New idea about our condition

Therapeutic Efforts
#1

I was stumbling upon a blogger who is quite knowledgeable about the male body.

Anyways, all this reading has made me come to a hypothesis that our condition is caused by excessive damage by our own body, mainly superoxide and ROS. These inflammatory markers are healthy in moderation but excess can cause damage to our brain, enzymes, blood vessels etc. We may overlook it because we are young and think that this damage shouldn’t effect us now, but it can happen at any age.

I have done my genetic test and I have a gene that causes IL-6 to be over-expressed, which increases superoxide. Many of you may also share this genetic trait.

Allow me to go into how ROS/inflammation may be what caused our problems.

  1. NADPH oxidase is an enzyme that creates superoxide (damaging molecule). It requires NADPH, a molecule that is responsible for creating allopregnanolone from 5DHP (Allo is a neurosteroid we have very little of).

  2. NADPH oxidase causes an inflammatory state which will cause an enzyme Arginase to be up regulated. This enzyme competes with Nitric Oxide Synthase (NOS) for arginine as they use the same substrate. NOS is what causes erections, so if Arginase is taking away arginine from NOS due to the upregulation by inflammation, nitric oxide will not be produced. This explains why perfectly healthy guys are getting ED. In fact, arginase activity is associated with CVD and many other diseases. To inhibit arginase, you can use Ornithine, citrulline, coffee, tongkat ali and/or rhubarb. Ornithine works well for me on an empty stomach.

  3. NADPH oxidase is the next enzyme that needs to be inhibited. It is stimulated by inflammatory markers like IL6 and TNF alpha, alcohol, excessive body fat and glucose. Inhibitors of NADPH oxidase are nitric oxide (cialis) and apocynin (found in kutki/picrorhiza kurroa) and a ketogenic diet, likely because of BHB and butyrate.

  4. Big scavengers of ROS/superoxide are upregulated on a ketogenic diet and fasting or both (exercise as well). The ketones actually reactivate silenced antioxidant genes by inhibiting HDACS. Niacin seems to be a great supplement as it also blocks ROS and supplies NAD for NADPH.

  5. With NADPH oxidase inhibited, it will allow for more NADPH to be used in the conversion of 5DHP into Allo.

TLDR, my thoughts on fixing PFS:

  1. Inhibit NADPH oxidase to reduce inflammation and also Arginase
  2. Do this by getting into a ketogenic state via fasting or exercise or both to inhibit NADPH oxidase and arginase. Exercise also upregulates ROS scavenging enzymes such as superoxide dismutase (SOD).
  3. Supplements to help is BHB, Kutki, niacin, ornithine, coffee, rhubarb, tongkat ali, cialis (only when arginase is inhibited)

Let me know what you guys think on my superoxide inflammation theory.

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#2

One would expect such a kind of effect to cause a slow, gradual worsening of symptoms.
This is often not the case. For instance, myself as well as many others had an instant ‘crash’ which made us worse within a day or so, and it has remained that way for years.

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#3

Hello, I have very similiar theory that what is leading to this proposed cascade of ROS/Inflammation is mitochondrial damage. SSRI’s were already confirmed to be able to do this, my guess is Finasteride does this too. Check out my thread on PSSD forum: https://pssdforum.org/viewtopic.php?f=22&t=3886

You said ketogenic diet / BHB, this might not be enough to fix excessive ROS, I’m looking into peptides like SS-31 which are very expensive unfortunately. There is also other mitochondrial targeted antioxidants like MitoQ or SkQ1 but Ss-31 looks more promising.

