Acne.org Products
ver the past few years, we have heard from a few PWCs (people with
chronic fatigue syndrome) who have reported that they were given Accutane as a treatment for severe acne, and that this contributed to the onset of CFS in their cases. I have not understood the mechanism of this in the past.
Recently, I learned that one of the actions of Accutane (also known as
Roaccutane, isotretinoin, and 13-cis retinoic acid) is to raise the gene
expression for the enzyme glycine N-methyltransferase.
This enzyme normally acts as sort of a safety valve on the methylation cycle, to keep the ratio of SAMe to S-adenosylhomocysteine from going too high. It shunts some of the methylation capacity into methylation of the amino acid glycine to form sarcosine. This uses up some of the SAMe and forms S-adenosylhomocysteine. Sarcosine then contributes to the production of methylene tetrahydrofolate.
Since a partial block in the methylation cycle appears to be very important in the pathogenesis of many or most cases of CFS, I suspect that this action of Accutane is what is involved in the onset of CFS in some people who have had Accutane treatment for acne. A big boost in the activity of glycine N-methyl transferase would cause a major drop in available methylation capacity, and this would have a number of effects, including lowering the production of creatine, phosphatidylcholine, coenzyme Q10, and carnitine, as well as many other substances that require methylation, and lowering the methylation of DNA, which in turn would affect the expression of a number of other genes.
One thing Im wondering is how long these effects might last after termination of Accutane treatment. Would there be a long-lived epigenetic effect because of the impact on methylation of DNA? I dont know. If so, this might explain why some people have reported long lasting effects.
Rich Van Konynenburg, Ph.D.
Independent Researcher
Use of ribose and NADH supplements have been reported to boost levels of adenosine-5'-triphosphate, or ATP -- a primary fuel source for the body and the brain. The supplements have also been shown to be helpful in treating chronic fatigue.
The research team explored use of ribose and NADH supplements as treatments for autism in two parallel studies using ribose and NADH.
One study investigated the effect of supplementation with NADH, an important co-factor for many enzymatic reactions in the body.
Another study investigated the effect of supplementation with ribose, a special sugar made by the body from glucose.
The studies found use of ribose and NADH supplements had similar effects, boosting levels of methylation, glutathione and ATP after only two weeks of therapy.
Levels of ribose and NADH also improved substantially, without adverse effects. After just two weeks of therapy, one child in each group was reported to have some improvement in energy level.
The biochemistry of both NADH and ribose is well-established, as well as how both affect production of ATP, glutathione and methylation
ACCUTANE LOWERS NADH IN CELLS. Making connections one day at a time.
1 hour ago, guitarman01 said:http://www.gordonmedical.com/unravelling-complex-chronic-illness/rich-van-konnyenberg-died-early-tuesday/
Rich believed it is possible that amethylation block, causing glutathione depletionwas an important trigger in causing symptoms in Chronic Fatigue Syndrome, and he developed the Simple Methylation Protocol as an over the counter treatment for patients to experiment with.
This is the same dr that was in contact with someone from that other forum I linked. Believed and tested? accutane caused some methylation block even years after treatment. Accutane causing a hyperactive Glycine N-Methyltransferase
http://phoenixrising.me/research-2/glutathione-depletionmethylation-blockades-in-chronic-fatigue-syndrome/glutathione-depletion-methylation-cycle-block-a-hypothesis-for-the-pathogenesis-of-chronic-fatigue-syndrome-by-richard-a-van-konynenbury-ph-d
What evidence suggests that this same dysfunction and similar genetic factors are also present in chronic fatigue syndrome?
1. Methionine concentrations are reported to be below normal in both plasma (19) and urine (20) in CFS patients. Low methionine can be caused by a methylation cycle block.
According to this Hypothesis, when reduced glutathione is sufficiently depleted and the oxidative stress therefore becomes sufficiently severe in a person having the appropriate genetic predisposition, a block is established at methionine synthase in the methylation cycle (95,2,3). Because the methylation cycle is located upstream of cysteine and glutathione in the sulfur metabolism, these are further depleted, and a vicious circle is formed.
we might have a problem right here with the MAT1 enzyme that takes methionine and converts it to SAM-E, which then leads to all of the the other metabolites. Taking massive SAM-E skirts this process... we have a loophole.
It all starts here...and then becomes chronic. I think our livers might be damaged to where we cant contvert even the methionine from foods. 20+ years of eating a fairly high methionine diet produced nothing. one month of taurine supplementation reversed stool color (absorbing fats now) and hair shedding. so something was blocking taurine from being made.
paper linking liver damage and poor methionine conversion to SAM-E
upping SAM-E to 1200mg per day
taurine (providing end metabolite for fat digestion and bile thinning)
TMG (providing the methyl groups we need, also some glycine needed for GSH)
B6 (to recycle back to SAM-E)
If we have any Gene expression problems .. this is also the goto....
https://en.wikipedia.org/wiki/S-adenosylmethionine_synthetase_enzyme
S-adenosylmethionine (SAM) is amethyldonor and allowsDNA methylation. Once DNA is methylated, it switches the genes off and therefore, S-adenosylmethionine can be considered to controlgene expression.[3]
SAM is also involved ingene transcription,cell proliferation, and production of secondary metabolites.[4]Hence SAM synthetase is fast becoming a drug target, in particular for the following diseases:depression,dementia, vacuolar myelopathy,liverinjury,migraine,osteoarthritis, and as a potentialcancerchemopreventive agent.[5]
I knew if I started talking about meth(ionine) I'd hear from tryingtohelp. 1200mg Sam - eis a lot. I'm sure your gona feel something from that. I got my money on nadh atm just ordered some
study I linked showed it was actually decreased in live cells treated with retinoids. Anyone tried this supplement yet?
