Forget everything you thought you knew about food…
At the world-renowned Weizmann Research Institute, Dr Eran Segal and Dr Eran Elinav have been looking at what and how we eat differently. In one of the largest ever studies of nutrition and health they have proved conclusively that every food affects every body differently. In other words, what is healthy for one person could be unhealthy for another.
The Personalized Diet offers the groundbreaking knowledge, tools and life hacks to re-examine how you think about food, health and well-being, and discover the right foods for you. There are no foods that are just good or bad, there is no one-size-fits-all diet; instead, there is The Personalized Diet.
Welcome to your blueprint for a healthier, happier, longer life.
DR. ERAN SEGAL was born in Tel Aviv, Israel, and received a BSc summa cum laude in computer science from Tel Aviv University in 1998, and a PhD in computer science and genetics from Stanford University in 2004. After holding an independent research position at Rockefeller University, he joined the Weizmann Institute of Science in Israel in 2005, where he is a professor in the Department of Computer Science and Applied Mathematics. Dr. Segal heads a research lab with a multidisciplinary team of computational biologists and experimental scientists in computational and systems biology. His group has extensive experience in machine learning, computational biology, statistical models, and analysis of heterogeneous large-scale data. His research focuses on nutrition, genetics, microbiome, and gene regulation and their effect on health and disease. His aim is to develop personalized nutrition and personalized medicine. The lab website is http://genie.weizmann.ac.il.
Dr. Segal has published more than 120 publications that were cited by more than 25,000 research articles and has received several awards and honors for his work, including the Alon Foundation award (2006); the EMBO Young Investigator award (2007); the Overton Prize (2007), awarded annually by the International Society for Computational Biology (ISCB) to one scientist for outstanding accomplishments in computational biology; the Levinson Prize in biology (2009); and the Michael Bruno award (2015). The Scientist named him a “Scientist to Watch” (2009), and Sonima elected him as one of fifty innovators. In 2012, he was elected as a member of the Young Israel Academy of Science, and in 2015, he was elected as an EMBO member.
Dr. Segal is married to Keren and lives in Ramat Hasharon, Israel, with his three children, Shira, Yoav, and Tamar; their cat Blue; and their dog Snow. He is an avid long-distance runner who has completed ten full marathons.
DR. ERAN ELINAV was born in Jerusalem and completed his medical doctor’s (MD) degree at the Hebrew University of Jerusalem summa cum laude in 2000, followed by a clinical internship, residency in internal medicine, and a clinical and research position at the Tel Aviv Medical Center Gastroenterology Institute. In 2009, he received a PhD in immunology from the Weizmann Institute of Science, followed by a postdoctoral fellowship at Yale University School of Medicine. Dr. Elinav is a professor heading a multidisciplinary research group of more than thirty immunologists, microbiologists, metabolic experts, and computational biologists at the Department of Immunology, Weizmann Institute of Science. His lab focuses on deciphering the molecular basis of host-microbiome interactions and their effects on health and disease, with a goal of personalizing medicine and nutrition. The Elinav lab employs diverse, state-of-the-art experimental, genomic, and computational methods to study the involvement of gut microbes in diverse multifactorial diseases, including obesity and its metabolic complications, inflammatory and autoimmune disorders, neurodegenerative disease and cancer, with an aim to develop microbiome-targeting personalized treatment modalities for these disorders. His lab website is http://www.weizmann.ac.il/immunology/elinav.
Dr. Elinav has published more than 120 publications in leading peer-reviewed journals and has received several awards for his discoveries, including the Claire and Emmanuel G. Rosenblatt award from the American Physicians for Medicine (2011); the Alon Foundation award (2013); the 2015 Rappaport Prize for biomedical research, awarded annually to a single scientist for breakthrough biomedical discoveries; the 2016 Lindner award; Israeli Society of Endocrinology’s highest prize; and the 2016 Levinson award for basic science research (2016). Dr. Elinav is also a senior fellow at the Canadian Institute for Advanced Research (CIFAR), an elected member of the European Molecular Biology Association (EMBO), and is an international scholar at the Howard Hughes Medical Institute (HHMI).
Dr. Elinav is married to Hila and lives in Mazkeret Batya, Israel, with his three children, Shira, Omri, and Inbal, and their dog Herzl. In his spare time, he likes to mountain trek and ski.
