Dialogue: Nutrigenomics and Personalized Medicine

Kristi Hughes, ND, and Yael Shapiro, PhD, RD

Based on an interview with Nancy Faass, MSW, MPH

Dr. Hughes: The new genomic testing ushers in the ability to create a more specific, individualized approach to meet our patient’s true needs. These tests give us the capacity to discover unidentified genetic influences that put the patient at potential risk. Frequently there are predispositions that may not manifest for decades. Genetic testing allows us to intervene with diet and lifestyle and make choices at a reasonable point in time that can influence and transition that patient toward a greater state of health. This reduces the likelihood that we will have to work our way backwards from coronary risk, from diabetes, dyslipidaemia, and hypertension. Rather than having to intercede at a later stage in the disease process, these tests enhance our ability to foresee where things could go wrong. At that point, we have the insight to intervene with more appropriate diet, lifestyle, and environmental factors, matched to that specific individual’s genomic potential. We are at the beginning of the clinical application of this science, but this approach takes the reality of personalized medicine and personalized nutrition to the next level.

PCR DNA Nutrigenomic Testing

Dr. Hughes: Dr. Shapiro holds a doctorate in nutrigenomics from Cape Town University in South Africa. Tell us about the uniqueness of the test panels you have developed and why they are so clinically relevant.

Dr. Shapiro: DNAlysis is my company and we designed and built the test panels here in South Africa. We have a partnership with Nordic Laboratories, a Danish company in Copenhagen that helps us distribute the tests around the world, in Europe, the United States, and India. The tests originate from us, and we only work with practitioners.

At DNAlysis all of our testing is focused within the field of nutrigenomics. Everything we do is about clinical relevance and utility to support effective clinical practice. When we are deciding what kind of test to develop and which genes to include in a particular panel, we apply a strict set of criteria to evaluate whether a genetic polymorphism is clinically meaningful.

Optimizing Genetic Expression

Dr. Shapiro: In selecting the genes that are included on a particular panel, first we need to know whether a particular genetic polymorphism has an impact on some form of metabolic function. Obviously, there has to be good science to confirm this genetic activity, so we ask for at least three validated studies.

We select for genetic influences that cause changes we can measure in response to clinical interventions, changes that will guide treatment. Testing is used to answer questions such as:

• What is interacting with that gene that is changing our phenotype in some way?
• What type of environmental input will alter the course of this metabolic disturbance?
• Which nutrient(s) will alter the expression of a particular gene?

The point is that every gene and polymorphism included on the test must be clinically useful—there must be a lifestyle intervention that we can recommend, based on the presence of the gene and the associated research literature.

Exclusions

Dr. Shapiro: The BRCA gene is an example of a SNP (a single nucleotide polymorphism) that is impacted very little by diet or environmental factors. External influences on the expression of this gene are exceptionally low–almost negligible. BRCA is a single-gene mutation; by simply having that polymorphism, a woman’s chances of developing cancer are as high as 80% to 90%. Although only 5% of breast cancers will be accounted for by the BRCA gene, unfortunately the gene has very little responsiveness to what we can do environmentally. Women who carry the BRCA gene usually have an early onset of breast cancer. Consequently, we do not test for BRCA.

The majority of cancers are quite different. They are the result of a number of different polymorphisms that are influenced by diet and lifestyle, affecting inflammation, oxidative stress, methylation, and detoxification—usually reflecting altered enzymatic or metabolic activity that is interacting with diet or the environment. These cancers develop over decades in response to complex genetic influences rather than as the result of a single gene.

Genetic Panels

Dr. Hughes: What I like about these panels is the selection. In the first test panel, key risk factors are brought together in an overall health profile. The second test is focused on weight management and obesity trends, developed for patient struggling with weight loss. The third test evaluates estrogen metabolism and risk factors associated with detoxification functions. Their fourth test looks at genetic aspects of fitness with an emphasis I haven’t seen anywhere else. This profile helps us understand the patient’s genetic susceptibility to injury, their recovery processes, and optimal types of exercise for that individual.

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Test 1: Health Factors

Dr. Shapiro: Our primary health panel takes a broad look at metabolic health, focusing on factors such as inflammation, oxidative stress, insulin metabolism, and bone health. A SNP in any of the 28 genes analyzed on the test can result in impaired metabolism and eventually in disease. Since these genes influence underlying metabolic factors, rather than causing frank disease, in the past it took extensive testing to fine-tune treatment. For patients with these issues, the DNA Health panel can take some of the guess work out of diagnosis.

