Personalized Medicine How SNPs, Ox Stress, and Inflammation Are Creating a Revolution in Healthcare
Decker Weiss, NMD, FASA
The economist Adam Smith’s The Wealth of Nations contains a parable about a pin-maker who, working alone, creates scarcely 20 pins a day. But within the same 8 hours, a team of 10 that divides the labor of shaping, sharpening, and painting produces not just 20 times 10, but tens of thousands.
Over the decades, that model was applied beyond factory production to many industries, including our US medical system. Like workers in a pin factory, it’s assumed that doctors are more efficient as they develop a specialized skill and practice it over and over again. In the years following World War II, the explosion of new medical knowledge and new technologies resulted in an increasing number of specialties and specialists, and caused a rapid decline in the number of developing physicians choosing general practice as a career.1 Up until that time, general practitioners provided the majority of healthcare in solo practices. Currently, the American Board of Medical Specialties (ABMS) oversees 24 member boards that certify physicians in more than 145 specialties and subspecialties.2
Specialists earn up to 4 times as much as primary care physicians in the United States – a differential that far surpasses all other developed countries.3
While specialization works on the factory line – and undoubtedly manages routine care and single diseases with quality and efficiency – benefits break down for people with chronic diseases.
Chronic Illness & the Limits of Specialization
Chronic diseases are costly. According to the Centers for Disease Control (CDC), 75% of American healthcare dollars go toward treatment of chronic diseases such as diabetes, heart disease, and cancer. National estimates for cancer care peg the annual price tag at about $125 billion.4 While costs are impressive, the results are not. According to Frank Wiewel, former Chairman of the Pharmacological and Biological Treatments Committee at NIH, and founder of People Against Cancer, “Cancer incidence is up. Cancer death is up. By every measure, we are losing the war on cancer.”5
In the book, Chronic Care in America: A 21st Century Challenge, authors Catherine Hoffman and Dorothy Rice estimated that there would be 105 million people with chronic conditions by the year 2000, and that this number would grow to around 134 million by 2020. With updated data, we now estimate that the number of people with chronic conditions exceeds that projection, having reached 125 million in 2000 and growing to an estimated 157 million by 2020.
Other Signs of Trouble
- According to a 2012 JAMA paper, “the most common chronic condition experienced by adults is multimorbidity, the coexistence of multiple chronic diseases or conditions.”8
- Obesity rates worldwide have doubled in the last 3 decades, even while blood pressure and cholesterol levels declined.9
- Heart disease is currently the #1 killer of men and women in the United States, responsible for 597 689 deaths in 2010.10
- From 2000 to 2010, congestive heart failure (CHF) resulted in an estimated 1 million hospitalizations. Of particular concern, the share of CHF hospitalizations for those under age 65 increased from 23% to 29%.11
Some argue that humans are simply living longer, so the incidence of chronic illness will naturally rise. Others point to better diagnosis these days. Whatever the cause, it’s clear that the system we have today is not effective at reducing the burden of chronic disease. We need a true paradigm shift in the way healthcare is delivered.
From Specialization to Personalization
Forward-thinking healthcare practitioners – led by integrative and naturopathic physicians – are seeking solutions to curb the runaway spending and poor outcomes related to chronic diseases. Increasingly, answers are being found through a model that, in many ways, is in direct contrast to the conventional specialist model: Personalized Medicine.
For example, heart disease cannot be managed with just 1 drug or a single approach. Heart disease, like all chronic diseases, is a complex metabolic system that is related to the way a patient’s genes interact with his or her individual environment. Thus, heart disease and all chronic diseases are best managed from a perspective that looks at multiple factors. A personalized approach must be developed, considering such factors as genetic susceptibility and lifestyle.
Fortunately, accurate and reliable testing methods are now available that provide a personalized snapshot of patient biomarkers and genetic history. Innovative diagnostic tools provide for more precise understanding of a patient’s health complaints and uncover a bigger health picture. Results help healthcare practitioners uncover the physiological imbalances that underlie patient conditions, leading to better prevention and outcomes.
