Dubious Genetic Testing

Stephen Barrett, M.D.
Harriet Hall, M.D.

During the past year, a few companies have begun offering genetic testing combined with guidance on diet, supplement strategies, lifestyle changes, and/or drug usage which they claim can improve health outcomes. This article explains why such testing should be avoided.

Until recently, hereditary tendencies were determined mainly by examining the family history of the individuals involved. Within the past decade, however, genes have been identified that cause or contribute to Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), cystic fibrosis, neurofibromatosis, familial colon cancer, Huntington's disease, myotonic dystrophy, and many other conditions. Many laboratories and clinics provide genetic testing and counseling; and scientific research in this field is progressing very rapidly.

Genetics tests analyze human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable disorder. Tests that identify carriers of various diseases can be used to help couples decide whether or not to have children. Scientists hope that further research will lead to strategies for preventing or treating hereditary diseases. Genetic tests can also help diagnose inherited diseases caused by problems with a single gene and lead to earlier treatment. At present, however, only a few such strategies are known, and none justify the commercial activities described in this article.

Most of the tests being marketed directly to consumers are for common gene variations that have been linked to major illnesses, such as coronary heart disease, which have hereditary aspects but are heavily influenced by lifestyle and environmental factors. At best, for such diseases, genetic testing can indicate that an individual is more susceptible than most people, but it cannot predict with certainty that the disease will develop [1]. For these reasons, the screening tests described in this article are not recommended by any authority and are not FDA-approved as a basis for recommending supplementation.

Sciona's "Body Benefits" Tests

Sciona, a British company, offers a "Body Benefits" test that yields "a personalised report describing your lifestyle results and genetic results, together with further informative sections on food groups, vitamins & minerals and an easy to understand guide to the science behind the service." The report is based on a lifestyle questionnaire and a DNA sample obtained by rubbing a brush swab on the inside of your cheek. The DNA sample is said to involve testing of several genes related to free radical damage, detoxification, alcohol metabolism, and skin and hair repair. According to Sciona:

Small differences in your genes can influence how well your body metabolises foods, utilises nutrients and excretes damaging toxins, all of which can affect your general state of health. By finding out if you have any of these small variations, Body Benefits nutrition can provide you with specific dietary information that cannot be obtained from any other source [2].

The test is now available through physicians, pharmacists, and nutritionists. In 2002, the company began marketing it through retail stores on High Street, but protests from GeneWatch UK caused the shopkeepers to stop offering it [3]. GeneWatch UK had three main objections:

After GeneWatch UK protested, Sciona changed its policy so they now destroy the test samples (although they keep the data) [5].

Great Smokies' Genovations™ Test

Great Smokies Diagnostic Laboratory (GSDL), of of Asheville, North Carolina, claims that its Genovations test line "empowers physicians and patients to realize earlier, more effective preventive interventions—years before disease develops; precise, customized therapies that truly address each individual's needs; and improved clinical insight into patients with treatment-resistant 'chronic' conditions." [6 ] Genovations testing is one of many questionable tests that GSDL offers through "holistic physicians," chiropractors, and other offbeat practitioners or directly to the public. According to the Genovations Web site:

Genovations™ tests measure individual genetic variations, called single nucleotide polymorphisms (SNPs) that, under the influence of environmental triggers, can make even a healthy person more prone to develop certain diseases or physiological imbalances. Knowledge of these variations will allow physicians to intervene with customized preventive therapy earlier and with greater specificity than ever before, to reduce a patient's disease risk years before symptoms appear. With Genovations™, Great Smokies Diagnostic Laboratory becomes the first clinical laboratory to provide predictive genomic tests to the primary care physician [7].

