This is not a cure-all, this is a universal…
Don’t Be Deceived Easily
If someone is saying this is simple, they are either lying to you, or are deceiving themselves (and hopefully not you).
When I was so sick, I was too easily deceived by miracle products and cure-alls.
Because I so eagerly wanting to feel better, I would fall prey to this.
I've been approached by many MLMs, sales people, etc over the years during my practice, and it's left a bitter taste in my mouth, so good thing I like digestive bitters LOL.
I'm not going to name anyone in particular, but I’ve rapped about them. :)
During that time I have found some things that are close to a panacea, like sulforaphane from broccoli sprouts (if your redox is in check) and cruciferous vegetables, or heat shock protein (HSP) based modalities like sauna (if your vascular adaptation mechanisms are in check which we’ll discuss in the next post).
I really dislike when influencers put the problem for any topic based on one thing.
Usually it's a complexification of many things as I discussed in the my goal section.
If you have ever read any of my blog posts you will see how I like to use by whatever means necessary that works, whether that's herbs, nutritional supplements, lifestyle changes, psychotechnologies, modalities and devices, hormones, Gene pathways, drugs, etc.
I have personally found a lot of ways to mimic drugs without having to use them.
There are so many tools available, but knowing how to use them and when to use them makes all the difference.
Focus In + Look Back
I used to write a blog post a day, which later turned into a blog post every few days as I learned more research, and as I became healthier and was working with more clients I posted a lot less.
And then amazing opportunities happen for me where I was able to shoot documentaries for public television and fly all around the world for that.
That all changed when the pandemic started as I was cognitively associated with what's going on.
Anyway, after learning so many mechanisms about the body, I stopped honing in so small and started looking back to look for universals, and that is when it hit me that tight junctions make up so many of cell lines we need to thrive and are implicated in the pathologies I had suffered and my clients as well.
I could see it happening all over the world as people would get ARDS, sepsis, systemic capillary leak syndrome, etc (but labelling it as covid which I believe blurred the general population's understanding of post viral illness).
So now today I look for universals, the things that are in everyone.
One I had been a huge fan of for many years was the pathway called Nuclear Erythroid 2–Related Factor 2 (NRF2).
It even inspired me to write a song about it in 2017 and I'll include that as a resource if you want to listen and dance to it.
I plan on making a music video to it later as it's such a highly visual song.
Getting Into the Glycocalyx
Ok so we’re going to zoom in.
In the Junction Dysfunction (not released yet) post, we will pull back.
So the glycocalyx is on so many prokaryotes and eukaryotes.
The term “glycocalyx” literally translates to “sweet husk”: R
Sweet - indicates its key building units – various sugars (or monosaccharides) like glucose, mannose, galactose, and many others
Husk - points toward the location of these sugars – they reside extracellularly on the cell membrane, surrounding the cell like a cloak
It has a negative charge (Zeta Potential) to it, and I believe it's one part of nature's amazing electro-physical miracles. R
By having a negative charge, it repels against the cholesterol sulfate on your Red Blood Cells (RBCs, aka erythrocytes), so it can flow freely through your blood vessels. R
cholesterol sulfate - https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/slct.202103084
The glycocalyx lines your blood vessels, in which (blood vessels) travel for thousands of miles around your body.
The glycocalyx is a part of the gaseous exchange of your lungs, it protects the precious lining of the blood brain barrier, it plays protection roles from your external environment on the epithelium in your nose and enterocytes in your gut, they line the filters of your kidneys, and they are in your highly vascular eyes.
I am sure it's elsewhere, yet I have so much literature to still peruse and devour (please share)!
Why Haven’t You Or Your Doctor Heard About The Glycocalyx In This Context?
You're probably wondering why you've never heard of the glycocalyx, and that's because it hasn't been able to be imaged inside humans until just this past decade.
Just like how research on the microbiome took multiple decades to get from science to practice, this is where the glycocalyx is heading in my personal opinion.
When I started My Biohack I was writing all about the microbiome and no one was talking about it, now you can't go into a (good) doctor's office without them mentioning it.
I had found supplement companies looking at the glycocalyx (with expired patents and starting new companies and slightly different formulas to create new patents to sell products off of), but only purely on the level of the vascular system.
That's phenomenal as that led me to the discovery of the microcapillary system glycocalyx degradation leading to vascular maladaptation in things like POTS.
I have seen other subreddits briefly discussing the glycocalyx in terms of getting better erections (NSFW).
I have not tried the practices in that subreddit FYI.
Although, none of them are talking about the polarity systems or universal junctions.
How does it work in the vascular system? … Shear Stress
A good analogy about the endothelial glycocalyx is trees in the wind ~ wooooshhhhh ~.
As red blood cells brush past the glycocalyxs this causes “shear stress”, which tells endothelial smooth muscle cells to dilate. R
This feedback mechanism allows more red blood cells to flow through. R
So you could think of the glycocalyx like the trees, the Extracellular Matrix (ECM) and receptors for the endothelial cells as the grass. R
Shear stress triggers the release of Nitric Oxide (NO) via a process called Endothelial Nitric Oxide Synthase (eNOS) which hangs out inside the ECM under the glycocalyx. R
Lots of cofactors for this are involved, but some of the most important ones are vitamin c, BH4 and nitrites (more on this in the oral microbiome section).
Tetrahydiobiopterin (BH4) is a cofactor for a lot of different processes including neurotransmission, but it's role in the endothelial system helps keep integrity of eNOS.
