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

[nandixon]

So possibly, if we can find the chemical name or brand name of the triheptanoin that is sold to the food industry or cosmetic industry, we may be able to obtain this oil.

@Hip, the FDA in the US, and the equivalent in the EU, made triheptanoin an orphan drug - which makes something that is otherwise cheap extraordinary expensive and hard to obtain. I would like to try that one too.

 

[Hip]

@Hip, the FDA in the US, and the equivalent in the EU, made triheptanoin an orphan drug - which makes something that is otherwise cheap extraordinary expensive and hard to obtain. I would like to try that one too.

I wonder if heptanoic acid (aka: enanthic acid) would substitute for triheptanoin? Triheptanoin is made from the reaction of glycerol and heptanoic acid. The triheptanoin molecule basically contains three heptanoate molecules.

Unfortunately heptanoic acid has a rancid smell, but perhaps something like ethyl heptanoate, which is used in the flavor industry because of its odor is similar to grapes, might work. You can buy 4 kilograms of ethyl heptanoate here for $103. But I don't know whether ethyl heptanoate would be safe or effective.

 

[junkcrap50]

Allithiamine has a bit of a cult following out there, for good reason. Not many people know about this Japanese product but if you google allithiamine and dysautonomia you'll find some interesting testimonials. The Japanese are experts on this vitamin because of their white rice & beriberi situation.

Sulbutiamine, as you note, effectively crosses the BBB which allithiamine does not, at least not in my experience. Allithiamine got rid of my physical limitations but helped only marginally with my main problem which is severe loss of cognitive function, especially executive function. Even while I was doing 10k steps a day I couldn't possibly function in my former academic occupation, the brain fog and loss of intelligence and especially sustained attention was just too impairing.

I'll add this link to my post above too. Cort took a survey of those who tried high dose thiamine and the comments provide annecdotal experienes. There was some discussion in the comments whether or not the fat soluble forms of thiamine (sulbutiamine and benfotiamine) worked the same on the high dose protocol as the plain thiamine HCl.
http://www.healthrising.org/blog/20...survey-fibromyalgia-chronic-fatigue-syndrome/

One other supplement of potential interest in terms of boosting the Krebs cycle is triheptanoin, which is a dietary oil.

So possibly, if we can find the chemical name or brand name of the triheptanoin that is sold to the food industry or cosmetic industry, we may be able to obtain this oil.

Some chemical information about triheptanoin (including its chemical synonyms) is given here. As a chemical, its CAS number is 620-67-7.

You can buy triheptanoin on Alibaba, but there are only 2 sources. https://www.alibaba.com/trade/search?fsb=y&IndexArea=product_en&CatId=&SearchText=triheptanoin You would have to email them to ask what grade purity it is. Personally, I do not feel comfortable buying any supplements, medicines, etc off Alibaba, but I do know there is a group who buys methylfolate and B12 in bulk from China on Alibaba. So, it's upon oneself to decide the widsom and safety of doing so. As for a US source, there ARE some custom labs which make peptides and workout supplements for sale that may be willing to make it if there was large enough demand and if asked, but I have no idea what the cost would be. I would refind those labs.

 

[eljefe19]

@junkcrap50 We could organize a group buy and approach a U.S. lab to synthesize.

 

[junkcrap50]

@junkcrap50 We could organize a group buy and approach a U.S. lab to synthesize.

One company/lab that I was thinking of was this company: http://prototypenutrition.com/about/ They've since changed their website now that their ketone beta-hydrobutyrate supplementh has taken off, and they no longer appear to advertise their custom synthesis capabilities and/or services. They may still do it however. Might be worth an email to them. They may even be interested in it or have tried it already as a workout supplement.

 

[eljefe19]

My brain fog sucks right now, I would advise that someone else handle communication. I'm just starting to learn about the compound.

 

[Hip]

You can buy triheptanoin on Alibaba, but there are only 2 sources. https://www.alibaba.com/trade/search?fsb=y&IndexArea=product_en&CatId=&SearchText=triheptanoin You would have to email them to ask what grade purity it is.

Thanks junkcrap50. Though Alibaba will only do business with companies, so you would either have to buy through a company, or pretend that you are a company (which may not be easy to do).

 

[nandixon]

The sphingosine-1-phosphate (S1P) hypothesis can also explain the "It's in the blood" finding. From the Fluge & Mella study:

Exposing cultured muscle cells to serum from ME/CFS patients indicated the presence of blood-borne substances affecting energy metabolism.

So the problem would be perhaps not something in the blood that shouldn't be there, but instead too little of something (S1P) that should be there.

