Ehlers danlos syndrome, commonly referred to as EDS is a vastly under-diagnosed connective tissue disorder in the human population. EDS is classified as having at least 13 different subtypes, and there is much confusion as to the relationship with other connective tissue disorders. The implications for EDS are vast, and extend into areas of immunology, endocrinology, neurology, cardiology, mitochondrial function, autoimmunity, osteogenesis, mast cell disorders, CFS/ME, POTS, chronic inflammatory response (CIRS).
EDS involves various deficiencies in the ability to form collagen, the most abundant protein in the human body. Consequently, one of the driving characteristics of EDS is joint hypermobility. However it must be understood that the implications for EDS extend far beyond joint hypermobility.
Credit must be given to Sharon Meglathery, MD for elucidating the pathophysiology and various related theories of EDS. Credit also goes to Deborah Cusack for elucidating what is now referred to as "The Cusack protocol" and the use of polysaccharides as a viable treatment.
Here is a summary of notes:
- EDS and related connective tissue disorders are grossly under-represented in the population
- EDS and other related phenotypes are genetically predisposed to have a deficiency of various forms of collagen. Collagen is the most abundant protein in the human body. Collagen is the constituent of connective tissue, including myofascia, surrounds bones, forms matrices, and through its hydroxapatite has piezoelectric properties
- EDS and the phenotypes of hyper joint mobility may present with an assortment of other characteristics, namely: mitral valve prolapse, tricuspid and bicuspid valve fragility, small veins, stretchy or sagging skin, postural orthostatic tachycardia syndrome, high histamine and mast cell disorders, elevations in TGFß-1 (a growth factor and immune modulator), motor neuron disease, autoimmune activation
- The genetics of EDS is sparse at best, with significant research studies severely lacking. Many genetic reporting systems such as 23andme do not identify key EDS-related SNPs
- Genetics of EDS & connective tissue disorders, suspect genes:
- TNXB - Tenascin-X. A deficiency of tenascin X is etiological in at least one form of EDS. Tenascin X is a glycoprotein which possesses anti-adhesive effects. Of interest is that TNXB is functionally related to Complement C4a, an immune protein involved in the inhibition of mast cell activation
- COL5a1 and COL5a2 - Type 5 collagen, type 5 collagen alpha chain 2
- COL3a1 - Collagen 3 alpha chain 1
- CYP21a2 - Involved in converting progesterone into cortisol. Suspected to involve copper as a cofactor.
- ATP7a - Copper transporter across intestines into circulation and across cell membranes. Copper is an important cofactor in collagen synthesis
- LOX - Lysyl oxidase a copper-dependent enzyme that catalyzes formation into collagen and elastin precursors
- EDS and endometriosis combination is rampant - Could be due in part to high TGFß-1 levels, which is commonly found in EDS. TGFß-1 (transforming growth factor beta 1) is used in growth differentiation as well as functions as a key modulator of immunological balance. EDS and endometriosis may also be associated with CYP21a2 deficiency, which is proposed (at least in early stages of illness) to cause depletions in copper and progesterone, while upregulating cortisol synthesis. PCOS is often found with elevated TGFß-1, and more research is needed to study the relationship between PCOS and EDS
- Per Shoemaker, elevated TGFß-1 can increase epithelial junction permeability aka leaky gut and leaky blood brain barrier (BBB)
- Elevated TGFß-1 represents an imbalance between adaptive and innate immune responses
- Metabolites of Losartan potassium, a blood pressure medication can effectively lower TGFß-1
- CBD, cannabidiol, non psychoactive cannabis is immunomodulatory, and has shown to reduce elevated MMMPs (metalloproteinases) and upregulate TREGs (T-regulatory cells). Inhibition of MMP9 is thought to be significant with certain forms of EDS, including vascular forms
- VIP (vasoactive intestinal polypeptide) may be a candidate for EDS and complications. Per Shoemaker, MD, VIP lowers TGFß-1, increases TREGs cells, normalizes testosterone and estrogen, improves Vitamin D, reduces C4a
- Polysaccharides play a significant role in collagen and connective tissue formation
- Whole food vitamin C may raise ceruloplasmin, a primary copper-transporting protein
- Distilled aloe vera (rich source of polysaccharides) has been shown to reduce joint hypermobility in as little as 30 days, as well as mitigate symptoms of skin bruising and hyperelasticity