Unfolded Protein Response and A Possible Treatment for CFS

[Needinghelp]

@mariovitali 7 months ago i took accutane for only 2 weeks and developped a lot of side effect who still persist today including: erectile dysfunction,numb penis, IBS, tinitus, joint pain, depression, tired all the time, problems with peeing, dry eyes and lower back pain. Do you have any tips for me to get rid of these side effect i am only 19 years old and at the moment see no way out of this. I hope you can help me.

 

[jump44]

Well thats just great. The imunivor that Im on supposedly does a remarkable job of raising uric acid levels. Its like everything we try to put in our bodies to fight this has some other effect that is bad for us. WTF

 

[jump44]

whats everyones thoughts on SAM-e? I always have felt better, sometimes much better, when taking it. I know its a huge part of methylation, but methylfolate, B12(besides in the very beginning) have always brought me inconsistent and sometimes detrimental results. I think the effect wears off after taking for awhile, but just curious what sam-e might tell us or where it could fit in w your theory, @mariovitali. I know its supposedly great for the liver ,etc

 

[mariovitali]

@Needinghelp

Yes i believe i can help. I will PM you.

@jump44

I need to study more about Methylation. But then again, according to my Theory Methylation is just one part of the problem. How many people have you heard that became symptom-less by using just methylation?

How are you doing BTW? Are you still taking TUDCA?

 

[jump44]

@mariovitali

Doing ok, had a weird setback last week that felt like a massive histamine problem, bad mood, fatigue.. Left ear hearing loss etc. I have to order more TUDCA I ran out last thursday.. I asked specifically about SAM-e because I took some when I awoke early this morning and am having a very good day. Its that feeling of all the sudden realizing your brain has been functioning at about 30 percent and like a light sort of switching on, Im sure most here can relate. Sam-e always seems to do something nice for me if I take it periodically. Methylfolate never does this for me and sometimes makes me worse, so I was curious if it could be relevant to ER stress etc in a seperate way than the typical methylation supplements/vitamins. Still taking most of the supps for your regimine, but need to get more TUDCA as I said.

 

[mariovitali]

@jump44

OK Thanks. So would you say that this setback might be attributed to stopping TUDCA?

Anytime you have your DNA Data please send them over. I coded an R Program that scans through the DNA and summarises the problems as discussed in this thread (i should change RiskAllele to minorAllele to be honest) :

And the summary :

 

[jump44]

I cant rule out that stopping TUDCA did hurt me, yes. Could be one of those things that I got used to its effects and didnt realize how much it was helping. All I know is when some of the familiar symptoms start coming back I almost ALWAYS have this weird dull right sided ache in my GB/liver area, along with "pulsing' or ringing in my left ear. The Sam-e I took this morning relieved both , btw.

edit forgot to add that there has been some wild weather/temperature swings where I am this past week. Just mention it because I know thats another precipitator of ER stress

 

[mariovitali]

@jump44

can you have a test for Liver panel and also Total Bile acids?

 

[jump44]

@mariovitali

Ive had a lot of liver tests done over the course of the years, the only thing thats ever been out of range high are the bilirubins(direct, indirect,etc).. As far as total bile acids I can look through my records and see but I dont think Ive had that one done..What do I ask for? just total bile acids? I apologize if this has been covered

 

[mariovitali]

@mariovitali

Ive had a lot of liver tests done over the course of the years, the only thing thats ever been out of range high are the bilirubins(direct, indirect,etc).. As far as total bile acids I can look through my records and see but I dont think Ive had that one done..What do I ask for? just total bile acids? I apologize if this has been covered

The fact that you have elevated Bilirubin is not a good sign and confirms my Theory about Liver Injury. As discussed, lack of elevated Liver enzymes does NOT rule out Liver Injury. The only way to confirm lack of Liver Injury is to take a Liver Sample.

Yes, all you ask for is for is "Total Bile Acids". If they are elevated then Cholestasis is possible and as a result your Liver gets damaged even more very slowly as time passes by. This eventually will bring even more problems.

However, the fact that you already started TUDCA means that your Total Bile acids may well be normal now (TUDCA is used for Cholestasis). Nevertheless the test may indicate that you need to increase TUDCA dosing.

Since i am not a Doctor, I would advise you to see a Hepatologist with whom you will need to confirm whatever i discussed here.

