People are obsessed with food. We love to eat it and to cook it. We also love to worry about how much of it we are eating and how little of it we are cooking. We love to tinker with our diets, too, eliminating gluten or red meat, eating less trans fat or more omega-3.
As our diets shift along with our attention from one vilified or exalted ingredient to another, there are simple rules to fall back on. Every five years since the 1980s, the U.S. Department of Agriculture and Health and Human Services have issued dietary guidelines, meant for everyone over the age of 2, including those at increased risk for one chronic disease or another. The most recent recommendations as of this writing, announced in 2010, offered simple and surely good advice: Drink more water and less soda, pay attention to the salt in packaged foods, fill half of your plate with fruits and veggies, use low-fat or skim milk instead of whole.
Those guidelines are based on a review of the scientific evidence, but to a large extent, they have very little to do with you specifically — your lifestyle and food preferences, your genome, your metabolism, or the way your body reacts to particular foods. Of course, our genetically encoded preferences for certain foods and disdain for others probably do play a role in our diets: our sensitivity to the bitter taste of greens, for example, or our insensitivity to salt.
What if we had more to go on? We’ve all heard that we are what we eat, and surely that’s in many respects true. But what if the reverse were also possible? What if we could find a path to better health by eating some foods and avoiding others based meaningfully on who we are as individuals, all the way down to our DNA? In other words, what if we could eat for who we are, not the other way around?
Eating for You
In questions about what to make for dinner, it’s fair to say we’ve grown rather confused as a Western culture. “Nutrients have faced a problem that there is a lot of conflicting information in the public,” says David Mutch, a researcher at the University of Guelph in the field of nutrigenomics, the study of the interaction between nutrients and our genes. Take dietary fats, for example. We’ve heard that omega-3s are good for heart health, he says, but then another recent study says they increase prostate cancer risk.
“What should I do?” he asks. “I don’t know. That’s where nutrigenomics can help us sift through conflicting data. Many studies don’t consider that not all people are the same and will respond differently to foods. The idea that everyone will respond positively to any type of nutrient is probably incorrect.”
While tailoring dietary advice to individuals or, perhaps more realistically, to particular subsets of people is still very much a work in progress, there are some clear and classic examples. People with phenylketonuria (PKU) lack an enzyme needed to break down the amino acid phenylalanine. By limiting phenylalanine in the diet, those with the mutation can avoid mental retardation and other problems, which explains why babies in the U.S. and many other countries are screened for PKU at birth.
“Who thinks asparagus and broccoli and salmon would make you feel awful?”
Some people are genetically programmed to digest milk all throughout their lives, making dairy products a good source of calcium and protein. Others, especially those from Asian countries, are lactose intolerant and can’t really stomach the stuff once they graduate from toddlerhood. Although the underlying genetics are much more unclear and complicated, celiac disease is another high-profile case in which a dietary change to eliminate gluten — a protein found in wheat and related grains — can resolve intestinal symptoms.
New work by nutrigenomics researchers is adding to the list. Mutch has found that genetic variation for particular enzymes can influence how readily people will respond to healthy omega-3 fatty acids. He himself is a poor converter of the essential fatty acids based on his genotype, which has led him to increase the dose of fish oil he takes every day.
Nutrigenomics pioneer Jose Ordovás of Tufts University and his colleagues recently showed that individuals carrying a particular genetic variant have healthier blood lipid profiles and lower stroke risk than other people do, especially when they follow a Mediterranean diet rich in grains, beans, nuts, fruits, and vegetables. Another recent study by Ordovás indicates that higher-fat dairy foods will lead some to be overweight but not others, depending on which versions of the functional apolipoprotein A2 gene they carry.
A panel of seven genes is now available via licensed dietitians and the Canadian company Nutrigenomix to answer questions, according to the company brochure, including “Are you drinking too much coffee? Are you getting enough omega-3 fat? What about salt?” (Many older nutrigenomics companies, fueled by early optimism following the completion of the Human Genome Project, have come and gone over the years. Experts also urge extreme caution when it comes to any company offering information for the purpose of selling nutritional supplements or other products.)
