I think that’s a very good sign. It’s certainly better than no reaction at all. Do you get like a weak one like it’s trying to fill but failing or a full erection?
Also, I don’t really understand what’s going on in this thread, but I’d like to. Is it some kind of treatment to get our genes working right again?
Thanks Droit,
I will see how i can order the test from where i am.
Basically, i feel as if i am getting a “quick fix” from NAC. It is seems that NAC gives a short boost of Glutathione and this boost quickly wears off. I am waiting for the rest of the 2 supplements Metafolin + Phosphatidyl Serine to add to the protocol and so to have a proper treatment for my Methylation cycle.
Apart from that i am feeling still great. Libido to 100%. Oily skin, dreaming like a normal man, memory getting slowly better. I also wanted to add that i am more than certain that there is some neuronal degeneration taking place. I am probably one of the oldest users of Finasteride in here ( i took it back in 1998-1999 if i remember correct). Yesterday i bumped my hand to this point near my elbow where you get an electric shock. Didn’t feel the same. If that would have happened 5 years ago it would have been really painful. Could be my age? I really don’t know and i am curious to see whether there will be any regeneration happening .
No it will turn into a full erection if I can help it! I have never had much trouble with getting an erection, but my libido is lower than it should. That being said, I can still “perform” about 3 times a day if needed. Not sure how others are compared to this. It seems like ED is the one side I never got. My morning erections are still sometimes on and off, but have been a lot better since I started taking Melatonin before bed, I also sleep a solid 6 hours straight usually without waking.
Most of my sides seem to be Hypothyroid, gyno/weight and water gain, and mental. I get mild anxiety and depression sometimes, but a lot of times I just feel uninterested in doing things. Vision is somewhat hazy too, as if I have smoked marijuana or am drunk. Short term memory is pretty bad at times.
But in terms of the Methylation process, I have been taking this B Complex since January and haven’t really felt a difference. http://www.amazon.com/Metagenics-Glycogenics-60-Tablets/dp/B004GLIZ60/ref=sr_1_1?ie=UTF8&qid=1367133315&sr=8-1&keywords=metagenics+b+complex
Don’t know if I need to add a few things to it to make it work correctly or what…
Not sure if Methylation is part of my specific problem or not.
FeedMeMore,
I just wanted to respond to your comments about the various types of methylation discussed on this board.
Also, Cap wanted some more details on the discussion in this thread, so I’ve written up a simple explanation of the theory I am proposing in this thread: ‘the methylation block.’
What is methylation
Methylation is simply the passing around of methyl groups (one carbon + 3 hydrogens) to different biomolecules. This is a very broad area, but I think there have just been two applications of methylation discussed on the forum.
Given the PFS symptoms it’s reasonable to suspect that something is broken down in the pathway from testosterone synthesis to androgen receptor creation and activation. I think people on this forum have wanted to look at whether or not something in that chain is unusually methylated at the DNA level, thus silencing the effect of testosterone. But I don’t think there has been any publications or test evidence to suggest this is something specific we should investigate.
http://www.co-cure.org/scan0003.bmp
The methylation cycle, acts as a little factory to supply methyl groups to a large number of reactions in the body. Some of these reactions make things like creatine, carnitine, coenzyme Q10, phosphatidylcholine, melatonin, and lots of other important substances for the body. Additionally the methylation cycle regenerates SAMe and the body’s MASTER ANTIOXIDANT, glutathione.
What runs the Methylation cycle and how does it break down
Active B12 and active Folates feed the Methylation cycle. A key concept to this thread is that B12 is very fragile. B12 can not be in an oxidative environment - so it there must be enough antioxidant in the cell to protect the B12 supply.
For example, if you were to magically take away all of the glutathione in the cell, B12 would become oxidized (sort of inert) and there would be nothing to fuel the beginning steps of the cycle.
So the methylation cycle is this weird thing where the end result, glutathione, is the thing that protects the raw material - B12. This cyclic cause and effect makes a breakdown in the methylation cycle persistent without the right intervention. And if the methylation cycle stopped running, then all the things that relied on the methylation cycle would stop working.