To our teachers, colleagues, and students for making our joint truth-pursuing journey an enjoyable and moving experience
Imagine that there was no single food that was bad for everyone or good for everyone—not chocolate, not kale, not cookies, not a big salad, not a banana, not coffee. Imagine something you love to eat—something you think is a terrible dietary choice (but that constantly tempts you, like a juicy, fat steak or a bowl of mintchip ice cream)—is actually okay to eat and won’t have a negative impact on your health. What if a food you hate—something you force down because you think it is good for you and will help you lose weight or avoid health problems, something like rice cakes or steamed fish—is exactly the wrong thing for you? What if we told you that carb-loading with pasta before endurance sports might be bad for you and slow you down, that diet soda might be directly contributing to your weight gain, or that sushi might be making your blood sugar spike in a way that could increase your risk of diabetes?
Imagine no longer having to suffer through painful diets that restrict too many foods. Imagine never having to go through another cleanse, another “induction phase,” another fast, another starvation diet. Imagine eating carbs again, eating fat again, or eating meat again, if that is what you’ve been longing for. And imagine not having to pay attention to the never-ending stream of confusing and contradictory dietary information telling you the foods to eat, or not eat, in order to lose weight or fight chronic disease. Imagine that science has finally begun to scratch the surface of the complex question about the optimal diet and that you no longer have to wonder what is right for you to eat, because you finally understand that there is no single correct diet philosophy that will work for all people. What if each person requires a different diet tailored to his or her own body composition? And that science is only beginning to discover a methodology so an individual can determine exactly what his or her diet should be? What if you finally understood how and why optimal nutrition must (and can) be personalized?
What if you could use that information for the benefit of your own health and weight-loss efforts, right now?
We are Dr. Eran Segal and Dr. Eran Elinav, researchers and colleagues at the Weizmann Institute of Science, an internationally renowned, multidisciplinary research institution dedicated to advancing science for humanity’s benefit. We have been collaborating on an ambitious and far-ranging research effort called the Personalized Nutrition Project that we believe has the potential to shift the very foundations of nutrition science.
In The Personalized Diet, we will explain how we arrived at our conclusions; give you the genuine, hard science behind the surprising claims we are now able to make; and show you how you can get a jump on those changes now, in your own life and for the sake of your own health, by applying our personalized nutrition approach to the way you eat and the lifestyle choices you make. The insights we gained in our studies, based on new, large-scale data that we collected, may be life-transforming, as it may have you looking at your dietary choices in a completely new way. It’s very likely that many of the foods you love, that you think you shouldn’t eat, aren’t harmful for you at all. It’s possible that many of the foods you thought were healthy aren’t good for you—not the general “you,” but you personally. How can you know for sure? This is the future of dieting. What we discovered in our groundbreaking and internationally publicized research has the potential to change your health, your weight, your energy level, and your sleep quality—indeed, your life.
Most people want to lose weight, get healthier, feel better, and generally get control of their appetites and lower their risk for chronic disease. That’s why scientists and research institutions have spent countless hours and billions of dollars researching and publishing studies to answer one simple question: What is the best diet for humans?
Maybe you think you know. Maybe you are already in the low-carb camp, the vegan camp, or the Mediterranean diet camp, or you have worked with a dietitian and that person has told you what to eat. In any case, perhaps you are sure science knows. After all, the question sounds straightforward and direct enough. With all the scientific advancements that have been made over the centuries, surely we know the answer to this seemingly small question by now.
The reality is that although there are many convincing books, articles, and websites written by people claiming to know the truth, many of them citing tens and sometimes hundreds of scientific studies to prove their theories, there isn’t one definitive answer. Some of those who support one diet over another are doctors, or dietitians, or nutritionists, or exercise trainers, and some of them are people who have successfully lost a lot of weight and want to share how they did it. Each claims to know what really works, the absolute truth. It’s no wonder that so many people flock to this kind of information, even constantly changing their opinions and strategies based on the latest thing they’ve read. When one diet or philosophy doesn’t work, they jump to another, and then another, and then another, thinking they are being discerning because they are listening to experts.
The problem is that these books, articles, and websites all seem to champion completely different and often directly contradictory information. Even well-constructed research on any one nutritional principle or strategy can almost always easily be refuted by different research on a different nutritional principle or strategy. There are numerous studies that support or oppose every single dietary intervention available.
So, what is the real answer to the question about the best diet? Maybe science would have uncovered an irrefutable answer by now, were it not for one increasingly unavoidable reality that science is only beginning to uncover: There is no answer to the question of the perfect diet because it is the wrong question.
