Finasteride causes glutathione depletion and leads to CFS?

General Discussion
#21

@bryce54,

I had not seen 23andme before. I have been particularly interested in getting some form of genotyping related to methylation pathways, but was looking at the below test which strictly looks at methylation related genes.

holisticheal.com/health-test … lysis.html

Upon a quick scan, I had a hard time seeing the list of genes this 23andme assay looks at. I want to find out how much overlap there is because it seems this 23andme test is cheap.

Also, take a look at this thread: viewtopic.php?f=1&t=7293, we’ve got an interesting discussion about some genotyping results going on.

#22

very interesting stuff droit. very happy to see someone who is looking into this very extensively… really good stuff man, great value you are bringing here.

btw, have you heard of people who have had issues on SAM-E or phosphatidyl choline? someone mentioned to me some serious issues with supplmenting sam-e, but not sure how serious it really is. same with phosphatidyl choline.

#23

@bryce54,

Unfortunately I am not up on SAM-E or phosphatidyl choline from my blog reading. Right now I’m focused on the B’s. There is a post from Freddd (known to have healed himself of CFS) where he describes how he layered the supplements and eventually incorporated SAM-E at the below link - look for his response to Nicola.

forums.phoenixrising.me/index.ph … 42/page-35

#24

My reduced glutathione was low, as tested with the Methylations Pathway panel. It points toward excessive oxidative stress in my body.

I think I’ve now seen 3-for-3 guys on the board report low glutathione. It’s a very small sample size, but if it bore out as a pattern, it would suggest oxidative stress as a factor in PFS. I find this interesting in terms of understanding the etiology of the disease – what is it about PFS that results in excessive oxidative stress? It could be a clue in the research process.

If anyone is thinking of testing this… the Methylation Pathways test has two main advantages over other glutathione tests:

  • I believe most tests only measure “total glutathione”, which lumps the used-up stuff in with the fresh stuff. The Pathways panel reports these separately, telling a much more useful story about oxidative stress
  • I believe most tests include red blood cells in the sample. Rich said this has a tendency to artificially skew the result artifically high, b/c RBC’s are a net exporter of glutathione.

There’s another marker of oxidative stress I know of: 8-hydroxy-2’-deoxyguanosine on the Metametrix Comprehensive Organix profile. If anyone has done the Organix test, can you volunteer what your result was?

As Droit indicated, direct glutathione supplementation has mostly been a failure in the CFS/ME and autistic communities, despite the fact that both diseases are charcterized by glutathione depletion (and excessive oxidative stress). But I’m not sure anyone has figured out exactly why it usually (not always) fails. More success has been seen from supplementing precursors (i.e., NAC), and through the Simplified Methylation Protocol (SMP), which primarily features a combination of 2mg vitamin B12 and 400mcg 5-MTHF (“methylfolate”), which helps kick the methylation cycle into gear and has been shown in research to somehow or another spur glutathione production.

I’ve actually been taking the SMP as part of my supplements. I can’t say it’s changed how I feel, but I wouldn’t necessarily expect it to – I think oxidative stress is more likely to be another symptom, not the cause of PFS. (It’s a symptom worth fixing, though, b/c oxidative stress ages the body and affects health in many ways, whether we feel them or not.)

#26

mariovitali,

I’m glad to see someone else is experimenting with building up glutathione. Before you do too much treatment, would it be possible to get a Methylation Pathways Panel from Vitamin Diagnostics to look at your Reduced glutathione?

It’s true that NAC is a precursor to glutathione (there are lots of studies, one good one is “Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration”). And it is an anti oxidant on it’s own. But I want to note that if anyone wants to experiment with this angle, in addition to NAC they should work on supplementing for the methylation cycle. When the methylation cycle is running, you’re body will produce perpetual glutathione (assuming you don’t exacerbate the biochemistry with oxidative stress).

The basic plan is:

  1. Active folate (5-methyl tetrahydrofolate) - Solgar’s Metafolin is the cheapest
  2. hydroxocobalamin (B12 that is not cyanocobalamin some use methylcobalamin)
  3. General Vitamin Neurological Health Formula (most important ingratiate is trimethylglycine)
  4. Phosphatidyl Serine Complex

The full explanation of this treatment and dosing is here:

phoenixrising.me/treating-cfs-ch … nburg-ph-d

joetz’s recovery period described here: renewlife.com/heavy-metal-cleanse.html) has a low dose of NAC.

#27

Hi Droit,

A lot of good info on your post, thanks Man. I will check this regimen ASAP. One more thing : I believe that our problems also have to do with neuro-degenaration and if i am not mistaken Glutathione has neuro-protective effects. I must find the relevant papers and send them.

I am also experimenting with Sideritis. I have seen several papers that state that it has neuro-protective abilities, probably protects from Alzheimer’s AND raises Glutathione. All in one package. Check out Sideritis here :

en.wikipedia.org/wiki/Sideritis# … d_benefits

and

google.com/patents/US20130022693

Unfortunately i cannot have the Methylation Pathway Test where i am.

