May 2019 Issue

Update on Genetic Testing
By Jill Weisenberger, MS, RDN, CDE, CHWC, FAND
Today’s Dietitian
Vol. 21, No. 5, P. 36

Is it ready for prime time to inform personalized nutrition advice?

Personalized advice has long been the cornerstone of MNT. Dietitians routinely encourage clients to make reasonable diet and lifestyle changes, and they base their recommendations on the client’s current diet, health status, health goals, income, cultural and food preferences, health literacy, willingness to make changes, and more. Genetic testing may provide additional information on which to base personalized recommendations.

Research studies examining weight loss, insulin sensitivity, risk factors for CVD, and more demonstrate outcomes of various dietary interventions on average, but there’s a wide variation in response. Some participants are responders to the intervention, and others are nonresponders. Why? Genetic differences may explain part of it. With the sequencing of the human genome in 2003, the idea that providing actionable lifestyle and nutrition guidance based on one’s own genetic makeup looked to be a possibility.

What Is Nutritional Genomics?
Nutritional genomics involves the ways in which nutrients and genes interact and are expressed to reveal phenotypic outcomes, including disease risk.1 In practical terms for consumers, it attempts to answer the question of how diet and genes affect each other.

The human genome consists of about 3 billion base pairs, and only about 0.1% of these bases differs between individuals. The most common type of genetic variation is called a single nucleotide polymorphism (SNP), which is a variation involving a single base pair of a nucleotide, the building blocks of DNA. For example, at a specific spot in the DNA sequence, an individual may have inherited a cytosine nucleotide from both parents, which confers typical risk of a health trait. Or, that individual may have inherited two copies of a thymine nucleotide at that same position, which may confer greater risk. Each person has approximately 4 to 5 million SNPs. Most occur outside of genes, but when SNPs occur within a gene or in a regulatory area near a gene, they may affect the gene’s function and play a direct role in disease.2

Gene Testing
When dietitians or other health care providers gather information about a client’s family history of obesity or disease, they’re glimpsing genetic data by inference. However, it’s impossible to know the role of shared genetics vs the role of shared environment. Actual gene testing might uncover genetic variants that influence how dietary components are absorbed, metabolized, and used, and whether individuals are at risk of obesity or other health conditions.3

Increasing interest in personalized health care and piqued curiosity about ancestry has led to a boom in direct-to-consumer (DTC) genetic testing, as well as nutrition-related genetic testing interpreted by dietitians. In recent years, improvements in testing technologies have significantly reduced the expense and turnaround time of genetic tests. “While it used to take months to genotype dozens of SNPs, millions of SNPs can now be genotyped rather quickly,” says Scott Thompson, chief operating officer of Genetic Direction, a genetic testing provider in Dallas. He says the cost of genotyping has dropped industrywide and, in the last five years, the cost at Genetic Direction has decreased by more than 50%. Thus, testing is available to more people. According to the Centers for Disease Control and Prevention, millions of people have participated in DTC genetic testing to learn ancestry data, which frequently is coupled with health data.4

Genetic testing companies offer a host of programs for weight loss, heart health, athletic performance, macronutrient and micronutrient metabolism, and more. Consumers access genetic tests directly through the internet, weight loss programs, and dietitians.

How the Tests Are Done
Typically, the consumer puts a sample of saliva or cells from the inside of the cheek into a package provided by the testing company and mails it to the lab. In the lab, the DNA is extracted from the sample, isolated, and analyzed to determine the consumer’s genotype for a specific set of SNPs. Finally, the company interprets the SNP genotypes and generates a report, which goes directly to the consumer for self-interpretation, or the report may be sent to a dietitian or weight loss counselor for discussion with the consumer.

The content of a report and actionable advice will vary by genetic testing company. One company may test 45 genetic markers, while another may test 50 or only 30 markers. In addition, each company may look at different markers for the same health trait. For example, one company may examine seven genes to assess how the body metabolizes fat, and another will look at more or fewer. This can lead to differences in the interpretation of a health trait and subsequent dietary recommendations. Even if two companies look at the same genes, their proprietary algorithms may weight the genes differently and yield different recommendations.

Scientific advisors review the literature to determine which genetic markers to consider for specific traits and create algorithms when more than one marker is used to assess the same trait, eg, the ability to lose and maintain weight. A variety of studies may provide these data. For example, large studies including the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial have identified genes that play a role in weight loss, says Mark Sarzynski, PhD, FACSM, FAHA, an assistant professor at the Arnold School of Public Health at the University of South Carolina and the director of genomics research at Genetic Direction. In the POUNDS LOST study, 811 subjects with obesity or overweight were assigned to one of four heart-healthy eating plans with varying levels of macronutrients for two years. Though weight losses were similar among the various plans, later analysis suggested that individuals with a particular genotype dropped more pounds on a high-carbohydrate diet while those with a different genotype fared better on a high-protein diet. Some observational studies also have found significant gene-diet interactions.5 Though research is clear that a variety of eating plans facilitates weight loss, it’s the goal of genetic testing companies to identify an optimal focus for each person and provide DNA-based diet and lifestyle advice in general.

