So 186 up regulated genes in our brain study

General Discussion
#13

The DNA is not modified. 171 genes in the brain are upregulated and 15 are downregulated. It’s the gene expression that has changed and that’s epigetic. Our epigenome changes constantly (some of you may have noticed the fluctuations). This research is a confirmation of what we already knew and it shows how widespread the epigenetic alterations are.

I would not be surprised if they found epigenetic alterations in other places in the body. An old person, say 100 years, has excessive overall accumulated epigenetic alterations and it’s called aging. Dr. David Sinclair has been studying how to undo obsolete alterations and has successfully done so on rats. He has lots of ways to do it safely with humans, although the results are not as dramatic as with the rats.

I’ve been doing some of those things myself with positive results, while some supplements he suggests are not doing well with PFS. Do your research.

I did a thread about repairing the epigenome and it has been delisted.
As evidence of epigenetic alterations are building up, I would ask the moderators if they could consider bringing back this thread. It has lots of useful ways to remove past epigenetic alterations that are no longer needed (some are still needed).

There’s hope, lots of people have gotten better. Check the success story compilation. There must be two dozen stories there, most of those way inside the thread. I know of an additional 3 cases that are not documented and I myself am almost over detoxing benzodiazepine and getting back my natural sleep, insomnia being the last of my symptoms.

Don’t let yourself be dragged down. It’s a serious condition and it can be downright debilitating at times but there’s people that did recover. Don’t give up !

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#14

The genes in my whole body are altered. Skin, hair, everywhere it’s not just the brain it’s body wide. Can you please link me to the thread or if you have a copy of it?

#15

Maybe we don’t have to correct all of the genes at one go. Maybe sexually or mentally affected genes can be corrected first.

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#16

It’s difficult to target specific genes. Some research indicate it’s possible to make the body promote such repairs but ultimately it’s the body that chooses what it does.

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#17

Wonder if this is why randy Santmann had hippocampal atrophy on autopsy after his suicide?

#18

Many genes all over the body were altered already from past adaptations to situations we encountered in our lives. What’s different with fin is that the situation was extreme, with the drug attaching itself to specific receptors, and the alteration to balance that made it so the body is not working as it should.

Please PM me for the link.

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#19

@Ozeph, how does this new epigenetic evidence relate to the neurotransmitter solutions posted about before? With amino acids to take when feeling certain ways:

L-Tyrosine:

  • Brain fog, Mentally fuzzy, Low energy, Cognition impairment: Concentration, Memory

GABA/Taurine/5-HTP:

  • Anxious, Stressed, Tense, Trouble sleeping

5-HTP:

  • Irritable, Agitated
#20

Those neurotransmitter precursor/amino acids can help reduce some symptoms or make them worst depending if a particular neurotransmitter is currently deficient or in excess. They are dose dependant and not a cure. That’s a path I took early but I don’t follow that path anymore because it’s not easy to find the proper balance

GABA: Not efficient as it doesn’t pass the brain barrier.

Taurine: Does attach to the GABA receptors and produces a calming effect but it also prevent intercellular oxidation of testosterone in the testicles which results in higher T levels. It’s can make symptoms worst depending on how someone is sensitive to increased androgen. Caution is required.

5 HTP: transforms into serotonin. It can create or fix an imbalance with Dopamine. Important to note: 5-HTP is dangerous if taken with SSRI or St- John’s worth extracts.

L-Dopa: Can create or fix an imbalance with serotonin.

L-Tyrosine: I had good results with that one. It helps with thyroid function and dopamine. It’s also a precursor to adrenaline and nor-adrenaline which could be bad but I didn’t have any problem with it.

I tested those but I found the carnivore/ketogenic diet to produce better results

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#21

I am 100% confident dementia patients will have abnormal gene expression profiles in their brains compared to those with normal brains. The same for patients with brain cancer versus those with healthy brains. I am also confident those with penile cancer will have abnormal gene expression profiles compared to those without penile cancer. The pancreas of a diabetic patient will have an abnormal gene expression compared to those without diabetes. Those who have suffered a heart attack will have different gene expression profiles in their hearts compared to those who never had a heart attack. An obese patient and an emaciated patient will have differences in gene expression. Do you get the hint? There is no good reason to panic about gene expression changes. Gene expression abnormalities happen in every disease state. Come on, folks. This is not unique or exclusive. The way I see it, epigenetics is a red herring. Not trying to be argumentative, just offering a different perspective with critical reasoning behind it.

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Question on supp combination
#22

I agree with your point of view. I am not good at biology, but I believe that changes in gene expression are only a result of PFS and not a cause

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#23

The genetic expression levels are of course increased in all types of cancers , thats why it can cause unregulated cell hyperplasia.
There are obv. epigenetic factors driving those expression levels, for ex. smoking in lung cancer.
Or in our case Finasteride.
That’s why medications that regulate methylation levels of genes are used for cancer treatment.
Restoring those methylation levels woud most certainly reduce all of our symptoms, since they influence numerous pathways.
Attacking these expressions levels individually will be a difficult task if not even impossible and surely won’t translate into a treatment.
The signaling pathway that regulates the 5-alpha-reductase gene expression should def. be better understood.
This is still a black box and from my knowledge standpoint we don’t know if there’s a negative or positive feedback loop causing evident changes of the signaling pathways in the presence of a strong 5-alpha-reductase inhibitor.

