The immune system‘s role is to be the “protectors” of the body by attacking invaders that enter the body, cleaning up old cells, and making room for new cells to flourish in the body. The body needs the immune system to function and be healthy from many environmental triggers the body is exposed to daily. When environmental triggers come in contact with the body, it can cause many disruptive factors over time and causes the immune system to mistakenly attack healthy, normal cells as they see it as a foreign invader, thus causing the body to develop autoimmune diseases. Some environmental triggers like toxic metals could be associated with autoimmune diseases that can affect the body, causing various symptoms to affect the body. Today’s article looks at the effects of toxic metals on the body, how it affects the immune system, and ways to manage the impact of toxic metals on the immune system. We refer patients to certified providers specializing in autoimmune treatments to help many individuals with autoimmune diseases associated with toxic metals. We also guide our patients by referring to our associated medical providers based on their examination when it’s appropriate. We find that education is the solution to asking our providers insightful questions. Dr. Alex Jimenez DC provides this information as an educational service only. Disclaimer
The Effects of Toxic Metals On the Body
Have you been experiencing abdominal pain in your gut? Do you have a bitter metallic taste in your mouth? What about experiencing inflammation affecting not only your joints but your gut as well? Many of these symptoms are signs correlating that you might suffer from toxic metals in your body. The body is constantly exposed to various environmental factors that affect many individuals over time. It can be the foods consumed, the environment a person is exposed to, and their physical activity. Studies reveal that heavy metal pollutants from environmental pollution can enter the human body through various pathways like the respiratory, cutaneous, and gastrointestinal paths and begin to accumulate in different organs. When the body suffers from autoimmune diseases associated with toxic metals, symptoms of inflammation will start to affect the joints in the body. To that point, toxic metals will begin to facilitate their interaction with the immune system, causing the development of autoimmune disease symptoms.
How Does It Affect The Immune System
So how do toxic metals affect the immune system, thus causing symptoms associated with autoimmunity? As stated earlier, the immune system is the body’s protector and, when exposed to environmental disruptors over time, leads to the development of autoimmune diseases. For toxic metals, many people are usually exposed to low levels of metals through consuming fish and shellfish (containing low levels of mercury). However, when individuals are exposed to high levels of heavy metals, studies reveal that certain metals can seriously affect the immune system by overstimulating the different muscle tissues and soluble mediators that cause chronic-inflammatory reactions associated with heavy metals. Some of the symptoms associated with toxic metals causing autoimmunity in the body include:
Numbness
Prickly sensation down hands or feet
Abdominal pain
Inflammation
Joint pain
Muscle weakness
Introduction The Immune System-Video
Have you been experiencing inflammation in your joints? How about feeling muscle weakness in your back, arms, legs, or neck? Or have you been feeling overall discomfort in your body? Many of these symptoms are signs of autoimmune diseases associated with toxic metals. The video above introduces the immune system and how it plays its role in the body. When the body gets exposed to environmental factors like heavy toxic metals, it can cause the development of autoimmune diseases associated with chronic issues like joint inflammation and muscle pain. Different heavy toxic metals can affect other body parts, as studies reveal that these different heavy toxic metals are systemic toxicants that induce adverse health effects on the body. When an individual has been exposed to high levels of heavy toxic metals, chronic issues like joint inflammation can progressively cause pain over time unless treated early on. Luckily, treatments are available to help manage the effects of toxic metals in the immune system associated with joint inflammation.
Managing The Effects Of Toxic Metals In The Immune System
Since the body is exposed to environmental factors constantly, if it is not treated right away, it can lead to autoimmunity associated with chronic symptoms like joint inflammation. Fortunately, there are ways to manage the effects of environmental factors, like lowering the impact of toxic metals on the body system. Studies reveal that incorporating essential minerals protects the DNA sequence from further oxidative damage in the body’s immune system. Other treatments like chiropractic care utilize spinal manipulation on spinal subluxation or spinal misalignment on the joints to reduce inflammation associated with toxic metal autoimmunity. Since there are many ways that autoimmunity can affect the body through environmental triggers, the symptoms associated with autoimmunity are treated through chiropractic care. Chiropractic care not only utilizes spinal manipulation but can help improve the immune system in the body by increasing lymphatic fluid circulation and loosening stiff muscles surrounding the joints. To that point, it allows the body to get rid of toxins and waste that is in the body. Incorporating treatments like chiropractic care can help restore the body to its functional state.
Conclusion
The immune system is the body’s protector from foreign invaders that enter the body. When there are environmental triggers that the body is being exposed to, it can put the body at risk of developing autoimmune disease associated with chronic symptoms like inflammation of the joints. Environmental triggers like heavy metals can be associated with joint inflammation and cause pain in the body. When this happens, the body experiences pain and dysfunction due to inflamed joints. Fortunately, chiropractic treatments utilize spinal manipulation on subluxation (spinal misalignment) to reduce joints’ inflammation and improve lymphatic system circulation. These treatments can help the body manage autoimmunity associated with heavy metals and their symptoms.
References
Ebrahimi, Maryam, et al. “Effects of Lead and Cadmium on the Immune System and Cancer Progression.” Journal of Environmental Health Science & Engineering, Springer International Publishing, 17 Feb. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203386/.
Jan, Arif Tasleem, et al. “Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants.” International Journal of Molecular Sciences, MDPI, 10 Dec. 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691126/.
Lehmann, Irina, et al. “Metal Ions Affecting the Immune System.” Metal Ions in Life Sciences, U.S. National Library of Medicine, 2011, https://pubmed.ncbi.nlm.nih.gov/21473381/.
Tchounwou, Paul B, et al. “Heavy Metal Toxicity and the Environment.” Experientia Supplementum (2012), U.S. National Library of Medicine, 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144270/.