Follow the Mystery
The connections between nutrients, the genes we carry, and our health often won’t be as simple as those Nutrigenomix promises to answer. To get a flavor for how devastating and downright mysterious the complex interplay between health and nutrition can be, meet Colleen Urben of Madison, Wisconsin, a 52-year-old mother of two grown daughters.
Formerly a researcher in a molecular biology lab, Urben has recently launched a second career in the sale of molecular biology products. In talking to her over the phone, her voice is full of energy as she tells me how “awesome” she feels. Not so long ago, after years of growing sicker and sicker, Urben thought she’d be on disability soon, if not already. Instead, she runs, lifts weights, and practices yoga regularly, when she isn’t traveling for work.
The health problems first surfaced with a Graves’ disease diagnosis at the age of 40, prompted by symptoms of sweating, nervousness, agitation, tremors, and weight loss. Graves’ disease is an immune system disorder linked to the overproduction of thyroid hormone. Doctors treated the condition by destroying her thyroid. Although that problem was solved, Urben didn’t get well.
She found many doctors to be frustratingly dismissive of her illness. She recalled one saying to her, “You can’t be this sick. If you were, you’d be dead by now, you’ve been sick so long.” Finally, Urben found someone equally stumped, who decided to order a full autoimmune workup.
The results were striking: Urben’s antinuclear antibody test, a blood test used as a measure of the body’s propensity to fight itself, was “off the charts.” She was also anemic, and her electrolytes were out of whack. Urben ended up not with a single autoimmune diagnosis, but with a list of them: celiac disease, Sjogren’s disease, possibly lupus, maybe rheumatoid arthritis, too.
Two years later, it got even worse. Urben developed numbness in the left side of her body. She could barely lift her leg, making it difficult to walk. It was later determined that her immune system was attacking the myelin insulating her nerves. She started a course of intravenous immunoglobulins, going in for four-hour infusions on two consecutive days once a month.
Right Foods, Wrong Person
Finally, Urben decided to take matters into her own hands and to apply what she knew about the science to her condition. It struck her that inflammation was at the root of all of her problems. She stumbled across a video about a man who changed his life by juicing fresh fruits and vegetables. She bought a juicer and stopped at a grocery store. “I decided that I was going to change it,” she says.
Shortly thereafter, she read a book by dietitian Lyn-Genet Recitas called The Plan, which espouses an elimination diet designed to ferret out those foods that cause your body to react negatively. Urben followed that plan dutifully and came to the conclusion that her body doesn’t tolerate asparagus or garbanzo beans or salmon, among other seemingly healthful foods.
She says her diet before wasn’t bad by today’s standards, but it apparently did include the wrong foods. “Who thinks asparagus and broccoli and salmon would make you feel awful?” she asks.
Within a month of her dramatic dietary shift, Urben began to taper off the IVIG infusions. She takes no medications today except those needed to fill in for her ablated thyroid. Her diet now consists of 90 percent fresh fruits and vegetables. She eats some grass-fed beef, chicken, and white fish, never salmon or dairy. She avoids anything packaged or pre-made. Before a recent bit of travel, she did research ahead of time to find the nearest smoothie bar.
“I was in there every day to get my green smoothie,” she says. “I can tell if I don’t eat well. I quickly start to feel really bad.”
Urben isn’t cured. Her antinuclear antibody tests still show some aberrant activity. Doctors have labeled her condition a spontaneous remission, although Urben argues there is nothing “spontaneous” about what has happened to her.
No one knows at this stage just how unique Urben’s experience with autoimmune disease might be. Obviously, says Robert Plenge, a clinical rheumatologist who recently made the move from Harvard Medical School to become the head of genetics and pharmacogenomics at Merck, celiac disease can be addressed by removing gluten from the diet, “and that’s a treatment.”
“I would tell my patients, ‘I don’t know if [a healthy diet] will help, but it certainly can’t hurt.’ It’s the right thing to do in general. Whether people find improvement in their symptoms because they are generally in better health or because they are reversing the underlying autoimmune process is difficult to tell.”
