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

[ZeroGravitas]

The MES is calculated just by multiplying the 5 efficiency figures together.

I tried to calculate someone's MES in this post, but I am not entirely sure I am doing it right.

Oh, that simple, eh? A straight forwards multiplication would certainly accentuate any differences (far more than, say, some kind of averaging across the 5 figures).

And no worries, don't push it. (I'm not giving this all my energy right now anyway.)

 

[Hip]

Oh, that simple, eh? A straight forwards multiplication would certainly accentuate any differences (far more than, say, some kind of averaging across the 5 figures).

I remember Dr Norman E. Booth, one of the authors of the Myhill papers, saying that in a process involving many sequential steps, the overall efficiency of the process is equal to the product of the efficiencies of the individual steps (ie, the individual efficiencies multiplied together). So that's the basis of why these 5 individual efficiencies are multiplied together in order to get the MES.

 

[ahmo]

@Marylib Don't know if this will be enough for you, but I used to put my aminoes and minerals into footbaths. This was when I was using large amounts of potassium, would have been revolting to drink it. I've written a pr blog about my footbaths

 

[boolybooly]

Responses from Dr Myhill and Dr John McLaren Howard. (Not entirely sure if this has been posted, am a bit foggy and airheady at the moment, still, if a thing is worth saying...)

Response to the paper 'Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test' by Cara Tomas et al

https://drmyhill.co.uk/wiki/Response_to_the_paper_'Assessing_cellular_energy_dysfunction_in_CFS/ME_using_a_commercially_available_laboratory_test'_by_Cara_Tomas_et_al

 

[MrTwoToedSloth]

I'm curious to know what everyone has tried and if they've had success? I was dx'd with fibro and cfs a few years back and have largely been an nonfunctional human being since.

Ironically, I was looking through some of the same studies and others, and I decided to take one last stab at the mitochondria theory(I had tried a lot of these supps by themselves with little to no effect) and I decide to throw everything at the wall and see if anything stuck this time. To my surprise, I've had really good results primarily taking a high dose of coq10(300mg), Acetyl - L - Carnitine, a B vitamin complex, nicotinamide riboside, NA-R-ALA.

Other things that have helped but I think are more supplemental have been a good protein powder, creatine monohydrate 5g/day, D-Ribose 5g/day. I've also been taking Red Resihi Mushrooms. I can't remember why I decided to try it, but I tend to feel better on days I take it so I've continued to take it for now. I'm guessing it's just another anti-oxidant to help with mitochondrial health.

Noticeable improvement at 1 month, huge improvement at 2 months and another decent improvement at month 3.

My symptoms have honestly been at least 75% better. General energy levels are way up, flares/PEM last hours at most instead of days, weeks, or months. I went on a long 3 week trip to europe (which I expected to spend most of holed up in my room) and only flared twice for a couple hours each time. I was even stuck in an airport for over 24 hours due to an issue and did not flare. During that trip I did not have access to creatine, protein powder, or D-Ribose which is why I'm not convinced they are absolutely necessary. I do notice some improvement on them though so they are worth mentioning.

So I'm now I'm very interested to see if anyone else with fibro or cfs has had luck with a similar combination.

 

[Learner1]

I am on a similar protocol, which has been quite helpful. NR does not work on me, but NMN and NAD+ help instead. I also take phospholipids (NT Factor) to repair damaged mito membranes. My labs and symptoms have improved with this approach.

 

[Hip]

To my surprise, I've had really good results primarily taking a high dose of coq10(300mg), Acetyl - L - Carnitine, a B vitamin complex, nicotinamide riboside, NA-R-ALA.

Can you quantify the improvement you experienced from these supplements in terms of where you were before on the ME/CFS scale of: very severe, severe, moderate, mild, remission, and where you moved up to on this scale as a result of these supplements?

Na-R-ALA (the sodium salt of R-alpha lipoic acid) is the only unusual supplement in your list that I have not seen before. I've only used the regular alpha lipoic acid.

 

[Pyrrhus]

Na-R-ALA (the sodium salt of R-alpha lipoic acid) is the only unusual supplement in your list that I have not seen before. I've only used the regular alpha lipoic acid.

Just in case anyone is interested:

Regular alpha-lipoic acid (ALA) is a racemic mixture of R-ALA and L-ALA. Only R-ALA is naturally found in the human body. There is some evidence that L-ALA may be harmful. Therefore, some people prefer to take R-ALA instead of regular ALA...

 

[MrTwoToedSloth]

I probably fit more in the moderate - severe bracket for the past few years. Never used a wheel chair but mostly housebound outside of maybe one activity a week which usually would lead to a flare up/recovery period for the rest of it. Rinse and repeat. I would easily say that I'm currently in the mild category and maybe a bit further beyond that. I don't think a low stress, part time job would be an issue right now.