Nadh required in folate cycle. That Dr thought folic acid was missing in the Methylation Block. But it wasn't folic acid
On 1/11/2016, 10:57:20, Branches said:Hey Justmom,I'm sorry for what happened to your son. I also suffer from severely impaired sexual function (alongside many other side effects) as a result of isotretinoin and have tried making and using a cannabis concentrate to resolve the issue. I have taken detailed notes and could perhaps guide you through the process of producing and using the concentrate if you're interested.
I highly recommend that you make your own concentrate so you know exactly what goes into it (no dangerous stuff!). I know that Rick Simpson recommends using all kinds of highly toxic solvents to extract the oil from the plant matter, but I st
rongly discourage you from doing this. It is needlessly dangerous, and I find it hard to believe that you can truly remove ALL the solvent from the oil (and a few tests have backed up this notion). Please stick to food grade solvents so you don't have to worry about it (190 proof grain/drinking alcohol, such as Everclear, works well enough. I can provide you with a few options if you're interested).I feel that I cannot say whether or not this treatment could work due to the fact that, because I was in college at the time, I couldn't always ingest the potency that I would have liked to, my first few batches were weak, and I ended up cutting my treatment short for various external reasons. If your son is still at home, this is a good time to try it as he'll have your help and the free time necessary to stick to his dosages and complete his course/s.
Though I can't claim to have definitely experienced any lasting benefits from the incomplete course that I went through (which lasted under two months), I admit that it does perhaps show at least SOME promise as I do reliably get good erections when I get high from vaporizing cannabis. I don't, however, remember ingesting it providing quite the same effect, but perhaps that was just due to the delay before it hits you after ingestion (inhalation is more immediate). I know off the top of my head that at least one person who claimed to have successfully regained sexual function through this method did so after 5 months and another after 3 months. The positive improvements for at least one of these people remained for a least a few months after stopping the cannabis concentrate because he checked back in and gave an update before dropping off the radar for good. I've collected a number of anecdotal claims of marijuana's effectiveness in treating this issue which I could provide you with if you wish (it's rather long so I won't post it here).
Dosage
As far as dosage I can only say that it sounds like most others attempt to follow the dosage that Rick Simpson suggests for cancer treatment. One course of treatment involves the ingestion of 60 grams of oil over a period of 90 days. 1 ounce of flowers should produce about 3 - 4 grams of oil. As I stated above, some people didn't feel fully recovered until 5 months, so you may want to plan for 2 courses.You will want to incorporate a ramp up period so his body can get used to the dosage slowly. If you start him off at full dosage it will probably knock him out for a few days. If you acclimate him slowly he will be functional. I can provide you with details on my dosage progression if you're interested.
Strain
As far as which strains, I can tell you that I've only ever used indica dominant strains. This is due to Rick Simpson's recommendation. I assume the others probably followed his advice as well.I'll check back here soon to see if you have any questions, etc.
Branches, thank you for replying! Since I cant keep a houseplant alive and medical mmj places are as abundant here as Starbucks, I will most likely buy it rather than grow it. I would be interested in having the anecdotal claims you mention, as I may have to document some success stories to get a medical mmj card for my son. I havent been through that process yet, but I know that sexual dysfunction is not on the list of approved maladies. I would also be interested in knowing your dosage progression. Ive had others suggest dosing amounts, but at this point am interested in all options.
- The lipophilic nature will then suggest that the cyclodextrin may be able to complex with it if the accutane is in high enough levels where the drug gets to.
- I don't know how to explain the reaction, but it is of significant concern because any number of lipohilic substances could be affected (not just retinoids). I would be very concerned about continuing this approach without medical supervision in a controlled setting.
- I haven't been involved in the care of such patients, but the dermatology and toxicology communities would be appropriate to approach for this experience
I would also not recommend taking additional trimethylglycine (TMG, also called betaine) or additional forms of choline, such as phosphatidylcholine or lecithin, since that may stimulate the BHMT pathway too much at the expense of the methionine synthase pathway. The betaine-HCl used to augment stomach acid is something that may have to be omitted while doing this treatment, too, since it will contribute to this stimulation.
http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/simplified-treatment-approach-based-on-the-glutathione-depletion-methylation-cycle-block-pathogenesis-hypothesis-for-chronic-fatigue-syndrome-cfs-by-rich-van-konynenburg-ph-d
One of the things Roaccutane (or Accutane or isotretinoin or 13-cis retinoic acid) does is to raise the gene expression of the enzyme glycine N-methyltransferase. This enzyme normally limits the ratio of SAMe to SAH in the methylation cycle. When the activity of this enzyme is increased, the ratio of SAMe to SAH is decreased, and this causes a methylation deficit, so that the many methyltransferase reactions in the body are downregulated. I think this is the connection to ME/CFS. Over the past few years, I have heard from several people who developed ME/CFS after being treated with Accutane. I don't know why this happens to some people, but not to most. I'm aware of one case in which testing indicates that glycine N-methyltransferase has remained upregulated even years after Roaccutane treatment was ended. I don't know why.