Genetic SNP Testing
Single nucleotide polymorphisms, or SNPs, are the most common type of human genetic variation. Each SNP represents a variation within a single DNA building block, or nucleotide. For example, a SNP may cause the nucleotide thymine (T) to be replaced with the nucleotide cytosine (C) in a certain area of DNA.12
Most SNPs do not impact a person’s health or development. However, studies have shown that SNPs that may help predict an individual’s susceptibility to environmental toxins, the response to certain medications, as well as risk of certain diseases.12
SNPs may be the link between genetics and disease susceptibility that scientists have been seeking and practitioners have been dreaming of. As SNP technology becomes more available, SNPs may be increasingly linked to the action or inaction of a gene, and then to a particular disease. Here are some examples:
- SNPs in methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C) and catechol-O-methyltransferase (COMT) are related to neurotransmitter degradation and methylation, which in turn can be related to stress issues, chronic fatigue, and heart disease via homocysteine and other factors.13,14
- Genetic expression of superoxide dismutase (SOD)-1,2, and 3, catalase (CAT), and glutathione peroxidase-1 (GPX1) can influence oxidative stress, which can then dictate the susceptibility of endothelial dysfunction, oxidation of lipids, and heart disease.15
- SNPs involving CYP27B1 expression, the vitamin D-binding protein (GC gene), and the vitamin D receptor (VDR) relate to vitamin D metabolism, and have been associated with colon cancer,16 atherosclerosis,17 and bone loss,18
- Human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 are involved in gluten sensitivity and celiac disease,19 and may also exacerbate irritable bowel syndrome.20
- Glutathione-S-transferase (GST)M1 influences detoxification capacity, which can thus affect heavy metal toxicity.21 It may help explain why some people are more susceptible to toxicity than others. GSTs also affect blood-brain barrier permeability.22 For those practitioners using chelation, it may be prudent to examine this SNP prior to treatment.
Free Radical/Oxidative Stress Testing
Oxidative stress results from an imbalance between free radical activity and the body’s antioxidant system. Free radicals are dangerous because they are extremely unstable molecules that attach themselves to important biological molecules, impairing or inhibiting their normal activity. Oxidative stress has been linked to dozens of chronic conditions, including heart disease and cancer.23
Identifying the cause of oxidative stress can be a challenge. While habits such as poor diet, emotional stressors, and smoking may be obvious contributors, other factors such as metal toxicity, chemical exposure, and pesticides may not be as apparent. Urinary levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), the tryptophan metabolite 5-hydroxyindoleacetic acid (5-HIAA), taurine, and norepinephrine are related to free radical exposure, which can be quantified and treated.24 Neurotransmitters can be measured in the urine, and at a relatively low cost.25
Balancing free radicals may require several strategies, including antioxidant supplementation and lifestyle modifications. A patient’s genetic history, age, and other factors affect response to treatment, thus ongoing testing and monitoring are critical to success.
Many experts claim that inflammation is the root of all chronic disease.26 To control the incidence of chronic disease, we need to test and treat the actual causes of inflammation, not just the effects. There are several approaches available through advanced testing to help uncover the underlying cause(s).
First, a look at genetic SNPs such as SOD-1,2,3, catalase, and GST can provide information, from a genetics perspective, about the body’s ability to manage oxidation.
Second, neurotransmitters (specifically dopamine and norepinephrine) are part of the regulatory mechanism for the immune system.27 A more focused treatment plan for inflammation will encompass both the immune system and neurotransmitters.
Finally, a look at the cytokine expression from the immune system can be used as a gauge for both specific and non-specific inflammation.28 Based on results, the practitioner can assess the patient’s ability to buffer free radicals through genetic testing, check the patient’s status of SNS (adrenal function and neural sympathetic function) and begin root cause interventions. These interventions may include addressing food sensitivities, emotional issues, organ dysfunctions, and/or removing viral, bacterial, yeast or parasite infections.
