Connective Tissue Disorders/Ehler Danlos, the ECM and Chronic Issues - MCAS, CIRS, POTS, CFS, IBS, Dystonias, Pain, Proprioceptive Disorders, ETC.!

Thanks for the info!
I don't know if it's good for me yet. I never tried it nor paid much attention to it because I thought it was helpful only for extreme cases, such as autoimmune diseases, which I don't have. But this recent info makes me think twice...

I'm still at the stage of trying to implement the basic Metal / Candida Detox plan from Laura, but I'm struggling to implement it firmly. This said, a Low FODMAP diet would be more realistic considering my tendency to cheat all the time.

The next step I need to investigate is whether there are psychological or emotional aspects to the way I relate to food that would explain why I can't stop cheating. Laura's words keep echoing in my mind from the last session: "It's not worth it. Being in pain for days just for a bite of tasty food."

Cheating is usually a result of victimhood thinking, laziness, entitlement, and suffering avoidance. that's how it was for me, and I think the same could be applied generally. Have you read George K Simon's Character Disturbance or Inside the Criminal Mind by Samenow? Reading those two books, and taking them as VERY personal criticisms, helped me a lot with my tendency to cheat. Then it became easier to do what is right, not what 'it' wants.
 
FWIW, MCAS mainstream protocol:

Montelukast 10 mg once a day (for those sensitive or with Ehler Danlos, preferably in the morning as opposed to the evening).
Sodium cromoglycate 100 mg three times per day 30 minutes before eating
Famotidine 40 mg once a day
Bilastine 20 mg twice a day

It does help to have it around for those affected, even if not taken every day. Fish and other MCAS triggering foods are doable with this protocol.
 
An update on my experiment with low dose doxycycline.
I’ve been taking a subantimicrobial dose of 20mg daily for 3 weeks.

I believe I have hyper mobile EDS. I suffer chronic pain that can be anywhere in any joints, muscles or ligaments though primarily in my left pelvis and hip and anywhere in the left leg. I have a whole cache of other symptoms too though pain is the most challenging. I also have had chronic gut issues for longer than I want to remember and a tilted uterus, both backward and slightly to the left. In a major flare up I can barely walk, flare ups correlate with incorrect food choices (which I still struggle with) and severe prolonged sleep interruption. If I eat well, sticking to mainly beef I have less pain, though still enough to need daily massage and stretching for several hours.


Since starting the doxy I have had significantly less pain, the little nodules in my muscles and ligaments have reduced in size, I have much less gut discomfort from wrong foods and feel like I’m coping better with the sleep disturbances- most of which are out of my control, sometimes I’m awake because I’m wired/tired but usually it’s something else, my 2 year old, the neighbour’s dog barking, or my partner coughing from aspirating with his disease.

Yesterday I forgot to take the doxy and woke up this morning hurting. I took a dose and within half an hour the pain was almost gone, I give it a 1/10. I’ve also incorporated using a tens machine on painful areas though hadn’t had to use it since last week.

So far it looks promising.
 
One treatment for these kinds of stealth syndromes is Low Dose Naltrexone. There is a research trust with a lot of information detailing all the ins and outs of this treatment. Looks like it could be promising for reduction of symptoms.

How Low Dose Naltrexone (LDN) Works – Updated 2021 with the latest information

The History, Pharmacology and Mechanism of action of Low Dose Naltrexone (LDN)

Understanding how LDN works requires a grasp of three fundamental biological principles.

First, opiate receptors are present in multiple biological systems in the human body, as they regulate a great number of biological functions via the central release of natural opiates (endorphins/met-enkephalins). (1) (2)

Second, a class of proteins called toll-like receptors (TLRs) are part of the immune system, providing a first line of defense against microbial invasion and possessing the ability to recognize and be activated by not only pathogens but also endogenous signaling molecules. (3)

Lastly, naltrexone, when given at a low dose, has antagonistic activity in both of these areas, and is able to modify biological functions of these receptor groups by suppressing unwanted immune reactions, or by stimulating disease-suppressed immune activity. (4)

