Have any UK or Europeans amongst you dealt with the Vitamin Diagnostics lab in Holland?
I contacted them and they e.mailed me the following:
‘We can do the methylating Pathways Panel for 300 Euro + 10 Euro administration fee.’
Does this sound right, or is there any other lab you would recommend?
I’ve been following this thread with interest and I think it’s a good idead for me to take these tests.
Keep up the good work.
mariovitali and dgreen,
You can refer to the below which is the same but improved in all variables. I definitely feel the best I’ve felt years.
viewtopic.php?f=27&t=7178&start=40#p70956
I want to stress that I don’t like this type of question for this thread. This thread is dedicated to gathering lab data and research on oxidative stress/glutathione and the methylation cycle in our population to determine the prevalence this theory in PFS.
The methylation protocol is borrowed from the CFS community. While we hear here, and I hear in PMs that there are a improvements for those who have stuck with the protocol, this is in no means a complete reflection of the theory. For example, why haven’t my methylation metabolites reached a normal level?
I have already spoken out against treatment driven exploration:
viewtopic.php?f=27&t=7178&start=160#p72790
After we have data that gives us confidence either way on this theory, the next step would be working to determine what the best protocol would be. That would include working with experts in everyone’s respective locale. I think the best way to get that sort of commitment, you have to see your lab values. Otherwise you’ll just dabble and go on to the next supplement.
Bluejaysfan, has done the pure protocol and has the most exciting update.
to.robin,
Thank you for the question. I don’t know anyone who’s done the test in Europe.
The Vitamin Diagnostics in Europe and New Jersey are the only ones that do the Methylation Pathways Panel. I don’t know of another that is as acclaimed at testing this exact pathology.
Droit,
I do understand that this is your thread. However, the ultimate Goal for all of us is to feel better and gain back our normal lives.
I believe that oxidative stress/glutathione & the methylation cycle is a large part of the solution (= our ultimate goal) but there are also other things that forum members should look at.
Since i now have the latest blood results, i wanted to share with the forum that i have returned to normal levels of Free Testosterone and normal Levels of Thyroid Stimulating Hormone (after 2 years of having secondary hypogonadism and secondary hypothyroidism) without any treatment (HCG for hypogonadism, T4 for Hypothyroidism) for more than 2 months.
Free T : 15.6 pg.ml (8.7 - 54.7)
TSH : 2.8 μIU/ml (0.3 - 4.5)
I also believe that Forskolin (an inducer of P450scc aka CYP11A1) was also a large part of the (my) solution. I do not know whether CYP11A1 is the primary part of the solution or not and i do not make such claim. I also believe that induction of P450scc via Forksolin has ceased my neurological problems because it boosted Pregnenolone production :
from Wikipedia entry for P450scc :
Doctors were saying to me that my pituitary was not working right for some reason and that this was why i was hypothyroid/hypogonadic. From the Wikipedia entry for Forskolin :
I now have a new girlfriend and a perfect sexual life. I also realized that i should start Minoxidil because i started losing hair on my temples.
Regimen :
Forskolin 100 mg
Metafolin (Solgar) : 2400 mcg / day
No one dispute that. That is everyone’s goal.
This is exactly what I am talking about. I believe you that Forskolin has made you feel better. But why? Is it because of the cholesterol to pregnenolone transition? Possibly.
But the more likely reason for your response is the interplay of Forskolin and Androgen Receptor: Forskolin is amplifies androgen stimulation of Androgen Receptor (1,2).
Remember that you’ve done months and months of various methylation cycle stimulation + glutathione pre-cursors, and now you’re stimulating AR. That is reminiscent of my comments here:
viewtopic.php?f=27&t=7178&start=220#p74416
Now that we’ve exposed something that stimulates androgens, I’m sure there will be interest. I want to avoid polluting this thread with a Forskolin discussion. If people are interested in Forskolin, I would say a separate thread is warranted.
“Androgen Receptor Activity at the Prostate Specific Antigen Locus: Steroidal and Non-Steroidal Mechanisms,” mcr.aacrjournals.org/content/1/5/385.long
“The role of protein kinase A pathway and cAMP responsive element-binding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus,” jme.endocrinology-journals.org/c … 1/107.full
Droid,
Agreed. The Thread about Forskolin should also mention Methylation treatment. Whether these are connected and how i do not know. All i know is that both regimens were needed to keep me functioning in the long run.
Again, i am not suggesting that this will happen to all ex-Finasteride users but if Finasteride brings havoc to neurosteroids then in the long run you will have even more severe problems.
I will have an MRI on my spine for possible nerve degeneration due to lack of Pregnenolone. The fact that my blood results are showing normal Thyroid function and Free T without any medication is nothing less than miraculous.
You know what, I was skeptical reading this but I’ve really felt improvements in my mental state since taking Solgar and Forskolin.
Is there any tolerance to these supplements? Should they be cycled on and off, or can they be taken every day?
I haven’t noticed any tolerance so far, it’s been around 1.5 month since i upped my dose for both supplements (i think).
We got our 3rd Methylation Pathways Panel from AnnonXXX (anonymous user ID) and 4th on the way.