But before we get to the right question—the truly important question, and the question that actually has an answer that may transform your life—we would like to introduce ourselves.
Before I ever conceived of the notion of personalized nutrition, I was a scientist and a marathon runner married to a clinical dietitian. Because of my wife’s profession, I was fairly certain I already knew how to eat healthfully, and I thought I made good decisions about my meals. But a few years ago, I became interested in ways I could improve my athletic performance, and in my free time, I took to researching sports physiology. This led me to start thinking about how diet might improve my performance. I wondered if adjusting what I ate could give me more energy to sustain my long runs or make me faster. If I could find good evidence for any dietary changes that might increase my speed and endurance, I was willing to try them.
Being a scientist, I am not that interested in popular literature about diet and fitness fads, so instead I turned to books with a more scientific slant, with solid research backing up their claims. I wanted to know what real, hard science had to say about the question of diet for athletic performance—specifically, my own. I respect science, and therefore I trusted science to tell me the truth. I approached this new personal project with energy and expectation, hoping to find something interesting and useful for my life.
However, the more I researched the question of how diet might help or hinder athletic performance, the more I realized that the dietary advice that was widely available for athletes (and everyone else) was often contradictory. Some of it even sounded suspiciously inaccurate. As I investigated further, I discovered, to my surprise, that the science upon which this advice was supposedly based was sometimes not up to standard, involved very small studies with only a handful of subjects, had been misinterpreted by writers and journalists, or was outdated. What at first looked like good solid science in many cases turned out to be, when more carefully examined, not very scientific at all. Most shocking to me was the discovery that the dietary advice I had always practiced (almost religiously, because I was confident that it was based in science) had no real scientific underpinnings. How could this be? How could I have missed this? How could professional curriculums about nutrition, government guidelines for diets, and nutritional advice from exercise science be based on what seemed increasingly to me to look like nothing? I had taken for granted that mainstream dietary advice was true—that is, based in proven scientific principles. The more I read, the more I realized it was not.
Many of the contradictions, misinterpretations, and especially what I perceived to be missing science had to do with dietary carbohydrates. These are the sugars, starches, and fiber in food that the body breaks down, to varying degrees, into glucose to feed the cells. Athletes think about carbs a lot. Many of us “carb-load” the night before a big athletic event like a marathon and don’t worry much about eating carbs because we have been taught that carbs equal energy. Dieters often focus on carbs as well, either emphasizing them as a replacement for fat (such as with many vegetarian or low-fat diets) or eliminating them because of the belief that they are responsible for weight gain and health issues (such as with the many iterations of low-carb diets). The more I investigated, the more I saw that there was plenty of evidence both for and against carbohydrates, as well as many different approaches to carbohydrates, including some that considered them all the same and others that considered some “good” and some “bad.” What was a scientist to make of all this seemingly well-researched and scientifically supported but conflicting information?
But I was still primarily interested, for personal reasons, in the exercise aspect of carbohydrates, so I decided to focus on that. For example, I read a study (this was long ago and I can’t recall the source) in which people ate dates, which contain fast-digesting (or “simple”) carbs, 30 to 60 minutes before running or doing intense exercise. The effect of eating these dates at first seemed inconclusive—some people eating the dates were energized and had better workouts, but others felt exhausted to the point that, a few minutes into their runs, they had no energy and had to stop. I remember stopping to think about this. Why would people respond so differently to the same food when doing the same activity at approximately the same intensity? I wondered whether this might be related to differences in how people’s blood sugar levels responded to dates, because blood sugar crashes are associated with low energy. If eating dates gave one person a moderate rise in blood sugar, then that could indeed provide energy during strenuous activity. But if another person had a huge spike in blood sugar and then an imminent blood sugar drop, this could result in exhaustion. I thought about this in my own life. Sometimes I felt energized from carbohydrates, and other times I felt the opposite. Maybe you have noticed something similar in your own experience—do certain carbohydrate-rich foods give you energy while others seem to sap your strength? The more I thought about it, the more I realized that some of the foods that seemed to give me the most energy were not always carbohydrate-heavy. Sometimes they were foods higher in protein and/or fat. Interesting.