Everyone tries to make healthy life choices by boosting their immune system. Getting adequate sleep, eating plenty of fruits and vegetables, drinking plenty of water, and exercising all help increase the immune system. The immune system is known as the “protector” of the body as it eliminates foreign invaders that enter the body and causes chaos to the effective systems. The immune system releases cytokines to the alien invaders causing inflammation in the affected area. When environmental factors affect the body over time, the immune system mistakenly attacks its cells, thinking it’s a foreign invader causing autoimmunity. Today’s article looks at autoimmunity, its triggers, how inflammation plays its role in the body, and what is D.I.R.T. We refer patients to certified providers specializing in autoimmune therapies to help many individuals dealing with autoimmune diseases and inflammation. We also guide our patients by referring to our associated medical providers based on their examination when it’s appropriate. We find that education is the solution to asking our providers insightful questions. Dr. Alex Jimenez DC provides this information as an educational service only. Disclaimer
What Is Autoimmunity?
Have you been dealing with abdominal issues that affect you when you eat something? How about pain and swelling in your joints? How about unexplained skin problems? Some of these symptoms are signs that many individuals risk developing autoimmunity. Autoimmunity is defined as a self-directed inflammation of the body’s tissue, which results from a loss of tolerance by aberrant dendric cells and B & T cell responses. This causes the development of immune reactivity towards native antigens. When autoimmune diseases occur in the body, studies reveal that this is due to the immune system attacking self-molecules; many disorders are strongly associated with many predisposing factors.
Things That Trigger Autoimmunity
When it comes to the link between the triggering factors and the immune system, studies reveal that the cause and pathway of many autoimmune diseases affecting the body are unknown but that the many factors that trigger the progression of autoimmune diseases are associated with different chronic issues. The adaptive immune response consists of antibodies and activated T lymphocytes that play a predominant role in clinical conditions. The multiple pathways that autoimmune diseases do to the body are ongoing and multifactorial due to the initial trigger for systemic and organ-specific disorders that may predate clinical diseases by many years. Some of the factors that may trigger autoimmunity in the body include:
Gut
Endothelial
Brain
Stress
Toxins
Infections
Food
Biotoxins (innate)
What Is Inflammation?-Video
Have you been dealing with swelling around your joints and muscles? Do the foods seem to cause issues in your gut? What about feeling radiating pain traveling down your arms or legs? These are signs that your body is experiencing inflammation. The video above gives an excellent explanation of what inflammation is and its role in the body. Inflammation is the immune system’s natural defenses triggered by various factors that affect the body while it promotes healing to the affected area. Inflammation can be good or bad; it depends on the severity of the body’s injury and location. Inflammation has a casual relationship with the immune system in acute and chronic forms. In its acute form, inflammation can minimize the injury or infection to promote healing in the affected area with heat, redness, and swelling. However, in its chronic condition, where the damage is more profound, various pathogens affecting the body’s tissues may result in chronic issues associated with inflammation. Luckily, there are ways to manage autoimmunity-related inflammatory symptoms.
What Is D.I.R.T?
The body needs the immune system to protect itself from foreign invaders that enter the body. Studies reveal that the immune system does more than protect the body; it can flush out old, damaged cells in the body and replace them with new ones. The immune system also mobilizes responses to the invaders with its ability to distinguish self from non-self. As stated earlier, the immune system has a causal relationship to inflammation. It may succumb to triggering factors that could be involved with the muscles and joints associated with pain. The immune system uses the acronym D.I.R.T. to regulate and defend the body when needed.
D: Detect & Defensive
The immune system in the body has a mechanism that identifies potentially threatening molecular structures like:
Strange signals found in microbes, food, plants & fungi, chemicals
Danger signals (alarmins) that are found in tissues or secreted by stimulated leukocytes or epithelia
When these structures attack the body, the immune system begins to detect and becomes a defense mechanism that will mount the appropriate responses to the threat level. Once the threat is eliminated, the body can regenerate new, healthy cells.
I: Internally Regulated
The body has immune responses that are tightly controlled and actively resolved through multiple cellular, genomic, and enzymatic mechanisms. Some of the regulations that the immune system provides are:
T regulatory lymphocytes
Lipid-derived pro-resolution mediators
Redox balance: Nrf2-ARE activation
Even though it is difficult to manipulate the immune system, finding ways to regulate the immune system from going crazy and finding the right balance for a healthy immune system is essential for a healthy body.
R: Restorative
The immune system’s function is to repair any damages resulting from injury or negative encounters that the body has gone through. When the body becomes injured, the immune system sends inflammatory cytokines to the affected area and begins the healing process. Other cellular structures that help the immune system restore the body include:
Phagocytes
Fibroblasts
Stem cells
Endothelial cells
There are other ways to restore the body and improve the immune system. Eating healthy foods to boost the immune system, exercising, and even getting chiropractic care may help the immune system. But isn’t chiropractic care used for the back? Yes, chiropractic care focuses on the musculoskeletal system, but they also support many individuals in maintaining their health and wellness. The immune system will function to its total capacity when any spinal misalignments or subluxations are corrected through spinal manipulation.
T: Tolerant
The immune system helps the body build a tolerance to the pathogens that are affecting the body. For example, food allergens. With many common food allergens, like nuts, gluten, milk, fish, and eggs, the body will begin to build a tolerance to these allergens when it is introduced slowly. Other healthy boundaries that the immune system provides to the body include:
Self or fetal antigens
Innocuous environmental antigens
Microbes
Plants and fungi
By building a healthy tolerance to these pathogens, the body has a solid chance to build up immunity to the pathogen. It can help the immune system be stronger when reencountering these pathogens.
Conclusion
Overall the immune system is the primary protector of the body from foreign invaders. When harmful pathogens enter the body, the immune system sends out cytokines to where the invaders are and get rid of them. This causes inflammation in the affected area in the body, causing swelling and redness in the skin. When these pathogens infect the body over time, the immune system mistakenly attacks the body, especially the vital organs causing chronic inflammation associated with autoimmunity. Autoimmunity is a cluster of disorders that causes body dysfunction, which overlaps with inflammation causing the body to be dysfunctional. Luckily it is treatable with the right foods, exercises, and treatments that can help lower inflammation and help regulate the immune system back to its original self.
