The Diet Code: Will Personalized Weight-Loss Plans Work?

More and more businesses are peddling the ultimate personalized weight-loss plan -- one determined by your individual DNA. But how much can genes tell us?

You've just arrived at the gym. You change, stow your clothes, grab a towel, and spend the next five minutes spitting into a test tube. No, that's not a joke. A year and a half ago, the fitness chain Equinox introduced its Genetic Report, a service based on the analysis of participants' individual DNA. The theory behind the (not inexpensive) offer is that different people are genetically inclined to process calories in different ways and are better off eating and working out using methods that sync with those predisposed metabolisms. Once the DNA extracted from the saliva has been sent to a lab and analyzed, an Equinox trainer consults with the gym goer on why his or her predominant musclefiber type might be better suited to a weight-lifting or cardio workout or to a low-carb or low-fat diet.

While it might sound like something out of Woody Allen's Sleeper, the service is just the latest in a lifestyle genetics craze that's been gaining traction over the past few years. Since the human genome was first decoded, in 2000, the cost of sequencing DNA has dropped steadily, and a decade ago the first direct-to-consumer genetic tests hit the mark et. Suddenly, a cotton swab or test tube of saliv a, extracted at home and mailed to a lab, was all a person needed to unlock clues for mapping out a family tree or, more controversially, identifying heightened vulnerability to diseases like breast cancer. A few years ago, it became possible for companies to offer genetic panels, or screenings, that identified a much broader array of genes, including those involved in such everyday processes as the metabolism of carbs and fats. Is it any wonder the nation's multibilliondollar diet industry jumped right on board?

"The market for this is what some call the 'healthy wealthies,' " says Lawrence C. Brody, a senior investigator at the National Human Genome Research Institute, part of the National Institutes of Health (NIH). Elite as the patron group (and as nascent as the science) may be, Brody concedes that the idea of being able to definitively answer, from genetic analysis, how a person should eat to lose w eight is an undeniably intriguing one.

A Custom Diet

Nancy Dell, 56, a dietitian in western Massachusetts, was a model of weight consistency, hewing to a low-fat diet and holding steady at the same w eight she'd been since her twenties. "That was my training: low fat, low fat, low fat," she says. Then she took the $169 weight-management genetic panel offered by Waltham, Massachusetts-based Interleukin Genetics and was told she should be a "Carb Reducer." (Other categories include "Fat Trimmer" and "Better Balancer.") She began eating eggs in the morning instead of high-fiber cereal with skim milk. She added nuts to her repertoire but didn't change her calorie intake. "I lost nine pounds," she says, "and I never lose weight."

Pathway Fit, a "nutrigenetic" test from San Diego- based Pathway Genomics, offers a similar diet panel (for $400), though it tests for a wider range of genetically based outcomes related to diet, nutrition, and exercise. Marcelle Pick, a nurse practitioner and the cofounder of the Women to Women health clinic, in Yarmouth, Maine, has used the Pathway Fit panel to help provide tailored dietary direction to more than 100 weight-loss patients: "The notion that we should all eat the same diet doesn't make sense," she says. "We don't all look good in the same clothes."

Interleukin and Pathway are arguably two of the more credible names in a suddenly booming genetic-diet market that the NIH's Brody likens to the "Wild West." (Interleukin has a track record of collaborating on published academic studies, and Pathway, a newer kid on the block, boasts a collection of scientific advisers that includes some leading lights in the emerging field of nutrigenomics.) The U.S. Food and Drug Administration has taken action against certain of the other nutrigenomics companies that have made insufficiently substantiated health or medical claims -- in some cases resulting in the discontinuation of their products -- but for the most part these outfits have been given a free pass.

And skeptics abound. "It's just golden," says Ahmed El-Sohemy, a nutrition and genetics professor at the University of Toronto. "Low fat was all the rage and then low carb was all the rage. 'Hey, let's find something that evaluates both!' " El-Sohemy, it should be noted, has just launched his own genetics company, Nutrigenomix, offering a screening by dietitians that makes nutritional recommendations about things like coffee and salt consumption. The company also hopes to introduce a weight-loss panel. El-Sohemy says he's waiting for the science to catch up with market demand. He also has concerns about the privacy of genetic test results in casual settings like gyms. "With fitness trainers handling that kind of information, securit y becomes an issue," he says. (Government agencies, including the Federal Trade Commission, advise consumers to check the privacy policies of any direct-to-consumer genetic tests.)