Without BH4, and it's proper recycling from BH4 back to BH4, oxidation and inflammation can leave the endothelial system in a Peroxynitrate (ONOO) loop, in which Martin Hall calls this NO/ONOO cycle, and when he came out with this research I don't believe he understood the full pathology.
This is the reason why the amino acid citrulline works so much better than arginine in creating a vasodilative effect (there are MAJOR downsides to using nitric oxide boosters, which I discuss in the oral microbiome section).
Like I said earlier, nitrites are an essential cofactor and created in the nasal epithelium and the oral microbiome.
I will talk about the oral microbiome a little bit later.
Boosting Nitric Oxide Naturally
I wrote a song that you can hum to that will help your nasal epithelium create more nitric oxide naturally.
The song is the total length that the research shows and try to hit the derivative note. R R
Feel free to hum this as a (possible) adjunct to products like enovid.
If you hum this song right, you should feel your sphenoid bone vibrating your upper teeth.
It’s pretty cool.
Nasal Breathing
You must be a nasal breather.
It is paramount.
Mouth breathing increases your risk of oral diagnosis, as well as creating physical structural changes.
Snoring while asleep and sleeping with your mouth open is highly correlated with vascular issues.
Just saying.
If you can go to an ENT and check for a deviated septum, even if it requires minor fess, or working on techniques to make your nose breathing work better like mouth taping (closed) and nasal bridge taping (widening openings).
Be sure to rinse out your nose at least once a day.
You hopefully brush your teeth at least twice a day or after every meal.
So you should be doing that with your nose.
In order from least powerful to most powerful tools for sinus rinsing:
Neti Pot (easy to clean and uses only gravity)
Neil Med (can do some cool techniques with this like being upside down and I travel with this)
Nevage (this is good if you have congestion as it has a sucking mechanism for maxillary and ethmoid sinuses)
Sinupulse Elite (this is my favorite as it gets further to the sphenoid and frontal, but least portable)
Also, if you have congestion that's not from an acute bacteria, fungi, or virus, check your air quality.
Microbial VOCs are the biggest culprit I've found outside of IgE based allergies.
What pathologies are implicated with glycocalyx loss and Junction Dysfunction?
I'll just make this a list without further elucidation.
Maybe in the next edition and as more research comes out, I can explain all the mechanisms as to why.
Of course, I will for sure be speaking of this in terms of postal illness further below.
PEM
MCAS
Connective tissue disorders
POTS
Food intolerance, sickness behavior, fatigue and brain fog
FM
AIDS
T2D
Gestational diabetes
Low birth weight (ELBW) survivors
Acute Covid
Long Covid
AC/LC systemic inflammatory-reactive microvascular endotheliopathy (SIRME)
Cancer
Stroke
Epilepsy
Heart failure
Dengue
Kawasaki disease
Hypertension
Cognitive Impairment
Preeclampsia (a pregnancy-specific hypertensive disorder characterized by endothelial dysfunction and activation)
Angina
Systemic Sclerosis
Chronic Kidney Disease
Periodontal disease
Obesity (although in some case studies higher glycocalyx thickness)
Allergies
Sinus infections
Alzheimers
Parkinsons
Schizophrenia
Autism
What does a healthy glycocalyx look like vs an unhealthy one?
Here are a few diagrams:
left healthy, right unhealthy…
Uniquely, lectins bind specific carbohydrates and can be used to target GAGs within the eGlx. R
This is why Dr. Gundry promotes all of his lectin stuff for endotoxemia.
Endotoxemia is a hallmark of microsepsis, which we will discuss in a following post.
How about another pic?
Doesn’t look to fun, right?
What Makes Up the Glycocalyx?
Here’s a basic list: R
Sugars
Proteins
Lipids
Ok now more specifically:
Soluble proteoglycans like glycosominoglycans
Hyaluronan and hyaluronic acid
Heparin Sulfate
Albumin
Biomarkers for JD and Glycocalyx
The biomarkers I've been seeing for this are when inflammatory enzymes cleave (cut like scissors) the glycocalyx and are found freely in the blood.
Like for example MMP9.
Metallomatrix proteins (MMPs) cut off the the glycocalyx, which is necessary for tight junctions to open up for immune cells or platelets to be able to get into tissue.
It's essential.
What is not essential is being stuck like that.
Anyway back to mmp9 is big in the shoemaker mold CIRS community.
I used to have a very high levels of mmp9, and now it makes sense as to why it would be a relevant biomarker to assess inflammatory states, glycocalox loss, and junction widening.
Other biomarkers for Glycocalyx Loss and Thus Junction Dysfunction
Here is a basic list of other biomarkers (if you’ve been labeled as CIRS, you can see why it’s BS, IMO):
Lp(a)
TMAO
OxLDL
Fibronigen
Lipoprotein Phospholipase A2
ANGPT1
VEGFa
CCR7
CD56
TGF-B1
HIF1a
EP/p300
P-Selectin
Endothelin-1
Syndecan-1
I have like 30+ other biomarkers in my notes, but it’s sooooo long and hard to test for.
Albumin is a protein that the super easy to test and can show you the tissue pressure gradient between the plasma, tissue, and lymph - your general practitioner can order this in a CMP.
I’ll make a post in the future about how simple this biomarker works for gradient dysfunction via tight junctions, if you can’t guess yourself currently. :)
Imaging the Glycocalyx
There are some neat imaging testing methods being developed right now for looking at the endothelial glycocalyx.
One is called the glycocheck and its instruments are noninvasive.
Essentially it's measuring the glycocalyx hair thickness (pretty neat, right?)
They studying with it at some hospitals, research facilities, and universities.