Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers

[Murph]

Forgive me if this is a stupid question, I'm no biochem expert - but could my recently discovered significant energy boost from eating large amounts of coconut oil possibly be relevant to this discussion? https://nutritionreview.org/2013/04/medium-chain-triglycerides-mcts/

i read your link and was somewhat unsure whether to trust it. But this paper I found on PubMed suggests medium chain triglycerides may be very relevant *if* some of the Krebs cycle intermediaries are deficient.

https://www.ncbi.nlm.nih.gov/pubmed/27868154

(edit at a later date to ping @Hip who I seem to recall was very interested in anaplerotic supplementation in another thread)

Nb this paper suggests a risk for females in long-term supplementation https://www.ncbi.nlm.nih.gov/pubmed/25887160 (for mice at least).

 

[Alexi]

I suspect the mito blockage also triggers some kind of allergic / anaphylaxis response. IMO all roads lead to the immune system and one way or another. Would be interested to hear your thought on this....

 

[nikefourstar]

Everybody talks about the immune system being involved, but what about the people that didn't get sick before getting cfs, that just woke up one day and then boom they had it, I could tell you the exact day I'll never forget it. I don't think my immune system has anything to do with it, knock of wood I haven't even had a cold for like 3 years.

 

[lansbergen]

I haven't even had a cold for like 3 years.

How does that prove the immunesystem is not involved?

What makes you immune for cold agents?

 

[nikefourstar]

Maybe it is for some people but wouldn't I have gotten some kind of infection or virus before getting cfs? If it was involved wouldn't I be getting sick all of the time?

 

[arewenearlythereyet]

Exactly.....immune response is the key rather than thinking of it as an "infection" there is a lot of confusion with so called "pathogens". You may have inflammation and not know it/have symptoms that you don't associate with it. It's not necessarily about having an attacking agent that invades the body (although this does seem to happen with some people e.g. glandular fever). Many people may have had a compromised immune system without knowing it until an opportunistic microbe that you already have been living with comfortably for years decides to move into places it shouldn't be. Others report that their immune system is out of control the other way and don't seem to get colds at all.
Research to help a compromised immune system or a treatment to get this back working is the key. The current research is very early stages but immunity seems to be a common thread with many pwcfs so will hopefully pave the way for other work.

The current study needs a lot more work to adequately explain all peoples onset and I suspect on its own will not account for all cases or lead to a one size fits all treatment.

 

[nikefourstar]

Then wouldn't an aids cocktail work for us?

 

[arewenearlythereyet]

the problem is finding a doctor that would prescribe you anything I'm afraid. I'm not sure what an Aids cocktail is ...I prefer red wine myself (when my histamine level allows it). Why don't you start by looking at the suggestions. Pacing, sleep hygiene, diet....there just isn't a magic pill available I'm afraid (believe me I've looked, as have many here)....just learning to live with it for the moment is your best strategy. I record symptoms on an App (T2Moodtracker). Are you doing something similar? I found this quite useful to predict bad days and look at patterns over the medium term. I do take a cocktail of supplements for methylation but these are not a cure, just improves some of the symptoms.

 

[nikefourstar]

Anything you doing for unrefreshioned sleep or muscle weakness?

 

[arewenearlythereyet]

Sleep hygiene is the key. Examples I use are:

Set a go to bed and get up time and stick to it ( I go to bed at 9 pm and get up at 6 am...even at weekends)
Aim for 9 hrs sleep
Don't nap in the day
Turn off all devices after 9 am (tv phone tablet etc) and turn off overhead lights
Instal Phillips hue lights that slowly dim to a sunset orange to try and trigger sleep
Eat light for evening meal (600-700 calories)
Don't be energetic (that's a joke) or do stressful activities (rowing with your partner) beyond 6 pm
Use lavender and chamomile essential oils by the bed (I'm not a hippy btw but these do seem to help)
Have a sleep time ritual that you stick to.... Routine helps switch off your thinking brain ready for sleep
No caffeine after 11am
Understand your circadian rhythm and target being in bed for your cycle
Keep the bedroom window open even in winter aim for room temperature to be 16-18deg (not sure where you are btw)

Getting 9 hrs sleep is not possible for a load of people. If you are lucky like me and manage to do all the above and get mostly 7 hrs a night that will help a lot. Part of my problem was I was so wired going to bed that I was only getting 4 hrs sleep most nights.

Muscle weakness. Hmm. I have no upper body strength left. To avoid PEM I just don't lift or carry weights greater than 2kg for 5 minutes. Carrying a small shopping basket in the supermarket can make me crash. I ask others to carry or lift for me ( or use a shopping trolley for 5 items). You sort of get over the humiliation after a while. I also don't run, jump or skip. Seriously I use my heart rate monitor to make sure I never do any cardio exercise whatsoever. This also crashes me. I limit my steps to 5000 per day, I never stand when I can sit down, I plan trips with sit down breaks in advance, I have a foldaway suitcase trolley in the back of the car so I don't have to carry things too far...I could go on. Once I was pacing correctly within my energy envelope my muscle and joint pain went into remission (I only have a dull all over body ache now). It took a year of strict self discipline though. I do set myself little targets. My last one was whether I could saw the end off the Xmas tree in less goes than the year before. Managed to do it in 2 goes this year...previous year I needed to take 3 rests. However this is probably because I conserved my energy that day better than the one last year.

It's boring but there is hope with proper pacing you can have a better quality of life. In remission I monitor weak legs as one of my symptoms and make sure I rest up if this starts coming back. I still crash once every 3 weeks though.