Naltrexone, taken at the full dose of 200mg daily, has been licensed for use for the treatment of addictions since 1984. (5) It is currently used for both opiate and alcohol addiction, as a full dose is able to completely block endogenous (endorphins released by the brain) and exogenous (recreational drugs such as heroin) opiates. In the licensed dose, it is used as an oral tablet, a long-acting injection, and as an additive in painkillers to prevent them from being abused. (5)

As have many drugs that have been widely used for an extended period, naltrexone has been found to have different actions when used in lower doses than originally intended. These in part are due to the chiral nature of the molecule and the different, dose-dependent effects of the Levo and Dextro isomers of naltrexone.

The concept of chirality is not new, (chiral chemistry was discovered by Louis Pasteur in 1848), like all drugs when synthesized are produced as a racemic mixture of 50:50 left- and right-handed molecules. (6) Half of the mixture synthesized is a left-handed shape and the other half is a right-handed shape. Although consisting of the same components, and being chemically identical, they have different shapes (as with left and right hands), enabling the different isomers to interact with different groups of receptors in the body.

In general, most drugs only have biological activity in the human body in Levo (left) handed shape, as this is how most of the receptor groups in the human body are arranged. Common examples of these drugs—such as levothyroxine, levocetirizine, levobutanol—are manufactured as racemic mixtures of 50:50 Levo and Dextro isomers; however, the manufacturer discards the Dextro isomer and presents the medication in the Levo-only form, sometimes because the Dextro isomer carries unwanted side effects, or is not active on the intended target receptor. (7)

In the case of naltrexone, the Levo isomer interacts with the commonly understood opiate (endorphin) receptors group and the Dextro isomer interacts with the toll-like receptor group. (8) (9)

The basic effects of LDN can be summarized as follows:

DEXTRO-Naltrexone


  • Blocks (antagonises) some TLR receptors
  • Reduces production of pro-inflammatory cytokines
  • Suppresses cascade inflammation
  • Central and system effects as TLR receptors are present on microglial cells, mast cells, and macrophages
LEVO-Naltrexone

  • Blocks opiate receptors for a brief period
  • Increases natural production of anti-inflammatory endorphins
  • Upregulates opiate receptors
  • Has direct effect on some cell proliferation rates
Again, these mechanisms are fully elucidated in both volumes of The LDN Book, but the main point is that LDN is extremely useful in the treatment of many poorly managed autoimmune and oncological conditions.

1.Mørch H, Pedersen BK. Beta-endorphin and the immune system--possible role in autoimmune diseases. Autoimmunity. 1995;21(3):161-71. doi: 10.3109/08916939509008013. PMID: 8822274

2. Zagon IS, McLaughlin PJ. Endogenous Opioids in the Etiology and Treatment of Multiple Sclerosis. In: Zagon IS, McLaughlin PJ, editors. Multiple Sclerosis: Perspectives in Treatment and Pathogenesis [Internet]. Brisbane (AU): Codon Publications; 2017 Nov 27. Chapter 8.

3. El-Zayat, S.R., Sibaii, H. & Mannaa, F.A. Toll-like receptors activation, signaling, and targeting: an overview. Bull Natl Res Cent 43, 187 (2019). Toll-like receptors activation, signaling, and targeting: an overview - Bulletin of the National Research Centre

4. The LDN Book 1. Chelsea Green Publishing.

5. Srivastava AB, Gold MS. Naltrexone: A History and Future Directions. Cerebrum. 2018;2018:cer-13-18. Published 2018 Sep 1.

6. Gal J, Cintas P. Early history of the recognition of molecular biochirality. Top Curr Chem. 2013;333:1-40. doi: 10.1007/128_2012_406. PMID: 23274573.

7. Nguyen LA, He H, Pham-Huy C. Chiral drugs: an overview. Int J Biomed Sci. 2006;2(2):85-100.

8. Cant R, Dalgleish AG, Allen RL. Naltrexone Inhibits IL-6 and TNFα Production in Human Immune Cell Subsets following Stimulation with Ligands for Intracellular Toll-Like Receptors. Front Immunol. 2017 Jul 11;8:809. doi: 10.3389/fimmu.2017.00809. PMID: 28744288; PMCID: PMC5504148.

