AGE, RAGE and Soluble RAGE
Ever listen to rage against the machine?
I think we’re the machine in this case, while RAGE acts against us… let me explain.
What Is RAGE?
Not aging…but it can lead to it.
Studies recently have shown that covid (spike) can also bind to and activate the Receptor for Advanced Glycation End-products (RAGE) receptor. R
Active rage is no fun, pun intended.
Well it's not all about active RAGE, but soluble RAGE (sRAGE).
sRAGE is formed when the RAGE receptor is free flowing in the blood after being bound by Advanced Glycation End-products (AGEs).
It's a balance and let's talk about it.
When AGEs bind to the RAGE receptor, AGEs cause more RAGE receptors to form and the binding action creates soluble RAGE (sRAGE).
sRAGE is very inflammatory, activating NF-kB which turns up inflammation leading to Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS).
ROS and RNS cause the endothelial glycocalyx to shed and as you know by now that causes endothelial inflammation. R
This shedding causes the tight junctions to open up (Junction Dysfunction) and block Nitric Oxide (NO) from being able to signal. R
So you could take NO boosters and it wouldn't help. :(
Covid, RAGE and Macrophages
As you may have guessed, sRAGE concentrations are elevated in COVID-19 patients as disease severity increases. R
In the absence of the “conventional” high-affinity receptors (like ACE2), lower-affinity receptors (like RAGE) might be hijacked by SARS-CoV-2 for internalization. R
Through RAGE, covid can infect monocytes and macrophages.
RAGE is a multi-ligand receptor recognizing several Damage-Associated Molecular Pattern (DAMP) molecules. R
DAMPs turn on TLR4 and thus open up tight junctions via the shedding of Metallo Matrix Proteins and Hyaluronidase (HA-ase) and other remodeling enzymes. R R
Let’s Talk More About AGEs
What are advanced glycation end products?
They are any protein or lipid that comes from oxidizing (called the maillard reaction) together with their sugar structures essentially. R
AGEs come from:
Smoked foods and smoking inhaleables
Processed foods like meats, cheeses
Frying foods like French fries, chips
BBQ-ing or grilling food
It's a big list I can update later but start with cutting out the processed, smoked, and fried crapola
Foods lower in AGEs:
Fresh meats
Fresh seafood
Fresh fruits and veggies
So don't oxidize your food at high heat or use dry heating methods.
How to Prepare Cooked Food
Don't worry, microwaving doesn't increase ages unless you do it for a long time (past 6 min). R
When preparing food, boiling or steaming them would be much better than broiling or baking.
Essentially you want to use lower temperatures that retain most of the moisture in your foods such as poaching, boiling, stewing, or steaming.
More on Hyperglycemia
Let's talk about spiking blood sugar.
Hyperglycemia has been shown to be responsible for altering sulfation patterns (of glycosominoglycans) and can prevent hyaluronan from binding to the glycocalyx. R R
Essentially high blood sugar makes it hard to grow back the glycocalyx. R
Ketosis, Fasting and Carnivore
Generally when rebuilding the gut I use this same technique, but it seems to work for the endothelial system as well.
Fasting for 2-3 days or higher if you can tolerate it.
Then from there go into a carnivore or healthy fat keto diet.
Carnivore is much softer on the gut and easier imo, while keto is more friendly to having a larger a variety of foods.
Fasting helps jumpstart the repair process of the glycocalyx, thus opening up the thrombosis of microcapillaries, and beta hydroxybutyrate (ketones) helps enhance the repair process by dampening the cleavage by MMPs.
If you don't have gut issues and choose keto, be sure your vegetables come from sulfurous and nitrate filled, low plant toxin ones.
Supplement on Low Carb Diets
If you go into ketosis or you go carnivore, you need to supplement with vitamins, minerals, and/or organ extracts.
Well water soluble vitamins can be taken every day as well as minerals, organ extracts and fat soluble vitamins need to be cyclically taken.
What I mean by this is taken one round (bottle) in the fall, one round in the winter, one round in the spring, and one round in the summer.
You can overdose on fat soluble vitamins if you supplement everyday all year long.
Nitrites and Sulfur in the Diet
Sulfur
Sulfur in the diet is simple to get through eggs and cruciferous vegetables.
It's also found in allium veggies, dairy products, nuts and seeds, legumes, most meats and seafoods, and most fruits.
I do not recommend getting it from dairy products, nuts and seeds, legumes, or fruits when you're still leaky, as they have lots of plant toxins that can enhance the leakiness via Toll-Like Receptors (TLRs).
Eggs will be best the least cooked as possible, such as poaching and not frying.
If you're going for raw eggs make sure to take them with an antiparasitic (code WrNETza8).
Cruciferous vegetables need to be cooked such as steaming to reduce their plant toxins.
Cruciferous vegetables (glucoraphanin) can synergize with myrosinase (for example, from mustard) to create an even greater effect on the antioxidant system creating sulforaphane.
I eat all my cruciferous vegetables with mustard.
If you react poorly to sulfur, it's necessary to take molybdenum and copper.
It’s paramount to stay away from plant toxins while you’re healing your gut, especially gluten.
Nitrates
Like we discussed in the Oral Microbiome section, it’s important once you glycocalyx is working well, to be feeding that oral microbiome with nitrates.
Dietary nitrates can be found in things like beets, celery, and leafy greens in general.