References
Chaplin, David D. “Overview of the Immune Response.” The Journal of Allergy and Clinical Immunology, U.S. National Library of Medicine, Feb. 2010, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923430/.
Chen, Linlin, et al. “Inflammatory Responses and Inflammation-Associated Diseases in Organs.” Oncotarget, Impact Journals LLC, 14 Dec. 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805548/.
Smith, D A, and D R Germolec. “Introduction to Immunology and Autoimmunity.” Environmental Health Perspectives, U.S. National Library of Medicine, Oct. 1999, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566249/.
Vojdani, Aristo. “A Potential Link between Environmental Triggers and Autoimmunity.” Autoimmune Diseases, Hindawi Publishing Corporation, 12 Feb. 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945069/.
Stomach pain, burning, or aching 1-4 hours after eating?
Offensive breath?
Unpredictable abdominal swelling?
If you are experiencing any of these situations, then you might be exposed to mercury in your body.
When it comes to autoimmune diseases, there has been a slight increase in autoimmune diseases that have been around over the past few decades. Everyone knows that when the immune system starts to attack itself, it can cause the body to develop autoimmune disruptors, and even some significant triggers can cause a malfunction in the body as well.
There are many ways that autoimmunity can occur in the body in many different ways. The first one is when the cells are mistaken as a foreign pathogen, and the body attacks itself. The second one is called molecular mimicry. This happens when the body starts to make an antibody to a specific antigen, and these antigens can take the resemblance of any specific proteins; thus, the body’s antibodies will attack the tissues. The third one is when the body becomes affected by environmental triggers and genetic stress; it starts to develop T-cells in the immune system.
Many local integrative doctors and health care professionals are working with functional medicine. They all understand that environmental triggers are one of the factors that can cause dysfunction in the body. With food sensitivities, environmental triggers, and lifestyle factors can cause a person’s body to have inflammation. Inflammation is not only in the joints, but it can also affect the gut’s health as well, causing leaky gut and dysbiosis. There are even toxins that the body can be in contact with that can also affect the immune system significantly. Heavy metals and xenobiotics can cause a total toxic burden in the body, and one of them is mercury.
Mercury
Also known as quicksilver, mercury is a liquid metal and is a naturally occurring element that is found outside in the air, water, soil. Most people are usually exposed to low levels of mercury by consuming fish and shellfish. Although it is safe to consume fish and shellfish, when humans are exposed to high levels of mercury is highly toxic and can lead to mercury poisoning, thus affecting the body.
Studies have found that the connection link between gut health and autoimmune diseases has been in the news regularly with the exposure to high levels of mercury and becoming one of the most significant risk factors for the body to develop autoimmunity. In a 2015 study, author Emily Somers Ph.D. Sc. M. stated that even though mercury at low levels is generally safe are still associated with autoimmunity, and the exposure to mercury has stood out to be the leading risk factor for autoimmunity in the body.
Mercury Poisoning Symptoms
There are many signs and symptoms that mercury poisoning can cause the body to dysfunction. The effects of mercury poisoning can vary depending on the exposure level and on a person�s age. When mercury affects the nervous system, thus can lead to neurological symptoms like:
Physical tremors
Anxiety
Mood swings
Numbness
Memory problems
Other symptoms from mercury poisoning can appear even more if levels of mercury rise in the human body. Some of the severe symptoms can include:
Muscle weakness
Nausea and vomiting
Metallic taste in the mouth
Lack of motor functions
Muscle numbness
Difficulty walking or standing straight
There are more studies about mercury poisoning as they stated how mercury can increase the activation of the T-cell receptor and how self-reactive cells can escape the elimination process during T-cell selection. Other studies have found that mercury can induce autoimmune diseases in humans. For many local chiropractors and health professionals would always ask their patients if they have had any dental fillings in their teeth. If they do, then it turns out that the dental fillings may have mercury in them.
What many people do not know is that dental fillings, especially silver fillings, can contain about forty to fifty percent of mercury. If a person still has these types of fillings their teeth, they might have an increased risk of mercury exposure in their system. In order to reduce the mercury exposure in the body, anybody who has silver fillings can get them replaced with newer and safer alternatives for their fillings.
Conclusion
Mercury is a toxic element that can harm the human body and can develop autoimmune diseases in the immune system. Mercury can also cause many symptoms in the body can cause harm and dysfunction to a person. Sometimes a person may have silver fillings that may cause them to be exposed to mercury and can get them replaced to limit their exposure. Once there is no exposure to mercury in the immune system, the body will start to heal and function properly through a healthy diet and functional medicine. Some products are here to help support the immune system by providing the essential formula to the body and its many functioning systems.
The scope of our information is limited to chiropractic, musculoskeletal, and nervous health issues or functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or disorders of the musculoskeletal system. Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900.
References:
Bigazzi, P E. �Autoimmunity and Heavy Metals.� Lupus, U.S. National Library of Medicine, Dec. 1994, www.ncbi.nlm.nih.gov/pubmed/7704000.
Johnson, Jon. �Mercury Poisoning: Symptoms and Early Signs.� Medical News Today, MediLexicon International, 9 Jan. 2018, www.medicalnewstoday.com/articles/320563.php.
Pollard, K Michael, et al. �Toxicology of Autoimmune Diseases.� Chemical Research in Toxicology, U.S. National Library of Medicine, 15 Mar. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC3076021/.
Team, DFH. �Mercury Exposure and the Autoimmune Connection.� Designs for Health, 9 Oct. 2018, blog.designsforhealth.com/mercury-exposure-and-the-autoimmune-connection.
