Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS (Fluge et al., 2016)

[nandixon]

You can actually buy phytoceramides (plant based ceramides) as a supplement. Perhaps this is worth experimenting with.

Oral phytoceramide supplements apparently can create younger looking skin.

Hmmm, a potential treatment for ME/CFS that not only reduces PEM but also the "appearance of fine lines and wrinkles"!

 

[Michelle]

@Michelle the question is are Opiods a sustainable long term treatment option? Similarly Ketamine boosts mTOR but I've been a bit hesitant to try and score it for a few reasons but sustainability is one.

Well, there are additional questions. As @nandixon pointed out, there is the question about whether the experience of the opioid subgroup would fit with his theory about impaired S1P signaling. Which was the main question I had.
Many of us are puzzled about this response to opioids and would love to have an answer about why. Moreover, if we could find that answer, it might point the way to a "sustainable" treatment that is not necessarily an opioid but may be able to work in a physiologically similar way.

 

[valentinelynx]

@Michelle the question is are Opiods a sustainable long term treatment option? Similarly Ketamine boosts mTOR but I've been a bit hesitant to try and score it for a few reasons but sustainability is one.

Yes. Been taking them for over 20 years with excellent effect.

 

[valentinelynx]

Can fatty liver be tested for?

CT scan

 

[Gondwanaland]

CT scan

An ultra sound detects it as well with no radiation

 

[valentinelynx]

An ultra sound detects it as well with no radiation

Sure. But mine was discovered through a CT scan done to try to ID the source of my severe abdominal pain. In fact, come to think of it, the report of my liver ultrasound, done at the same ER visit to evaluate for gallstones makes no mention of fatty liver.

So I looked it up. This is what the Cleveland Clinic website has to say about it:

"A liver ultrasound examination is useful for confirming steatosis. Fatty infiltration of the liver produces a diffuse increase in echogenicity (a bright liver) and vascular blurring (Figure 2). Unfortunately, ultrasound cannot rule out steatohepatitis or fibrosis, and its sensitivity drops sharply when <30% of hepatocytes contain fat droplets. It also has low accuracy in obese patients. Both computed tomography (CT) and magnetic resonance imaging (MRI) studies, especially the new technique of magnetic resonance spectroscopy, are more sensitive modalities for quantifying steatosis."

 

[Gondwanaland]

It also has low accuracy in obese patients.

When my steatohepatitis was diagnosed back in mid 2012 I wasn't overweight, and the dr performing it (a very experienced one) was pretty sure it was fat and not fibrosis. One year later I repeated the test with the same dr and he was very surprised to see it was gone (I had gone gluten free just a couple of months earlier).

I think a CT scan is a high price to pay to detect mild steatohepatitis (at least in non-overweight people AFAIK). If NAFLD is supspected, the treatment is carb reduction anyway.

PLUS there are a few blood markers that predict NAFLD with even no need of US to confirm it.

Many drs I have seen tried to push me expensive and harmful tests, surgeries and treatments that would have just addressed symptoms rather than causes.

 

[MeSci]

Yes. Been taking them for over 20 years with excellent effect.

I see you say in the 'Information' section of your profile: "Ketamine, tramadol (these no longer work). Opioids (for pain, also help energy some)." Is that up to date?

 

[Gondwanaland]

ER visit to evaluate for gallstones

Now I have no experience with gallstones, but am under the impression they are indeed a bit tricky to detect.

 

[valentinelynx]

I see you say in the 'Information' section of your profile: "Ketamine, tramadol (these no longer work). Opioids (for pain, also help energy some)." Is that up to date?

Yep, pretty much.

 

[eljefe19]

Yep, pretty much.

how long did Ketamine work for you?

 

[valentinelynx]

how long did Ketamine work for you?

Well, that's not as simple a question as it seems. First, I had an infusion of 25 mg in a bag of saline over I think it was an hour, in Goldstein's office, back in 1997. It "cured" me for 1 week: I had no pain, and my energy was restored, and I could even exercise without adverse consequence. I recently found my journal from that period. The effect gradually wore off and was pretty much gone at 1 week.

I tried to repeat the effect with weekly IM injections, accompanied by guided relaxation/visualization tapes (since taking the whole dose at once IM causes a pretty altered state, the guided visualization tapes gave me something to do while I was in the Twilight Zone ). However, I never re-achieved the "cure" effect, though I believe the weekly ketamine injections helped my mood and perhaps my pain levels.

Because of my positive response to ketamine, I also began taking pain medication with NMDA receptor antagonist activity (methadone) and continued that for many years until I realized it wasn't really helping my pain, and switched to a different opioid. Most recently, I had been taking levorphanol, another opioid with strong NMDA receptor antagonist activity, and it worked very well for my pain (and energy). Unfortunately, I had to switch insurance on January 1 (due to Blue Cross Blue Shield leaving the individual marketplace in my county and the insurance company offering individual market plans in my county deciding not to cover levorphanol—it is now very expensive, having been sold to a little company that charges thousands of dollars for a month's supply). So, I have weaned off levorphanol.