#28

mariovitali,

The methylation cycle is certainly responsible for stabilizing myelin by methylating myelin-basic-protein - the raw material of nerve sheaths (a Google search brings up numerous descriptions of how the ‘methylation cycle’ is essential for myelin production but a few citations: “Biological methylation of myelin basic protein: enzymology and biological significance,” “Effects of the disruption of transmethylation in the central nervous system: an animal model,” and “Studies on myelin-basic-protein methylation during mouse brain development”).

When the Methylation Cycle is blocked, the cycle’s end-products, such as glutathione and methylated myelin-basic-protein are not produced produced. Therefore normal turnover of the myelin is not repaired.

In communities that are known to have wide spread ‘Methylation Block’ (e.g. chronic fatigue and autism groups), they report ‘de myelination.’ Amy Yasko, an autism doctor talks about the Methylation Cycle and myelination in her book (dramyyasko.com/wp-content/fi … 2_file.pdf).

And Rich Van Konynenburg, a popular CFS theoretical scientist, talks about ‘white spots’ in the brain seen in MRIs of CFS patients, similar but not as severe as in M.S. patients in his video lecture (bryce54 posted a link to this lecture earlier in this thread).

Remember that if you think you’re in this state, you won’t get the benefit of myelin protein production with just NAC. You’ll have to stimulate the Methylation Cycle with active B12 and active folate to get methyl groups passing around.

#29

This makes perfect sense.

I will say something that i haven’t said before. It sounds crazy but i will say it. Believe it or not i can understand when i am turned on when i see a hot woman because immediately i feel the signal sent from my brain to my penis (…!)

What worried me is that the intensity of this signal has been steadily deteriorating over the past couple of years. I am more than certain that this is neuro-degeneration in action . OTOH if i feel the intensity of the signal getting more intense then i will now that whatever i am doing is working. I know that this is a very slow process because i have seen how slowly this deterioration occurred.

Above all try to listen to your body Guys. It tells you everything you need to know.

I will hit the shops tomorrow to buy all the supplements you discussed to support the Methylation Cycle. Thanks very much droit, i really appreciate your help.

#30

My question for you mariovitali is why do you have to buy all these supplements when you say you are recovered?

#31

I have the same question.

#32

tim1911, that’s a good question, and it’s the central theme of this thread.

mariovitali has said the below in this other thread (viewtopic.php?f=27&t=7762&start=20#p70443):

This observation is inline with reports from communities who do have glutathione depletion (autismpedia.org/wiki/images/d/da … -cycle.jpg) produces glutathione in a perceptual cycle, but the biochemistry can become blocked upon exposure to high oxidative stress (the level of stress a person can take is proportional to the genetics in his/her methylation cycle enzymes).

Of course, we don’t know if mariovitali has depleted glutathione, as he hasn’t taken a test to indicate this. But I suspect mariovitali is taking his above referenced experience and this information and seeing what will happen when stimulating the methylation cycle directly.

If you want to learn more about this methylation-cycle-block/‘vicious cycle’ mechanism I would recommend listening to the podcast I posted at the beginning of this thread, or the video lecture posted by bryce54.

#33

I think we should donate to the PFS foundation so that the scientists can figure it out because no one here is going to and to think otherwise is just stupid. The scientists are looking into genetics and epigenetics.

#34

Thanks droit,

Just to also add that NAC is a Mucolytic and i do not know what is the impact on lungs if taking a mucolytic for a long time. I will have to check with a Doctor about this ASAP (This was also discussed in my previous thread).

#35

Hi Guys,

Yesterday was my first day using supplements which support the Methylation Cycle. More specifically :

  1. NAC 300mg
  2. B12 - Methylcobalamin
  3. TrimethylGlycine (TMG) 500 mg
  4. Haven’t found Active Folate so i ate Spinach + Asparagus which are good Folate Sources
  5. Selenium, Zinc, Magnesium, D3

The morning wood today was… unbelievable :slight_smile:

I continue to feel great, no side effects, remembering my dreams, Libido continues to be 100%, no “ups and downs”.

I don’t want to get excited but i feel very positive about this regimen. I was almost in pain from the intensity of my morning wood. Let’s hope it stays that way…will keep you updated as always

#36

mariovitali,

That is a lot of TMG. I only get 25 mg from my vitamin source.

TMG stimulates the ‘short cut’ around the methylation cycle. Most use it at the beginning to get things running and build up some glutathione. You can see the shortcut on this diagram: TMG stimulates the BHMT enzyme.

autismpedia.org/wiki/images/d/da … -cycle.jpg

However, Dr. Van Konynenburg and Dr. Yasko say that you should only use the short cut to get some glutathione built up, then ideally get the ‘long way around’ running so everything to the left spins. In fact, after sometime they recommend cutting the TMG and supplement ‘DMG’ to back up the ‘short cut’ to force the long way around the methionine cycle.

You’ve already front loaded NAC so your glutathione may be go for lower doses of TMG.