I decided it was time for an experiment, with myself as test subject. The first thing I tried was changing what I ate prior to my long runs (approximately twenty miles). I wanted to see what would happen if, instead of carb-loading, I ate protein and fat. The reason I tried this particular experiment was because I had heard more and more “low-carb athletes” claiming they could burn fat instead of carbs for energy and that it was even more efficient. It sounded strange, but I was curious enough to try it. I wanted to know how it might affect my physical hunger and my motivation, as well as my performance. I was a little hesitant to do this because I had always carb-loaded before exercise, eating three or four large bowls of pasta the night before a run and having a few dates or energy bars the next morning about 30 to 60 minutes before a run. I almost always felt extremely hungry about 15 to 30 minutes after my run, but I figured that was just because I had burned up all those useful carbs, and I was ready for more. After a run, I would always eat even more carb-rich foods, thinking I was responding to my body’s needs. I had always believed that this was necessary to give me enough energy to run that distance, but what if I (and all those other athletes and coaches and fitness professionals I knew) was wrong?
So, one evening, instead of carb-loading, I ate a big salad with lots of fat sources like tahini, avocado, and nuts. In the morning, I set out for my twenty-mile run without eating anything (against the advice of many professional running coaches).
I was surprised at what a positive effect this diet had on both my energy level and my performance! During my run, I had just as much energy, if not more, than I had with the carb-loading. Moreover, my ravenous postrun hunger completely disappeared. After my run, I couldn’t believe that I wasn’t hungry. I surmised that my body must have switched to burning fat rather than carbohydrates, and this must have been responsible for these significant changes in my energy level and hunger.
I then considered what I knew about how the human body works. When we eat carbs, we store some of that energy in our livers in the form of glycogen, for use during strenuous activity. However, we can store only 2,500 to 3,000 kilocalories’ (what we typically call calories) worth of glycogen. Over the course of a twenty-mile run, it is easy to burn 2,500 calories or more, so if your source of fuel is glycogen, you can see how those stores could be depleted quickly. This could certainly trigger fatigue and postrun hunger.
Even lean people have about 60,000 Kcals (calories) of fat available for energy. This is a much bigger storehouse of energy, so it makes sense that burning fat rather than carbs is more efficient for long-term exertion. If we deplete 2,500 Kcals of fat, we consume only a small percentage of the available fat energy stores, and the need for replenishment will feel (and be) less urgent.
It all made sense to me. Switching my body from burning glycogen to burning fat on a run might finally be the answer I had been seeking. As an endurance athlete, I felt like I had hit on a eureka moment. I continued eating low carb in my daily life and noticed that I had more energy, even when I wasn’t exercising. This was an unexpected benefit. I also lost some of the excess weight I was carrying, and best of all, my athletic performance steadily improved until I met my goal of running a marathon in under 3 hours: In 2013, I finished the Paris Marathon in 2:58! Then, in 2017, I broke that 3-hour mark again running a marathon in Vienna.
As I continued with my life and athletic pursuits, I couldn’t help noticing that there were some successful athletes I encountered—as well as friends and colleagues—who were not eating the way I was eating. Despite my low-carb evangelizing, some of them swore by their carb-rich diets and seemed to do just fine … even fantastically, including some vegans performing at a very high athletic level after carb-loading. Maybe my eureka moment wasn’t universal. Maybe it was personal. Maybe not everyone would react to this kind of dietary adjustment the way I did. Perhaps I had found the optimal Eran Segal Diet, but maybe I still had not discovered the optimal universal diet. Based on my observations so far, I couldn’t be sure.
I began to think more seriously about dietary carbohydrates. Were they, as I had previously believed, the primary and most desirable source of energy for the athlete—the across-the-board best source of fuel for the body and brain—or was a diet based on carbohydrates (even the complex type I had always thought were so valuable, such as oatmeal, pasta, and whole-grain breads) inhibiting my athletic performance, energy level, muscle growth, and brain function?
I was still in the mind-set that a diet based on complex carbohydrates as a primary energy source was good for the human body, neutral, or bad. But I kept coming back to all that contradictory research. Carbohydrates could not possibly be both good and bad.
Or could they?
That’s when I thought: Why do some people seem to thrive on diets that are high in carbohydrates, while others quickly gain excess weight or suffer from low energy? Why were some of those people who ate the dates energized and some were exhausted? I knew people who, for example, were vegetarian and ate only fruit, vegetables, and plant foods such as legumes and whole-grain rice. They lived primarily on foods rich in carbohydrates, with relatively low levels of protein and fat. Some of them seemed to thrive, some claimed to have reversed their heart disease, and some had significant muscle and strength. Others didn’t seem very healthy and were always tired and pale.