There is also a exegoneus BHB analogue coming out in a few months which looks interesting:

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(Taken from keto.swiss)

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#4

I got PSSD from first from Trazodone and then Venlafaxine withdrawal. I’ve particularly looked at what happens in Venlafaxine withdrawal:

First, Venlafaxine was confirmed to be able to damage the mitochondria: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241410/

Then, Venlafaxine is an opioid and also a NMDA antagonist: https://www.martincwiner.com/venlafaxine-tramadol-and-tapentadol-are-all-opioids/

What happens when you withdraw from Venlafaxine? Opioid withdrawal / excess glutamate will lead to a inflammatory/oxidative cascade which damages the mitochondrial membrane. Excess ROS -> oxidative stress -> neuroinflammation -> low allopregnanolone -> all symptoms are downstream of that. Thats my hypothesis.

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#5

Yet you believe this cascade could be caused by a person taking a single quarter-dose of a pill of Finasteride? And why is only a very small subset of the population so severely impacted?

#6

My PSSD was triggered by a few quarters of trazodone. I suspect we are genetically vulnerable, plus taking this in a high cortisol state would probably further contribute to this.


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#7

My understanding of the biological processes involved isn’t sophisticated enough to be able to give a reasoned reply I’m afraid.

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#8

You had my attention. Plausible hypothesis indeed. I’ve started all of this assuming it was merely an issue with hormonal imbalances (T;E2; DHT, etc.). I now see it as an issue with systemic inflammation. My over simplified explanation is that these drugs (Fin; SSRIs; Accut, etc.) may lead to some sort of damage to cells or induce a shift to gut microbiome. Guess what’s the body response to such damage? Yep inflammation.

Chronic inflammation can wreak havoc to all body systems and adrenals takes the biggest hit. They respond by releasing stress hormones to counter inflammation and this results in issues with blood sugar, maldigestion and even lower sex hormones. I’ve been working with this theory for over 2 years and the improvements are incremental. I think some people are lucky enough that damage isn’t severe. Body can usually bounce back given the “right environment”.

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#9

So how can we diagnose if we have gut microbiome change?

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#10

It is known that DHT inhibition will upregulate IL6. When this happens our body produces oxidative damage via increased NADPH oxidase. If our body is naturally high in IL6 like me, it will cause severe damage. This is likely why not everyone who takes fin gets PFS, because there is a genetic predisposition.

Additionally, many of us have tested our DHT and it is through the roof now. I suspect it is to compensate for the high IL6 chronically. A sign of high DHT is poor wound healing.

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#11

What you suggest to test? I can test IL-1beta , IL-6, IL-8, IL-10, IL-12, TNF-alfa, gut microbiome. What else?

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#12

Thank god we got some smart people on this forum, cause I don’t understamd anything that is being said here :sweat_smile:

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#13

I don’t think fasting / BHB is enough to scavenge ROS, many people have tried this from what I know.

#14

I do believe it is the best way to inhibit NADPH oxidase and reactivate antioxidant genes. It’s important to do keto properly by not consuming poly fats as these create ROS and defeat the purpose. You need to consume saturated fats and do serious fasting and exercise.

I think the people who do keto and don’t get results are doing it wrong because they aren’t producing enough BHB and consuming polys.

Losing body fat is important to inhibit NADPH oxidase as fat cells produce inflammatory cytokine as well.

The substance you mentioned seems promising I have yet to research it myself. Let me know when you get it, it’s damn expensive though.

The only other substances I know that can inhibit NADPH oxidase is NO and apocynin found in kutki. I am trying to find kutki to add to my protocol.

#15

It is expensive and I’m planning on running a 1 month trial, then 3 months.

What do you think of the company I showed you, I think their product looks interesting too.

I will most likely combine your strategy and running the peptide.

1 Like
#16

Hey man what about we try those things together? Are they helpful for mental sides? Could you tell me the price for peptides and the this other thing, it is kutki or something else?

#17

Tried to reply to you and something went wrong.

Hey man what about we try those things together? Are they helpful for mental sides? Could you tell me the price for peptides and the this other thing, it is kutki or something else?

#18

My biggest concern is that the excess ROS lead to DNA damage…

#19

Not to my knowledge.

#20

please test these cytokines and report back! I am also interested in testing these as my theory is Th1/Th2 imbalance.