Chapter 1: Outsmarting Your Genetic Legacy

Why a Phenotype-Based Diet?

The Link Between Genetics and Weight

Though weight problems may be hereditary, they need not be a life-long affliction. Our experience as nutrition professionals upholds this, and emerging genomic data demonstrates why. You can stop thinking of your genes as a curse. This book will show how your genes can work for you, instead of against you. The right foods in the right proportions with the right supplements, tied specifically to your genetic profile, will produce genetic equilibrium and the weight loss you want. Within days, you will feel healthier and more satiated. This weight loss can work, for a lifetime, because the diet is exactly tailored to your body and health concerns, as portrayed in the physical expression of your DNA called your phenotype.

The logic behind our new individualized phenotypal approach is evident in a truism that anyone who has ever dieted knows firsthand -- that the diet that works great for some people is for others an exercise in futility. Diets are almost as diverse as people -- low-calorie diets, high-protein diets, low-fat diets, grapefruit diets, cabbage soup diets, vinegar diets...the list goes on and on. Diet effectiveness is inconsistent because the dietary chemicals within food act at a molecular level on specific genes, and no two people's genes are the same. Added to the problem of not knowing which diet will work for you is the fact that most trendy diets are unhealthy. Even if they result in weight loss, they work against long-term well-being and may actually do irreversible damage, especially as dieters keep trying new ones to counteract recurring weight gain.

The good news is that the uncertainty is over and that these unhealthy diets are no longer necessary! With the help of science, we can now characterize more than ever before the molecular activity of dietary chemicals. We can explain why diets don't come in one-size-fits-all. This has taken the guesswork out of dieting and revolutionized weight loss. It has also made weight loss far more healthy.

Unlike gimmick dieting, gene-based nutrition diminishes the likelihood of weight-related maladies such as high blood pressure, diabetes, and cardiovascular disease. In fact, this program is entirely unique because it provides an individualized diet, guaranteed to succeed, that will alleviate the weight-related malady to which you're most vulnerable. You'll lose weight and feel better on a phenotype diet because the foods are compatible with you, on a cellular level.

Even though our program is structured around micromechanisms, you needn't visit a clinic or register for a program. You needn't spend a lot of money on gene profiling. Everyone can match him- or herself to one of our diets right away, using this book as a guide.

We have confidence in your ability to make the most of your genetic inheritance, because this program has helped hundreds of our patients and clients synchronize their foods and eating habits with their genes. Consistently, good health and weight loss flowed from their efforts. One patient, a cardiologist who had just been diagnosed with type 2 diabetes, came to us because she was not getting results from the high-carbohydrate, heart-healthy diet recommended at the time. Whenever she ate a plateful of pasta, her blood sugar rocketed. A glucose receptor problem related to her genes and extra weight barricaded her cells against blood sugar. Glucose accumulated in her bloodstream. We knew she needed a diet personalized to her genetic risk for diabetes, not the general recommendation. A lower-total-carb diet, combined with high-fiber carbohydrates and protein, worked better. When we customized her diet, she lost weight and kept it off.

In another example, an overweight and hypertensive police officer couldn't meet his department's rigorous fitness requirements. With his excess weight and high blood pressure, this client was a heart attack waiting to happen as he rolled through the city on his motorcycle. He needed a personalized diet to tame his sodium-sensitive genes into directing the hormones that control blood pressure more effectively. We loaded his cycle saddlebags with dried fruit and restricted his trips to sodium-loaded fast-food joints. He lost weight and decreased his blood pressure.

The secret to both these patients' successes wasn't the diet trend of the week. It was in their genes.

GENE DISCOVERIES REVOLUTIONIZE DIETING

For more than ten years, we developed individualized dieting programs like these, based on empirical evidence. At the same time, researchers were striving to understand the genetic basis of weight. Then, in 1994, a Rockefeller University team, under Dr. Jeffrey M. Friedman, identified the first "obesity gene." The discovery of one of the obesity genes shouldn't have been so amazing, since everyone had always taken the hereditary nature of obesity for granted. But in a popular, trend-driven field such as weight control, it was a watershed for researchers and practitioners alike.

If science could explain how obesity occurred, it might also explain how to undo it. That was the hope. Researchers continue to move between models and microscopes, hastening to expose other obesity genes. Concurrent with the well-publicized race to create a comprehensive Human Genome Map, the Human Obesity Genome Map was launched at the 1994 International Congress on Obesity, using research from all over the world. In it, data from published reviews is extensively cross-referenced, then linked to databanks internationally. Scientists found, importantly, that specific genes or gene mutations mismanage the body's ability to utilize nutrients, including protein, fats, and carbohydrates. Over seventy genes are now on the Human Obesity Genome Map. Tellingly, common obesity genome sequences often contain genes that increase the likelihood of disease. Only infrequently do mutations in one gene cause trouble. More often, illness and weight problems stem from complex interactions between numerous genes and other stimuli. This fact mirrored conditions we had witnessed in our patients and clients.

