Fat Chance

Fat Chance Robert Lustig Sugar is addictive, toxic and everywhere. Find out how your sweet tooth might be nibbling you to death in this straight-talking expos?. ‘Fat Chance’, documents the science and the politics that has led to the pandemic of metabolic syndrome – which results in conditions like obesity, diabetes and heart disease. Dr Robert Lustig exposes how changes in the food industry and in our wider environment have affected our collective metabolisms and our waistlines, and he shows how industry and political forces, motivated by greed, don’t want things to change. To help us lose weight and recover our health, Lustig presents personal strategies to readjust the key hormones that regulate hunger and reward and suggests societal strategies to improve the health of the next generation. Discover how every calorie is different and that cutting out sugar is not just about making us thin – it’s about making us healthier, happier and smarter. Robert H. Lustig, M.D., M.S.L FAT CHANCE The Hidden Truth About Sugar, Obesity and Disease FOURTH ESTATE London Copyright First published in Great Britain by Fourth Estate An imprint of HarperCollinsPublishers Ltd 1 London Bridge Street London SE1 9GF www.4thestate.co.uk (http://www.4thestate.co.uk/) First published by Hudson Street Press, a member of the Penguin Group (USA) Inc. Copyright © Robert H. Lustig 2012 The right of Robert H. Lustig to be identified as the author of this work has been asserted by him in accordance with the Copyright, Designs and Patents Act 1988 A catalogue record for this book is available from the British Library All rights reserved under International and Pan-American Copyright Conventions. By payment of the required fees, you have been granted the nonexclusive, non-transferable right to access and read the text of this e-book on-screen. No part of this text may be reproduced, transmitted, downloaded, decompiled, reverse engineered, or stored in or introduced into any information storage and retrieval system, in any form or by any means, whether electronic or mechanical, now known or hereinafter invented, without the express written permission of HarperCollins. PUBLISHER’S NOTE While the author has made every effort to provide accurate telephone numbers, Internet addresses, and other contact information at the time of publication, neither the publisher nor the author assumes any responsibility for errors, or for changes that occur after publication. Further, the publisher does not have any control over and does not assume any responsibility for author or third-party websites or their content. Ebook Edition © December 2012 ISBN: 9780007514137 Version: 2018-08-03 Dedication This book is dedicated to all the obese patients worldwide who suffer daily, and the family members who suffer with them. The children who will not know a normal childhood, who will endure an inhuman existence, and will die a slow and early death. The parents who are engulfed by guilt. The unborn children, who are already imprisoned by changes in their brains and their bodies. But most of all, I dedicate this book to those of you who are or have been my patients; for it is you who taught me the science of your affliction. You also taught me more than medical school ever did or could; and that each life is valuable, precious, and worth saving. You maintained your dignity in the face of the most adverse circumstances imaginable. You shared with me your misery, and your joy in small victories. We cried and we laughed together. I hope I was of some service and comfort. This book is my way of returning the favor. This book is written only for those of you who eat food. The rest of you are off the hook. INTRODUCTION: Time to Think Outside the Box “We just eat too damn much.”     Governor Tommy Thompson (R-Wisc.), U.S. Secretary of Health and Human Services, Today, NBC, 2004 Indeed we do. That’s it, thanks for buying this book, you’ve been a great audience, I’m outta here. Well, that’s what the U.S. government would have you believe. All the major U.S. governmental health agencies, the Centers for Disease Control (CDC), the U.S. Department of Agriculture (USDA), the Institute of Medicine (IOM), the National Institutes of Health (NIH), and the U.S. Surgeon General, say that obesity results from an energy imbalance: eating too many calories and not getting enough physical activity. And they are right – to a point. Are we eating more? Of course. Are we exercising less? No doubt. Despite knowing this, it hasn’t made any difference in the rates of obesity or associated diseases. More to the point, how did this epidemic happen and in such a short interval of just thirty years? People say, “The food is there,” and it is. But it was there before. People say, “The TV is there,” and it is. But it was there before, and we didn’t have this caloric catastrophe. There’s more to this story, way more, and it’s not pretty. Everyone blames everyone else for what has happened. No way is it their fault. Big Food says it’s a lack of activity due to computers and video games. The TV industry says it’s our junk food diet. The Atkins people say it’s too many carbohydrates; the Ornish people say it’s too much fat. The juice people say it’s the soda; the soda people say it’s the juice. The schools say it’s the parents; the parents say it’s the schools. And since nothing is for sure, nothing is done. How do we reconcile all these opinions into a cohesive whole that actually makes sense and creates changes for the better for each individual and for all society? That’s what this book is about. Food is not tobacco, alcohol, or street drugs. Food is sustenance. Food is survival. Most important, food is pleasure. There are only two things that are more important than food: air and water. Shelter’s a distant fourth. Food matters. Unfortunately, food now matters even more than it should. Food is beyond a necessity; it’s also a commodity, and it has been reformulated to be an addictive substance. This has many effects on our world: economically, politically, socially, and medically. There is a price to pay, and we’re paying it now. We pay with our taxes, our insurance premiums, and our airline fares – nearly every bill we receive in the mail has an obesity surcharge that we underwrite. We pay in misery, worsening school scores, social devolution, and we pay in death. We pay for all of it, one way or another, because the current food environment we have created does not match our biochemistry, and this mismatch is at the heart of our medical, social, and financial crisis. Worse yet, there is no medicine for this. There is no edict, ordinance, legislation, tax, or law that can solve this alone. There is no quick fix, but the problem is resolvable if we know what’s really going on – and if we really want to resolve it. In his 2004 book Food Fight, Kelly Brownell of Yale University talks about obesity and the “toxic environment” we now live in, a euphemism for our collective bad behaviors. I am going a step further. I’m interested in whether there is something actually toxic, I mean poisonous, going on here. Even laboratory animal colonies have been getting fatter over the past twenty years! Every good story needs a villain. While I am loath to reveal it this early in the book, I won’t keep you in suspense. It’s sugar – the Professor Moriarty of this story, a substance that now permeates nearly all food and drink worldwide. It’s killing us…slowly, and I’ll prove it. Every statement throughout this book is based on scientific study, historical fact, or recent statistics. I’m a physician. We take an oath: primum non nocere (first do no harm). But there’s a paradox in this statement: when you know the final disposition – that the outcome is going to be bad – then doing nothing is causing harm. I certainly did not start out as an advocate. I wasn’t looking for a fight. I didn’t come to this controversy with a preconceived agenda. Indeed, I was fifteen years into my medical career before I stepped up to deal with obesity as an issue. Until 1995, like my medical colleagues, I did my best to avoid seeing obese patients. I had nothing to tell them except “it’s your fault” and “eat less and exercise more.” At that time, seeing an obese child with type 2 diabetes was an anomaly. Now it is an almost everyday occurrence. The problem of obesity is now inescapable in medical practice. You can’t avoid it any more. The concepts elaborated here didn’t just wake me from sleep one day in a divine revelation. This book is the culmination of sixteen years of medical research, medical meetings, academic discourse with colleagues, journal clubs, policy analysis, and a whole lot of patient care. I have no conflict of interest in espousing the information here; I am not a pawn of the food industry or a mouthpiece for any organization. Unlike many authors addressing the devastation of obesity, I don’t have a product line designed to enrich my bank account. I came by these views honestly and through rigorous data analysis. And the data are out there for everyone to examine. I’m just putting them together somewhat differently. As a scientist, I have personally contributed to the understanding of the regulation of energy balance. As a pediatrician, I get to watch the interaction between genetics and environment that causes obesity play out in my examining room every day. And now, as a fledgling policy wonk, I have seen how the changes in our society have sprouted this global pandemic. It is this panoramic view that allows me to connect the dots for you, and they don’t connect in the way you’ve been told. To blame obesity on the obese is the easy answer, but it is the wrong answer. The current formulation of gluttony and sloth, diet and exercise, while accepted by virtually everyone, is based on faulty premises and myths that have taken hold in the world’s consciousness. Obesity is not a behavioral aberration, a character flaw, or an error of commission. When we think about the ravages of obesity, our minds often go first to adults. But what about kids? One quarter of U.S children are now obese; even infants are tipping the scales! Children don’t choose to be obese. They are victims, not perpetrators. Once you understand the science, you realize what applies to children also applies to grown-ups. I know what you’re thinking: adults are responsible for their own choices and for the food they give their children. But are they? An esteemed colleague involved in the obesity wars once said to me, “I don’t care what’s causing the obesity epidemic. I just want to know what to do about it.” I respectfully disagree. In order to pull ourselves out of this ditch, we have to understand how we drove into it. Indeed, our current thinking is based on correlation, supposition, and conjecture. I wrote this book to persuade you, the reader, to take up this cause, for your own health and for our country’s. However, you can’t truly advocate for a cause unless you know what is going on. And you can’t disagree with me until you know all the facts. And that means the science. After you’ve read this book, if you think it’s a crock or that I’m a crank, tell me. I want to know. In fact, I’ll make a promise to you right now: there is not one statement made in this entire book that can’t be backed up by hard science. My reputation in the field is built on the science. It’s also my protection against those who would try to discredit me, including the food industry and, as you will see, the federal government. Indeed, it’s the only reason I haven’t been discredited yet. And I won’t be, because I stick to the science. Now and forever. However, in four places in the book, I let my imagination run wild. I will try to explain how obesity fits within the process of evolution, how our evolutionary biochemistry works to keep us alive, and finally how our food environment has altered that biochemistry to promote this global catastrophe. These fits of speculation will carry the section heading “Deconstructing Darwin.” This book is targeted at the patients who suffer, the doctors who suffer along with them, the U.S. electorate who pays for this debacle, the politicians who must take up arms to dig us out of the mess that has been created out of our economy and our health, and the rest of the world, so they don’t make the same mistakes (although they already have). In Part 1 of this book, I will challenge some of the theories you’re used to hearing in the media, and indeed from the medical profession. Parts 2 and 3 will focus on the science of obesity, and how the body deals with energy burning versus storage. No, you don’t need to be a biology or medical expert to understand the science. I’ve worked hard to reduce it down to its essence, and to keep it interesting, light, and accessible. In Part 2, I’ll also explain how your brain has developed, evolutionarily and in utero, to thwart your attempts at dieting. You truly are hormonal when it comes to the foods you crave, just not in the ways you think. Part 3 will elaborate on the science of fat tissue, and when and how it can make you sick. In Part 4, I will prove that our current environment is indeed “toxic.” I will show how the “American diet,” which is now the “industrial global diet,” is killing us…slowly. I will identify the poison and the antidotes, why those antidotes work, and why they’ve been added to or removed from our diet for the food industry’s purposes. Part 5 elaborates what you, as an individual, can do to protect yourself and your family by changing your “personal environment.” Finally, in Part 6, I argue that governments around the world have been co-opted by the food industry, and I will outline how they must instead partner with the populace and exert influence over the food industry to stop the obesity pandemic before we all reach the medical and financial Armageddon now within sight. PART I The Greatest Story Ever Sold Chapter 1 A Fallacy of Biblical Proportion Juan, a 100-pound six-year-old Latino boy whose mother is a non-English-speaking farm worker from Salinas, California, comes to my clinic in 2003. He is wider than he is tall. I ask the mother in my broken Spanish, “I don’t care what your kid eats, tell me what he drinks.” No soda, but a gallon of orange juice per day. On calories alone, this accounts for 112 pounds per year of body fat. Of course, some of that is burned off, and it might influence total food intake. I explain to the mother, “La fruta es buena, el jugo es malo (the fruit is good, the juice is bad). Eat the fruit, don’t drink the juice.” She asks, “Then why does WIC [Women, Infants, and Children, a government entitlement program for the poor run by the U.S. Department of Agriculture] give it to us?” One kid, one mother, one question, my life was changed – and the need for this book was born. Why does WIC give it to them? There is real science behind our worldwide obesity catastrophe. And science should drive policy, but as you will see, the politics get in the way. This is the most complex issue facing the human race this side of the Middle East conflict. And it has become incrementally more complicated over time, with multitudes of stakeholders with set agendas, and bigger than the individual parties involved. Devoid of simple solutions, it has destroyed families and claimed the lives of countless people. You can’t pick up a newspaper or log on to the Internet without seeing some new statistic on the obesity pandemic. It’s all obesity, all the time. And how many of them have something good to report? You can bet that any tabloid headline is about one of two things – either the statistics are getting worse or another obesity drug was denied or withdrawn by the Food and Drug Administration. I’m sure you’re sick of it. I know I am. And weight loss has turned into a blood sport – just tune in to The Biggest Loser. In 2001, Newsweek reported that six million kids in America were seriously overweight. We have tripled that number in a decade, and the numbers are now surpassing twenty million. Yet for all the media attention, visibility, discussion, and weight loss programs, even Michelle Obama can’t put the genie back in the bottle. While we’re getting fatter, we’re also getting sicker. Our risk for illness is increasing faster than the increase in obesity. Indeed, the cluster of chronic metabolic diseases termed metabolic syndrome – which includes obesity, type 2 diabetes, hypertension (high blood pressure), lipid (blood fat) disorders, and cardiovascular (heart) disease – is snowballing by leaps and bounds. And then there are the other obesity-associated metabolic diseases, such as nonalcoholic fatty liver disease, kidney disease, and polycystic ovarian syndrome. Add to that the other comorbidities (related medical conditions) associated with obesity, such as orthopedic problems, sleep apnea, gallstones, and depression, and the medical devastation associated with the obesity pandemic is staggering. Every one of these diseases has become more prevalent over the past thirty years. What’s more, all of them are now found in children as young as five years old. We even have an epidemic of obese six-month-olds![1 - J. Kim et al., “Trends in Overweight from 1980 Through 2001 Among Preschool-Aged Children Enrolled in a Health Maintenance Organization,” Obesity 14 (2006): 1164–71.] The human damage in this scourge of metabolic syndrome is showing. In 2005 one study showed that despite the increased availability of medical care, our children will be the first generation of Americans who will die earlier than their forebears.[2 - S. J. Olshansky et al., “A Potential Decline in Life Expectancy in the United States in the 21st Century,” New Engl. J. Med. 352 (2005): 1138–45.] The study placed the blame squarely on the obesity epidemic. In the United States, quality-adjusted life years lost to obesity have more than doubled from 1993 to 2008. Emergency rooms are taking care of forty-year-old heart attack victims. Teens with type 2 diabetes used to be unheard of; now they are one third of all new diagnoses of diabetes. In the United States alone, 160,000 bariatric surgeries (to reduce the size of the stomach) are performed per year, at an average cost of $30,000 per surgery. Over 40 percent of death certificates now list diabetes as the cause of death, up from 13 percent twenty years ago. The loss in American productivity due to time off from work is staggering, the waste in medical expenditures ($147 billion per year) is breaking the bank, and this amount is predicted to increase to $192 billion by the end of the decade. Guess what? There’s no money to pay for it all. The Affordable Care Act (ACA, or “Obamacare”) is going to put thirty-two million sick people on the insurance rolls by 2019. The president says we’ll make up for the costs in savings from preventative care. However, it is unlikely to improve our health in any significant way, as there are no provisions for the prevention of chronic disease, most notably those that attend obesity. How do you prevent all the ravages of chronic metabolic disease when we bust the scales and when the statistics show no sign of improvement? It’s often been said that we wouldn’t need health care reform if we had obesity reform. It would be one thing if obesity were an isolated problem in America, but it’s happening everywhere. The obesity pandemic has expanded the world’s collective waistline. The World Health Organization (WHO) has shown that the percentage of obese humans globally has doubled in the past twenty-eight years. In fact, obesity’s contribution to the burden of chronic disease has been equal to if not greater than that of smoking. Even people in developing countries are obese. After only one decade, there are now 30 percent more people who are obese than are undernourished worldwide. The WHO reported in 2008 that approximately 1.5 billion adults were overweight and at least 400 million were obese globally[3 - World Health Organization, Fact Sheet: Obesity and Overweight (2011), www.who.int/mediacentre/factsheets/fs311/en/.]; these numbers are projected to reach about 2.3 billion and 700 million, respectively, by 2015. In September 2011 the UN General Assembly declared that non-communicative diseases (diabetes, cancer, and heart disease) are now a greater threat to world health than are infectious diseases, including in the developing world (see chapter 22). Is the whole world now composed of gluttons and sloths? Over the next fifteen years, these diseases will cost low- and middle-income countries more than $7 trillion.[4 - UN General Assembly, “Prevention and Control of Non-Communicable Diseases,” New York, 2010.] People are dying earlier, and national economies are losing billions of dollars in lost productivity while governments pay for the medical expenditures. Millions of families end up in poverty, guaranteeing that the cycle will not be reversed. For the 55 percent of adults who are overweight or obese, listen up. I’m talking to you, at a doctor-to-patient level, at a person-to-person level. Obesity is not an automatic death sentence. A full 20 percent of morbidly obese persons are metabolically healthy and have normal life spans.