One consequence would be: SAMe stops getting produced so serotonin can’t be converted in to melatonin (http://ars.els-cdn.com/content/image/1-s2.0-S0006899398002625-gr5.gif), and you can’t get restful sleep.
The state of not having enough glutathione to protect the B12 in the cell is a vicious circle called a ‘methylation block.’ This state is confirmed in a test called the ‘Methylation Pathways panel.’
Doctors in the chronic fatigue (CFS) communities think the methylation block happens when oxidative stress over comes the glutathione supply. There seems to be a pattern in the CFS community of getting a serious infection, possibly coupled with high stress before someone reports CFS.
How does this relate to Finasteride?
Finasteride is oxidative stress in a pill. See the below paper which says that Finasteride generates oxidative stress and reduces glutathione.
“The Effect of Different Doses of Finasteride on Sperm Morphology and Motility and Reactive Oxygen Species Concentrations in Rats” http://98.131.141.166/Admin/PDF/1-9-77Med.5.pdf
Quote the paper’s abstract:
From the paper’s results section:
Small number of confirming results on the board
As far as I know, we have only 3 forum members on the board who have taken tests for oxidative stress. All of them show excessive oxidative stress.
Per the methylation pathway panel, AJ72 and myself have depleted reduced-Glutathione.
Also, per a Metametrix Organix test, I also have elevated 8-Hydroxy-2-deoxyguanosine which is break down product of DNA from oxidative stress.
moonman1 also has taken the Metametrix Organix and has posted very high lipid peroxides which is a marker for the break down in lipids (fats) from oxidative stress.
So again, I am proposing that Finasteride is a glutathione depleter in a pill and it can exert enough pressure on one’s glutathione stores that it causes a block in the methylation cycle.
Thank you for that write up! Very interesting. Going off of that theory, what do you think we can we do or take to boost that process and knock things back into place?
Hey Guys,
Here is an update regarding my recovery.
I am still feeling great with no side effects. Libido to 100%. However something happened on Monday which makes me a more firm believer on what Droit discussed previously.
I was “attack-free” for over 1.5 months by having a specific protocol (which i will not discuss here). By “attack” i mean a short tinnitus on either left or right ear which would then signal several problems including low libido, depression, numbness in hands etc.
So on Monday i had one attack after 1.5 months. The reason : I was writing exams and i was really stressed. This was not a coincidence. My analysis did not show a very positive correlation between stress and my problems but again, i believe this was not a coincidence. It all has to do with balancing the right amount of anti-oxidants in your body and the factors that bring havoc to your body such as psychological stress. I totally postulate on what droit says and the interesting thing is that we reached the same conclusion (about methylation) totally independently. The idea about methylation came to me after the fact that i saw that N-Acetyl-Cysteine has effectively cured me in the sense that as long as i take it i do not have any problems. But with the latest tinnitus incident it appears that if i am running a stressful period then i should increase the dosage (currently around 250-300mg / day)
Again i do not know if this theory applies for all PFS sufferers. But it appears to me that methylation is definitely one way to go.
@Droit : Good post Man! Haven’t tried Metafolin yet but i am trying to increase Folate intake by other means for now. BTW have you tried taking NAC?
Will keep you guys posted as always.
Regards,
Mario
PS : For all of you wondering why i am still trying different things even though i have no issues at the moment : I just want to get to the root of the problem.
Cap,
It would be helpful to get some more testing from people on the forum. I know there are some ambitious people on the forum so a lot is possible.
The most ideal test would be the Methylations Pathways Panel.
hdri-usa.com/tests/methylation/
europeanlaboratory.nl/
It’s $300, and they don’t bill insurance directly. They will give you a receipt so that you can file a claim with your insurance. I’m going through that process now, so I don’t how much insurance is going to cover.