Team, WHO. �Mercury and Health.� World Health Organization, World Health Organization, 31 Mar. 2017, www.who.int/news-room/fact-sheets/detail/mercury-and-health.
The University offers a wide variety of medical professions for functional and integrative medicine. Their goal is to inform individuals who want to make a difference in the functional medical fields with knowledgeable information that they can provide.
Autoimmunity:�One of the most common things is to leave the doctor�s office with a diagnosis of an autoimmune disease and no nutritional or lifestyle changing insight. Autoimmune diseases are related to inflammation. Keeping� the inflammation down is the goal with autoimmune attacks. The foods you eat make a huge difference in the frequency and severity of flare-ups. Steady dietary changes can help you reach your optimal self.
Is Autoimmune Disease A Result Of The Collective Perturbations Of The Exposome & Its Impact On The Immunometabolic System?
Food:�Genes that determine illness are triggered by what we put into our bodies, literally what we eat. Our cells are literally created out of the foods we put into our bodies. Like most people do, we are likely eating nutrient-poor foods that create damaged dysfunctional cells. When we learn to eat foods that nourish the body, our cells repair themselves, and the new cells created will be optimal functioning cells.
Unhealthy foods create chronic inflammation, which is destructive to the body. Inflammation is normally the body�s healthy response to injury or infection. However, when inflammation becomes chronic, from constant assault on the gut by consuming the wrong foods, inflammation becomes the cause of destructive diseases, i.e. Lupus, Rheumatoid Arthritis, Colitis and other inflammatory diseases.
Disclosure
Terry Wahls, MD disclosed no relevant financial relationships with any commercial interest.
The two routes by which diet can influence our health:
(A) the metabolism of our cells and
(B) the population of our gut microbiota.
Paolo Riccio, and Rocco Rossano ASN Neuro
2015;7:1759091414568185
Copyright � by SAGE Publications Inc, or the American Society for Neurochemistry, unless otherwise noted.
Manuscript content on this site is licensed under Creative Commons Licenses.
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Low-Fat, Plant-Based Diet In Multiple Sclerosis: A Randomized
Controlled Trial
This was a randomized-controlled, assessor- blinded, one-year long study
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Exclusion Diets
Eliminated specific protein sources � RA Sx ?
Raw vegan, vegan and gluten free vegan
Systematic review of 14 RCTs
Dietary benefits uncertain
Small studies with risk of bias
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Exclusion Diets
Atopic dermatitis improved n=20
UC � fewer symptoms n=18
Crohn�s food sensitivities identified in half n=42
Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in MS – Inducing antibodies reacting with myelin oligodendrocyte glycoprotein (MOG) and Cerebellar peptides
Liquid cow milk (not cheese) and MS prevalence was highly correlated (rho = 0.836) across 27 countries and 29 populations.
�By eliminating lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.�
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Nutrient Triage
Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.
Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose response meta-analysis of prospective cohort studies.
16 studies – 833,234 participants
Risk Of All Cause Mortality Associated With Servings/Day Of Fruit & Vegetables
Dose-Response Relation Between Fruit & Vegetable Consumption & Risk Of All Cause Mortality
BMJ. 2014; 349: g4490.
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14. Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann N Y Acad Sci.2002 Apr;959:128-32.
15. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr.2005 Jan;81(1 Suppl):313S-316S.
16. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. Blueberry supplementation improves memory in older adults. J Agric Food Chem.2010 Apr 14;58(7):3996-4000.
17. Funding for the studies was provided by the US Highbush Blueberry Council, the National Institute on Aging, and Wild Blueberries of North America. Dr. Krikorian has disclosed no relevant financial relationships.
18. Lobo GP Amengual J, Baus D, Shivdasani RA Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX. J Biol Chem.2013 Mar 29;288(13):9017-27
?-carotene Is Not Retinol (Vitamin A)
?-Carotene is converted to vitamin A in the intestine by the enzyme ?-carotene-15,15′- monoxygenase (BCMO1) to support vision, reproduction, immune function, and cell differentiation.
Considerable variability in BCMO1 exists and can effect individual vitamin A status
Nutritional Adequacy (%RDA) US Diet Vs. Study Diet
Multimodal Intervention Improves Quality Of Life
Mood & Cognition
In the setting of progressive MS Improved thinking ability and reduced anxiety and reduced depression
Average daily servings of the study diet recommended (vegetables/fruits) and excluded (gluten/dairy/eggs) foods p < 0.01 difference from baseline to 12 months
Average Scores On The Mood Measures At Each Study Visit
Average Scores On The DKEFS & WAIS Sub-Scales At Each Study Visit.
Relapsing Remitting MS
Reduce Fatigue
?Mental & Physical QoL 16% (> 5 points)
Improved Motor Function
A Simplified Model Of FMD?Mediated Effects On Glucocorticoid, Immune Suppression & Oligodendrocyte Regeneration & Differentiation In MS
N=60 6 Month Human Clinical Trial
FMD 100 ml broth, 1 T flax oil tid, 200 � 350 Kcal, Plus enema as needed 7 days Mediterranean diet
Ketogenic(KD) 160gmfatm<100gPro,<50g CHO
Usual diet
Change at 3 month of (k) overall quality of life, (l) change in health, (m) physical health composite, and (n) mental health composite. The dotted line represents a threshold that is thought to be clinically important
The Two Routes By Which Diet Can Influence Our Health:
(A) the metabolism of our cells and
(B) the population of our gut microbiota.
Paolo Riccio, and Rocco Rossano ASN Neuro
2015;7:1759091414568185
Copyright � by SAGE Publications Inc, or the American Society for Neurochemistry, unless otherwise
noted. Manuscript content on this site is licensed under Creative Commons Licenses.
Gut Brain Immune Axis
Gut microbiota influence the brain and immune system balance
Diet influences the microbiome strongly
Exercise, sleep, stress level also important
Changes in the colon mucosa every early in the disease process
The composition of gut microbiota is influenced by multiple factors, such as diet and host genotype. Within the gut, ecological processes such as selection and evolution take place. The use of antibiotics reduces the numbers and diversity of gut microbiota.