[5 - J. M. Chan et al., “Obesity, Fat Distribution, and Weight Gain as Risk Factors for Clinical Diabetes in Men,” Diabetes Care 17 (1994): 961–69.] As for the other 80 percent, you don’t have to be in poor health; everyone has it within his reach to improve his health and regain those years the actuaries say will be lost. But success in doing so depends on identifying the cause of the problem, assessing your metabolic risk, and changing your biochemistry. Okay, full disclosure: despite your best efforts, you may never lose your stubborn subcutaneous fat (the fat that pads your thighs and derri?re). And if you do, you’ll gain it back in short order – unless you become a gym rat, because vigorous exercise is the only rational way to prevent weight regain (see chapter 13). In fact, if you lose meaningful amounts of subcutaneous fat and keep it off for more than a year, I’ll be shocked. Pleasantly so, but shocked nonetheless. For the 45 percent of adults who are normal weight, pay attention. You either sneer at or pity the other 55 percent of your brethren who take up two seats on the bus. You look down on them as weak, overindulgent, and lazy. You resent them, and you show it financially and socially. You’re indignant that they cost you money. And you think you’re out of the woods and home free. You’ve been told that you’ll live a long and happy life. Whatever you’re doing, it must be right. For those of you who are “naturally” thin, you’ve been told that you have great genes and can consume all the soft drinks and Twinkies you want without gaining a pound or getting sick. Would that it were true. A few years ago, you were the majority of Americans. Now you’re the minority. And you’re losing your percentage year by year. This means that many of you are flipping – that is, gaining weight and going over to the dark side. Indeed, current projections suggest that by 2030, the United States will be 65 percent overweight and 165 million American adults will be obese.[6 - S. L. Gortmaker et al., “Changing the Future of Obesity: Science, Policy, and Action,” Lancet 378 (2011): 838–47.] The 2008 movie Wall-E is a prophecy: that’s where we’re all headed. We’ll all be so fat, we’ll have to ride around on little scooters, just like at Walmart. And as you get older, your risk for gaining weight keeps going up. Your genes won’t change, but your biochemistry will. So, if you’re flipping (which more and more of you are), something must be sending you over to the “dark side.” And if that’s not your fate, it will be that of your children. Nobody knows this better than I, because I take care of those children every day. Here’s the kicker. Being thin is not a safeguard against metabolic disease or early death. Up to 40 percent of normal-weight individuals harbor insulin resistance – a sign of chronic metabolic disease – which will likely shorten their life expectancy. Of those, 20 percent demonstrate liver fat on an MRI of the abdomen (see chapter 8).[7 - K. C. Sung et al., “Interrelationship Between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes,” J. Clin. Endocrinol. Metab. 96 (2011): 1093–97.] Liver fat, irrespective of body fat, has been shown to be a major risk factor in the development of diabetes. You think you’re safe? You are so screwed. And you don’t even know it. The overriding thesis of this book is that your fat is not your fate – provided you don’t surrender. Because people don’t die of obesity per se. They die of what happens to their organs. On the death certificate, the medical examiner doesn’t write down “obesity”; instead it’s “heart attack,” “heart failure,” “stroke,” “diabetes,” “cancer,” “dementia,” or “cirrhosis of the liver.” These are diseases that “travel” with obesity. They are all chronic metabolic diseases. But normal-weight people die of these as well. That’s the point. It’s not the obesity. The obesity is not the cause of chronic metabolic disease. It’s a marker of chronic metabolic disease, otherwise known as metabolic syndrome. And it’s metabolic syndrome that will kill you. Understanding this distinction is crucial to improving your health, no matter your size. Obesity and metabolic syndrome overlap, but they are different. Obesity doesn’t kill. Metabolic syndrome kills. Although they travel together, one doesn’t cause the other. But then, what causes obesity? And what causes metabolic syndrome? And what can you do about each? Read on. I wrote this book to help you and your kids get healthy and improve your quality of life, increase your productivity, and reduce the world’s waste of medical resources. If you get thin in the process, great. But if that’s what you expect, go find your own diet guru, and good luck with that. Want to get healthier? Want to get happier? Want to get smarter? It’s your visceral (around your abdominal organs) fat and hepatic (liver) fat that’s keeping you down. And getting rid of visceral fat is not as hard as you might think. This is the more metabolically active fat, and there’s plenty you can do to shrink it. A proverb says, “A journey of a thousand miles begins with a single step.” This book is a journey into the workings of the body. It is a journey into the biochemistry of our brains and our fat cells. It is a journey into evolution, the mismatch between our environment and our biochemistry. And it is a journey into the world of business and politics, too. This journey starts with a single but very large step, in which we abandon our current thinking of obesity by challenging the age-old dogma “a calorie is a calorie.” Chapter 2 A Calorie Is a Calorie – or Is It? “If folks want to maintain a healthy weight, they have to be sensitive to the calories in and calories out…Not every calorie is the same.”     Governor Tom Vilsack (D-Iowa), U.S. Secretary of Agriculture, upon release of the 2010 Dietary Guidelines, January 13, 2011 Wait a second. If people have to be sensitive to calories in and out, then why aren’t calories the same? Does anyone see the contradiction here? This was the first time that any government official had even remotely hinted that calories might not be interchangeable, and it was buried in this cryptic double-speak. Everyone is a dietitian. Everyone thinks he or she understands obesity. Believe it or not, this is one of the harder medical conditions to comprehend. Why? Obesity is a combination of several factors: physics, biochemistry, endocrinology, neuroscience, psychology, sociology, and environmental health, all rolled up into one problem. The factors that drive the obesity pandemic are almost as myriad as the number of people who suffer from it. The Venus Von Willendorf is an eleven-inch statue carbon-dated to 22,000 BCE that was unearthed in Austria in 1908 (see figure 2.1). It depicts the torso of a morbidly obese adult woman. This shows us that the ancients knew about obesity long before they knew about fast food. There are other ways to gain weight aside from potato chips and pizza, soda and suds. The medical literature lists at least thirty diagnoses that include obesity as a symptom. These include problems of the brain, liver, and adipose (fat) tissue; genetic disorders; various hormonal imbalances; and the effects of certain medications. But none of these medical causes explain what’s happened to the world’s population over the last thirty years. Until 1980, statistically only 15 percent of the adult population had a body mass index – or BMI, an indicator of body fatness that is calculated from a person’s weight and height – above the eighty-fifth percentile, indicating either overweight or obesity. Now that statistic is 55 percent. And by 2030 it’s expected to be 65 percent.[8 - S. L. Gortmaker et al., “Changing the Future of Obesity: Science, Policy, and Action,” Lancet 378 (2011) 838–47.] Something’s happened in the last thirty years, but what? Fig. 2.1. A Venus FatTrap. The Venus von Willendorf is an 11-cm-high statuette of a female that carbon-dates to between 24,000 and 22,000 BCE. It was discovered in 1908 in Austria, and is on display in the Naturhistorisches Museum in Vienna. It shows that obesity is as old as man (or woman) himself. The First Law In order to understand obesity, and energy balance in general, we must acquaint ourselves with the first law of thermodynamics, which states, “The total energy inside a closed system remains constant.” For you math and science geeks: U = Q – W where U is the internal energy of a system, Q is the heat supplied by the system, and W is the work done by the system. Work and heat are due to processes that either add or subtract energy; when work = heat, the internal energy stays constant. The first law is a law. It is elegant and airtight. If you don’t like it, file a grievance with Sir Isaac Newton. I subscribe to the first law. The basis for our current understanding of the causes and consequences of the obesity pandemic lies not with the first law itself, but rather in how you interpret it, for, as with all laws, there is plenty of room for alternative interpretations. The prevailing wisdom on the first law can be summed up by one widely held dogma: a calorie is a calorie. That is, to maintain energy balance and body weight (the U in the equation), one calorie eaten (the Q) must be offset by one calorie burned (the W). The calorie eaten can come from anywhere, from meat to vegetables to cheesecake. The calorie burned can go to anywhere, from sleeping to watching TV to vigorous exercise. And from this dogma comes the standard and widely held interpretation of the first law: “If you eat it, you had better burn it, or you will store it.” In this interpretation, the behaviors of increased energy intake and decreased energy expenditure are primary (and presumably learned); therefore, the weight gained is a secondary result. Thus, obesity is routinely thought to be the natural consequence of these “aberrant behaviors.” As you will see hereafter, virtually all the stakeholders in the obesity pandemic have signed up on the side of personal responsibility. The Seating Chart at the Table of Blame The Head of the Table: The Gluttons and the Sloths Personal responsibility occupies the biggest seat at the Table of Blame. The common assumption in obesity hinges on its being a personal choice: We control what we eat and how much we exercise. If you are obese, it must be because you chose to either eat more, exercise less, or both. Over the past twenty-five years, various government agencies have accumulated ample evidence of the increased caloric intake during that time frame, both in children and in adults. During this time, the CDC has documented that Americans have increased their caloric consumption by an extra 187 calories per day for men, 335 calories per day for women. The behaviors associated with the rise in obesity include increased consumption of sugar-sweetened beverages and decreased consumption of whole fruits, vegetables, and other sources of dietary fiber. On a societal level, obesity is also associated with less breastfeeding, skipped breakfasts, fewer family meals, and more fast food dining. Alternatively, a wealth of evidence supports a role for decreased physical activity and increased “screen time” (TV, computers, video games, and texting) in causing obesity. It is from this perception of choice that we derive our current societal mantras around obesity: gluttony and sloth, two of the original “seven deadly sins.” I should note here that people exhibiting the other five deadly sins (greed, pride, lust, envy, and wrath) have gotten a pass in the press and in society as a whole. They are frequently extolled in the media – just watch the reality shows The Apprentice (envy, greed, pride, wrath—“You’re Fired!”), Millionaire Matchmaker (lust, greed, pride), or Jersey Shore (all known sins and then some). We’ve found absolution for nearly every vice and sin we can commit, except for these two. They continue to defy our society’s ability to forgive. This despite the fact that 55 percent of Americans are either overweight or obese. Thin people are now in the minority, yet our culture continues to punish the majority. The average woman in the United States wears a size 14, yet many stores do not carry anything above a size 10. Although many women’s clothing stores now have “vanity sizes” (what was a size 10 in 1950 is now labeled a size 6), a large percentage of the population still can’t find anything on the rack. Approximately ten years ago in San Francisco, a billboard advertising the local 24-Hour Fitness health club depicted an extraterrestrial with the tag line “When they come, they’ll eat the fat ones first.” Our society continues to glorify thinness even though it appears to be less achievable every year. Those of us who are overweight or obese are immediately assumed to be gluttons and/or sloths. The obese are passed over for employment because it’s assumed they’ll be as lazy on the job as they are in caring for their bodies. They are among the last groups about which you can still make pejorative comments in public. From this condemnation, it’s a quick jump to the determination that obese people became so due to a behavioral defect. This formulation serves many purposes. It certainly justifies society’s desire to place blame. Even the obese have bought into the thesis of personal responsibility (see chapter 20). They would prefer to be portrayed as “perpetrator” rather than “victim.” If you’re a perpetrator, you maintain control and make your own choices, which is more hopeful than the alternative. If, instead, you’re a victim, you have no power, obesity is your fate, and there is no hope. You’re doomed, which is far more depressing. Finally, “personal responsibility” serves as the cornerstone of both the government’s and the insurance companies’ restriction of obesity care delivery. Seat 2: The Health Insurance Industry Much of the public views doctors as moneymaking mountebanks who care less for their patients than for their wallets. Well, we lose money on every patient we see. While our hospital’s general pediatric health insurance reimbursement averages 37.5 cents on the dollar (a pittance), our pediatric obesity clinic collects only 29.0 cents per dollar billed. The reason for this? The health insurance industry refuses to pay for obesity services, saying, “Obesity is a behavior, a flaw in your character, a psychological aberration. And we don’t pay for behavior.” This is the reason that, despite having enough business many times over, childhood obesity clinics and treatment programs are closing across the country. The insurance industry has decided that obesity is a lifestyle choice; therefore, it won’t pay. And when insurance companies do pay, they pay the absolute minimum. The insurance industry hates this obesity epidemic almost as much as we doctors do. They are hunkering down for a long siege. Why do they continue to deny reimbursement for obesity services? Because if they paid for all the services required by today’s pandemic, it would break their piggybank. Instead, they keep plugging holes in the dike by ascribing blame to the individual. They know that if they ever admit that obesity is the fault of no one person, the waters will engulf them all. Seat 3: The Medical Profession Twenty years ago, obesity was a social issue, not a medical one. At the beginning of my career, a colleague in pediatric endocrinology (the study of hormones in children) would send a form letter to the parents of children referred for obesity that read, “Dear parent, thank you for your interest in our pediatric endocrinology division. Your child has been referred for obesity. Obesity is a problem of nutrition and activity, not one of endocrinology. We suggest that you seek general advice from your child’s pediatrician.” And despite the undeniable onslaught of patients referred, many of my colleagues still feel this way. As the problems have soared and the research dollars have poured in, the American Diabetes Association (ADA), the American Heart Association (AHA), and countless others professional organizations have devoted a substantial portion of their agendas to the obesity pandemic. The standard mantra espoused by the medical establishment is, “Lifestyle causes obesity, and obesity causes metabolic syndrome.” We doctors recognize our role in mitigating the negative effects of obesity. But, again, for most physicians, the behaviors come first. The fault still lies with the patient. Seat 4: The Obesity Profiteers They say, “You’re weak. You’ve failed. Let us help you.” They profess to have the answer for your obesity problem and are peddling one solution or another. They are the obesity profiteers, and they represent large and vast industries, most of which are ostensibly trying to “do the right thing,” while making a fortune in the process. We have the otherwise reputable peer-group weight-loss programs such as Weight Watchers and Jenny Craig, which strongly recommend the option of buying their trademarked cuisine (often loaded with sodium) to bolster profits. There are the diet supplement people such as Nutri-System, who demand that you purchase their food if you want to see results. Gym programs such as Curves and 24-Hour Fitness charge initiation and renewal fees for membership. Then there are the companies that make home exercise equipment. Their late-night infomercials invariably show a buff guy stretching a rubber band with the implicit message, “You can look like this if you stretch a rubber band.” And then we have the “obesity authors” (gee, I’m one now!). Some are M.D.s, some Ph.D.s, some journalists, some pop culture phenomena, and some charlatans (none of which is mutually exclusive). All profess to have the answer to your obesity problem, peddling one diet or another. A few of these authors have developed corporations that want to sell you their food line, such as Atkins or the Zone. And each provides just enough science and nuggets of truth to hook the public. Some weight-loss doctors and clinics peddle prescription appetite suppressants or other weight-loss remedies – all of which are paid for out of pocket. Some of these doctors are reputable and brilliant academics at medical universities who are trying to save people’s lives while studying the physiology of obesity. Some are surgeons who perform liposuction for cosmetic purposes and bariatric surgery for metabolic and cardiac rescue. But some of them are “cut-and-run” surgeons operating out of small airplanes and flying around to little towns to perform quickie lap-band surgeries or gastric bypasses. They take their victims’ money, have no quality control, never see the patient in follow-up, and sometimes leave medical catastrophes in their wake. While the insurance companies refuse to shell out funds for this problem, the research money is pouring in. The pharmaceutical industry has spent a lot of money to come up with the “obesity blockbuster,” that magic bullet that will work long-term and for everyone. But that’s a pipe dream because, first, obesity isn’t one disease, it’s many; second, our bodies have many redundant pathways to maintain our critical energy balance, so one drug can’t possibly be effective for everyone; and third, there’s no one drug that will treat metabolic syndrome (see chapter 19). Each of these people and industries have one thing in common: they are trying to make a buck off the misfortunes of the obese, to the tune of $117 billion a year. And they’re all charging retail. Out of pocket, cash on the barrelhead. No insurance reimbursements here. No discounts. In case you hadn’t noticed, the obese will do anything not to be obese, even throw their money away on “get-thin-quick” schemes. That’s why these industries are the obesity profiteers. Do any of their “solutions” work? Fat chance. If you just did what they told you, the fat would magically disappear. If it fails, it’s your fault – you must have been noncompliant! Yet another reason for the obese to be depressed. Think about it – if any of these books, diets, or programs actually worked for the entire population, there would be only one. The person who makes this discovery will likely win the Nobel Prize, move to a mansion in Tahiti, and be featured on Lifestyles of the Rich and Famous. Seat 5: The Fat Activists There’s nothing socially or medically wrong with being fit and fat; you’re doing better than the people out there who are thin and sedentary. But there is something medically wrong with being fat and sick. Especially if you’re suffering metabolically, which 80 percent of obese people are. If you fall into this category, you are costing society money in caring for your metabolic illnesses, reducing productivity, and clogging up (and bringing down) the health care system. Not to mention digging yourself an early grave! The vocal proponents for the political and social rights of the obese, primarily the National Association to Advance Fat Acceptance (NAAFA), say, “Being fat is a badge of honor. Be fit and fat, be fat and proud.” No victimization here. And I agree. But NAAFA is also opposed to academic obesity research where its primary goal is weight loss – because why would you investigate a condition that is totally normal? They don’t think attention should be paid to how much kids weigh. This is puzzling to me. There is something highly paradoxical about enabling your child to be fat and sick. The majority of obese kids will be diabetic and cardiac cripples by the time they’re fifty. The science and research that NAAFA’s policy would seem to exclude are critical to studying this epidemic and determining what we can do about it. It’s my job as a pediatrician to protect these kids from such misguided thinking. Seat 6: The Commercial Food Industry The commercial food industry responds to the obesity pandemic with two mantras. First, “Everyone is responsible for what goes into his or her mouth.” Is that true? What goes into our mouths depends on two things: selectivity and access. Second, “Any food can be part of a balanced diet.” True but irrelevant because, thanks to the food industry, we don’t have a balanced diet, and they’re the ones that unbalanced it. They are a major instigator of the obesity pandemic through both their actions and the kind of rhetoric they use to