Methylation & SNP’s: the Chiropractic Adjustment, and Taking Our Patients to the Next Level of Health
FEATURE
Marc Harris
N.D.
What does methylation have to do with it all? As a profession, doctors of chiropractic have helped innumerable patients. The struggle has been to delineate the mechanism of action of the chiropractic adjustment and the problem of low funding for chiropractic studies. The studies that have been done indicate a release of adhesions and proposes release of muscle spindle cells, Golgi tendons, and most commonly pinched nerves impacting nerve function. While these are all plausible, the studies have not proven mechanism of action. Data show that the chiropractic adjustment decreases inflammatory markers. Is there more we can do?
In 1911, Daniel David (D. D.) Palmer theorized that inflammation was the central characteristic of all disease. With advances in physiology concentrating on acute inflammatory responses, Palmer’s theory was not in forethought for chiropractic training. Inflammation and oxidative damage have now been recognized as the primary cause in all chronic diseases1-2-3-4-5-6. We now have the data to show that the chiropractic adjustment reduces cortisol12. What about inflammation? Yes, the data are clear 7 8-9. We also know no single therapy is a panacea. What can we do to bring our patients to the next level?
After its discovery in 195124, the field of epigenetics had its nascent beginnings. After the completion of the human genome project in 2003, there was fervor and little result, but the burgeoning field of epigenetics stemmed from it. The most studied aspect of epigenetics is methylation, which is the master controller of our genes. Arguably, the most important part of methylation and the next 100 years of biology is the single nucleotide polymorphism (SNP).
At its last collation in 201625, there have been 162,000,000 SNPs described. Are all of them important? Since there are many redundancies in our genome, the most important SNPs are where there are fewer redundancies.
The SNPs of inflammation: We can think of these SNPs as either doing good things or doing bad things. Genes that should be providing crucial function have a mutation that changes their function. They code for a protein that is then less functional. This can result in a 30 to 100% failure in protein function. Some of these SNPs are inconsistent with life. For those that are, we can do something about it.
When a protein is miscoded, it can be a problem in the site where a cofactor binds, or it may be in a site that affects a product (e.g., instead of making glutathione, you make ammonia21).
Fig 7. Inflammatory mediator response for both treatment and control groups. Error bars represent SEM for the sake of clarity. Dark bars represent control. Gray bars represent treatment. Numbers above bars represent the significance level (P, a error) and Cohen effect size factor (d coefficient, see "Statistical analysis" in "Methods") based on between-subject differences (control vs treatment). Tx, Treatment; CTL, control; Pre, before treatment period; Post, after treatment period.
SNPs have been implicated in contributing to chronic inflammatory diseases15161718: Parkinson’s, asthma, cancer19, diabetes: Not the only cause but are contributory causes. Said another way, if we do not correct our patients’ SNPs, we have not done everything we can for our patients. This can be taking our “stuck” patients and moving them toward being healthy.
There has been the enduring debate of nature versus nurture. Our SNPs can join this debate. If a protein needs a vitamin or mineral cofactor to function, an SNP may have caused a mutation in the site where the cofactor binds. This is nature. If a person eats a standard American diet (SAD), they may not be getting the needed nutrients in their diet and may have compromised absorption. This is nurture. They may have an SNP and poor absorption, and they probably can’t get all the nutrients they need from their diet.
We can also see the complementary nature of the chiropractic adjustment and SNPs in the area of the autonomic nervous system. The type A personality has probably made society possible. Every field is driven by those individuals. Those movers and shakers are also the people getting myocardial infarctions and cancer.
The chiropractic adjustment lowers cortisol levels. Short-term stress raises cortisol levels25. Raising cortisol short term stimulates the immune system, but long-term raises decrease the HPA axis2227 by several methods, including chronic elevation of IL-6.
We have another caution in correcting SNPs, which has too narrow a focus. We see this in the most common of SNP tests: MTHFR (methylenetetrahydrofolate reductase). A patient will walk in with this test from his or her doctor. They will take 1-methylfolate and begin feeling worse. The problem is when one SNP is affected, another can be as well. Correcting one SNP may cause a problem in another SNP.