On the other hand, I also knew some “low-carb” people who didn’t eat any grain-based foods or legumes and consumed hardly any fruit. They lived on green vegetables, meat, nuts, and seeds, and added fat, such as olive oil, coconut oil, and even lard. Many of them were exceptionally vigorous athletes with excellent endurance, and many were quite lean. Others gained excess body fat and suffered from dangerously high cholesterol.
How could this be? Either some of these people were lying about what they were eating—the cheating vegan secretly eating meat on the sly, or the cheating Paleo aficionado sneaking cookies and toast under dark of night—or some of these people were simply not responding positively, personally, to the dietary philosophy they had adopted. I didn’t think the people I knew were lying about what they ate. Many of them were smart people with dietary knowledge, and they were likely to be choosing good, high-quality, high-nutrient sources of carbs, protein, and/or fat.
What else could be going on?
Perhaps, as I was beginning to suspect, it wasn’t just about the food. Perhaps, it was also about the person eating the food. This led me to a completely new line of thinking, as I wondered:
What are the effects of different foods on different people?
Now this was an interesting and far more complex question than what I had first considered as I sought out the best foods for my exercise performance. As I began to apply myself to this new question, I considered how many factors could influence how any one person reacted to food. For example:
If the individual, rather than the food, was the wild card, then perhaps the question of how any one person will react to any one food was too complex to answer. So how was I ever going to figure out what to eat to be a better marathoner? The more I kept coming back to my original, personal reasons for investigating these questions, the more I could feel the scientist in me getting intrigued and engaged.
But the more I read, the more I realized that there was not enough data on the subject. I knew that a data-driven approach, without prejudice or bias, was the only way to answer my questions. If I really wanted to find out more, and nobody had the answer yet, I might just have to do it myself. I would need to find something that would measure an individual response to food that would include and encompass personal genetics, individual microbiomes, and clinical parameters like blood tests, weight, and age, and lifestyle factors like physical activity, sleep, and stress. It was a lot to consider. Would such an experiment even be possible?
Because I have a background in computer science, it made sense to approach this problem by using machine learning and algorithms—basically, in these fields, we take large amounts of data and try to get computers to identify patterns and rules in the data. The interesting thing about this is that when given large amounts of data, these algorithms can identify patterns that are impossible for people to find because we can’t take in and process that much information. A computer’s ability to see patterns and derive rules far better than what we can see is why computers are now better than people at games like chess and the Chinese game Go.
I’d never seen this data-driven approach applied to nutrition research, but I thought, Why not? Nutrition is a complex issue with many variables. What better way to sort it all out than with big data and a computer algorithm? I thought this might be just the way to plug the right data into the right places to learn for sure what foods would and would not increase athletic performance, as well as improve health and support weight control, for any given person. I had no idea what information such an approach might yield, but I was already eager to find out when I met Dr. Eran Elinav.
I came into the world of personalized nutrition from a completely different angle than my colleague Dr. Segal. As far back as I can remember, I have been intrigued by the complexity of machines. As a child, I once opened my grandfather’s transistor radio and took it apart without asking permission. I did the same with my parents’ record player, only to discover a multitude of wonderfully colorful and strangely shaped metallic components, interwoven with wires. I was amazed and delighted by the complexity created by human beings just like me. Of course, after dismantling many appliances, I was left with a handful of neglected parts following my attempts at reconstruction.
But no machine compared, in my estimation, to the mysterious human body. Even as a child, I thought of the body as the ultimate complex machine, containing seemingly endless hidden parts, concealed from my eyes yet easily perceptible—the beat of my heart; the wheezing sounds my lungs would produce when I had a cold; even the feelings, dreams, and sensations emerging from my brain and nervous system. The body was a machine I couldn’t take apart, of course (at least not until I got to medical school), but it occupied much of my thought and imagination. When I found my grandparents’ old encyclopedia of the human body, I was elated. I spent hours flipping through the pages, gazing at the many differently shaped and colored organs, tubes, and structures perfectly fitted together. Bodies were even more complex than I realized. I wondered if I would ever truly understand them.
It was no surprise to me or to anyone around me that biology became my passion and the focus of my studies. Following a four-year military service on a submarine (another fascinating machine), I joined the Hebrew University of Jerusalem School of Medicine and finally found a place where I could attain answers to the many years of questions about the functions and intricate secrets of the human body. I embraced my studies, voraciously consuming the thousands of anatomical details I was finally able to see directly in dissection classes, the endless cellular structures I discovered through the light microscope in my histology classes, and the multitude of strange-sounding medical terms revealed to me in my pathology classes. The human machine was gradually being revealed in front of my eyes.
