Methylation Cycle and The P450 Systems

mariovitali · May 25, 2018, 7:52am

Update : I had another crash because i was not careful. I took DIM (wanting to boost Phase I and Phase II detox) which is a DHT inhibitor. The crash had the usual side effects : Low Libido, no erections,negative thoughts and not good sleep quality.

I believe that i am close in finding the final remaining culprit which -in my case- is Cortisol production. It might also be the case that i have high 11-beta-hydroxysteroid-dehydrogenase activity which changes the effect that cortisol has to your body (even though if Cortisol level is normal) and also makes you fat. I have pronounced fat specifically on the waist line.

I’ve also read that Barometric pressure changes raise/lower Cortisol production. Believe it or not, upon waking i know exactly what happened during the night in terms of Barometric pressure. My girlfriend believes me now after numerous trials : If upon waking i do not have oily skin then that means that Barometric pressure had a downward trend during the night. If OTOH i have oily skin then i know that during the night baro pressure was either steady or rising. So I am beginning a regimen to lower Cortisol ASAP (Induction of Growth Hormone, Holy Basil Extract, Polymethoxylated Flavonoids, Sugar Elimination and Shed fat from waist line).

mariovitali · May 25, 2018, 7:53am

It seems that DHT inhibitors are everywhere. I researched Holy Basil (which contains Ursolic Acid). I then found the following entry at PubMed

So Holy Basil should be also added to the list of DHT Inhibitors.

DerProfessor · May 25, 2018, 7:53am

Mario, I apologise if I’m asking something you have already outlined in this thread.

But just how severe was your erectile dysfunction BEFORE the methylation protocol?

Can you give a % for before and after? And also for where you are now? That would be very useful. I am about to embark on the methylation protocol myself.

spstriken · May 25, 2018, 7:53am

I put a study here long ago that DIM is not good also broccoli is not good.I don’t remember the exact mechanism but the study said Broccoli or DIM first reduce your estrogen but then some how you end up with more Estrogen. I used to drink broccoli juice but I felt the exactly the way the study described so I stopped it. The study suggested using TMG instead.

thinksteroids.com/community/thr … 134236632/

ok here I found my own post
viewtopic.php?f=6&t=3295&p=19087&hilit=TMG#p19087

mariovitali · May 25, 2018, 7:53am

I would have days with very good erections and some days i couldn’t have an erection at all. The Methylation protocol gave me a minor boost but mainly it significantly attenuated Brain Fog and Insomnia and my Emotional well-being.

Actually this is the reason that i felt that something is missing with the plain methylation Theory. What drastically changed my erections quality is when i boosted P450 through diet and avoidance of specific substances that inhibit these enzymes.

depressedguy · May 25, 2018, 7:53am

mariovitali:

Hey Guys,

For those who haven’t seen this : ncbi.nlm.nih.gov/pmc/articles/PMC4064044/

The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression
We wish to point out from the outset that 5α-RI therapy was FDA-approved for treatment for LUTS related to BPH. Treatment of symptomatic men with finasteride or dutasteride results in approximately 17%-19% reduction in prostate volume, thus alleviating urinary tract symptoms [8,13,14,53]. Furthermore, 5α-RI therapy reduces urinary tract infection and minimizes the risk of potential acute urinary retention and the need for surgical intervention related to BPH. These positive effects of finasteride and dutasteride contribute to improvement in the quality of life in men suffering from BPH symptoms [8,53]. However, a substantial body of evidence exists which points to serious and potentially ill-health effects of 5α-RIs’ therapy. These include loss or reduced libido, erectile dysfunction, orgasmic and ejaculatory dysfunction (Table 2) [99], development of high grade PCa tumors (Fig. 4), potential negative cardiovascular events, and depression. The side effects are potentially harmful in some individuals and in young men may be persistent or irreversible [100].