The tests currently offered include: CardioGenomic™ Profile (to identify SNPs associated with cardiovascular disease), OsteoGenomic™ Profile (to identify SNPs associated with osteoporosis), DetoxiGenomic ™ Profile (to identify SNPs associated with "detoxification defects" related to with increased risk for certain cancers, chronic fatigue, multiple chemical sensitivity, and alcoholism), and ImmunoGenomic™Profile (to identify SNPs associated with immune system defects, asthma, atopy, osteopenia, heart disease, and infectious diseases). [8] The Genovations Web site further states:

Seeing the results of your Genovations™ test is like seeing the cards you've been dealt by Nature. Once you know the cards, you can develop the most effective strategy to play out your hand. That means working with your healthcare provider to carefully develop a diet, lifestyle, and supplement program that matches the unique health risks for your body. . . .

Are you plagued by a chronic condition that resists medical treatment? Testing can reveal whether you have genetic variations that make you more vulnerable to the harmful effects of toxins. Or if you are less likely to respond well to certain drugs or nutrients.

Do you have a family history of a condition like heart disease or osteoporosis? When conditions "run in families" they often have a genetic component. Testing can show what specific genetic factors could pose a potential problem for you. For example, are your cholesterol levels more sensitive to a fatty diet than other people? Is your blood more likely to clot during long periods of inactivity? Do your bones properly utilize the nutrients they need? Is your blood pressure apt to be highly influenced by your salt intake? Once you have this information, you can develop a focused, plan to "break the pattern"—and better prevent your family risks from turning into realities.

Do you take a very active role in optimizing your health? These tests can help you and your practitioner design a preventive program that works best for your body's unique needs and health risks. One that "takes aim" at your most important targets years before symptoms ever have a chance to develop. Knowing your genetic "strong" points and "weak" points allows you to devise a targeted, personal approach that increases your chances of remaining fit and active as you grow older. . . .

Based on your genetic test results, your health care practitioner can work with you to develop a customized treatment plan. But the support doesn't stop there. Testing is also available that can monitor whether your personal healthcare strategy is having a positive impact on your genetic risks. These tests, called "functional assessments," give your physician a concrete way to evaluate how your body is responding to treatment. This is an important way to ensure that powerful environmental factors, such as hormones and nutrients, are in a state of optimal balance that minimizes your in-born genetic health risks [9].

The above quotations clearly promise more than Genovations can deliver. In order for a test to be cost-effective, it has to provide information that is not available elsewhere that can steer the patient toward beneficial treatment. No studies have shown that genetic testing is as good as a simple family history or ordinary laboratory tests for determining what people should do to prevent osteoporosis or cadiovascular disease. And the idea that people who have "chronic conditions" are likely to benefit from genetic testing is preposterous. Nor have any studies demonstrated that nutrient formulas based on genetic testing are as good as standard medical treatment based on appropriate diagnostic testing or that GSDL's nonstandard "functional assessments" are valid.

Most of the conditions related to Genovations testing are either poorly understood (such as chronic fatigue syndrome) or are known to be have many contributing factors (eg, coronary heart disease). Many different genes are involved, often on different chromosomes, and the expression of the genes is affected by environmental factors. The same gene might be good for one person and bad for another, depending on the rest of the person's genetic makeup and environment. Genetic variants may well influence the development of common diseases, but it is far too early to be guessing what variants affect what disease, much less to be recommending "treatment" in the form of diet and supplements. Commenting on the claims made for Genovations' "Osteo" "Cardio," and "Immuno" profiles, GeneWatch UK concluded:

These claims are misleading and unethical because: the risks associated with particular genes are still poorly understood and for most people diet, lifestyle and environment will be much more important than genetic make-up in the development of common future illnesses; selling supplements, medicines and follow-up tests to people based on their genetic make-up means treating them for illnesses they do not have but are worried they will get. At best, this is exploiting people's fears in order to make a profit. Taking unnecessary medication could also be harmful to your health, as could being unnecessarily worried or falsely reassured about your risk of future illness; you may be informed of risks you didn't want to know about without proper counselling or advice (for example, an increased risk of Alzheimer's Disease has been associated with one of the genes in Genovations' "Cardio" genetic test). [10]

CARE Clinics, of Austin, Texas, is using Genovations to test children with autistic spectrum disorders. The tests are part of an expensive test package that is claimed to guide "biomedical treatment" with dietary supplements and other modalities said to correct "biomedical imbalances" and provide "detoxification." In 2008, one of us (Dr. Barrett) examined test reports and concluded that the tests do not appear to be related to autism and contain no information that would provide a rational basis for treatment [11].

