides, over 100 mg/dL—particularly when equal to or exceeding cholesterol levels

·   having osteoporosis

·   having problems falling or staying asleep

·   high blood pressure

·   regularly craving sugar or stimulants like caffeine

·   the presence of “love handles”

Don’t panic if you have reason to believe you’re leptin resistant. The program outlined in chapter 10 will set you back on track.


One more appetite-related hormone I should mention before moving on: ghrelin. It’s the yin to leptin’s yang. Ghrelin is secreted by the stomach when it’s empty and increases your appetite. It sends a message to your brain that you need to eat. As expected, a disruption in the tango between leptin and ghrelin will wage war on your cravings, sense of fullness, ability to resist temptations in the kitchen, and waistline. In sleep studies, ghrelin levels soared in response to inadequate pillow-time in men. This triggered a bigger appetite and a propensity to gravitate toward high-carb, low-nutrient foods that, once consumed, easily get turned into fat. When your appetite hormones are not behaving properly, your brain becomes essentially disconnected from your stomach. It deceives you into thinking you’re hungry when you’re not, and further stimulates hard-to-resist cravings for foods that will perpetuate that vicious cycle of fat formation. This cycle then feeds the larger feedback loops that play into blood sugar balance, inflammatory pathways, and, of course, risk for brain disorder and disease. Put simply, if you cannot control your hunger and appetite, good luck managing your blood chemistry, metabolism, waistline, and, in the bigger picture, the prospect of crippling your brain.

During the third week of the program, I’ll ask you to focus on achieving high-quality sleep on a routine basis so you can gain control of the hormones that have everything to do with the fate of your brain. And you won’t have to reach for a sleep aid. The best sleep for the brain comes naturally.