Diet Design, One Pair of "Genes" at a Time
In years gone by, your business suits were tailored on Saville Row in London, your diamonds cut in Antwerp. Today, your mountain bike is built for your frame, the seat for your gender, your ski pants and jacket for the altitude or time of year. You can hire a personal chef to cater to your culinary preferences, but can they cook for your genotype? Is it feasible that the future of how you manage your health and choose your food will be determined by genetic tests that pinpoint risk and how to manage it?
At no time in the history of America has there been a more acute focus on health. Recent declarations by public health officials of an obesity crisis have spurred overwhelming interest in the management of disease, specifically obesity and its associated diseases (such as diabetes and heart disease). Dietary intervention and increasing physical activity are critical pivot points. The relationship between diet and disease is not new. Epidemiological analysis has provided the foundation for public health and dietary recommendations for the population at large. Recent developments in genetic research, and the particularly spectacular progress of the Human Genome Project, have revealed "one-size" dietary recommendations do not fit all, and that finely targeted approaches to disease prevention are in the wings.
What We Know
The use of genetic tests and targeted nutrient intervention is not a new phenomenon. Diseases collectively known as inborn errors of metabolism long have been treated by diet manipulation. A defect in one gene can cause a defect in a critical protein that leads to critical symptoms manageable by diet changes. For example, phenylketonuria (PKU), caused by a single gene defect in the enzyme phenylalanine hydroxylase, results in the accumulation of phenylalanine in the bloodstream and will cause subsequent neurological damage if left unmanaged. Galactosemia is a rare recessive defect in galactose-1-phosphate uridyltransferase (GALT) that can lead to mental retardation if excessive levels of galactose accumulate in the bloodstream.
Both of these defects can be detected in infants shortly after birth, and can be successfully managed through diets low in phenylalanine and lactose, respectively. While PKU and GALT are single-gene traits, chronic diseases are believed to be caused by more than one gene and, therefore, are even more challenging to accurately test for and treat.
According to Jim Kaput and Raymond Rodriguez, in a January 2004 article published in Physiological Genomics, the underlying assumption of non-molecular epidemiology studies is that individual genetic variation is insignificant and that each individual responds similarly to their environment. These assumptions have led to the current broad-based dietary guidelines for chronic disease states, which now are being challenged by research at the molecular level. Of the thousands of genetic changes (mutations) that have been associated with human disease, 97% are caused by a mutation in a single gene. Chronic diseases, in contrast, appear to result from mutations in more than one (probably many) genes that involve multiple metabolic pathways.
Furthermore, researchers observe an interaction between the environment and genetic material, which adds another layer to unraveling the mystery of personalized nutrition. Studies involving identical twins reared in different environments have shown they experience different health outcomes, although they have the same genotype. It is this level of complexity that will dictate the rate at which nutrigenomics can produce health and diet management applications. Conversely, this level of preciseness also will dictate the accuracy with which future dietary recommendations can be made.
Research indicates that, although 99.9% of the genetic material is the same between individuals, that 0.1% difference is what has important implications for our health. When a particular change in the genetic material is shared by greater than 1% of the population, it is called a single nucleotide polymorphism (SNP). SNPs lead to the unique responses among individuals that differentiate how they look, how they function, and whether they are predisposed to being healthy or sick and how they respond to therapy. These differences become clear when standard dietary intervention and treatment for one subset of the population works and fails for another, even though the individuals present with the same diagnosis, such as type 2 diabetes. Proponents of nutrigenomics maintain that understanding an individual's genotype, or genetic make up, permits more sensitive dietary interventions, with subsequent improvement and success.
Recent advances in the field of pharmacogenomics underscore the importance of the field of nutrigenomics. In research studies in which the genotypes of participants have been analyzed, genetic variation can alter the effectiveness and number of side effects for drugs. By categorizing individuals on the basis of their genetic profile, pharmaceutical companies can more accurately formulate drugs, reduce toxicity and hone in on non-responsive subgroups of the population. In the same way, researchers predict nutrition can be personalized on the basis of understanding how certain nutrients alter molecular processes, gene expression and metabolism and how, in turn, these impact the onset and progression of disease.
Applications for the Food Industry
The field of nutrigenomics has not escaped the attention of major food processors. The first international nutrigenomics conference was held in 2002 in the Netherlands, and was attended by leading processors. Central to the conference was interpreting the value of nutrigenomics to the food industry. While this emerging science is captivating the research community, and consumers are getting a glimpse of what this could mean to self-directed health care, the value proposition for processors may still be nebulous.
Clearly, there is a correlation between food, diet and disease. An outgrowth of this from the food industry side has been the plethora of food products marketed with associated health claims. The emergence of the functional foods market shows acknowledgement from food industry partners that nutritional components impact health. Of interest, herbal and homeopathic remedies long have been used in medical and health practice worldwide for their role in health improvement, ailment management and prevention. But this is where the paved road turns into the dirt track.