9. Hutchinson MR, Zhang Y, Brown K, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci. 2008;28(1):20-29. doi:10.1111/j.1460-9568.2008.06321.

Here is a list of documentaries:


Here is the LDN YouTube channel with thousands of videos, some of which include patient testimonies pointing to reduction of symptoms with LDN.


There is also a symptoms list tab, and the number of conditions currently being treated by LDN is remarkable.

 
From what I recall in reading about low dose naltrexone is that the basic mechanism that produces healing results is that it encourages the production of endorphins - the bodies own pain killers, mood enhancers and stress relievers. It's thought that during the windows of endorphin flushes that last for an hour or so, IIRC, that healing takes place.
 
I honestly don't know if I have some of the symptoms because of the adverse childhood experience or is genetic. It could be both. I don't have hypermobility but my small blood vessels in arms or palms just crack and bleed since childhood. I feel the pain and I seem crazy to people I mention that. But it's even visible. I have broken capillaries all over my face and once when I was a kid I scratched myself over the area where I felt the cracking and I was bleeding for so long that my whole sheet was covered in blood.
I have to read all of this again but thank you all for all of the information.
 
FWIW, MCAS mainstream protocol:

Montelukast 10 mg once a day (for those sensitive or with Ehler Danlos, preferably in the morning as opposed to the evening).
Sodium cromoglycate 100 mg three times per day 30 minutes before eating
Famotidine 40 mg once a day
Bilastine 20 mg twice a day

It does help to have it around for those affected, even if not taken every day. Fish and other MCAS triggering foods are doable with this protocol.

As far as I can tell all of the above are prescription only and I'm not so sure how to obtain these without in the UK? Personally I think the Bilastine anti histamine would be most beneficial for me to have on hand, as it's mostly skin issues and joint/ muscular/ nerve pains I suffer from when I have a flare.

I was reading alot of stuff on MCAS on Reddit last night how it relates closely to endometriosis, and how estrogen and histamine basically help eachother fire or something like that (really not getting alot of time to research or keep it stored in my brain recently) -- I guess this is why lots of folks benefit from progesterone (even in contraceptive measures) in managing endometriosis, and battling against the rise in or dominance in estrogen.

Anyway I started looking into it again because recently I ate lots of foods I shouldn't have with people visiting, that kicked up a flare of pain, brain fog etc. I haven't taken codeine for a long while and relied on that for a few days. I took naproxen too... Well, that made my eczema flare back up and my skin overall itchy, and the pain/ inflammation inevitably worse days after.

So for those that have this condition, the very obvious message is not to delve away from a carnivore/ low carb/ low histamine diet because you can't even use certain pain relief to ease the consequences, without more consequences! :lol:

I also asked grok about berberine and how that may help MCAS

Berberine, a natural compound found in plants like goldenseal and barberry, has been studied for its potential anti-inflammatory and mast cell-stabilizing effects, which could be relevant to managing symptoms of mast cell activation syndrome (MCAS) and related flares like eczema. In MCAS, mast cells release excessive mediators (such as histamine and cytokines) that drive allergic-like reactions, inflammation, and symptoms including skin issues.

Triggers like certain foods or medications (e.g., codeine, which can promote mast cell degranulation) often exacerbate this, leading to cascades like joint pain followed by eczema worsening.

Based on available research, berberine may help in the following ways:
Suppressing mast cell activation and degranulation: Studies indicate that berberine inhibits IgE-mediated mast cell responses and reduces the release of inflammatory mediators. For instance, it has been shown to suppress Syk phosphorylation, a key step in mast cell signaling, which could help dampen overactive mast cell responses during a flare-up. This might reduce overall allergic inflammation triggered by food or codeine.

Reducing allergic and inflammatory responses: Berberine appears to regulate pathways like FcεRI-mediated signaling and MAPK, which are involved in mast cell-driven allergies. In experimental models, it has suppressed passive cutaneous anaphylaxis (a mast cell-related reaction) and decreased pro-inflammatory cytokine production, potentially easing symptoms like swelling, hives, or eczema associated with MCAS flares.