Furthermore, my pain doctor, the well-known pain expert, Forest Tennant, has essentially been driven out of the business of pain management by the new, crazy CDC "guidelines." Even though he is well-known as a national expert in pain management, because he is not "board-certified" in pain, the powers-that-be have threatened him with prosecution if he continues to help his severely afflicted pain patients as he has been, with well-regulated, albeit high-dose opioid therapy. So, he is retiring. A major catastrophe for the pain world, and especially his patients. I'm sure some will choose to leave this world rather than return to a life of uncontrolled pain.

So, my options for continued pain control are rapidly vanishing. I am currently using kratom to quash withdrawal symptoms as I wean down my opioids. Whether this will be adequate for pain control I do not know. I still need several hundred "morphine equivalents" per day. The CDC is trying to force all pain patients to be on less than 100 grams of morphine equivalents per day. Which is simply absurd.

I didn't realize I was going to be spilling all this when I started this post!

Bottom line: yes, opioids have been the mainstay of keeping me functional over the past 20 years. My doses are very high, partly because I have a genetic mutation that makes me only half as sensitive to opioids as the average person, partly because my pain is very bad and constant, requiring constant levels of opioid in my system. However, I have never had any problems from taking them. Even constipation was easily managed. I am not sedated, stupefied or otherwise altered. My reflexes are excellent. I have never caused an auto accident (knock on wood!) and I frequently drive over a hundred miles a day for work. Without opioids, I can barely move and find it hard to think.

The current anti-opioid hysteria may mean the end of my functionality. We shall see.

 

[MeSci]

PLUS there are a few blood markers that predict NAFLD with even no need of US to confirm it.

NAFLD = Non-alcoholic fatty liver disease?

 

[MeSci]

The current anti-opioid hysteria may mean the end of my functionality. We shall see.

I do hope not.

 

[eljefe19]

It's hard for me to get Opiod based drugs because of some drug abuse in my past, unfortunately

 

[eljefe19]

NAFLD = Non-alcoholic fatty liver disease?

Exactly. As I follow the current theory, the Bile Acid Receptor aka FXR receptor may be underagonized, causing some fatty liver to build up. This is as far upstream a target to treat the low ceramides that Naviaux found, that we have come up with yet. I've even developed a little supplement regimen perhaps it deserves it's own thread but all credit goes to nandixon.

 

[eljefe19]

Btw if anyone is interested, here is the strongest known FXR agonist known to mankind and it's available for purchase. Obeticholic Acid. It's pricey, so I'm hoping there's enough interest for a group buy. I can organize it if there's any interest at all.

 

[nandixon]

Btw if anyone is interested, here is the strongest known FXR agonist known to mankind and it's available for purchase. Obeticholic Acid. It's pricey, so I'm hoping there's enough interest for a group buy. I can organize it if there's any interest at all.

Just to mention that it would only make sense to try obeticholic acid (brand name "Ocaliva") if a person had first found that taking regular bile acids (e.g., Jarrow Bile Acid Factors) improved symptoms at least a little.

It would also be good if a person had test results showing, for example, that natural killer (NK) cell function and/or aldosterone levels are low or at least low-normal, since both of these are impacted by sphingosine-1-phosphate (S1P).

The idea here is that by helping activate the farnesoid X receptor (FXR), which is normally activated by natural bile acids like cholic acid and chenodeoxycholic acid in the intestinal tract and liver, that it might stimulate more ceramide synthesis and in turn lead to higher levels of S1P. FXR might be under-activated in ME/CFS due to, for example, dysregulation of the microbiome or autoantibodies against that receptor. This is just a theory.

It appears clear (to me) that all of the signaling and metabolic pathways that use S1P, including ones for energy*, endothelial function, blood pressure/volume regulation, the immune system, etc, are impaired in ME/CFS, but whether increasing the levels of S1P can improve this is unknown. (*In particular, the Akt/mTORC1 pathway, which is activated in part by S1P, could lead to the PDH complex impairment found by Fluge & Mella.)

The use of obeticholic acid would be totally experimental, especially since the activation of FXR is complicated and there is no guarantee that obeticholic acid, even though a very potent FXR agonist, would actually activate it in the way desired to increase ceramides. It is not known whether obeticholic acid can in fact increase ceramides.

Obeticholic acid is the first FDA-approved FXR agonist. It is a simple modification of a naturally occurring bile acid. Note that no ME/CFS patients are likely to have ever tried this drug (or any potent FXR activator for that matter).

A daily dose would probably not exceed 5 mg. (Reference) A person with ME/CFS probably wouldn't want to start with more than a quarter of that, so the amount and cost would actually not be that great if it worked.

Note that one consequence of taking obeticholic acid is that it might reduce a person's own natural production of bile acids enough to require that bile acids be supplemented. The main potential side effect of obeticholic acid is pruritis (itching).

 

[adreno]

Note that one consequence of taking obeticholic acid is that it might reduce a person's own natural production of bile acids enough to require that bile acids be supplemented.

I would first try treatments that stimulate endogenous release of bile acids.

 

[eljefe19]

I would first try treatments that stimulate endogenous release of bile acids.

I'm taking Jarrow Bile Acid factors and TUDCA, what else were you referring to?