Twenty-five years ago, two Scandinavian scientists revived a century-old hypothesis: Chronic infections and inflammation are positively correlated with vascular disease.1
Fast-forward to the present, and today a multitude of studies support this assumption through the statistical measurement of comorbidities. For example:
- According to the American College of Rheumatology, rheumatoid arthritis nearly doubles the risk of a heart attack within the first 10 years of diagnosis.2
- A study analyzing data from more than 150,000 patients with irritable bowel disease (IBD) found a 10% to 25% percent increase in the risk of stroke and heart attack.3
- Patients with psoriasis appear to be twice as likely to carry risk factors for heart disease, such as diabetes and metabolic syndrome.4
- After two decades of research, the connection between periodontal disease and cardiovascular disease (CVD) has been confirmed.5
In addition to these chronic conditions, inflammation is also associated with humankind's second-largest cause of mortality: cancer.6 As early as 1863, after finding immune cells in tumor samples, the German pathologist Rudolf Virchow discovered that cancers tend to occur at sites of chronic inflammation.7,8 More recently, in 2007, a meta-analysis demonstrated an increased risk of small bowel, colon, extraintestinal cancers, and lymphoma in patients with Crohn's disease. 9
In another interesting study, a team of researchers from Imperial College in London and Harvard University delved into the statistical health records of 50,000 patients, which were collected over a period of 21 years. The researchers discovered that among those patients with periodontal (gum) disease, there was a 33% increase in the risk of lung cancer, a 50% rise in the risk of kidney cancer, and a 30% higher incidence of blood cancers such as leukemia.
Additionally, in patients with chronic advanced gum disease, researchers found patients had an additional fourfold increase in head and neck cancer for each millimeter of related bone loss around teeth.10 (As this study illustrates, your dentist's oral care reminders may go beyond saving your teeth, to in fact saving your life!)
From 1863 in Germany, to 1989 in Scandinavia, and continuing to the present day, the scientific research overwhelmingly indicates that inflammation is at the root of many life-threatening illnesses. But how can we determine which patients are at risk? Which person has just a bad tooth, versus a bad tooth and an increased risk of cancer? Are there measurable biomarkers that can serve as predictive tools?
The answer is yes, if you utilize the science of neuroimmunology – the study of neurological and immunological changes that result from the interaction of the nervous and immune systems. Backed by two decades of research and clinical study, neuroimmunology provides a more comprehensive understanding of the physiological and biological interactions underlying complex chronic diseases.
All diseases of the nervous system affect immune functions, and all diseases of the immune system affect the nervous system. The nervous and immune systems use neurotransmitters as chemical messengers to maintain a constant crosstalk. When neurotransmitters deplete, pro-inflammatory cytokines are produced. In contrast, as neurotransmitters are balanced, central control of inflammation is returned.
This is why research scientists and clinicians rely upon a neuroimmunological panels of tests. When performed properly by a CLIA-certified lab (such as Pharmasan Labs in Osceola, Wisconsin), neuroimmunology lab assessments give health-care providers an opportunity to assess a patient's neuroinflammation levels and directly address the underlying issues, before damage becomes extensive.
Case Study: J. S.
J. S. is an athletic, 62-year-old white female who eats a healthful diet. Still, she has a history of irritable bowel, sports injuries, and chronically bleeding gums. J. S.'s lab work was normal (including lipid levels within ranges of American Heart Association guidelines). The only exception was a slight elevation in three markers: oxidized LDL, myeloperoxidase, and CRP-HS.
Her treatment consisted of statin medication (lipids and CRP-HS), several botanical anti-inflammatories, frequent dental work that required antibiotics, and a fish oil product. J. S. was not responsive to traditional or alternative treatments aimed at getting her inflammation under control. Frankly, her case was a bit of a mystery.