I'm now trying to figure out recovery and consistency and will probably be looking for part time, low stress work this week if I'm still alright(currently stress testing with increased exercise to see how good recovery is!).

None of the supplements are outside of the norm, but I didn't get a huge boost individually. For instance, I've tried CoQ10 probably 3 separate times before this with pretty much no effect.

 

[MrTwoToedSloth]

I am on a similar protocol, which has been quite helpful. NR does not work on me, but NMN and NAD+ help instead. I also take phospholipids (NT Factor) to repair damaged mito membranes. My labs and symptoms have improved with this approach.

Oh that's interesting! What happened on NR? Did you just have no effect? NR and NMN should be fairly interchangeable in theory for NAD+ production I think? Did you start taking them both at the same time or did you try one before the other? Phospholipids also make sense. I'll add these to things to consider trying!

 

[Hip]

None of the supplements are outside of the norm, but I didn't get a huge boost individually. For instance, I've tried CoQ10 probably 3 separate times before this with pretty much no effect.

Can I ask, which brand of nicotinamide riboside do you use, and what daily dose?

And what doses of Na-R-alpha lipoic acid and acetyl-L-carnitine?

I think I have probably taken your cocktail of supplement altogether at the same time before in the past, though with the exception of nicotinamide riboside. So that might be a supplement worth trying in combination with the others.

 

[MrTwoToedSloth]

Can I ask, which brand of nicotinamide riboside do you use, and what daily dose?

And what doses of Na-R-alpha lipoic acid and acetyl-L-carnitine?

I think I have probably taken your cocktail of supplement altogether at the same time before in the past, though with the exception of nicotinamide riboside. So that might be a supplement worth trying in combination with the others.

Taking Tru Niagen 300mg/day. May be cheaper options since it all seems to be produced from the same place(chromadex) but most seem to be around $40/month.

NA-R-ALA at 125mg from Nootropics Depot.

Acetyl - L - Carnitine at 500mg from Nootropics Depot. I started taking this one due to good results from a pilot study for fibro. They used 1500mg/day but I found that it made me tense up too much and agitated at that dosage. Felt like too much, so I throttled it down and settled on 500mg.

Forgot to mention that I also take L-Theanine primarily at night(200mg).

Other supps I've considered adding: PQQ, Nigella Sativa(black seed oil), and Shilijat. But I'm not really sure how many more anti-oxidants I want to throw into the pile at the moment. Things to consider though for sure.

 

[gregh286]

I'm curious to know what everyone has tried and if they've had success? I was dx'd with fibro and cfs a few years back and have largely been an nonfunctional human being since.

Ironically, I was looking through some of the same studies and others, and I decided to take one last stab at the mitochondria theory(I had tried a lot of these supps by themselves with little to no effect) and I decide to throw everything at the wall and see if anything stuck this time. To my surprise, I've had really good results primarily taking a high dose of coq10(300mg), Acetyl - L - Carnitine, a B vitamin complex, nicotinamide riboside, NA-R-ALA.

Other things that have helped but I think are more supplemental have been a good protein powder, creatine monohydrate 5g/day, D-Ribose 5g/day. I've also been taking Red Resihi Mushrooms. I can't remember why I decided to try it, but I tend to feel better on days I take it so I've continued to take it for now. I'm guessing it's just another anti-oxidant to help with mitochondrial health.

Noticeable improvement at 1 month, huge improvement at 2 months and another decent improvement at month 3.

My symptoms have honestly been at least 75% better. General energy levels are way up, flares/PEM last hours at most instead of days, weeks, or months. I went on a long 3 week trip to europe (which I expected to spend most of holed up in my room) and only flared twice for a couple hours each time. I was even stuck in an airport for over 24 hours due to an issue and did not flare. During that trip I did not have access to creatine, protein powder, or D-Ribose which is why I'm not convinced they are absolutely necessary. I do notice some improvement on them though so they are worth mentioning.

So I'm now I'm very interested to see if anyone else with fibro or cfs has had luck with a similar combination.

That is a very good supp pack and not unlike mine. I have went.from moderate to working full time since feb this year.
I operate with liquid carnitine...way better than tablets. ALA which is just the s**t....on empty stomach. I avoid major glucose spikes in morning and also a B vit super strength solgar. D ribose i think is a bit of a faker. High doses of glycine needed if your joints are weedy. (No pun intended).
Was Europe hot...did you sweat daily?

 

[MrTwoToedSloth]

That is a very good supp pack and not unlike mine. I have went.from moderate to working full time since feb this year.
I operate with liquid carnitine...way better than tablets. ALA which is just the s**t....on empty stomach. I avoid major glucose spikes in morning and also a B vit super strength solgar. D ribose i think is a bit of a faker. High doses of glycine needed if your joints are weedy. (No pun intended).
Was Europe hot...did you sweat daily?