Addressing eczema specifically: For eczema flares, which can be worsened by mast cell activity or secondary infections (e.g., from Staphylococcus aureus, common in atopic dermatitis), berberine has demonstrated anti-inflammatory effects by inhibiting eotaxin and cytokine expression. It also shows antibacterial activity against S. aureus and reduces mast cell degranulation in eczema models, which might help mitigate skin inflammation exacerbated by triggers like codeine.

Much of this evidence comes from in vitro (cell-based) and animal studies, with limited human clinical trials specifically for MCAS or eczema. Anecdotal reports from communities (e.g., on Reddit) vary, with some users noting benefits for related issues like blood sugar control or post-exertional malaise, but not consistently for MCAS flares. Berberine is generally considered safe at typical doses (500–1,500 mg/day), but it can interact with medications (e.g., affecting cytochrome P450 enzymes) and may cause gastrointestinal side effects. It's not a substitute for standard MCAS treatments like antihistamines or mast cell stabilizers, and individual responses vary.
 
I also asked grok about berberine and how that may help MCAS

That's interesting, thanks for sharing!

I heard that quercetin is also helpful for histamine issues.

Quercetin inhibits the production and release of histamine and other allergic and inflammatory substances, possibly by stabilizing cell membranes of mast cells [79,80]. In particular, quercetin is an inhibitor of allergic (IgE-mediated) mediator release from mast cells and basophils, another type of white blood cell involved in immune reactions. Quercetin is also an inhibitor of human mast cell activation through the inhibition of Ca2+ influx, histamine, leukotrienes and prostaglandins release and proteinkinase activation [27]. Mast cells are influential immune cells important for the pathogenesis of allergic responses and autoimmune disorders. They also affect release of many cytokines involved in the inflammatory reactions such as IL-8 and Tumor necrosis factor (TNF) [81,82]. It is a reason why quercetin is suitable for the treatment of mast cell-derived allergic inflammatory diseases such as asthma, sinusitis, and rheumatoid arthritis [8].
The anti-allergic and anti-inflammatory properties of quercetin have been proved by several studies, in animal models and in vitro, as presented in Table 1.


Quercetin acts as a natural antihistamine, inhibiting the release of histamine from mast cells. This makes quercetin for histamine intolerance and MCAS an effective tool for reducing symptoms like hives and digestive discomfort.


Also, in that article, there's this bit which is relevant to this thread:

Quercetin’s Impact on Connective Tissue and Gastrointestinal Health
Preserving Fascia, Muscle, and Connective Tissue
The overproduction of inflammatory mediators like histamine and tryptase can weaken connective tissues. This is especially concerning for people with conditions like Ehlers-Danlos Syndrome (EDS), where tissue fragility is already an issue. Quercetin’s mast cell stabilization effects help protect fascia, muscle, and connective tissue from further degradation, making it a helpful option in supplements for mast cell activation.

Supporting Gut Health
Mast cells in the gastrointestinal (GI) tract play a major role in gut function. When overly active, they can trigger symptoms like bloating, diarrhea, and pain. Quercetin stabilizes mast cells in the gut, reducing inflammatory mediators and promoting healthier digestion. This is particularly beneficial for people with quercetin histamine intolerance or MCAS-related gut symptoms.
 
That would be Serena from "Hard to get Meds" thread. She'll see the powder and you'll have enough doses for your entire neighborhood, though.

If you can handle it with natural remedies, that would be the way to go.

Thank you Gaby, and yes an amount for the entire neighborhood seems unnecessary. :lol:

I've ordered some Quercetin too Yas, when I was working through grok with it all it suggested that also and that they work well together, and perhaps dandelion root.

Just another thing I've noticed with the inflammation from foods and painkillers, now the bad pains and brain fog have lifted -- the pain and low mood is really not worth eating/ taking things you shouldn't! It affects literally everything.
 
