Methylation Cycle and The P450 Systems

General Discussion
#1

Dear All,

Here i propose a theory for PFS which in a few lines is as follows :

Finasteride not only affects the Methylation Cycle but also P450 cytochrome is affected in some way.

I also give some guidelines both for Supplements and Diet that could potentially be of benefit to some sufferers. Before continuing i would like to say that user “Droit” was the first one that proposed the theory about PFS affecting the methylation cycle. Through analysis and a very detailed record which i kept, i came to the same conclusion although at a later time from Droit.

[b]What i am putting to the table as new information/theory is the fact that the following CYPs of the P450 systems may be affected :

CYP1A1, CYP1A2, CYP11A1, CYP3A4 and possibly CYP2E1
[/b]
Please let me say that i do not know whether/how the P450 system and methylation are connected and in which ways. I am hoping that some of you will be able to look at this.

I managed to find what is going with CYPs after careful record keeping and analysis. [b]In order to overcome PFS the following things should be addressed :

  1. Good Methylation
  2. Induction of specific CYPs through diet and supplements while avoiding specific substances that act as inhibitors[/b]

Finding the right supplements (TMG, Phosphatidylserine, B12, P5P, 5-MTHF) to use for proper methylation and at which dosage is individual-specific and the complexity rises even further with how many CYPs and in what extend are affected.

[b]For achieving proper Methylation (and the theory relating it to PFS) please refer to the following Topic started by Droit : viewtopic.php?f=27&t=7178

Regarding P450 induction the following is advised :

  1. Use Forskolin to induce P450scc (aka CYP11A1) to ensure proper Testosterone production and Thyroid function (With Forskolin i stopped being Hypothyroid and having Secondary Hypogonadism within a month of usage)

  2. Avoid the following at all costs : Bioperine, Citrus Fruits and specifically Grape Fruit. Black Pepper, Quercetin (Capers are very rich sources), Milk Thistle, Ginko Biloba, Cumin, Turmeric. All of these are inhibitors of very important CYPs. Please visit the respective CYPs in Wikipedia to get a full list of P450 CYP Inducers/Inhibitors

  3. Eat anything smoked (Salmon, Cheese). Supplement with K2 Vitamin and Vitamin D3 (both induce CYP3A4 through Pregnane X Receptor). For example, Smoked Gouda is both an inducer and contains K2 vitamin

  4. Eat Broccoli, Cauliflower because they induce CYP1A2. I failed to understand that this gene was affected because i tried DIM from Source Naturals and felt really bad. I then realized that the specific brand used also Bioperine which inhibits other CYPs.

  5. Refrain from taking Vitamin A because it appears that Vitamin A interferes with MTHFR Gene on the methylation cycle.[/b]

I also believe that PFS affects Nerve Growth Factor (NGF) if left untreated (where treatment is proper Methylation and/or CYP induction?) and for this purpose Lion’s Mane could be used.

Needless to say that different areas may be affected per individual. Please let me know if anyone would like to try the protocol of Methylation and P450 induction and report back.

2 Likes
#2

Very interesting post Mario, I have been using Forskolin and methylation supplements too with good/moderate results, and I can also attest the adverse effects of DIM (at least the one sold by Nature’s way with Bioperine) and Milk Thistle.
However, we cannot surmise that the cause is P450 just by associating the inhibitors of the cytochrome with some of the food/supplements that induce a PFS relapse, do you have any other evidence?

#3

Elijah,

I am not suggesting that inhibitors of cytochrome P450 would lead to a PFS relapse. All i am saying with my post is that P450 systems should be looked at as well apart from Proper Methylation. Of course this could be true for certain individuals while for others, only fixing Methylation might give the solution.

If possible please try the protocol of inducing P450 CYPs, namely with smoked cheese/salmon, Vitamin K2 (you are already using Forskolin) and Vitamin D3. Supplement with DIM but without any Bioperine to induce the CYP that aids in Estradiol clearance and be careful not to get through diet and/or medicines any inhibitors.