Higher quality diet (food), stress reduction, movement � are relatively safe with large favorable benefits for all cause mortality
3 month trial of a grain free, dairy free, sugar free vegetable rich (or gluten free vegetarian) diet is relatively safe with potential for many favorable benefits
Dietary Approaches to Treating MS Related Fatigue RRMS & Fatigue Study funded by NMSS MSDietStudy@healthcare.uiowa.edu Live within 500 Miles of Iowa City, Iowa info@wahlsinstitute.com
Autoimmunity is the reaction of cells (lymphocytes) or antibodies�of the immune system along with the body�s own tissues leading to certain pathology. Autoimmunity can produce various conditions, which depend upon the target of the attack.�While intrinsic factors, which include age, sex, and genetics contribute to autoimmunity, it is believed that extrinsic factors such as drugs, chemicals, microbes, and/or the environment can trigger the initiation of autoimmune responses.
Autoimmune Disease & Environmental Toxicants
Educational Objectives
Review air pollution, cigarette smoking, and citrullination as models for the genesis of autoimmune disease
Explore the role of general cell stressors in autoimmune disease
Discuss the impact of lung and gut barrier disruption by environmental toxins and food additives in autoimmune disease
Utilize the Functional Medicine ATM model to illustrate the various mechanisms by which toxicants could contribute to the pathophysiology of autoimmune disease.
�Mild forms of the autoimmune response probably occur naturally in most people. But, for people with a predisposition to autoimmunity, environmental factors, such as toxic chemicals, drugs, bacteria or viruses, may trigger a full?fledged response.�
�NOVEL CRYSTAL BALL: One day Y?shaped molecules called autoantibodies in a patient�s blood may tell doctors whether a patient is �brewing� certain diseases and may even indicate roughly how soon the individual will begin to feel symptoms.�
Autoimmune Disease: �Delayed Gratification�
Scientific American, March, 2007
Many autoimmune diseases do not develop spontaneously, but instead evolve through an extended germination period before they become clinically evident…
Well over 10 million people test positive for ANA, years before they have any symptoms.
This implies the presence of additional environmental factors that dampen or amplify the process over time.
Arbuckle MR, et al, N Engl J Med. 2003 Oct 16;349(16):1526?33.
Elevated Levels Of Antibodies Against Xenobiotics In A Subgroup Of Healthy Subjects
Vojdani, A, Kharrazian, D, Mukherjee, PS
Some environmental chemicals, acting as haptens, can bind to a high? molecular?weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self?tissue as an invader and launch an immune response against it, leading to autoimmunity
The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors.
10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin?HSA adduct.
The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM).
Detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals
J Appl Toxicol. 2015 Apr; 35(4): 383�397.
Could Environmental Toxins Be A Key Missing Link That Pushes The Immune System Over The Brink To Permanently Lose Control Of Its Tolerance To Self?Antigens?
(A Corollary Question: Does The Persistent Presence Of Autoantibodies Or Autoreactive T Cells Imply An Inevitable Progression To Full?Blown Autoimmune Disease?)
Rheumatoid Arthritis: Swan neck deformity from chronic synovitis
Anti?Cyclic Citrullinated Peptide Antibody
Current method is 96% specific for RA
Elevated titers detected >10 years before onset of clinical disease
Sensitivity (likelihood of positive test) increases from 50% at Dx to >75% over course of disease
Likely involved in pathogenesis
Citrullinated Ags are highly expressed in inflamed joints
Citrulline is formed by posttranslational modification of arginine residues by peptidyl arginine deiminases (PADs)
PADs are upregulated by inflammation, injury, and toxicants
Inflammation and injury thus increases citrullination of multiple synovial proteins
Multiple HLA?DR variants (shared epitope) associated with RA preferentially display citrullinated Ags on MHCII � activating citrulline?specific autoreactive T cells
Smoking increases risk of +anti?CCP when coupled with HLR?DR shared epitope
Floris van Gaalen et al. J Immunol 2005;175:5575-5580
Autoimmunity To Specific Citrullinated Proteins Gives The First Clues To The Etiology Of Rheumatoid Arthritis
Four citrullinated whole protein antigens, fibrinogen, vimentin, collagen type II, and alpha?enolase, are now well established, with others awaiting further characterization All four proteins are expressed in the joint, and there is evidence that antibodies to citrullinated fibrinogen and collagen type II mediate inflammation by the formation of immune complexes Antibodies to citrullinated proteins are associated with HLA ‘shared epitope’ alleles
Porphyromonas gingivalis, pathogenic bacteria that is a major cause of periodontal disease, expresses endogenous citrullinated proteins
Thus, both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunity triad of RA.
Wegner N, Lundberg K, Kinloch A, et al, Immunol Rev. 2010 Jan;233(1):34?54
�More than 20,000 physicians, after Luckies had been furnished them for tests, basing their opinions on their smoking experience, stated that Luckies are less irritating than other cigarettes.�
Mad Men?
Holy Smokes!!
Cigarette Smoking Has Been Strongly Linked To Numerous Autoimmune Diseases
Cigarette Smoking & Autoimmune Disease: What Can We Learn From Epidemiology?
Rheumatoid arthritis and cigarette smoking:
Risk is highest in men: OR up to 4.4 X
Smoking increases risk of seropositive RA 2.4X in women
Smoking intensity and duration both greatly increase risk
Smoking increases severity of symptoms
Increased risk remains for 20 yrs after cessation
�Cigarette smoking is the most conclusively established environmental risk factor for RA�
Smoking & Air Pollution As Pro?Inflammatory Triggers For The Development Of Rheumatoid Arthritis.
Smoking initiates chronic inflammatory events in the lungs.