We know from the CDC that over 100 million people in the U.S. have some type of chronic health condition, and almost 80 million struggle with obesity. This DNA Health genetic panel is an excellent screening tool for patients with the symptoms of, or full expression of, chronic diseases of lifestyle. All the genetic variants selected for the DNA Health Report can be influenced by lifestyle factors, which means that all can be addressed through proactive interventions.

This panel is also relevant for patients concerned with risks associated with a family history of cardiovascular disease, stroke, diabetes or cancer. In addition, the test meets the needs of patients interested in peak performance—those who want ideal health and body composition. This is the perfect way to learn how optimally a patient’s metabolic processes are functioning, the best possible diet, and the best supplements, with implications for issues such as lactose intolerance and caffeine tolerance. In sum, you can use this test to support peak performance, reduce risk, or manage chronic illness.

Test 1:

Test 2: Obesity and Weight Management

Dr. Shapiro. A large portion of the population battle to lose weight. Research from the science of nutrigenomics has found that at a minimum, genetics can account for 50% of obesity and can be an influencing factor as high as 80% in a given individual. In short, genetics is a far more powerful factor in weight management than anyone has acknowledged.

When I was studying dietetics, there was no acknowledgement of genetics. Everything was about diet and lifestyle. Genetics has turned out to be the missing link. Given what we know now, we’ve come to realize that we will never be effective in weight management until we understand how genetics interacts with weight.

In the past, when we thought about genetics and weight, we thought primarily in terms of factors like metabolic rate (some patients seem to gain weight just by looking at food—others can eat as much as they want and never gain weight). In reality there are actually many factors that work together to impact weight, establishing individual risk and susceptibility to obesity: for example, the efficiency of fat absorption in the gut, with a resultant level of fats and calories coming into the system.

Genetic resistance to weight loss is common. People do not all lose weight in the same way, nor do they gain weight in the same way, and the speed at which someone gains or loses weight is also influenced by genetics. It is important for the individual patient to understand where they are on the weight loss spectrum, what is realistic weight loss, and how they can best optimize their weight loss management.

Genetics also determine how efficient each of us is at metabolizing carbohydrates and fats, how rapidly we burn calories and fats, and how we respond to exercise. What about cravings, sweets, and snacks? Is low carb the best diet or low fat?

Another aspect of working with obesity is to understand clearly how our patients experience hunger, appetite, and satiety, because that is often genetically driven. Some patients do not experience normal satiety. They are not being irresponsible or lacking willpower—they are hungry. Similarly, taste preferences and food cravings are individual and can have a genetic basis.

Dr. Hughes: In my training, we were taught to think of food cravings as the way we respond to blood sugar—insulin levels, metabolism, and blood sugar fluctuations that can set us up for cravings. But you described genes that have an impact on the way we experience the taste of sweetness and whether we crave sugar.

Dr. Shapiro: Insulin is only one part of an individual’s blood glucose management. Actually, there is an entire group of genes that give us information about how people respond to sweet foods and we discovered that there is a huge variability in how these genes are expressed. Traditionally, we believed that taste was localized to our tongue, through sensors for sweet, salty, bitter, or spicy. What we’ve discovered today is that glucose sensors are located throughout our bodies, in our gut, our pancreas, and the hypothalamus. Taste is not isolated to our tongue. So the question of why one individual craves sweets more than another turns out to be much more complicated than just blood sugar management. Successful weight management includes understanding the source of cravings and determining whether genetics is driving those cravings.

The DNAlysis Diet Panel is an excellent tool for answering those questions, given the focus on key metabolic factors: obesity risk; absorption and metabolism, including carbohydrate metabolism; fat metabolism and storage; obesity and satiety; regulation of metabolism and food consumption; insulin sensitivity and regulation of energy intake; inflammation; circadian rhythms; and exercise responsiveness.

Test 3: Estrogen Metabolism

Dr. Hughes: Many women come to my office to discuss the use of bio-identical hormones as an approach to anti-aging. This topic is very complex and includes assessing family history, the current state of the patient’s health, and looking at potential risks. How can genetic assessment of estrogen metabolism and detoxification pathways inform those clinical decisions?