This is the lab that measure glutathione and methylation cycle levels. The values are shockingly similar and continue to overwhelmingly support this theory. The values are consistently worst that the values of the Chronic fatigue study Rich Van Konynenburg. I’ve post our numbers in the below spreadsheet and included the CFS numbers for reference.
Below are my notes on AnnonXXX’s results, but they all apply to me too. I have discussed the consequences a lab result like this throughout the thread.
If you want to read what Rich says about each of these, he posted an explanation here:
mecfsforums.com/index.php?topic=290.0
For your reference co-cure.org/scan0003.bmp
Glutathione
Glutathione-reduced (GSH) is the good glutathione that should be as high as possible in range. Glutathione-oxidized (GSSH) is the bad kind, which should be excreted or recycled back to GSH, and should be as low as possible in range.
You’re GSH is very low. This is Glutathione depletion.
AnnonXXX’s GSSH is high, suggesting an oxidative stress environment and/or an inability to recycle glutathione.
The ratio of GSH to GSSH is the ‘redox potential of the cell.’ The redox potential is basically one of the most important cell environment measurements. When that ratio is low, there is a very oxidative environment. I can research to get examples, but one of the typically examples is how an oxidative environment disrupts proteins with cysteine amino acids. Rich talks about this in his lecture.
There is an equation the papers use, but a straight division of GSH by GSSH can tell how oxidative or reductive an environment. AnnonXXX’s is: 6.27. Mine was 5.35 at the start. Any ideal ratio (from the middle of the range) is maybe 15.
I haven’t previously discussed Redox Potential, but it will be very important and I will post on it later.
SAMe and SAH
SAMe is the major methyl-donor in the cell. A methyl-group is taken from methyl-folate, it makes it around to SAMe. SAMe goes and puts that methyl group on something that is biologically significant (like DNA methylation). When SAMe loses it’s methyl group, it is turned into 'SAH, which is converted to homocyestine, which can go back around the cycle or down to GSH.
SAMe is low, meaning the methylation cycle is not turning to get new methyl groups around. SAH is high, again suggesting the cycle is not recycling the contents.
Per Rich, this indicates a Methylation Cycle block. The metabolites are just sitting there not going to the next step.
Folates
Most of the folates are in range.
Methyl-folate (5-CH3-THF), which is the one we supplementing the protocol, is barely in range. But the interesting result is the THF (tetra-hydro-folate). This is what is left after the methyl-group is removed from the methyl-folate (see diagram). When THF is low it is, again, an indicator that the methylation cycle is not running. If it were running, methyl groups would be pulled off of Methyl-folate and THF would be building up. But THF is low.
I don’t have the 2nd panel because that person has not been around. But he references his data here:
droit - I have been trying the limited simplified protocol of 400 mcg methyl folate and approx 125 mcg methyl b12 about every 2 or 3 days. If I take it more often than that I get really dragged out mentally (more tired and brain fog than when I started). However by taking it every 2 or 3 days there is usually a day or so when I sleep well and feel generally better. I was looking at Dr Konynenburgs protocol and was looking at the multi vitamin supplement he recommended ( holisticheal.com/all-in-one- … sules.html ) and was wondering what you thought of it? I am leary of trying something with so many different ingredients. What do you think of the value of the 23andme test.
Effects of PNU157706, a dual 5-reductase inhibitor, on gene expression in the rat epididymis
Droit- have you been able to out your theory in the context of the Italian Nuerosteoids findings?
Jarrow’s B Right, a popular B vitamin supplement on this forum, claims it contains Folate: Folate (from folic acid and Quatrefolic® (6S)-5-methyl-tetrahydrofolic acid glucosamine salt)
The folic acid kind of turned me off, but I still thought it might be a small percentage of the formulation.
Nope. It’s a fraud. Check out the following review on Amazon:
amazon.com/Jarrow-Formulatio … 7s+b+right
Some other choices for B-Complexes (which may still need further scrutiny and vetting) are:
swansonvitamins.com/swanson- … 0-veg-caps
seekinghealth.com/b-complex-supplement.html
thorne.com/products/vitamins/prd~b104.jsp
vitacost.com/vitacost-synerg … capsules-1
Not disclosing how much of the “traditional” form and “active” forms w/in the same line item also appears to occur with B6, so keep that in mind.
Also note that a lot of supplement/vitamin products have added crap in them, including Spirulina. According to the book “Could it Be B12?”, Spirulina contains a pseudo-form of B12 which actually competes with B12 absorption.
Genetic Analysis Report Cheat Sheet
vsan.org/rok-az/methylation/ … heet_1.pdf
Study on Glutathione levels and erectile dysfunction
ncbi.nlm.nih.gov/pubmed/15910541
Yasko’s latest book
scribd.com/doc/81963801/113/BHMT-Status
I’m going to have my bloods taken for the methylation panel; but, I’m taking Testosterone 200mg jabs every 2 weeks - does this have any effect on when I should have the bloods drawn ?
I just got my methylation blood test results back from Health Diagnostics (BTW, here is a link to the test if you want to get your doctor to order the test for you: http://www.hdri-usa.com/tests/methylation/).
