EDS, the Extracellular Matrix, & Toxin Overload

In EDS (Ehlers-Danlos Syndrome) and other connective tissue disorders, we see impaired collagen structure or formation. Connective tissue is found throughout the body. We see it in bone, bone marrow, tendon, ligament, fat, cartilage, the gastrointestinal wall, skin, and blood vessel walls. Connective tissue also encloses the brain and spinal column. It is everywhere and, when it is compromised, can cause significant issues throughout the body.


It's taken us a long time in the medical field to look past the musculoskeletal system (muscles, joints, and bones) with connective tissue disorders. Now that we've zoomed out to see bigger systemic picture with EDS and HSD (hypermobility spectrum disorder), we need to zoom back in to the cellular level.


One crucial regulator of our body is being over looked: the extracellular matrix (ECM). The ECM may be able to explain many of the issues we see in failing systemic health in those with connective tissue disorders. The importance of the ECM in long term treatment approaches is why we, at Elevation Wellness, have developed our own way of healing the ECM. This approach needs to be specific to those with connective tissue disorders. Impaired connective tissue will respond differently than regular connective tissue and this needs to be respected in treatment approaches.


What is the ECM?

  • The ECM is the 3-dimensional area surrounding a cell that acts as a filtering system between the cell and the environment outside.

  • The ECM is made up of electrolytes, glycosaminoglycans, polysaccharides, collagen, and proteins.

  • Collagen is the main structural stabilizing component of the ECM, providing the tensile strength, regulating cell adhesion (how neighboring cells interact with each other), supporting chemotaxis (the cell's reaction to chemical stimulus), cell migration (movement to areas it is needed), and tissue development.


What does the ECM do?

  • It acts as a mediator for things that pass in and out of the cell. It regulates and responds to those things, communicating to other systems.

  • It is responsible for cell nutrition, eliminating waste products and toxins.

  • All things that go into or out of a cell pass through the ECM.

  • It's the site of metabolite and toxin accumulation, acting as a buffer to all stresses (physical, chemical, biological, electromagnetic, and psychological).

  • It communicates to other systems of the body using prostaglandins (inflammation and blood flow), cytokines (inflammatory and immune system regulation), lymphokines (immune system regulation and modulation), neuropeptides (nerve communication), and proteases (break down proteins).

  • It's connected to the endocrine system through capillaries.

  • It's connected to the central nervous system by peripheral nerves and neuropeptides.

  • The ECM regulates as a system to communicate with the vascular system, connective tissue cells, lymphatic system, and the ANS (autonomic nervous system).

  • It is involved in all inflammatory reactions and is responsible for most vital reactions in the body.

  • Growth factors (TGBF - Transforming Growth Factor Beta, VEGF - Vascular Endothelial Growth Factor, CIGF - Connective Tissue Growth Factor) depend on a fully functioning, healthy ECM. The Growth Factors assist in:

Immune System homeostasis and regulation

Vascular funciton

Oxygen delivery

Stem cell differentiation (changing of one cell type to a more specific type)

Muscle function

Blood vessel formation

Growth and development

Quality of life and overall wellness is directly related to the efficiency and health of the

ECM.

  • Chronic diseases are the consequence of the dysfunctioning ECM to effectively deal with toxins and/or stressors.


Connective Tissue Disorders and the ECM

  • Those with a connective tissue disorder (Hypermobility Spectrum Disorder, EDS, Marfan's, etc) are predisposed to a structurally compromised ECM secondary to impaired connective tissue function in the components of the ECM (namely collagen).

  • If there is a structurally compromised ECM, there is a greater susceptibility and impact to toxins and infections, and abnormal immune responses.

  • Any sort of toxin can damage the ECM.

  • When toxin damages a structurally compromised ECM (as we see in connective tissue disorders), this exacerbates the toxic reaction and worsens the dysfunctional reaction of the cell. The response will be more intense and more abnormal in those with a connective tissue disorder.

  • The relationship of EDS and endometriosis is thought to be in part from increased TGFB-1 levels that have been found in EDS, or with a CYP21a2 deficiency (this will deplete copper and progesterone while increasing cortisol production). These are potential issues stemming from a dysfunctional ECM.

  • TGFB-1 (a Growth Factor regulated by the ECM) can also increase permeability at the epithelial junctions, causing leaky gut and a leaky blood brain barrier.

  • The lymph system runs through conenctive tissue. The lymph system removes metabolic waste products and toxins from the cells of our organs. Connective tissue disorders with dysfunctional ECM will negatively influence the individual's capacity to transport toxins out of the lymph to be eliminated.

What Happens When an ECM is Not Functioning Efficiently?

  • ECM dysfunction can be seen in many chronic illnesses such as Lyme Disease, mold illnesses, CIRS (Chronic Inflammatory Response Syndrome), cancer, and connective tissue disorders (EDS).

  • Dysfunctional ECMs are correlated with fibrosis, joint hyper mobility syndromes, autoimmune diseases, and arthritic disease.

  • Other diseases suspected to have ECM dysregulation are fibromyalgia, viral infections, ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), autism spectrum disorders, motor neuron disease, and neurodegenerative diseases.

  • As the ECM communicates inefficiently with systems throughout the body, it can cause a wide variety of signs and symptoms.


MCAS (Mast Cell Activation Syndrome) and the ECM

  • Mast cells can bind to the ECM proteins, which activates a number of inflammatory cytokines. The correct signals must be sent from a healthy ECM to carry out the reaction needed by the body. A dysfunctional ECM will not be able to communicate efficiently with the mast cell.