Dr. Shapiro: I believe women should have a DNA Estrogen test before they make decisions regarding hormone supplementation or contraception. Estrogen hormones affect the growth, differentiation, and function of a number of target tissues. Improving estrogen metabolism is of benefit to women who suffer from estrogen-dominant conditions such as endometriosis, premenstrual syndrome, and uterine fibroid tumors, or where there is a family history of breast, uterine, or ovarian cancer.

The importance of both estrogen and progesterone in breast cancer development is well established. However, there is a great deal of variability from one woman to the next in the metabolism of steroid hormones and carcinogens, and in phase I and phase II detoxification. Variations in the genes involved in these processes help identify a sub-population of women with higher lifetime exposure to estrogens, estrogen metabolites, and other carcinogens. Understanding an individual’s genetic risk factors makes it possible to target our clinical interventions.

The DNA Estrogen Metabolism and Detoxification test includes 10 genes involved in estrogen biosynthesis, estrogen metabolism, and phase I and phase II detoxification. The results provide unique information to guide personalized diet, lifestyle, hormones, and supplement recommendations.

Test 4: Fitness Profile

Dr. Hughes: This profile reveals the types of exercise that are going to be most effective for a given individual, based on genetic predisposition, as well as insight into the recovery process. The test expands our ability to tap into our patients’ athletic capacity, to provide guidance for people in their training programs, and to customize nutrition for improved recovery… We haven’t seen that anywhere.

Case in point: this test provided me with key insight into challenges my 10-year-old daughter was having in her sport, gymnastics. We all know that gymnastics can be hard on the young developing body, but when I got back my daughter’s report I realized that the emphasis of her nutrition and supplement plan to address her intermittent joint pain was focused in the wrong area. I had been providing her with anti-inflammatory support when my direction should have been towards more optimal mitochondrial functional with an emphasis on key antioxidants. Making some adjustments to her nutrition plan was helpful for both her training and overall sense of health.

Ms. Faass: That’s amazing! So the test shows how to support optimum performance.

Dr. Shapiro: On the DNA Sport Report, we look at three different areas. One is an individual’s potential in terms of performing endurance-type exercise (such as distance running or cycling) compared with power-type exercise (like weight training). Some people have the ability to do both. However, there are others who excel in an endurance environment, but if they emphasize weight training, that can actually be quite ineffective.

We also look at injury potential, which can be a huge issue. Some individuals seem to constantly suffer injury, particularly associated with collagen tissue, such as the Achilles’ tendon, the ACL, or the rotator cuff. There are genetic susceptibilities to those injuries that we can look for in the genes, based on strong research literature confirming those susceptibilities. This aspect of the test will help patients reduce their risk of injury, by emphasizing the best sports and even the best position to play to maximize health.

Another important aspect of exercise is recovery, with an emphasis on the differences in how people recover from training. Some people recover extremely well and can get back on the road the next day, and others need greater recovery time. These individual tendencies all have a genetic basis.

We’ve been working with fitness clients on two levels. Elite sports teams such as rugby teams or cycling teams in Europe are utilizing the tests primarily to minimize injury and maximize recovery. We also work with recreational athletes who just want to make their training time count—people who are already running or training and want to take that to the next level. They want to make sure they are using the limited amount of time they have to work out in a manner that is genetically compatible. These tests are very empowering for both the practitioner and the patient.

Benefits of Genetic Testing

Researching Test Impact

Ms. Faass: Excellent. Do you have outcomes data on patients who have made lifestyle changes based on their test results?

Dr. Shapiro: That’s a question that we’ve discussed in great detail. One of the limitations in evaluating the impact of nutrigenomics testing is that nutrition and lifestyle interventions involve so many factors, it is extremely difficult to tease out the influence of genetic information on patient outcomes. Rather, we prefer to view access to genetic information as another good tool in a practitioner’s toolbox. We give providers an additional layer of information , so they can evaluate health at an individual metabolic level, identify imbalance, and focus their interventions on fundamental health issues based on individual genetic predispositions. This provides a real clinical advantage to the practitioner. However, once the practitioner decides which intervention plan to put into practice, there are a tremendous number of factors that could influence whether that patient is going to make those behaviour changes.