That's great to hear! That's a huge improvement and gives me hope that this is isn't just a flash in the pan! I'm hoping that getting back into work is going to go alright. I have quite a bit of anxiety about it since I've tried and failed before.

Liquid Carnitine is interesting. Is it still Acetyl or is it just L-Carnitine? Mine is just powder in a capsule. And yeah, you're right about the ALA... I made the same mistake once and don't plan to again. Haha.

What do you mean that D-Ribose is a faker? Like you think it's just placebo and that the theories don't hold up with it?

I was primarily in Italy. It was very hot. Probably averaged high 80s and air conditioning was rare in some of the places. So yeah, lots of sweating and lots of walking! But it was very enjoyable. Such a beautiful country!

 

[gregh286]

Yeah the sweating helps a lot to lower lactic levels pretty quickly and keep.cell functioning high. I have a home sauna....great job.
Never really got anything much from ribose...yea think its placebo..
Certainly factors than stimulate metabolism are the ticket. Its liquid l.carnitine by h+b. Take about 3g daily.
Whatever works to move up metabolism a few years!

https://www.hollandandbarrett.com/s...ine-bottle-lemon-1500mg-60015904?skuid=015904

 

[boolybooly]

Dr Karl Morten has commented in this MEA blog.

https://www.meassociation.org.uk/20...n-in-me-cfs-by-dr-karl-morten-21-august-2019/

 

[tiabuf]

Re above link
''Interview with Dr Karl Morten on Science 4 ME forums'',

I went on there when the paper hit the news via MEA apparently I had joined a couple of years ago, I remembered I wasn't impressed back then & certainly wasn't impressed last week either.

I also noticed this in the link above:-
''We carried out a range of studies which are documented in our report. This report has not been peer reviewed and is our interpretation of our data''.

One of the many things that really stood out to me was the way the original was worded and they are still doing it ''Myhill Group'' ???? not as per professional Science (Myhill et al 2009) or referring to Acumen Labs etc

Released in Nature.com too known for this sort of thing whereas their other papers were released in PeerJ etc

Shouldn't this just have been

We were unable to replicate Acumen Labs Mitochondria Dysfunction test using a NHS Commercially available test (obviously worded better than that but you know what I mean)

 

[olegsel]

Thanks for this thread, @Hip , @paolo , @Norman E. Booth
Very relevant.
A ketogenic diet helped me. But after 1.5 months of being on a diet, there was a sharp breakdown and even greater fatigue, a fog in the head, "in general" no strength. The condition is similar to a pre-glycemic coma.
Vitamin B3, thyroid hormones have a positive effect.

In a post, you can give links to forum threads on substances that may be useful.
thank

 

[olegsel]

Neurons are excitable cells that require large amounts of energy to support their survival and functions and are therefore prone to excitotoxicity, which involves energy depletion. By examining bioenergetic changes induced by glutamate, we found that the cellular nicotinamide adenine dinucleotide (NAD+) level is a critical determinant of neuronal survival. The bioenergetic effects of mitochondrial uncoupling and caloric restriction were also examined in cultured neurons and rodent brain. 2, 4-dinitrophenol (DNP) is a chemical mitochondrial uncoupler that stimulates glucose uptake and oxygen consumption on cultured neurons, which accelerates oxidation of NAD(P)H to NAD+ in mitochondria. The NAD+-dependent histone deacetylase sirtulin 1 (SIRT1) and glucose transporter 1 (GLUT1) mRNA are upregulated mouse brain under caloric restriction. To examine whether NAD+ mediates neuroprotective effects, nicotinamide, a precursor of NAD+ and inhibitor of SIRT1 and poly (ADP-ribose) polymerase 1 (PARP1) (two NAD+-dependent enzymes), was employed. Nicotinamide attenuated excitotoxic death and preserved cellular NAD+ levels to support SIRT1 and PARP 1 activities. Our findings suggest that mild mitochondrial uncoupling and caloric restriction exert hormetic effects by stimulating bioenergetics in neurons thereby increasing tolerance of neurons to metabolic stress.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645538/

 

[olegsel]

How much a major problem in the disease can be the pathology of mitochondria?
Indirect or direct preparations: carnitine, ubiquinone, magnesium; keto diet; thyroid hormones ...
Indirect: immunomodulators removing autoimmunity; antiviral drugs ... Everything is aimed at restoring the functioning of mitochondria.

The controllability of ion channels, the production of cortisol, the functionality of the immune system depends on the state of mitochondria ????

@Hip , @paolo, @Mary