  • Mast cell activation most likely occurs after tissue injury and toxic exposure to the ECM. If the ECM is dysfunctional, this must be carefully addressed to help regulate the mast cells efficiently.


ECM and Toxins

  • Toxins can easily damage the ECM (this can include, but is not limited to mercury, mold, aluminum, glyphosate, and certain drugs).

  • Glyphosate can accumulate in animal bone, collagen, bone marrow, and ligaments. Increased exposure can potentially lead to autoimmune attacks against the collagen itself.

  • Mold can activate MMP9 (metalloproteinase) that is involved in breaking down the ECM and increases immune cells released through the ECM. TGFB-1 and VEGF (growth factors) can be dysregulated by mold illness or CIRS (Chronic Inflammatory Response Syndrome).

  • Metals like mercury can inhibit the enzymes that suppress MMP9 (degrades the ECM proteins, activating cytokines and chemokines) and MMP2 (degrades collagen).

  • Lyme Disease releases MMP9 while the ECM becomes a central hiding place for boriella. Boriella binds to the plasminogen system which allows free plasmin to break down the ECM.

  • Fluoroquinolones (antibiotics such as Cipro) will change the ECM, increasing metalloproteinases (responsible for breaking down the ECM). This can lead to a break down of collagen in the body and increase in the risk of tendon rupture. Those with an already compromised ECM (HSD, EDS, Marfan's) are at the greatest risk for toxicity to Fluoroquinolones.


The Science of Toxin Overload

  • Mycotoxins can be inhaled, eaten or touched. They commonly come from molds as well, which create them as a byproduct in the sinuses and gut.

  • Mycotoxins will enter in to our fat cells, binding to a receptor on the outside of the cell. This relates a messenger that then moves into the cell where it binds to and activates a third messenger (NF-kB). This NF-kB moves into the nucleus of the cell and turns on gene transcription for a DNA segment that is coded for the production of cytokines (immune system messengers). This process triggers a severe inflammatory response. In short - mycotoxins will activate the immune system and cause inflammation.

  • When cytokines are triggered, the body engages the immune system to respond with more help. This recruits immune cells (macrophages and lymphocytes) to help. These will also trigger more cytokines to be released.

  • The increase in cytokines will block the body's leptin receptors. Leptin are made and found in fat cells and regulate our satiety, the feeling of fullness. When these leptin centers are blocked by cytokines, the fat cells try to produce more and more leptin to promote a better chance of binding to the receptor sites. Although massive amounts of leptin may be produced, cytokines continue to block them from binding. The body will eventually become used to this process and become leptin resistant.

  • With leptin resistance and lack of binding to its receptor sites, the body (specifically the hypothalamus) is unable to make enough MSH (alpha-melanocyte stimulating hormone - affects the production of adrenal hormones, sex hormones, thyroid hormones, anti-diuretic hormone, and can create leaky gut, increase the risk of autoimmune diseases and decrease the body's ability to respond to invaders) and VIP (Vasoactive Intestinal Polypeptide - a vasodilator that regulates smooth muscle activity, epithelial cell secretions, decreases blood flow in the digestive tract, normalizes testosterone and estrogen, improves vitamin D levels, and decreases C4a levels; aides in immunoregulation and helps control inflammation). In short, it limits the body's ability to regulate the immune system, hormonal system, and nerve function with suppressing MSH and VIP production.

  • The immune system should be able to register when the fight has been won with an invader. It will then send out signals to stop the cycle of reactions. An abnormal system will not necessarily know when to turn the cycle off.


What Goes Wrong in Detoxification?

  • Genetics usually gives us an advantage in knowing how to bind and get rid of toxins before damage is caused. However, about 25% of the general population lack this gene. These people will be more profoundly impacted by toxins.

  • If a toxin is persistent (the type that chronically resides in the body or the body undergoes repeated exposure), and you have an impaired ECM (as in connective tissue disorders) or are part of the 25% of the general population with the genetics that make it difficult to remove toxins, the inflammatory reactions will continue and not stop.

  • Some people are part of the 25% of the population with difficulty removing toxins AND also have a connective tissue disorder. Double whammy. This can cause serous issues in the body's capacity to detoxify invaders.

  • Toxins can also influence our body's antigen recognition system that is responsible for recognizing the foreign invader and making the antibody to fight it off. This can cause the body to create incorrect antibodies that will be ineffective at fighting off the invader.

  • Without these correct antibodies, the only way left for the body to attempt to rid itself of a foreign invader is through an organic anion transport system found in the small ducts of the liver. These ducts secrete the toxins into our bile where the toxins bind to the bile itself and is transported into the small intestines. They stay bound to the bile, so they are not excreted or eliminated. They end up being reabsorbed before getting to the colon and return to the liver and gall bladder.


The Problem with Detoxification in a Compromised ECM

  • Damaged ECM cannot detoxify normally. Those with chronic exposure or connective tissue disorders affecting the ECM need a different approach.

  • In common detox strategies, the treatment attempts to free toxins for the body to eliminate. Compromised ECM or those 25% of the population with impaired genetics regarding detoxification, will not be able to handle the release of toxins from the fat cells and will have negative reactions (Herx reactions). Some reactions can be severe depending on the overall health of the person and state of the ECM.

  • Simple fasting that burns fat cells can also cause the release of toxins from the fat cells into a system that is not able to efficiently bind and excrete them. Fasting may make these people with compromised ECM or impaired genetics feel more ill.

  • Those with compromised ECM or are part of the 25% with impaired genetics, need to work on restoring the ECM first, reduce the toxic load, and take a modified and closely monitored approach to a detoxification plan. This should be done with a professional that is skilled in working with a compromised ECM throughout a detox program.