Optimistic about the ramifications of the burgeoning obesity genome, a growing number of people are jumping on a revolutionary new bandwagon called nutritional genomics or "nutrigenomics." The University of California at Davis is leading the way with its new Center of Excellence for Nutritional Genomics. Duke University is partnering with the Center for the Advancement of Genomics on the Genomic-Based Prospective Medicine Project to develop a truly modern and individual-based form of healthcare. The European Union has launched NuGO, a network for integrating this new branch of research.

Like most scientists, nutritional scientists had always turned to nature and nurture for explanation. Nutrigenomics connects nature and nurture, putting them on the same two-way street. Just as nature (i.e., genes) affects nurture (i.e., environmental influences such as foods, stress, and habits), nurture also affects nature. Nutrigenomics shows that nutrition can actually alter an individual's "nature," i.e., their genetic expression.

Nutrigenomic scientists scrutinize this nature-nurture interaction through a fine lens. Doctors and dietitians continue to assess concentrations of nutrients found in the urine, blood, and body tissue. With the help of technology, scientists are beginning to ascertain the actual molecules that food contains and how cells use those molecules to maintain or disrupt well being. As an example, naturally occurring phytochemicals such as the flavonoids in red grapes and berries slow the onset of heart disease. In another example of nutrigenomic research in practice, people with an explicit genetic profile may have a risk of heart disease due to the high levels of amino acid homocysteine. Increasing the B vitamin, folate, in their diet diminishes homocysteine in their blood. Foods high in antioxidants, such as fresh produce, protect the cells' ability to function normally, which is particularly important for diabetics and people with metabolic syndrome. These examples are germane because heart disease and diabetes often accompany weight problems.

In sum, we are what are genes tell us to be and we are what we eat, too, right down to the distinct chemical constituents of any given food product. The interface is nutrigenomics, a field almost unknown as recently as five years ago. In the future, the nutrition-gene link will use data from personalized gene testing to assemble even more personalized food prescriptions for health.

Inexpensive, applicable gene profiling is still years off, but our practice was already changing people's lives with diets based on their specific relationship of family history (i.e., genetics), weight, and diet. Immediately, incontrovertible scientific evidence of the hereditary character of weight problems validated the approach we had developed over the years. It verified the logic of our applied nutrition techniques, right down to their impact on individual receptors on cell surfaces. Our methodology, we learned, was based on phenotypes.

THE PHENOTYPE FACTOR

Being clear about what a gene is and what it isn't will help explain phenotypes. A gene is a recipe for making a protein. Our very lives depend on these proteins because they precipitate each and every physiological action at a molecular level. However, each gene just sits there, as though in a recipe box, unless it is activated. For its particular protein to get made, a gene has to be turned on, or expressed, by a trigger. These triggers are chemical, a confluence of interactions first among genes, and second between genes and added elements like food and stress. The chemicals bind to receptors on the cell surface, then a trigger goes off and the protein is produced. The gene is expressed, doing what it was designed to do.

Genes that are expressed result in physical manifestations called phenotypes. (Pheno is from the Greek word for "shining.") Thus, genotype is what your genes are, the fifty-fifty inheritance from your mother and father's contributions; phenotype governs what you shine like, or look like, and determines your predisposition to health as well as to specific diseases. Only the expressed genes -- usually a whole linkage of expressed genes -- matter (except in relationship to passing the genes on to one's offspring that might express them). Only they result in a phenotype.

How do genes turn on and turn off? And at what point? Research suggests that expression begins in utero, influenced by the mother's habits, eating and otherwise. After birth, the chemical triggers are either induced from outside the body (as from eating, breathing, or absorption through the skin) or from inside the body (as when emotions precipitate an infusion of hormones). The whys and wherefores of phenotypes are still poorly understood.

As is so often true, the explanation is evident in the exceptions. Research indicates that children of overweight parents aren't necessarily doomed to stoutness, even as embryos. The proof of this is in small-size people whose DNA contains obesity genes. Even carrying around, cell by cell, a genetic arsenal of fat-fate tendencies, the gun never goes off. According to the emerging understanding of the way genes work, that is because, for one reason or another, their obesity genes were not expressed, or activated. These exceptions seem to prove that genetic destiny is not immutable. If everyone whose genome holds obesity genes isn't fat, then clearly phenotype manipulation is the answer.

We knew this from our practice, not from people who weren't overweight, but from people who were. From years in the weight loss trenches, we had accumulated all kinds of proof that diet influences the messages delivered to the brain. Take, for example, people who reach for carbs during times of stress. Genetically, they usually have low levels of serotonin, which increase the risk for depression and overeating. Stress produces a release of the hormone cortisol, which triggers their desire for carbohydrate. The carbohydrates then catalyze reactions that increase serotonin production, sending soothing messages to the brain. Unfortunately, the excess calories this generates tend to accumulate at the waist.

Altering the amount and type of food our patients and clients consumed, and when they consumed it, delivered dietary chemicals to cells in ways that let them lose weight instead. Following custom diet plans, they became thinner and healthier, with different eating impulses and improved satiety. According to the science, they were altering their genetic expression, manipulating their phenotype by changing their habits and food choices to facilitate explicit chemical reactions.