Proprioception is from Latin proprius, meaning "one's own", "individual", and capio, capere, to take or grasp. Thus, it means to grasp one's own position in space, including the position of the limbs in relation to each other and the body as a whole.

Explaining how does it feel to have proprioceptive problems is practically impossible to convey. It is as if you have to have it in order to grasp the concept. If you don't have it, all explanations remain in the field of "esoteric" knowledge.

For those who want to understand it better, you can read the research of proprioceptive problems found on astronauts who have spent a lot of time in outer space:

Astronauts experience significant proprioceptive problems during and after spaceflight due to the microgravity environment. In microgravity, the body is unloaded, which decreases the utilization of proprioceptive input, a key factor contributing to balance dysfunction upon return to Earth. This disruption manifests as a loss of awareness of limb position, with astronauts reporting they can lose track of their arms and legs, sometimes feeling as if their limbs are not present. The altered proprioceptive function affects the feedback control of movement, leading to delayed movement strategies and impaired mass discrimination during tasks like accelerating a ball up and down with whole-arm movements.

The central nervous system adapts to spaceflight by reinterpreting vestibular and somatosensory inputs, which are no longer suitable for the 1G environment upon return. This results in sensorimotor dysfunction, including excessive postural sway, spatial disorientation, and alterations in muscle activation and joint kinematics. After landing, astronauts often perceive the floor as moving up toward them when hopping down or being pushed down under them when hopping up, a phenomenon linked to impaired proprioceptive feedback. These proprioceptive deficits, combined with vestibular disturbances, contribute to post-flight postural ataxia and locomotor control deficits.

AI-generated answer. Please verify critical facts:

Developing Proprioceptive Countermeasures to Mitigate Postural and Locomotor Control Deficits After Long-Duration Spaceflight - PMC
Weightlessness and Its Effect on Astronauts

Probably the most common causes of impaired proprioception is aging, which favors falls in the elderly. It's impaired in genetic disorders such as joint hypermobility or Ehler Danlos syndromes, autistic spectrum disorders, Parkinson's disease and traumatic injuries. It has also been described after a stroke, viral infections, when a person is very tired, as a consequence of excess vitamin B6, chemotherapy, weight loss or weight gain, etc.

Proprioception encompasses the internal body and the external body and its movements, but also the immediate environment perceived by the skin, joints, the feet, the eyes, sense of smell, the manducatory system contributing to posture, the vestibular (inner ear) perception of the head's position.

This highlights the problems with impaired proprioceptive where there is attenuation (anesthesia and pseudo paralysis) of perceptions, or exaggeration of perceptions (pain). Perception of the environment is different from others, and often people with proprioceptive problems have difficulty in making themselves understood.

The brain is normal, though, but it's embedded in a peculiar body which is often very performing due to its softness and laxity, and it's greater hearing capacity, which could explain a greater capacity of observation and adaptation.

Proprioceptive problems introduce the concept of a "somatopsychic" disease mentioned earlier and how many with proprioceptive problems have extrapyramidal symptoms such as dystonias (trembling).

Receptors at the muscle level, which inform the brain about the body's motor activity, send wrong signals to the automated regulatory system for automatic movements, giving rise to shaking and involuntary muscle movements. There can be bruxism, permanent muscle contractions, generalized tonique seizures of non-epileptic origin, and restless leg syndrome.

The problem with proprioception is not due to a problem in the central or peripheral nervous system, which is why these tests are always normal, but from a generalized problem at the level of the conjunctive tissue which is modified in its structure and its mechanical behavior. It is in these tissues where multiple sensors in the entire body inform the person of what is going on. Signals that these sensors transmit to the brain for perception purposes or signals transmitted for automatic regulatory purposes in the entire body are either nonexistent, exaggerated or modified, producing a great difficulty in localizing the body or things in the environment.

The conjunctive tissue is either too elastic or its sensors won't react or, on the contrary, they overreact. Vulnerable or thinned conjunctive tissue and/or its deformation don't do the job of protecting the body properly from overpressure, or it creates problems from contracting muscles and its coordination with other muscles and its movements, with other sensors in the eyes or the feet, explaining visual fatigue or double vision.

