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Efficacy of MB for Inflammation Induced mito Dysfunction

mitochondria methylene blue cox fnirs vascular function

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#1 Infinite1

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Posted 01 May 2014 - 04:26 PM


Ok, So I figured I would take the time to post this as it seems to be a rather unique opportunity to explore this objectively utilizing research equipment here at work. Granted this probably bears little weight as the sample size is n=1, regardless it may have some carry over.

 

The Background: I've had Lyme's Disease and Babesia Duncati for at least 4-5 years, it went undiagnosed for at least 3 of those years in which I experienced significant inflammation and was characterized in a myriad of traditional Lyme/CFS symptoms. I suspect that this brought about damage to my mitochondrial cells as vascular dynamics are quite unique as evidenced by near Infrared Spectroscopy and looking at relative concentration changes of O2 (HbO) and deoxy Hb (HbR).

 

The Paradigm: A typical exercise physio cycling paradigm in which exertion is varied and relative concentrations of HbO and HbR are observed. Optodes were placed on vastus lateralis (lateral) quadriceps.

 

Periods are coded as follows:

 

E- End of warm-up and start of moderate intensity

R- Rest

H- High intensity period

C- Cool down

S- Stop

 

Attached File  Relative Concentrations.png   94.39KB   2 downloads

 

Red- HbO

Blue- HbR

Green- total Hb

 

In comparison here is a more normal response. 

 

Attached File  Normative Data.png   117.89KB   1 downloads

 

In my opinion it seems that there is a bottleneck somewhere in my Electron Transport Chain, most likely COX, and as a result instead of oxygen decreasing it paradoxically increases after the lactic acid threshold. I still need to do some more research but ran across this article which explains this phenomena.

 

Mol Cell Biochem. 1997 Sep;174(1-2):7-10.


Diagnosis of defects in oxidative muscle metabolism by non-invasive tissue oximetry.

Abstract
The dynamics of oxygen delivery and utilization are examined in a variety of mitochondrial disorders during rest, exercise and post exercise. We used a non-invasive optical technique to measure the oxygen consumption in the exercising limb in normal subjects and 5 patients with cytochrome c oxidase deficiency. We also examined 6 patients with MELAS and MERRF syndrome. We measured near-infrared spectra of hemoglobin in the gastrocnemius muscle during treadmill exercise. Normal subjects demonstrated a sustained deoxygenation during exercise, indicating an efficient utilization of delivered oxygen. Patients with cytochrome c oxidase deficiency demonstrated consistent oxygenation during exercise indicating an under utilization of delivered oxygen. Patients with MELAS and MERRF syndrome showed similar under utilization of oxygen during exercise. Non-invasive tissue oximetry during exercise demonstrates specific abnormalities in a variety of mitochondrial disorders, indicating abnormal oxygen utilization, and will be a useful addition to the clinical investigation of such disorders.

 

 

 

I am trying to come up with a suitable form of therapy and I believe Methylene Blue would be an ideal candidate given it increases COX expression.  Any thoughts??

 

Low-concentration methylene blue maintains energy production and strongly improves survival of Leigh syndrome French Canadian skin fibroblasts.

Abstract
Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein). These mutations induce a cytochrome c oxidase (COX) deficiency resulting in episodes of acute acidotic crisis that will often lead to death. There is no effective treatment. Methylene blue (MB) is a redox dye that increases COX content and activity in vitro and in vivo suggesting that MB could prevent and treat LSFC. In this study, the protective effect of low-concentration MB was tested on two LSFC cell lines, including LSFC-F1, homozygous for the mutation A354V, and LSFC-F2 a compound heterozygous for the mutations A354V and C12775STOP. MB effect on metabolic activity was assessed on both LSFC cells in stable and acidotic conditions. For LSFC-F1, results showed that metabolic activity drastically decline after 96 hours in both conditions but not LSFC-F2 and normal cells. MB completely prevents the decrease of metabolic activity in LSFC-F1. Intracellular ATP content was also measured in both culture media. After 96 hours in acidotic medium, ATP content was almost completely depleted for both LSFC cells. Interestingly, MB completely restores ATP content in LSFC-F1 and LSFC-F2 cells. Finally, MB strongly improves the survival of both LSFC cells.

 

 


Edited by Infinite1, 01 May 2014 - 04:36 PM.


#2 Infinite1

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Posted 01 May 2014 - 07:59 PM

So I ran across this article "Mitochondrial respiration as a target for neuroprotection and cognitive enhancement", see attached.

Attached File  Mito respiration and cognition.pdf   1.7MB   10 downloads

 

In this they reference a study in which "low" doses of .5-4mg/kg of MB is beneficial, I know this dosage is well beyond what most individuals report taking on this forum. 

 

Attached File  MB dose.png   126.63KB   2 downloads

 

Though it states that too high of a dose is detrimental, low doses increase COX activity by 30-60%....and later refers to a study where a "low" dose of 2.57mg/kg was effective. 

 

Attached File  MB3.png   139.04KB   1 downloads

 

 

Interestingly later in the article it covers low-level light/laser therapy and indicates that infrared light enhances COX expression...I do have some fNIRS equipment around that would be more than capable of performing this but I think at least for now I'll stick to MB, just need to determine a dose. 

