The Phenotype Factor, DNA-Based Weight Loss

Fat Is Not Your Fate
by Susan Mitchell, Ph.D., R.D., Catherine Christie, Ph.D.

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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.

Moreover, 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

About the Author

Dr. Susan Mitchell is a Registered Dietitian, Certified Nutrition Specialist, and Fellow of the American Dietetic Association. A nationally recognized authority on nutrition and stress, she is the nutrition expert for ThirdAge.com and a consultant to the Produce for Better Health Foundation's 5 A Day the Color Way program.

Dr. Catherine Christie is the Director of Nutrition Programs at the University of North Florida. A Registered Dietitian, Certified Nutrition Specialist, and Fellow of the American Dietetic Association, she is President-Elect of the Florida Dietetic Association and a former Chairman of the Dietetics and Nutrition Council, which regulates the nutrition profession in Florida. Mitchell and Christie are the coauthors of I'd Kill for a Cookie and Eat to Stay Young.