72 replies to this topic

[FunkOdyssey]

It's great to see a thread like this being a fellow CFS sufferer.

rwac, is there anything you've found that has removed the constant anxiety? I have found ashwagandha and curcumin to work temporarily, but the effect was not sustainable. Taurine also works, but only for a few hours. I've ordered some theanine in the hope that this will help..

In my case both an SSRI and St. John's Wort (not taken at the same time, in separate trials) have eliminated anxiety. I was also taking certain supplements that were exaggerating the problem, which I didn't figure out until much later, including such supposedly harmless things as methyl-b12 and fish oil. Getting rid of those was also key.

[rwac]

I presume you're also using methylene blue from Korda---which is wild---but you're taking an amount that has dubious clinical efficacy, and consuming a highly impure substance that crosses the blood brain barrier with great difficulty---if at all.

It's not nearly as impure as you think it is. Fish are very sensitive and would definitely notice any impurities in the MB.

Why would it have trouble crossing the BBB ?
Methylene Blue tends to concentrate in areas of high metabolism.
The liver, and the brain, for instance.
It's even used to stain tumors in vivo.

[Rational Madman]

I presume you're also using methylene blue from Korda---which is wild---but you're taking an amount that has dubious clinical efficacy, and consuming a highly impure substance that crosses the blood brain barrier with great difficulty---if at all.

It's not nearly as impure as you think it is. Fish are very sensitive and would definitely notice any impurities in the MB.

Why would it have trouble crossing the BBB ?
Methylene Blue tends to concentrate in areas of high metabolism.
The liver, and the brain, for instance.
It's even used to stain tumors in vivo.

Quantitative assays of its BBB penetration and bio-availability are reasons for my skepticism of its therapeutic potential without structural re-engineering, since its structure is believed to be the most important impediment. And while there is no evidence that you'll be placing yourself in peril by taking small doses, there's is a paucity of evidence to support the efficacy of the dose that you're self-administering, which is likely too low to provide a statistically meaningful effect that can be ruled out as not placebo. But, when doses are administered at higher therapeutic doses, the presence of toxic constituents of the low grade Korda solution become more problematic. For the treatment of CFS, the mitochondria is an important target, but there are dozens of more viable and empirically supported modalities that I would consider first before embarking on the more uncertain low dose methylene blue therapy---which to be sure, I'm not entirely dismissing. But, the combination of desire, conviction, and opioid system can be a very powerful combination that I think many here (including myself) have failed to take account of in spite of our better judgement.

Edited by Rol82, 29 September 2010 - 04:39 AM.

[rwac]

Quantitative assays of its BBB penetration and bio-availability are reasons for my skepticism of its therapeutic potential without structural re-engineering, since its structure is believed to be the most important impediment.

Can you point me to these assays ?

Methylene blue improves brain oxidative metabolism and memory retention in rats.

The Brain Metabolic Enhancer Methylene Blue Improves Discrimination Learning in Rats

Besides, if it needs structural re-engineering so badly, how did it go through clinical trials and become a drug ?

Edited by rwac, 29 September 2010 - 05:02 AM.

[Rational Madman]

Quantitative assays of its BBB penetration and bio-availability are reasons for my skepticism of its therapeutic potential without structural re-engineering, since its structure is believed to be the most important impediment.

Can you point me to these assays ?

Methylene blue improves brain oxidative metabolism and memory retention in rats.

The Brain Metabolic Enhancer Methylene Blue Improves Discrimination Learning in Rats

Besides, if it needs structural re-engineering so badly, how did it go through clinical trials and become a drug ?

It should be noted, that the structure and grade is likely different than the Korda source that you're using, and that the doses per/kg are radically different. To be clear, I wasn't doubting the potential of methylene blue, but rather, I was dubious about the therapeutic efficacy of the relatively impure and unmodified source that you're using, that was designed for a completely different indication. If you look at the latest entries in my regimen thread, for instance, it should be clear that I remain convinced about it's potential value.