Yet not all experts agree that the science the DNA testing companies provide is ready for widespread use. According to George P. Patrinos, PhD, a professor at the University of Patras department of pharmacy in Patras, Greece, and full member and national representative for the European Medicines Agency’s CHMP Pharmacogenomics Working Party in Amsterdam, the Netherlands, there’s insufficient evidence to support that diet can be individualized based on a panel of a few genomic variants. Patrinos and others conducted a meta-analysis of approximately 1,200 studies involving 38 gene variants offered by commercial nutrigenetic testing companies. They concluded that these 38 gene variants weren’t associated with the occurrence of nutrient-related conditions such as obesity and diabetes.6 Genetic testing companies often exploit the public’s lack of genetic literacy and provide them with expensive reports of no value, Patrinos says.

Timothy Caulfield, LLM, FRSC, FCAHS, Canada Research Chair in Health Law & Policy and a professor and faculty of law and of the School of Public Health at the University of Alberta, also finds the research surrounding nutrition-related genetic testing underwhelming. “For me, the data isn’t definitive enough to justify the kind of marketing and pop culture noise we are seeing. Not even close,” he says.

How Dietitians Use Genetic Testing
Experts agree that physicians should order tests to diagnose or treat a disease. Disease risk genes are ones that directly predict the likelihood of developing a disease. They’re called high-penetrance genes if there’s a very high likelihood of developing the condition just by having the genetic variant, explains Ahmed El-Sohemy, PhD, a professor and Canada Research Chair in Nutrigenomics at the University of Toronto and founder and chief scientific officer of Nutrigenomix Inc, a multinational genetic testing company with more than 8,000 practitioners in 35 countries. An example of a high-penetrance gene is BRCA1, which is a rare genetic variant with a very high likelihood of developing breast cancer. Fortunately, these types of genetic variants aren’t common, but they “require guidance from a medical doctor or genetic counselor,” he says.

Nutrigenomix, Genetic Direction, and many other companies typically test for and provide reports for low-penetrance genes, which are genes that suggest increased disease risk, or modifier genes. Modifier genes affect the metabolism or response to nutrients and various dietary factors such as caffeine, sodium, and gluten, El-Sohemy explains. For example, having a risk variant of the CYP1A2 gene doesn’t influence the known risk of any condition by itself. “But having the risk variant means you’re inefficient at metabolizing or detoxifying caffeine. So being a slow metabolizer of CYP1A2 will increase your risk of heart disease if you drink more than two cups of coffee,” he adds. However, research linking coffee consumption to CVD risk based on genetic variants is mixed.7 Another modifier gene is the ACE gene, which directs the body to produce the angiotensin-converting enzyme. Individuals with a risk variant for the ACE gene are at risk of high blood pressure in the presence of a high-sodium diet.

Dietitians are implementing genetic testing in a variety of settings. Cindy H. Carroll, MS, RD, LDN, RN, IFNCP, of Bedford, Massachusetts, has used genetic testing in her private practice for about five years within a variety of clinical areas, including weight management. She frequently provides tests through PureGenomics. One interesting application is an SNP linking weight gain to saturated fat intake. “Not everyone is sensitive to saturated fat, in terms of their weight, but some people with this SNP may be,” she explains. High saturated fat intake may stall weight loss even when calorie intake is reduced, she adds.

According to Kristin Kirkpatrick, MS, RDN, consultant of wellness nutrition services at Cleveland Clinic Wellness Institute, many patients more fully embrace dietary changes based on the results of genetic testing. For example, among other changes, one client included more omega-3 fatty acids based on a gene related to triglycerides and more whole grains based on a gene associated with increased risk of type 2 diabetes.

Kassandra Gyimesi, RDN, owner of Personalized Nutrition Concierges, LLC, a virtual practice based in Denver, provides nutrition-related genetic testing through Nutrigenomix. She notes that clients want dietary guidance unique to them. After seeing the cardiometabolic results of her DNA report, one recent client with hypertension and no genetic family history to draw on was motivated to cut back her caffeine and sodium intake. Both the client and her doctor were ecstatic with the results, Gyimesi says.

Nanci Guest, PhD, RD, CSCS, who sits on the scientific advisory board of Nutrigenomix, uses genetic testing in her private practice in Toronto, Ontario. Guest and colleagues conducted a randomized controlled trial of more than 100 athletes. They found that both 2 mg/kg and 4 mg/kg caffeine improved 10-km cycling time, but only in those with a specific genotype of the CYP1A2. Increased caffeine had no effect in athletes with a different genotype and even hurt performance in those with a third genotype. “CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance,” she explains.

Nutrisystem integrated an optional genetic testing component to their weight loss program last year. According to Courtney McCormick, MPH, RDN, LDN, manager of clinical research and nutrition at Nutrisystem, survey data showed that “3 out of 4 diet intenders believed the knowledge provided by genetic testing would increase their motivation for both dieting and exercise.” Nutrisystem, in partnership with Genetic Direction, developed a genetic-based report that includes data associated with weight management, eating behaviors, response to exercise, caffeine metabolism, and metabolism of specific micronutrients.