My results are very similar to the others I’ve seen here, and similar to what you’d see in CFS patients.
This is what a methylation block looks like.
And these results are taken after a three week course of adenosyl-B12, methyl-B12, SAMe, and Thorne’s ‘Methyl Guard’ product. (I stopped all supplements a week before testing to get back to some semblance of baseline.)
My current regimen consists of gradually increasing the amount of MTHF until I hit 8mg (recommended by a health care professional). I’m on 4mg daily now, along with SAMe, adenosyl-B12, methyl-B12, Methyl guard, and potassium.
Thank you MerryChristmas for posting your data. I’ve added you to the data sheet.
My notes on AnnonXXX apply to your results (viewtopic.php?f=27&t=7178&start=240#p74980).
The data continues to be the same for everyone. Depleted reduced-glutathione, high oxidized-glutathione low SAMe, etc. All directly supporting the theory described in this thread.
As I’ve said before, the redox-potential, which is indicated by the ratio of reduced to oxidized glutathione is one of the most important physiological state in the cell. We are getting measurements of a very oxidative ratio. The normal is ~14 or 15, we are about 6.
This has massive impact on a lot of basic biology.
We’ve got our 5th Methylation Panel result from Toadstool. His data is different from the other three - but indicate the same conclusion of methylation block/depleted glutathione.
The typical pattern we see is depleted good/reduced-glutathione (GSH) and high oxidized-glutathione (GSSG). And low SAMe and high S-Adenosylhomocysteine. Which is the mark of a methylation cycle block.
But Toadstool is just low on everything. He has the most several depleted GSH we’ve seen on this board, but he doesn’t have the high GSSG.
I would normally say the low GSSG is good because it indicates a less oxidative environment, but he’s so low on GSH. Its almost like everything as just been drained from the cycle. Or maybe he has other oxidative control so GSH isn’t getting oxidized.
I keep talking about the ‘redox ratio’ which is GSH:GSSG and is an measurement of redox potential in the cell - the higher the ratio, the better. So far everyone is ~6. The normal (based on the means of the normal range) ~14-15. Toadstool’s is something like 8, which alone is better than everyone else, yet he is the lowest on GSH.
So I don’t know if this is the healthiest data from our pool or the worst. Its very confusing.
Same thing with the folates. Everything but methyl-folate and Folic Acid is below range - all of which indicates the folate cycle is not spinning, which means the Methylation cycle is not moving.
The genetics could explain this pattern:
So this finding could be helpful to someone like Bluejaysfan show also has compound mutations in MTHFR.
MerryChristmas has said he is going up his Methyl-folate to 8mg over time. Maybe that’s something we should look at doing to get the folate pool up? Hopefully he’ll update us with his progress.
i hope you are right.
why nobody is trying a treatment to test it?
This is a very very good question.
This thread started based on a condition that matched up with PFS in that it is a multifactoral, core condition with an element of ‘persistence’ and a characterized ‘genetic’ predisposition.
As you read through the thread, the theory has matured from that to reverse engineering how you get from Finasteride to this condition and how the glutathione-depletion condition explains the symptoms in PFS, etc. I would challenge all PFSers to watch this 3 part lecture on the Methylation-Block/Glutathione-depletion condition: iaomt.media.fnf.nu/2/skovde_2011 … Bweburl%7D
From there we’ve gathered real genetic data which has shown that, for those tested, there is a real predisposition to this condition. We’ve also gathered startling lab data completely supporting this theory (based on 5 lab tests - sdrv.ms/1aVecBO).
We’re at the point where we can move out of the theories section and say with confidence: this is happening in us.
And I will continue to research the hypothesis that this is how it all starts, and everything else is downstream of it.
As far as I know, this the most well rounded, well supported explanation of PFS publicly available.
Given all that, why are only a handful of people testing the protocol?
I think there are a couple of reasons.
First, the ideas in this thread are in depth and it takes some time to understand. I’ve reflected on how best to make these posts, but in the end I figured completeness is best for future reference.
Second, and probably most important: We all want to log in one day and see a post that says ‘take this single pill, and in two weeks you’ll be recovered.’
From my understanding of the physiology described in this thread and in the test results, that is not the way it is going to work. The protocol we are using is borrowed from the CFS community, which is described as a longer term protocol.
Given that, you really have to see a test result confirming this to click your brain into committing.
A lot of people have responded, but we’re still trying to figure out what the best protocol is for us. That’s why I’ve set up the ‘treatment thread’ here viewtopic.php?f=6&t=8481.
CDNUTS has said the ideas and protocol in this thread were essential to his recovery (viewtopic.php?f=27&t=7178&start=220#p74436), but we havent had a recovery credited to this idea yet - maybe we need to look at what he has done in addition to the CFS protocol.
We’ve got a lot of ambitious men on this forum. Perhaps its time we get people trying various versions of the methylation protocols and working with local methylation experts and/or genetics oriented health care providers in respective locales.
If we get our health care providers to look through this oxidative stress lens, who knows… we might get a recovery.