SNPs are far more than inflammation. Correcting SNPs can help with emotional well-being, DNA regulation, inflammation, detoxification, organ function, immunity, and structural health. Correcting SNPs is complementary to everything else we do. Correcting SNPs does not have to be complicated. I tour the nation teaching methylation seminars to chiropractors helping them better treat patients needs
References:
1. Chronic Obstructive Pulmonary Disease: From Injury to Genomic Stability. Sergio LPDS, de Paoli F, Mencalha AL, da Fonseca AS. COPD [12 Jun 2017, 14(4):439-450]
2. A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of [3-Catenin. Jiang Z, Lao T, Qiu W, Polverino F, Gupta K, Guo F, Mancini JD, Naing ZZ, Cho MH, Castaldi PJ, Sun Y, Yu J, Laucho-Contreras ME, Kobzilc L, Raby BA, Choi AM, Perrella MA, Owen CA, Silverman EK, Zhou X. Am J Respir Crit Care Med [01 Jul 2016, 194(2): 185-197]
3. Lisa M. Coussens & Zena Werb. Inflammation and cancer. Nature volume 420, pages 860-867 (19 December 2002)
4. M.F.McCarty Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline. Medical Hypotheses Volume 52, Issue 5, May 1999, Pages 465-477
5. BEAL, M. F. (2003), Mitochondria, Oxidative Damage, and Inflammation in Parkinson's Disease. Annals of the New York Academy of Sciences, 991: 120-131
6. Ehab E. Tuppo, Hugo R. Arias, The role of inflammation in Alzheimer's disease, The International Journal of Biochemistry & Cell Biology, Volume 37, Issue 2, 2005, Pages 289-305
7. Roy, R. A., Boucher, J. P., & Comtois, A. S. (2010). Inflammatory response following a short-term course of chiropractic treatment in subjects with and without chronic low back pain. Journal of Chiropractic Medicine, 9(3), 107-114.
8. Song, X.-J., Gan, Q., Cao, J.-L., Wang, Z.-B., & Rupert, R. L. (2006). Spinal Manipulation Reduces Pain and Hyperalgesia After Lumbar Intervertebral Foramen Inflammation in the Rat. Journal of Manipulative and Physiological Therapeutics, 29(1), 5-13.
9. The contribution of the nervous system to inflammation and inflammatory disease. Allan I. Basbaum, Jon D. Levine. Canadian Journal of Physiology and Pharmacology, 1991, 69:647-651
10. Knutson, G. A., & Jacob, M. (1999). Possible manifestation of temporomandibular joint dysfunction on chiropractic cervical x-ray studies. Journal of Manipulative and Physiological Therapeutics, 22(1), 32-37
11. Licciardone, J. C. (2017). Changes in inflammatory biomarkers following spinal manipulation. Musculoskeletal Science and Practice, 30, e91-e92.
12. Tara L. Whelan, J. Donald Dishman, Jean Burke, Seymour Levine, Veronica Sciotti, The effect of chiropractic manipulation on salivary cortisol levels, Journal of Manipulative and Physiological Therapeutics, Volume 25, Issue 3, 2002„Pages 149-153
13. Padayachy, K., Vawda, G. H. M„ Shaik, J., & McCarthy, P. W. (2010). The immediate effect of low back manipulation on serum cortisol levels in adult males with mechanical low back pain. Clinical Chiropractic, 13(4), 246-252.
14. Immunoreactive ACTH, beta-endorphin, and cortisol levels in plasma following spinal manipulative therapy. Christian GF , Stanton GJ, Sissons D. How HY, Jamison J, Alder B. Fullerton M, Funder JW. Spine [01 Dec 1988, 13(12): 1411-1417]
15. Lio, D. (2003). Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 -1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP. Journal of Medical Genetics, 40(4), 296-299
16. Yue, P., Melamud, E„ & Moult, J. (2006). SNPs3D: Candidate gene and SNP selection for association studies. BMC Bioinformatics, 7(1), 166.