Glycine N-methyltransferase is normally inhibited by 5L-methyl tetrahydrofolate, which is a form of folate used in the methylation treatments. If glycine N-methyltransferase is responsive to it, as it normally is, the methylation treatment should downregulate it. In the case I refer to, this doesn't seem to work, and I don't know why. Perhaps there is a genetic polymorphism in glycine N-methyltransferase in some people that causes it to be unresponsive to methylfolate. http://forums.phoenixrising.me/index.php?threads/roaccutane-caused-depression-isotretinoin.12117/#post-206039
you guys really need to read all the comments from rich
talks about test that can be done
and treatment with a certain form of folate that none of us have tried.
maybe it will work
My current working hypothesis about cases of ME/CFS that apparently result from use of Roaccutane is that this drug causes a shift in the epigenetics (gene expression) of the enzyme glycine N-methyltransferase for some people, raising its activity, and this shift stays "stuck" in these people, so that the activity of this enzyme is then not under normal control. This drains off their methyl groups and thus "starves" the methyltransferase reactions in the body. This would be considered a vicious circle mechanism, because methyl groups are what are needed to silence gene expression, and the high activity of glycine N-methyltransferase prevents them from being available to do this.
My current hope is that using higher than usual dosages of 5L-methyl tetrahydrofolate (a component of the methylation treatment I have suggested), will eventually shift the epigenetics back to normal by suppressing the activity of glycine N-methyltransferase at the biochemical level, thus raising the available methylation capacity, and hopefully lowering the expression of this enzyme by methylating the DNA that controls its expression and breaking the vicious circle, so that things will come back to normal. This is unproven at this time, but I am hopeful that it will work.
I recommend that anyone trying this be under the care of a licensed physician, because it would be an experimental treatment and the detailed response in an individual could not be totally predicted. I will note that 5L-methyl tetrahydrofolate is a naturally occurring form of folate in foods, is normally the folate with the highest concentration in the human bloodstream, is an essential part of the metabolism of all the cells of the body, and is the only form of folate than can pass into the brain. The key part of this treatment would be the high dosage. I also note that in the U.S. the PamLab company supplies a prescription "medical food" called Deplin for treating depression that contains 15 milligrams of this folate, which is a much higher dosage than I have recommended as part of the methylation protocol for treating ME/CFS. Note that ME/CFS usually involves a different problem in the methylation cycle than what appears to be the problem in the apparently Roaccutane-caused cases. Most cases involve a partial block of the enzyme methionine synthase, and this same form of folate is a substrate for this enzyme, so it is included in the treatment for most ME/CFS cases, but not at as high a dosage as I think will be necessary to break the imputed vicious circle in the apparently Roaccutane-caused cases.
I do not know how high the dosage of 5L-methyl THF would have to be to break this imputed vicious circle. I think the prudent approach would be to come up slowly on the dosage, and if symptoms appear that are intolerable, to stop, at least until things calm down. It may take some time for the symptoms to die away, because folates have a long residence time in the body.
READ THAT ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
so any one tried taking up to 15 pills of folate in its active form per day? holy f@ck
54 minutes ago, trantran83333 said:Would this explain why we are always tired?
The amount of crap you've gotta go through just to stay healthy - don't you just love it when doctors say that the body wants to heal itself or stuff like, the liver has an incredible ability to regenerate, yeah right. If I sit around waiting to heal it will never happen.
If we sit around just waiting to get better through normal living and having a healthy diet etc, I guarantee nothing will happen. We need supplements or medicine to get out of this mess!!
There have been some really good insights over the last few pages - thanks for those who are finding all this info.
Thanks to Roche for nothing - just leave us all in the shit trying to work our own way out of it.....Pricks!!
@modeaa so you are the one I was reading about on the chronic fatigue forum at Phoenix rising. So have you tried high dose folate? If so how much per day? Thanks
On 1/19/2016, 9:03:07, trantran83333 said:Has anyone ever thought about candida/parasite infection? I was diagnosed with both, and leaky gut. I'm going to start my treatment today and update how I feel in a couple of weeks
i looked it up and found that I have a majority of the symptoms.
After all the gut is the most important organ in the body, if that doesn't function properly, the rest of your body suffers right?TRY GOOGLING CANDIDA AND SEXUAL DYSFUNCTION
Did you do actual blood and 3day stool tests?
If not you dont have candida or parasites or leaky gut. All alternative health workers will claim you do but its actually very rare to have it.
On 1/19/2016, 9:03:07, trantran83333 said:Has anyone ever thought about candida/parasite infection? I was diagnosed with both, and leaky gut. I'm going to start my treatment today and update how I feel in a couple of weeks
i looked it up and found that I have a majority of the symptoms.
After all the gut is the most important organ in the body, if that doesn't function properly, the rest of your body suffers right?
Did you do actual blood and 3day stool tests?