#24

Our bodies have never experienced a 50% DHT deprivation for the time of our existence.
So I wonder if the mechanisms in check to still guarantee normal cell functioning even in the presence of highly reduced DHT levels are even working properly.
Another question I might raise, is what happens to the Finasteride drug molecules that lose the competition for binding to their target receptors.
Which other receptors or molecules does Finasteride bind to?
This could potentially lead to Off-target Effects.

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#25

PfS do effect our brain chemicals, dopamine, neurosteroids and neurotransmitters genetically and derugaled. Many new gene therapy metodhs are curing different diseas. I think they Will use meds or gene therapy to regulate pfs.

It is not brain damage

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#26

Thanks for this update. Tried GABA for two nights… Seemed to promote less stressful sleep (said my sleep monitor app/device). I used topical Finasteride for 7 weeks which produced symptoms starting week 3 so I wonder if I’m more susceptible to blood/brain barrier personally and GABA did actually cross it? L-Tyrosine made me feel kinda weird, (anxious?) I’m dealing with fight or flight feelings at night waking me up even though cortisol levels were normal in last blood test. Maybe Tyrosine’s relationship to adrenaline isn’t the right fit for me? Took 5-HTP at 4am when I woke up to try to sleep and it didn’t help but I see you suggested using that during the day rather. I’m 3 months post stopping topical Fin. No sex side effects. All cognition and sleep disturbances.

#27

I never used finasteride; I used saw palmetto. I knew about the dangers of finasteride sometime around 2013 or 2014 when I was seeking answers for unrelated conditions. I came across a number of forums, among them a prostate forum, none of which I remember the names of, and this petition: https://sign.moveon.org/petitions/merck-fund-studies-into I also found out about PSSD. I said “sucks to be them” and carried on with my life until 2020 when that midget palm tree ruined my health overnight.

accutane inhibits 5AR type 1 but not type 2. finasteride inhibits 5AR type 2 but not type 1. This would explain why the former affects acne but not hair loss and why the latter affects hair loss but not acne. dutasteride and saw palmetto inhibit both 5AR type 1 and type 2.

Vinca alkaloids used for cancer treatment are extracted from the periwinkle plant. I wonder if dutasteride and/or finasteride are extracted from saw palmetto. Anyway, I have used periwinkle, an herbal DNMT inhibitor and HDAC inhibitor, and I feel it helped me, along with countless other things I did. Alas, chemotherapy/periwinkle and other forms of immune suppression open you up to nasty infections, possibly limb or life threatening infections.

Shout-out to my ketogenic brother, @Ozeph! Keto, another thing I found helpful.

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#28

You seem to have a leaky brain barrier. It’s not unusual at all and GABA supplements are used to verify if it’s the case or not. L-Tyrosine is not for everyone. If you don’t feel good with it, stop it. 5-HTP won’t solve the real issue which is IMO excess Glutamate. A pinch of MSG (mono sodium glutamate) instantly gives me anxiety.

I’ve seen this is many PFS sufferers including myself. The Androgen Receptors have been up-regulated (or over-expressed) in response to an androgen deprivation therapy (Fin). This is not from me, it’s from one of the researches from Dr. Roberto Cosimo Melcangi in Italy. He says AR are enlarged and oval shaped under the microscope.

I’ve read in another study that the AR are regulating the L Glutamine complex in the body. Over-expressed AR is said to create Glutamine complex toxicity, that is, too much of the Glutamine metabolites in the body. One of those metabolite is Glutamate which we end up having in excess. It’s the excitatory neurotransmitter that should transform into GABA at night to provide good sleep. For some of us, not enough Glutamate is transformed into GABA and we don’t sleep very deep or at all. Over the night, testosterone level goes up (as in all men). That makes our AR produce extra Glutamate at night and we wake up fully awake and lit up, as if we just drank 3 espressos.

There certainly has been many epigenetic alterations to counter-balance the excess Glutamine complex metabolites. In my opinion, to try and find them all is maybe educational but it misses the point. The initial problem is having been deprived of androgen and 5ar which has caused the AR to be over-expressed in order to capture what little androgen was present. I believe in putting the body in a state where epigenetic repairs can take place and then signaling to the body which direction it should take. For this, I’m fighting an androgen deprivation therapy (fin) with an androgen supplementation therapy (not TRT). It has made some long gone symptoms reappear but they are now receding. Sensitivity is much better, sleep is better on half the sleeping drugs compared to 2 years ago but I won’t know the final results until I stop the supplementation and let my androgen come back to normal. By then, I hope my AR will have adapted to higher androgen levels and normal ones will produce normal results. Let’s see.

