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

[frozenborderline]

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

This study says that triheptanoin, an odd-carbon triglyceride, is a source for both acetyl-CoA, and for propionyl-CoA (the latter provides anaplerotic replenishment of the Krebs intermediates).


The Wikipedia article says:


However, I could not find this triheptanoin oil for sale anywhere online.

This document contains a lot of info on triheptanoin, and says:


There is some info on triheptanoin here; it says that triheptanoin is added to some cosmetics, and added to butter in some European countries, but is not commercially available in the US for clinical use.

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.

it's hard to get triheptanoin but I am very interested in trying it. have you found any suppliers yet, hip?

 

[FMMM1]

triheptanoin

I'm not going to add much value here. If you Google "triheptanoin oil butter" [without the quotes] then a load of stuff comes up, including the extract below*. Try an APB on a larger electronic forum might get a result (facebook etc). If it's added as a food tracer then it may be available at relatively low cost; in a global market it may turn up at different prices in different markets. However, how could you check authenticity?

Also, I sent an email to Maureen Hanson's and Ron Davis's group to see if they've tested it on the Seahorse [or Ron Davis's impedance thing - which seems to do similar things i.e.to a Seahorse].

Hanson's/Davis's group probably don't mind emails about this type of idea and it might just establish whether there's a benefit. Hanson highlighted the lack of treatments at the 2017 Symposium so she's painfully aware of the issue. Hanson's gut bug thing (with the Norwegians) should be finished the clinical bit about now.


Triheptanoin in Glucose Transporter Type I Deficiency | Nutrition ...
https://jamanetwork.com/journals/jamaneurology/fullarticle/1893441
by JM Pascual - ‎2014 - ‎Cited by 32 - ‎Related articles
Triheptanoin was manufactured in oil form (Sasol Germany GmbH) and permitted, per the manufacturer (product information documentation, version 4.02; revision January 16, 2008), for applications in the food industry as a food additive (butter marker-fat) and commercialized as Spezialöl 107 (European Inventory of

 

[Hip]

have you found any suppliers yet, hip?

I have not looked into it any further. I did wonder here whether ethyl heptanoate might make a good substitute for triheptanoin, but I am not sure how safe or effective it might be.

 

[pattismith]

interesting abstract from this article:

"The most devastating phenotype of PDH deficiency presents in the newborn period. The majority of patients are male and critically ill with a severe metabolic acidosis. There is an elevated blood or CSF lactate concentration and associated elevations of pyruvate and alanine. These patients have seizures, failure to thrive, optic atrophy, microcephaly and dysmorphic features. Multiple brain abnormalities have been described, including dysmyelination of the cortex, cystic degeneration of the basal ganglia, ectopic olivary nuclei, hydrocephalus and partial or complete agenesis of the corpus callosum. A less devastating phenotype presents in early infancy. These patients demonstrate the histopathological features of Leigh's syndrome. Other patients affected in infancy survive with a chronic neurodegenerative syndrome manifested by mental retardation, microcephaly, recurrent seizures, spasticity, ataxia and dystonia.

Mutations involving the E1 α subunit behave clinically like an X-linked dominant condition. These mutations usually are lethal in boys during early infancy. The clinical spectrum in the heterozygous girl is more varied, ranging from a devastating condition in early infancy to a mild chronic encephalopathy with mental retardation. The least symptomatic woman may give birth to affected male and female progeny and pose a significant problem in clinical diagnosis and genetic counseling.

Treatment is largely symptomatic, and the prognosis ranges from dismal to guarded. Thiamine, lipoic acid, ketogenic diet and physostigmine have been tried in different concentrations and doses with equivocal results. Some patients with periodic ataxia resulting from PDHC deficiency may respond to acetazolamide."

 

[frozenborderline]

interesting abstract from this article:

"The most devastating phenotype of PDH deficiency presents in the newborn period. The majority of patients are male and critically ill with a severe metabolic acidosis. There is an elevated blood or CSF lactate concentration and associated elevations of pyruvate and alanine. These patients have seizures, failure to thrive, optic atrophy, microcephaly and dysmorphic features. Multiple brain abnormalities have been described, including dysmyelination of the cortex, cystic degeneration of the basal ganglia, ectopic olivary nuclei, hydrocephalus and partial or complete agenesis of the corpus callosum. A less devastating phenotype presents in early infancy. These patients demonstrate the histopathological features of Leigh's syndrome. Other patients affected in infancy survive with a chronic neurodegenerative syndrome manifested by mental retardation, microcephaly, recurrent seizures, spasticity, ataxia and dystonia.

Mutations involving the E1 α subunit behave clinically like an X-linked dominant condition. These mutations usually are lethal in boys during early infancy. The clinical spectrum in the heterozygous girl is more varied, ranging from a devastating condition in early infancy to a mild chronic encephalopathy with mental retardation. The least symptomatic woman may give birth to affected male and female progeny and pose a significant problem in clinical diagnosis and genetic counseling.