We also know that 5-AR has neuroprotective effects :

Neuroactive steroids elicit important neuroprotective effects during trauma and injury to the central nervous system [75]. AP is shown to be beneficial in the treatment of traumatic brain injury, attenuating edema, trauma, stress, inflammation, apoptosis, and reducing oxidative stress [76,77,78]. AP is not only a protective agent in ischemia, but also in maintaining blood brain barrier integrity, and in memory and learning [78,79,80,81]. Studies on CNS injury in which asphyxiation was induced in fetal sheep to stimulate neurological stressors, in the presence or absence of finasteride, showed an increase in apoptotic cell death in the cerebellum and hippocampus in the animals treated with finasteride (Fig. 5) [82]. Furthermore, treatment with an AP analogue, alfaxalone, prevented cell death as assessed by the increase in activity of caspace-3 and expression of ki-67 protein. This observation suggests that AP exerts a neuroprotective role in the brain, which is inhibited by finasteride.

So we have to keep in mind that we should also look at possible peripheral neuropathy due to less Pregnenolone production. Since i am one of the oldest users of Finasteride here (took it back to 1998 for the first time) i can definitely say that there has been neuronal damage. Although MRI did not show anything on my spinal cord, i believe that damage has been made.

What worries me is the fact that whenever i take a GABA Agonist (Taurine, Phospahtidylserine) and GABA itself, i got anorgasmia. Searching for answers i came up with this study :

Anorgasmia with gabapentin may be common in older patients.

ncbi.nlm.nih.gov/pubmed/21602106

Notice that older patients are involved. I did search for more entries for anorgasmia+GABA in young patients and found some entries. Recall also that it takes me quite some time to have an erection which is typically seen in older people.

I am sure that some damage has been made and i do not know if this is reversible. What protects neuronal health :

-Estradiol
-Creatine
-Phosphatidylserine (GABA Agonist)
-Taurine (GABA Agonist)
-GABA
-Progesterone
-Retinoic Acid
-Acetyl-L-Carnitine
-Lion’s Mane
-Forskolin

I will add to my regimen Acetyl-L-Carnitine and Lion’s Mane. It will take at least one month and up to 3 months for some results to be seen. There is a possibility that i will get anorgasmia from this regimen but i am willing to try. My girlfriend is supporting me through all this, which is great. In case that there is a reversal of problems i will know and -as always- will report back.

Do you think harvard study will show if there is a neuropathy?

mariovitali · May 25, 2018, 7:53am

depressedguy:

mariovitali:

Hey Guys,

For those who haven’t seen this : ncbi.nlm.nih.gov/pmc/articles/PMC4064044/

The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression
We wish to point out from the outset that 5α-RI therapy was FDA-approved for treatment for LUTS related to BPH. Treatment of symptomatic men with finasteride or dutasteride results in approximately 17%-19% reduction in prostate volume, thus alleviating urinary tract symptoms [8,13,14,53]. Furthermore, 5α-RI therapy reduces urinary tract infection and minimizes the risk of potential acute urinary retention and the need for surgical intervention related to BPH. These positive effects of finasteride and dutasteride contribute to improvement in the quality of life in men suffering from BPH symptoms [8,53]. However, a substantial body of evidence exists which points to serious and potentially ill-health effects of 5α-RIs’ therapy. These include loss or reduced libido, erectile dysfunction, orgasmic and ejaculatory dysfunction (Table 2) [99], development of high grade PCa tumors (Fig. 4), potential negative cardiovascular events, and depression. The side effects are potentially harmful in some individuals and in young men may be persistent or irreversible [100].