NuGenix

GeneLink, NuGenix, and Garden State Nutritionals have teamed up to market genetic tests accompanied by supplement recommendations. GeneLink, headquartered in Margate, New Jersey, provides the genetic tests. Its reports to the Securities and Exchange Commission state that it was formed to "to offer to the public the safe collection and preservation of a family's DNA material for later use by the family to determine genetic linkage [12], but a recent press release describes it as "a leader of genetic assessments direct-to-consumer" [13], which is a very different purpose. The company's Web site states:

GeneLink has recently created a breakthrough methodology for "genetic profiling" (patents pending) and is beginning to license these proprietary assessments to companies that manufacture or market to the $100 Billion plus nutraceutical, personal care, skin care, and weight-loss industries.

GeneLink's innovative Nutragenetic & Dermagenetic Profiles now offer companies the information they need to create and sell more effective products—unique wellness and "quality of life" products tailored to their customer's individual needs—based on the science of genetics.

No longer will people be forced to speculate, guess or use trial and error to determine which nutritional supplements or skin-care products are best for them. For the first time, by simply swabbing the inside of mouth (using GeneLink's Patented Collection Kit) and sending the collected sample to GeneLink's laboratories—people can be directed to personalized products - specifically formulated to help compensate for predicted deficiencies.

GeneLink's clear mission is to utilize the latest genetic research information and applied technologies to provide products and services that can assist in improving and extending human life [14].

Garden State Nutritionals, a custom manufacturer in West Caldwell, New Jersey, supplies the supplement products. NuGenix, of Berwyn, Pennsylvania, is operated by the children of GeneLink's president. It markets the testing through multilevel marketing structure. Its "medical advisor" is Alan H. Pressman, DC, PhD, DACBN, CCN, a chiropractor who for many years has hosted a supplement-promoting radio talk show called "Healthline" and marketed his own line of supplements.

In December 2002, NuGenix's "genetic profiling kit" plus a month's supply of the "Bodygenix Nutrition Regimen" cost $299.95 plus shipping and handling. The regimen is said to be "focused on" seven formulas:

The Web site doesn't indicate how the test results influence the composition of the supplement products the customers receive. But the descriptions of the ingredients make it clear that the final product is likely to be irrational. For example, the site correctly notes that high levels of amino acid homocysteine may be an important factor in causing coronary heart disease and that lowering homocysteine levels may be beneficial. But the correct way to deal with this is to measure blood levels and take the amounts of B-vitamins that can normalize high levels [15]. Genetic testing contributes nothing to this process. Similarly, the correct way to deal with abnormal cholesterol levels is to measure them with blood tests and use lifestyle and proven drugs to improve them.

Seryx's Signature Genetics

Seryx, which is based in Montreal Canada and Cherry Hill, New Jersey, invited patients to use its Signature Genetics ™ service to "discover how your genes hold the secret to your well-being." [16] The service, which is available by annual subscription, must be obtained from a doctor who has been trained by the company. The company promises—based on a genetic blood test and answers to a detailed questionnaire—"detailed, individualized, practical recommendations on nutrition, lifestyle, and medications—with actions you can take immediately to improve your well-being and uncover your optimal health." To obtain the service, patients must puchase a membership and pay an annual fee that entitles them to notification when new discoveries pertain to their genetic profile. The Web site offers physicians a "significant practice-building opportunity," but it offers no objective evidence that such practice-building will benefit patients. According to a company spokesperson, the cost of the service depends on how many test "modules" the doctor recommends after interpreting the patient's information. Payment is made to the doctor, with a minimum charge of $500.