These, in turn, promote the release of the enzymes, peptidylarginine deiminases 2 and 4 from smoke?activated, resident and infiltrating pulmonary phagocytes.
Peptidylarginine deiminases mediate conversion of various endogenous proteins to putative citrullinated autoantigens.
In genetically susceptible individuals, these autoantigens trigger the production of autoantibodies to anti?citrullinated peptide, an event which precedes the development of RA.
Anderson R, Meyer PW, Ally MM, Tikly M, Nicotine Tob Res. 2016 Jul;18(7):1556?65
Floris van Gaalen et al. J Immunol 2005;175:5575-5580
Cigarette Smoking & Autoimmune Disease: What Can We Learn From Epidemiology?
Systemic lupus erythematosis
Highest risk in current smokers
Current smokers have higher levels of anti?dsDNA Ab
Multiple sclerosis
Increased risk of MS in both current & past smokers
Risk increases with intensity of smoking (more cigarettes per day)
Increased severity of MS in current smokers
Cirtrullination of myelin?basic protein ?? antigenic
Graves� hyperthyroidism
Smoking is esp. strong risk factor for opthalmopathy
Industrial Air Emissions & Proximity To Major Industrial Emitters, Are Associated With Anti?Citrullinated Protein Antibodies.
Randomly sampled 1586 subjects out of 20,000 population from Quebec, Canada
After adjusting for age, sex, smoking, and ethnicity, found
Positive association between anti?CCPA and annual industrial PM 2.5 and sulfur dioxide emissions (i.e. living closer to emitters increases anti?CCPA)
Negative association between anti?CCPA and to a major industrial emitter of both PM 2.5 and SO2 (living further away from emitters decreases anti?CCPA)
�These analyses suggest that exposure to industrial emissions of air pollutants is related to ACCPA positivity.�
Bernatsky S, Smargiassi A, Joseph L, et al, Environ Res. 2017 Aug;157:60?63
Air Pollution As A Determinant of Rheumatoid Arthritis
The induction by air pollution of an inflammatory environment with high citrullination levels in the lung may induce iBALT formation, thereby causing a transition toward a more specific immune response via the production of anti?citrullinated peptide antibodies.
Air pollution not only triggers innate immune responses at the molecular level, increasing the levels of proinflammatory cytokines and reactive oxygen species, but is also involved in adaptive immune responses.
Thus, via the aryl hydrocarbon receptor (AHR), diesel exhaust particles can trigger a T?cell switch to the Th17 profile.
Sigaux J, et al Joint Bone Spine. 2018 Mar 7. pii: S1297?319X(18)30043?5
The Aryl Hydrocarbon Receptor Links TH17?Cell? Mediated Autoimmunity To Environmental Toxins
The aryl hydrocarbon receptor (AhR) is a ligand?dependent transcription factor that mediates a range of critical cellular events in response to halogenated aromatic hydrocarbons and non?halogenated polycyclic aromatic hydrocarbons such as dioxin (TCDD)
In a murine model of multiple sclerosis, which is mediated by Th17 cells, activation of cells using the AhR exacerbated disease, whereas mice deficient in the AhR had attenuated autoimmune disease.
This paper thus links activation of Th17 cells with environmental toxins, suggesting a plausible hypothesis for the increase in such diseases with industrialization.
Veldhoen, M., Hirota, K., Westendorf, A.M, et al Nature. 2008 May 1;453(7191):106?9
J Inflamm (Lond). 2015; 12: 48.
Does Rheumatoid Arthritis (& Other Autoimmune Diseases) Start In The Gut, Or In The Lungs?
Gomez?Mejiba SE, Zhai Z, Akram H, et al. Inhalation of Environmental Stressors & Chronic Inflammation: Autoimmunity and Neurodegeneration.
Mutation research. 2009;674(1?2):62?72.
Citrullination & Autoimmunity
Environmental exposure to cigarette smoke and nanomaterials of air pollution may be able to induce citrullination in lung cells prior to any detectable onset of inflammatory responses, suggesting that protein citrullination could be considered as a sign of early cellular damage
Citrullination has been reported to be a process present in a wide range of inflammatory tissues. Indeed, citrullinated proteins have been detected also in other inflammatory arthritides and in inflammatory conditions other than arthritides (multiple sclerosis, polymyositis, inflammatory bowel disease and chronic tonsillitis)
Histone hypercitrullination can activate neutrophil extracellular traps (NETS)� high inflammatory
These data support the hypothesis that rather than being a disease?dependent process, citrullination is an inflammatory?dependent condition that plays a central role in autoimmune diseases.
Valesini G, Shoenfeld Y, et al Autoimmun Rev. 2015 Jun;14(6):490?7 Wang S,
Wang Y.Biochim Biophys Acta. 2013 Oct;1829(10):1126?35
Air Pollution In Autoimmune Rheumatic Diseases: A Review
Environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica dust in rheumatoid arthritis and systemic lupus erythematosus
Scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica dust.
Primary vasculitis associated with anti?neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure
Air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity
Farhat SC, et al, Autoimmun Rev. 2011 Nov;11(1):14?21
Silica, Silicosis & Autoimmunity
Exposure to respirable crystalline silica (<10 ?m in size) occurs most often in occupational settings � the �dusty� trades
Epidemiological studies link occupational exposure to crystalline silica dust with systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis
Findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production (NLRP3 inflammasome), pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage
Pollard KM, Front Immunol. 2016; 7: 97.
Asbestos = Magnesium Silicate
Assessment Of Autoimmune Responses Associated With Asbestos Exposure In Libby, Montana, USA
The population in Libby, Montana, provides a unique opportunity for study because of both occupational and environmental exposures that have occurred as a result of the mining of asbestos?contaminated vermiculite near the community
Libby serum samples showed significantly higher frequency of positive ANA and ENA tests, increased mean fluorescence intensity and titers of the ANAs, and higher serum IgA, compared with Missoula serum samples
The results support the hypothesis that asbestos exposure is associated with autoimmune responses and suggests that a relationship exists between those responses and asbestos?related disease processes.