justify those actions. Corporations repeatedly say one thing, yet do another. McDonald’s now advertises a healthier menu, with commercials featuring slim people in exercise clothes eating salads. However, the vast majority of people entering McDonald’s, even if they come in with the idea of eating a salad, instead order a Big Mac and fries. And McDonald’s is well aware of this. Its recent billboard campaign, “Crafted for Your Craving,” says all you need to know. Carl’s Jr.’s promotion of the “Western Bacon Six Dollar Burger,” which has a whopping 1,030 calories and 55 grams of fat, generally depicts fit and attractive people consuming the company’s fare with relish. Do you really think they would continue to be thin if they ate this on a regular basis? Food has become a commodity (see chapter 21), with foodstuffs that can be stored being traded on the various commodities exchanges. Speculators can corner the market on anything, from pork bellies to orange juice, by betting how much the price will rise and fall. And it’s because individual foods are treated as commodities that the downstream effects of changes in the food supply, and subsequently food prices, are being felt worldwide (see chapter 21). Cheap food means political stability. There is an imperative to keep food highly available and the prices as low as possible. Everyone is for cheap food. The United States spends 7 percent of its gross domestic product (GDP) on food, which allows the populace to buy more DVDs and iPads and take more vacations. But cheaper food, loaded with preservatives for longer shelf life, costs you on the tail end, and way more than all your gadgets and vacations put together (with interest). Seat 7: The Federal Government Our government is extraordinarily conflicted about where it should stand on the obesity pandemic. In 2003, former U.S. surgeon general Richard Carmona stated that obesity was an issue of national security, a stance that current surgeon general Regina Benjamin has upheld (despite the fact that she herself is obese) and one to which the U.S. Army has signed on. The public health branches of the government tell us that we eat too much and exercise too little. Mrs. Obama’s Let’s Move! campaign centers on the idea that childhood obesity can be battled by planting school vegetable gardens, encouraging kids to get out and exercise, and remaking the School Nutrition Act. All necessary, but not sufficient. The U.S. government does everything it can to keep food cheap (see chapter 16). The USDA has chosen not to accept any responsibility for its role in the obesity pandemic, continuing to market our Western diet around the world. The Farm Bill (see chapter 21) maintains food subsidies to keep farmers employed and growing more crops. The growers make their profits on volume. The food processors make big markups and pass them along to the consumer. And the USDA subsidizes food entitlement programs to the poor, such as the Supplemental Nutrition Assistance Program (SNAP, formerly known as food stamps) and the Women, Infants, and Children nutrition program (or WIC, which supplies low-income infants and their mothers with food and health care), to keep them alive and complacent. Until 2007, WIC bowed to the pressure of food lobbyists. The foodstuffs provided were largely unhealthy, and included white bread and high-sugar juices. The “Food Pyramid,” the federal nutrition guide released in 1974 (see figure 2.2a) and revised every five years, cultimating with “MyPyramid” in 2005, was never based on science. Indeed it was top and bottom heavy – hardly a pyramid. In response to calls for revision from many in the medical community, the Food Pyramid was deep-sixed in 2011. “MyPyramid” has now morphed into “MyPlate” (see figure 2.2b). The most recent guidance from the Dietary Guidelines Advisory Committee (DGAC), released in 2010, says that obesity is a problem (shocker) so we should all eat less fat, sugar, and salt. We’re all supposed to eat more fruits and vegetables, and less of everything else. This is stating the obvious. Don’t we already know this? Eat less? How? If we could eat less, there wouldn’t be an obesity pandemic. But we can’t. Fig. 2.2a. The Ancient Pyramids. The traditional USDA Food Pyramid, circa 2005, which advised us to eat more grains and less fat and sugar. Alongside it, what Americans actually ate – more like an hourglass than a pyramid. Fig. 2.2b. The Modern Merry-Go-Round. Under pressure from consumer groups and in response to the emerging science, the Pyramid was relegated to ancient history, and MyPlate was adopted by the USDA in 2011. MyPlate advises us to eat approximately half a plate of vegetables or fruits, one quarter fiber-containing starch such as brown rice, and one quarter protein, preferably low-fat. It’s too early to tell if this change will have any effect on American eating habits. Each of the stakeholders in the obesity pandemic is singing the same tune: “Your obesity is your personal responsibility, it’s your fault, and you’ve failed.” And all these accusations are a variation on a theme based on one unflappable dogma: a calorie is a calorie. Calories Don’t Count If… The clues are all around us as to what’s really happened. It’s time to look at where those extra calories went, because it is in these data that we will find the answer to the obesity dilemma. There are three problems with “a calorie is a calorie.” First, there is no way anyone could actually burn off the calories supplied by our current food supply. A chocolate chip cookie has the equivalent calories of twenty minutes of jogging, and working off a Big Mac would require four hours of biking. But, wait! Olympic swimmer Michael Phelps eats 12,000 calories a day and burns them off, right? If this were the case for all of us, diet and exercise should work – you’d burn more than you ate and lose weight (see chapter 13). And diet drugs should work – you take the drug, eat or absorb less, and lose the pounds. Except the meds don’t deliver on their promises. They work for a brief period, and then patients reach a plateau in weight loss (see chapter 4).[9 - R. Padwal et al., “Long-Term Pharmacotherapy for Obesity and Overweight,” Cochrane Database Syst. Rev., Art. No.: CD004094. DOI: 10.1002/14651858 (2004). PMID: 15266516.] Why? Do the patients stop taking the pills? No. So why do the medications stop working? The answer: because the body is smarter than the brain is. Energy expenditure is reduced to meet the decreased energy intake. So a calorie is not really a calorie, because your caloric output is controlled by your body and is dependent on the quantity and the quality of the calories ingested. Second, if a calorie is a calorie, then all fats would be the same because they’d each release 9.0 calories per gram of energy when burned. But they’re not all the same. There are good fats (which have valuable properties, such as being anti-inflammatory) and bad fats (which can cause heart disease and fatty liver disease; see chapter 10). Likewise, all proteins and amino acids should be the same, since they release 4.1 calories per gram of energy when burned. Except that we have high-quality protein (such as egg protein), which may reduce appetite, and we have low-quality protein (hamburger meat), which is full of branched-chain amino acids (see chapter 9), which has been associated with insulin resistance and metabolic syndrome.[10 - C. B. Newgard et al., “A Branched-Chain Amino Acid-Related Metabolic Signature That Differentiates Obese and Lean Humans and Contributes to Insulin Resistance,” Cell Metab. 9 (2009): 311–26.] Finally, all carbohydrates should be the same, since they also release 4.1 calories per gram of energy when burned. But they’re not. A closer look at the specific breakdown of the carbohydrate data reveals something interesting. There are two classes of carbohydrate: starch and sugar. Starch is made up of glucose only, which is not very sweet and which every cell in the body can use for energy. Although there are several other “sugars” (glucose, galactose, maltose, and lactose), when I talk about sugar here (and in the rest of this book), I am talking about the “sweet” stuff, sucrose and high-fructose corn syrup, which both contain the molecule fructose. Fructose is very sweet and is inevitably metabolized to fat (see chapter 11). It is the primary (although not the sole) villain, the Darth Vader of the Empire, beckoning you to the dark side in this sordid tale. The third problem with “a calorie is a calorie” is illustrated by the U.S. secretary of health and human services Tommy Thompson’s admonishment in 2004 that we’re “eating too damn much,” would suggest that we’re eating more of everything. But we’re not eating more of everything. We’re eating more of some things and less of others. And it is in those “some things” that we will find our answer to the obesity pandemic. The U.S. Department of Agriculture keeps track of nutrient disappearance. These data show that total consumption of protein and fat remained relatively constant as the obesity pandemic accelerated. Yet, due to the “low-fat” directives in the 1980s of the AMA, AHA, and USDA, the intake of fat declined as a percentage of total calories (from 40 percent to 30 percent). Protein intake remained relatively constant at 15 percent. But if total calories increased, yet the total consumption of fat was unchanged, that means something had to go up. Examination of the carbohydrate data provides the answer. As a percentage of total caloric intake, the intake of carbohydrates increased from 40 percent to 55 percent.[11 - P. Chanmugam et al., “Did Fat Intake in the United States Really Decline Between 1989–1991 and 1994–1996?” J. Am. Diet. Assoc. 103 (2003): 867–72.] While it’s true we are eating more of both classes of carbohydrate (starch and sugar), our total starch intake has risen from just 49 to 51 percent of calories. Yet our fructose intake has increased from 8 percent to 12 percent to, in some cases (especially among children), 15 percent of total calories. So it stands to reason that what we’re eating more of is sugar, specifically fructose. Our consumption of fructose has doubled in the past thirty years and has increased sixfold in the last century. The answer to our global dilemma lies in understanding the causes and effects of this change in our diet. There’s one lesson to conclude from these three contradictions to the current dogma. A calorie is not a calorie. Rather, perhaps the dogma should be restated thus: a calorie burned is a calorie burned, but a calorie eaten is not a calorie eaten. And therein lies the key to understanding the obesity pandemic. The quality of what we eat determines the quantity. It also determines our desire to burn it. And personal responsibility? Just another urban myth to be busted by real science. Chapter 3 Personal Responsibility versus the Obese Six-Month-Old Sienna is a one-year-old girl who weighs 44 pounds. She was 10 pounds at birth and was delivered by caesarean section due to her size. Her mother is not obese, but her father is overweight. Her mother tested negative for diabetes during the pregnancy. Since birth, Sienna has had an incredible appetite. Her mother could not breastfeed her because she could not keep up with the baby’s demand for food. An average infant of Sienna’s age will eat one quart of formula per day. Sienna consumed two quarts per day. When Sienna was six months old, we told her mother to start feeding her solid foods. Sienna eats constantly and will scream if her mother does not feed her. She already has high cholesterol and high blood pressure. Is Sienna obese because of her behavior? Was this learned behavior? When would she have learned this behavior, and from whom? Has she, at age one, learned to control her mother to get what she wants? Should she accept personal responsibility for her actions? Based on “a calorie is a calorie,” behaviors come first. Personal responsibility implies a choice: that there is a conscious decision leading to a behavior. This behavior is formed because of learned benefits or detriments (e.g., a child placing her hand on a stove and learning it is hot). But does this make sense with regard to obesity? In everyone? In anyone? There are six reasons to doubt “personal responsibility” as the cause of obesity. 1. Obesity Is Not a Choice The concept of personal responsibility for obesity doesn’t always make sense. In our society today, one has to ask: Are there people who see obesity as a personal advantage? Something to be desired or emulated? Across the board, modern Western societies today value the thin and shun the obese. Obesity frequently comes with many medical complications, and those afflicted are more likely to develop heart problems and type 2 diabetes (see chapter 9). Obese people spend twice as much on health care.[12 - D. Thompson et al., “Lifetime Health and Economic Consequences of Obesity,” Arch. Int. Med. 159 (1999): 2177–83.] Studies show that the obese have more difficulty in dating, marriage, and fertility. The obese tend to be poorer and, even in high-paying jobs, earn less than their peers.[13 - J. Bhattacharya et al., “Who Pays for Obesity?” J. Econ. Perspect. 25 (2011): 139–58.] Now ask the same question about children. Did Sienna see obesity as a personal advantage? Did she become obese on purpose? Obese children have a quality of life similar to that of children on cancer chemotherapy.[14 - J. B. Schwimmer et al., “Health-Related Quality of Life of Severely Obese Children and Adolescents,” JAMA 289 (2003): 1813–19.] They are ostracized by their peers and are the targets of bullies. Many obese children suffer from low self-esteem, shame, self-hatred, and loneliness. One study showed children pictures of potential playmates. Each looked different and some had physical handicaps, such as being deformed or in a wheelchair. The researchers asked the children with whom they would rather play. The obese child came in dead last. Clearly, obesity is not something to which people, especially children, aspire. However, this view of obesity does not necessarily square with the beliefs of obese people themselves. They see themselves as perpetrators, not victims. They often state that they know their behavior is out of control and that this behavior is their own fault. They frequently experience yo-yo dieting. They lose weight for a period of time, and when they gain it back they blame themselves, seeing the gain as a character failing. They often recount binge eating, which suggests that a degree of dietary control is lost. These experiences of losing control make them think they had the control in the first place. Did they? 2. Diet and Exercise Don’t Work If obesity were only about increased energy intake and decreased energy expenditure, then reducing intake (diet) and increasing expenditure (exercise) would be effective. If obesity were caused by learned behaviors, then changing those behaviors would be effective in reversing the process and promoting weight loss. Specific and notable successes have led to behavior/lifestyle modification as the cornerstone of therapy for obesity. There are the anecdotal cases of weight loss by celebrities, such as Kirstie Alley or Oprah Winfrey, who publicly endorse their diets as if they were the latest fashionable handbags. They share their stories on TV and convince their viewers that this lifestyle change is possible for them, too, and that, as with adding the newest fall color to their wardrobe, losing weight will make them attractive and happy. There are reality television shows, such as The Biggest Loser, that document the weight loss (along with many a meltdown) of “normal people” through controlled diet and exercise. Publicity, cash prizes, and constant attention are often enough to change one’s diet and exercise response for a short time. In any magazine and many infomercials, peddlers of new weight-loss remedies provide before and after pictures of people who have lost 100 pounds. Whether this constitutes a true lasting change in behavior is doubtful. After all, Kirstie Alley and Oprah, celebrities who live in the public eye, have gained their weight back several times (until their newest miracle diet began, countless new diet books were sold, new gurus were anointed, millions of dollars were made, and the cycle repeated itself). There have been numerous reports of contestants on The Biggest Loser regaining much of their weight after the show ended. Most notably, Eric Chopin, the Season 3 winner, appeared on Oprah to tell his sorry tale of gaining at least half the weight back after his victory. He wrote in one blog post, “I’m still not back on track totally. I don’t know what it is.” Significant weight regain has been seen in up to one third of patients who have had surgery for weight loss (see chapter 19), because the reason for the obesity is still there. Unless it’s dealt with directly, regaining will be the norm, not the exception. Strict control of one’s environment through limiting caloric intake and increasing physical activity can result in weight loss. This is true as long as the environment remains regulated. A perfect example is the army recruit who consistently loses weight due to monitored diet and vigorous exercise. This also accounts for the number of “fat schools” and “fat camps” that have sprung up nationwide. Parents send their overweight child away for the summer and are thrilled when he returns thinner, if harboring parental resentment. There are numerous reports of Hollywood stars who bulk up for a role (remember Robert DeNiro in Raging Bull?) and then lose the excess weight after shooting. (Of course, they have the benefit of round-the-clock personal trainers and nutritionists to monitor their food intake.) While such results are dramatic, they usually cannot be sustained. Environmental control is different from behavioral control (see chapters 17 and 18). The real problem is not in losing the weight but in keeping it off for any meaningful length of time. Numerous sources show that almost every lifestyle intervention works for the first three to six months. But then the weight comes rolling back.[15 - T. A. Wadden et al., “Treatment of Obesity by Very Low Calorie Diet, Behavior Therapy, and Their Combination: A Five-Year Perspective,” Int. J. Obes. 13 (1989): 39–46; M. W. Schwartz et al., “Regulation of Body Adiposity and the Problem of Obesity,” Arterioscler. Thromb. Vasc. Biol. 17 (1997): 233–38.] The number of people who can maintain any meaningful degree of weight loss is extremely small (see figure 3.1). However, because behavior/lifestyle modification is the accepted treatment, the general explanation of weight regain is that it is the individual’s fault. Because he is “choosing” not to live a healthy lifestyle, the doctors and the insurance industry do not feel it their responsibility to intervene. The same is true for children. Due to some notable and individual successes, behavior/lifestyle modification is the cornerstone of therapy. However, this is not a winning strategy for most obese children. Research shows that dietary interventions don’t often work. Exercise interventions are even less successful. And unfortunately for children like Sienna, at one year of age they are unable to run on a treadmill. Also, the effects of altering lifestyle for obesity prevention are underwhelming and show minimal effect on behavior and essentially no effect on BMI. Fig. 3.1. The “Biggest Loser”—Not You. Percentage of obese individuals who were able to maintain their weight loss over nine years. 3. The Obesity Epidemic Is Now a Pandemic If obesity were just an American phenomenon it would be an epidemic, an outbreak of illness specific to a certain area. One might then blame our American culture for promoting it. Due to our slippage in education and technological superiority, we’re labeled as “fat and lazy” or “gluttons and sloths.” Yet obesity is now a pandemic, a worldwide problem. The United Kingdom, Australia, and Canada are right behind us. Also, in the past ten years, obese children have increased in France from 5 to 10 percent, in Japan from 6 to 12 percent, and in South Korea from 7 to 18 percent.[16 - S. Yoo et al., “Obesity in Korean Pre-Adolescent School Children: Comparison of Various Anthropometric Measurements Based on Bioelectrical Impedance Analysis,” Int. J. Obes. 30 (2006): 1086–90.] In fact, obesity and chronic metabolic diseases are occurring in underdeveloped countries that have never had such problems before.[17 - N. Gupta et al., “Childhood Obesity in Developing Countries: Epidemiology, Determinants, and Prevention,” Endocr. Rev. 33 (2012): 48–70.] Previously, poorer countries such as Malaysia had problems with malnutrition. Now Malaysia has the highest prevalence of type 2 diabetes on the planet. China has an epidemic of childhood obesity, at 8 percent in urban areas. Brazil’s rate of increase in obesity is predicted to reach that of the United States by 2020. Even India, which continues to have an enormous problem with malnutrition, is not immune – since 2004, the number of overweight children increased from 17 percent to 27 percent. Sienna is not a rarity; her obese peers are being born everywhere. The areas experiencing the greatest rise in obesity and type 2 diabetes include Asia (especially the Pacific Rim) and Africa, which are not wealthy areas.