Treatment is largely symptomatic, and the prognosis ranges from dismal to guarded. Thiamine, lipoic acid, ketogenic diet and physostigmine have been tried in different concentrations and doses with equivocal results. Some patients with periodic ataxia resulting from PDHC deficiency may respond to acetazolamide."

this suggests that CO2/carbogen might be effective. Acetazolamide is a carbonic anhydrase inhibitor

 

[taniaaust1]

Today's longshot: Could this be something worth trying out for Christmas?

from that article "Ketogenic diets (with restricted carbohydrate intake) have been used to control lactic acidosis with minimal success."

this is basically what I try to do now. I do very poorly with carbs and the less in my diet the better. I try to stick to a diet which is lower on carbs then a normal diabetic diet as it is what I do best on.

Im hoping they are getting on the right track with all this.

 

[frozenborderline]

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.

I'll have to try this

 

[FMMM1]

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.

Check out Ron Davis's talk at the Invest in ME Conference (2018) it's available from the OMF website (I think); I think Ron gave pretty much the same talk at the recent OMF Symposium. Point is Ron highlighted a case where a person with ME/CFS got ill with a bacterial infection and their ME/CFS symptoms improved. I think Cort Johnson highlighted that this happens in ME/CFS and autism. The reference to autism makes me recall Suramin i.e. the drug which appeared to improve symptoms in autism (Robert Naviaux trial). Any news regarding Suramin in ME/CFS?
There's some interesting stuff on leaky gut, i.e. increased translocation of LPS from gut bacteria into the bloodstream, here [https://forums.phoenixrising.me/ind...n-cause-of-me-cfs.60551/page-10#post-1005452]. Chris Armstrong proposed that the change to using amino acids (rather than glucose) for cellular energy/ATP production results in leaky gut; leaky gut maintains the change to using amino acids for cellular energy/ATP production - negative stable state i.e. ME/CFS. Check out Chris's (2016?) webinar.


Some of the areas where there is a lack of clarity could be resolved by research. Why not contact your elected representative i.e. to request funding for research into ME/CFS including the development of a diagnostic test?

Here's a potential blood based diagnostic test:
1) abstract: https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract;
2) full paper: https://sci-hub.se/10.1039/C8AN01437J.
It's based on the measurement of intracellular phenylalanine. Chris Armstrong, and Fluge and Mella, proposed that amino acids [including phenylalanine] were being used for cellular energy/ATP production in ME/CFS i.e. rather than the normal glucose.

I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) requesting that they lobby for funding for research into ME/CFS including the development of a diagnostic test [https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111].
Currently the ENVI Committee is lobbying for increased funding for research into Lyme disease and the development of a diagnostic test.
In 2016 the European Commission [European Union civil service] said that they had funded "Both basic research and the development of new diagnostics, treatments and vaccines for Lyme borreliosis are funded by EU research and innovation framework programmes. The total EU contribution to such projects since 2007 amounts to EUR 33.9 million [us dollars]" [http://www.europarl.europa.eu/doceo/document/E-8-2016-008631-ASW_EN.html].

ME/CFS received no funding from the European Union.

 

[MeSci]

Any news regarding Suramin in ME/CFS?

There is a huge range of hits for Suramin if you use the top right search box.

 

[FMMM1]

There is a huge range of hits for Suramin if you use the top right search box.

https://www.omf.ngo/2018/02/06/omf-newsletter-winter-2018/

There is a huge range of hits for Suramin if you use the top right search box.

Based on this Bob Naviaux is due to run a trial in Autism in 2019; a new (unnamed) company is currently manufacturing Suramin for that trial [https://www.healthrising.org/blog/2...th-bob-bob-naviauxs-predicting-autism-study/].

Didn't find anything regarding a Suramin trial in ME/CFS.


Some of the areas where there is a lack of clarity could be resolved by research. Why not contact your elected representative i.e. to request funding for research into ME/CFS including the development of a diagnostic test?

Here's a potential blood based diagnostic test:
1) abstract: https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract;
2) full paper: https://sci-hub.se/10.1039/C8AN01437J.
It's based on the measurement of intracellular phenylalanine. Chris Armstrong, and Fluge and Mella, proposed that amino acids [including phenylalanine] were being used for cellular energy/ATP production in ME/CFS i.e. rather than the normal glucose.

I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) requesting that they lobby for funding for research into ME/CFS including the development of a diagnostic test [https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111].
Currently the ENVI Committee is lobbying for increased funding for research into Lyme disease and the development of a diagnostic test.
In 2016 the European Commission [European Union civil service] said [regarding Lyme disease] that "Both basic research and the development of new diagnostics, treatments and vaccines for Lyme borreliosis are funded by EU research and innovation framework programmes. The total EU contribution to such projects since 2007 amounts to EUR 33.9 million [US dollars]" [http://www.europarl.europa.eu/doceo/document/E-8-2016-008631-ASW_EN.html].

ME/CFS received no funding from the European Union [http://www.europarl.europa.eu/doceo/document/E-8-2017-006901-ASW_EN.html].