Yet, I found that the more I learned, the less clear the big picture became. The more I zoomed in on the intricacies of the human body, the more the rules of its function became pixilated and blurry to me. The more answers I received, the more questions I had. I felt like I must be missing something. When you take apart a record player, at some point you understand it completely. Why was the human body still so elusive?
My favorite courses were in microbiology. My professors of microbiology and infectious disease revealed a world full of hidden enemies. You can’t see a virus or bacteria, but they can conquer a human, sometimes in a matter of days. A living world of tiny, strangely shaped and named invisible creatures—ordered into families and groups, including bacteria, viruses, fungi, and archaea (microbes with no cell nucleus)—was coming into focus before my eyes. This was next-level anatomy! And it was an exciting world—hostile, deadly, and obscure. My teachers were like the cavalry riding in to fight in this invisible war against our ultimate adversaries, teaching us medical students how to wield sophisticated antibiotic weaponry against our enemies, even as these foes developed resistance and emerged more potent and deadly than ever.
Next, I entered a phase of clinical practice, putting all those hours of studying, memorizing, and practicing into practical use. During these grueling years as an intern and resident in internal medicine, and as a gastroenterology fellow, I had a revelation: Even more complex than the secrets of the human body are the principles of its inner battle against dysfunction.
During this time, I was exposed to human suffering at its utmost severity. Especially troubling was a set of diseases collectively termed the metabolic syndrome. This included severe obesity, adult-onset diabetes, hyperlipidemia, fatty liver, and the many complications that come from all these conditions. I dealt with diabetes-associated limb amputations and blindness, kidney failure and the associated need for daily hemodialysis, heart attacks, heart failure, stroke, and sudden death. The vast majority of patients admitted to the internal medicine department where I worked suffered from this common syndrome, and the illnesses associated with it often caused severe debilitation and sometimes death. The need to deliver lifesaving cardiopulmonary resuscitation became almost a daily routine for me. This degree of suffering would have been unimaginable to me, had I not witnessed it. What was happening to people? Yet, I was surprised and disturbed that the treatments we offered these many patients, who were clearly in agony, focused on treating their many complications rather than doing anything to impact the course of their primary disease. My colleagues and I became increasingly frustrated by our inability to do anything about the vast epidemic itself and its horrible consequences. We were mopping up the mess after the fact rather than preventing the disasters before they could happen.
It was this sense of enormous failure to help my patients that, despite my years of focused study, pushed me to change directions. If I wanted to help people avoid coming to the extremes of health dysfunction, I needed to dig further into the depths of human biology, beyond the study of medicine and medical practice. Although I was already a senior physician, I decided to enroll as a graduate student at the Weizmann Institute of Science, Israel’s most elite academic institution and a world-renowned center of basic science research. I would start again.
There, in the lab of Professor Zelig Eshhar, a world-famous scientist and the inventor of a promising new cancer immunotherapy, terms like patient care, fluid charts, and medication dose were now replaced with new terms such as DNA, epigenetics, cytokines, and chemokines. I was intrigued and bewildered by this new world but excited by what I saw as the potential to gain a deeper understanding of many of the “incurable” diseases I had encountered as a physician. Here, instead of human patients, I worked with test tubes, microscopes, and animal models. I gradually learned to combine my clinical problem-oriented medical thinking with the deep mechanistic curiosity and drive of a basic scientist. I was feeling increasingly confident that my “toolbox” was expanding and I was reaching a new level of professional maturation.
I decided to dive even deeper into science and took a postdoctoral position at Yale University in the lab of Professor Richard Flavell, one of the world’s leading immunologists and cell biologists, where I was exposed to a new revolution in science and medicine that would eventually engulf me and my professional career for years to come: the study of microbes.
It was at this point that I started to think of my possible future contribution to science and medicine. What questions and topics would I pursue as an independent future researcher? For years, my teachers, colleagues, and I had considered microbes to be the ultimate enemies of human health and the invisible cause of most disease, or waste products irrelevant to our human physiology. Now I was learning that these internal microbes did much, much more. This was a new and exciting frontier in science and medicine, and there I was, on the forefront. New technologies, once regarded as science fiction, enabled us to probe deep into the nature of the trillions of microbes that live within every human body.