If not you dont have candida or parasites or leaky gut. All alternative health workers will claim you do but its actually very rare to have it.
new ideas for erection problems, 0 sex drive, low capacity muscle growth ? I'm 27, after cycles of accutane , ( 5 ) last in 2012, i destroy my life and my body
testosterone levels are normal, supplement L-carnitine INCREASE erection but stop work after a few weeks , arginine gives me palpitations and asthma, the only way to have erection is cialis , 20mg min
I stopped to turn doctors for search a solutions , they do not believe
On 1/22/2016 at 8:27 PM, Relentless1k said:Not to be a douche but that doc is a quack by the looks of it and if you paid any more than 10 dollars for that product you are being scammed. And that diet is pure bullshit, follow something like this instead: [removed] if that doesnt work you need to try an elemental diet (all nutrition but no actual food)
Stop focusing on bullshit unless you have tests to back it up.
-----
To everyone:
This forum is still stuck in looking at all the wrong places.
Here is the only 2 things to do: Optimize your lifestyle and diet in all regards (this is a boatload to do but i can provide resources if you send me a PM) and research possible mechanisms for why accutane does what it does and try to prove its still in you.ONLY EVER TREAT CANDIDA/LEAKY GUT/SIBO IF YOU HAVE ACTUAL CLINICAL PROOF DIAGNOSED BY A PROPER DOCTOR AND NOT SOME ALTERNATIVE QUAKERY "DOC"
DO NOT ASSUME YOUR THYROID OR DHT OR WHATEVER IS MESSED UP BEFORE YOU HAVE TESTING TO PROVE IT.
Stop wasting your hard earned money and free time into chasing all the wrong places.
Ive been through the same road that you are far behind on, ive believed i have candida, sibo, leaky gut, messed up thyroid, low testosterone, heavy metals, mold, etc etc. I have used pretty much every supplement that exists (not individual brands for the same ingredient but you get the point) and also used tons of medication. I dont smoke, drink or have any caffeine and my diet is flawless. Changing diet and lifestyle will make you better but its only a cure if your condition is extremely mild.
---
Personally im working with a really good doc that understands accutane and he is looking into any and all ways to figure out if its still in any part of the body. And im also testing biological systems as much as i can afford it. Also working with a scientist.Current testing that is awaiting results: All common blood tests including heavy metals, hormones etc, 3k worth of stool tests that will cover gut health in all areas including parasites/candida, SIBO test, 23andme genetic raw data, th1/th2 balance, sam/sah ratio and full methylation panel + a bunch more. 24hour urine testing etc. All being done with testing that are based on real clinical science and can be backed up. Im not going any alternative routes here. Either i test with government labs or really good private labs. Genova diagnostics for example for my stool testing.
I wont be very active in the thread because im putting so much work into figuring stuff out.
IM NOT SAYING PEOPLE DONT HAVE CANDIDA ETC BUT GET TESTING DONE FIRST. And that and other conditions are not accutane specific problems, 99% of people with leaky gut, sibo, candida etc have not taken it. So you need to also focus on accutane specific problems and treat those issues as not directly caused by accutane.
I will help anyone who needs help, but im morelikelyto respond to PM's.
@ Anyone who is actually looking into science and trying to figure out how to solve issues, thanks for your work.
@ People who just read about health stuff online and experiment with supplements: This will not get you anywhere near cured, ive done it for years. Especially if you still do stupid shit like smoking/drinking or generally being unhealthy. Fix your diet and lifestyle first..
Well i can only try, after all I did try all the supps thats reccomend here with little to no improvement and some made it worse.
My diet is clean, I eat healthy I make fruit and veg smoothies every day. That's the only thing I find that helped me get by.
I feel great in the morning, but I start crashing at 3pm everyday, I get all bloated and tired sometimes it hurts real bad too. But later in the afternoon when I start passing wind, lots of wind I feel somewhat relieved a little bit. Sorry for grossing everyone out lol. There are days where I can't pass no wind/gas and I continue being tired until bedtime.
i find I feel worse when it's a cloudy humid day.
It's too soon to say if anything has worked yet, also not going to make any claims or assumptions. I don't want to lead people down the wrong track, I am my own guinea pig. But I do suggest people look into it there is a possibility.
Im afraid prescribed antifungals won't work as I did lots of research on candida.
We all have something called a biofilm that the bugs can go and hide/ lay dormant until we finish the course of the drug and they can come back even stronger, the ones that survived. I just ordered parasite and anti fungal cleanse from Humaworm. I heard it's great from one of the threads I been following, It's herbal and also read that they can't become immune to herbal remedies
@Walden Rev@guitarman01
Who here purchased hydroxypropyl Beta-cyclodextrin powder?
Remember how oral ingestion is ineffective? Only IV will do according to the expert on it.
I just thought of something:
DMSO can carry the CD into the liver directly!
I personally use it to carry magnesium oil deep into my joints & muscles with great efficacy.
Active ingredient: 90% dimethyl sulfoxide (DMSO 900 mg/ml).
Inactive ingredient: Deionized water.
DMSO interview - Janet Perry:
[Edited link out]
DMSO interview - Morton Walker:
--
EDIT:Does anyone know what these are? Are these parasites? I have these. Some say it's Borrelia
[Edited link out]
thanks Modeaa for the info. and that was alot of info.