We cannot measure the impact of our genetic tests because they are part of a much bigger picture. This research is not comparable to that done on the BRCA gene, which tracks outcomes associated with a single gene and one intervention (whether or not to have a mastectomy). Nutrition and exercise recommendations are part of an entire treatment plan, and we are only one aspect of the intervention. We do not supersede other information that the practitioner has—we only add another level of information that they did not have access to previously.

Lifetime Relevance and Patient Compliance

Dr. Shapiro: These are tests that are only done once. This is information that does not change over a lifetime. Whatever they learn in their report will be relevant to their health for the rest of their lives.

What we do know is that using genetics in clinical practice changes behaviour and compliance. This is a decided advantage, given the world we live in, where we have so many nutritional choices. We are all confused about issues like diet and weight loss—in fact, most people are totally overwhelmed. We have found that patients can be very motivated by the idea that this their information, unique to them. There is a kind of a personal responsibility associated with that information. The research has found that nutrigenomics testing enhances behaviour modification and motivation for change. Particularly with nutrition, that motivation is a huge part of the work.

A Systems Biology Context

Dr. Hughes: What I really appreciate about the approach Yael’s team is taking is that they work within a systems biology, functional medicine framework. Their clinical feedback and their test reporting offer clinically relevant insight on how genetics can participate as underlying causes of disease. In functional medicine we call those factors antecedents. DNAlysis is doing a very nice job helping practitioners uncover antecedents and predisposing factors their patients may have. The tests provide genetic information in the context of specific functional disorders such as chronic inflammation—as well as health conditions—using a systems biology philosophy.

Triaging Clinical Interventions

Ms. Faass: And do the test results also focus the effort and recommendations of the clinician and narrow the amount of information that they have to deal with?

Dr. Hughes: I would say very much so. That’s one of the reasons we will be working with this new testing moving forward: it opens up the awareness of where you may want to go next in terms of further appropriate testing. I think it truly allows us to make better clinical choices about additional assessments without running too many tests or choosing to run the wrong tests when we have nothing to go on but suspicion or intuition.

Dr. Shapiro: The genetics allow you to see which of the metabolic areas need the greatest attention. When patients experience severe chronic illness, their presentation can be quite confusing, so we use the genetics to isolate the underlying dynamics. We recommend looking for the three metabolic areas that are the most compromised, three nutritional areas that need the greatest modification, and three supplements that would be the most effective, This helps to flag important issues, enabling practitioners to triage the interventions, and supports very specific, practical recommendations. From there practitioners can decide whether they need to do more functional laboratory tests, or whether they have to do a different kind of assessment. It gives them somewhere to start, based on specific genetic information at a metabolic level that identifies the processes that are not functioning optimally.

Clinical Support

Dr. Shapiro: We don’t expect the practitioner to see the genetic results and be able to work out for themselves the implications of the results; we do all the interpretation for them. We look at the impact of the genotypes. We look at how powerful particular genes are relative to other genes. The report provides a focused interpretation. Additionally, the data is color coded so the practitioner (and the patient) can see immediately the areas that need the greatest attention.

Dr. Hughes: For quite some time now we’ve seen the emergence of nutrigenomic testing, but much of it has been driven by patients. Our patients walk in the door with their 23andMe test results and say, “Here! Here is my genetic code. What does it all mean?” And they hand us a page full of numbers, without any reporting that might support a clinical direction. (In all fairness to 23andMe, they are currently precluded by federal policy from providing genetic health interpretations.)

Unfortunately, there is very little effective training available anywhere right now for the general practitioner to understand the scope of nutrigenomics and how that translates into clinical practice and clinical utility. There are experts who are dedicating their careers to this emerging field, but the primary care provider is often the one being asked directly. For quite some time, Genova was a leader in the practitioner field. Then we began to see different types of software companies emerge that would run the raw genetic data and generate a report identifying probabilities or patterns. The challenge is that when this kind of data is provided to patients, it is never put in full context. The concern many practitioners have is around how those programs were created, who determined the clinical correlations, and whether they are reliable. There are many opinions in this field about what to say regarding genomic risks; some practitioners voice the opinion that these reports tend to be over-stating or over-reaching in their suggestions.