[18 - A. Ramachandran et al., “Diabetes in Asia,” Lancet 375 (2010): 408–18.] No corner of the globe is spared. This is not an American problem, an Australian problem, a British problem, or a Japanese problem. This is a global problem. Could each of these countries be experiencing the same cultural shifts toward gluttony and sloth that we are? Childhood obesity knows no intellect, class, or continent. What change in the last thirty years ties all the countries of the world together? As I mentioned in the introduction, the “American diet” has morphed into the “industrial global diet.” Despite people in other countries disapproving of our fast food and TV culture, our diet has invaded virtually every other country. Our fast food culture is now global due to taste, shelf life, cost, shipping ease, and the “cool” factor (a result of effective marketing). Its acceptance is also a response to the contaminated water supplies in these areas: soft drinks are often safer, cheaper, and more available than potable water.[19 - B. M. Popkin, “Global Nutrition Dynamics: The World Is Shifting Rapidly Toward a Diet Linked with Noncommunicable Diseases,” Am. J. Clin. Nutr. 84 (2006): 289–98.] They are also cheaper and certainly more available than milk. 4. Even Animals Raised in Captivity Are Getting Fat A recent report documented that, in the past twenty years, animals raised in captivity exhibit increasing body weights. The study examined the records of 22,000 animals of 8 different species, from rats to orangutans.[20 - Y. C. Klimentidis et al., “Canaries in the Coal Mine: A Cross-Species Analysis of the Plurality of Obesity Epidemics,” Proc. Biol. Sci. 278 (2011): 1626–32.] These animals were housed in multiple human-built colonies around the world, including labs and zoos. They don’t eat our commercial food. However, their food is still processed and composed of the same general ingredients as our own. Also, these animals drink the same water and breathe the same air that we do. We don’t yet know why this is happening, but the fact that even animals are showing signs of weight gain argues both against personal responsibility and in favor of some sort of environmental insult to which all life on the planet is now exposed (see chapter 15). 5. The Poor Pay More As stated earlier, personal responsibility implies a choice, usually a conscious choice. Can one exercise personal responsibility if one doesn’t have a choice? It is well known that the poor have much higher rates of obesity and chronic disease than do the rich. There are many reasons for this difference, and it is difficult to pinpoint one factor that is responsible. In the United States the poor exhibit two separate traits that argue against personal responsibility. First, there are possible genetic issues. It is well known that African Americans and Latinos in the United States are more economically disadvantaged than their Caucasian peers. These demographic groups have higher rates of obesity than Caucasians—40 percent of Latinos and 50 percent of African Americans are obese – and are more likely to have associated medical problems, such as metabolic syndrome.[21 - W. Park et al., “The Metabolic Syndrome: Prevalence and Associated Risk Factor Findings in the US Population from the Third National Health and Nutrition Examination Survey, 1988–1994,” Arch. Intern. Med. 163 (2003): 427–36.] Certain genetic variations are more common in specific minority groups. These differences in DNA may, in part, explain the higher rates of obesity and certain metabolic diseases, such as fatty liver (see chapters 7 and 19). Genetic makeup is certainly not a choice. Second, there are issues of access. There is a difference between the “healthy” diet of the affluent, who can purchase fresh, unprocessed foods that are high in fiber and nutrients and low in sugar, but at high prices, and, the unhealthy diet of the poor, which consists mainly of low-cost processed foods and drinks that do not need refrigeration and maintain a long shelf life. But access does not refer only to what people can afford to buy. Many poor neighborhoods throughout America lack farmers’ markets, supermarkets, and grocery stores where “healthy” foods can be purchased.[22 - C. Gordon et al., “Measuring Food Deserts in New York City’s Low-Income Neighborhoods,” Health Place 17 (2011): 696–700.] Many supermarkets have pulled out of poor neighborhoods, mainly because of financial decisions based on revenue and fear of crime. The national supermarket chain Kroger, which is headquartered in Cincinati, in 2007 purchased twenty former Farmer Jack stores in the suburbs of Detroit, Michigan, but none within the Detroit city limits. The nearest branch is in Dearborn, eight miles away from downtown. Many who live in low-income areas also have limited access to transportation. Lower-class urban areas throughout America have been labeled “food deserts” because they are unable to sustain a healthy lifestyle. If the only place you can shop is a corner store for processed food, is what you eat really a choice? In wealthier areas of San Francisco, nearly every block has an organic food store, while in the city’s poorer areas, each corner is dotted with a fast food franchise. Even when all foods are available at low cost, the poor may not have access to refrigerators or even kitchens. Many SROs (single-room occupancy) hotels have only hot plates and no space for keeping or cooking healthy meals. Further, there is the issue of time. Many poor families are led by parents who work multiple jobs and are unable to come home and prepare healthy meals for their children, instead relying on fast food or pizza. Lastly, the poor suffer from issues of food insecurity. People experience massive amounts of stress when they don’t know where their next meal is coming from (see chapter 6). They eat what is available, when they can – usually processed food. That level of stress is incompatible with the concept of choice. Stressed people can’t make a rational choice, particularly one in which short-term objectives (e.g., sating their hunger) are pitted against longer-term objectives (e.g., ensuring good health). 6. The Greatest Rate of Increase in Obesity Is in the Youngest Patients When you look at U.S. trends in childhood obesity over the past forty years, you see that every age group is affected. However, the age group that shows the greatest rate of increase in the last decade is the two- to five-year-olds.[23 - M. de Onis et al., “Global Prevalence and Trends of Overweight and Obesity Among Preschool Children,” Am. J. Clin. Nutr. 92 (2010): 1257–64.] It is impossible to ascribe personal responsibility or free choice to this age group. Toddlers don’t decide when, what, or how much to eat. They do not shop for or cook their own food. However, as all parents know, they do have lungs and they do make their preferences known in the supermarket. Research has shown that children are not able to tell the difference between a TV show and a commercial until they are eight years old. Children in the United States watch an average of three to four hours of TV per day. The programs are interspersed with commercials that target these young viewers and convince them of what they need.[24 - Kaiser Family Foundation, “Food for Thought: Television Food Advertising to Children in the United States” (2007), www.kff.org/entmedia/upload/7618.pdf.] If you can’t discern what’s marketing and what’s not, how can you defend yourself against it? We even have an epidemic of obese six-month-olds.[25 - J. Kim et al., “Trends in Overweight from 1980 through 2001 Among Preschool-Aged Children Enrolled in a Health Maintenance Organization,” Obesity 14 (2006): 1164–71.] They don’t diet or exercise. They drink breast milk or formula and lie in their cribs. While our society easily puts the blame on our current diet and exercise practices, how does this explain the obese six-month-old? Whatever theory you have to explain the obesity epidemic, it has to explain them also. The concept of diet and exercise in an obese infant is a non sequitur. Sienna and other obese six-month-olds lay waste to the idea of personal responsibility for obesity. Instead of perpetrator, the obese six-month-old must be a victim. But a victim of what? Or whom? Who Is to Blame? So we are left with a conundrum. We’re all eating more and exercising less. By 2050, obesity will be the norm, not the exception. Do abnormal behaviors drive obesity? If so, behavior is primary, behavior is a choice, and personal responsibility is front and center. But what if it’s the other way around? What if our biological process of weight gain drives these abnormal behaviors (see chapter 4)? To argue against personal responsibility is to argue against free will. “Free will” is defined as “the power of making free choices that are unconstrained by external circumstances or by necessity.” Who is making the choices? Philosophers and scientists have argued this topic for centuries. Albert Einstein stated, “If the moon, in the act of completing its eternal way around the earth, were gifted with self-consciousness, it would feel thoroughly convinced that it was traveling its way of its own accord…so would a Being, endowed with higher insight and more perfect intelligence, watching man and his doings, smile about man’s illusion that he was acting according to his own free will.” Anthony Cashmore of the University of Pennsylvania recently proposed that free will was in reality an interaction between our DNA and our environment, along with some stochastic (random) processes.[26 - A. R. Cashmore, “The Lucretian Swerve: The Biological Basis of Human Behavior and the Criminal Justice System,” Proc. Natl. Acad. Sci. 107 (2010): 4499–504.] Because our DNA cannot be changed, and because random processes are random, we’re left with our environment, both as the sentinel exposure and the only factor than can be manipulated. The debate about who or what is to blame for obesity will not be settled anytime soon. But I would argue that ascribing personal responsibility to the obese individual is not a rational argument for an eminently practical reason: it fails to advance any efforts to change it. The obesity pandemic is due to our altered biochemistry, which is a result of our altered environment. Part 2 will demonstrate how our behaviors are secondary, and are molded by our biochemistry. PART II To Eat or Not to Eat? That’s Not the Question Chapter 4 Gluttony and Sloth – Behaviors Driven by Hormones Marie is a sixteen-year-old girl with a brain tumor of the hypothalamus (the area at the base of the brain that regulates the hormones of the body). When she was ten, cranial radiation was required to kill the tumor. Since then, she has gained 30 pounds per year; she weighed 220 pounds when I first saw her. Her insulin levels spiked to incredible heights every time she ate. She had a form of intractable weight gain due to brain damage called hypothalamic obesity. She wouldn’t do any activity at home, couldn’t study in school, and was severely depressed. As part of a research study, I started her on a drug called octreotide, which lowered her insulin release. Within one week Marie’s mother called me to say, “Dr. Lustig, something’s happening. Before, we would go to Taco Bell where she would eat five tacos and an encharito and still be hungry. Now we go, she has two tacos and she’s full. And she’s starting to help me around the house.” After beginning the medication, Marie commented to me, “This is the first time my head hasn’t been in the clouds since the tumor.” Within a year, she was off antidepressants and had lost 48 pounds. Who’s at fault here? Is this a case of free will? And what happened to cause Marie’s reversal? If obesity is truly a result of too much energy intake (gluttony) and too little energy burned (sloth), then my last sixteen years taking care of obese children has been a complete and utter waste. Because it’s become painfully evident, after years of motivating, pleading, and arguing, that I can’t change children’s behavior. And I certainly can’t change their parents’ behavior. It was this insight from Marie, and other children like her, that exposed the inherent problems in our current thinking. Biochemistry and hormones drive our behavior. The idea that biochemistry comes first is not a new one, but it is one that physicians, scientists, and the public should embrace. Think about the following: You see a patient who drinks ten gallons of water a day and urinates ten gallons of water a day (highly abnormal). What is wrong with him? Could he have a behavioral disorder and be a psychogenic water-drinker? Could be. Much more likely he has diabetes insipidus, a defect in a water-retaining hormone at the level of the kidney. You see a twenty-five-year-old who falls asleep in his soup. Was he up partying all night? Perhaps. But he may have narcolepsy, which is a defect in the hormone that stimulates arousal (orexins) in the midbrain. The biochemistry drives the behavior. Schizophrenia for one hundred years was a mental health disorder. Now we know that it’s a defect in dopamine neurotransmission and that no amount of psychotherapy is going to help until you treat the biochemical defect. Thus, we routinely infer “biochemical” defects in many “behavioral” disturbances. Introducing Energy Processing and Storage To appreciate how hormones control eating behavior, first we have to look at what happens to the food we eat. In response to various brain signals (hunger, reward, stress) we ingest various calorie-laden foodstuffs (combinations of fat, protein, carbohydrate, and fiber, with some micronutrients thrown in for good measure) to build muscle and bone for growth and/or to burn for energy. These calories arrive at the stomach, a muscular bag in the abdomen about the size of a baseball glove, which releases hydrochloric acid, to begin to digest the food into smaller components. The food makes its way into the next part of the digestive tract, called the small intestine. There, a bunch of enzymes (proteins) digest the food into even smaller components, such that dietary fats are digested into fatty acids, dietary protein is sliced into amino acids, and carbohydrate is cleaved into simple sugars (mostly glucose, with varying amounts of the sweet molecule fructose). But we can’t digest dietary fiber, so it remains intact. The fiber speeds the rate of transit of the food through the small intestine (see chapter 12), while limiting the rate of absorption of the other nutrients. Once absorbed in the small intestine, the amino acids and simple sugars travel via the portal vein to the liver for immediate processing. The fatty acids are transported to the liver by a different route (the lymphatic system). The liver has first dibs on the processing of each of these three classes of nutrient. Whatever the liver can’t take up appears in the general circulation. Rising levels of glucose or amino acids or fatty acids reach the pancreas, where the beta-cells release the hormone insulin. Insulin, in common parlance, is known as the diabetes hormone. Diabetics inject insulin to lower their blood glucose. But where does the glucose go? To the fat. Insulin’s actual job is to be your energy storage hormone. When you eat something (usually containing some form of carbohydrate), your blood glucose rises, signaling the pancreas to release insulin commensurate with the rise in blood glucose. (This is the theory behind the concept of glycemic index, which is discussed in chapter 17.) Insulin then tops off the liver’s energy reserve by making liver starch (called glycogen), and shunts any amino acids from the blood into muscle cells. Excess fatty acids, or blood lipids, are cleared into fat cells for storage for a “rainy day,” where they get turned into greasy triglycerides (such as the fat surrounding your steak). There is no energy storage without insulin – it is the key that unlocks the door to the fat cell to let energy enter and subsequently be stored as fat. Insulin makes fat – the more insulin, the more fat. And there it sits…and sits…as long as there is insulin around. When the insulin levels drop, the process goes in reverse: the triglycerides get broken down, causing the fat cells to shrink – when it happens, that’s weight loss! – and the fatty acids reenter the bloodstream and travel back to the liver, where they are burned by the liver or other organs. In this way, by cycling our insulin up and down, we burn what we need, and store the rest. Introducing the Hypothalamus For the past sixty years we’ve known that the brain, especially the one cubic centimeter at the base of the brain called the hypothalamus, controls this process of energy balance. It’s about the size of a thumbnail, and it is “ground zero” for the control of almost all the hormonal systems in the body. Imagine the organization of a taxicab company. At the bottom are the taxicab drivers, getting their orders from a central dispatcher by radio and shuttling passengers all over town. The target organs – the thyroid, the adrenal, the testicles, the ovaries – are like the cabbies. They receive their orders from the central dispatcher, or, in this case, the pituitary or “master gland,” which acts as the main control system. The hormones released are similar to the taxi’s computerized system, signaling to the pituitary to tell it how things are going out in the field. Like the central dispatcher who directs the cabs based on their location, the pituitary will then adjust its message. However, there is another layer of control: the chief executive officer, or CEO, who decides on hiring and firing, contracts, upgrades, and mergers and acquisitions. The company can’t turn a profit without the cabbies, be efficient without the dispatcher, or be sustainable long term without a CEO. Furthermore, the CEO can alter the direction of the company based on the profitability of its cabdrivers. The CEO is akin to the hypothalamus. It sends blood-borne hormonal signals to tell the pituitary what to do. It then makes large-scale decisions based on the function of the peripheral glands, which send it information via the bloodstream. And it integrates information from other areas of the brain to alter the long-term hormonal milieu. Marie’s hypothalamus was damaged beyond repair, which caused it to be ineffective in controlling her hormones and, therefore, her behavior. The Ventromedial Hypothalamus (VMH) and Energy Balance The hierarchy of energy balance is even more complicated. A subarea of this thumbnail is called the ventromedial hypothalamus (VMH), which serves the executive function of controlling energy storage versus expenditure. Because energy balance is so important to survival, there are redundant systems in case one goes amiss to ensure that the organism doesn’t die. It’s clear that energy balance is the most complex function we humans perform. It’s likewise apparent that energy storage, or the creation of fat cells, is the default strategy. Bottom line, we humans won’t give up our hard-earned energy without a fight. There are afferent (incoming) and efferent (outgoing) systems that control energy balance[27 - R. H. Lustig et al., “Disorders of Energy Balance,” in Pediatric Endocrinology, ed. M. Sperling (New York: Elsevier, 2008), pp. 788–838.] (see figure 4.1). The VMH receives acute meal-to-meal information from the GI (gastro-intestinal) tract on both hunger and satiety (not shown in the figure). Either one can turn the feeling of hunger on or off by itself. But that’s not all. In addition, the VMH receives more long-term information on one’s fat stores and nutrient metabolism: in other words, whether your body needs to consume more calories for longer-term survival. This information is conveyed via the hormones leptin and insulin to the hypothalamus, where it is decoded and either stimulates or suppresses appetite, and adjusts energy expenditure accordingly. Fig. 4.1. How the Brain and Hormones Work Together (or Don’t) to Regulate Energy Balance. The hypothalamus receives hormonal information from the fat cells (leptin). This information is processed into one of two signals: (a) anorexigenesis (I’m not hungry and I can burn energy) or (b) orexigenesis (I’m hungry and I want to store energy). Anorexigenesis turns on the sympathetic nervous system (responsible for muscle activity and fat loss), and turns off the vagus nerve (responsible for appetite and fat gain); while orexigenesis does the opposite. However, high insulin blocks the leptin signal, mimicking “brain starvation” and driving orexigenesis, so that we feel hungry even when we have eaten. From there, the hypothalamus sends signals from the brain to the body via two components of the autonomic nervous system. The autonomic nervous system is that portion of your body that controls your heart rate, blood pressure, and energy metabolism without your conscious effort. It is composed of two parts: the sympathetic nervous system (responsible for the fight-or-flight response) and the parasympathetic nervous system (responsible for “vegetative” functions such as food absorption and energy storage). The vagus nerve is one of the key components of the parasympathetic nervous system. There is a delicate balance and feedback loop between the sympathetic and parasympathetic systems. When that balance changes, that’s when problems ensue. The vagus nerve is fascinating. It connects the brain to all the digestive organs in the abdomen: the liver, the intestine, the pancreas, and also to the fat cells. It performs many different functions but with one ultimate goal: to store energy. The vagus is your energy storage nerve. The vagus has two parts: the afferent part (organs to brain), and the efferent part (brain to organs). The afferent vagus communicates the sensation of hunger between the stomach and brain, and also communicates information on energy processing during a meal between the liver and brain. The VMH interprets all these afferent signals, which leads to one of two physiologic states: anorexigenesis (I don’t need any more food, I can burn energy as needed, and I feel good) or orexigenesis (I don’t have enough food, I don’t want to burn any energy, and I will feel lousy until I get some more). The anorexigenesis signal turns on the sympathetic nervous system (SNS), which promotes energy expenditure by telling the adipose (fat) tissue and the muscles to burn energy, thereby resulting in weight loss and a sense of well-being. Anorexigenesis also turns off the vagus nerve and, in so doing, reduces appetite. Conversely, orexigenesis stimulates the vagus nerve to promote energy storage by increasing appetite. It accomplishes this by sending multiple signals through the vagus nerve: to the gastrointestinal tract to digest and absorb the food; to the adipose tissue to store more energy (make more fat); and to the pancreas to increase the amount of insulin released (promoting more energy storage into adipose tissue). Leptin and the Elusive “Holy Grail” of Obesity When the hormone leptin (from the Greek Leptos, for “thin”) was discovered in 1994, for the first time, scientists thought that obesity might have a biochemical basis. Leptin has been a veritable godsend to scientists who study obesity. It provided the starting point to understanding the biochemistry of the brain pathways that control food intake and the impetus for scientists and the National Institutes of Health (NIH) to believe that there was a simple way out of this mess, one that could be easily treated with medicine and science. The U.S. government began, and continues today, to shovel money at obesity research, hoping for a treatment that works. Conversely, leptin has been the biggest disappointment to those who suffer from obesity. And woe to the pharmaceutical industry, which hoped to harness its potential for a cure and generate megabucks in the process. The pharmaceutical company Amgen was so enamored of leptin’s blockbuster marketing potential that it offered $30 million for the exclusive marketing rights to the hormone, even before a human experiment had been performed. Amgen has since become so disillusioned that it has farmed leptin out to another company, Amylin Pharmaceuticals, to see if it will have better luck. Leptin is a protein made and released by fat cells. It circulates in the bloodstream, goes to the hypothalamus, and signals the hypothalamus that you’ve got enough energy stored up in your fat.