We also know that 5-AR has neuroprotective effects :

Neuroactive steroids elicit important neuroprotective effects during trauma and injury to the central nervous system [75]. AP is shown to be beneficial in the treatment of traumatic brain injury, attenuating edema, trauma, stress, inflammation, apoptosis, and reducing oxidative stress [76,77,78]. AP is not only a protective agent in ischemia, but also in maintaining blood brain barrier integrity, and in memory and learning [78,79,80,81]. Studies on CNS injury in which asphyxiation was induced in fetal sheep to stimulate neurological stressors, in the presence or absence of finasteride, showed an increase in apoptotic cell death in the cerebellum and hippocampus in the animals treated with finasteride (Fig. 5) [82]. Furthermore, treatment with an AP analogue, alfaxalone, prevented cell death as assessed by the increase in activity of caspace-3 and expression of ki-67 protein. This observation suggests that AP exerts a neuroprotective role in the brain, which is inhibited by finasteride.

So we have to keep in mind that we should also look at possible peripheral neuropathy due to less Pregnenolone production. Since i am one of the oldest users of Finasteride here (took it back to 1998 for the first time) i can definitely say that there has been neuronal damage. Although MRI did not show anything on my spinal cord, i believe that damage has been made.

What worries me is the fact that whenever i take a GABA Agonist (Taurine, Phospahtidylserine) and GABA itself, i got anorgasmia. Searching for answers i came up with this study :

Anorgasmia with gabapentin may be common in older patients.

ncbi.nlm.nih.gov/pubmed/21602106

Notice that older patients are involved. I did search for more entries for anorgasmia+GABA in young patients and found some entries. Recall also that it takes me quite some time to have an erection which is typically seen in older people.

I am sure that some damage has been made and i do not know if this is reversible. What protects neuronal health :

-Estradiol
-Creatine
-Phosphatidylserine (GABA Agonist)
-Taurine (GABA Agonist)
-GABA
-Progesterone
-Retinoic Acid
-Acetyl-L-Carnitine
-Lion’s Mane
-Forskolin

I will add to my regimen Acetyl-L-Carnitine and Lion’s Mane. It will take at least one month and up to 3 months for some results to be seen. There is a possibility that i will get anorgasmia from this regimen but i am willing to try. My girlfriend is supporting me through all this, which is great. In case that there is a reversal of problems i will know and -as always- will report back.

Do you think harvard study will show if there is a neuropathy?

Probably this will sound arrogant but i do not care what any study will show. I am certain that there has been neuronal degeneration and/or excitotoxicity involved due to impaired neurosteroid production :

When i hit my funny bone, the “electric shock” sensation is 50% of what it used to be.
Need for increased stimulation to achieve an erection
I could feel the signal sent by my brain to initiate an erection (i know it sounds crazy but trust me) and this signal slowly kept becoming less and less intense (within about 1.5 year). Now it is completely gone. Nothing there. Search my posts about this.

So when i say that i will know if Lions Mane / ALCAR works, hopefully there will be improvement to all the above. Let’s keep our fingers crossed.

PS : When i discussed the 3 points shown above to my neurologist, he just smiled. Bottom Line : I know how i feel because i know my body more than anyone else.

spstriken · May 25, 2018, 7:53am

"Although MRI did not show anything on my spinal cord, i believe that damage has been made. "
was it simple MRI? I have seen pictures of brain damage caused by Accutane but not simple MRI but through PET Scan. have you done pat scan?
propeciahelp.com/forum/viewt … f=9&t=7435

also I read GingKo Biloba is very good at brain reparing brain damage. what is your opinion/experience about it?

mariovitali · May 25, 2018, 7:53am

Hmm Good Point, it was simple MRI. Will try to see if i can have a PET Scan where i am located.

Ginkgo Biloba appears to be good but i see conflicting reports of being a CYP3A4 inhibitor.I’ve never used it. It is a potent PXR inducer which is good in our case. So i’d say that it might be a good candidate to test.

Basically, before buying a supplement one should research if :

-it inhibits P450
-Causes excitotoxicity
-It Is an Anti-androgen/DHT inhibitor
-it Raises Cortisol

I am preparing a rather large mind-map with all the research i have done which includes pros and cons for many supplements . I will post it soon.

depressedguy · May 25, 2018, 7:53am

mariovitali:

spstriken:

"Although MRI did not show anything on my spinal cord, i believe that damage has been made. "
was it simple MRI? I have seen pictures of brain damage caused by Accutane but not simple MRI but through PET Scan. have you done pat scan?
viewtopic.php?f=9&t=7435

also I read GingKo Biloba is very good at brain reparing brain damage. what is your opinion/experience about it?