Best Practices for RDs
When it comes to interpreting genetic testing results to counsel clients, it’s important for dietitians to first be well trained, says Martin Kohlmeier, MD, PhD, a professor of nutrition and director of the Human Research Core and Nutrigenetics Laboratory at the University of North Carolina (UNC) Nutrition Research Institute. Just as there are nuances in appropriately interpreting lab results and recommending treatment, there are careful distinctions that must be made with the review of genetic tests and the guidance that stems from them. So properly using genetic information can’t occur without additional effort and training, he adds. Both the UNC Nutrition Research Institute and the International Society of Nutrigenetics/Nutrigenomics offer training programs for health professionals. Dietitians should take the following guidance into consideration:

Research the genetic testing company. Before integrating nutrition-related genetic testing in their practices, dietitians should research genetic testing partners. Start by making sure the lab is either certified by CLIA (Clinical Laboratory Improvement Amendments) or accredited by the CAP (College of American Pathologists), Thompson says. And be sure that both the genes tested and the research used to make assessments are publicly available in the report, he adds.

Avoid companies that attempt to diagnose clients. Research the credentials and experience of the company’s scientific advisory board, and review a sample report for thoroughness and ease of use. Some companies couple their reports with recommendations for their own brand of supplements, which some dietitians will find helpful but others will view as a conflict of interest.

Interpret DNA tests cautiously. Mascha Davis, MPH, RDN, works with Pathway OME in her Los Angeles–based private practice. She emphasizes the importance of understanding that these tests aren’t diagnostic. They show predispositions only, and clients should understand that. Carroll points out that DNA testing must be used in conjunction with traditional assessment measures and clinical presentation. For example, a gene SNP predisposition to a nutrient deficiency shouldn’t lead to supplements without checking for an actual deficiency. But certain SNPs may help explain why some people need supplementation, she explains. Likewise, genetic tests should be combined with other proven strategies such as medications or calorie control, as indicated, Thompson adds. McCormick suggests using the DNA report as an opportunity to kick off the motivational interviewing process. Find out what areas the client wants to start with and plan small behavioral changes, she adds.

A client may bring in an unfamiliar report from an outside testing company. Recognize that some DTC testing companies have little science behind their reports, and it may be best to guide the client to other foundations for behavior change. As an extreme example, one DNA report noted a possibility of a choline deficiency. The user was directed to consume at least 550 mg choline daily, which, according to the report, could be met by consuming three cups of raw lentils or three items from a fast food restaurant daily—recommendations dietitians would be unlikely to make.

Additional Criticisms
Last year, the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study suggested that genotyping to pick an ideal macronutrient intake for weight loss doesn’t work. The study found no greater weight loss when dieters were randomized to their DNA-matched diet or to a mismatched diet. According to El-Sohemy, “This study didn’t find a gene-diet interaction because the researchers simply picked the wrong SNPs, which had not been linked to weight loss in any prior study.” It’s like looking at the lactase gene to predict response to gluten, he adds.

Patrinos emphasizes that much of the nutrition and lifestyle advice generated from DNA testing is similar or identical to general health guidance, such as to consume more fruits, vegetables, and whole grains, and reduce sodium intake. No one needs to pay extra money to get this advice, he says. Caulfield says that “given that a big hunk of the population doesn’t come close to meeting the basic nutrition recommendations, it seems absurd to focus on a high-tech niche technology backed by underwhelming science.” In addition, he worries that taking an individualized approach to nutrition will shift the policy focus away from the type of population-level actions that can have a real impact.

Whether experts are in favor of widespread use of nutrigenomics testing for healthy individuals or not, researchers agree that the science will continue to bring new insights.

— Jill Weisenberger, MS, RDN, CDE, CHWC, FAND, is the author of four books, including Prediabetes: A Complete Guide. She’s a freelance writer and a nutrition and diabetes consultant to the food industry, and has a private practice in Newport News, Virginia.


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2. What are single nucleotide polymorphisms (SNPs)? National Institutes of Health, US National Library of Medicine, Genetics Home Reference website. Updated March 19, 2019.

3. Ferguson LR, De Caterina R, Görman U, et al. Guide and the position of the International Society of Nutrigenetics/Nutrigenomics on personalised nutrition: part 1 — fields of precision nutrition. J Nutrigenet Nutrigenomics. 2016;9(1):12-27.

4. Bowen S, Khoury MJ. Consumer genetic testing is booming: but what are the benefits and harms to individuals and populations? Centers for Disease Control and Prevention website. Published June 12, 2018. Accessed February 22, 2019.

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6. Pavlidis C, Lanara Z, Balasopoulou A, Nebel JC, Katsila T, Patrinos GP. Meta-analysis of genes in commercially available nutrigenomic tests denotes lack of association with dietary intake and nutrient-related pathologies. OMICS. 2015;19(9):512-520.

7. Zhou A, Hyppönen E. Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: a prospective analysis of up to 347,077 individuals and 8368 cases. Am J Clin Nutr. 2019;109(3):509-516.