Pfau JC, et al Environ Health Perspect, 2005, Vol 113: 25-30
Air Pollution, Oxidative Stress & Exacerbation Of Autoimmune Diseases
Particulate matter present in air pollution can induce oxidative stress and cell death, both by apoptosis and necrosis of human cells leading to aggravation of chronic inflammation, i.e. the tissue damaging reaction observed in autoimmune diseases.
Therefore, identification of strong inducers of oxidative stress among components of PM seems to be crucial for their neutralization and elimination from the ambient environment.
It seems likely that PM 2.5 may exacerbate the onset of the SLE because they were attributed to a significant increase of the level of anti?dsDNA antibodies, and the presence of the renal casts in SLE patients
Exposure to ozone, sulphates, and other pollutants present in the air has been associated with type 1 diabetes in children
MS occurrence and hospitalization was associated with exposure to air pollutants such as PM10, SO2, NO2, and NOx
In addition to tobacco smoke and silica, pollution emissions from road traffic may be an environmental factor responsible for exacerbation of RA
Gawda, A, et al, Central European Journal of Immunology 2017; 42(3)
What Do Environmental Pollutants, Toxins, Infections & Unhealthy Diets Have In Common?
Increase inflammation and additional free radical production,
Which damages tissues (bystander effect), disrupts barriers, and/or modifies DNA…
Creating �foreign?like� tissues that break immune tolerance (eg anti?nuclear antibodies)
Cell Stressors
Macario, A. J.L. et al. N Engl J Med 2005;353:1489-1501
Damage Associated Molecular Patterns
Molecular structures that activate immunologic receptors
Released with cellular injury and/or necrosis after exposure to cellular stressors
DNA fragments
Mitochondria
Misfolded proteins
Advanced glycation end products have similar biological effects
Initiate and perpetuate inflammatory response (esp NLRP3 inflammasome)
Ojcius D, Sai?d?Sadier N. Alarmins, inflammasomes and immunity. Biomedical Journal. 2012;35(6):437.
Vakrakou AG, Boiu S, Ziakas PD, et al, Systemic activation of NLRP3 inflammasome in patients with severe primary Sjo?gren’s syndrome fueled by inflammagenic DNA accumulations.
J Autoimmun. 2018 Mar 15. pii: S0896?8411(17)30789?8.
Environmental Xenobiotic Exposure & Autoimmunity
We argue that localized tissue damage and chronic inflammation elicited by xenobiotic exposure leads to the release of self?antigens and damage?associated molecular patterns …
As well as the appearance of ectopic lymphoid structures and secondary lymphoid hypertrophy,
Which provide a milieu for the production of auto-reactive B and T cells that contribute to the development and persistence of autoimmunity in predisposed individuals.
Pollard KM, Christy JM, Cauvi DM, Kono DH, Current Opinion in Toxicology, Volume 10, August 2018, Pages 15?22
The Functional Medicine Paradigm (Slightly Modified)
Immune disruption = increased susceptibility to triggers
Overload in hepatic detoxification pathways
Effect on triggers:
Synergistic action (immunotoxicant)
Adjuvant: chemical modification of self?antigen to make it appear foreign or immunogenic (neoantigens)
Enhanced apoptosis: danger/damage signals (DAMPs)
Effect on mediators:
Amplified inflammatory pathways
Increased oxidative stress
Disruption of pro?resolution counter?regulatory mechanisms
Functional Toxicology
Changes In Intestinal Tight Junction Permeability Associated With Industrial Food Additives Explain The Rising Incidence Of Autoimmune Disease
The incidence of autoimmune diseases and food additive consumption are both increasing in parallel
Dysfunction of intestinal tight junctions is common in multiple autoimmune diseases
Commonly used industrial food additives including glucose, salt, solvents, emulsifiers, gluten, microbial transglutaminase, and nanoparticles increase intestinal tight junction leakage.
Intestinal entry of foreign antigen activates the autoimmune cascade
Lerner A, Matthias T. Autoimmunity Reviews 14 (2015) 479�489
Autoimmunity Reviews 14 (2015) 479�489
Autoimmune Disease: �Two?Hit� Signal Theory
Barrier disruption allows immune system to be repeatedly exposed to a combination of an autoantigen & an �adjuvant� [Adjuvants can be toxicants, microbes, foods]
This triggers a genetically predisposed immune system to react to the autoantigen as a non?self �stranger�
�Danger� signals released at the site of clearance of dead cells amplify the process; shaping the features & severity of the resulting autoimmune disease
Persistent �Stranger + Danger� = loss of tolerance
Based on this model, strategies aimed at preventing the accumulation of dying cells lowering the adjuvant (toxic) load may be beneficial for the prevention & treatment of autoimmune disease
Anaya JM, Ramirez?Santana C, Alzate MA, Molano?Gonzalez N, Rojas?Villarraga A, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
Oxidatively Modified Autoantigens In Autoimmune Diseases
Oxidative modification of proteins has been shown to elicit antibodies in a variety of diseases, including SLE, diabetes mellitus & RA.
Oxidatively modified DNA & LDL occur in SLE, a disease in which premature atherosclerosis is a serious problem. AGE pentosidine & AGE?modified IgG have been shown to correlate with RA disease activity.
In the face of overwhelming evidence for the involvement of oxidative damage in autoimmunity, the administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease…�
Kurien BT, Hensley K, Bachmann M, Scofield RH., Free Rad Biol & Med, 2006, Vol 41: 549-556
Oxidative Stress In The Pathology & Treatment Of Systemic Lupus Erythematosus.
Oxidative stress is increased in SLE, and it contributes to immune system dysregulation, abnormal activation and processing of cell? death signals, autoantibody production and fatal comorbidities.
Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE.