Clearly, change is needed to reverse the epidemic of chronic disease in this country – namely, medical specialization must be replaced with personalized medicine. Combining traditional SNP testing with routine laboratory diagnostics – along with focusing on lifestyle modifications for optimal health – provides the best strategy for avoiding or reversing the incidence of chronic disease.
While these are times of turbulent change in our industry, it’s exciting to be on the cusp of a new paradigm of what is soon to become a true revolution in American health care.
L.F. is a 56-year-old male with a history of coronary artery disease, stents placed in the mid-left anterior descending artery and proximal right coronary artery, chronic gout pain, constipation, and poor gums.
Conventional Specialization Approach
L.F. sees a dentist, cardiologist, rheumatologist, gastroenterologist, and general practitioner. Conflicting medications are prescribed. Eventually, his disease is stabilized and managed. However, medication interactions and issues with fatigue led L.F. to pursue an alternative route.
Personalized Medicine Approach
L.F. sees a dentist and a functional medicine practitioner. Labs for SNPs providing information on oxidation and methylation are run, along with a neuro/cardio panel including anti-inflammatory cytokines, inflammatory cytokines, neurotransmitters related to oxidation (to see any effect of the SNPs), an ApoB:ApoA1 ratio (to check concentration of oxidizable cholesterol), and oxidized LDL (to see if it is oxidizing), also high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (to examine endothelial inflammation).
A supplement regimen for L.F.’s gout and constipation are recommended, and lifestyle changes are discussed. Colon hydrotherapy is performed.
After examination of the lab results, an individualized antioxidant/anti-inflammatory protocol is created, including a combination fat-soluble antioxidant with high-gamma vitamin E, vitamins D, D3, K, and K2, and alpha-lipoic acid.
One month later, follow-up labs for the neuro/cardio panel were performed. Neurotransmitters, oxidized LDL, and cytokines change more quickly than markers such as myeloperoxidase and hs-CRP, thus L.F. did not have to wait 3-6 months for results. A third neuro/cardio test was performed at 3 months to look for general improvement.
Reviewing L.F.’s neurotransmitters, high glutamate and low serotonin were noted. A product containing L-theanine (100% L-isomer), taurine, and 5-HTP was recommended to assist with sleep, as well as a product containing tyrosine to support norepinephrine levels during daytime hours.
After 3 months, L.F. reported that his insomnia had resolved and his overall mood was improved. Since depression and sleeplessness are risk factors for heart disease and heart attack, this was welcome news.
The Personalized Approach brought a resolution to L.F.’s gout, constipation, and bleeding gums. L.F. has maintained patent stents without any repeat of coronary artery occlusion.
Decker Weiss, NMD, FASA, is the first naturopathic physician to complete a conventional internship, residency, and fellowship in a conventional medical system. Dr Weiss trained in the Columbia Hospital system, the Arizona Heart Hospital, and the Arizona Heart Institute. Founder of the Scottsdale Heart Institute and the Center for Neuro-Endo-Immunological Cardiovascular Studies, Dr Weiss consults with NeuroScience, Inc, on practitioner medical education.
- American Board of Medical Specialties. Expansion of Specialties and Growth of Subspecialties. ABMS Web site. http://abms.org/About_ABMS/ABMS_History/Extended_History/Expansion.aspx. Accessed June 10, 2014.
- American Board of Medical Specialties. Bedside Manner, Board Certification Matter: Survey Reveals Top Qualities for Consumers Choosing a Doctor. ABMS Web site. http://www.abms.org/News_and_Events/news_archive/release_ABMS_Consumer_Survey.aspx. Accessed June 10, 2014
- Rosenthal E. Patients’ Costs Skyrocket; Specialists’ Incomes Soar. January 18, 2014. New York Times Web site. http://www.nytimes.com/2014/01/19/health/patients-costs-skyrocket-specialists-incomes-soar.html. Accessed June 10, 2014.
- Courage KH. Is the “war on cancer” winnable? 40 years after the unofficial declaration, the disease is spreading throughout the globe. March 24, 2011. Scientific American Web site. http://blogs.scientificamerican.com/observations/2011/03/24/is-the-war-on-cancer-winnable-40-years-after-the-unofficial-declaration-the-disease-is-spreading-throughout-the-globe. Accessed June 10, 2014.