So again has anyone tried higher dose methylfolate? that would be similar to the Deplin prescription or even half that dose wise.which is anywhere between 7.5 to 15mgs
its important that its the right form of active folate and not folic acid that could have severe adverse effects at a higher dose, especially if b12 deficient. and we are not looking at deficiency we are looking at suppressing the hyper glycine enzyme that speeds up the conversion of sam-e and screws up the whole methylation process
I have tried doing a broad search on this forum on the word folate to see if this exact Idea has been discussed before, but the search doesn't seem to pull everything up.
On 1/19/2016 at 11:11 PM, trantran83333 said:"I just ordered parasite and anti fungal cleanse from Humaworm. I heard it's great from one of the threads I been following, It's herbal and also read that they can't become immune to herbal remedies "Cant actually post for some reason without using this quote mechanism so:
Again do you actually have stool testing done to prove you have said issues. And no herbals will not beat prescription ones. Antibiotics and such are natural even tho its pharma too, at least some of them. Herbs are great in general and as an add on. Also if you are looking for ways to deal with biofilms you prob can just buy enzymes for it cheaper than the cleanses.Its great that you try stuff but get diagnosed first with testing and then try out ways. Now you wont ever know if you had it in the first place and then you cant really know if you got rid of it either. Its like shooting in the dark and you dont know if there is a target or not.
- Relentless1k
11 hours ago, Modeaa said:GNMT mushup :
http://www.ncbi.nlm.nih.gov/pubmed/24746817
Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis.
http://jn.nutrition.org/content/131/7/1914.abstract?ijkey=087e6258431abcbf63153b4a7ec07316294cb9d1&keytype2=tf_ipsecsha
Earlier work demonstrated that increased methionine catabolism by dietary CRA resulted in a significant increase in hepatic taurine concentrations that was achieved in part at the expense of reduced inorganic sulfate excretion and diminished hepatic glutathione levels (10,29).
https://en.wikipedia.org/wiki/ Methionine_synthasehttp://jn.nutrition.org/content/133/12/4090.long
All-trans-Retinoic Acid Rapidly Induces Glycine N-methyltransferase in a Dose-Dependent Manner and Reduces Circulating Methionine and Homocysteine Levels in Rats1,2
''the elevated activity of MS suggests that remethylation of homocysteine by the one-carbon pool may be enhanced in ATRA-treated rats. Thus, it appears that the folate-dependent one-carbon pool may compensate for the retinoid-mediated loss of methyl groups by increasing their supply. ''
''
it appears that ATRA treatment increased the catabolism of methionine, as indicated by the reduction in circulating methionine levels. This observation supports our earlier work and that of others that retinoid compounds have the ability to enhance methionine catabolism under both normal and excess dietary methionine conditions (2932). This finding also underscores the implication that the effect of retinoids on hepatic sulfur amino acid metabolism may have an effect on reducing their availability for other tissues and cells.
modeaa, from these studies... retinol and methionine have an inverse relationship. excess retinol clears the body of excess methionine and SAM-E... wouldnt the reverse be true? retinoids reduce hepatic sulfur limiting their availability for every other function the body needs (this can account for EVERY SINGLE one of our side effects)
lets reverse this process!!!!!! by adding lots of SAM-E. today i went to get a serum b-12/homocysteine/full cbc panel and a methylmalonic lab test done. This should show if im not able to recycle homocysteine back into methionine. If we have damaged livers, we might need to take SAM-E direct to bypass this, as the MAT1 enzyme isnt working as well after accutane. Dr. Rich Van K thought to take high doses of folate to knockdown the GNMT enzyme. i believe we can do this by replacing the catabolized methionine in massive doses once and for all. I believe this will also be dose dependent.
these tests will also rule out pernicious anemia.
I will wait for the result of these labs before increasing the doses... but i 1000% believe this is the path. This should provide us with all of the GAGS (glucuronic acid) and taurine to conjugate anything we need to get rid of and or reverse any epigenetc switch.
you guys only speak about supposition, anyone try these mentioned supplement?
Do you know of a dosage and method of Assumption ? can I do to test
6 minutes ago, Ruvik said:you guys only speak about supposition, anyone try these mentioned supplement?
tryingtohelp2014 you know an idea of a dosage and method of Assumption ? can I do to test
On 1/23/2016 at 5:00 AM, yetanotheraccutanevictim said:@Walden Rev@guitarman01
Who here purchased hydroxypropyl Beta-cyclodextrin powder?Remember how oral ingestion is ineffective? Only IV will do according to the expert on it.
I just thought of something:
DMSO can carry the CD into the liver directly!
I personally use it to carry magnesium oil deep into my joints & muscles with great efficacy.
Highest quality. free of impurities (VERY important):
Jacobs labs
Active ingredient: 90% dimethyl sulfoxide (DMSO 900 mg/ml).
Inactive ingredient: Deionized water."This is made by the company that the original researcher into DMSO started. His name is Dr. Stanley Jacob. Unlike the company with the tree logo, who sells industrial grade (contaminated with all manner of nasty chemicals, including acetone), Jacob Lab sells only the purest stuff.Yes, it costs a bit more, but then it doesn't contain known carcinogens, like the other stuff."