What I really find exciting about the approach DNAlysis is taking is the way they present the information clinically. They look at each SNP as it relates to clinical care. For example, reporting on TNF- might emphasize risk for increased TNF- production in association with general inflammation or might flag TNF-or interleukin expression that is disrupting blood glucose management and accelerating metabolic disease.

What is unique and new about their approach is the way in which they are educating practitioners and physicians, putting the genetic results into context in relation to metabolic processes and applying that information to the physiology of the individual patient so that it translates into a clinical application. They are also leveraging their due diligence in ongoing review of the literature to validate the importance of those SNPs.

The testing includes only SNPs from the clinical research with reproducible interventions. They are not emphasizing rare genes that cause rare diseases. There’s no sensationalism around their work–they are not over-reporting or overstating the importance of the data (which is rampant right now, given the unregulated nature of this field online).

Practitioner Training

Dr. Shapiro: There is one more aspect of the DNAlysis program that I feel is extremely important, and that is the practitioner training we provide. Every time I come back to the United States, the lack of genetic training for health professionals is always striking to me.

Generally speaking it is extremely difficult for providers to access training. The IFM includes nutrigenomics in all their programs, but other than those courses, there isn’t really any place that practitioners can go and upskill themselves to the point where they feel comfortable working with these tests. This is true whether they are medical doctors, dieticians, chiropractors, naturopaths, or nutritionists.

At DNAlysis we realized this when we started— if we did not have practitioners who knew what to do with the information, it would be impossible for them to use our testing effectively. It can be more harmful than helpful if a practitioner does not understand what they are working with. So we knew early on that practitioners would need to go through a certain amount of training before they would be allowed to work with our tests. That has been my greatest area of concern and, as a result, the emphasis of my work in the last couple of years.

Ms. Faass: How is the training structured, and how many hours are required— what’s involved?

Dr. Shapiro: Originally we ran two-day training workshops. But there have been just two trainers world-wide and obviously we can only travel so much. So my company developed a correspondence training with a book and a CD, but even that has not been enough. So I have been working on developing an online training program for practitioners, focused on nutrigenomics in clinical practice. The course is based in functional medicine and systems biology. This is amazing information, but also highly practical. Our plan is to provide practitioners with this course in mid-2015.

Dr. Hughes: This is incredibly focused, in-depth training, compressed into a 12-week course that was developed with busy practitioners in mind. In addition, I really like their report form, the way it simplifies the information, identifying what is most important and what is truly a risk factor, putting that in the context of the scientific literature. This gives us is the ability to translate the data into a true clinical concern.

For the practitioner, I think there are layers of learning. The first is how to identify the biggest risks and move forward with general dietary and lifestyle modifications. Once you start to get comfortable addressing those risk factors, physicians can start to dive deeper and deeper into the individual meanings of the different SNPs and what to do about them. For me, this will be a lifelong interest and a part of my medical education journey. I am constantly trying to update and refresh my knowledge in this changing field. I believe that Yael’s course is going to be the springboard that takes practitioners to the next level of depth and individual competency, to the point where they rely a little bit less on the lab and start to really grasp the content. The training will help guide practitioners in this overwhelming field and improve their ability to frame this information in an effective way with their patients, while providing training to create more sophisticated and personalized approaches. This is truly the next era of personalized intervention.

Dr. Shapiro: We are happy to work with practitioners in the U.S. who have functional and integrative medicine training. Right now we work on a one-on-one basis to some degree. Practitioners who have never encountered nutrigenomics are not allowed to work with our tests until they have had proper training. But anyone who is working in an integrative or functional space has already been exposed to this information. With the new course, we hope to be able to take them to a much more powerful level, so they can use the test data to maximum potential. As Kristi said, the emerging field of clinical genomics is a journey that attracts leading edge practitioners, and we are happy to partner with them, providing the most current testing and information available.

Yael Shapiro, PhD, RD

Yael Shapiro obtained her doctorate in nutrigenomics from the University of Cape Town and specializes in the genetics of obesity. She is co-founder and director of DNAlysis Biotechnology and through her second company, Manuka, is developing an online course for health practitioners, Capturing The Nutrigenomics Conversation. A professional trainer, she has worked with thousands of health professionals in South Africa, the U.S., U.K., and Dubai, and her training DVD’s are used by health professionals throughout the U.K., Europe, Scandinavia, the Middle East, India, and Malaysia. She has developed and taught nutrigenomics courses at the post-graduate level and is also coauthor of a book for consumers on diet and lifestyle, It’s Not Just Your Genes. Dr. Shapiro has been involved in several research collaborations with academic partners, is currently an adjunct Assistant Professor teaching nutrigenomics at Rutgers University, and is completing an MS in the economics and public policy of food at Marylhurst University in Portland, Oregon.