The effectiveness and toxicity of most medications can vary considerably from patient to patient and that for many medications these individual differences are partly due to variations in the genes related to drug-metabolizing enzymes, drug transporters, and/or drug targets [17]. For example, someone who metabolizes a drug more slowly than someone else may respond to the drug at a lower dose and be more likely to develop side effects. On the other hand, the difference may not be significant and the effect may be influenced by other genetic factors or interactions with other drugs. In addition, the dosage of most drugs is easily adjusted to compensate for individual differences. No studies have shown improved patient outcomes from selecting drugs based on genetic information. Thus the idea of using genetic information for prescribing medications has considerable promise, but its time has not yet come.

Imagene

DocBlum.com offers Imagene™ "genetic testing for the millennium." The company's Web site states:

Are you compulsive? Have you ever wondered why you crave certain things and/or act in an irrational manner? Would you like to know if you have the genetic predisposition to abuse drugs and alcohol? Are you concerned about your children's future? Does your child have the genetic trait that leads to disruptive and addictive personalities? DNA testing can help you understand and manage a child's behavior before it gets out of control.

Imagene will test a panel of dopaminergic related Reward Deficiency Syndrome (RDS) genes. This will allow you to know if there is a genetic predisposition towards any of the associated addictions. The Reward product line is then available to treat the genetic predisposition towards RDS [1].

The test involves swabbing the inside of the cheek with a foam-tipped applicator, applying the applicator to an indicator card, and mailing the card to a lab. A home test kit sells for $275, and the products cost $59.95 per month for pills and $29.95 for a corresponding oral spray that is said to provide 1-2 hours of relief from "cravings." The Web site also includes an application for becoming a "Reward" distributor for Nutrigenomic products.

"Reward Deficiency Syndrome" is not a medically recognized disorder, but a hypothesis originated by Kenneth Blum, Ph.D., a pharmacology professor in Texas, and promoted through the Web site, which is registered to pediatrician Michael A Blum, D.O., of Overton Park, Kansas. The site indicates that the technology and products are patented or licensed by Kenneth Blum and that the University of Texas and the University of California own some of them [18].

The Blums consider dopamine (a neurotransmitter in the brain) to be the key factor in a cascade of neurophysiologic reactions leading to increased feelings of well-being and stress-reduction. They claim that a genetic defect in the D2 dopamine receptor gene causes "reward-seeking conditions" such as alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, sex addiction, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder, antisocial behavior, and other compulsive behaviors [18]. The tests are claimed to detect a genetic predisposition to such disorders. If the test is "positive," the corresponding formula is recommended for lifetime use [20].

The "Reward" product line is marketed by Nutrigenomics, Inc., of San Antonio, Texas. It includes six formulas: Alcoholism/Heroin, Cocaine/Stimulants, Smoking/Tobacco, Weight Management, INFOCUS/ADD, and PMS, each of which contains vitamins, herbs, and amino acids. The "anti-alcohol" formula, for example, contains vitamin C, vitamin E, thiamine, riboflavin, niacin, vitamin B-6, folic acid, vitamin B12, biotin, pantothenic acid, calcium, magnesium, zinc, manganese, chromium, 5-hydroxytrypthophan, dl-phenylalanine, l-glutamine, rhodiala rosea, chamomile flower, passion flower, hops flower, oat straw powder, skullcap herb, motherwort herb, valerian root extract, and Jamaican dogwood extract. As far as we can tell, neither the test kit nor the products have FDA approval for their intended uses.

The scientific literature does not support Blums' theories or methodology. Most scientists believe that alcoholism has both genetic and environmental factors and that the inheritable component is most involves multiple genes rather than something that could be detected with a simple test [21-25]. Tourette syndrome is hereditary; and autism, ADHD, and schizoid disorders may have as-yet-undiscovered genetic causes; but the rest of the Blums' list are probably unrelated to genetic makeup. Moreover, there is no scientific evidence that a combinations of vitamins, amino acids, or herbs are effective against any of the listed conditions. In fact, it is difficult to imagine any rationale for the large number of ingredients in the Reward formulas.

