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Nitric Oxide signalling pathway

nitric oxide pde5 inos enos nnos memory pfs finasteride accutane nadph

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#1 userCK

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Posted 14 January 2021 - 06:04 PM


Folks, I've been suffering from what's known as Post Finasteride Syndrome since age 32 (6+ years now). It really just happened overnight. No cure for the root cause so in absence of that, the best I can do is treat my symptoms. Some:

 

  • Insomnia, Fatigue, Buzzed/Wired feeling all day -> under control with Thyroid med (Levothyroxine)
  • Elevated Bad Cholesterol -> under control with statins but I actually just try to control it with diet/exercise
  • Elevated Blood sugar -> under control with Metaformin but I skip it several times a week, prefer to control blood sugar with intermittent fasting + exercise

These 3 approaches have allowed me to function day to day. However, there are 2 more aspects that I'm trying to fix and have not successed.

 

1. Sexual anhedonia and non-responsiveness to Cialis/Viagra/PDE5 inhibitors. Before PFS, I could take 5mg of Cialis and be good for 3-4 days. It worked really really well. All of a sudden (after taking Finasteride), body stopped responding. It seems to me that brain-penis connection is missing. The signaling is lost.

 

Upon closer analysis, it seems to me that brain -> nitric oxide signaling is missing. Normally, when you take Cialis/Viagara or L-Arg/L-Citrulline etc - your veins pop-out, you can feel a bit of fullness. But now, nothing happens. It's not just that penis doesn't respond to Cialis/Viagra. It's like even veins in my arms, wrist don't pop-out. It's like whatever is suppose to release nitric oxide no longer releases nitric oxide.

 

 

Does anyone know how to re-establish brain nitric oxide signaling? Can NAD/NMN/NR help? See the diagram/picture attached, right most, it mentions NADH, seems like it has a role to play.

Attached File  Screen Shot 2021-01-14 at 7.37.44 PM.png   644.14KB   0 downloads

 

 

Source (with more info)https://www.abcam.co...n-and-apoptosis

 

2. Other aspect is that my short-term/working memory seems to be declining like crazy. Overall memory has declined but short-term has declined even more. I have started taking Bacopa (Synapsa) and hoping it'd help.

 


Edited by userCK, 14 January 2021 - 06:19 PM.


#2 zorba990

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Posted 15 January 2021 - 12:04 AM

If this were me I would try Citrulline with Glutathione with Exercise.

based on this study:
https://www.nutraing...ost-blood-flow#
https://jissn.biomed...2970-015-0086-7

" Kyowa's Todd added that the study shows that Setria may play an important role in extending the life span for NO, probably due to protection against reactive oxygen species (ROS), and this is important because there are currently no products that extend the life span for NO.

"The combination of L-Citrulline plus Setria is very effective strategy for the long lasting benefit of enhancing blood NO levels following the resistance exercise,"​ she said.
"


Some people don't react well to glutathione directly and need to use NAC as a precursor instead. Just my observation of people trying it.
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#3 userCK

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Posted 15 January 2021 - 09:15 AM

If this were me I would try Citrulline with Glutathione with Exercise.

based on this study:
https://www.nutraing...ost-blood-flow#
https://jissn.biomed...2970-015-0086-7

" Kyowa's Todd added that the study shows that Setria may play an important role in extending the life span for NO, probably due to protection against reactive oxygen species (ROS), and this is important because there are currently no products that extend the life span for NO.

"The combination of L-Citrulline plus Setria is very effective strategy for the long lasting benefit of enhancing blood NO levels following the resistance exercise,"​ she said.
"


Some people don't react well to glutathione directly and need to use NAC as a precursor instead. Just my observation of people trying it.

Interesting. I've already tried L-Citrulline and Liposomal Glutathione but not NAC. I will try that combination.

 

That said, I am not sure if the problem is there is no nitric oxide in my body (If there wasn't, wouldn't I be already dead? arteries would have constricted!) but the problem seems to be that brain is not sending signal to produce more NO when required. So, there is some disconnection somewhere. 

 

When I look at the Nitric Oxide signaling pathway - so many enzymes are involved, I am at loss where to begin. 

 

Thanks for your reply :)



#4 zorba990

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Posted 16 January 2021 - 10:15 PM

Interesting. I've already tried L-Citrulline and Liposomal Glutathione but not NAC. I will try that combination.

That said, I am not sure if the problem is there is no nitric oxide in my body (If there wasn't, wouldn't I be already dead? arteries would have constricted!) but the problem seems to be that brain is not sending signal to produce more NO when required. So, there is some disconnection somewhere.

When I look at the Nitric Oxide signaling pathway - so many enzymes are involved, I am at loss where to begin.

Thanks for your reply :)


You may also wish to look into your methylation situation.

https://www.ncbi.nlm...les/PMC5155615/
Role of folic acid in nitric oxide bioavailability and vascular endothelial function

"Abstract
Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk.