- The Failed War on Cancer, Editorial. People Against Cancer Web site http://www.peopleagainstcancer.com/pdfs/news/20080916n2.pdf. Accessed June 10, 2014.
- University of CA, SF; Institute for Health & Aging; Robert Wood Johnson Foundation. Chronic Care in America: A 21st Century Challenge. Princeton, NJ: Robert Wood Johnson Foundation; 1996.
- Anderson G. Chronic Care: Making the Case for Ongoing Care. Robert Wood Johnson Foundation and Johns Hopkins University. Rwjf Web site. http://www.rwjf.org/content/dam/farm/reports/reports/2010/rwjf54583. Accessed June 10, 2014.
- Tinetti ME, Fried TR, Boyd CM. Designing health care for the most common chronic condition–multimorbidity. JAMA. 2012;307(23):2493-2494.
- Finucane MM. Stevens GA, Cowan MJ, et al. Lancet. 2011;377(9765):557-567.
- Centers for Disease Control and Prevention. FastStats, Heart Disease. http://www.cdc.gov/nchs/fastats/heart-disease.htm. Accessed June 10, 2014.
- Hall MJ, Shaleah L, DeFrances CJ. Hospitalization for Congestive Heart Failure: United States, 2000–2010. NCHS Data Brief. October 2012. CDC Web site. http://www.cdc.gov/nchs/data/databriefs/db108.pdf. Accessed June 10, 2014.
- What are single nucleotide polymorphisms (SNPs)? National Institutes of Health. Genetics Home Reference Web site, http://ghr.nlm.nih.gov/handbook/genomicresearch/snp. Accessed June 10, 2014.
- National Institutes of Health. Genetics Home Reference Web site. http://ghr.nlm.nih.gov/gene/MTHFR. Accessed June 10, 2014.
- Rakvåg TT, Ross JR, Sato H, et al. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain. 2008;4:64.
- Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-418.
- Dong LM, Ulrich CM, Hsu L, et al. Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk. Cancer Epidemiol Biomarkers Prev. 2009:18(9):2540-2548.
- Strawbridge RJ, Deleskog A, McLeod O, et al. A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7 interacts with type 2 diabetes status to influence subclinical atherosclerosis (measured by carotid intima-media thickness). Diabetologia. 2014;57(6):1159-1172.
- Cooper GS. Umbach DM. Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res. 1996;11:1841-1849.
- Kapitány A, Tóth L, Tumpek J, et al. Diagnostic significance of HLA-DQ typing in patients with previous celiac disease diagnosis based on histology alone. Aliment Pharmacol Ther. 2006;24(9):1395-1402.
- Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013;144(5):903-911.
- Helzlsouer KJ, Selmin O, Huang HY, et al. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst. 1998;90(7):512-518.
- Morales E, Sunyer J, Castro-Giner F, et al. Influence of glutathione S-transferase polymorphisms on cognitive functioning effects induced by p,p’-DDT among preschoolers. Environ Health Perspect. 2008;116(11):1581-1585.
- Poulsen HE. Oxidative DNA modifications. Exp Toxicol Pathol. 2005;57 Suppl 1:161-169.
- Villamena FA. Molecular Basis of Oxidative Stress: Chemistry, Mechanisms, and Disease. Hoboken, NJ: John Wiley & Sons, Inc. 2013:75-79.
- Kahane A. Urinary neurotransmitter analysis as a Biomarker for Psychiatric Disorders. Townsend Letter. 2009; January:70-72.
- Manabe I. Chronic inflammation links cardiovascular, metabolic and renal diseases. Circ J. 2011;75(12):2739-2748.
- Qiu Y, Peng Y, Wang J. Immunological role of neurotransmitters. Adv Neuroimmunol. 1996; 6(3):223-231.
- Chaturvedi AK, Kemp TJ, Pfeiffer RM, et al. Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1902-1911.