I decided to look at the relationship between J. S.'s central nervous system, her immune system, and her levels of inflammation. Quickly it was evident that at J. S.'s core, she was a very different person:
Interleukin 1: elevated
Interleukin 3: elevated
Interleukin 10: low
Interleukin 6: high
The interpretation of the labs indicated chronic inflammation as judged by the levels of two key neurotransmitters (histamine and glutamate) and the cytokine measurements (all of the listed cytokines).11 In addition, the IL-6 elevation may help explain why the CRP-HS and TNFa are increased, as this cytokine can drive these markers up and increase the risk of plaque instability or myocardial infarction.12 The elevated DOPAC and oxidized LDL may imply that free radical oxidation is also adding to J. S.'s risk of a life-threatening disease.13,14
However, the most important clinical interpretation is that of low sympathetic drive. The decreased levels of catecholamines or low sympathetic drive can lead to a lack of control of PGE2 and COX-2.15 This may be caused by an imbalance in the anti-inflammatory and inflammatory cytokines, thereby affecting the neuroimmune systems.16 Clinically, this can translate to inflammation and poor wound healing.17
Norepinephrine – the main neurotransmitter responsible for sympathetic drive – is released directly into the blood from the peripheral and the neurosympathetic fibers, affecting the locus coeruleus in the brain.18 The locus coeruleus can be damaged by free radical oxidation (hence the elevated DOPAC and oxidized LDL), while stress can decrease the adrenal medulla's production of norepinephrine and cortisol.19,20
Among the locus coeruleus's many functions is the responsibility for mediating many of the sympathetic effects during stress, suppression of the parasympathetic system as needed, and activation of the corticotrophin-releasing factor from the hypothalamus.21 This is important because norepinephrine influences inflammation via the cytokine system and through the hypothalamic-pituitary-adrenal axis and cortisol.22
We have now connected the central nervous system to immune and inflammatory control not only through the CNS but also throughout the brain (hypothalamus and pituitary) and into both parts of the adrenal gland. This supports the theory that the "core" of inflammation is in fact the central nervous system.
After interpreting these results, I added to the patient's regimen tyrosine, SAMe, and taurine, along with serotonin and theanine (to support the conversion of glutamate to GABA). The statin was removed due to concerns of an added inflammatory effect. Ubiquinol and a broad-spectrum, fat-soluble antioxidant (including A, beta carotene, D, D3, K, K2, high gamma and mixed tocopherols) was added. In order to suppress oxidation of lipids and protect the locus coeruleus, 600 mg of alpha-lipoic acid was added per day. An alkalinizing/anti-inflammatory diet with healthful oils and stress-reducing hot yoga were likewise recommended.
Within 2 weeks, J. S.'s neurotransmitters and cytokines showed signs of normalizing. Within 6 months, her clinical symptoms resolved, and her CRP-HS, oxidized LDL, and myeloperoxidase normalized.
The Future of Neuroimmunology
I foresee a day in the not-too-distant future that we practitioners no longer take a "best guess" at diagnoses and best options for nutritional supplementation. Routinely, neurotransmitter testing will be used in order to accurately assess neuroinflammation and address patients' underlying issues. All treatment will be based on the positive movement of lab results and the real data of clinical science.
I predict that in the coming years, addressing neuroinflammation will be the fastest-growing sector of the natural-medicine industry. As health-care providers become increasingly aware of the value of testing and supplemental nutrition to rebuild healthy immune and inflammatory function, the market will explode.
Working at the "core" of issues – that is, resolving a patient's presenting clinical symptoms in a way that helps prevent future life-threatening issues – sounds almost too good to be true. But rest assured that it isn't – it's just the emerging science of neuroimmunology.
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2. Heart disease and rheumatoid arthritis [Web page]. WebMD. March 2014. http://www.webmd.com/rheumatoid-arthritis/guide/heart-disease-rheumatoid-arthritis.
3. Crohn's and colitis may be tied to risk of heart attack, stroke [online article]. AMHC. http://www.amhc.org/32-crohns-disease-irritable-bowel/news/158972-crohns-and-colitis-may-be-tied-to-risk-of-heart-attack-stroke. Retrieved March 2014.
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18. Arnsten AF. Through the looking glass: differential noradenergic modulation of prefrontal cortical function. Neural Plast. 2000;7:133–146.
19. Chen K-B, Lin AM-Y, Chiu T-H. Oxidative injury to the locus coeruleus of rat brain: neuroprotection by melatonin. Journal of Pineal Res. October 2003;35(2):109–117. doi:10.1034/j.1600-079X.2003.00063.
20. Schommer NC, Hellhammer DH, Kirschbaum C. Dissociation between reactivity of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress. Psychosom Med. 2003 May–Jun;65(3):450–460.
21. Benarroch EE. The locus ceruleus norepinephrine system: functional organization and potential clinical significance. Neurology. 2009 Nov 17;73(20):1699–1704.
22. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002 Oct;53(4):865–871.
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.