Book - DMSO - Nature's Healer:[Edited link out]
DMSO interview - Janet Perry:
[Edited link out]
DMSO interview - Morton Walker:[Edited link out]
--
EDIT:Does anyone know what these are? Are these parasites? I have these. Some say it's Borrelia
[Edited link out]
I make it into an solution --> syringe -->little silicon tube --> up the ass. So that would get it into the bloodstream and liver directly.
i tend to stay away from people when I use it because I get irritated/aggresive as hell.
It also appears Im losing some bits of bellyfat which in the past wouldnt get away even with hard training.
Couple random thoughts atm. Took higher dose folate past couple days. Not even too high maybe 3 to 4mg. Definitely having an effect on my stomach it's a weird different feeling. Makes me want/need to crap a lot. No loose bowels. This reminds me similar to when I was taking higher dose taurine and I couldn't even eat without having to shit right after. Again not diarrhea. But it was kind of a scary feeling . so much so that I quit taking it awhile back. So is this to say the folate is working to suppress gnmt and create more taurine? Do normal people have these kind of reactions to high doses of these supplements?
this is from a post of someone who had test done post accutane confirming a methylation block
Per my previous posts, I've taken a Methylation Pathway Panel, which showed a classical methylation block as described by RichVank - depleted GSH, high GSSG, low SAMe, etc.
http://forums.phoenixrising.me/index.php?threads/methylation-protocol-depletes-zinc.27950/
long post from Rich, but alot of info
I you want to do some testing to see if what I've described is what is going on in your case, here are the tests I would suggest:
1. The methylation pathways panel offered by Health Diagnostics and Research Institute in New Jersey. It is a blood test, requires an order from a physician or a chiropracter, and costs $295, including the shipper to send the blood samples to the lab. For people outside the U.S., the shipping costs more. The contact info for this lab is pasted below.
2. The Metametrix 40 plasma amino acids test, which is available from [removed] without a doctor's order.
In the first test, the levels of SAMe and SAH are the items of special interest, though the panel will also evaluate the status of glutathione and the folate metabolism, which are important in determining ME/CFS.
In the second test, glycine and sarcosine are of most interest.
If the mechanism I discussed is going on, you will see low SAMe, high SAH, low glycine and high sarcosine. If you have ME/CFS, you will likely also have low glutathione.
Here's the contact info for the Health Diagnostics lab:
Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288
Lab Director: Elizabeth Valentine, M.D.
Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone, or you can use the guide below:
May 19, 2011
Interpretation of Results of the Methylation Pathways Panel
by
Richard A. Van Konynenburg, Ph.D.
Independent Researcher
[removed]
Disclaimer: The Methylation Pathways Panel is offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA. I am not affiliated with these laboratories, but have been a user of this panel, and have written these suggestions at the request of Tapan Audhya, Ph.D., Director of Research for the Health Diagnostics lab, for the benefit of physicians who may not be familiar with this panel. My suggestions for the interpretation of results of the panel are based on my study of the biochemistry involved, on my own experience with interpreting panel results as part of the analysis of a fairly large number of cases of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) over the past four years, and on discussion of some of the issues with Dr. Audhya. I am a researcher, not a licensed physician. Treatment decisions based on the results of applying this panel and its interpretation to individual cases are the responsibility of the treating physician.
Application: In addition to being useful in analyzing cases of ME/CFS, this panel can also be usefully applied to cases of autism and other disorders that involve abnormalities in glutathione, methylation and the folate metabolism.
The panel includes measurement of two forms of glutathione (reduced and oxidized), S-adenosylmethionine (SAMe), S-adenosylhomocysteine (SAH), adenosine, and seven folate derivatives.
According to Dr. Audhya (personal communication), the reference ranges shown on the lab reports for each of these metabolites were derived from measurements on at least 120 healthy male and female volunteer medical students from ages 20 to 40, non-smoking, and with no known chronic diseases. The reference ranges extend to plus and minus two standard deviations from the mean of these measurements.
Glutathione (reduced): This is a measurement of the concentration of the
chemically reduced (active) form of glutathione (abbreviated GSH) in the blood
plasma. The reference range is 3.8 to 5.5 micromoles per liter.
Glutathione plays many important roles in the biochemistry of the body, including serving as the basis of the antioxidant enzyme system, participating in the detoxication system, and supporting the cell-mediated immune response, all of which exhibit deficits in CFS. The level of GSH in the plasma is likely to be more reflective of tissue intracellular glutathione status than the more commonly and more easily measured red blood cell or (essentially equivalent) whole blood glutathione level, which is about three orders of magnitude greater, because red blood cells are normally net producers of glutathione. Also, knowledge of the level of the reduced form, as distinguished from total (reduced plus oxidized) glutathione, which is more commonly measured, is more diagnostic of the status of glutathione function.
In order to be able to approximate the in vivo level of reduced glutathione when blood samples must be shipped to a lab, it is necessary to include special enzyme inhibitors in the sample vials, and these are included in the test kit supplied by these two laboratories.
