Could Antioxidant Regulation Play a Role in Endometriosis?

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Respond to this comment this idea that endometriosis is basically about stopping glycolysis and lowering estrogen and I understand why that sounds scientific and logical but this is linear thinking and this is when it gets a little bit dangerous because while yes endometriosis does show altered mitochondrial function it shifts towards glycolysis and hypoxia inducible factor one alpha helps this metabolic rewiring and also estrogen does matter but. This is where we kind of have to draw the line because when you start to look at that you're looking at one singular layer layer you can make the mistake of highlighting an adaptation as a root cause glycolysis may not be the beginning of the disease but it may be what the cell uses after it has already entered survival mode and endometriosis cells are not just metabolically broken they're actually metabolically plastic.

That means they can adapt they can survive they can shift fuel sources they know how to use low oxygen environments they know how to use inflammation to help themselves so this isn't so clear as just one thing we're not wanting to focus on just one switch alone the deeper question is why did that cell need glycolysis in. The first place because what was the driving hypoxic signal what was happening under this mitochondrial stress and what's happening to the iron and and this is kind of what I talk about in in my research where we're looking at something much much different because the reality is in the endometrial and then the endometrial like cell or an endometriotic cell facing a hostile environment once leaves the uterus this means low oxygen immune attacks low nutrients reactive oxygen species or oxidation where it should kill the cell but somehow it survives.

So if it survives the real question is not just how do we block one fuel pathway or how do we block one hormonal pathway the real question becomes how did it become so adaptable how did it learn how to survive in a place that it should have been destroyed and. This is where we start to look deeper into my hypothesis and I will be publishing that paper here soon the my framework argues that endometriosis may survive through selective redox survival so this is kind of what we're talking about right here it has enough Protection to avoid death specifically through systems antioxidant systems like GPX4 and SOD2 while still leaving enough oxidative signaling to become pathogenic like hypoxia inducible one factor inflammation blood vessel growth fibrosis so the lesion is not fully healthy but it's also not fully collapsing and.

This is where it becomes super dangerous when it's living right there in the middle ground because it's it's still activated because of this pathological signaling but is still protected it's a sweet spot for a disease mitochondria on this condition that is endometriosis is not just glycolysis is not just energy the mitochondria can actually use the pent pentose pathway pentose phosphate pathway to create building blocks of the mitochondria it's not just glycolysis and and if you can squeeze it hard enough medical term here I guess if you want us to call it that if you can put enough pressure to the mitochondria and try to starve it of glycolysis it can actually re adapt to oxidative phosphorylation or.

In other words use oxygen to create energy and we've seen that there's medical literature that talks about that so. This is why it's incomplete it's not a just a two switch disease estrogen is also not the problem because if that were the case birth control or Alyssa all of these hormonal therapies would have worked for the majority of women we don't see that to be the case if anything we see that you can turn the estrogen down but the disease keeps going the pathology is still there you're just turning down the symptoms so the problem is not estrogen existing the problem is there's broken machinery that learns how to use estrogen pathologically it's a disease that learns how to use energy pathologically so endometriosis lesions can produce local estrogen but estrogen's not the problem they can increase inflammatory messaging through Cox two PG two they can become estrogen receptor beta beta bias they will lose progesterone response so there's multiple shifts going on in my redox fear we're talking about got a 2 and got a 6 where got a 2 becomes hypermethylated so it becomes shut off and got a 6 becomes hypomethylated so it be basically becomes on and this machinery becomes a weapon for estrogen because it's not just using estrogen to just function normally it's gonna use it to kick start an inflammatory loop and we can look deeper into here but this might be too much and too long for this video but it's a multi step process is not just a singular pathway so again it's a very good statement if we focus on glycolysis and estrogen but the bigger question should be why is that cell adapting why is it just past glycolysis why is it just past estrogen.

So when I release my paper I'll let you guys know but for right now this is this is something that we do need to address it's not just a one to switch disease it's metabolic is vascular it's immune it's a network and that's kind of what we can see here. So let's focus on that and not just simple solution.