The Imagene Web site lists 27 references to studies that supposedly support claims for the products [26]. We have not read the full text of these articles, but the titles or abstracts indicate that most do not involve tests of either the products or the ingredients. A few involve tests of products similar to one or more ingredients of the Reward products, but none of the studies appears to involve the actual products. Some of the studies lack proper controls; some are too short to be meaningful; and one even has a negative result. Many of the conditions that the Reward system is supposed to help are not covered by any of the studies; and none of the studies appears to involve use of genetic testing to select any of the products or their ingredients. Documents related to patents held by Kenneth Blum include additional studies that relate the various disorders to genetic factors but, again, these do not appear to be studies in which actual Reward products were administered to patients or selected on the basis of genetic testing [27]. In short, the references absolutely no support for use of the system. Moreover, since the products are recommended for lifetime use and involve alleged manipulations of chemicals in the brain, any such use should be supported by long-term safety studies—which do not appear to have been done.

The Bottom Line

Genetic testing to identify alleged risk factors that have no proven corrective measures is simply a waste of money. As noted by Helen Wallace, Ph.D., Deputy Director of GeneWatch UK: "For most people, tailoring your diet to your genetic make-up is about as scientific as tailoring your diet to your star sign." [28] GeneWatch has also expressed concern that without proper regulation, genetic testing could be used to expand the drug market to healthy people identified as at high genetic risk; many people could receive unnecessary medication and suffer the associated side effects, and the underlying causes of heart disease, cancer, obesity, adult-onset diabetes, and other diseases could be ignored, with serious implications for future health [28].

Addendum

GAO's Undercover Investigation

In 2005 and 2006, the U.S. Government Accountability Office purchased genetic tests from four Web sites. The investigators then submitted 12 DNA samples taken from a cheek swab of a 9-month-old female and two from an unrelated 48-year-old man but described the specimens as coming from adults of various ages and lifestyle descriptions. Three of the sites made different recommendations for nine of the infant's samples. Since the DNA of these samples was identical, this showed that these recommendations were not actually based on the sender's "unique genetic profile" as advertised. Two of the sites recommended "personalized" supplement regimens that, in addition to being senseless, cost more than 30 times as much as comparable products available at retail outlets. Experts who reviewed the test reports concluded that they made predictions that were medically unproven, ambiguous, and provided no meaningful information for consumers. Click here to read the full text of the report. The report was presented at a Congressional hearing

Internet Survey

In October 2006, Rene Sterling PhD, MHA from the University of North Carolina's Center for Genomics and Society conducted a systematic search of Web sites that promoted nutrigenomic services:

  • Of the 64 organizations hosting websites, 29 organizations offered (24 of 29) or promoted (5 of 29) at-home testing and 26 organizations sold services on-line (17 of 26) or provided a direct link to on-line sales (9 of 26).
  • A lack of transparency made it difficult to identify unique tests; however, three organizations were linked to 56% of all test mentions.
  • Most organizations were healthcare/wellness service providers (50%) or laboratories/biotech companies (27%)
  • Few organizations provided on-line information about laboratory certifications (20%), nutrigenomic test or research limitations (13%), test validity or utility (11%), or genetic counseling (9%).
  • Affiliation opportunities were offered by 15 organizations.

Sterling concluded:

Organizations did not provide adequate information about nutrigenomic services and at-home genetic testing. Affiliation opportunities and distribution agreements suggest the promotion and sale of nutrigenomic services will continue, increasing the importance of consumer and provider education. In absence of federal regulation, organizations promoting nutrigenomic services should equate websites to product labels and include information to facilitate informed decision-making [30].