Keywords: endothelial function, folic acid, 5-methyl tetrahydrofolate, nitric oxide


......


CONCLUSION
Bioavailable folates, primarily the circulating metabolite 5-MTHF, contribute to enhanced endothelial function by increasing NO bioavailability within the vascular endothelium. In patient populations in whom endothelial function is compromised, folic acid supplementation at ≥5 mg/d can effectively restore endothelium-dependent vasodilation, even in those who previously met the RDA of 400 µg/d for folate. There are two putative mechanism(s) by which bioavailable folate restores NO bioavailability: (1) increased NOS coupling, via direct interaction with the NOS dimer and/or increased availability of the essential NOS cofactor BH4; and (2) direct scavenging of deleterious reactive oxygen species, which preserves bioavailable NO. It remains unclear if, as previously thought, the homocysteine-lowering effect of folic acid supplementation directly benefits the endothelium; however, careful consideration of the literature suggests that simply lowering plasma homocysteine does not improve CVD outcomes and that higher daily doses (≥5 mg) of folic acid are required to confer endothelial benefits, even if they do not lower plasma homocysteine further. Further in vivo mechanistic research in humans will shed light on the specific role of folate in endothelial NO production and NO bioavailability, while clinical trials of daily folic acid doses ≥5 mg are essential for the assessment of folic acid supplementation as a viable long-term strategy for the prevention and treatment of endothelial dysfunction in CVD. Collectively, folic acid represents a well-tolerated and readily available potential treatment for endothelial dysfunction, which may translate to improved outcomes in patients with overt CVD and/or elevated CVD risk. Further clinical trials should help clarify the long-term efficacy of high-dose folate in the prevention and treatment of CVD."
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#5 userCK

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Posted 17 January 2021 - 12:18 AM

You may also wish to look into your methylation situation.

https://www.ncbi.nlm...les/PMC5155615/
Role of folic acid in nitric oxide bioavailability and vascular endothelial function

"Abstract
Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk.

Keywords: endothelial function, folic acid, 5-methyl tetrahydrofolate, nitric oxide


......


CONCLUSION
Bioavailable folates, primarily the circulating metabolite 5-MTHF, contribute to enhanced endothelial function by increasing NO bioavailability within the vascular endothelium. In patient populations in whom endothelial function is compromised, folic acid supplementation at ≥5 mg/d can effectively restore endothelium-dependent vasodilation, even in those who previously met the RDA of 400 µg/d for folate. There are two putative mechanism(s) by which bioavailable folate restores NO bioavailability: (1) increased NOS coupling, via direct interaction with the NOS dimer and/or increased availability of the essential NOS cofactor BH4; and (2) direct scavenging of deleterious reactive oxygen species, which preserves bioavailable NO. It remains unclear if, as previously thought, the homocysteine-lowering effect of folic acid supplementation directly benefits the endothelium; however, careful consideration of the literature suggests that simply lowering plasma homocysteine does not improve CVD outcomes and that higher daily doses (≥5 mg) of folic acid are required to confer endothelial benefits, even if they do not lower plasma homocysteine further. Further in vivo mechanistic research in humans will shed light on the specific role of folate in endothelial NO production and NO bioavailability, while clinical trials of daily folic acid doses ≥5 mg are essential for the assessment of folic acid supplementation as a viable long-term strategy for the prevention and treatment of endothelial dysfunction in CVD. Collectively, folic acid represents a well-tolerated and readily available potential treatment for endothelial dysfunction, which may translate to improved outcomes in patients with overt CVD and/or elevated CVD risk. Further clinical trials should help clarify the long-term efficacy of high-dose folate in the prevention and treatment of CVD."

 

 

Thanks. Unless I am confused about which versions of B Vitamins to take, I've been taking this One Elevated Double Strength & Most Bioactive Methyl Folate (see pictures attached) Is this not the right one? And when I got tested for B vitamins, I was in normal range.

Attached File  Screen Shot 2021-01-17 at 1.50.38 AM.png   235.05KB   0 downloadsAttached File  Screen Shot 2021-01-17 at 1.50.46 AM.png   353.28KB   0 downloads



#6 MikeDC

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Posted 14 February 2021 - 11:53 AM

https://sexualmed.or...al-dysfunction/

#7 MikeDC

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Posted 14 February 2021 - 11:55 AM

The dose of finasteride is too high. I have looked at dose response before . You only need to take 0.2mg to get good results. It will reduce side effects.

#8 MikeDC

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Posted 14 February 2021 - 12:02 PM

This study shows you get almost the same response with 0.2mg as 1mg and 5mg.





Also tagged with one or more of these keywords: nitric oxide, pde5, inos, enos, nnos, memory, pfs, finasteride, accutane, nadph

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