[rwac]

It should be noted, that the structure and grade is likely different than the Korda source that you're using, and that the doses per/kg are radically different. To be clear, I wasn't doubting the potential of methylene blue, but rather, I was dubious about the therapeutic efficacy of the relatively impure and unmodified source that you're using, that was designed for a completely different indication. If you look at the latest entries in my regimen thread, for instance, it should be clear that I remain convinced about it's potential value.

Yes, the doses used are much higher. I don't believe that the impurity has a significant effect here.

What do you mean when you say "structure" of the Methylene Blue ?

[Rational Madman]

It should be noted, that the structure and grade is likely different than the Korda source that you're using, and that the doses per/kg are radically different. To be clear, I wasn't doubting the potential of methylene blue, but rather, I was dubious about the therapeutic efficacy of the relatively impure and unmodified source that you're using, that was designed for a completely different indication. If you look at the latest entries in my regimen thread, for instance, it should be clear that I remain convinced about it's potential value.

Yes, the doses used are much higher. I don't believe that the impurity has a significant effect here.

What do you mean when you say "structure" of the Methylene Blue ?

I'm referring to chemical structure of Methylene Blue, which diminishes its therapeutic value. As for specific differences, I would probably only be able to provide an incomplete explanation if reliant only on readily accessible memory. So, I'll consult the literature tomorrow, and provide a more satisfying explanation, because many on this board use it, and because its value remains shrouded.

[Lufega]

Is chronic fatigue syndrome a connective tissue disorder? A cross-sectional study in adolescents.
van de Putte EM, Uiterwaal CS, Bots ML, Kuis W, Kimpen JL, Engelbert RH.

Department of Pediatric, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands. e.vandeputte@wkz.azu.nl


Abstract
OBJECTIVES: To investigate whether constitutional laxity of the connective tissues is more frequently present in adolescents with chronic fatigue syndrome (CFS) than in healthy controls. Increased joint hypermobility in patients with CFS has been previously described, as has lower blood pressure in fatigued individuals, which raises the question of whether constitutional laxity is a possible biological predisposing factor for CFS.

DESIGN: Cross-sectional study.

PARTICIPANTS: Thirty-two adolescents with CFS (according to the criteria of the Centers for Disease Control and Prevention) referred to a tertiary hospital and 167 healthy controls.

METHODS: The 32 adolescents with CFS were examined extensively regarding collagen-related parameters: joint mobility, blood pressure, arterial stiffness and arterial wall thickness, skin extensibility, and degradation products of collagen metabolism. Possible confounding factors (age, gender, height, weight, physical activity, muscle strength, diet, alcohol consumption, and cigarette smoking) were also measured. The results were compared with findings in 167 healthy adolescents who underwent the same examinations.

RESULTS: Joint mobility, Beighton score, and collagen biochemistry, all indicators of connective tissue abnormality, were equal for both groups. Systolic blood pressure, however, was remarkably lower in patients with CFS (117.3 vs. 129.7 mm Hg; adjusted difference: -13.5 mm Hg; 95% confidence interval [CI]: -19.1, -7.0). Skin extensibility was higher in adolescents with CFS (mean z score: 0.5 vs. 0.1 SD; adjusted difference: 0.3 SD; 95% CI: 0.1, 0.5). Arterial stiffness, expressed as common carotid distension, was lower in adolescents with CFS, indicating stiffer arteries (670 vs 820 mum; adjusted difference: -110 mum; 95% CI: -220, -10). All analyses were adjusted for age, gender, body mass index, and physical activity. Additionally, arterial stiffness was adjusted for lumen diameter and pulse pressure.

CONCLUSIONS: These findings do not consistently point in the same direction of an abnormality in connective tissue. Patients with CFS did have lower blood pressure and more extensible skin but lacked the most important parameter indicating constitutional laxity, ie, joint hypermobility. Moreover, the collagen metabolism measured by crosslinks and hydroxyproline in urine, mainly reflecting bone resorption, was not different. The unexpected finding of stiffer arteries in patients with CFS warrants additional investigation.

[Lufega]

Effects of Applephenon and ascorbic acid on physical fatigue.
Ataka S, Tanaka M, Nozaki S, Mizuma H, Mizuno K, Tahara T, Sugino T, Shirai T, Kajimoto Y, Kuratsune H, Kajimoto O, Watanabe Y.

Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.


Abstract
OBJECTIVE: We examined the effects of Applephenon and ascorbic acid administration on physical fatigue.

METHODS: In a double-blinded, placebo-controlled, three-way crossover design, 18 healthy volunteers were randomized to oral Applephenon (1200 mg/d), ascorbic acid (1000 mg/d), or placebo for 8 d. The fatigue-inducing physical task consisted of workload trials on a bicycle ergometer at fixed workloads for 2 h on two occasions. During the test, subjects performed non-workload trials with maximum velocity for 10 s at 30 min (30-min trial) after the start of the test and 30 min before the end of the test (210-min trial).

RESULTS: The change in maximum velocity between the 30- and 210-min trials was higher in the group given Applephenon than in the group given placebo; ascorbic acid had no effect.

CONCLUSION: These results suggest that Applephenon attenuates physical fatigue, whereas ascorbic acid does not.

[rwac]

CONCLUSION: These results suggest that Applephenon attenuates physical fatigue, whereas ascorbic acid does not.

Nice!

Two sources of Apple Polyphenols:

http://www.swansonvi.../ItemDetail?n=0
http://www.ktbotanic...ols-p-7878.html

[longevitynow]

I've had CFS for decades, but under control 95% of the time for years. I'd be cautious with stimulants,

" Armodafinil/Modafinil, a MAO inhibitor, amphetamine salts, Strattera, Wellbutrin".

In my experience while they give me more energy they often throw the immune system out of balance (i.e. stimulate a temporary relapse). I like deprenyl, but it adversely affects my sleep (like a lot of other stimulants), so ends up being counter productive long term. I've had good luck with adrenal glandulars/supplements, DHEA and other things. But monitor your reaction to stimulants.
Also, it is good to ask yourself, "Do I have CFS/CFIDS (an immune system disorder), or merely chronic fatigue/excess tiredness.

[rwac]

Also, it is good to ask yourself, "Do I have CFS/CFIDS (an immune system disorder), or merely chronic fatigue/excess tiredness.

How do you tell the difference ?

[longevitynow]

Also, it is good to ask yourself, "Do I have CFS/CFIDS (an immune system disorder), or merely chronic fatigue/excess tiredness.

How do you tell the difference ?

The CDC criteria is a good place to start, but somewhat flawed. That is, many people will meet many of the criteria but not enough to be formally diagnosed. Most important criteria is extreme fatigue AND Chronic Flu-like symptoms. You could possibly still have CFIDS (Chronic Fatigue Immune System Disorder) without the Flu-like symptoms, but the Flu-like Symptoms are one of the biggest indicators that the immune system is out of balance (Hyper- or hypo-active), rather than just fatigue.

[ajnast4r]

if you have digestive issues combined with CFS... i HIGHLY suggest you buy a bottle of 'digest spectrum' by enzymedica and give it a try. life changing stuff for me

[FunkOdyssey]

Thanks for the tip, I'll try it.

[rwac]

I'm referring to chemical structure of Methylene Blue, which diminishes its therapeutic value. As for specific differences, I would probably only be able to provide an incomplete explanation if reliant only on readily accessible memory. So, I'll consult the literature tomorrow, and provide a more satisfying explanation, because many on this board use it, and because its value remains shrouded.

Interesting. I believe Methylene Blue does not enter cells, unless the tissue is permeabilized.[1]
BUT, oxidative stress permeabilizes cell membranes[2] and Methylene Blue is a small molecule which should be able to cross over comparatively easily.

This might account for tiny doses of MB being effective as a nootropic. Prersumably, infected or otherwise stressed cells will have more permeable cell membranes, leading to a higher concentration of MB locally.

[Animal]

if you have digestive issues combined with CFS... i HIGHLY suggest you buy a bottle of 'digest spectrum' by enzymedica and give it a try. life changing stuff for me

Yeah I'm going to try that too, have always has gastrointestinal problems.

