Hippocrates counseled that food "can be thy medicine and medicine thy food."

Two thousand years later, geneticists may soon quantify for us just how medicinal-or detrimental-food can be, right down to our genes.

By pairing nutrition with the genetic variations that can cause disease, researchers in the new field of nutrigenetics hope to update the old apple-a-day proverb and dangle before us the proverbial golden apple: diets customized to our genetic makeup, guaranteed to keep us well.

Consumers are already sending in cheek-swab samples to genetic laboratories, paying anywhere from $200 to $1,200 for their own genetically tailored, disease-fighting eating plans.

"We eat 85,000 meals in a lifetime if we eat three meals a day and we live to 75," says Kathy O'Neil-Smith, MD, an internist in Boston who offers nutritional recommendations to as many as 15 patients a week based upon their genetic profiles. "That is an opportunity to give your patients the materials, substrates and ingredients they need to keep their bodies healthy."

Critics, however, question the clinical utility of gene-guided diets, which are based on a science still very much in its infancy.

What Is Nutrigenetics?

Genetic variation makes up just 1 percent of human DNA, but it explains why your eyes might be blue and those of your co-worker, brown.

An out-of-place A, C, G or T in the human genome sequence (called a single nucleotide polymorphism, or SNP) reveals key information about chronic disease development.

Nutrigeneticists explore the influence of diet on these variations. Because nutrients activate or silence gene expressions, food can, in fact, be our best medicine, they contend: diet can help reduce chronic diseases such as type 2 diabetes, heart disease, stroke and cancer.

Consider the APOE gene, which plays a role in removing cholesterol from the blood stream. About 20 percent of the U.S. population carries a variant known as APOE-4, a polymorphism associated with elevated total cholesterol, increased risk of type-2 diabetes and Alzheimer's disease.¹ Studies show people with the APOE-4 variant should skip wine at dinner-regular consumption may put them at increased risk for vascular disease. These people also tend to accumulate triglycerides from fish oil. On the plus side, though, they benefit more from a low-fat diet than others; their levels of low-density lipoprotein (LDL), i.e., the "bad" cholesterol, will decrease more.  

Knowing all this, physicians can customize a low-fat diet for patients with the APOE-4 variant, minus wine and fish.

Questionable Measures

As fascinating as nutrigenetics seems, critics warn it may be too early to draw these kind of sweeping conclusions.

Genetic variations represent just one component of disease risk, making up 1 percent to 3 percent of common diseases, says Charis Eng, MD, PhD, chairperson of the Genomic Medicine Institute and director of the Center for Personalized Care at the Cleveland Clinic.

Our genetic codes are voluminous and the risk of developing disease from a single genetic variant is quite low, says Dr. Eng, a specialist in ovarian cancer research. For example, a woman's risk for ovarian cancer is just 0.50 percent in her lifetime. A common genetic variant may nudge this up to a 0.55 percent lifetime risk. A nutritional recommendation based on a tiny fraction of a percentage point is innocuous, she says. 

Moreover, genetic variations denote only risk-not certainty of contracting disease. The 20-or-so genetic variations at play in type-2 diabetes only account for 3 percent of people with that disease, explains Raymond Rodriguez, PhD, director of the Center of Excellence for Nutritional Genomics at the University of California, Davis.

"Companies are selling a test and saying we'll look at your SNPs and tell you risk factors for a particular disease and we'll recommend a diet that will help prevent, mitigate or delay the onset of disease," Dr. Rodriguez says. "There is just not enough information in those tests to even come close to predicting these types of associations."

Paying for Common Sense?

Proponents counter that nutrition does indeed promote health. Studies validate it.

"No one is saying this is the whole picture," says Ken Kornman, PhD, founder of Interleukin Genetics, based in Waltham, Mass. "But if you ask, 'Do we have the genetic technology today to tell you about your HDL and inflammation and the diet components that optimize these genes?' then the answer is yes."

Like other forms of medicine, nutrigenetics works even without knowing all the many factors at work in a patient, Dr. O'Neil-Smith adds. "All the information is not there, but the information we have is very valid," she says.

Still, many schooled in genomics believe nutrigenetics companies are overreaching themselves when they sell supplements offering customers a "full solution" to their nutritional shortcomings. "They want to make you a lifetime customer, someone who is going to be buying that special product because [they purport] that's the only way to be healthy," says Jose Ordovas, director of the nutrition and genomics lab at Tufts University in Boston.

"With very few exceptions, these companies don't have the grounds and the scientific support to promise what they are promising."

Other nutrigenetic recommendations are criticized as just high-tech versions of age-old wisdom. For example, genetic tests commonly look for a variant in the 5,10-methyltetrahydrofolate reductase (MTHFR) gene.

If this gene is maladaptive, patients have more homocysteine circulating in their bodies, an amino acid that can up the risk for heart disease, thrombotic disease and stroke. Eating folate-rich leafy green vegetables can modulate the gene's expression, ensuring homocysteine levels stay low. But the recommendation to eat leafy greens is hardly an earth-shattering revelation.

"In reality, you are paying for common sense," Dr. Rodriguez says. "It's a situation where the information being provided isn't wrong, but it just may not be worth the price."

Disease Prevention

But some experts believe patients who explore nutrigenetics are making a smart investment and doctors should be leading the charge, according to Dr. O'Neil-Smith.

"Traditionally, the medical professional has focused its energy on illness. We now need to focus on primary prevention," she says, pointing to record rates of chronic diseases at least partially explained by poor diet.

Furthermore, she adds, nutritional recommendations from genetic laboratories come in easy-to-understand formats that can help physicians open a much-needed dialogue about nutrition with patients.

It could turn out that nutrigenetics, even in its infancy, may succeed in persuading people to eat medicinally, as Hippocrates urged: people may be more willing to comply with a healthy diet if they've paid a geneticist for it. 

In 2007, Greek researchers divided 93 patients into two sets. Half were tested for 24 variants in 19 genes involved in metabolism; the other half received no nutrigenetic testing. Both groups were counseled on the heart-healthy merits of the Mediterranean diet.

After 300 days, the group tested nutrigenetically showed a 5.6 percent BMI loss, compared with a 2.2 percent weight gain in the other group. In addition, more than half of the tested group had fasting blood glucose levels in the optimal range, compared with just 25 percent in the non-tested group.²

"We are noticing in studies a strange placebo effect for people undergoing this testing," Dr. Ordovas observes. "People may feel this is specifically created for [them] and are more likely to comply."

Is that bad? "Obviously, it's not optimal," he says. "But it is one way to get people to a new way of thinking."

For people who struggle with healthy eating, it may be just the push they need.

References

1. Mead, N. Nutrigenomics: The genome-food interface. Environ Health Perspect. 2007 Dec; 115(12): A582-A589.

2. Arkadianos I, Valdes AM, Marinos E, Florou A, Gill, RD, Grimaldi, KA. Improved weight management using genetic information to personalize a calorie controlled diet. 2007; 6:29.

Marci A. Landsmann is managing editor. She can be reached at mlandsmann@advanceweb.com.