S1P is initially made inside the cell but then, remarkably, is transported outside the cell to bind to its receptor on the cell surface. (Reference)

This "inside-out signaling" by S1P can also explain Julia Newton's study results of impaired AMPK in cultured ME/CFS muscle cells where she thought she had effectively removed the possibility of any blood borne factors.

 

[Sasha]

I'm glad that the research is catching up to my personal observations and experiences re: pyruvate dehydrogenase.

Massively supraphysiologic doses of thiamine, particularly transdermally applied allithiamine (which is fat-soluble and penetrates the cells much more effectively) and sublingual thiamine pyrophosphate to a lesser extent, were effective for me in combination with low dose lipoic acid and sublingual FMN around the clock. Regular orally administered thiamine hydrochloride you'd get in most supplements did nothing whatsoever, not even at 1,500 mg/day. The effect lasted about 4 months but it was very pronounced. I went from housebound to being able to climb hills with no PEM essentially overnight.

Deconditioning plays absolutely no role in the metabolic abnormalities in ME/CFS and no graded anything was required to restore functional capacity. Within 20 minutes of first dose of allithiamine I just felt I could go for a walk despite not having done that for years.

This is both amazing and gutting at the same time. I had a similar experience back in the 80s when I tried cold-bath therapy. Within a few short weeks I went from having been bedbound for years to being able to walk four miles one day, it lasted maybe a couple of weeks, and then I caught a bug (it seemed), was forced back to bed, and remained there for many years, despite continuing the (horrible, uncomfortable) therapy for another 18 months because I was so desperate to get the effects back. Equally inexplicable in terms of deconditioning.

It so often seems that on the rare occasions when we find something that kicks us out of whatever maladaptive state we're in, something just kicks us back.

The trick will be to understand why that happens and support the healthy steady-state.

 

[A.B.]

Deconditioning plays absolutely no role in the metabolic abnormalities in ME/CFS and no graded anything was required to restore functional capacity. Within 20 minutes of first dose of allithiamine I just felt I could go for a walk despite not having done that for years.

It's fairly obvious deconditioning has nothing to do with the illness. Functional capacity changes too rapidly for that when people get sick or have a remission, and exertion leads to an objectively measurable decline in function that lasts for more than 24 hours, whereas with deconditioning you'd see an increase in functioning. Plus deconditioning is easy to reverse. I strongly suspect that most patients do too much to even become deconditioned to any meaningful degree. If they're still walking around the house and leaving to buy groceries and take out the trash they will have poor fitness but not really sffer from any meaningful deconditioning. The most severely ill would presumably benefit the most from exercise if deconditioning was the main problem, but instead we see the opposite: they are at the highest risk of exercise related deterioration.

 

[Snow Leopard]

There are several S1P receptors (e.g., S1P1 aka S1PR1) located on different types of cells, and some of these receptors are necessary to properly activate mTOR.

S1P doesn't appear to be in the list of raw data from the PNAS study.
http://www.metabolomicsworkbench.or...SEARCH_TYPE=KNOWN&STUDY_TYPE=MS&RESULT_TYPE=1

Nor is it explicitly in the published list in the recent Hanson study.

S1PR1 is on my list of potential autoantibody targets, given it's role in lymphocytes, endothelial function. (and potential role in eye diseases...)

One of my hypotheses is that it is dysfunction (perhaps autoantibodies) of a receptor like this, rather than say, low levels of S1P (which itself requires a cause).

So the problem would be perhaps not something in the blood that shouldn't be there, but instead too little of something (S1P) that should be there.

Too little of something doesn't really explain the results - there has to be something in the serum that actively stimulates or blocks something (and is not cleared out)

Interestingly, S1P has fairly slow kinetics when expressed following muscle injury (matching PEM timeframes)
https://www.researchgate.net/public...uscles_through_a_S1PR2STAT3_Signaling_Pathway

 

[eljefe19]

https://www.researchgate.net/public...uscles_through_a_S1PR2STAT3_Signaling_Pathway

That's interesting. Part of my stack includes trying to block STAT3 signaling pathway, for its theoretical anti viral and pro interferon properties. I've had some mild gains in QOL but not much.

 

[Snow Leopard]

That's interesting. Part of my stack includes trying to block STAT3 signaling pathway, for its theoretical anti viral and pro interferon properties. I've had some mild gains in QOL but not much.

One of my hypotheses is that reduced STAT3 activity is part of the problem... ¯\_(ツ)_/¯

 

[eljefe19]

One of my hypotheses is that reduced STAT3 activity is part of the problem... ¯\_(ツ)_/¯

I wouldn't be surprised to be totally on the wrong side of the issue. I'm just a patient forced to play researcher and guinea pig. Interestingly the only supplement selfhacked has for STAT3 activators is Leucine, which keeps coming up in this thread.