Most people with chronic fatigue syndrome (PWCs), but not all, are found to have values of GSH that are below the reference range*. This means that they are suffering from glutathione depletion. As they undergo treatment to lift the partial methylation cycle block, this value usually rises into the normal range over a period of a few months. I believe that this is very important, because
glutathione normally participates in the intracellular metabolism of vitamin B12, and if it is low, a functional deficiency of vitamin B12 results, and insufficient methylcobalamin is produced to support methionine synthase in the methylation cycle. In my view, this is the mechanism that causes the onset of ME/CFS. This functional deficiency is not detected in a conventional serum B12 test, but will produce elevated methylmalonate in a urine organic acids test. In my opinion, many of the abnormalities and symptoms in ME/CFS can be traced directly to glutathione depletion.
Anecdotal evidence suggests that PWCs who do not have glutathione depletion do have abnormalities in the function of one or more of the enzymes that make use of glutathione, i.e. the glutathione peroxidases and/or glutathione transferases. This may be due to genetic polymorphisms or DNA adducts on the genes that code for these enzymes, or in the case of some of the glutathione peroxidases, to a low selenium status.
Glutathione (oxidized): This is a measurement of the concentration
of the oxidized form of glutathione (abbreviated GSSG) in the blood
plasma. The reference range is 0.16 to 0.50 micromoles per liter.
Normally, oxidized glutathione in the cells is recycled back to reduced glutathione by glutathione reductase, an enzyme that requires vitamin B2 and NADPH. If this reaction is overwhelmed by oxidative stress, the cells export excess GSSG to the plasma. In some (but not all) PWCs, GSSG is elevated above the normal
range, and this represents oxidative stress. It is more common in CFS to see this level in the high-normal range. This value may increase slightly under initial treatment of a partial methylation cycle block.*
Ratio of Glutatione (reduced) to Glutathione (oxidized): This is not shown explicitly on the panel results, but can be calculated from them. It is a measure of the redox potential in the plasma, and reflects the state of the antioxidant system in the cells. The normal mean value is 14. PWCs often have a value slightly more than half this amount, indicating a state of glutathione depletion and oxidative stress. This ratio has been found to increase during treatment of a partial methylation cycle block.*
S-adenosymethionine (RBC): This is a measure of the concentration of S-adenosylmethionine (SAMe) in the red blood cells. The reference range is 221 to 256 micromoles per deciliter.
SAMe is produced in the methylation cycle and is the main supplier of methyl (CH3) groups for a large number of methylation reactions in the body, including the methylation of DNA and the biosynthesis of creatine, carnitine, coenzyme Q10, melatonin and epinephrine. This measurement is made in the red blood cells because the level there reflects an average over a longer time and is less vulnerable to fluctuations than is the plasma level of SAMe.
Most PWCs have values below the reference range, and treatment raises the value.* A low value for SAMe represents a low methylation capacity, and
in CFS, it usually appears to result from an inhibition or partial block of the enzyme methionine synthase in the methylation cycle. Many of the abnormalities in CFS can be tied to lack of sufficient methylation capacity.
S-adenosylhomocysteine (RBC): This is a measure of the
concentration of S-adenosylhomocysteine (SAH) in the red blood cells. The reference range is 38.0 to 49.0 micromoles per deciliter.
SAH is the product of the many methyltransferase reactions that utilize SAMe as a source of methyl groups. In CFS, its value ranges from below the reference range to above the reference range. Values appear to be converging toward the reference range with treatment.
Sum of SAM and SAH: When the sum of SAM and SAH is below about 268
micromoles per deciliter, it appears to suggest the presence of
upregulating polymorphisms in the cystathionine beta synthase (CBS)
enzyme, though this may not be true in every case. For those considering following the Yasko treatment program, this may be useful information.
Ratio of SAM to SAH: A ratio less than about 4.5 represents low
methylation capacity. Both the concentration of SAM and the ratio of
concentrations of SAM to SAH are important in determining the
methylation capacity, because they affect the rates of the methyltransferase reactions.
Adenosine: This is a measure of the concentration of adenosine in the
blood plasma. The reference range is 16.8 to 21.4 x 10(-8) molar.
Adenosine is a product of the reaction that converts SAH to homocysteine. It is also exported to the plasma when mitochondria develop a low energy charge, so that ATP drops down to ADP, AMP, and eventually, adenosine. Adenosine in the plasma is normally broken down to inosine by the enzyme adenosine deaminase.
In some PWCs adenosine is found to be high, in some it is low, and in some it is in the reference range. I don't yet understand what controls the adenosine level in these patients, and I suspect that there is more than one factor involved. In most PWCs who started with abnormal values, the adenosine level appears to be moving into the reference range with methylation cycle treatment, but more data are needed.
5-CH3-THF: This is a measure of the concentration of 5L-methyl
tetrahydrofolate in the blood plasma. The reference range is 8.4 to 72.6 nanomoles per liter.
This form of folate is present in natural foods, and is normally the most abundant form of folate in the blood plasma. It is the form that serves as a reactant for the enzyme methionine synthase, and is thus the important form for the methylation cycle. It is also the only form of folate that normally can enter the brain. Its only known reactions are the methionine synthase reaction and reaction with the oxidant peroxynitrite.
When there is a partial block in methionine synthase, 5L-CH3-THF drains from the cells into the blood plasma by the so-called methyl trap mechanism. As other forms of folate are converted to 5L-CH3-THF, this mechanism depletes the cells of folates in general.