[ajnast4r]

Thanks for the tip, I'll try it.

check out this thread for more detailed info

http://www.imminst.o...g-my-digestion/

[Rational Madman]

if you have digestive issues combined with CFS... i HIGHLY suggest you buy a bottle of 'digest spectrum' by enzymedica and give it a try. life changing stuff for me

Although I don't doubt your experience, I think we need to be reminded of the limitations of digestive enzymes: ability to penetrate acid barriers, empirical effectiveness for said indication, and the availability of more effective options.

Edited by Rol82, 06 October 2010 - 02:46 PM.

[Rational Madman]

I'm referring to chemical structure of Methylene Blue, which diminishes its therapeutic value. As for specific differences, I would probably only be able to provide an incomplete explanation if reliant only on readily accessible memory. So, I'll consult the literature tomorrow, and provide a more satisfying explanation, because many on this board use it, and because its value remains shrouded.

Interesting. I believe Methylene Blue does not enter cells, unless the tissue is permeabilized.[1]
BUT, oxidative stress permeabilizes cell membranes[2] and Methylene Blue is a small molecule which should be able to cross over comparatively easily.

This might account for tiny doses of MB being effective as a nootropic. Prersumably, infected or otherwise stressed cells will have more permeable cell membranes, leading to a higher concentration of MB locally.

Sure, but is there any quantitative evidence to validate the notion of using small doses?

[rwac]

Sure, but is there any quantitative evidence to validate the notion of using small doses?

None, it's subjective. Anyway, those small doses don't work for me anymore.

[Rational Madman]

Sure, but is there any quantitative evidence to validate the notion of using small doses?

None, it's subjective. Anyway, those small doses don't work for me anymore.

Well, that's why I'm dubious.

[FunkOdyssey]

if you have digestive issues combined with CFS... i HIGHLY suggest you buy a bottle of 'digest spectrum' by enzymedica and give it a try. life changing stuff for me

Although I don't doubt your experience, I think we need to be reminded of the limitations of digestive enzymes: ability to penetrate acid barriers, empirical effectiveness for said indication, and the availability of more effective options.

Gut is leaky in CFS, undigested food particles provide constant antigenic stimulation of the immune system, it actually makes excellent sense. Reducing intestinal permeability would be ideal but if that is impossible, thoroughly digesting all food, particularly proteins, before they reach permeable sections of the small intestine should reduce symptoms and food sensitivities/allergies. The plant based enzymes are much more flexible than our own digestive enzymes with regard to activity over a wide range of pH.

Evidence of "leaky gut" in CFS pathology

Is the mechanism of systemic immune activation in XMRV positive
CFS patients similar to that observed in HIV ?

K. De Meirleir1, K. Metzger2, M. Fremont2, C. Roelant3
1Vrije Universiteit Brussel, Medical physiology, Brussel, Belgium; 2RED LABORATORIES, Science Departement, Zellik, Belgium;
3Protea Biopharma, Science Departement, Brussel, Belgium

Introduction
HIV-1 infection results in chronic activation of the immune system. It was suggested
(Brenchley et al., Nature 2006) to occur through a breakdown of the mucosal barrier and stimulation of
immune cells by microbial products. CD14+ monocytes/macrophages secrete soluble CD14 (sCD14),
which binds LPS and pro-inflammatory cytokines. In the study cited above it was shown that LPS directly
stimulates sCD14 production in vivo. Earlier our group reported that serum LPS is significantly higher in
Chronic Fatigue Syndrome (CFS) patients compared to contact and non-contact controls. Our hypothesis
is that XMRV positive CFS patients also present with immune activation related to mucosal translocation
in the gut

Material & methods: Fifteen XMRV positive CFS patients who fulfilled the Fukuda et al. criteria (1994)
and matched controls were studied. The detection of XMRV was performed by LNCaP co-culture with
PMCs as described by Lombardi et al. (2009). We used commercially available ELISA's to quantify levels
of sCD14, C4a and cytokines. Stool IgA was determined by Diagnos-Techs,Inc
(Tukwila,Washington,USA). Statistical analysis was performed using an ANOVA T-test

Results: XMRV positive CFS patients showed statistically significantly (p<0.05) higher serum levels of
sCD14, C4a, IL-8 and MIP1-beta. Stool IgA levels were extremely low (p<0.01) compared to those of
healthy controls