17. Valdes, A. M., Hassett, G., Hart, D. J., & Spector, T. D. (2005). Radiographic Progression of Lumbar Spine Disc Degeneration Is Influenced by Variation at Inflammatory Genes. Spine, 30(21), 2445-2451.
18. Loza MJ, McCall CE, Li L, Isaacs WB, Xu J, et al. (2007) Assembly of Inflammation-Related Genes for Pathway-Focused Genetic Analysis. PLOS ONE 2(10): el035
19. Chunquan Li, Junwei Han, Desi Shang, Jing Li, Yan Wang, YingYing Wang, Yunpeng Zhang, Qianlan Yao, Chunlong Zhang, Kongning Li, Xia Li, Identifying disease related sub-pathways for analysis of genome-wide association studies, Gene, Volume 503, Issue 1, 2012, Pages 101-109
20. Meijer MJ, Mieremet-Ooms MA, van Hogezand RA, Lamers CB, Hommes DW, Verspaget HW. Role of matrix metalloproteinase, tissue inhibitor of metalloproteinase and tumor necrosis factor-alpha single nucleotide gene polymorphisms in inflammatory bowel disease. World J Gastroenterol. 2007; 13(21):2960-6.
21. Tokuhiro, S., Yamada, R., Chang, X., Suzuki, A., Kochi, Y., Sawada, T., ... Yamamoto, K. (2003). An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nature Genetics, 35(4), 341-348.
22. Tyrka, A. R„ Price, L. H., Gelemter, J., Schepker, C., Anderson, G. M., & Carpenter, L. L. (2009). Interaction of Childhood Maltreatment with the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity. Biological Psychiatry, 66(7), 681-685.
23. Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes S, J: Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome. Neuropsychobiology 2007;55:112-120
24. Van West, D., Del-Favero, J., Aulchenko, Y., Oswald, P., Souery, D., Forsgren, T., ... Claes, S. (2004). A major SNP haplotype of the arginine vasopressin IB receptor protects against recurrent major depression. Molecular Psychiatry, 9(3), 287-292
25. WYATT GR. Recognition and estimation of 5-methylcytosine in nucleic acids. Biochem J. 1951 ;48(5):581 -4.
26. Institute for Systems Biology, Kaviar database db.systemsbiology. net/kaviar/
27. Steensberg, A., Fischer, C. P., Keller, C., Moller, K., & Pedersen, B. K. (2003). IL-6 enhances plasma IL-lra, IL-10, and cortisol in humans. American Journal of Physiology-Endocrinology and Metabolism, 285(2)
28. Crofford, L. J., Kalogeras, K. T., Mastorakos, G., Magiakou, M.-A., Wells, J., Kanik, K. S., ... Wilder. R. L. (1997). Circadian Relationships between Interleukin (IL)-6 and Hypothalamic-Pituitary-Adrenal Axis Hormones: Failure of IL-6 to Cause Sustained Hypercortisolism in Patients with Early Untreated Rheumatoid Arthritis. The Journal of Clinical Endocrinology & Metabolism, 82(4), 1279-1283.
29. Rutters, F., Nieuwenhuizen, A. G., Lemmens, S. G. T., Bouwman, F., Mariman, E., & Westerterp-Plantenga, M. S. (2011). Associations between anthropometrical measurements, body composition, singlenucleotide polymorphisms of the hypothalamus/pituitary/adrenal (HPA) axis and HPA axis functioning. Clinical Endocrinology, 74(6), 679-686.
Marc Harris, MD, ND, PhD3, is one of the most knowledgeable authors and practitioners on methylation in chiropractic clinics.
Research Biochemist - Los Alamos National Lab Education: N.D., M.D., Ph.D. University of Washington, Ph.D. Colorado State University.
He has his own methylation line of supplements through Optimal Health Systems. Dr Harris currently teaches methylation seminars around the nation on a limited basis. His tour schedule can be learned by calling OHS at 1-800-890-4547.