I was intrigued by the work of pioneers such as Jeffrey Gordon and Rob Knight, who developed means of connecting this microbial world within a world, now termed the microbiome, to almost any feature of our human existence. I began to recognize that the microbiome is a significant source of health, including the prevention or cure of disease. The microbiome, I learned, was indispensable in digesting food and extracting nutrients, was an instrumental part of the human immune system, and was influential in many other biological systems. The human body is impossibly complex, and when I saw that within the body was an entire universe of microbes, I decided that this was to become my world, my mission, and the source of my contribution to science. I would be an explorer of this newfound universe, seeking the answers to the resolution of our most common and debilitating health conditions.
Finally, it was time to establish my own research group. I was fortunate to have been offered an independent position at my former graduate institution, the Weizmann Institute of Science. It was time to go back home. I established the first fully dedicated microbiome research laboratory in the institute and in Israel, established the unique infrastructure that is critically needed for this interdisciplinary research, and recruited a group of highly driven, intelligent, and ambitious students and postdocs from across the globe, who joined me in this journey that would define me and my career for years to come. Our goal: to understand how our interactions with our internal microbes affect our health and risk of disease.
It was during my transition back to the Weizmann Institute on a rainy, farewell day trip to Manhattan that I had a life-changing phone conversation. A friend, Professor Eran Hornstein, a molecular biologist from the Weizmann Institute, suggested I meet a future colleague, Professor Eran Segal, a mathematician and computational biologist also from the Weizmann Institute. Professor Hornstein said, “Trust me, this is a great guy who has developed interests very close to yours.” Trusting my friend’s intuition, I arranged a phone call with Dr. Eran Segal to discuss common interests, questions, and projects we might pursue upon my arrival in Israel.
My friend was correct—the more Dr. Segal and I chatted, the more our commonalities emerged. Although our personalities were quite different, we discovered that we were distinctly complementary in our expertise, life experiences, and problem-solving approaches. We looked at research questions from different angles, used different techniques, and had different points of view, but we were both interested in the same questions: how human nutrition, environmental exposures, genetics, and immune function impact the internal microbiome and how these mysterious, poorly understood, and vastly important communications between people and their microbes impact the course of health and disease. On that rainy New York day, a partnership was formed.
Because we both had a strong common interest in nutrition and metabolism, and because our areas of knowledge were complementary, we conceived (almost from our first meeting) the idea of a massive personalized nutrition study. We were both convinced that nutrition very likely should be personalized according to each person’s unique makeup, including microbiome and genetics, but we didn’t yet know how. We envisioned a personal nutrition study that would be massive and wide-ranging, encompassing and controlling for a multitude of variables to discover why different people respond differently to the same foods. We knew this would be complex to design, as all good nutrition studies must be. We spent a long time on the specifics: What questions would we ask? What health measures would we consider? We wanted to measure an outcome that was important—weight loss following a diet seemed an obvious choice. However, we realized that a study focusing on weight loss alone as a primary objective to assess the effects of personalized nutrition had some problems:
If you go on a diet, it is very difficult to isolate the exact reason why you did, or did not, lose weight. Was it because of the addition of certain foods, or the absence of particular foods, or because of other lifestyle changes, or a combination of all these things? Which factors were influencing weight loss and which were extraneous, perhaps added or subtracted to the diet unnecessarily? As scientists, we like to design studies that allow us to isolate the effect of individual variables on an outcome of interest. We needed something that was more directly related to the food consumed, with a more immediate but also quantitative, measurable response. We wanted a metric that would be relevant for weight loss but would also be relevant for metabolic (diet-related) disease. The metric needed to be measured easily and accurately across a large study group. All of these parameters led us to consider blood glucose levels, or more precisely, blood glucose levels following a meal. We call this a meal glucose response, or postprandial glucose response—or in nontechnical language, postmeal blood sugar response.
Comparison of weight and postmeal blood glucose levels as measures of healthy nutrition
One reason we liked the idea of measuring blood sugar after meals was that large spikes in postmeal blood sugar promote both weight gain and hunger. After we eat, our body digests the carbohydrates in food, breaks them down into simple sugars, and releases them into the bloodstream. From that point, with the help of insulin, glucose is moved into the cells and into the liver, where it is used to synthesize glycogen, for later use as energy. But insulin also signals cells to convert excess sugar into fat and store it. This extra sugar storage is a primary reason for weight gain. Also, if too much glucose flows into the blood from food, this may cause the body to react with an overproduction of insulin; this can push glucose levels too low, even below what they were before eating. This makes us feel hungry and causes the impulse to eat more, even though we have already had enough (or more than enough) food to cover our energy needs.