The second best would be a Metametrix organic acids test. It has the marker for oxidative stress and markers for B12 and Folate.
metametrix.com/test-menu/pro … prehensive
Metametrix has a simple urine oxidative stress test. I assume that would be the lowest cost, but still helpful.
metametrix.com/test-menu/pro … ive-stress
Metametrix bills insurance directly, so I don’t know how much is out of pocket.
(if anyone has 23andMe data, please PM me)
As far as treatment, we should run a trial with variations of the ‘Simplified Treatment Protocol’ (SMP) I spoke about in an earlier post in this thread. mariovitali has already added NAC and swapped out hydroxy-B12 for methyl-B12 with good results. I have started doing the same.
As, I’ve said, the SMP is about $25 a month. There was a trial of Chronic Fatigue people where they took the SMP and got Methylation Panels at 0, 3 and 6 months to measure glutathione (and other methylation cycle markers) and on average the trial participates went from bad to in range.
But the methylation cycle can be stubborn to reboot. Dr. Van Konynenburg says that 2 out of 3 people will respond to the SMP. The others may need personalized attention. For example, in the chronic fatigue world, heavy metals can be continuing source of problems so some have to get chelation therapy while doing the SMP.
It’s possible that since we all have the same source, we’re all closer in what we need.
I think some people will be interested, and some will be able to get some tests, and some will want to try the protocol. It would be great if, once we get some test results, if people could see practitioners that specialize in this stuff in their respective cities and feedback.
Bryce54 was on the verge of talking to Dr. Van Konynenburg about PFS, but Dr. Van Konynenburg died shortly after they began communicating.
I’ve been on the SMP for 5 months and have absolutely had consistent improvement symptomwise, but very very slowly - which is consistent with my lab values.
I’ve had 2 methylation panels, 1 right before starting the SMP and one at 4 months. My reduced glutathione (GSH) went from 3 to 3.5 mircoM/L (where the normal range is 3.8-5.5). So its still too low but coming into range. My SAMe started at 216 mircoM/dL, then at 4 months it was 221 (normal range: 221-256).
I’m doing other testing to look at what else I need to address. But I feel like I’ve improved proportionally with those numbers.
There is no doubt that myself and Aj72 have ‘methylation blocks.’ My numbers are actually worst than the women in the chronic fatigue study Dr. Van Konynenburg - they start the trail at an average of 3.31 mircoM/L.
Note that I am summarizing the research I’ve done and mostly the work of Dr. Yasko and Dr. Van Konynenburg. I only post citations when necessary for simpilicity. I’ll post some more stuff later, but for now if you need citations you can reference this document by Dr. Van Konynenburg which really has all the non Finasteride citations. He also talks about neurotransmitters if you’re anxious to read about that.
Thank you again for the information. As your glutathione improved over those 5 months, how did you notice that translate to how you felt? What improvements did you see in your symptoms?
It seems that NAC is like taking a shortcut in boosting Glutathione Levels and thus getting results more quickly. However, as discussed previously i have seen that taking NAC is like a “quick fix”. You get a spike of Glutathione in your body but this then drops because your internal mechanism (=methylation cycle) of Glutathione production is not working right. I also think that the best way to take NAC is to take small doses 3 times a day so that you have Glutathione production evenly spread out across the day.
I am currently trying the SMP and by looking at my symptoms and the supps i am using i have the impression that NAC (Note : NAC is not a part of the SMP Protocol) is the most useful supplement -because it boosts Glutathione directly- and then high Folate intake (Spinach, Green Asparagus, Fresh Mint leaves).
Yesterday my libido skyrocketed, i felt like a 25-year old and i believe that high folate intake did the trick. I will have to keep testing like this though until i get my hands on Folate (as Metafolin) from Solgar. Once i will have all of the supplements for methylation boosting i will drop NAC again to see what happens.
Droit, something to think about : how does the methylation block theory could explain the “Post-Finasteride crash”?
In other words…what exactly happens when the crash occurs? The best way that i can describe my crash is that it was as if my immune system got out of control. I had hives, joint pains, tinnitus, you name it. I thought it was autoimmune disease and the doctors had me checked for SLE and Scleroderma.