 

[mariovitali]

whats everyones thoughts on SAM-e? I always have felt better, sometimes much better, when taking it. I know its a huge part of methylation, but methylfolate, B12(besides in the very beginning) have always brought me inconsistent and sometimes detrimental results. I think the effect wears off after taking for awhile, but just curious what sam-e might tell us or where it could fit in w your theory, @mariovitali. I know its supposedly great for the liver ,etc

Yes it can be a Big thing since it helps in Cholestasis :

Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis.
Almasio P1, Bortolini M, Pagliaro L, Coltorti M.
Author information

Abstract
Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.

 

[jump44]

Thanks @mariovitali. That makes sense, personally SAM-e can take me from feeling like hell to pretty good within an hour at times..something is definitely going on there. Wonder if it may be a good idea to add a smalle daily/eod dose to my regimine. I am very confused about methylation etc since as I said my results with methylfolate range from disastrous to decent. SAM-e seems to work in an entirely different way for me.

 

[mariovitali]

@jump44 we will have a much better idea on what could be wrong when you get hold of your DNA Data.

 

[jump44]

Yeah I have to get that done @mariovitali.. Money is tight and Ive had to spend a lot on supps/meds etc. My order Of TUDCA arrived this am so I will experiment with increasing the dose a bit. Also been on imunovir for 3 weeks now and have had some moments of "normalcy" energy and brain wise that have been encouraging. The other supps seem to somehow be working a bit better for the most part since starting on the imunovir. SAM-e Im just taking every other day at a low dose for now. still on

selenium
resveratrol(Every other day)
Ubiquinol
Active B complex
LDN
Imunovir
Choline/inositol
B-2(seem to be needing less of this lately)
Betaine hcl before meals
magnesium spray before bed
vitamin c
zinc 5o mg every other day
B12(rotate methyl, hydroxy, and dibencozide)
stopped methylfolate, as there is some in the active B complex, extra methylfolate seems to be a weird proposition for my body. It can either slightly help or send me into a tailspin.
TUDCA
iodine
armour/synthroid..interestingly lately Ive missed some days of thyroid meds and it hasnt made me feel bad at all. maybe someday I will be able to get off of them.

Part of me hates taking all of it because if things start going bad Idk what is causing what but for now most of it seems to be helping so Im keepin on.

 

[Stacey1121]

For the Post-accutane sufferers reading this Thread... please see below :






and more (Note the role of Selenium)

I have very high (unexplained) levels of selenium. I take no supplements with selenium and do not eat any "high" selenium foods that would account for this. I am also hypothyroid. I have been making gains with Freddd's methylation protocol - with body pain and weight gain - but not as great with fatigue. I find that I have needed a lot of r-lipoic-acid to "mop" up the inflammation from the protocol (my hands swell) - and after taking the RLA my hands shrink to normal asap. I think I must be having a NO response to something. I never took Accutane but I think there maybe something with regard to your experience here that may relate to my condition. I am an artist and this whole world of scientific "thinking" is challenging for me navigate - but I am (really) trying. I did a course of steroids for my adrenals last year and I felt a lot better - but also gained a lot of weight - and eventually they did not seem to work as well anymore (but I was not working on methylation at that time) and I stopped. Any thoughts you might have - I would be very interested. Thanks so much!!

 

[wastwater]

Does any of this tie in with SERPIN https://en.wikipedia.org/wiki/Serpin
thyroxine and cortisol binding mentioned

 

[mariovitali]

@Stacey1121

Could you have the following blood tests and send over the results? Also, do you have your DNA Data?


ALT/AST
Albumin
Bilirubin
Gamma-glutamyl transpeptidase (GGT)
Lactate dehydrogenase(LDH)
Alkaline phosphatase (ALP) Levels
Total Bile Acids (TBAs)
Homocysteine

 

[mariovitali]

@jump44

As your body heals so will your Thyroid. If you are able to hold your TSH values steady within normal limits then you are moving to the right direction. FYI, i was for more than 5 years hypothyroid (actually subclinical hypothyroidism).

I Just had a test for my Thyroid. TSH is in optimal levels and i haven't touched T4 for quite some time (almost a year)

 

[ahmo]

As your body heals so will your Thyroid.

Not necessarily true. lucky you.

 

[mariovitali]

@ahmo

Ah yes you are right. Getting a bit excited here..Being hypo may be completely irrelevant to CFS so it doesn't necessarily mean that you will get well in case that one sorts out CFS