Here is how dietary chemicals work. Not everything we swallow gets metabolized for fuel or storage. For example, vitamins, minerals, and phytochemicals are not stored or used for fuel but are highly involved in controlling metabolic processes. Some dietary chemicals, called ligands, peel off and bind to proteins, effectively "turning on" certain genes. When diets are out of balance, genes that would be better unexpressed light up. This might change carbohydrate metabolism or increase blood pressure. It might elevate blood glucose or increase blood homocysteine levels or any number of other bad effects. Alternatively, eating conscientiously limits damage to the cells and protects their ability to function normally. Importantly, as everyone's genetic mix differs slightly in composition, people react differently to the same ligands. Two people, even two related people, will not necessarily react to dietary chemicals the same way. One person's balanced diet is another person's increasing pants size. Clearly, therefore, one key to optimizing genetic equilibrium is personalized nutrition.

DNA-BASED WEIGHT LOSS THAT WORKS

As we said, we had always accepted that some diets worked for some people and not for others. Each client or patient completed our assessment before treatment, and its outcomes then shaped the individualized nutritional prescription. As we started looking at our cases, and reading the emerging data on nutrigenomics, we realized that we were phenotyping people with these assessments. And the specific nutritional programs we designed for these phenotypal patients and clients were the last and only diet they'd ever need.

The phenotypes provide a shortcut to genotyping, because they can be profiled easily and inexpensively. Again, this means that gene-based nutritional programs are not just for the future, and not just for people who can afford gene profiling. We knew people could outwit their genetic destiny, because our patients were doing it. Our approach already included specific tools for converting problematic phenotypes into mechanisms for weight loss. However, what was needed was an effective strategy to help, not just people who came to us directly, but swaths of people with essentially the same problems.

Grouping the data according to parallels, six distinct phenotype categories -- each associated with unwanted weight gain -- became apparent. These are as follows:

SIX WEIGHT GAIN PHENOTYPE CATEGORIES

Phenotype A: Addiction-linked weight gain

Phenotype B: High blood pressure-linked weight gain

Phenotype C: Cardiovascular disease-linked weight gain

Phenotype D: Diabetes-linked weight gain

Phenotype E: Emotional eating-linked weight gain

Phenotype H: Hormone-linked weight gain

People in these six groups share a very similar genetic destiny. Just as the research indicated, these weight gain-causing phenotypes also correlate with disease-causing conditions -- addiction, high blood pressure, cardiovascular problems, diabetes, emotional eating, and hormone imbalance.

Our objective was to design six weight loss regimes, matched to the six phenotypes, with the right balances of nutrients that feel satisfying because they are satisfying. First we developed assessments to help people determine their predominant phenotype, then carved out six diets to guide them toward weight loss and better health. We will explore the diets in detail in subsequent chapters.

We began systemizing, testing, and refining the approach. Client after client, class after class, people asked us to tell them what to eat, how much to eat and when to eat it. Before suggesting regimes, we presented the latest nutrition research. We asked questions. We asked them to fill out our assessments. The clients and patients investigated which of the six phenotype programs applied to them specifically. Feeling empowered to buck their genetic fate, they made changes in their diets and environments.

A client named Tamara was a case in point. She was an emotional-eating virtuoso, alternating between deprivation and indulgence. Her husband regularly accused her of "cheating" on her various diets. His hurtful comments sabotaged her weight loss, made her feel deprived, and actually increased the emotional eating, part of what characterized her as a Phenotype E. Hers was a clear pattern of revenge eating. After five weeks of following the Phenotype E Diet, she lost 12 pounds and gained more energy plus felt like she had control over her eating.

Jay, 5'8" and 260 pounds, was barely 30 years old when he had a liver transplant. His poor eating and exercise habits were not only keeping him from losing weight; they had compromised his liver and blood lipids, particularly cholesterol. Clearly, something had to give. After six months on the Phenotype C Diet, Jay had dropped a total of 50 pounds. It's been more than five years and Jay is still following the diet. He's taken 100 pounds off, and, more importantly, he's kept it off.

Specific diets worked on a molecular level to modify these people's genes and their phenotypal expression. Tamara and Jay were leaner and healthier within two weeks. Similarly, one of these six diets will bring you the weight loss you seek. Because you are on the right diet for you genetically, you will feel better, look better and have more energy. It will also work preventively to minimize the diseases historically associated with your weight problems.

rdMoreover, the right foods that contain beneficial dietary chemicals reduce the influx of problem ligands that have been turning on your disease-causing, weight gain-causing genes. Potentially and by contrast, they will also encourage the expression of genes that will optimize your health, longevity, and well-being. In this manner, phenotype dieting actually changes who you are. It's as easy as first determining your genetic and personal risks through our assessment and quiz, then following the regime designed for that phenotype. Your genes define you -- they should define your diet.

Copyright 2005 by Dr. Susan Mitchell and Dr. Catherine Christie