It’s tough to have exciting answer when my numbers are still not even within ‘normal’ range… not even low-normal. As I said, my numbers were lower than the women in chronic fatigue study, and some of their participants couldn’t go to work because of the symptoms they had.
But I have certainly improved in proportion with the improvement in those numbers.
After looking at my notes, my progress isn’t actually that bad. I feel maybe 40% better, but all improvements are consistent and stay. Aj72 has felt much better than me. He’s hasn’t been around lately so I assume he’s doing good.
I’m still way out of range, which means I shouldn’t even feel near normal. And when you have these numbers, the research says you should feel like I do.
From the CFS study, most people improve much faster. I must just be deep down the hole. So I’m putting my effort into finding out what else is preventing me from normalizing the numbers in that panel. I recently took an Organix test which showed that I’m depleted in CoQ10 (no surprise, created by the methylation cycle), B2 (riboflavin), and need free amino acids (specifically calling out cysteine - which is what NAC is and is a rate limiting step in glutathione synthesis).
Just again want to add that progesterone and its metabolites like allopregnanolone upregulate glutathione activity.
ncbi.nlm.nih.gov/pubmed/19229376
Could it be by supporting both elements you can significantly boost the effects?
19,
Thank you for investigating this angle. There certainly is a lot of excitement around 5alpha-reductase metabolites on the forum these days.
I think the below paper is equally compelling, which (on a very quick scan) says NAC (precursor of reduced glutathione) is as good as allopregnanolone at reducing oxidative stress (Figure 1).
europepmc.org/articles/PMC2832077/
In presenting this theory I want to stick to the well established and direct model of: reduction in androgens leads to oxidative stress (1,2) which leads to pressure on glutathione production which has effects on the methylation cycle’s (methionine cycle) ability to run and has ripples to other systems.
I think this keeps the investigation simple and gives us a model to test.
While these papers are showing allopregnanolone helps reduce oxidative stress, neuroprotection is just one dimension. One of the most exciting things about this theory in explaining a lot more of the symptoms of PFS is the fallout from blocking the methylation cycle.
I do think there could be another thread that would tease out whether the weakness in 5alpha-reductase is downstream or parallel with this model. The thing I would start with is: is allopregnanolone reduction while on finasteride a secondary or even the primary way finasteride weakens the body’s ability to keep oxidative stress under control.
Again, this is not an area of research for me but I wanted to comment on the interest.
mariovitali,
The theory being discussed on this thread would give us a starting point for a lot of answers in terms of explaining PFS just from the chronic fatigue research. For example: Why some people get chronic-fatigue/PFS, and others don’t (there is a genetic component - I can post on this later). Additionally, there is a lot of overlap in the symptoms just from comparing the symptoms at our member stories template and those from the chronic fatigue forum - and many are well researched. Here are a handful:
(remember this is in the context of a break down in the Methylation cycle)
Androgens are a prime interest to this forum, but they are not typically discussed in the CFS circles. I suspect because typically older women get this pathology. There are some theories about why this effects primarily women and not men in the CFS community. One has to do with oxidative stress from estrogen metabolism. However, there is a lot of sexual dysfunction on phoenixrising.me. But there is more about androgen dysfunction in the Methylation cycle block theory that I will post on later.
In regards to the intermittent crashes you’re talking about, what I can say is the people in the CFS boards complain about the same thing. You can search for ‘crash’ on the phoenix.org forms and get lots of discussion on it. I seem to remember that their average description of a ‘crash’ is related to energy plummeting.
Regarding to your comments about a feeling of a hyperactive immune system, the methylation block does lead to an interesting effect on the immune system.
The methylation block, leads to low T cells (1,2) and a spike in B cells. B-cells are the allergic and inflammatory cells. Elevated B-cells can give you that chronic immune activation feeling. In fact, some doctors treat chronic fatigue with Rituximab which is a drug that selectively kills B-cells (3).