Reactive oxygen intermediates (ROI) mostly originate from mitochondria, and T cells from patients with SLE exhibit mitochondrial dysfunction
In T cells from patients with SLE and animal models of the disease, glutathione, the main intracellular antioxidant, is depleted and serine/threonine?protein kinase mTOR undergoes redox?dependent activation.
In turn, reversal of glutathione depletion by application of its amino acid precursor, N?acetylcysteine, improves disease activity in lupus? prone mice; pilot studies in patients with SLE have yielded positive results that warrant further research.
Antioxidant therapy might also be useful in ameliorating damage caused by other treatments.
Oxidative stress (OS) plays an important role in the pathogenesis of a variety of autoimmune diseases (ADs) and many environmental agents participate in this process.
Environmental agents, including trichloroethylene (TCE), silica, pristane (TMPD in mineral oil), mercury, and smoke, are known to induce an autoimmune response, potentially through OS?mediated mechanisms.
Antioxidants can attenuate SLE disease activity by down regulating NLRP3 inflammasome activation and activating Nrf2 signaling.
Khan MF, Wang G. Curr Opin Toxicol. 2018 Feb;7:22?27.
Metals & Minerals Associated With Autoimmune Diseases
Heavy metals
Mercury
Cadmium
Lead
Gold
Minerals & Metalloids
Silica (crystalline silicon dioxide)
Asbestos (chrysotile = magnesium silicate)
Arsenic
Lithium
Iodine
Bigazzi PE., Metals and kidney autoimmunity. Environ Health Perspect. 1999 Oct;107 Suppl 5:753?65
Biologic Markers in Immunotoxicology National Research Council (US) Subcommittee on Immunotoxicology. Washington (DC): National Academies Press (US); 1992.
Garza, A, Drug?Induced Autoimmune Diseases. Pharmacy Times 1?20?16
http://www.pharmacytimes.com/publications/issue/2016/january2016/drug?induced?autoimmune?diseases
�Lupus Erythematosus & Other Autoimmune Diseases Related To Statin Therapy: A Systematic Review�
28 published cases of statin?induced autoimmune disease:
10 cases SLE (2 with autoimmune hepatitis)
3 cases subacute cutaneous SLE
14 cases dermatomyositis & polymyositis
Most cases needed systemic immunosuppression
In many patients, antinuclear antibodies were still positive many months after clinical recovery
Anaya JM, et al, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
Messages To Take Home
Autoimmune and autoinflammatory diseases are steadily increasing in our society
The rise in exposure to environmental pollutants and other toxins is increasing the total body burden of xenobiotics
A central theme in the development of autoimmune diseases is the loss of immune tolerance
Immune tolerance can be broken by disruption of barriers (skin, lung, gut, brain) and/or immune dysregulation
Numerous xenobiotics have been shown to disrupt healthy barriers and dysregulate immune responses
Xenobiotics may play a central role in the initiation and perpetuation of autoimmune disease
Explosion Of Autoimmune Diseases: The Mosaic Of Old & Novel Factors
Modern life and exposures to novel chemical and xenobiotic compounds may lead to the development of new complexes of symptoms that do not necessarily belong to one of the well?known autoimmune diseases
As physicians and scientists, we must continue to study novel pathogenic mechanisms and susceptible alleles to help us identify new therapeutic venues.
Agmon?Levin N, Lian Z, Shoenfeld Y. Cell Mol Immunol. 2011 May; 8(3): 189�192.
IFM Annual International Conference Hollywood, Florida May, 2018
Robert Rountree, MD
Robert Rountree, MD is a speaker, consultant, and advisory board member for Thorne and Balchem. He is also a clinical trial board member for Thorne Research.
IFM's Find A Practitioner tool is the largest referral network in Functional Medicine, created to help patients locate Functional Medicine practitioners anywhere in the world. IFM Certified Practitioners are listed first in the search results, given their extensive education in Functional Medicine
The Ecology Of The Exposome
Exposome & The Alteration Of �Self�
The Exposome Connections To Autoimmune Diseases Converting Self Into Non?Self
Multi?Organ Network Biology
In Autoimmunity, Warburg Metabolism Is Increased Through Increased Activity Of GAPDH
Origin Of IL?17 Producing Th17 Cells
What Is The Relationship Of The Gut Microbiome To Autoimmune Disease?
80% Of Patients With Autoimmune Disease Are Female
4?Hydroxyestrogens & DNA reactivity
Relationship Of Hepatic Drug Detoxification To Anti?Nuclear Antibody Development
Nat Rev Rheumatol. 2017 Jun;13(6):348-358.
Paolo Riccio, and Rocco Rossano ASN Neuro
BMJ. 2014; 349: g4490.
Reduce Fatigue
The composition of gut microbiota is influenced by multiple factors, such as diet and host genotype. Within the gut, ecological processes such as selection and evolution take place. The use of antibiotics reduces the numbers and diversity of gut microbiota.
Arbuckle MR, et al, N Engl J Med. 2003 Oct 16;349(16):1526?33.
Floris van Gaalen et al. J Immunol 2005;175:5575-5580
J Inflamm (Lond). 2015; 12: 48.
Gomez?Mejiba SE, Zhai Z, Akram H, et al. Inhalation of Environmental Stressors & Chronic Inflammation: Autoimmunity and Neurodegeneration.
Macario, A. J.L. et al. N Engl J Med 2005;353:1489-1501
Autoimmunity Reviews 14 (2015) 479�489
Anaya JM, Ramirez?Santana C, Alzate MA, Molano?Gonzalez N, Rojas?Villarraga A, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
Bannerjee, B.D., Toxicology Letters, 1999, Vol 107: 21-31
Garza, A, Drug?Induced Autoimmune Diseases. Pharmacy Times 1?20?16
Anaya JM, et al, The Autoimmune Ecology., Front Immunol. 2016 Apr 26;7:139
IFM Annual International Conference Hollywood, Florida May, 2018