Hmm Good Point, it was simple MRI. Will try to see if i can have a PET Scan where i am located.

Ginkgo Biloba appears to be good but i see conflicting reports of being a CYP3A4 inhibitor.I’ve never used it. It is a potent PXR inducer which is good in our case. So i’d say that it might be a good candidate to test.

Basically, before buying a supplement one should research if :

-it inhibits P450
-Causes excitotoxicity
-It Is an Anti-androgen/DHT inhibitor
-it Raises Cortisol

I am preparing a rather large mind-map with all the research i have done which includes pros and cons for many supplements . I will post it soon.

Mario, if i remember correctly, you mentioned you have demyelination on your somewhere or do i remember wrong?

mariovitali · May 25, 2018, 7:53am

That is correct. They found regions in my brain with demyelination however the neurologist said that this is in an area of the brain which is asymptomatic. I had a new MRI after 8 months which showed no progression on the lesions. He also dismissed me from talking to him about Finasteride and the implications of its usage to key Neurosteroids.

I had also a Spine MRI which showed no demyelination. However i do not know if PET should have been used instead as sprstriken said.

Nevertheless, I know there is something wrong going on.

mariovitali · May 25, 2018, 7:53am

I am posting the Mind-map with my notes on PFS. Some key points :

Notice what D-Limonene does. I think this is a very interesting compound with a lot of benefits. Please also read what Vitamin K2 achieves.
Some branches are not expanded since i am working on them.
Of particular importance could be the “Mito-cocktail” regimen. I believe that ENADA NADH+D-Ribose are very important. If anyone is taking/trying the Mito cocktail please let me know how you are doing.

I will post an update next week.

Mario

spstriken · May 25, 2018, 7:54am

mariovitali
what is your experience with Ginkgo Biloba? I read a lot of info singing the praise for it.
for example
ncbi.nlm.nih.gov/pubmed/19593336
Positive correlation between platform crossings in SE during the probe trial and neurotransmitter turnover suggest improvement of spatial memory. Long-term administration of Ginkgo biloba extract can improve spatial memory and motivation with significant changes in the content and metabolism of monoamines in several

ncbi.nlm.nih.gov/pubmed/?ter … a+erectile
ncbi.nlm.nih.gov/pubmed/20411379
Ginkgo biloba extract treatment increases noncontact erections and central dopamine levels in rats: role of the bed nucleus of the stria terminalis and the medial preoptic area.

mariovitali · May 25, 2018, 7:54am

I have no experience with Ginkgo and i’ve read conflicting reviews (possible inhibition of CYP3A4). Definitely, It’s worth a try (mine is on the way from iHerb) : There is a good chance that we have impaired dopamine production and -possibly- this is the culprit behind incidences of anorgasmia or difficulty reaching orgasm among us. So boosting dopamine in this situation should be beneficial.

xptriado · May 25, 2018, 7:54am

Im pretty sure i have impaired dopamine production as i need extra sun, more than other people, to feel good and i have plmd and fasciculations during the day.
I had epileptic fits when i took midazolam, which is antidopaminergic. So i guess i had something already before fina…

23andme returned some snps connected to parkinsons, prolatin is elevated , i have sexual probs and serotonin increases seems to make matters worse.