Some of us are lucky enough to get by without knowing much about how our bodies are put together and what it might mean for the food we put on our plates. For others, like Urben, food really might be the best medicine and maybe, down the road, genomics can help point toward a more tailored menu. In Urben’s case, a family history of autoimmune disease and her 25-year-old daughter’s recent diagnosis with Graves’ disease do suggest an inherited component.
“Obviously [Colleen] is very methodic and has reached the solution on her own,” Ordovás says. “The idea of using the genomic information is precisely to decrease the amount of trial and error and go directly to the problem. In some cases this will be possible in the short term, and in others it will take a longer time until we have in our hands the needed information.”
The Big Picture
Ordovás says we shouldn’t forget that other factors, such as beneficial gut microbes, also play an important part in questions of nutrition and the delicate balance between health and disease, which explains the rising popularity of probiotics. (A healthy microbiome is perhaps best encouraged by diets including plenty of plants. See “Change Your Microbiome, Change Yourself” in the spring 2014 issue of Genome for more on this topic.) While the field of nutrigenomics goes back almost three decades, progress has been slow. But Ordovás has grown “mildly optimistic” in recent years that a clearer picture might begin to take form.
“Nowadays, we have the technology, and we have substantially increased our knowledge about the genome,” he says. “However, we were missing an important component: the huge number of subjects needed to carry out solid gene-diet interaction studies.”
Ordovás began his work many years ago by taking advantage of long-term studies involving 3,000 or 4,000 people. What’s needed from a statistical point of view are studies involving at least 10 times those numbers. “Before, we were doing the work,” he says, “but we didn’t have the power to come out with results that were convincing.”
He points to the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, based on a collection of independent, relatively large, and long-running studies, as one new and hopeful example of where the science needs to go. There are challenges to overcome to quantify what food people eat and what’s really in that food, and Ordovás says, from his perspective, “we are still at the very early stages of the journey.”
James Kaput, head of the Clinic Translation Unit at the Nestle Institute of Health Sciences in Lausanne, Switzerland, and the former director of the Division of Personalized Nutrition and Medicine at the FDA National Center for Toxicological Research, is also working hard to put the nutrigenomics puzzle pieces together. Kaput is advocating for a systems approach to nutrition, involving genomic analysis together with measures of comprehensive nutrient profiles and more.
“Many studies don’t consider that not all people are the same and will respond differently to foods. The idea that everyone will respond positively to any type of nutrient is probably incorrect.”
No one really knows how many “essential nutrients” there are, he says, but he and other Nestle scientists are working to develop the capability to capture profiles representing 100 important nutrients. That’s in contrast to most studies done so far, which often focus on one nutrient at a time.
So far at Nestle, he has expanded a study begun while at the FDA to characterize the nutrient status in kids attending a community day program to include populations representing various parts of the world. In a broad sense, he says progress will require that more nutrition studies incorporate genetics and more genetics studies incorporate nutrition, along with other aspects of the environment.
“I think if we don’t include genetic makeup as a part of studies, which is what we’ve been promoting in the nutrition community for 30 years, I don’t think we will ever go forward in understanding causal mechanisms for why you respond the way you do,” Kaput says.
Thankfully, Urben didn’t need to wait for the science to progress any further. As tricky as her condition and its causes may be, her solution for feeling better isn’t risky or complicated: “You’ve got to get back to basics,” she says. “Get all the processed junk and chemicals out of our lives.”
That sentiment and Urben’s diet call to mind the famous and infinitely simple (if not always simple to pull off) advice of Michael Pollan, the best-selling author of many books, including The Omnivore’s Dilemma, Food Rules, and Cooked: “Eat food, not too much, mostly plants.” By food, Pollen doesn’t mean “edible, foodlike substances,” but recognizable, whole foods that don’t come with a list of mystifying ingredients.
On the other hand, manufactured foods are a fact of life for many people, and understanding how human bodies — representing people all around the world — respond to nutrients, and respond to them differently, could be key in making them that much better.