#4

Man congratulations for your recovery through your research. I ordered all these supplements and i’m starting the protocol as soon as i get them. I have 2-3 questions about it.
a)Do the methylation and p450 recovery have to be simultaneously, or first methylation and after p450 inducement? and if yes how long after? Also, is the methylation treatment for life or untill things get back working?
b)I noticed you mention P5P and 5-MTHF. Is p5p essential for methylation protocol or is it an extra? and do we really need 5-mthf or plain solgar folate would do fine for starters?
c)I read articles about lion’s meme and its beneficial effect on NGF. I believe you are right on this one too. I sense that nerve signaling is not working correctly, something is blocked or weakened in the whole process. Do you believe that people who had developed neurological symptoms (penis curvature, muscle/genital tissue wasting, spasms etc, have already got the neurological impact of pfs? And also in the studies i saw they used big amounts of lions meme, near 4-5 grams per day. How much do you think we need?
That is all my friend, thank you for your contribution and lets hope this works for everyone!

#5

I made a post discussing the P450 enzymes a couple weeks ago but really, there no evidence to support Finasteride inhibits or inducers any of these.

Epileptics have similar sexual dysfunction to us. This is resulting from the induction of the CYP19A1 Aromatase enyzme from use of Anti-Epileptic drugs, spiking their estrogen.

But where have the other enzymes you listed come from? What is each of their functions in the body? This thread seems far too speculative at the minute.

#6

You can try to simultaneously induce P450 Enzymes and also Methylation. You have to be aware that by inducing P450 enzymes the effect of many medicines is degraded. Regarding for how long you should take supplements for Methylation / P450 i am not sure so i cannot really tell if you will have to follow this regimen for life.

P5P could help you but you need to know which genes are affected and to which extent. You definitely need 5-MTHF (called Metafolin from Solgar) the methylated version of Folic Acid and not simple Folic Acid.
[/quote]

Yes there is definitely something wrong there. I do not know if it is possible to reverse the damage completely although to some extent maybe you can (i say this based to my own experience).

I use 2.4 grams per day and i believe it is helping me not only with enhancing NGF but also blunts excitotoxicity from Glutamate from what i have read.

#7

First of all i do not know if/how finasteride has affected our P450 Systems. All i know is that if certain CYPs are not functioning properly then :

  1. You get high Estrogen problems because Estrogen is not excreted, hence Gynecomastia
  2. Your hormones get out of control. I experienced that by becoming Hypothyroid and also having Hypogonadism. I was injecting HCG and taking T4 tablets for many years to support my thyroid. From Wikipedia for Forskolin :

cAMP also boosts P450scc aka CYP11A1 which is needed for Pregnenolone and Steroid Production

Regarding CYP3A4 : Induced by Vitamin D3, Forskolin, Vitamin K2. There are people here that have felt much better with Vitamin D3 (i know i have) although the effect seems to diminish with time. At some point i had to take Dexamethasone which is a CYP3A4 inducer. I felt much better then and now i understand why.

CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by fluoroquinolones and macrolides and induced by aromatic hydrocarbons. I believe that this is affected because my erections would skyrocket if i ate smoked salmon or anything else char-grilled.

CYP1A2
involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP1A2 localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. Brocolli, Cauliflower, Cabbage, high insulin also induce the enzyme

I do not know if other CYPs are affected or how this thing started from Finasteride and what is the root cause. I just posted what i have seen in myself and hoping that others may benefit from that as well and hoping that you Guys could also help in finding out what exactly is going on.

#9

Just a guess, but the induction of P450 by Ethanol may explain why some people experience benefits with alcohol consumption:

ncbi.nlm.nih.gov/pubmed/9922992
ncbi.nlm.nih.gov/pubmed/16487260

#10

Exactly. But things are not that simple… So for example a potent inducer of CYP3A4 is St. John’s wort while at the same time this compound inhibits other enzymes of P450.

The most pronounced effect (=feeling much better with stronger erections) i had it when i would eat too much sugar, sweets etc in one day. High insulin induces P450 but -again- things are not that simple. So my body may not tolerate high sugar well and as a result i will get high insulin circulating levels in my blood whereas someone else might not have any problem with high sugar intake and his insulin levels in the blood will stabilize very soon… so this person will see no benefit with having a high sugar intake.

#11

Dear All,

I am also looking at ways to increase Superoxide Dismutase (SOD) through Zinc / Copper supplementation and/or Manganese as SOD reduces Oxidative Stress.

I will report back ASAP.