[28 - J. S. Flier, “What’s in a Name? In Search of Leptin’s Physiologic Role,” J. Clin. Endocr. Metab. 83 (1998): 1407–13.] The discovery of leptin closed the loop, providing a servomechanism (like your home’s thermostat) in which the body’s fat cells told the hypothalamus whether the animal was in energy surplus (obesity) or dearth (starvation). Obese animals and humans deficient in leptin respond immediately to leptin treatment with remarkable losses of fat and also with increased activity.[29 - I. S. Farooqi et al., “Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency,” N. Engl. J. Med. 341 (1999): 913–15.] Leptin replacement corrected both behaviors, the gluttony and the sloth. The thought was, if you’re obese, then your leptin doesn’t work – you must be deficient and you just need more. Problem solved, right? Unfortunately, for the obese population, this simple-minded explanation was just that. Defective Leptin Signaling: Brain Starvation The VMH is constantly looking for the leptin signal. In the short-term, hormonal inputs can govern the size or the quality of this meal or that, but long term it’s all about leptin. Leptin tells the VMH that you have enough energy on board to burn the excess, feel good, reduce your long-term food intake, and remain weight stable. When your leptin signal works, you’re in energy balance, burning energy at a normal rate and feeling good.[30 - R. L. Leibel, “The Role of Leptin in the Control of Body Weight,” Nutr. Rev. 60 (2002): S15–S9.] Every human has a “personal leptin threshold” above which the brain interprets a state of energy sufficiency. Thus, the leptin-replete state is characterized by appropriate appetite, normal physical activity, and feelings of well-being. Woe to the 97-pound weakling who can’t bulk up and gain weight; his leptin threshold is set too low, and his leptin is telling his brain to burn off any excess. But what if leptin doesn’t work or the threshold is set too high? When the VMH can’t see the leptin signal, the brain interprets this as “starvation” and will direct the rest of the body to do whatever it can to increase its energy stores. The VMH relays messages to the sympathetic nervous system (SNS) to conserve energy and reduce activity. Energy expenditure is reduced by 20 percent, a great reason to feel like a sloth.[31 - R. L. Leibel et al., “Changes in Energy Expenditure Resulting from Altered Body Weight,” N. Engl. J. Med. 332 (1995): 621–28.] Furthermore, the VMH wants the body to increase energy storage. It will increase the firing of the vagus nerve in order to amplify insulin release from the pancreas and shunt more energy into fat cells, with the ultimate goal of making more leptin. The vagus makes you hungry in order that you store more energy (gluttony). Simply put, defective leptin signaling in the VMH is what brain starvation is all about. This phenomenon occurs in two ways: Leptin deficiency. Dr. Jeff Friedman of Rockefeller University is credited with cloning the leptin gene from leptin-deficient mice,[32 - Y. Zhang et al., “Positional Cloning of the Mouse Obese Gene and Its Human Homologue,” Nature 393 (1994): 425–32.] which are the rodent equivalents of a 400-pound couch potato. While normal weight at birth, these mice immediately eat like there’s no tomorrow and just sit there – the only time they ever get off their behinds is if you put food on the other side of the cage; then they’ll waddle over to it, devour it, and sit there instead. These mice are deficient in leptin due to a genetic mutation. Their behaviors of gluttony and sloth are genetically determined. Their brain can’t see their fat and in turn thinks the body is starving. Friedman’s lab also showed that giving these mice back the leptin they were missing by daily injection reduced their food intake and increased their physical activity back to normal. They lost the weight. Not only that, but all the physiological problems associated with their obesity – the diabetes, the lipid problems, and early death from heart disease – all disappeared. This made leptin look for all intents and purposes like the “holy grail” of obesity. If leptin deficiency was the cause of this pandemic, we could simply replace it, and all the unfortunate souls afflicted could be saved. Thus far, fourteen children with mutations of the leptin gene have been identified in the entire world. These children cannot make leptin no matter how big their fat cells are, and their brains are in constant starvation mode. Amazingly, with a shot of leptin every day, they lose weight rapidly, and it’s all fat (no muscle). They stop their ravenous behavior, start moving, and their puberty goes into gear.[33 - I. S. Farooqi et al., “Genetics of Obesity in Humans,” Endocr. Rev. 27 (2006): 710–18.] For these patients, leptin is hormone-replacement therapy; while not a cure, it’s the next best thing. Leptin resistance. This is the key to the obesity epidemic. With a few rare exceptions, the other 1.5 billion overweight or obese people on the planet suffer from this. Deciphering leptin resistance is the “holy grail” of obesity. These people have plenty of leptin, and each one’s blood leptin level correlates with his or her amount of body fat. This suggests that obese people are not leptin deficient but rather leptin resistant.[34 - H. Munzberg et al., “Molecular and Anatomical Determinants of Central Leptin Resistance,” Nat. Neurosci. 8 (2005): 566–70.] Their hypothalami can’t see their leptin, so their brains think they’re starving, and will therefore try to increase energy storage (gluttony) and conserve energy usage (sloth). In 1999, Steven Heymsfield, then at Columbia University, gave daily injections of leptin at varying doses to obese adults for six months. All these people had high leptin levels to start. The degree of weight loss, even with the highest dosage of leptin, was underwhelming.[35 - S. B. Heymsfield et al., “Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial,” JAMA 282 (1999): 1568–75.] Clearly these obese people were leptin resistant. They couldn’t respond to their own leptin, and no amount of extra leptin was going to make a difference. Heymsfield’s study was the end of the promise of leptin as a stand-alone therapy for obesity and the end of Amgen’s interest. Hypothalamic Obesity: Behavior or Biochemistry? This is where I enter the story. In 1995, I arrived in Memphis to start work at St. Jude Children’s Research Hospital as a pediatric neuroendocrinologist. My training is in taking care of kids with brain tumors, and St. Jude had a large population of survivors, Many of these children develop hormonal deficiencies because of damage to the hypothalamus – due to the tumor itself, the neurosurgery to remove it, or the radiation and chemotherapy they receive to try to kill it. The good news is that we endocrinologists can treat these children by replacing most of the hormones that are missing – we can affect their growth, energy metabolism, and cognitive status; induce puberty when the children are age appropriate; and improve their overall health. However, a relatively small number of children like Marie (and adults) who survive their brain tumors become massively obese after their tumor therapy is complete. Their hypothalamus is damaged, and their weight skyrockets. Their appetites aren’t that different from those of other obese children, but their energy expenditure is markedly decreased. (Marie didn’t move.) Those affected sit on the couch, watch TV, eat, poop, sleep, and generally lose interest in the world around them. As one parent stated, “It’s double jeopardy. To think you might lose your kid to a cancer, and survive it, but then to lose your kid to a complication instead.” Patients with this form of obesity, called hypothalamic obesity, can’t lose weight. Even if these kids eat only 500 calories a day, they gain weight.[36 - G. A. Bray et al., “Manifestations of Hypothalamic Obesity in Man: A Comprehensive Investigation of Eight Patients and a Review of the Literature,” Medicine 54 (1975): 301–33.] The neurons in the hypothalamus, which sense the leptin signal, are all dead. The “servo-mechanism” for energy balance had been short-circuited. This is leptin resistance at its worst – an anatomic leptin resistance. Rodent studies dating back to the early 1950s show that when you damage the VMH, the animal will become massively obese, and not even food restriction will reverse that. The VMH-lesioned rats ate more than they needed and burned less than they should have. Unlike the leptin-deficient mice, no amount of leptin would fix the problem. These animals had anatomic leptin resistance.[37 - N. Satoh et al., “Pathophysiological Significance of the Obese Gene Product, Leptin in Ventromedial Hypothalamus (VMH)-Lesioned Rats: Evidence for Loss of Its Satiety Effect in VMH-Lesioned Rats,” Endocrinology 138 (1997): 947–54.] The leptin had no place to act. The obese children I saw at St. Jude were similar to these VMH-lesioned rats. There was no fixing them because there was no way to regrow those neurons. Those kids were stuck forever in bodies that just kept storing energy instead of burning it,[38 - M. G. Shaikh et al., “Reductions in Basal Metabolic Rate and Physical Activity Contribute to Hypothalamic Obesity,” J. Clin. Endocr. Metab. 93 (2008): 2588–93.] with brains that constantly thought the bodies were starving. They would forever get fatter on fewer calories, never feel good, and would lose interest in everything around them. If this isn’t hell on earth for parent and child, I don’t know what is. Worst yet, there was no treatment. Diet and exercise is notoriously ineffective in these children. Weight loss drugs also didn’t work. In 1995, I was faced with a clinic full of patients with hypothalamic obesity following their brain tumor therapy. How to help them? I couldn’t give them leptin, because the block at the hypothalamus would not allow leptin to work. If any therapy were to be successful, it would have to work downstream of the leptin neuron, somewhere between the brain and the fat cell. Insulin: The “Leptinator” Normally, the amount of insulin released in response to a meal is yoked to the blood sugar rise. But there are a few things that force the pancreas to make extra insulin, the vagus nerve being chief among them. When the brain can’t see the leptin signal, as in children such as Marie, it interprets starvation. The vagus nerve goes into overdrive to store more energy, and kick-starts the pancreas to make extra insulin – even more than the glucose rise would predict. This excess insulin release drives nonstop energy storage and nonstop weight gain. As it happens, there is a drug available that can lower insulin secretion as a side-effect. It is called octreotide (Sandostatin, made by Novartis Pharmaceuticals) and is what we used to treat Marie. It is normally used to reduce pituitary growth hormone secretion in patients who have tumors of the pituitary gland, a disease called acromegaly. But it also happens to reduce pancreatic insulin secretion. It doesn’t wipe it out completely – that would cause diabetes – but it does reduce the rapid early release of insulin in response to a meal or a glucose tolerance test. But it’s expensive, requires injections, has side-effects, and with regard to obesity, it is for experimental studies only. We have treated many children with hypothalamic obesity with octreotide.[39 - R. H. Lustig et al., “Octreotide Therapy of Pediatric Hypothalamic Obesity: A Double-Blind, Placebo-Controlled Trial,” J. Clin. Endocr. Metab. 88 (2003): 2586–92.] When we were successful in reducing their insulin release, the patients lost weight and started to feel better. Parents were calling me up within the first few weeks, saying, “I’ve got my kid back!” Most amazingly, the children had started to be active. When we got the insulin down, Marie and patients like her improved physically, mentally, and socially. These studies highlight a crucial concept of obesity. Each of us is really two compartments: lean body mass (heart, liver, kidneys, brain, and muscles), which burns energy; and fat, which stores energy. Every molecule of energy consumed has a choice: to which compartment does the energy go? Is the energy burned or stored? Your consumption of energy is never high enough to overwhelm both compartments at the same time; no one can eat that much. This means that there is an issue of energy flux to the two compartments. What factor determines which compartment gets the energy? Your insulin does. The more insulin there is, the more energy goes to fat. Normally your fat makes more leptin, which would feedback on your hypothalamus and decrease your insulin by reducing appetite and limiting your energy intake. In this way, the “servo-mechanism” between leptin, the brain, your pancreas, your insulin, and your fat cells maintains normal energy balance. But…if your hypothalamus can’t see your leptin (in this case, because those neurons are dead from a brain tumor), then your brain thinks it’s starving. It will reduce your activity to conserve energy, and increase your appetite to store more energy. When leptin doesn’t work, the biochemistry comes first and the behaviors of gluttony and sloth are secondary. This is all well and good for Marie and the few unfortunate souls with hypothalamic obesity. They have a brain tumor. They have a legitimate excuse for being fat, and at least there is now a rational, if painful and expensive, approach to treatment. For them, the biochemistry dictates the behavior. However, the overwhelming majority of obese people do not have a goombah sitting in the middle of their heads wreaking havoc on their energy balance pathway. What does this phenomenon have to do with the obesity pandemic? As you will see, everything. Back in 1998, after three years of my working at St. Jude, the response of these patients was quite a revelation. My colleagues at the University of Tennessee and I wondered, “Is it possible that an adult population without brain tumors might manifest the same problem? Did they also have increased vagal tone driving excess insulin secretion and causing their obesity? If we gave them octreotide to suppress their insulin, might they lose weight, feel better, and start exercising?” We didn’t know what these patients looked like. So we did a pilot study in forty-four morbidly obese adults recruited from off the street. We treated all of them with octreotide for six months, courtesy of Novartis Pharmaceuticals. No dieting, no exercise, just the drug. We told them, “If the drug works, it will work by itself.” We’ve done this experiment twice, first as a pilot and then as a placebo-controlled trial. The majority of patients did not respond to the drug. But in about 20 percent of the adults, there was big-time weight loss. The thing that predicted their success was their insulin status. The lucky responders released insulin rapidly and in high amounts at baseline, just like the brain tumor kids,[40 - P. A. Velasquez-Mieyer et al., “Suppression of Insulin Secretion Promotes Weight Loss and Alters Macronutrient Preference in a Subset of Obese Adults,” Int. J. Obesity 27 (2003): 219–26; R. H. Lustig et al., “A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial of a Long-Acting Formulation of Octreotide in Promoting Weight Loss in Obese Adults with Insulin Hypersecretion,” Int. J. Obesity 30 (2006): 331–41.] and their quality of life improved with the drug. There is one final lesson to glean from these studies. All these obese adult subjects had high leptin levels. They were leptin resistant; if their leptin worked right, they wouldn’t have been obese. If leptin falls, the brain should interpret this as starvation and reduce the patient’s resting energy expenditure accordingly. But these patients’ resting energy expenditures went up! And their improvement in energy expenditure correlated with the suppression of their insulin levels, the same as with the brain tumor kids. When we were successful in getting their insulin down, their leptin resistance improved.[41 - R. H. Lustig et al., “Obesity, Leptin Resistance, and the Effects of Insulin Suppression,” Int. J. Obesity 28 (2004): 1344–48.] This suggests that insulin can block leptin signaling in the brain, and therefore insulin acts as a “leptin antagonist.”[42 - R. H. Lustig, “Childhood Obesity: Behavioral Aberration or Biochemical Drive? Reinterpreting the First Law of Thermodynamics,” Nature Clin. Pract. Endo. Metab. 2 (2006): 447–58.] Many scientists have now shown that insulin actions in the VMH block leptin signaling.[43 - M. Kellerer et al., “Insulin Inhibits Leptin Receptor Signalling in HEK293 Cells at the Level of Janus Kinase-2: a Potential Mechanism for Hyperinsulinaemia-Associated Leptin Resistance,” Diabetologia 44 (2001): 1125–32; J. W. Hill et al., “Acute Effects of Leptin Require PI3K Signaling in Hypothalamic Proopiomelanocortin Neurons in Mice,” J. Clin. Invest. 118 (2008): 1796–805; T. Kl?ckener et al., “High-fat Feeding Promotes Obesity via Insulin Receptor/PI3K-Dependent Inhibition of SF-1 VMH Neurons,” Nat. Neurosci. 14 (2001): 911–18.] A reduction in insulin concentrations results in a decline in leptin. Insulin and leptin are independent hormones that bind to separate receptors in the VMH. They have their own separate pathways of action, but they share the same signaling cascade. When insulin levels at the VMH are chronically high, leptin cannot signal the hypothalamus. Deconstructing Darwin Whenever paradoxical events occur in biology, one has to look for an evolutionary explanation. Why should insulin block leptin signaling? What’s the advantage for insulin, the hormone that tells the body to store energy, to block leptin, the hormone that tells your brain to burn energy? Leptin is a necessary signal to the VMH for the initiation of high-energy processes, such as puberty and pregnancy. If leptin always worked right, then nobody could gain weight. Think of the 97-pound weakling at the beach. The crucial weight gain during puberty and pregnancy would be compromised, and our reproductive capacity would be shot. Twice in our lives we need to stop leptin from working, or we can’t gain the weight, and the species dies out. Since insulin drives energy storage, it makes sense that it should do double-duty, and also be the central blocker of leptin – one hormone, two coordinated actions. Indeed, both puberty and pregnancy are hyperinsulinemic states. When adulthood or the postpartum state is reached, the insulin levels fall, weight stabilizes or is lost, and leptin levels return toward baseline.