 

[frozenborderline]

I've ordered 25 grams of dichloroacetate (DCA) for £32, and will be trying it soon.

I am going to take benfotiamine, alpha lipoic acid and acetyl-L-carnitine with the DCA in order to try to prevent any neuropathy (as recommended by the article quoted in this post).

Other side effects of DCA can include heartburn, nausea, vomiting, indigestion, but these can be countered with a proton pump inhibitor drug (see the same post). I wonder if DCA can be administered as a suppository or transdermally to try to avoid these stomach issues.

The one forum member who tried DCA said:

I want to try to avoid these stomach side effects.

I read that caffeine can boost the effects of DCA, which then allows for lower doses of DCA, and thus lower side effects. However, I have also read articles advising caution when taking caffeine with DCA, perhaps because it boosts the effects of DCA too much. One article said taking caffeine with DCA is more likely to cause the fatigue and weakness side effects.

Daily DCA dose recommendations for cancer treatment that I saw here are 10 to 20 mg per kg body weight (20 mg/kg to treat cancer, and 10 mg/kg as a maintenance dosage and to help prevent cancer).

In a study of treatment of congenital lactic acidosis in children, a DCA dose of 12.5 mg per kg body weight was given every 12 hours.

In patients with severe lactic acidosis associated with septic shock, 50 mg of DCA per kg body weight was used; see here.

In a rat study, 5 mg per kg body weight of DCA was used to reduce lactate accumulation in endurance exercising. For humans, that equates to a human dose of 0.8 mg per kg body weight. So for an 80 kg person, the dose would be 64 mg of DCA.



So judging by the cancer doses, typical DCA doses for an 80 kg person would equate to around 800 to 1,600 mg daily. I may try 300 mg of DCA three times daily to start with.

Did u ever try this

 

[Hip]

Did u ever try this

Yes, but after I tried a single dose, I experienced a period of depression that lasted about a month. It may have just been coincidence, but I have not yet tried DCA again.

But it looks to be a drug worth trying: a study found DCA improves fatigue, brain fog and pain in just over 1 in 3 ME/CFS patients (those with comorbid autoimmune conditions are less likely to respond). Refs: 1 2

 

[Learner1]

@debored13 You may find this interesting:

http://www.townsendletter.com/AugSept2018/metabolic0818.html

 

[Zuheb]

it's hard to get triheptanoin but I am very interested in trying it. have you found any suppliers yet, hip?

There's one pharmaceutical company based in the US that manufactors this for lipid oxidation disorders. Ultragenyx Pharmaceutical Inc - Website link. https://www.dojolvi.com/

Am not sure how you can procure this though? I am based out of Asia, so any further leads in identifying ways to get this would be great.

 

[Pyrrhus]

Related discussion:

Pyruvate dehydrogenase deficiency does not lead to fatigue: Fluge & Mella's PDH impairment revisited
https://forums.phoenixrising.me/thr...-fluge-mellas-pdh-impairment-revisited.56378/

 

[Wishful]

Pyruvate dehydrogenase deficiency does not lead to fatigue

ME seems to cause central fatigue, which is not physical fatigue, so that statement may not mean much.

 

[frozenborderline]

ME seems to cause central fatigue, which is not physical fatigue, so that statement may not mean much.

I dont think that's really true. We may not have enough data either way, but the cpets are moderately strong data in one direction.

But honestly wed need Like 10x the number of studies to be able to say either way.

 

[percyval577]

ME seems to cause central fatigue, which is not physical fatigue, so that statement may not mean much.

It doesn´t matter which kind of fatique, @Wishful. though I like to agree with central fatique.

 

[frozenborderline]

It doesn´t matter which kind of fatique, @Wishful. though I like to agree with central fatique.

It always matter what specific type of things, bc to treat s disease u need to understand the etiology.

 

[Learner1]

It always matter what specific type of things, bc to treat s disease u need to understand the etiology.

There seems to be more than one etiology for ME/CFS, and several subsets of patients with a variety of symptoms and comorbidities.

ME seems to cause central fatigue, which is not physical fatigue, so that statement may not mean much.

I'm not sure what definitions you're referring to, but Wikipedia has this definition of physical fatigue:

Physical fatigue, or muscle fatigue, is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include sleep deprivation and overall health. Fatigue can be reversed by rest.[7] Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the neuromuscular junction or by a reduction of the drive originating from the central nervous system.[8] The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system.[9] During motor activity, serotonin released in synapses that contact motoneurons promotes muscle contraction.[10] During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axon initial segment of motoneurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited.[11]

As an ME/CFS patient, I do experience physical fatigue after increasing activity, in addition to post-exertional malaise, and plain old ME/CFS fatigue. My ME/CFS was triggered by chemotherapy, which led to cancer-relatef fatigue. At some point, as my fatigue worsened and need for sleep increased, my doctors and I realized I had ME/CFS.

It's not black and white.

Both the IOM Report and Ron Tomkins have said we need an individualized approach to this disease which sure makes sense to me.