From an investment standpoint, investigating the interactions between proteins and genes is a costly business. Among the various research groups working on the human genome project, agreement on all gene-protein interactions for the estimated 30,000 to 40,000 human genes is far from over. Until there is definitive agreement on what does what, would a food company invest its money and reputation in product development when there are still too many unknowns? An even grayer area is where food ends and pharmacology begins. If nutrigenomics reveals that certain nutrient components in various concentrations can prevent or reverse disease, where is the boundary between food as nutrition and food as medicine? These are profound issues that the food industry will need to address, with possible opposition from the pharmaceutical industry. Alternatively, it may spur potential partnerships.
Further to the argument of cost and investment, the question arises as to how prudent it might be for food companies to invest in specialized product lines for a market with capped market potential. Current dietary and health intervention guidelines are based on large, long-term epidemiological data that permit broad macro- and micro-nutrient recommendations for the population at large. This allows food companies to develop and market generic, health-appropriate products that are suitable for the majority of consumers.
According to Fredric Abramson, founder and CEO, AlphaGenics (Rockville, Md.), the science of nutrigenomics is very bright for the food industry, with unlimited potential. Citing nutrigenomics as a revolution that will be driven by consumer preferences, Abramson predicts that genomics will fundamentally change food, pharmaceuticals and supplements. He sees the food industry as a natural partner in developing products that could, for example, target broad-spectrum conditions such as menopause or breast cancer. Based on genetic tests which would help (women) determine how their genes are changing over time, foods could be developed to deliver the right nutrient profile at the right time to produce health-conducive results. These foods could also help to diminish symptoms which may compromise health in the long run. The key, says Abramson, is pinpointing how food interacts with an individual's genes over time, and producing the right food product formulations to intersect with those given points in time. This, he says, is the opportunity.
Ruth DeBusk, a registered dietician, sees definite potential in developing food products for segments of the population with a shared common genetic defect. Genetic polymorphisms that are diet-responsive are emerging. A recent study found that Mexican women were more likely to carry a polymorphism that alters folate synthesis and may require higher levels of folate than thought. Inadequate folate is known to predispose infants to neural tube defects and, possibly, to increased risk of cardiovascular disease in adults. If further studies determine these women are particularly susceptible to low-folate status, folate-rich, culturally appropriate foods for this population would be a market opportunity for the food industry. DeBusk cautions that before this type of product development and target marketing are acceptable, â€œwe need to get to the point where your genotype is as common as your blood pressure reading, or your height and weight.â€? In other words, people would have to be comfortable with sharing the intricacies and intimacies of their genetic information.
Due to its relative infancy, an undetermined factor in marketing genetically appropriate foods is consumer acceptance. On the positive side, two clear factors drive the notion that customized foods might become acceptable. Firstly, the emergence of a small number of companies providing specialized nutrition profile testing with customized supplements and diets supplied after analysis. Secondly, an increasingly health-conscious consumer associated with the burgeoning Baby Boomer population. Growth in dental and eye health categories as well as expansion in specialty supplements and herbal remedies associated with age-related conditions, directly support the fact that the aging population is looking for, and willing to pay for, health solutions. Using the science of nutrigenomics, consumers would have a physician or genetic counselor interpret the results of their genetic profile. A nutrition professional would then tailor a diet specifically to the genotype, emphasizing foods that would confer protection or enhance functionality.
On the negative side, consumer skepticism about anything involving genetics or genetic modification cannot be underestimated. While genetically modified (GM) foods cannot be equated with genetically sensitive (customized) diets, consumer acceptance is an unknown. In Europe, widespread skepticism about GM foods has hampered market growth for food products containing GM ingredients. In the U.S., consumers have shown broad acceptance for such food products. However, evidence of growing resistance and skepticism among U.S. consumers, coupled with growth in the organic foods sector, most likely indicates significant efforts will be needed to build consumer confidence in customized foods.
Servicing the Consumer
The field of nutrigenomics and its application to food, health and the consumer has spurred rampant discussion on ethics. Issues relate to privacy of information, access to testing, access to results and equity among different population groups and countries. There is little doubt, in this age of customization, that the consumer will be interested in any service that can provide customized solutions. Apply this to the realm of health care and medical information, and the waters get muddy.
While genetic testing can identify risk factors that can possibly prevent chronic health problems, who should have access to this information? If genetic testing is affordable by a small subset of the population with the lowest risk for chronic disease, at what point in time should genetic testing be made available as part of a public health program that might ultimately reduce long-term health costs? From manufacturers' perspectives, if different population subgroups have different nutrient composition requirements, which subgroup should they develop products for, and what is the financial and ethical impact of choosing one group over another?
At the end of the day, customized foods and personalized nutrition will be driven by consumer demand. Once consumers realize that food choices can be tailored to their genetic make up, they will seek out food companies and food products that can help them eat right for their genotype. NS
Editor's note: Prepared Foods wishes to acknowledge the insights of Ruth DeBusk, Ph.D., .R.D., and Frederic Abramson, Ph.D. in writing this article. Ruth DeBusk is the keynote speaker for the 2004 New Products Conference. See page 118 for more information, or visit www.PreparedFoods.com.
Human Genome Project Goals