Many PWCs have a low value of 5L-CH3-THF, consistent with a partial block in the methylation cycle. Most methylation treatment protocols include supplementation with 5L-CH3-THF, which is sold over-the-counter as Metafolin, FolaPro, or MethylMate B (trademarks), and in the prescription medical foods supplied by PamLab, including Deplin, CerefolinNAC and Metanx. There are some others on the market that include both racemic forms (5L and 5R) of this folate.
When methylation treatment is used, the level of 5-CH3-THF rises in nearly every PWC. If the concentration of 5-CH3-THF is within the reference range, but either SAM or the ratio of SAM to SAH is below the reference values, it suggests that there is a partial methylation cycle block and that it is caused by inavailability of sufficient bioactive B12, rather than inavailability of sufficient folate. A urine organic acids panel will show elevated methylmalonate if there is a functional deficiency of B12. I have seen this combination frequently, and I think it demonstrates that the functional deficiency of B12 is the immediate root cause of most cases of partial methylation cycle block. Usually glutathione is low in these cases, which is consistent with such a functional deficiency. As the activity of the methylation cycle becomes more normal, the demand for 5-CH3-THF will likely increase, so including it in the treatment protocol, even if not initially low, will likely be beneficial.
10-Formyl-THF: This is a measure of the concentration of 10-formyl
tetrahydrofolate in the blood plasma. The reference range is 1.5 to 8.2 nanomoles per liter.
This form of folate is involved in reactions to form purines, which form part of RNA and DNA as well as ATP. It is usually on the low side in PWCs, likely as a result of the methyl trap mechanism mentioned above. This deficiency is likely the reason for some elevation of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) often seen in PWCs. This deficit may also impact replacement of cells lining the gut, as well as white blood cells.
5-Formyl-THF: This is a measure of the concentration of 5-formyl
tetrahydrofolate (also called folinic acid) in the blood plasma. The reference range is 1.2 to 11.7 nanomoles per liter.
This form is not used directly as a substrate in one-carbon transfer reactions, but it can be converted into other forms of folate, and may serve as a buffer form of folate. Most but not all PWCs have a value on the low side. It is one of the
supplements in some methylation protocols. It can be converted to 5L-CH3-THF in the body by a series of three reactions, one of which requires NADPH, and it may also help to supply other forms of folate until the methionine synthase reaction comes up to more normal activity.
THF: This is a measure of the concentration of tetrahydrofolate in
the blood plasma. The reference range is 0.6 to 6.8 nanomoles per liter.
This is the fundamental chemically reduced form of folate from which several other reduced folate forms are synthesized, and thus serves as the hub of the folate metabolism. THF is also a product of the methionine synthase reaction, and participates in the reaction that converts formiminoglutamate (figlu) into glutamate in the metabolism of histidine. If figlu is found to be elevated in a urine organic acids panel, it usually indicates that THF is low. In PWCs it is lower than the mean normal value of 3.7 nanomoles per liter in most but not all PWCs.
Folic acid: This is a measure of the concentration of folic acid in
the blood plasma. The reference range is 8.9 to 24.6 nanomoles per liter.
Folic acid is a synthetic form of folate, not found in nature. It is added to food grains in the U.S. and some other countries in order to lower the incidence of neural tube birth defects, including spina bifida. It is the oxidized form of folate, and therefore has a long shelf life and is the most common commercial folate supplement. It is normally converted into THF by two sequential reactions catalyzed by dihydrofolate reductase (DHFR), using NADPH as the reductant. However, some people are not able to carry out this reaction well for genetic reasons, and PWCs may be depleted in NADPH, so folic acid is not the best supplemental form of folate for these people.
Low values suggest folic acid deficiency in the current diet. High values, especially in the presence of low values for THF, may be associated with inability to convert folic acid into reduced folate readily, such as because of a genetic polymorphism in the DHFR enzyme. They may also be due to high supplementation of folic acid.
Folinic acid (WB): This is a measure of the concentration of folinic acid in the whole blood. The reference range is 9.0 to 35.5 nanomoles per liter.
See comments on 5-formyl-THF above. Whole blood folinic acid usually tracks with the plasma 5-formyl-THF concentration.
Folic acid (RBC): This is a measure of the concentration of folic acid in the red blood cells. The reference range is 400 to 1500 nanomoles per liter.
The red blood cells import folic acid when they are initially being formed, but during most of their lifetime, they do not normally import, export, or use it. They simply serve as reservoirs for it, giving it up when they are broken down.
Many PWCs have low values of this parameter. This can be caused by a low folic acid status in the diet over the previous few months, since the population of RBCs at any time has ages ranging from zero to about four months. However, in CFS it can also be caused by oxidative damage to the cell membranes, which allows folic acid to leak out of the cells. Dr. Audhya reports that treatment with omega-3 fatty acids has been found to raise this value over time in one cohort.
If anyone finds errors in the above suggestions, I would appreciate being notified at[Edited link out]
* Nathan, N., and Van Konynenburg, R.A., Treatment Study of Methylation Cycle Support in Patients with Chronic Fatigue Syndrome and Fibromyalgia, poster paper, 9th International IACFS/ME Conference, Reno, Nevada, March 12-15, 2009. [Edited link out]
Best regards,
Rich