We also knew that sharp glucose spikes after a meal are a risk factor for diabetes, obesity, cardiovascular disease, and other metabolic disorders. A recent study (one of many) that followed 2,000 people for more than thirty years found that higher meal glucose responses predicted higher overall mortality during the study.1
Finally—and this is important—recent technological advances allowed us to measure blood glucose levels continuously for an entire week. Because the average person eats approximately fifty meals per week, this technology gave us the opportunity to measure fifty meal glucose responses in one week. This would directly measure the effect of every single meal, as opposed to the more common practice of measuring someone’s blood sugar once—for example, in the morning after a night fast—as the result of his or her overall diet. (Note that this technology is not widely or affordably available to everyone, but in the program in this book, we will show you how to test your own postmeal blood sugar, without having to use a continuous glucose monitor.)
Of course, we knew that there were many factors beyond blood glucose levels that influence weight and health, but we also knew it was an important one, and using it as a metric to determine food responses seemed promising and potentially informative.
Once we had hit on the metric to use, there were many small yet critical details to work out, and it took a couple of years to build the infrastructure. We were lucky to have stellar PhD students and research associates to carry out the research. We also hired people to do the logistical work, including inviting people to join the study, meeting with them, and drawing their blood. We explained how to use our app, log their meals, and collect samples from them, and we hired programmers to write the mobile apps that the test subjects would use to log foods.
We also needed to find study subjects willing to participate. We mentioned the project informally to friends, and many were intrigued by our plans and interested in the result. Some were somewhat skeptical, but we faced more interest than skepticism. The Weizmann Institute was also interested in our project, so we set up a seminar to explain our research, including our goals and motivations. We advertised the seminar by sending out mail to the Institute, hoping for at least a small audience. The room had 300 seats, but people registered so quickly that we had to close the registration—something we did not anticipate. After the seminar, approximately 100 people registered on our website to take part in the study, and after they took part, word of our study spread quickly without any advertisement. We issued invitations to register, but so many people told their friends and family that before we knew it, we had 1,000 recruits. Throughout the study, people continued to register on the website, and by the end of the study, we had 5,000 people signed up and interested in participating.
This level of response is very unusual for a clinical trial. Typically, in clinical trials, researchers work very hard to recruit participants and often must pay as an incentive. By design, we didn’t want to pay because we didn’t want money to be the motivation. Frankly, we were quite surprised by the response—we found that people were very eager to learn about themselves. The nature of our study required many lab tests and measurements, and participants were fascinated to know these hidden aspects of their own bodies and health. We were gratified to learn that the interest was widespread and genuine.
Later in this book, we’ll explain how we set up the study, the kind of results we got, and how the app we used can help you, but for now let’s skip ahead. When the study was complete, we wrote up the results in a paper that was published in Cell (one of the most prestigious science journals in the world), and the journal set up a virtual press conference, inviting journalists to attend. The Cell editors’ journal suspected that interest in the research would be high, but although our previous works had received very broad international coverage, nothing could have prepared us for the response to this paper.
Within hours of the moment the paper was available to an international audience, reporting about it began to appear online and in print. Within one day, more than 100 articles were published internationally, both covering and speculating on our results. A crew from the BBC came to Israel for a week to film us. We subjected the reporter and a crew member to the same tests as those we gave to our study participants and gave them personal dietary recommendations based on their results. Our recommendations surprised the BBC reporter, but she was even more surprised when she experienced significant weight loss after following her personalized recommendations. The results were aired in the United Kingdom in prime time. As of this writing, more than 1,000 articles have appeared in major media outlets all over the world, including CNN, Time magazine, the New York Times, Forbes, CBS News, the Atlantic, and the Independent, as well as in the most prestigious science journals, including Science, Nature, and Cell.
This avalanche of publicity that caused so much excitement in major media outlets all over the world was no fluke. It was a significant and enthusiastic response to the fact that we have now demonstrated, clearly, definitively, and for the first time on a large number of people, that individual people react differently to the same foods. Specifically, we have shown that foods that create a healthy response in some people produce a physically and metabolically damaging effect in other people. Our study allowed us to:
This changed everything we thought we knew about nutrition, and the implications of our discoveries are broad, providing strong evidence that general dietary advice will always be limited, because it only takes into account the food, and not the person eating it.
personalized