On that note, calling exertion crashes Post Exertional Malaise is like saying a person with a severe peanut allergy having a reaction after eating peanuts is experiencing "meal-induced discomfort."
No wonder nobody takes it seriously.
Too early to know if it's just a random good week but I haven't felt this good for so long in a long time. I have continued pacing and acting as if I'm just as sick as ever, but I feel... normal. Ironically just after getting hit hard by a 3 week cold.
What's different recently for me:
Things less recent but still more recent-ish (new in the last 3 months):
Longer term:
I've been taking a few drugs (Zyrtec, LDN) and very large list of supplements (won't list them all but EPA/DHA/DPA combo, NAC, Liposomal C, and Vitamin D are all in the list and relatively uncontroversial). I pace carefully, I keep as active as I can without approaching the PEM threshold, I drink a huge amount of water with salt and electrolytes (no B6!), I am eternally optimistic and positive.
My theory:
I feel that Long Covid is a self-sustaining state that we get into like a ball that rolls to the bottom of a hill. Health is also a self-sustaining state, but it's a different hill. It takes a lot of work to push the ball up over the hill. For us, Covid pushed us over the hill and we left the health minimum to the Long Covid minimum. I don't think any one thing can push you back over the hill (pending a major scientific discovery), but if you push with enough things at once, I believe it's possible to get over that hill and settle back into the self-sustaining local minimum of good health. Hope that's what has happened for me! If I feel good for another 2 weeks I'm going to try exerting myself/ exercising.
I've been going deep down a rabbit hole that started with the benefits of Nitric Oxide. Nitric Oxide is this miraculous molecule with all sorts of benefits. However, it can backfire when you are under oxidative stress because it binds with Superoxide to form Peroxynitrite which is very very bad for you.
This led me to understanding the role of eNOS, which are basically Nitric Oxide building machines that can easily malfunction, and when they malfunction ("uncouple"), they produce dangerous Superoxide. As you age, the average ratio of coupled/uncoupled NOS decreases from 100%. By age 40, it's down to 50% for the average American. It really seems like a key component of youthfulness.
We have solid information about what causes eNOS to malfunction, including:
* Sugar
* AGEs (Advanced glycation end products from overheating some types of oils)
* Sedentary lifestyle
* Hypertension
* Obesity
* Inflammation / cytokines
* Poor sleep
* Aging
The problem is that once an eNOS is uncoupled for any reason, it basically begins a self-destructive death spiral. It fails to produce an Oxygen linked to a Nitrogen (Nitric Oxide) and just produces an Oxygen linked to an Oxygen (Superoxide) which very easily forms into the even more destructive Peroxynitrite which causes widespread havoc, but one of the seemingly small things it does is it converts BH4 into BH2. This matters because eNOS uses BH4, but it can just as easily use a BH2 instead, and when it uses a BH2 instead of a BH4, the eNOS malfunctions and produces Superoxide, which perpetuates the cycle.
So it really makes sense why the older you get, the more of your eNOS are uncoupled: this process is incredibly difficult to reverse! Having more eNOS uncoupled means constant inflammation, rising blood pressure, cognitive decline, fatigue, insulin problems, slower healing from injuries and wounds, worse sleep, worse libido, plus all the diseases that can be caused by Peroxynitrite (cardiovascular diseases, neurodegenerative diseases, inflammatory diseases, metabolic disorders, lung dysfunction, renal failure, cancer...).
Basically BH2 is the devil. And the devil tempts eNOS into becoming evil. When eNOS is good, it produces Nitric Oxide, the angels of youth. But when it is evil, it produces the demons of aging: Superoxide, Peroxynitrite, and more BH2!
So I spent months researching how to improve BH4 and eliminate BH2. I went through a lot of crazy ideas and also real treatments in use today, but it's amazing how balanced the system is. It felt like no matter what you do, your body will always regress to the default state.
The breakthrough I had was when I realized I was barking up the wrong tree. If you were to use a transporter from Star Trek and perfectly teleport every single BH2 molecule out of your system and replace it with a perfect BH4 molecule, you'd be back to the old ratio within hours.
Even though eNOS determines a lot of your health, eNOS itself is defined by the complex environment of your body, which includes the eNOS coupled/uncoupled and BH4/BH2 ratio, but also stress, NOX, dysfunctional mitochondria, Xanthine Oxidase, and more.
The solution to all of this is unsatisfying: exercise, eat well, etc... all the stuff you already know that everyone always says makes you healthy. But this isn't an option for me because I have ME/CFS and exercise triggers PEM crashes which create long-term systemic damage. So I kept digging and finally discovered SGLT2 inhibitors and Metformin, which have really amazing ability to give you the benefits of exercise and stop the cycle of oxidative stress, reduce NOX, repair mitochondria and most important of all: restore your ratio of coupled eNOS.
Both SLGT2 inhibitors and Metformin have incredible benefits:
Metformin is unique in that it also upregulates DHFR, which recycles BH2 into BH4.
So to put it short: they’re miraculous for fixing your eNOS and getting your system into a state that can maintain that healthy eNOS.
I don’t think that the solution is to be on Metformin permanently. There are some downsides to being on Metformin. But I think it’s possible to put together a plan to carefully take Metformin for a period and then support your system to lock in the changes and get a long-lasting reset.
My personal goal with this is to develop a protocol to restore my eNOS and get myself to a state where I can exercise again (basically: I want to open up a window where I’m cured, if only temporarily, of ME/CFS). Then I will hit the health metrics hard to try to make it last as long as possible, and maybe even get out of it.
But I think you all will be interested in this even without ME/CFS, because if it works, it’s essentially setting your biological clock back a number of years. I’m having a hard time finding physicians willing to listen to my hours of meticulous biological mechanisms and get on board with this theoretical treatment protocol. So I’m hoping that this community will help me validate the theory, raise safety concerns, and identify a testing protocol to validate the health gains as well as to identify potential problems e.g. kidney damage.
What I have today (and will share in future posts if there’s interest) is a detailed explanation of what Metformin does, a 4 phase plan for what to do to support Metformin during and after, and a testing protocol to validate benefits and check for problems.
If you’re interested in joining me on this journey, here are some topics that you might want to read up on:
Very odd sensation, but last night I couldn't sleep due to an RLS feeling centered on my heart.
I've had leg RLS years, but never anywhere else. This was so strange.