 

[Hip]

i read your link and was somewhat unsure whether to trust it. But this paper I found on PubMed suggests medium chain triglycerides may be very relevant *if* some of the Krebs cycle intermediaries are deficient.

https://www.ncbi.nlm.nih.gov/pubmed/27868154

(edit at a later date to ping @Hip who I seem to recall was very interested in anaplerotic supplementation in another thread)

Thanks for posting that.

I wonder if coconut / MCT oil and triheptanoin oil help replenish the Krebs cycle intermediates by virtue of the fact that they provide an energy input to the mitochondrial Krebs cycle (when converted into acetyl-CoA)?

When these oils supply energy to the mitochondrial Krebs cycle, that may mean that it takes some of the energy demands off pyruvate, which is the other energy input to the mitochondrial Krebs cycle (when converted into acetyl-CoA); if there is less demand on pyruvate to supply energy, then more of the pyruvate can be used to supply new intermediates to the Krebs cycle, rather than providing energy to the Krebs cycle.

Remember that pyruvate has a dual role in the Krebs cycle: it can either supply energy to the Krebs cycle (by being converted to acetyl-CoA), or can supply new Krebs cycle intermediates (by being converted into either oxaloacetate or alpha-ketoglutarate — see this post).



In the Myhill, Booth and McLaren-Howard studies, they found that Group A2 ME/CFS patients appear to be short in Krebs cycle substrates — see this post.

 

[keenly]

Basically TOXINS interfere with the mitochondria.

Increasing ATP with CoQ10, Idebenone, NADH etc, does not remove the toxins.

I was found to have plastics and copper stuck to my mitochondrial DNA. If I could remove these I might not have symptoms of CFS.

 

[Kenny Banya]

@arewenearlythereyet
In some people, full blown ME/CFS can develop literally overnight, or within two or three days, of contracting a viral infection, or more rarely, within days of getting a vaccination. That is far too fast to be due to any dietary deficiencies. Whatever the mechanism for ME/CFS, it is clear this mechanism can switch from fully off to fully on within a matter of days. So what sort of mechanism can act that fast, you might ask?

It's interesting you mention this.
Taking Modafinil (Modavigil/Provigil) was a clear catalyst for CFS going from 'mild' to 'moderate' (working able to unable to work) within a couple of days. I wish I could turn back time & never have taken Modafinil. But then I would have never been diagnosed with CFS, if it hadn't gone to 'moderate' (took 24 years to diagnose CFS, since it had been 'mild' all that time)

 

[ahmo]

Basically TOXINS interfere with the mitochondria.

Increasing ATP with CoQ10, Idebenone, NADH etc, does not remove the toxins.

I was found to have plastics and copper stuck to my mitochondrial DNA. If I could remove these I might not have symptoms of CFS.

I've certainly had fewer symptoms and better function after detoxxing metals, bacteria, Candida. My energy is still extremely limited, but my quality of life so so much better.

 

[Learner1]

Basically TOXINS interfere with the mitochondria.

Increasing ATP with CoQ10, Idebenone, NADH etc, does not remove the toxins.

I was found to have plastics and copper stuck to my mitochondrial DNA. If I could remove these I might not have symptoms of CFS.

Alpha Lipoic Acid removes toxins from mitochondria, with additional support to fully remove it from the body.

My doctor has me using PolyMVA, a polymer form of ALA, which has definitely mobilized arsenic and lead, and needed Phase II and III detox support to remove it. It's slow going, but is working.

 

[keenly]

Actually, just to clear things up. Dr Myhill was issued a warning by the GMC that expires in 2017. From the GMC website:

The GMC are scum.

 

[keenly]

These tests are BRILLIANT.

Screw those criticizing Dr Myhill. Mclaren Howard is a genius BTW.

 

[flitza]

Brilliant!

 

[Jesse2233]

I think MyHill's classification of A and B patients based on how well glycolysis is functioning may explain the differing results of Davis and Naviaux / Fluge+Mella.

Davis showed a problem with pyruvate kinase implicating glycosis (like MyHill's severe B group) and Naviaux/Fluge+Mella showed a problem with pyruvate dehydrogenase implicating the Krebs cycle (like MyHill's more moderate A group). This lines up with the fact that Davis measured samples from the severely ill (bedridden) while all of Naviaux's and most of Fluge+Mella's patients were more mild / moderate

@Hip thoughts?

 

[Hip]

@Hip thoughts?

I am too tired at the moment to try to mentally grasp a big picture overview of all this; but I think the Booth and McLaren-Howard (MBM) classification of group A and group B patients is defined on how oxidative phosphorylation is functioning, rather than how glycolysis is functioning (although all these things are connected, and MBM say that the group A patients tend to ramp up glycolysis to compensate for their energy shortfall).

MBM found that more severe ME/CFS patients tend to be group B patients (defined as having a blockage in their oxidative phosphorylation — the major ATP-producing process in the mitochondria), and the less severe ME/CFS patients tend to be the group A patients (defined as having oxidative phosphorylation running normally, but along with the group B patients, may have problems with the translocator protein, a term which Myhill et al use to refer to the adenine nucleotide translocator).


I did try to connect the MBM studies with the Fluge & Mella study in this post (though some doubt was cast on this possible connection further on in that thread).

MBM said in their 2012 study that when the translocator protein (adenine nucleotide translocator) is blocked, pyruvate dehydrogenase automatically becomes inhibited. So then I thought this might explain the inhibited pyruvate dehydrogenase Fluge & Mella found.