If the Genes Fit

Everything we know about genetics tells us that genes are important to weight loss. Identical twins fed the exact same meals in a contr olled research setting will lose or gain almost exactly the same amount of weight, for example, while the results for everyone else will be all over the map. But how genes determine weight remains largely mysterious, and we have an incomplete picture of how different people respond to diet, exercise, stress, even exposure to toxic chemicals. If, as Pathway's medical director, Michael Nova, says, reading a genetic panel "is like looking at an individual's blueprint," there's precious little consensus on how best to interpret it.

But something, or some combination of things, must explain the results of the famous 2007 Stanford University "A TO Z" study. It found that, on average, there wasn't a huge difference in the weight lost by four groups of women on four different popular diets: Atkins (low carb), "traditional" (a standardissue "balanced" diet), Ornish (low fat), and Zone (a 40:30:30 ratio of carbs, fat, and protein). "But then you look within the diet groups," says study author Christopher Gardner, "and somebody lost twenty-five pounds while somebody else gained five." As Gardner, the director of nutrition studies at the Stanford Prevention Research Center, explains, it's less a matter of crowning a single winning diet than of finding the winning match between a diet and an individual. But unless a person tries each one in a fairly methodical way, how could she know which would be most effective for her?

The diet panels aim to address that challenge by drilling down to the level of DNA. Much of our genetic code has tiny variations that have crept in over the generations -- a single letter in a DNA basepair that has been added, subtracted, or altered in some way. These "single-nucleotide polymorphisms," or SNPs (pronounced "snips"), can account for a gene that makes a protein that does its job in a way that's different from the way a corresponding protein in your friend, who has a different SNP, would do it. Hence the great race to develop a diet panel that can identify the genes that regulate carbohydrate and fat metabolism and, trickier yet, locate the key SNPs in those genes. Every company in the business has its own "special sauce."

Sitting on the Couch, Eating Chips

The challenge, Brody says, is that most of the science is based on association rather than on cause and effect. Let's say you have a particular SNP that a study has found is associated with people who eat higher-than-average amounts of the monounsaturated good fats found in olive oil and avocados and who appear relatively slim. In the Pathway Genomics panel, having such a SNP increases the odds that the company's software will recommend a Mediterranean diet, as opposed to a low-carb, low-fat, or "balanced" one. But do we know for certain that eating monounsaturated fats is the thing that's keeping weight down for these people? No. And even if we did know that, do we know that it would also help you stay slimmer? No.

Thing is, since the diets that Pathway and Interleukin recommend are regarded by most nutritionists as healthy, these new services aren't exactly keeping medical ethicists up at night. "I think we can be pretty confident," says David Kaufman, director of research and statistics at the Johns Hopkins Genetics and Public Policy Center, "that none of these panels are going to tell you that the recommendation is to sit on your couch and channel surf and eat chips and smoke. What we don't know is whether the diet recommendation is better than what you'd get from a nutritionist."

Researchers hope to have better answers soon. Stanford's Gardner is about to embark on a study that will test the Interleukin patterns, while Ken Kornman, the company's CEO, is reviewing DNA samples to reanalyze the data from the "A TO Z" study. Kornman says he can now make a more compelling case that the women who follow diets that match their "type" have a statistically and clinically significant chance of doing better than the law of averages would suggest -- and a lower-than-average chance of doing poorly. But that's hardly a guarantee of infallibility. As Kornman says, "No one should ever translate this as, 'you've got a ninety percent chance of fitting into your bikini next year.' "

The genetics entrepreneurs themselves, then, concede that today's tests are a long way from providing the final word on genes and diet. But for people who've plateaued at 5 or 10 pounds over their target weight, tweaking their fats and carbs based on an admittedly imperfect genetic test could w ell provide a breakthrough. And even skeptics agree that the imprimatur of hard science can help people wrestle with the hardest part of a diet -- staying on it. "With the gene test," says nutritionist Dell, "you have a different commitment, you give it a chance." If nothing else, we can consider the money spent on these tests a donation to the cause of toppling the fallacy of the one-size-fits-all diet.

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