"Genetic Horoscopes"

GeneWatch UK is skeptical that a day will come when lifestyle advice, medication, and perhaps the food you eat can be tailored to individual genes so that the diseases they would otherwise get can be prevented. GeneWatch lists seven reasons why such "genetic horoscopes" should be considered a dangerous myth:

  • A bad strategy for health
  • The marketing of fear
  • Undermining public health
  • Creating a genetic underclass
  • Undermining civil liberties
  • The patenting of life
  • Wasting resources and eroding trust [31]

For Additional Information

References

  1. Unregulated genetic testing on the High Street and the Internet. GeneWatch UK, April 2002.
  2. Body benefits - nutrition. Sciona Web site, accessed Dec 29, 2002.
  3. High Street stores reject Sciona's human genetic testing. GeneWatch press release, June 7, 2002.
  4. Genetic testing on the High Street. GeneWatch UK, March 2002.
  5. Wallace H. Email to Dr. Stephen Barrett, Jan 7, 2003.
  6. Genovations™ is the advent of truly personalized healthcare. Genovations Home page, accessed Dec 29, 2002.
  7. Great Smokies Diagnostic Laboratory announces new Genovations™ product line: Predictive genomics for personalized medicine. GSDL news release, March 15, 2002.
  8. Genovations profiles. Genovations Web site, accessed Dec 29, 2002.
  9. Patients guide to genomics. Genovations Web site, accessed Dec 29, 2002.
  10. "Genovations" genetic test kits. GeneWatch UK, July 2002.
  11. Barrett S. Be wary of CARE Clinics and the Center for Autistic Spectrum Disorders (CASD). Autism Watch, Nov 26, 2008/
  12. GeneLink, Inc. Form 10-QSB quarterly report for the quarterly period ended September 30, 2002.
  13. GeneLink, Inc. reports revenue for third quarter. 2002. Business Wire, Nov. 14, 2002.
  14. GeneLink Inc —Growing, Expanding, Evolving! GeneLink Web, site accessed, Dec 29, 2002.
  15. Barrett S. Homocysteine: A cardiovascular risk factor worth considering. Quackwatch, Aug 29, 2002.
  16. Evans WE., Johnson J. Pharmacogenetics: the inherited basis for interindividual differences in drug response. Annual Review of Human Genetics 2:9-39, 2001]
  17. Imagene: Genetic testing for the millenium. Docblum.com, accessed May 30, 2003.
  18. Patents (awarded and or licensed to DocBlum). Docblum.com, accessed May 30, 2003.
  19. Blum K and others. Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 5:121-141, 1995.
  20. Frequently asked questions. Docblum.com, accessed May 30, 2003.
  21. Freund G. Biomedical causes of alcohol abuse. Alcohol 1(2):129-131, 1984.
  22. Goldman D and others. A functionally deficient DRD2 variant is not linked to alcoholism and substance abuse. Alcohol 16:47-52, 1998.
  23. Chen WJ and others. Psychiatric Genetics 11:187-195, 2001.
  24. Hill EM and others. Antisocial alcoholism and serotonin-related polymorphisms: association tests. Psychiatric Genetics12:143-153, 2002.
  25. Goldman D and others. Linkage and association of a functional DRD2 variant and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians. American Journal of Medical Genetics 74:386-394, 1997.
  26. Product support page. Docblum.com, accessed May 30, 2003.
  27. GeneWatch UK response to the Human Genetics Commission's announcement of a consultation into genetic testing services. GeneWatch press release, July 18, 2002.
  28. Genetics and 'predictive medicine': Selling pills, ignoring causes. GeneWatch UK Briefing Number 18, May 2002.
  29. Blum K. Allelic polygene diagnosis of reward deficiency syndrome and treatment. Patent #6,132,724, October 17, 2000.
  30. Sterling R. The on-line promotion and sale of nutrigenomic services. Genetics in Medicine 10:784-796, 2008.
  31. Genetic horoscopes. Genewatch Web site, accessed Nov 24, 2008.

Dr. Hall is a retired family practitioner and Air Force colonel who resides in Puyallup, Washington.

The main article above describes the marketplace as it was in 2002–2003.
The addendum was posted on November 24, 2008.