 

 

 

 



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#3 niner

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Posted 02 May 2014 - 02:12 AM

What are the symptoms of this mitochondrial dysfunction? Essentially CFS symptoms? It's very cool that you have access to that instrumentation. MB sounds like a plausible treatment, but ordinary MB at the doses that you would probably need may be difficult to take. When TauRx had their first Rember (MB) trial for Alzheimer's, the majority of patients had unpleasant side effects. TauRx is now trialing leucomethylene blue (LMB), which has significantly improved bioavailability and tolerability. You could try to score some of the trial drug, perhaps on a compassionate use basis? (Good luck, you'll need it...) or you might be able to synthesize it. I think all you have to do is reduce MB with ascorbate. Some people here have tried it; it's curiously slow, but over a few hours it becomes nearly colorless. You'd want a molar excess of ascorbate and should try to exclude oxygen.

Another thing you really ought to look at is c60-olive oil. It appears to improve the efficiency of OSPHOS, and not in a small way. It's at a level that people really notice. This might make up for whatever defect is present. Would it be possible for you to do before/after measurements of Hb redox balance with c60-oo? That would be very interesting. It's extremely well tolerated with no major side effects. Get a small bottle from carbon60oliveoil.com, and use it on food just like regular olive oil, but don't heat it. I pour it over vegetables and salad, and dip bread in it. It's air sensitive so don't let it sit around- I would consume the entire 30ml bottle (2 tablespoons) in a day; this is enough for a month. The compound has phenomenal pharmacokinetics.
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#4 Infinite1

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Posted 02 May 2014 - 02:56 PM

Thanks for the response niner, yes most symptoms could be characterized as CFS like though I am 100x better today than I was a year or two ago. Mostly now I am easily fatigued after excertion, mentally dull, and vague feelings of discomfort/achiness.  

 

If I attempt any form of aerobic exercise like running I start out feeling great then soon thereafter I hit the wall- legs physically can't move etc. Basically my lactic acid threshold is quite low and this will clear after a minute or so of rest and then I can continue running as if it never happened.

 

I read an article recently that indicated during septic insult COX is severely down regulated leading to a reduction in cellular respiration, I believe that the researchers were surmising that this may account for a least one mechanism of post infectious fatigue. I suspect this is likely the case for myself, though I still do have an active babesia infection. 

 

I will have to look into the synthesis of MB with ascorbate, thanks for the info. I think for the moment I'm going to ramp up my dosage of MB slowly starting at 2mg and seeing if I can reach some therapeutic window without the sides- probably won't be reaching the doses indicated within the studies. I'll take this with a couple grams of vit. c and go from there. After a few weeks I'll run the cycling paradigm once more to see if I've made any progress. 

 

I could also test out the c60-olive oil. I honestly know nothing about this so I would be needing to research it a bit. Do you have any references for it's efficacy of improving OXPHOS?

 

One more thing I may try later on is supraphysiologic T3, there is solid support for it having a role in mitogenesis. 


Edited by Infinite1, 02 May 2014 - 03:40 PM.


#5 Infinite1

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Posted 16 October 2014 - 02:22 PM

For those following this, I haven't given up on this however my doctor has had me on an intense babesia protocol for the last several months consisting of almost a dozen different meds. One medicine in particular, Mepron, has a unique mechanism of action in which it functions as a sort of co-q-10 antagonist, or rather a non-functional analog of co-q-10 effectively inhibiting the ETC. For obvious reasons MB is contraindicated. 

 

It's clear from my reactions to these medications that I'm not out of the woods yet, however things are getting better. I'll pick this back up once I have finished this protocol, unfortunately there is no way to know for sure when this may be. Some people treat for as little as 4 months and others for years, unfortunately the Duncani strain is quite difficult to eradicate- such is my life. 



#6 Logic

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Posted 19 October 2014 - 11:58 PM

CMV is a lipid coated virus.
Medium chain fatty acids and monoglycerides, especially monolaurin and Lauric acid as found in Extra Virgin Coconut Oil are known to disrupt the lipid layer of lipid coated virii.

I have no doubt that someone will post that its doubtful that EVCO will help due to unknown pharmacokinetics etc-etc.
I agree that more research should be done on the substance but don't hold your breath as its a natural = unpatentable = unprofitable substance.

The great thing is that you can happily try EVCO for yourself and see if it works.
A fact that seems not to have occurred to many people here.

Here is some info:

http://www.apinchofh...98-Coconut-Oil/

http://cocos-mct-vco...g-mct&Itemid=16

Evaluation of the In-vitro Digestion Profiles of Long and Medium Chain Glycerides and the Phase Behaviour of Their Lipolytic Products
http://www.ncbi.nlm....pubmed/11833493

Interrelationship of triglycerides with lipoproteins and high-density lipoproteins.
http://www.ncbi.nlm..../pubmed/2203246

BHT, Butylated hydroxytoulene has a similar and possibly more powerful effect.

Edited by Logic, 20 October 2014 - 12:01 AM.


#7 Infinite1

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Posted 20 October 2014 - 03:05 PM

Thanks for the information Logic however I'm not sure how this pertains to Babesia/Lyme or MB for that matter. I have however heard of people utilizing coconut oil for the purpose of degrading biofilms in the GI tract etc...



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#8 Logic

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Posted 20 October 2014 - 09:00 PM

Oops; I was thinking CMV. soz :)

The MCTs may help with energy as the are directly absorbed but I don't think Lyme bacteria are among those affected by EVCO.





Also tagged with one or more of these keywords: mitochondria, methylene blue, cox, fnirs, vascular function

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