[44 - V. D. Castracane et al., “Serum Leptin in Nonpregnant and Pregnant Women and in Old and New World Nonhuman Primates,” Exp. Biol. Med. 230 (2005): 251–54.] However, in maladaptive conditions, when insulin is high all the time and leptin signaling is impaired, the energy gets stored yet the brain sees starvation, and obesity worsens. When you examine the symptoms of obese and starved individuals, they are very similar. On first thought this sounds ludicrous, but it actually makes sense. Both claim fatigue, malaise, and depression. The reason for this in both groups is the inability to adequately respond to the leptin signal – in starvation because of the inadequacy of leptin, and in obesity because of the resistance to leptin. Furthermore, leptin concentrations drop precipitously during periods of short-term fasting (within twelve hours), declining faster than body fat stores. You haven’t lost any weight in that time, but your fat cells are already telling your brain you’re starving, driving your food intake back up. By the time you’re one day into any weight-loss regimen you’re already leptin deficient on top of being leptin resistant, meaning, you really can’t see the signal. Trying not to eat for a day to fit into that little black dress? Oops. This actually drives gluttony and sloth to return your weight to its baseline level. In a nutshell, this is the recidivism of obesity. If your brain thinks there’s no leptin (due to either leptin deficiency or leptin resistance) you’re pretty miserable. Your sympathetic nervous system goes into conservation mode, driving down your energy expenditure, physical activity, and quality of life. Your vagus nerve then goes into overdrive, driving up your appetite, your insulin, and your energy storage. The Alternate Interpretation of the First Law No matter the mechanism, insulin blocks leptin signaling both in rodents and in humans. In the body, insulin causes energy storage in fat cells. In the brain, insulin causes leptin resistance and “brain starvation.” Insulin delivers a one-two punch to drive gluttony and sloth, weight gain, and obesity the world over. Insulin is the bad guy in this story. This idea turns obesity on its head. The standard thinking in obesity is: “If you eat it, you had better burn it, or you’re going to store it”—in which case the weight gain is secondary to the two behaviors of increased energy intake (gluttony) and decreased energy expenditure (sloth). What these data are telling us is that it is the other way around. Storing energy is a biochemical process not under the patient’s control. Burning energy is synonymous with quality of life. Things that make you burn energy faster – such as exercise, ephedrine (off the market now), and caffeine (for about two hours) – make you feel good. Conditions that make you burn energy slower – starvation and hypothyroidism, for example – make you feel lousy. So, the first law needs to be reinterpreted: “If you are going to store it, and you expect to burn it, then you will have to eat it.”[45 - Lustig, “Childhood Obesity,” pp. 447–58.] In this interpretation, the biochemical process is primary, the weight gain is secondary, and the behaviors are a result of the biochemistry. Obesity is a biochemical alteration in the brain promoting leptin resistance with resultant weight gain and secondary changes in behavior to maintain energy balance. The apparent character defects of gluttony and sloth are not the cause of the problem; they are the result of the problem. The biochemistry drives the behavior, not vice versa. The linchpin in this biochemical alteration is the hormone insulin. The majority of humans, regardless of weight, release double the insulin today that we did thirty years ago for the same amount of glucose. Now we’re left with the $147 billion (the annual financial cost of obesity) question: If insulin is the bad guy and we’re all hyperinsulinemic as never before in the history of humankind, where did the excess insulin come from? And how do we reverse it? The plot thickens. Chapter 5 Food Addiction – Fact or Fallacy Salvador is a fifteen-year-old Latino boy with obesity, a fatty liver, and high blood pressure. He drinks four sodas a day. His mother does not buy them for him or keep them in the house. Rather, he buys them at the convenience store on the way to and from school. Salvador enrolls in our research study whereby each day, for ten days, he will consume the same number of calories from our hospital’s Metabolic Kitchen, which will provide all his food, prepared by a chef and sugar free. Nonetheless, each day, he buys a can of soda and brings it home, putting it on his dresser, next to those from the day before. He tells his mother, “When the study is over, I’m drinking them all.” Indeed, the evening of the end of the study, he drinks every last one, to his mother’s chagrin. He may not have been addicted physically, but the mental obsession and craving indicated dependence, and could not be suppressed. Life’s too short to eat bad food, even if it’s cheap. Eating is supposed to be an enjoyable experience, especially when the food is special. There’s nothing quite like going to a nice restaurant with the sights, sounds, and smells of a well-prepared meal. It’s one of the true enjoyments of life. Yet familiarity breeds greater cravings. Ask Philadelphians about their cheesesteaks, New Orleans denizens about their Po-Boys and beignets, or Memphians about their barbecue. Surprise! Those are among the three most obese cities in the country. Coincidence? As prodigious as some American cuisine is, is there really anything special about a soda, a French fry, or any item in a fast food restaurant? Yet we devour fast food as if it were going out of style. Americans consume Big Macs as if each one might be our last. (Given the mortality rates in the obese, each one just might be.) Fast food comprises a growing portion of food eaten outside the home. In the United States of the 1950s, fast food accounted for 4 percent of total sales of food outside the home. In 1997 it accounted for 34 percent. Each day, 30 percent of U.S. adults eat at a fast food outlet, and McDonald’s feeds forty-six million Americans. What about the rest of the world? They didn’t experience fast food growing up, yet it’s now the biggest seller in developing countries. There is no familiarity here; they weren’t raised on the stuff; they’re consuming it de novo. Why do they eat fast food when it’s not their traditional fare? Because it’s cheap? It certainly isn’t abroad. Why do the locals frequent Taco Bell in Mexico when the original tacos are cheaper and ostensibly healthier? Something more is going on here. Is the world addicted to fast food? The biology of addiction is at the center of this question. Might as Well Face It, We’re Addicted to… Our brains are wired for reward – it is the primary force behind human survival. Reward is the reason to get up in the morning. If you take away reward, you take away the reason to live. We know this from recent experience with the anti-obesity drug rimonabant, which was deep-sixed after it failed to gain approval from the FDA in 2007. Rimonabant is an endocannabinoid antagonist, or the “anti-marijuana” medicine – which means it’s also “anti-munchies.” It inhibits the sense of reward. While it worked to promote weight loss, 20 percent of the subjects who used it experienced serious psychiatric side effects, especially depression, and there were several suicides. Kill the reward system, and you just might want to kill yourself. Although the brain’s reward system is complex and has many inputs, it can be reduced to the “hedonic pathway.” This pathway is where primal emotions, reproductive drive, and the survival instinct are all housed and expressed. These reward mechanisms are thought to have evolved to reinforce behaviors that are essential for perpetuation of the species and survival: such as sex for reproduction and the enjoyment of food so that you eat. This is also the pathway that reinforces the positive and negative aspects of drugs of abuse such as nicotine, cocaine, morphine, and alcohol. In order to maintain eating as one of the most powerful urges in animal and human behavior, evolution has also made it a rich source of pleasure and reward. The hedonic pathway comprises a neural conduit between two brain areas: the ventral tegmental area (VTA) and the nucleus accumbens (NA, also known as the reward center), both of which are deep-brain structures. Pleasure occurs when the VTA signals the NA to release dopamine, a neurotransmitter. It’s a signal from one brain center to another. When the released dopamine binds to its specific dopamine D receptor in the NA, the sense of pleasure is experienced.[46 - K. D. Carr et al., “Evidence of Increased Dopamine Receptor Signaling in Food-Restricted Rats,” Neuroscience 119 (2003): 1157–67.] So what are neurotransmitters and receptors? Think of keys and locks. Each neuron is a cell body, and at its end is an axon (special fiber of the neuron that sends information). This axon has a synapse, or pathway, that connects to the dendrites (specialized fibers of the nerve cell that receive information) of the next neuron. When a neural impulse is generated in the first cell, it pulses down to the end of the axon, which contains little packets of neurotransmitters that are then released. These are the keys. They travel across the synapse to the receptors (locks), located in the dendrites of the next cell. There are many keys that take the path along the synapse, and not all of them make it to their destination. Along their way via the synapse, some are metabolized and some are “re-uptaken.” Dopamine is one of these types of keys traveling to fit into the locks of the D receptors in the next cell, thus determining the triggering and firing of the next cells down the chain. Food intake is just one readout of the hedonic pathway.[47 - M. L. Pelchat, “Of Human Bondage: Food Craving, Obsession, Compulsion, and Addiction,” Physiol. Behav. 76, (2002): 347–52.] It appears to mediate feeding on the basis of palatability rather than energy need: I’m stuffed, but that chocolate cake looks so good. When functional, the hedonic pathway helps to curtail food intake in situations where energy stores are replete: I don’t need to finish that macaroni and cheese. However, when dysfunctional, this pathway can increase food intake, leading to obesity. If you feed a rodent a palatable food (e.g., a high-fat, high-sugar food such as cookie dough), the animal experiences reward because dopamine is released from the VTA and binds to the D receptor in the NA. As long as that continues, the animal will continue to eat and experience reward. There are three processes that modulate this system in one direction or another: 1. Anything that increases the dopamine transmission to the NA increases the feeling of reward. 2. Anything that clears dopamine from the NA will extinguish the feeling of reward. 3. Anything that reduces the number of D receptors in the NA, or binding of dopamine to those receptors (such as chronic overuse of a substance), will shortchange reward. You then need more dopamine, and hence more of the substance, to get the same feeling of pleasure. These precepts are as true for food as they are for addictive drugs. And food and drugs cross over. With time we can become sensitized to a substance and need more of it to get the same effect. Once sensitized, animals and humans may become hyperresponsive to a new substance; this is known as cross-sensitization. In other words, if the brain has been wired for addiction, it’s easy to switch from one substance to another. Ask recovering alcoholics about their incessant need for coffee, tobacco, and/or sugar. A reinforcer is a stimulus that increases the probability that an animal or human will respond to the addictive drug. Food is a form of positive reinforcement. Dopamine stimulation in the NA reinforces the intake of drugs or alcohol and also of food. The reinforcing effect of dopamine is attributed to D receptor stimulation. As stated before, food intake increases as a result of morphine and marijuana use. The film Harold and Kumar Go to White Castle details the odyssey of two very stoned guys who seek to overcome seemingly insurmountable obstacles in their quest for a hamburger. We can measure this by dopamine release and D receptor signaling. Why does dopamine matter so much? In a normal person, dopamine will be cleared from the D receptors after he is satiated. If you have a decreased dopamine binding capacity, there is a perceived need for compulsive food intake to provide excess stimulation of these depressed circuits, thereby driving continued weight gain. The Usual Suspects: Leptin and Insulin Yup, them again. Not only are they central in the starvation response, but they are also key players in this hedonic pathway, modulating reward in response to meals. In normal circumstances, after you’ve eaten a sufficient amount, leptin sends a signal to the VTA to suppress the release of dopamine, thereby reducing the reward of food.[48 - I. S. Farooqi et al., “Leptin Regulates Striatal Regions and Human Eating Behavior,” Science epub, August 9, 2007/science.1144599 (2007).] So leptin extinguishes reward. But what if you are leptin resistant? That’s what obesity is: leptin resistance. If leptin can’t act, then the dopamine isn’t cleared from the NA, and the impetus for further consumption persists. If you’re leptin resistant, do you really think you have the willpower to ignore both the starvation signal and the reward signal, when every food outlet you pass by provides you with sight or smell cues to chow down? Starvation and reward conspire to thwart every obese person. What about insulin, leptin’s accomplice? Normally, people are sufficiently sensitive to insulin. Insulin’s job is to clear dopamine from the synapses (that pathway between the cells) in the NA.[49 - L. Carvelli et al., “PI3-Kinase Regulation of Dopamine Uptake,” J. Neurochem. 81 (2002): 859–69.] Thus, the rise in insulin that occurs during a meal blunts the reward of further food intake (I’ve eaten enough – I really don’t need a second helping). This acts as a servomechanism built into the hedonic pathway to prevent overfeeding. But what happens when you are insulin resistant? Insulin resistance leads to leptin resistance in the VTA, contributing to increased caloric intake by preventing dopamine clearance from the NA. Increased pleasure is then derived from food when energy stores are full.[50 - E. Anderzhanova et al., “Altered Basal and Stimulated Accumbens Dopamine Release in Obese OLETF Rats as a Function of Age and Diabetic Status,” Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (2007): R603–R11.] Insulin and leptin resistance lead not only to increased food intake but to increased palatable food intake or anything that is high in both fat and sugar: the muffins, the Cinnabons, the cookies, the cheesecake. Is it any wonder Mrs. Fields is in every shopping mall? Defining Food Addiction: Liking, Wanting, and Needing Look, we all like fast food. And why wouldn’t we? It’s designed to contain the greatest concentration of fat, sugar, salt, and caffeine, and is placed into as small a package as possible. Yummmm. It provides food cheaply, quickly, and without table service. The pretty packaging and restaurant environment increase its salience (the properties that make you like it more). Ten years ago, fast food locations in the United States generated more than $125 billion, which accounts for 15 percent of sales of the entire U.S. food industry. But liking it isn’t the same as wanting it. And wanting it isn’t the same as needing it.[51 - K. C. Berridge, “ ‘Liking’ and ‘Wanting’ Food Rewards: Brain Substrates and Roles in Eating Disorders,” Physiol. Behav. 97 (2009): 537–50.] Liking is an aesthetic state. You can turn it on and turn it off. As dopamine is released into the NA, our consumption of a Big Mac heightens our sense of reward. Then comes the insulin rush, and that should be the end of it. But when you’re insulin resistant, wanting is a psychological state and needing becomes a physiologic state. You can’t turn it on and off anymore. This is the nature of addiction to any substance of abuse. It’s what happens with nicotine, morphine, cocaine, and alcohol – and it happens with food. It can happen to anyone. It can happen to you. Substance dependence, in this case synonymous with addiction, is defined by the American Psychiatric Association (APA) as “a maladaptive pattern of substance abuse leading to clinically significant impairment or distress.” There is currently no standardized definition for food addiction despite many hypotheses in the medical literature. There are seven criteria for substance dependence according to the APA Diagnostic and Statistical Manual, the DSM-IV-TR. The first two are considered physiologic, whereas criteria 3–7 are considered psychological dependence. All these are seen in the obese, especially those who frequent fast food restaurants. To be considered addicted to any substance of abuse, one must meet at least three of the seven. 1. Tolerance. This is defined as the need for more substance to get the same effect, or when the same amount of substance produces less effect with continued use. That Big Mac still generates the dopamine rush, but the reward isn’t maintained, as your insulin won’t clear the dopamine from the NA. Since insulin resistance generates leptin resistance, you can’t stop the dopamine neurons in the VTA from firing in the first place. So your NA is awash in dopamine, and the insulin rush from the meal can’t turn it off. Since your hypothalamus and your NA won’t respond to the leptin signal, the drive to eat just keeps coming. And here’s the kicker: the more and the longer your NA is exposed to dopamine, the more those D receptors are going to be down-regulated. After chronic dopamine exposure, the D receptors themselves start to disappear. The locks vanish, much to the chagrin of the keys, which have nowhere to go. Now it takes more dopamine to ensure that the few receptors that don’t disappear are occupied. You need to eat more Big Macs just to get the same level of reward. 2. Withdrawal. This is characterized by physical signs (such as tremors) and psychological ones (anxiety, depression). This occurs due to lack of dopamine D receptor occupancy. In animals, anxiety and depression are indicated by unwillingness to spend time in a risky environment. In humans, withdrawal is expressed as symptoms of depression and anxiety. If you try to stop eating those Big Macs, your dopamine drops and you are consumed by feelings of anxiety and depression (just like those patients treated with rimonabant – the “anti-munchie” medicine). The only choice is to increase the dopamine, reoccupy those diminished D receptors, and maintain the vicious cycle of Big Mac consumption. If you need proof, I suggest you rent the 2004 documentary Super Size Me. The film’s author and star, Morgan Spurlock, began as a reasonably healthy specimen at 6 feet 2 inches and 185 pounds (for a BMI of 23.8, within the normal range). He was eating a reasonably healthy diet (his girlfriend was a vegan chef) before beginning a thirty-day ordeal of eating every meal at McDonald’s. By day eighteen, he relates to the camera, “You know, I was feeling awful. I was feeling like s-t. I was feeling sick, and unhappy…. Started eating; now I feel great. I feel so great, it’s crazy.” Mr. Spurlock just described withdrawal. In eighteen days, he went from being a person with healthy eating habits to a fast food addict. 3. Bingeing. This is defined as an escalation of intake, using a greater amount of the substance or using for a longer duration than intended. In animals, this can be measured by an increase in the number of times the animal presses a lever to self-administer a drug – or, in the case of a human, continuing to eat after satiety has been achieved. One can easily conceptualize binge drinking (think of the movie Animal House or your stereotypical chug-a-lug frat guy), but binge eating is harder to define. It is highly subjective, since what is a large amount to some may not be perceived as unusual by others. Binge eating disorder includes eating until uncomfortable; eating when not hungry; eating alone due to shame; feeling disgusted, depressed, or guilty after overeating; and marked distress over the bingeing. Many afflicted people will consume massive amounts of food, such as an entire sheet cake, alone and in the dark of their kitchen, with massive shame. 4. Desire or attempts to cut down or quit. As mentioned previously, diets and miracle drugs generate over $160 billion annually. Those who are overweight or obese are almost always on some new diet kick and are frequently “weight cycling,” or yo-yoing. Juicing, cleansing, meat only, carbs only – they grasp for any possible solution. And it’s almost never sustainable. After a period of days, weeks, or months, they frequently binge on the substance from which they were abstaining (often sugar), and the weight is gained back. The sense of failure and ensuing depression can be overwhelming. The obese then read a new article or book about the latest craze and begin the cycle again ad infinitum. It’s not that they aren’t trying. Their lives are often consumed by these attempts. 5. Craving or seeking. This is described as an intense drive to self-administer drugs. In food addiction research, craving is illustrated by the motivation to seek food. Drug craving and seeking have been experimentally described as a form of learning, where dopamine signaling facilitates the consolidation of memory; past experiences are used to inform future decisions. Rats “press the lever” for drugs because they have learned that it is rewarding. We press the credit card button for Frappuccinos.™ 6. Interference with life. This is defined by important work, social, or other life activities being compromised. Obesity can significantly hamper an individual’s quality of life. Mobility is markedly more difficult. Airlines may refuse you passage if you don’t fit into the seat. Employers may refuse to hire you based on your weight. Diabetes can lead to limb amputation, requiring use of a wheelchair. During the thirty days of Spurlock’s Super Size Me adventure, he gained 24.5 pounds, experienced mood swings, sexual dysfunction, and fat accumulation in his liver. While his experience of eating every meal at McDonald’s may be deemed extreme, these physical and physiological effects occurred within only a thirty-day period. 