DNAlysis

DNAlysis tests are distributed globally by DNALIFE®, a collaboration between Nordic Laboratories and DNAlysis Biotechnology

Test panels will be available in the U.S. beginning June 2015.

www.dnalife.co.uk info@dnalife.eu or hg@dnalife.eu +45 33 75 10 00

For information on practitioner accreditation programs contact info@dnalife.eu or +45 33 75 10 00

Manuka

Manuka was founded to provide a global platform for the provision of progressive, cutting-edge, and credible nutrition education for health practitioners. In February 2015, Manuka will launch with a one-day training conference in Translational Nutrigenomics, to be followed by the launch of an online Nutrigenomics training course Capturing the Nutrigenomics Conversation in June 2015. Anyone interested in the Translational Nutrigenomics conference DVD or the online Nutrigenomics course should contact Yael.

email: yael@manukascience.co

telephone: +27825670749

Skype: yjoffe

www: manukascience.co

Kristi Hughes, ND

Dr. Hughes serves as Director of Medical Education for IFM, where her role includes the development and supervision of teaching teams in the Functional Medicine Certification Program and the Path to Functional Nutrition. She is involved in the creation of clinical tools and patient education resources that empower healthy lifestyle change. As a trainer in lifestyle and functional medicine, she has lectured extensively throughout the U.S. and internationally for more than 15 years and has been instrumental in providing functional medicine resources for clinicians and nutrition professionals through her role as the Director of Medical Education at Functional Medicine South Africa. Founder and director of the Dynamic Healing Centers in Minnesota, Dr. Hughes also manages a team of health care providers and naturopathic practitioners. The Dynamic Healing Centers support preceptorships, host a naturopathic residency program, and model the integration of functional medicine with a naturopathic foundation. Through the Centers she provides distance consulting to physicians and to patients in conjunction with their physician’s participation, with an emphasis on therapeutics such as supervised detoxification.

Dynamic Healing Center

2585 Sandhill Lane NE

Alexandria, MN 56308

(320) 762-4295

Institute for Functional Medicine Annual International Conference

May 28-30, 2015

JW Marriott Austin, TX

The evidence that almost all disease results from the interaction of genes with the environment is now extremely convincing. The emerging science continues to confirm that, in the overwhelming majority of cases, genes don’t actually cause disease; rather, they influence a person’s susceptibility to disease. It’s not nature vs. nurture, but nature and nurture. Our genetic heritage (or genotype) is still unchangeable (at least for now), but how those genes behave (our phenotype) is very much affected by the environment in which we bathe them.

The 2015 Annual International Conference will focus on the exploding literature that describes how variations in single nucleotide polymorphisms (SNPs) can, in concert with environmental triggers, change the way we metabolize drugs, affect how we excrete or biotransform toxins, modify how we respond to stress, and control how we assimilate and utilize nutrients. In short, these genetic SNPs, in concert with the environmental milieu, can increase or decrease our risk for a variety of diseases. This reflects our changing understanding of personalized medicine and brings the decoding of our personal DNA fingerprint much closer to reality.

For clinicians, the challenge is how to translate complex, molecular technologies in the laboratory, and a growing body of human research into actionable information that has clinical relevance. We have to be able to explain and apply the science to patients in meaningful ways. The 2015 Annual Conference will delve into the science of individual genomic fingerprints as well as their phenotypic expression and plasticity. It will help clinicians adapt this leading edge of medical science to practical, personalized, clinical applications.

For more information, see www.FunctionalMedicine.org under Upcoming Conferences.

Editorial

Nancy Faass, MSW, MPH, is a writer and editor in San Francisco who has worked on more than 40 books for publishers that include Elsevier, Harper, New Harbinger, and others. Director of the Writers’ Group, she also provides articles, white papers, and writing for the Web and can be reached at info@HealthWritersGroup.com.