#12

[b]I am also looking at the hypothesis that Testosterone induces Oxidative Stress to our bodies. I have read conflicting information that Testosterone induces / reduces Oxidative Stress markers.

That theory could suit also with the “Androgen Resistance” scenario. [/b]

I already started taking Zinc/Cu (Copper) Mix supplement and so far it seems that it definitely helps. Of course more time is needed, i am waiting to start supplementing with Manganese (will have it this coming Tuesday) so that SOD is further increased and as a result oxidative stress is brought down to a minimum. I am still staying well away from P450 inhibitors of any kind.

I am completely symptom-free, no tinnitus / neurological side effects / Brain Fog. Sleep is normal and Orgasm intensity back to 100%. Erection Quality to 80% and most importantly, consistent performance. I hope it stays that way and if in any case anything changes i will let you know.

#13

Hey All,

Just received my Blood Tests for Thyroid, DHT, Free T. All within range although Free T and DHT are somewhat towards the low end. Zinc was in the lowest level.

I;ve seen some posts from Awor regarding 3β-HSD. I am looking at this as well and perhaps this is the missing key for erections of a 25-year old :slight_smile: We will see.

More specifically from what i’ve read :

Magnesium, Alpha Lipoic Acid may be our friends. Olives and Olive Oil are enemies as they reduce its activity. Of possible benefit could be Chicory Root.

I will update you Guys soon,

Mario

#14

How did you make these conclusions?
I think you are on right track. MAny CAnadian Universities show 5AR inhibitors destroy Mitochondria in cells of testicles. They impair/ reduces the gonadal steroid biosynthetic capacity by destroying cholestrol homeostasis in the cells.

ncbi.nlm.nih.gov/pubmed/7570607
These results suggest that beta-sitosterol reduces the gonadal steroid biosynthetic capacity through effects on cholesterol availability or the activity of the side chain cleavage enzyme P450SCC. These findings raise the possibility that beta-sitosterol could be a contributing factor to the reproductive dysfunction observed in fish exposed to BKME.

and not very old

ncbi.nlm.nih.gov/pubmed/17196966
This reduction in StAR transcript abundance in conjunction with decreased plasma T and altered plasma lipoprotein fractions demonstrates a non-estrogenic effect of beta-sit. This is the first study to show that beta-sit has the capacity to alter gonadal StAR transcript abundance, offering a mechanism by which beta-sit disrupts reproductive endocrine endpoints.

#15

So what is your expreince with Alpha lipoic Acid as I am reading it reverses/repairs Mitochondreal damage. Have you used it? how long?

#17

the study you post is good. So far we think in primary gonadism LH /FSH are always high but this is only true if balls are damaged or cut off. IF balls are partially damaged like in the study you posted then hormone production can be impaired and LH/FSH might be low.

“Serum testosterone, luteinizing hormone and follicle-stimulating hormone levels significantly decreased in the Cd(2+) -exposed rats…”

This is exactly going on with us.Despite bad production of Testosterone our LH/FSH are low.
I think we have enough supporting research pointing towards testicular damage.

#18

@sprstriken,

There are times when i have erections of a 25-year old (however this was not possible so frequently a year ago) which means that something is blocking the correct usage of androgens. Now i can have a normal relationship but why not try to get even better… So there is hope. At one point i will post all the side effects i experienced in the past and the fact that i am how i am is nothing less than a miracle for me.

#19

did you have skin thinning, joint pain, pot belly, nausea etc. Did these all get improved?

#20

Hypothyroidism, Hypogonadism, Restless Leg Syndrome, Insomnia, Involuntary Movements (especially towards night), Dysphagia, Bradycardia, Impotence, Joint Pains, Tinnitus, Sudden Hearing Loss, Anorgasmia, Urticaria, Brain Fog, Memory problems, Depression and Suicidal Thoughts.

This is what i can think of so far. There could be more but all is gone (at least for now)

#21

that is promising. I will wait and see the effects of ALA.

#23

I just had an experience that might corroborate your theory. I was using goldenseal for a while, and it had a bad effect on me. It turns out that it’s a potent CYP3A4/5 inhibitor.

http://www.ncbi.nlm.nih.gov/pubmed/15900287

Do you have any good resources for foods that induce enzymes in the P450 system?