7. Use despite negative consequences. This is defined as continued use despite knowledge that use will make the problems worse. The health consequences associated with obesity are numerous (see chapter 19). Despite knowing and experiencing these health problems, the eating pattern continues unabated. What Makes Fast Food Addictive? In humans, food addiction is often compared to established criteria for substance dependence.[52 - A. K. Garber et al., “Is Fast Food Addictive?” Curr. Drug Abuse Rev. 4 (2011): 146–62.] One problem with this approach is that it shifts focus away from the potentially addictive properties of the food and onto the individual “afflicted” with the addiction. We prefer to focus on the addictive potential of the food itself by placing it in the scope of other identified substances of abuse. Alcohol is the most analogous substance to fast food for several reasons, including its biochemistry (see chapters 11 and 22). Fast food is high in calories, sugar, fat, salt, and caffeine. It is highly processed, energy dense, and specifically designed to be highly palatable. The majority of the fiber and a portion of the vitamins and minerals present in the original food have been extracted in processing (see chapter 14). Sugar, salt, and other additives are used to boost flavor. The end product is packaged and sold conveniently to deliver the contents. Which of these components could be addictive? Or are they addictive all together? A market share analysis of McDonald’s, the largest hamburger chain in the world, shows that its Big Mac and French fries are the top two most popular menu items. Extra value meals constitute 70 percent of purchases at McDonald’s, Wendy’s, and Burger King. The most popular combination at McDonald’s is a Big Mac, medium French fries, and medium regular soda, providing 1,130 calories for $5.99.[53 - T. Dumanovsky et al., “What People Buy from Fast-Food Restaurants: Caloric Content and Menu Item Selection, New York City 2007,” Obesity 17 (2007): 1369–74.] But we’re talking about addiction here. So let’s make it a large. Consider a food label for a typical fast food meal, consisting of a Big Mac, large French fries, and large Coke (32 ounces) (figure 5.1). No percentage daily value (%DV) is listed for sugar because there is currently no recommended daily intake for sugar (see chapter 16). Keep in mind that 50 percent of the American population is consuming this or a similar meal at least once per week. Fig. 5.1. Supersize Me? A McDonald’s Meal and Its Nutritional Value. A Big Mac, large fries, and a large soda provide 1,360 calories (two thirds of a standard day’s allotment) and 1,380 milligrams sodium (almost an entire day’s allotment). While the fat content is 38 percent of calories (which is not bad), the sugar content is 95 grams, or 19 teaspoons, or 390 calories, which is more than double what the American Heart Association recommends for one day. Salt This sample meal contains 1,380 milligrams of sodium (salt). The 2005 Dietary Guidelines for Americans provided a “tolerable upper intake level” of 2,300 milligrams of sodium per day, which is why the %DV of the sample meal is 54 percent. Processed foods of many sorts contribute more than 3,400 milligrams of sodium per day to the average American diet. Salt is one method by which the food industry can preserve foods and increase their shelf life. So salt and calories almost always go together. (Think potato chips.) But is it addictive? Data to support addiction to salt are currently confined to animal models. Studies in rats show dopamine signaling in response to salt, and administration of opioids encourages bingeing on salt. However, in humans, salt intake has traditionally been conceived as a learned preference rather than an addiction. The preference for salty foods is likely learned early in life. Four- to six-month-old infants establish a salt preference based on the sodium content of breast milk, water used to mix formula, and the rest of their diet. But clearly people can modulate their salt intake. For example, patients who crave salt due to diseases of the adrenal gland can reduce their salt intake when given the appropriate medicine. Also, people’s taste for salt can be retrained; hypertensive adults can be retrained to a lower-salt diet within twelve weeks.[54 - R. D. Mattes, “The Taste for Salt in Humans,” Am. J. Clin. Nutr. 65 (1997): 692S–97S.] So, based on the criteria for an addictive substance, salt doesn’t make the cut. Fat The high fat content of fast food is vital to its rewarding properties. This sample fast food meal contains 89 percent of the daily fat intake for an individual on a 2,000-calorie diet. In feeding studies, excess calories from fat are more efficiently stored than excess calories from carbohydrates (90–95 percent versus 75–85 percent). Therefore, fat intake has always traditionally been assumed to be the major determinant of weight gain. Animals will binge on pure fat when given intermittent access to it. They binge regardless of the type of fat ingested, which suggests that it is that fat content and not the type of fat present in fast food that encourages overeating (see chapter 10). However, rat models do not demonstrate other features of addiction to fat, such as tolerance or withdrawal. Keep in mind, however, that so-called “high-fat foods” are almost always also high in starch (e.g., pizza) or sugar (e.g., cookies). In fact, adding sugar significantly enhances preference for high-fat foods among normal-weight people.[55 - A. Drewnowski et al., “Cream and Sugar: Human Preferences for High-Fat Foods,” Physiol. Behav. 30 (1983): 629–33.] Thus, the combination of high fat along with high sugar is likely to be more addictive than high fat alone. Caffeine Soda is an integral part of the fast food meal. If you consumed a large soda with your McDonald’s value meal, the caffeine content would be approximately 58 milligrams. Soft drink manufacturers identify caffeine as a flavoring agent in their beverages, but only 8 percent of frequent soda drinkers can detect the difference in a blind taste test of caffeine-containing and caffeine-free cola.[56 - G. A. Bernstein et al., “Caffeine Withdrawal in Normal School-Age Children,” J. Am. Acad. Child Adolesc. Psychiatry 37 (1998): 858–65.] Thus, the most likely function of the caffeine in soda is to increase the salience (the quality that makes it “stand out”) of an already highly rewarding (sugared) beverage. Dependence on caffeine is well established, meeting all the DSM-IV-TR criteria for both physiologic and psychological dependence. In fact, up to 30 percent of people who consume caffeine may meet the criteria for dependence. Headache (attributed to increased cerebral blood flow velocity), fatigue, and impaired task performance have all been shown during caffeine withdrawal. In addition, reinforcement of intermittent caffeine consumption leads to tolerance. While children get their caffeine from soft drinks and chocolate, adults get most of their caffeine from coffee and tea. An 8-ounce cup of brewed coffee contains 95–200 milligrams of caffeine, depending on how it is brewed. The late comedian and social commentator George Carlin famously referred to coffee as “Caucasian crack.” However, few customers these days order a regular brewed coffee at chain restaurants. A study of Starbucks customers showed that the majority of them order blended drinks.[57 - C. Huang et al., “Calories from Beverages Purchased at 2 Major Coffee Chains in New York City, 2007,” Prev. Chronic Dis. 6 (2009): A118.] The ever popular “grande” (extra large) Mocha Frappucchino (without whipped cream) has 260 calories and 53 grams of sugar. Thus, as a known substance of abuse, caffeine in coffee drinks and soda is part and parcel of the phenomenon of food addiction. Sugar Although anecdotal reports abound supporting human “sugar addiction,” we are still not completely sure whether this is full-fledged dependence or merely habituation. Adding a soda to a fast food meal increases the sugar content tenfold. While Coca-Cola estimates that currently 42 percent of soft drinks sold nationwide are diet drinks (e.g., Coke Zero), when purchased at McDonald’s, 71 percent are the sugar-sweetened variety. In fact, in 2009 only seven items on the McDonald’s menu did not include sugar – French fries, hash browns, sausage, Chicken McNuggets (without dipping sauce), Diet Coke, black coffee, and iced tea (without sugar). While soda intake is independently related to obesity,[58 - L. R. Vartanian et al., “Effects of Soft Drink Consumption on Nutrition and Health: A Systematic Review and Meta-Analysis,” Am. J. Public Health 97 (2007): 667–75.] fast food eaters clearly drink more soda. It is likely that the widespread phenomenon of “soda addiction” is driven by the inclusion of caffeine, a known addictive substance. All criteria for sugar addiction have been demonstrated in rodent models.[59 - N. M. Avena et al., “Evidence for Sugar Addiction: Behavioral and Neurochemical Effects of Intermittent, Excessive Sugar Intake,” Neurosci. Biobehav. Rev. 32 (2008): 20–39.] First, rats exposed to intermittent sugar access (following restriction) will binge. Second, these animals show signs of withdrawal (teeth chattering, tremors, shakes, and anxiety) when the sugar is withdrawn. Third, seeking and craving have been demonstrated where animals consume more sugar after a two-week imposed abstinence – just like Salvador and his soda. Elevated dopamine levels perpetuate the binge, and overconsumption increases with time, consistent with tolerance. Finally, cross-sensitization has been demonstrated in sugar-addicted rats who readily switch to alcohol or amphetamine use. So, based on the data, sugar is addictive, and soda is doubly so. Deconstructing Darwin There is some evidence that sugar may be addictive in humans. Experimental studies show that obese subjects will use sugar to treat psychological symptoms. Overweight women who were self-reported carbohydrate cravers reported greater relief from various mood disorders in response to a carbohydrate-containing beverage as compared to a protein drink. But perhaps the best evidence for an opiate-like effect of sugar is the product Sweet-Ease. This is a sugar solution into which hospitals dip pacifiers for newborn boys undergoing circumcision, to reduce the pain of the procedure. Evolutionarily, sweetness was the signal to our ancestors that something was safe to eat because no sweet foods are acutely poisonous. (Even Jamaican vomiting sickness occurs only after consumption of unripe ackee fruit, which is not sweet.) So we gravitate to sweetness as a default. How many times do parents have to introduce a new food before a baby will accept it? About ten to thirteen times. But if that new food is sweet, how many times do you have to introduce it? Only once. And if a sucrose solution on a pacifier can provide enough analgesia for performing a circumcision, that’s an evolutionary winner, isn’t it? Pleasure versus Happiness You may have heard of the “gross national happiness index,” an indicator that measures quality of life or social progress in more psychological terms than does the economic indicator of gross domestic product (GDP). By all accounts, America is not very happy. Despite having the highest GDP, we score forty-fourth on the happiness index. Of course, our workaholic attitudes (Americans are afforded the least vacation time in the developed world) and the recent economic downturn all contribute to our unhappiness. But could our unhappiness be related to our food?[60 - M. L. Kringelbach et al., “The Functional Neuroanatomy of Pleasure and Happiness,” Discov. Med. 9 (2010): 579–87.] By all estimations, obese people are not happy. The question is whether their unhappiness is a cause or a result of their obesity. At this point we can’t say for sure, and it is entirely possible that both are correct. Here’s how. Happiness is not just an aesthetic state. Happiness is also a biochemical state, mediated by the neurotransmitter serotonin. The “serotonin hypothesis” argues that deficiency of brain serotonin causes severe clinical depression, which is why selective serotonin reuptake inhibitors (SSRIs) which increase brain serotonin, such as Wellbutrin and Prozac, are used as treatment. Interestingly, these medications are also used for obesity. One way to increase serotonin synthesis in the brain is to eat lots of carbohydrates.[61 - L. Christensen et al., “Changing Food Preference as a Function of Mood,” J. Psychol. 140 (2006): 293–306.] You can see where this is going. If you’re serotonin-deficient, you’re going to want to boost your serotonin any way you can. Eating more carbohydrates, especially sugar, initially does double duty: it facilitates serotonin transport and it substitutes pleasure for happiness in the short term. But as the D receptor down-regulates, more sugar is needed for the same effect. The insulin resistance drives leptin resistance (see chapter 4), and the brain thinks it’s starved, driving a vicious cycle of consumption to generate a meager pleasure in the face of persistent unhappiness. And this vicious cycle can happen to anyone. Just substitute a little pleasure for a little unhappiness, and presto! Addiction in no time at all. You, the Jury… There is one obvious hole in this thesis, and I’m sure you’ve been chomping on it throughout this entire chapter. Can anyone become addicted to fast food? Everyone in America eats fast food, but not everyone is addicted. With narcotics, chronic use pretty much assures addiction – ask Rush Limbaugh about his OxyContin – but fast food doesn’t fit this paradigm. There are lots of habitual fast food consumers who can stop if they wished. Instead, is there a subset of people who are “addictable” and who have chosen food as their preferred substance of abuse? This might explain why people who stop smoking start eating. Doctors are starting to come around to the concept of food addiction. Nora Volkow, the head of the National Institute on Drug Abuse (NIDA) is on record supporting the concept of food addiction.[62 - Can food really be addictive? Yes, says a national drug expert. See http://healthland.time.com/2012/04/05/yes-food-can-be-addictive-says-the-director-of-the-national-institute-on-drug-abuse/.] Yet not everyone is sold on the idea that obesity and addiction are related. For instance, in 2012 a British group challenged the obesity-addiction model,[63 - H. Ziauddeen et al., “Obesity and the Brain: How Convincing Is the Addiction Model?” Nature Rev. Neurosci. 13 (2012): 279–86.] arguing that not all obese people demonstrate addiction, that not all obese people have reduced dopamine receptors on neuroimaging, and that rats are not humans (although, of course, some humans are rats). By that token, not everyone who drinks becomes an alcoholic, but we do know that some people become addicted. So what’s your verdict? Is Salvador addicted to his sodas? Is fast food addictive? After treating obese children for the last fifteen years, I can categorically say that there are loads of people who can’t kick the habit. In fact, it’s more likely that children are unable to – perhaps because they were raised on the stuff or because their brains are more susceptible.[64 - M. E. Bocarsly et al., “Effects of Perinatal Exposure to Palatable Diets on Body Weight and Sensitivity to Drugs of Abuse in Rats,” Physiol. Behav. (2012) epub May 4, doi:10.1016/j.physbeh.2012.04.024.] There are several caveats to declaring fast food addictive. How often do you partake (consistently or intermittently)? With whom do you partake (with your family, or alone)? What do you order? How old are you? And, most important, do you have a soda (or sweet tea in the southeastern United States) with your meal? I’ve laid out the data that demonstrate that fat and salt increase the appeal of the fast food meal, but it’s the sugar and the caffeine that are the true hooks. We’ll come back to this time and again throughout the book, as this is where the action is. Chapter 6 Stress and “Comfort Food” Janie is thirteen years old. When she was five she developed a hypothalamic brain tumor, which was surgically removed. In the subsequent seven years, she gained 160 pounds (to a maximum weight of 242 pounds) and her oral glucose tolerance test showed massive insulin release, consistent with hypothalamic obesity. On an experimental protocol, our surgeons performed an experimental operation on Janie, which cut her vagus nerve. In the nine months following the surgery, she lost 22 pounds, reduced her hunger, had more energy, and felt much better. Then she disappeared from the clinic for nine months. When she returned, she had regained the 22 pounds and was back up to her maximum weight. She stated that the surgery had removed her hunger. So how and why did she gain it all back? It turns out she switched schools in sixth grade. The kids in the new school hurled insults, calling her Fatso, Miss Piggy, and The Blob. Despite a lack of hunger, the stress of her new situation caused her to eat incessantly. Janie switched to a new middle school, where she got along better with her peers, and lost weight again. This poor young lady is triply cursed. First she gets a brain tumor. Then she gets obese as a complication of the brain tumor. To top it all off, she has the misfortune of being a teenager (possibly the worst of the three). Even though we did our best to treat this girl’s biochemical difficulty, the social difficulty turned out to be even more potent. I take care of kids for a living. While the majority of them are cute and adorable, some kids can be downright mean. Especially adolescents. Bad behavior is de rigueur nowadays. How many movies out of Hollywood play on this adage? Rent Mean Girls, Sixteen Candles, or Can’t Buy Me Love in case you’ve forgotten what high school is like. Maybe it’s the testosterone and estrogen of puberty that makes some teenagers angry and turns them into bullies. Perhaps they build themselves up by taking other kids down with degrading remarks and slurs. Maybe it’s their upbringing. They see how their parents handle social issues and they emulate them. (Beware the mothers of the PTA in the San Fernando Valley.) But I do know one thing: many kids (and adults) respond to psychological stress by eating. Coincident with the rise in obesity throughout our society is an increased prevalence and severity of psychological stress.[65 - B. M. Kudielka et al., “Human Models in Acute and Chronic Stress: Assessing Determinants of Individual Hypothalamus-Pituitary-Adrenal Axis Activity and Reactivity,” Stress 13 (2010): 1–14.] Two mechanisms by which stress leads to obesity are stress-induced eating and stress-induced fat deposition.[66 - P. Bjorntorp, “Do Stress Reactions Cause Abdominal Obesity and Comorbidities?” Obes. Rev. 2 (2001): 73–86.] Both animals and humans have been documented to increase their food intake following stress or negative emotion, even if the organism is not hungry. Further, the type of food eaten tends to be high in sugar, fat, or both. There’s a load of evidence that humans are more stressed today than we were thirty years ago, which correlates directly with the expansion of our waistlines. Cortisol: Can’t Live with It, Can’t Live Without It The relationship between stress, obesity, and metabolic disease begins with the hormone cortisol, which is released by your adrenal glands (located on top of your kidneys). This is perhaps the most important hormone in your body. Too little cortisol, and you can die. If you’re missing any other hormone in your body – growth, thyroid, sex, or water-retaining hormones – you’ll feel lousy and your life will be miserable, but you won’t perish. But if you’re missing cortisol, you can’t handle any form of physical stress. As David Williams stated in the 2008 PBS series Unnatural Causes, “Stress helps to motivate us. In our society today everybody experiences stress. The person who has no stress is a person who is dead.” The acute rise in cortisol keeps you from going into shock when you dehydrate, improves memory and immune function, reduces inflammation, and increases vigilance. Normally cortisol will peak in a stressful situation (when you’re being chased by a lion or your boss is yelling at you for not getting the memo). Cortisol is necessary, in small doses and in short bursts. Conversely, long-term exposure to large doses of cortisol will also kill you – it’ll just take longer. If pressures (social, familial, cultural, etc.) are relentless, the stress responses remain activated for months or even years. When cortisol floods the bloodstream, it raises blood pressure; increases the blood glucose level, which can precipitate diabetes; and increases the heart rate. Human research shows that cortisol specifically increases caloric intake of “comfort foods” (e.g., chocolate cake).[67 - P. A. Tataranni et al., “Effects of Glucocorticoids on Energy Metabolism and Food Intake in Humans,” Am. J. Physiol. 271 (1996): E317–E25.] And cortisol doesn’t cause just any old weight gain. It specifically increases the visceral fat (see chapter 8), which is the fat depot associated with cardiovascular disease and metabolic syndrome. Beginning in the 1970s and lasting more than thirty years, the seminal “Whitehall study” charted the health of twenty-nine thousand British civil servants.[68 - M. Elovainio et al., “Socioeconomic Differences in Cardiometabolic Factors: Social Causation or Health-Related Selection? Evidence from the Whitehall II Cohort Study, 1991–2004,” Am. J. Epidemiol. 