Conclusion: Although it is too early to conclude that XMRV is a cause of CFS, the similarity with HIV-1
where microbial translocation is a cause of systemic immune activation is striking. A study in rhesus
macaques infected with XMRV showed infected CD4+ T cells in the gastrointestinal tract. The frequency
of infected XMRV cells in the gastrointestinal tract in these macaques increased from acute to chronic
infection (Sharma et al.). The data of our study along with the findings in XMRV infected macaques ask
for confirmation by performing gastrointestinal biopsy studies in XMRV positive CFS patients

Edited by FunkOdyssey, 06 October 2010 - 07:19 PM.

[ajnast4r]

Although I don't doubt your experience, I think we need to be reminded of the limitations of digestive enzymes: ability to penetrate acid barriers, empirical effectiveness for said indication, and the availability of more effective options.

animal based enzymes are limited but the plant based enzymes are able to be created to be active of a very wide ph. enzymedica & biocore brands use 'blending' processes to make sure the amylases, lipases, proteases are active throughout the entire gi tract. i know biocore, and im sure enzymedica, has done extensive testing with their enzymes & models of the human digestive system.

http://www.enzymedic.../therablend.php

http://www.nationale.../optimum-bg.pdf

There is a general misconception among many scientists
and consumers that supplemental enzymes do not survive
the acidic conditions of the stomach, and must therefore
be enterically coated. This may be true for animal enzymes
but fungal microbial enzymes are especially resistant to
stomach acid. To prove that Biocore® Optimum survives the
acidity of the stomach gastric survivability experiments were
conducted on the various enzyme activities that comprise
Biocore® Optimum. The experiment involved the incubation
of Biocore® Optimum in a gastric solution for 1 hour followed
by transfer to intestinal juices and then testing for activity.
Figures 3, 4 and 5 show the activities of protease, lipase and
amylase in Biocore® Optimum after exposure to gastric acid and
reconstitution in intestinal juices. This data demonstrates that
the enzymes in Biocore® Optimum

[notlupus]

For me, a gluten free diet made a huge difference. I'm sure it has to do with the gut permeability issues mentioned. I'm also very low corn at this point (which is often contaminated with mold or gluten in processing).

If you have been on abx and haven't taken a course of diflucan it's worth looking into. Made a big difference for me.

[rwac]

For me, a gluten free diet made a huge difference. I'm sure it has to do with the gut permeability issues mentioned. I'm also very low corn at this point (which is often contaminated with mold or gluten in processing).

If you have been on abx and haven't taken a course of diflucan it's worth looking into. Made a big difference for me.

I've been gluten free for the last year or so. Low corn, but I may eat some if I go out which is quite rare.
I'm pretty sure that the olive leaf I've been taking is anti-fungal.
I've not taken antibiotics for 3 months or so now, plus I'm on a low carb diet, so fungal issues don't seem very likely.

Although I was getting my AI of choline (550mg), I seem to respond well to an additional 250mg a day.
Maybe this is the cause of my liver problems ...

Edited by rwac, 17 October 2010 - 04:36 PM.

[Rational Madman]

Any updates? Concerns?

[rwac]

I dropped the CLO, vit C.
Added some Viragraphis.

Sorry, been very lethargic the last couple of weeks or so, and I've not been able to do much.
I feel like sleeping all the time, just barely recovering from it.

Maybe something to do with the weather change. Who knows.

[Sillewater]

Maybe something to do with the weather change. Who knows.

Hope you feel better!

[scandic]

I dropped the CLO, vit C.
Added some Viragraphis.

Sorry, been very lethargic the last couple of weeks or so, and I've not been able to do much.
I feel like sleeping all the time, just barely recovering from it.

Maybe something to do with the weather change. Who knows.

You could try raw garlic, it has helped me quite a bit with my CFS. It's a natural antibacterial/fungal. Eat a few raw cloves of garlic, remember to chew it. It's dirt cheap.

http://www.ncbi.nlm....pubmed/17955479

Edited by scandic, 27 October 2010 - 09:06 PM.