Disturbance of the body's perception can result in sensorimotor disconnections resulting in falls, pseudoparalysis, falling objects, difficulty executing certain tasks, stumbling against door handles. Parking a car can be very difficult, as the environment is not integrated properly and there are referential/space problems.

Proprioceptive problems from the conjunctive tissue at the respiratory level has several consequences such as fatigue, shortness of breath specially when going up the stairs, sleep apnea. There can problems swallowing food and gastric reflux.

There's a like a dissociation between the brain where the body doesn't obey the brain. The body might feel like a foreign object to the person.

There might attention deficit disorder secondary to the conjunctive tissue anomaly. The antennas and sensors are hyper-tuned, but there's too much information coming in without proper grounding.

The difficulty of "keeping your feet in the ground" and/or not being grounded properly in the body, is due to proprioceptive problems. There's a real problem feeling the sense of self in space due to malfunctioning receptors. This can go beyond the physical realm. Depending on programming, background and the genetic recombination dice, they're more easily manipulated by their environment and/or people. "We can take over because there's no one home" kind of energy. Alternative practitioners have reported a higher quantity of spirit attachments in people with hypermobility spectrum disorder of the Ehler Danlos kind, who are often very empathetic despite problems in expressing themselves properly.

Despite psychiatric diagnosis in people with spectrum Ehler Danlos, one of the most experienced experts in the field claims without hesitation that the brain is the only organ that works in Ehler Danlos. It's the perception that is askew, leading to misdiagnosis of bipolar disorder, ADHD, severe anxiety, etc. It's a sensory problem at the level of the conjunctive tissue where the body gets constantly the message of "freeze" or "fight or flight" to quote the polyvagal theory. The conjunctive tissue is the richest sensory organ in the body, more sensory than the skin.

Physiotherapy for the proprioceptive system becomes essential for getting healthier. There's no way around it. No biochemical molecule, peptide or vitamin will ever completely compensate the malfunction of millions of receptors with very complex functions at the level of the entire conjunctive tissue located in viscera, fascias and throughout the entire body. Adapted physical therapy is essential.

Among the most useful treatments to correct the defect of proprioception stemming from malfunctioning fascia or conjunctive tissue are compressive garments, which stimulates proprioception and prevents positions and movements that are painful by informing the brain that the right stretch is that one, and not the one of the malfunctioning conjunctive tissue.

I have had patients that are like textbook cases of conjunctive tissue disorder who don't believe me that they have a problem and who after years of trying multiple treatments finally recover from their pain by using a compressive garment. Then, they finally believe me.

Garments are made by very precise measures. For gloves, every finger is measured and each finger at each articulation. Despite garments triggering pressure urticaria in my body, I persisted in wearing them, if only for the grounding effect it had on me.

People who were not able to walk anymore, were finally able to do it with specialized compressive garments that stabilized all their joints, including at the level of their hips.

More info, see:



 
Among the most useful treatments to correct the defect of proprioception stemming from malfunctioning fascia or conjunctive tissue are compressive garments, which stimulates proprioception and prevents positions and movements that are painful by informing the brain that the right stretch is that one, and not the one of the malfunctioning conjunctive tissue.

I have had patients that are like textbook cases of conjunctive tissue disorder who don't believe me that they have a problem and who after years of trying multiple treatments finally recover from their pain by using a compressive garment. Then, they finally believe me.
Great info, thank you for this, Gaby!

I have been suffering from Fasciitis Plantaris, which refers to the plantar fascia, a thick band of tissue on the bottom of the foot that support the arch. "Fasciitis plantaris" is the term for inflammation of this fascia, commonly known as plantar fasciitis. This condition often causes heel pain, especially with the first steps in the morning or after periods of rest. And I have to say: this is very painful and annoying, since I have to walk a lot in my work.

I haven't been to the doctor yet, but with this info I'm going to start wearing short compression stockings specially designed for this condition, which I didn't know it existed: https://www.amazon.com/s?k=short+co...ps,619&ref=nb_sb_ss_p13n-pd-dpltr-ranker_1_28
 

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