 

[JaimeS]

It doesn't appear that Naviaux measured S1P, or that S1P has ever been measured in any ME/CFS study. Can anyone confirm this?

Hard to confirm a negative, but I feel relatively certain this is the case. It's not mentioned in even Naviaux's supplemental materials, and I can find no articles on Pubmed with either the abbreviation or the full name and even 'myalgic'. If you just put in the full name sphingosine-1-phosphate, though, there are a lot of interesting articles in general on its role in inflammation, allergy, and neurological illness.

I am going to take benfotiamine, alpha lipoic acid and acetyl-L-carnitine

I take these together EVERY day! The benfotiamine is really helpful for me in particular. I've noted very similar supplements to the one I'm taking don't have the same degree of helpfulness if they don't have the benfotiamine.

 

[alex3619]

a group of us appears to have high NK cell activity - and I have classic M.E.

What version of the test did you have, in your own serum, or isolated or in other serum? The results are opposite. If you were tested in your own serum then it establishes a subgroup, if you were tested the other way then it demonstrates nothing that can be certain.

 

[justy]

What version of the test did you have, in your own serum, or isolated or in other serum? The results are opposite. If you were tested in your own serum then it establishes a subgroup, if you were tested the other way then it demonstrates nothing that can be certain.

I don't really understand the question.
I was tested by a blood test for Perforin Expression, which for me was very high. The lab says this:

Perforin expression assay
Natural Killer cells (NK) are cytotoxic cells that mediate the immune response against certain cancer and virus-infected cells. NK cells are normally found in the peripheral blood and are classified by their cell surface markers such as CD3-/CD56+ cells.
The activity of NK cells is altered in several disorders such as multiple sclerosis, lupus and CFS. The activity is very sensitive to various environmental pollutants. Since NK cells have a significant role in the defense against viruses, decreased NK activity can lead to the development of opportunistic viral infections. NK cells exert their cytotoxic effect by releasing perforin. Perforin is a protein that will destroy the cytoplasmic membrane of target cells and finally kill them. The expression of perforin mRNA can be measured as a mean to evaluate NK cell activation.

http://www.redlabs.be/ifa

 

[Cheesus]

I don't really understand the question.

Some tests of NK cell function leave the cells in the patient's blood when testing. This is the test that would give you usable information.

Other tests of NK cell function take the cells out of the patient's blood. From what we know so far, it appears that something in the blood is depressing NK cell function, so if your cells were taken out of the serum they could be expected to perform normally. These tests would be essentially useless in determining your NK cell function.

 

[Mary]

The edginess might perhaps be due to increased glutamate in the brain, as glutamine and glutamate freely interconvert (although I not aware of any way that glutamine can raise brain glutamate).

To counter this edginess or anxiety, you might try some of the supplements that I found have good anti-anxiety effects, such N-acetyl-glucosamine, flaxseed oil or turmeric (see this thread). I suspect these reduce anxiety by reducing brain inflammation (brain inflammation releases glutamate).

Well, yesterday I had the best day I've had in a very long time, I had energy but I didn't push it too hard, but I felt a real difference. It was great. And then I couldn't sleep! I slept very lightly from 10 to 1:00, and then wide awake till at least 4:30 (I couldn't look at the clock any more by that time), finally asleep and then awake again at 6:30. All my usual GABA supplements (niacin, inositol, l-theanine, theanine serene) and melatonin did nothing for me.

So I'm not taking any glutamine today - I don't want to stop it but I have to sleep. But I'm still taking the BCAAs. And then hopefully I will sleep better tonight and can go back to 500 mg. glutamine.

I'm ordering turmeric and flaxseed oil today to see if they help. I'm skipping the NAG - I don't have IBS-related anxiety (or even anxiety in general) and money is an issue, I buy so many supplements it's beyond absurd and expensive too. I am very sensitive to MSG - it causes severe insomnia for me. I don't have MCS, but I was reading about nutritional approaches and read that large doses of vitamin C are supposed to be helpful for that. And I was taking a good dose of vitamin C regularly and recently slacked off so maybe that was a contributing factor. I'm just guessing that my rather extreme reaction to the glutamine (which I've tolerated okay in the past) may have some relation to MCS and hence vitamin C may help - at least it won't hurt. I'm anxious to get back to what I did which made me feel so good yesterday! (though I'm very aware that it was quite likely a transient thing, though I would like to feel that way again at least for a couple of days!)

 

[eljefe19]

@nandixon https://en.m.wikipedia.org/wiki/Fingolimod

What do you think about this S1P receptor agonist? Says it prevents lymphocytes from contributing to an autoimmune reaction.