I certainly identify with this since for the first time in my life I have food allergies.
You describe your reactions as very acute. I don’t know if the B-cells have this sort of quick off/on reaction so I’m not sure if this explains the phenomena you’re describing.
The most interesting thing is the initial crash that most people describe where they quit Finasteride. This seems to be a progression of: quit Finasteride -> androgens coming back -> crash -> locked in PFS.
This is one major thing I can’t understand or tie back to the Methylation cycle. If I think through it, its reasonable to suspect that: Upon quitting Finasteride cold turkey, testosterone and progesterone start rushing through the unblocked 5-reductase.
Given a burst of activity, maybe something is unregulated that chews up the remaining glutathione, thus cementing the block? Does the Methylation cycle go into overdrive eating up the ME cycle raw materials (mainly B12)? Thus creating a deeper ME block. Maybe something starts using glutathione up?
I think honestly to know what is happening in the initial crash in the Methylation cycle context, we would have to run a Methylation Panel and a Metametrix Organix test every day while someone is crashing - which is obviously not realistic.
“Altered functional B-cell subset populations in patients with chronic fatigue syndrome compared to Healthy Controls” onlinelibrary.wiley.com/doi/10.1 … 3/abstract
“Glutathione Depletion in Rats Impairs T-Cell and Macrophage Immune Function” archsurg.jamanetwork.com/article … eid=595577
“Is Chronic Fatigue Syndrome an Autoimmune Disease?” blogcritics.org/culture/article/ … utoimmune/
Bottiglieri, T.“Homocysteine and folate metabolism in depression,” Progress in Neuro-Psychopharmacology & Biological Psychiatry 29 (2005) 1103 – 1112 (jain-resources.info/uploads/ … lin_ds.pdf)
“Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats” ncbi.nlm.nih.gov/pmc/articles/PMC1566059/
An intramolecular disulfide bridge as a catalytic switch for serotonin N-acetyltransferase.
J Biol Chem. 2002 Nov 15;277(46):44229-35. Epub 2002 Sep 4. (interpreted here forums.phoenixrising.me/index.ph … cfs.11728/)
Yasko, A (2004). "Autism: Pathways To Recovery” dramyyasko.com/wp-content/fi … 2_file.pdf
Richard van Konynenburg’s lecture on ME/CFS in Sweden video: iaomt.media.fnf.nu/2/skovde_2011 … tssyndrom/ (slides linked on page)
Effects of Mercury on Methionine Synthase: Implications for Disordered Methylation in Autism legacy.autism.com/medical/research/deth.htm
Sounds interesting I’m going to order those supplements.
Joe78 made good progress since taking multi vitamin that contains all the key ingredients discussed in this thread (mB12, NAC, TMG, Magnesium, Zinc, folic acid, …). Maybe worth further investigation.
Hey Droit,
I’ve been following this post for a while and am definitely interested in the theory presented. I wondered if you could speak to any changes to spontaneous/morning erections. I know mariovitali has indicated progress from this treatment - have you experienced any similar results?
Also, you both talk about the return of oily skin. Do you think this is due to changes in DHT? It is my understanding that DHT plays an important role in keeping oil in the skin (along with loss of hair). Any increase in hair loss as well?
Thanks for your thoughts
This product has a lot of good stuff in it, like that it has Quercetin (an anti oxidant), CoQ10, NAC… But here are my criticisms in meeting the requirements for this protocol:
It has folic acid, which is chemically stabilized version, not the active form: 5-methyltetrahydrofolate. Maybe this guy doesn’t have mutations in his MTHFR so maybe he can process this version.
It does contain the active version of B12, methylcobalamin, but it is in too low a dose and taken orally. This protocol requires 2,000 mcg and sublingually because absorption of B12 in the stomach can be bad.
I’m a purest when it comes to this protocol so I don’t consider this a data point for this thread. He’s also doing a lot of other things.
Just wondering if fasting would help the Methylation Cycle ?