Be careful - you don’t want to overrun the methylation cycle, thus chewing up raw materials. From what I’ve read, I would pull back and maybe just do a crumb of that.

You’ll defiantly want to keep looking for the active folate (methyl-tetra-hydrofolate), as that is a critical methyl-donor. Sometimes its call metafolin in case that’s helpful.

metagenics.com/mp/products/folapro
vitaminshoppe.com/store/en/b … XZzRCtAQ_Q

I personally have a mutation in the MTHFR enzyme (just like moonman1 viewtopic.php?f=1&t=7293&start=20 – kazman has two mutations in that enzyme) that weakens my ability to convert the folic acid found in vitamins to active folate. So active folate is an absolute must for me. That was smart to eat some Spinach.

It would be great to get more data and get some people experimenting with different things. I think mariovitali’s NAC angle is going to be interesting. If anyone wants to try this, the base protocol costs ~$25 a month. I am happy to answer any questions.

#37

OK Thanks, will do. Imagine that the brand i am using (Life Extension) says to take 2 tabs of 500mg daily.

Yes i am about to order it from US because it just doesn’t exist where i am and Amazon does not send it here so i will have someone to send it to me. It won’t be another 15 days until i get it unfortunately.

So how do you know about these mutations? What kind of test did you have?

Actually i tried yesterday stopping NAC and at night i started feeling like crap again. So for now it appears that NAC is essential. One more thing : When i get the dose of all the supplements discussed i feel a bit sick for 20-40 minutes, as if i am about to get temperature if you know what i mean. This was more evident when i first started NAC but now it appears to be wearing off.

Did you have this happening to you? I read that by starting the protocol you might feel strange and well, this happened to me.

#38

I think this theory holds a lot of water, I had also talked to Freddd on another website, but I have not followed his specific protocol. I am taking an active form B vitamin though. I think this theory could go a long way into the research on how we can find a cure.

Just a few random questions: Ok now I know a lot of guys here have trouble with libido (including me). I am in a fairly new relationship and have not had sex yet, not because of ED but it’s just not at that stage yet. But when I hang around her and touch her (hold hands, kiss, etc.) I start to get an erection. I honestly don;t know what this means. Not sure how bad other guys ED, but is this a good sign of a recovery for me, or at least my chances?

Also, I am still in the process of finding a legit Chinese Traditional Acupuncturist, and am wondering what would be the best treatment to ask for? Should I have them specify on treating the endocrine system, the methylation pathways, etc? I’m just curious to get some others thoughts since I have read a lot about Acupuncture helping methylation.

#39

Not sure about Acupuncture…Never heard b4 using it for Methylation. Regarding your other question, if you can have an erection then this is definitely a good sign isn’t it? :wink:

#40

Well when I search it, many results came up. But someone told me once that there is more than 1 type of methylation? It was brought up to me while talking about Awor’s theory, but I don’t know too much about methylation really.

And yes I suppose you’re right!! But that could be because my T/E2 ratios are good, as I have low E2 and moderately low T and free T. It seems like I have every other side though: Weight/water gain, gyno, decreased testes size, dry skin, cold body temp, brain fog, poor oral health, general fatigue. Man we need a cure.

#41

I had a 23andMe (23andme.com) test done, which is a near-full record of known SNPs for $99. Its been really great, because they give you the your genome data so if you know how to use the SNP ids you can reverse engineer the results of different publications that talk about SNPs. For example, in “Common variants of FUT2 are associated with plasma vitamin B12 levels” (ncbi.nlm.nih.gov/pmc/articles/PMC2673801/) they identify SNPs responsible for B12 status. I was able to use that data to determine I have heterozygous mutations in a gene that results in lower B12 (which is actually fairly common: 53% of the population).

Also, there is a wizard at geneticgenie.org what will take in raw 23andMe data and give you your methylation related genotype. moonman1 was cool enough to post his results from this wizard here:

viewtopic.php?f=1&t=7293#p65035

He’s got a couple of mutations of interest: 1) MTHFR (the gene that converts folic acid to its active form) and 2) mutations in BHMT - the gene I talked about in the eariler post. I wonder if he would feel better with methylfolate and TMG?

I’ve been amazed at how quickly you respond to NAC. Now that I started taking it, I also have felt some improvement like energy and oily skin, but not to the level you’ve had. I’m wondering if your response is from replenished glutathione, the general anti-oxidant feature of NAC or repleted cysteine. Probably all of the above.

As far as reactions to the methylation treatment, I don’t get acute response like you, but I have had 'start up symptoms."

Those that have been sick for a long time have start up symptoms when beginning methylation treatment. Most think its related to rebooting the detoxification and immune systems. The biggest symptom for me was hypokalemia (low potassium). I was getting very tired and having strong muscle spasms. Then I read the message boards and figured out it was related to depleted potassium - which most people get. They think that once you start supplying the body with folates from a depleted place (which I was from two independent tests), the body can begin cell division again and new cells need positive cations like magnesium and potassium. So I took this as a good sign. I started drinking coconut water and eating bananas and that went away.