174 (2011): 779–89.] In the beginning, the scientists hypothesized that the high-power executives would have the highest rates of heart attack and coronary disease. The opposite proved to be true. Those lowest on the totem pole exhibited the highest levels of cortisol and of chronic disease. This held true not just on the bottom rung: the second person down on the social ladder had a higher likelihood of developing diseases than the person on the top rung, the third had a higher predisposition than the second, and so on. Death rates and illness correlate with low social status, even after controlling for behavior (e.g., smoking). The same holds true in America. The prevalence of diseases such as diabetes, stroke, and heart disease are highest among those who suffer from the most stress, namely middle- and lower-class Americans. These stressors are acutely felt in children as well. Almost 20 percent of American children live in poverty. The lifelong consequences of food and housing insecurity are toxic to the brain and alter its architecture early in life.[69 - J. P. Shonkoff et al., “Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention,” JAMA 301 (2009): 2252–59.] In particular, cortisol kills neurons that play a role in the inhibition of food intake.[70 - R. M. Sapolsky, “Depression, Antidepressants, and the Shrinking Hippocampus,” Proc. Natl. Acad. Sci. 98 (2001): 12320–22.] Whether one builds a strong or weak foundation in childhood is a great determinant of later health and eating patterns. Thus, childhood stress increases the risk of obesity during adolescence and adulthood. Some of the factors associated with lower thresholds for stress and higher “cortisol reactivity” are low socioeconomic status, job stress, being female, scoring high in dietary restraint (a measure of chronic dieting), and an overall lack of power and confidence. Taking three buses to get anywhere, working two or more jobs, figuring out how to put food on the table, and not knowing whether you will be able to pay the rent – all significantly affect not just your state of mind but also your physiological state. And if you are not Caucasian, the stresses associated with racism will double these health effects. African Americans and Latinos suffer from higher mortality rates of nearly every disease than their white counterparts. While there are certainly genetic influences, stress plays a major role in health disparities among the races. The Science of Stress The stress response is a cascade of adaptive responses that originate in the central nervous system. When an individual perceives stress (anything from a plane crash to a calculus test), the body interprets and processes the threat in an area of the brain called the amygdala. From there, the amygdala switches on two other systems. First, like a game of telephone, the amygdala tells the hypothalamus, which tells the pituitary, which tells the adrenal gland to release cortisol. In an acute situation, cortisol feeds back on the hypothalamus to stop further secretion, and its effects would be short term and limited. (I escaped the lion! Ah, sweet relief. Time for a nap.) This negative feedback loop should protect the brain and body from prolonged, detrimental cortisol exposure. Second, the amygdala activates the sympathetic nervous system (SNS), raising the heart rate. Both cortisol and the SNS raise blood sugar and blood pressure, to prepare the individual for meeting and adapting to stress. These systems should shut off after the stress has passed. However, either chronic stress or heightened responses to stress due to ineffective coping strategies will unleash a long-term cortisol cascade. In these prolonged stressful situations, the cortisol is unregulated. Why doesn’t the cortisol feed back in the state of chronic stress to control its own release? This is one of the biggest questions in science today. Apparently, the amygdala’s ability to perceive the cortisol signal becomes reduced in response to the excess cortisol supply. Chronic exposure suppresses the negative feedback of cortisol on the brain. How and why this happens is still unknown. Whatever the mechanism, it’s a vicious cycle: stress breeds more cortisol, which in turn breeds more stress.[71 - M. F. Dallman et al., “Chronic Stress and Comfort Foods: Self-Medication and Abdominal Obesity,” Brain Behav. Immun. 19 (2005): 275–80.] “Stressed” Is “Desserts” Spelled Backward Over several years, prolonged cortisol leads to excessive food intake – but not just any food. Human research shows that cortisol specifically increases caloric intake of “comfort foods” (those with high energy density or high fat and high sugar). Your spouse is late and the kids won’t stop whining? Break out the Ben & Jerry’s. What predisposes certain people to stress-induced eating? For one thing, it’s not the stress itself; it’s the response to stress. Stress, like art, is in the eye of the beholder. The same level of stress can have varying effects on different people. The perception of chronic stress causes increased caloric intake of “comfort foods,” but only among those with high cortisol reactivity. People who are “stress eaters” exhibit significant increases in insulin, weight, and cortisol at night (normally the time for cortisol to be very low) during a stressful period. My colleague Elissa Epel at the University of California, San Francisco showed that those subjects who generated the greatest amount of cortisol in response to a psychological stressor also consumed the greatest amount of high-fat, sugary food.[72 - A. J. Tomiyama et al., “Comfort Food Is Comforting to Those Most Stressed: Evidence of the Chronic Stress Response Network in High Stress Women,” Psychoneuroendocrinology 36 (2011): 1513–19.] Stress has also been postulated to play a role in metabolic syndrome in childhood, a time when eating patterns and fat cells are “programmed.” Stress may affect food intake in several ways. One outcome of stress is reduced sleep, which is both a contributor to and a consequence of obesity. We’re all getting less sleep than we used to, especially children (Janie included).[73 - A. Sadeh et al., “Sleep Patterns and Sleep Disruptions in School-Age Children,” Dev. Psychol. 36 (2000): 291–301.] BMI increases over time among short sleepers. And just because you sleep less does not mean you are filling your waking hours with exercise. At the biochemical level, acute sleep loss is associated with elevations in markers of systemic inflammation and signs of metabolic syndrome. Sleep deprivation has been shown to increase cortisol and reduce leptin, and in doing so, mimic starvation and hunger. At the brain level, sleep deprivation increases the hunger hormone ghrelin, which increases the “value” each of us puts on food, and also activates the reward system,[74 - C. Benedict et al., “Acute Sleep Deprivation Enhances the Brain’s Response to Hedonic Food Stimuli: An fMRI Study,” J. Clin. Endocr. Metab. 97 (2012): E443–47.] making you eat even more chocolate cake. Conversely, poor sleep is common among obese individuals. This is in part because high BMI is a strong predictor of obstructive sleep apnea, which, due to retention of carbon dioxide, appears to make obesity even worse. The role of stress and cortisol in eating extends from the physiologic to the pathologic, and from overeating to undereating. When I was a pediatric resident working thirty-six hours out of every forty-eight, our group was divided into two cohorts: those who hit the cafeteria and those who lived on coffee. I tried the coffee, but my hands shook too much when I was threading catheters into umbilical arteries on premature infants, so I turned to food. I gained 45 pounds during residency, and I haven’t taken them off yet. A monkey model that drives cortisol up is called the variable foraging demand model, which is the animal equivalent to “food insecurity.”[75 - D. Kaufman et al., “Early-Life Stress and the Development of Obesity and Insulin Resistance in Juvenile Bonnet Macaques,” Diabetes 56 (2007): 1382–86.] In this model, monkeys have access to food in one of three ways: (1) ad lib, in which the food is available all the time; (2) at every meal, the animal has to work to find food that has been hidden in a maze of tubes; or (3) a random combination of the two, called variable foraging. Despite the fact that the animals in the second group have to work at finding their food, their body weights and cortisol levels are similar to those of the ad lib monkeys: they know what they have to do to attain their next meal. However, for the third group, the variable foragers, the uncertainty of the food availability drives up their cortisol levels and they become markedly obese. Stress and cortisol also promote faster addiction to various drugs of abuse and likely food as well. Experiments in animals emphasize that stress or cortisol administration (particularly uncontrollable stress) increases the likelihood of abusing drugs such as cocaine. Another way to drive up cortisol in monkeys is by placing them in group housing, thereby exposing them to social hierarchy. Invariably, one animal will rise in the social order to become the alpha male, or the leader of the cage. This animal, akin to an all-powerful CEO, will have the lowest cortisol levels. The cortisol levels of the subordinates will be much higher. When all the monkeys are then provided access to cocaine for self-administration, while the alpha male won’t get hooked, the subordinates become addicts. This can also happen with food. Thus the stress and reward systems are linked, making food addiction among those who eat to manage their stress a fa?t accompli Конец ознакомительного фрагмента. Текст предоставлен ООО «ЛитРес». Прочитайте эту книгу целиком, купив полную легальную версию (https://www.litres.ru/dr-lustig-robert/fat-chance-the-bitter-truth-about-sugar/?lfrom=688855901) на ЛитРес. Безопасно оплатить книгу можно банковской картой Visa, MasterCard, Maestro, со счета мобильного телефона, с платежного терминала, в салоне МТС или Связной, через PayPal, WebMoney, Яндекс.Деньги, QIWI Кошелек, бонусными картами или другим удобным Вам способом. notes Примечания 1 J. Kim et al., “Trends in Overweight from 1980 Through 2001 Among Preschool-Aged Children Enrolled in a Health Maintenance Organization,” Obesity 14 (2006): 1164–71. 2 S. J. Olshansky et al., “A Potential Decline in Life Expectancy in the United States in the 21st Century,” New Engl. J. Med. 352 (2005): 1138–45. 3 World Health Organization, Fact Sheet: Obesity and Overweight (2011), www.who.int/mediacentre/factsheets/fs311/en/. 4 UN General Assembly, “Prevention and Control of Non-Communicable Diseases,” New York, 2010. 5 J. M. Chan et al., “Obesity, Fat Distribution, and Weight Gain as Risk Factors for Clinical Diabetes in Men,” Diabetes Care 17 (1994): 961–69. 6 S. L. Gortmaker et al., “Changing the Future of Obesity: Science, Policy, and Action,” Lancet 378 (2011): 838–47. 7 K. C. Sung et al., “Interrelationship Between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes,” J. Clin. Endocrinol. Metab. 96 (2011): 1093–97. 8 S. L. Gortmaker et al., “Changing the Future of Obesity: Science, Policy, and Action,” Lancet 378 (2011) 838–47. 9 R. Padwal et al., “Long-Term Pharmacotherapy for Obesity and Overweight,” Cochrane Database Syst. Rev., Art. No.: CD004094. DOI: 10.1002/14651858 (2004). PMID: 15266516. 10 C. B. Newgard et al., “A Branched-Chain Amino Acid-Related Metabolic Signature That Differentiates Obese and Lean Humans and Contributes to Insulin Resistance,” Cell Metab. 9 (2009): 311–26. 11 P. Chanmugam et al., “Did Fat Intake in the United States Really Decline Between 1989–1991 and 1994–1996?” J. Am. Diet. Assoc. 103 (2003): 867–72. 12 D. Thompson et al., “Lifetime Health and Economic Consequences of Obesity,” Arch. Int. Med. 159 (1999): 2177–83. 13 J. Bhattacharya et al., “Who Pays for Obesity?” J. Econ. Perspect. 25 (2011): 139–58. 14 J. B. Schwimmer et al., “Health-Related Quality of Life of Severely Obese Children and Adolescents,” JAMA 289 (2003): 1813–19. 15 T. A. Wadden et al., “Treatment of Obesity by Very Low Calorie Diet, Behavior Therapy, and Their Combination: A Five-Year Perspective,” Int. J. Obes. 13 (1989): 39–46; M. W. Schwartz et al., “Regulation of Body Adiposity and the Problem of Obesity,” Arterioscler. Thromb. Vasc. Biol. 17 (1997): 233–38. 16 S. Yoo et al., “Obesity in Korean Pre-Adolescent School Children: Comparison of Various Anthropometric Measurements Based on Bioelectrical Impedance Analysis,” Int. J. Obes. 30 (2006): 1086–90. 17 N. Gupta et al., “Childhood Obesity in Developing Countries: Epidemiology, Determinants, and Prevention,” Endocr. Rev. 33 (2012): 48–70. 18 A. Ramachandran et al., “Diabetes in Asia,” Lancet 375 (2010): 408–18. 19 B. M. Popkin, “Global Nutrition Dynamics: The World Is Shifting Rapidly Toward a Diet Linked with Noncommunicable Diseases,” Am. J. Clin. Nutr. 84 (2006): 289–98. 20 Y. C. Klimentidis et al., “Canaries in the Coal Mine: A Cross-Species Analysis of the Plurality of Obesity Epidemics,” Proc. Biol. Sci. 278 (2011): 1626–32. 21 W. Park et al., “The Metabolic Syndrome: Prevalence and Associated Risk Factor Findings in the US Population from the Third National Health and Nutrition Examination Survey, 1988–1994,” Arch. Intern. Med. 163 (2003): 427–36. 22 C. Gordon et al., “Measuring Food Deserts in New York City’s Low-Income Neighborhoods,” Health Place 17 (2011): 696–700. 23 M. de Onis et al., “Global Prevalence and Trends of Overweight and Obesity Among Preschool Children,” Am. J. Clin. Nutr. 92 (2010): 1257–64. 24 Kaiser Family Foundation, “Food for Thought: Television Food Advertising to Children in the United States” (2007), www.kff.org/entmedia/upload/7618.pdf. 25 J. Kim et al., “Trends in Overweight from 1980 through 2001 Among Preschool-Aged Children Enrolled in a Health Maintenance Organization,” Obesity 14 (2006): 1164–71. 26 A. R. Cashmore, “The Lucretian Swerve: The Biological Basis of Human Behavior and the Criminal Justice System,” Proc. Natl. Acad. Sci. 107 (2010): 4499–504. 27 R. H. Lustig et al., “Disorders of Energy Balance,” in Pediatric Endocrinology, ed. M. Sperling (New York: Elsevier, 2008), pp. 788–838. 28 J. S. Flier, “What’s in a Name? In Search of Leptin’s Physiologic Role,” J. Clin. Endocr. Metab. 83 (1998): 1407–13. 29 I. S. Farooqi et al., “Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency,” N. Engl. J. Med. 341 (1999): 913–15. 30 R. L. Leibel, “The Role of Leptin in the Control of Body Weight,” Nutr. Rev. 60 (2002): S15–S9. 31 R. L. Leibel et al., “Changes in Energy Expenditure Resulting from Altered Body Weight,” N. Engl. J. Med. 332 (1995): 621–28. 32 Y. Zhang et al., “Positional Cloning of the Mouse Obese Gene and Its Human Homologue,” Nature 393 (1994): 425–32. 33 I. S. Farooqi et al., “Genetics of Obesity in Humans,” Endocr. Rev. 27 (2006): 710–18. 34 H. Munzberg et al., “Molecular and Anatomical Determinants of Central Leptin Resistance,” Nat. Neurosci. 8 (2005): 566–70. 35 S. B. Heymsfield et al., “Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial,” JAMA 282 (1999): 1568–75. 36 G. A. Bray et al., “Manifestations of Hypothalamic Obesity in Man: A Comprehensive Investigation of Eight Patients and a Review of the Literature,” Medicine 54 (1975): 301–33. 37 N. Satoh et al., “Pathophysiological Significance of the Obese Gene Product, Leptin in Ventromedial Hypothalamus (VMH)-Lesioned Rats: Evidence for Loss of Its Satiety Effect in VMH-Lesioned Rats,” Endocrinology 138 (1997): 947–54. 38 M. G. Shaikh et al., “Reductions in Basal Metabolic Rate and Physical Activity Contribute to Hypothalamic Obesity,” J. Clin. Endocr. Metab. 93 (2008): 2588–93. 39 R. H. Lustig et al., “Octreotide Therapy of Pediatric Hypothalamic Obesity: A Double-Blind, Placebo-Controlled Trial,” J. Clin. Endocr. Metab. 88 (2003): 2586–92. 40 P. A. Velasquez-Mieyer et al., “Suppression of Insulin Secretion Promotes Weight Loss and Alters Macronutrient Preference in a Subset of Obese Adults,” Int. J. Obesity 27 (2003): 219–26; R. H. Lustig et al., “A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial of a Long-Acting Formulation of Octreotide in Promoting Weight Loss in Obese Adults with Insulin Hypersecretion,” Int. J. Obesity 30 (2006): 331–41. 41 R. H. Lustig et al., “Obesity, Leptin Resistance, and the Effects of Insulin Suppression,” Int. J. Obesity 28 (2004): 1344–48. 42 R. H. Lustig, “Childhood Obesity: Behavioral Aberration or Biochemical Drive? Reinterpreting the First Law of Thermodynamics,” Nature Clin. Pract. Endo. Metab. 2 (2006): 447–58. 43 M. Kellerer et al., “Insulin Inhibits Leptin Receptor Signalling in HEK293 Cells at the Level of Janus Kinase-2: a Potential Mechanism for Hyperinsulinaemia-Associated Leptin Resistance,” Diabetologia 44 (2001): 1125–32; J. W. Hill et al., “Acute Effects of Leptin Require PI3K Signaling in Hypothalamic Proopiomelanocortin Neurons in Mice,” J. Clin. Invest. 118 (2008): 1796–805; T. Kl?ckener et al., “High-fat Feeding Promotes Obesity via Insulin Receptor/PI3K-Dependent Inhibition of SF-1 VMH Neurons,” Nat. Neurosci. 14 (2001): 911–18. 44 V. D. Castracane et al., “Serum Leptin in Nonpregnant and Pregnant Women and in Old and New World Nonhuman Primates,” Exp. Biol. Med. 230 (2005): 251–54. 45 Lustig, “Childhood Obesity,” pp. 447–58. 46 K. D. Carr et al., “Evidence of Increased Dopamine Receptor Signaling in Food-Restricted Rats,” Neuroscience 119 (2003): 1157–67. 47 M. L. Pelchat, “Of Human Bondage: Food Craving, Obsession, Compulsion, and Addiction,” Physiol. Behav. 76, (2002): 347–52. 48 I. S. Farooqi et al., “Leptin Regulates Striatal Regions and Human Eating Behavior,” Science epub, August 9, 2007/science.1144599 (2007). 49 L. Carvelli et al., “PI3-Kinase Regulation of Dopamine Uptake,” J. Neurochem. 81 (2002): 859–69. 50 E. Anderzhanova et al., “Altered Basal and Stimulated Accumbens Dopamine Release in Obese OLETF Rats as a Function of Age and Diabetic Status,” Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (2007): R603–R11. 51 K. C. Berridge, “ ‘Liking’ and ‘Wanting’ Food Rewards: Brain Substrates and Roles in Eating Disorders,” Physiol. Behav. 97 (2009): 537–50. 52 A. K. Garber et al., “Is Fast Food Addictive?” Curr. Drug Abuse Rev. 4 (2011): 146–62. 53 T. Dumanovsky et al., “What People Buy from Fast-Food Restaurants: Caloric Content and Menu Item Selection, New York City 2007,” Obesity 17 (2007): 1369–74. 54 R. D. Mattes, “The Taste for Salt in Humans,” Am. J. Clin. Nutr. 65 (1997): 692S–97S. 55 A. Drewnowski et al., “Cream and Sugar: Human Preferences for High-Fat Foods,” Physiol. Behav. 30 (1983): 629–33. 56 G. A. Bernstein et al., “Caffeine Withdrawal in Normal School-Age Children,” J. Am. Acad. Child Adolesc. Psychiatry 37 (1998): 858–65. 57 C. Huang et al., “Calories from Beverages Purchased at 2 Major Coffee Chains in New York City, 2007,” Prev. Chronic Dis. 6 (2009): A118. 58 L. R. Vartanian et al., “Effects of Soft Drink Consumption on Nutrition and Health: A Systematic Review and Meta-Analysis,” Am. J. Public Health 97 (2007): 667–75. 59 N. M. Avena et al., “Evidence for Sugar Addiction: Behavioral and Neurochemical Effects of Intermittent, Excessive Sugar Intake,” Neurosci. Biobehav. Rev. 32 (2008): 20–39. 60 M. L. Kringelbach et al., “The Functional Neuroanatomy of Pleasure and Happiness,” Discov. Med. 9 (2010): 579–87. 61 L. Christensen et al., “Changing Food Preference as a Function of Mood,” J. Psychol. 140 (2006): 293–306. 62 Can food really be addictive? Yes, says a national drug expert. See http://healthland.time.com/2012/04/05/yes-food-can-be-addictive-says-the-director-of-the-national-institute-on-drug-abuse/. 63 H. Ziauddeen et al., “Obesity and the Brain: How Convincing Is the Addiction Model?” Nature Rev. Neurosci. 13 (2012): 279–86. 64 M. E. Bocarsly et al., “Effects of Perinatal Exposure to Palatable Diets on Body Weight and Sensitivity to Drugs of Abuse in Rats,” Physiol. Behav. (2012) epub May 4, doi:10.1016/j.physbeh.2012.04.024. 65 B. M. Kudielka et al., “Human Models in Acute and Chronic Stress: Assessing Determinants of Individual Hypothalamus-Pituitary-Adrenal Axis Activity and Reactivity,” Stress 13 (2010): 1–14. 66 P. Bjorntorp, “Do Stress Reactions Cause Abdominal Obesity and Comorbidities?” Obes. Rev. 2 (2001): 73–86. 67 P. A. Tataranni et al., “Effects of Glucocorticoids on Energy Metabolism and Food Intake in Humans,” Am. J. Physiol. 271 (1996): E317–E25. 68 M. Elovainio et al., “Socioeconomic Differences in Cardiometabolic Factors: Social Causation or Health-Related Selection? Evidence from the Whitehall II Cohort Study, 1991–2004,” Am. J. Epidemiol. 174 (2011): 779–89. 69 J. P. Shonkoff et al., “Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention,” JAMA 301 (2009): 2252–59. 70 R. M. Sapolsky, “Depression, Antidepressants, and the Shrinking Hippocampus,” Proc. Natl. Acad. Sci. 98 (2001): 12320–22. 71 M. F. Dallman et al., “Chronic Stress and Comfort Foods: Self-Medication and Abdominal Obesity,” Brain Behav. Immun. 19 (2005): 275–80. 72 A. J. Tomiyama et al., “Comfort Food Is Comforting to Those Most Stressed: Evidence of the Chronic Stress Response Network in High Stress Women,” Psychoneuroendocrinology 36 (2011): 1513–19. 73 A. Sadeh et al., “Sleep Patterns and Sleep Disruptions in School-Age Children,” Dev. Psychol. 36 (2000): 291–301. 74 C. Benedict et al., “Acute Sleep Deprivation Enhances the Brain’s Response to Hedonic Food Stimuli: An fMRI Study,” J. Clin. Endocr. Metab. 97 (2012): E443–47. 75 D. Kaufman et al., “Early-Life Stress and the Development of Obesity and Insulin Resistance in Juvenile Bonnet Macaques,” Diabetes 56 (2007): 1382–86.