New Era of Consumer Genetics Raises Hope and Concerns

By ANDREW POLLACK

ome people can eat slabs of steak and butter without gaining weight or raising their cholesterol levels. Others assiduously shun fats and still have a high risk of heart disease. The different response to diet is determined in part by one's genes.

Now scientists are beginning to apply genetics to diet, a new field known as nutritional genomics, or nutrigenomics. In the near term, the study is expected to reveal how particular diet ingredients affect health. The ultimate goal will be to tailor one's diet to genetic makeup.

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Mass market products like corn flakes may one day come in different varieties, geared to different subsets of people based on their genes. And dietary guidelines issued by the government or medical societies will have to make more distinctions based on genetic profiles.

"We're moving into an era where the one-size-fits-all public health strategy for disease prevention will not apply as it currently does," said Dr. Muin J. Khoury, director of the Office of Genomics and Disease Prevention at the Centers for Disease Control and Prevention.

Pharmaceutical companies are working on a related field known as pharmacogenomics, with the goal of developing so-called personalized medicine. It is known that people with certain genetic variations will not receive benefit from certain painkillers or will suffer serious side effects from a dose of a cancer drug that helps others.

Nutrigenomics would expand the idea of personalized care into the consumer world. "This will take the benefit of the Human Genome Project and extend it from the hospital to the home," said Dr. Raymond L. Rodriguez, a professor of molecular and cellular biology at the University of California at Davis.

Already there are some examples. People with phenylketonuria, a rare inherited disease that leads to mental retardation, can avert problems with a special diet low in proteins. People with a particular gene variant cannot digest milk.

The advent of consumer genetics is also raising concerns. Already some small companies are offering vitamins or dietary advice customized to people based on genetic tests. Customers swab the inside of their cheeks with cotton to obtain their DNA.

But many experts say not enough is known yet to support the claims of these companies. "I'm really skeptical that this is going to lead to health benefits at the stage of knowledge we're in," said Dr. Ronald M. Krauss, a senior scientist at the Lawrence Berkeley National Laboratory who was the chairman of the dietary guidelines committee of the American Heart Association.

The companies defend their tests. "This is not voodoo; this is science," said John R. DePhillipo, chief executive of GeneLink, of Margate, N.J., which is developing customized vitamins and skin products based on gene tests. NuGenix, a company owned by Mr. DePhillipo's children, recently began selling customized vitamins at $300 for the test and a one-month supply.

GeneLink does not make public which genes it tests for, but one of them is manganese superoxide dismutase, which is involved in reducing so-called oxidative stress. A variant of the gene that is not as efficient as other forms has been shown to raise the risk of breast cancer, Parkinson's disease and other diseases, said Dr. Robert P. Ricciardi, a professor of microbiology at the University of Pennsylvania and a founder of GeneLink.

People with this variant would be given vitamins with an extra dose of antioxidants. "It's giving some sort of rational approach to nutrients and formulations," said Dr. Ricciardi. "A lot of people are just mega-dosing on stuff."

Sciona, a British company, is selling customized dietary advice for about $200. The company tests for 19 variations in nine genes. Six genes are involved in removing toxins from the bodies. Consumers who have variations that the company says slow this process are advised, for instance, to avoid well-done red meats, which have higher levels of certain toxins.

Another test is for the gene that produces Mthfr, an enzyme involved in using folic acid, an important vitamin. People with a less efficient version of this gene are told to eat more liver, broccoli and other foods rich in the vitamin.

Outside experts acknowledge that scientific papers link certain diseases to genetic variations and diet. But they say dozens or hundreds of genes may be involved. In some cases, data on genetic variations can be conflicting. In addition, they say, the companies have not proved that the diet or vitamins they recommend will really make a difference. For instance, Dr. Khoury of the C.D.C. said, it is not clear that people with the Mthfr variant need more folic acid than they are already getting.

"There is so much uncertainty about the meaning of these genetic tests," he said. "Right now we are telling people to exercise, eat well, eat a diet high in fiber, low in fat. From what I see, so far there is no added clinical benefit from the genetic tests."

Dr. Helen Wallace, deputy director of GeneWatch U.K., a group that led opposition to Sciona's test, said the advice was too generalized to be worth paying for. "Most of us could probably do with eating more broccoli," she said.

Dr. Chris Martin, Sciona's chief executive, said that although some of the advice was common sense, people took it "much more seriously" because it was personalized. He said the company had sold more than 600 tests so far.

Genetic tests that are offered as services, in contrast to those offered as testing kits, are not stringently regulated by the Food and Drug Administration. Companies do not have to prove claims, for example, that a particular genetic variation is linked to a higher risk of disease or the inability to use a vitamin. And dietary supplements and cosmetics are also lightly regulated.

Another concern is that some genes that may be tested for dietary purposes are risk factors for serious diseases. Should consumers be told, and do they risk being denied insurance or jobs if that information leaks out? Do they need medical advice? Sciona initially sold its advice through retail stores, but after controversy arose, it is now selling only through doctors and dietitians.

People with a version of a gene called APOE, for instance, tend to have their cholesterol go up or down more rapidly in response to dietary changes, Dr. Krauss said. But this same gene variant, known as APOE4, also means a higher risk of Alzheimer's disease. "We don't even like to measure APOE anymore because it would get people worried about Alzheimer's," he said. In some cases, he and others said, it is not necessary to test genes. Other tests, like those for cholesterol, can help guide diet decisions.

Still, despite skepticism about some early applications, interest is growing. Several companies, some still operating in their founders' living rooms, have sprung up: Galileo Laboratories in Santa Clara, Calif.; Alphagenics of Gaithersburg, Md.; NutraGenomics of Chicago; and NuDisCo of St. Louis.

Bigger food and consumer products companies like Unilever, Nestlé and Kraft are at least monitoring the field. Interleukin Genetics, a company that studies variations of genes involved in inflammation, announced last month that it was in talks with a "major consumer products company" about developing nutritional supplements and skin care products based on genetic information.

But much of the early focus is not on customizing foods but on using genomics to unravel the mechanisms by which certain food ingredients affect the body. "We'd like to know the molecular mechanism of nutrients," said Dr. Young S. Kim, a program director at the National Cancer Institute, which recently held a workshop on nutritional genomics and cancer prevention.

Scientists at Johns Hopkins have found which genes are turned on by sulforaphane, a compound in broccoli that helps prevent cancer. Dr. Len Augenlicht, professor of medicine and cell biology at the Albert Einstein Cancer Center in the Bronx, found that different genes were turned on and off in mice when they ate the rodent equivalent of an unhealthy Western diet than when they ate a healthy diet.

Dr. Jose M. Ordovas, director of nutrition and genomics at the Agriculture Department's Human Nutrition Research Center at Tufts, said dietary guidelines would soon have to be customized. "There are some people at very high risk of cardiovascular disease who, if they follow the current recommendations, they make it even worse," he said.

Moderate alcohol consumption, he said, is considered to reduce risk of heart disease. But for people with the Alzheimers-linked APOE4 gene, alcohol consumption raises the level of bad cholesterol. People with a certain variant of a gene called APOA1 should eat more polyunsaturated fats than called for in the guidelines.

Nutrigenomics could raise questions about policies to fortify foods. If it is found that only a subset of the population benefits from fortified foods, "do you give a whole population a higher exposure than normal to a nutrient, without knowing what the risk is?" asked Dr. Patrick J. Stover, the director of the Cornell Institute for Nutritional Genomics.