I don’t suggest anyone try this. I’ve worked many years to make my body stabilize and my symptoms were almost all gone before I was strong enough to get worst. It still remains to be seen if I will actually get better from this. I’m a guinea pig in this experiment.

#29

The study does not specify at what level the genes have been altered, just the overall signaling I believe.
So that means it could be at the Dna damage level all the way to RNA level.

#30

This company could be an option for solving this

#31

Wow. How much longer are you taking supplements in this experiment before you stop to see if your body’s androgen pendulum swings back to center?

Got my Adrenal-Neurotransmitter tests back. Took the test before trying any supplements including GABA. I have high GABA, high Dopamine and high Epinephrine, all in the red above normal range. In the yellow, slightly under normal range I have low Seratonine, Phenethylamine, and Creatinine.

Results also showed high Cortisol at night, above normal range, in the morning and before bed with low Cortisol during the day (HPA dysfunction?). And results show very low DHEA at 29, well below normal range (137-336)

This mixed with my high SHBG results. Normal Testosterone levels though. I’m now taking 4-6mg of Boron daily to try to bring that down. I’m eating greens, proteins, fats, and exercising.

Seeing my hormone doc tomorrow to discuss new neurotransmitter results.

What’s your take @Ozeph?

#32

It shows you have deregulated genes in the brain as I believe most of us have. I sure do myself. Continue with your healthy diet and exercise, I think you can’t go wrong with that. My advise would usually be a carnivore / ketogenic diet. It shows improvements in all those who successful got into it but it’s clearly not a complete answer to our predicament.

Boron is the androgen promoter I’m currently taking. It has shown to have a very effective, fast and direct effect at lowering SHBG and thus increasing free T (and all sexual hormones as shown by the increased Free Androgen Index, FAI, results).

I took 12mg Boron per day, tested and free T was 2.25x above maximum range. I started being irritable, aggressive, sometime furious and then I blew up the top. Sex drive dropped, heavy brainfog, difficult sleep and lots of long gone PFS symptoms re-surging. 11.3mg Boron a day showed similar results but slightly less brainfog. Still unsustainable.

I reduced to 6mg of Boron a day and tested again. Free T was very high but within range, Old re-surging symptoms disappeared, sex drive, sensitivity and orgasm depth improved.

I increased to 8mg Boron a day. Tested again. Free T only 4.3% above max. No or very little brain fog, sex drive and sensitivity decreased, old symptoms didn’t come back.

All trials were done for a month before testing and correcting Boron dosage. I find it fascinating how Boron alone, via free T, can exacerbate PFS symptoms. In 6 years, with all I tried, I never had such accurate control on this disease’s expression in my body.

I currently increased to 9.5mg Boron a day. Sensitivity, sex drive and depth of orgasm are low. Slight brainfog but tolerable. No old symptoms re-surging.
In 15 days I’ll test again, post my results and then drop Boron to 2.5mg (which does nothing to SHBG) I want to see where my sexuality is without artificially increased free T. I won’t test free T, it will be within range.
If I end up with a better sexuality and better motivation compared to before I started all this, then I’ll start to believe the elevated free T and free androgen will have reversed some of the PFS epigenetic de-regulations. If not, then I did all this for nothing and spared you the trouble of making yourself worst to test a theory.

I don’t suggest anyone try this. Again I was quite stable and strong before I tried so I could afford getting worst in an attempt to get better.

Before doing the Boron experiment, I took a 6 months HCG treatment at 300iu three times a week. That’s very low, some 15 times lower than what the doctor prescribed to one of my friend with PFS. I did this to increase natural T production persistently. The increased T remains after HCG is stopped. SHBG was high and free T low which shows my body was correcting for the increased T. I was worst at first but became used to it and was better at the end. I took Boron afterward to stop the attempts my body was making at dampening elevated androgen. I wanted my AR to capture the new elevated androgen levels.

Curiously, 3 weeks after starting HCG and for 1 day only, sex drive was high, sensitivity and connection was very high (as I remember it when I was a teenager) and orgasm was an explosion in the brain just like old time. It was gone the next day. In my opinion, it shows that the DNA is intact underneath all the epigenetic alterations. DNA is hard to change and seldom does whereas the epigenome is fluid and responsive to changes in current conditions.It constantly changes.

Also keep in mind I’ve been on a carnivore / ketogenic diet, one meal a day, for 6 years. This has stabilized my body and according to some research I read, it promotes epigenetic repairs but without sending a clear signal to the body as to what the repairs should be.
The HCG / Boron experiment is meant to send a signal that my body is too sensitive to free androgen and thus needs to repair the AR. Increasing SHBG is the first attempt my body has made to prevent the AR from being overwhelmed. Boron makes SHBG irresponsive to the body’s attempt to do this. The theory I’m testing is that the next available solution would be for my body to downregulate the AR. I’m not saying it’s working. Let’s see.

Those are my results so far. I’ll post again in 3 weeks for those interested in knowing what happened.

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