So yeah…low dopamine i guess

On thr sleep thematic, i noticed larginine with l lysine help…but i see it increases oxidative stress…irs a pittu because jt increase d libido and managed my insomnia last two nights…
I have some supps on the way to help this, namely magnesium malate, relora and bacopa.
Also dibencozide and sunflower lecithin to help methylation. Im motivated niw that i saw results from arginine.
Next supps will be tmg, thingz for mitochondri and uridine/gdp choline for dopaminergic system normalization

By the way mario i think i know what u mean with barlmetric changes influencing mood.

mariovitali · May 25, 2018, 7:54am

As i have described i keep a very detailed Log of the supplements i take and how i feel. Yesterday at 20:30 i had a severe tinnitus attack and i informed my girlfriend about it.

One hour later, wind started to pick up and all through the night the wind had gusts up to 45 Km/h and temperature dropped significantly. I woke up in the middle of the night without a reason at 3:00 am from pain on my Waist area (this also signals problems with weather). Sure enough wind became ever more pronounced after 10 minutes.

For me it’s not only mood xptriado. Abrupt barometric changes (only when barometric pressure drops) affect :

-My Sleep
-My Mood
-(Possibly) increased incidences of excitotoxicity
-Erection Quality

elijah · May 25, 2018, 7:54am

This map is awesome, Mario. Is there a web version where you can search for keywords in the browser? For example I was looking for Vitamin K, but since {ctrl + F} doesn’t work it took me a while to find it.

About the Holy Basil /Tulsi, I’ve been drinking it regularly for the past two years because it benefits the adrenal system and lowers cortisol. It’s an adaptogen like Ashwagandha, and it never caused me any adverse effects. True, it may be a mild DHT inhibitor like pretty much every anti-inflammatory, however the inhibition of DHT is almost negligible in comparison with other things like green tea, fish oil, curcumin, not to mention Lycopene, Astaxanthin, Sea Buckthorn, etc. Believe me, if I drink Green Tea for three days in a row my erection will get weaker right away, but I can drink Tulsi every day with no issue. My DHT level is high, so I don’t think the inhibition of DHT per se is the main cause of crashes, the adverse effect of DHT inhibitors may well be the byproduct of the inhibition of another enzyme/neurosteroid.

mariovitali · May 25, 2018, 7:54am

elijah:

mariovitali:

I am posting the Mind-map with my notes on PFS.

This map is awesome, Mario. Is there a web version where you can search for keywords in the browser? For example I was looking for Vitamin K, but since {ctrl + F} doesn’t work it took me a while to find it.

About the Holy Basil /Tulsi, I’ve been drinking it regularly for the past two years because it benefits the adrenal system and lowers cortisol. It’s an adaptogen like Ashwagandha, and it never caused me any adverse effects. True, it may be a mild DHT inhibitor like pretty much every anti-inflammatory, however the inhibition of DHT is almost negligible in comparison with other things like green tea, fish oil, curcumin, not to mention Lycopene, Astaxanthin, Sea Buckthorn, etc. Believe me, if I drink Green Tea for three days in a row my erection will get weaker right away, but I can drink Tulsi every day with no issue. My DHT level is high, so I don’t think the inhibition of DHT per se is the main cause of crashes, the adverse effect of DHT inhibitors may well be the byproduct of the inhibition of another enzyme/neurosteroid.

There is no Web Version unfortunately elijah but i can export it to OPML. The problem is that i cannot attach OPML files…i tried to switch the extension to .txt but this didn’t work. I uploaded it here : http://www24.zippyshare.com/v/69893477/file.html

mariovitali · May 25, 2018, 7:54am

GUYS…IT’S OVER.

I waited for the day to see whether i will have Side Effects and for the first time in years, severe weather has not affected me. This is not a coincidence. This has never happened before. The vicious cycle of feeling great and like *&^@ is over!

The solution which worked for me is unbelievably simple. Boosting Basal NO/NOx production.

I added a new post in Theories, complete with the regimen that you can try to see for yourselves :

http://www.propeciahelp.com/forum/viewtopic.php?f=27&t=9478

SeeYouInHellMerck · May 25, 2018, 7:56am

what about other side effects?

edit: NVM, I just checked out the link itself and it has all the information hahaha