384 replies to this topic

[Logan]

MB now being investigated as a possible treatment to alleviate residual cognitive issues with bipolar.

http://www.google.co...WS2m0jBuLfwxyXg

Bipolar Disorder a Treatable Illness

"The first take-home message is that methylene blue is a good treatment for patients with bipolar disorder who have not stabilized on their current treatment," Dr. Alda said.

"The second message is that people with bipolar disorder can actually do quite well with treatment and can often improve to the point of full functioning. When we see patients who are quite a bit better, we should not be fully satisfied, and instead should aim for as complete a recovery as we can."

"The treatment is ideal for patients who do not improve 100% who are instead maybe at 70% to 80%, so they have stopped having depression and manic episodes but they are not quite there," he added. "These patients would be candidates for methylene blue. It's a 'fine-tuning' rather than a primary mood stabilizing treatment."

The study was funded by Stanley Medical Research Institute in Washington DC. Dr. Alda has disclosed no relevant financial relationships.

Has this study been posted already?

Edited by MorganM, 10 September 2011 - 05:01 PM.

[robosapiens]

One could try some NO Donors such as L-Arginine, L-Citruline

[lamprecht]

is mb as effective when applied directly to the skin for fungal infections? i have some light pink splotches on my arm that are often covered in dried up dead skin [i used to use lotion to moisturize so they don't seem as noticeable] that i think are a fungal infection.

[unregistered_user]

I wouldn't hesitate to try it but beware, it will stain you blue unless you use ascorbic acid to make it clear.

[manic_racetam]

All this talk of topical use has got me doing a trial for the pitted keratolysis (little holes in the skin on the bottom of my feet) I've had for years. It's basically asymptomatic but it would be cool if I could get rid of it. Been treating the soles of my feet with quite a bit of MB every two days. Not sure if it's effective against bacterial infections but it's so cheap that it's worth a try at least.

Blue feet, blue socks and blue shower-floor though. I was worried at first that an excessive amount would be absorbed through the skin but my urine isn't blue so it can't be too high a dose in the bloodstream right?

[MrHappy]

I've found vinegar, particularly apple cider vinegar, to be very effective as an anti-fungal and anti-bacterial. It also kills warts and shrinks/kills moles. Probably something to do with how acidic it is, but I think there may be more to it. ACV smells much like that sweet smell you get on large scabs when they are healing. I wonder if the body somehow treats it similarly and cranks up the immune response in that area.

This works best if the area is scratched to allow access to the bloodstream. Get a strip a gauze and pour on the vinegar. Apply the gauze over the affected area (mild sting). Cover and seal over the gauze with a plastic strip or similar. Change daily for about a week, depends on the application.

I shrank a 4mm mole to nothing in about a week, whereas a 20mm mole took about 2 weeks. It gets right into the 'roots' of the mole and kills it.
Warts take about 4-7 days.
Fungus takes around the same.

Can also be ingested - suggest around 1 shot / 30mL of ACV with water or juice (taste is strong, but you do get used to it easily.)
Helps alkalize your blood.
Seems to have good effects on liver function as well as bowel / autoimmune issues, such as gluten intolerance.

[treonsverdery]

The unblue methylene blue might be where Se replaces S at the molecule.

 methylene spring green.png   26.15KB   18 downloads

Edited by treonsverdery, 30 September 2011 - 05:55 PM.

[Brainbox]

I just stumbled upon this nice infotainment overview. Don't know if it has been posted already. Nothing new though, but this is the first publication I'm aware of that mentions the biphasic dose response as being the result of hormesis. You don't need to be a rocket scientist to dream this up, but good to see that medical professionals seriously mention it.

Also interesting that the metabolite and impurity Azure B is responsible for part of the effects of MB.

click.

Edited by Brainbox, 02 October 2011 - 08:54 PM.

[thedevinroy]

It's not an 'instafix'. You need to take it for a week or so to improve cognitive ability. The 'focus' is likely just the extra monoamines sloshing around your head. That effect will lessen as you develop a tolerance. I'd suggest 2 weeks and then stop for at least a week and reassess.

How do you figure? I notice it the day I take it. Does mitochondrial complex IV take that long to inhibit?

[MrHappy]

My understanding is that MB assists / induces COX IV not inhibits it?

[noos]

I was reading some posts about aquariums treatments with MB and it seems it kills bacteria. Can MB kill good bacteria (or create resistance) in the human gut or the dose you are using is too low?. .

[maxwatt]

Good question. Too low a concentration if using less than a milligram, I would think but I need to check the concentration recommended on a bottle of the fish medicine. Primarily used to tread fungus infections and Ich, a protozoan infection.

From the Kordon website:

Methylene Blue is not indicated for forfothe treatment of Oodinium, bacterial infections, flukes (monogenetic trematodes) or for moderately-severe to severe fungal infections. It is not indicated for use as a net disinfectant or sterilizer.
The use of Methylene Blue is primarily for the control of fungus on eggs, and to assist the transport of oxygen in fish poisoned by cyanide and nitrite ion. Secondary uses are for the control of some external protozoan parasites of fishes.

Edited by maxwatt, 05 October 2011 - 10:54 AM.

[manic_racetam]

I've been putting ascorbic acid powder in the bottom of my cup, then dropping the MB directly onto the powder. It changes to a very light blue within one minute. Then I just add water to the cup and stir for 30 seconds. Is this just as effective as stirring the MB into solution?

I'm hoping it's just as good because it saves a lot of stirring.

[MrHappy]

Sounds rather fast.
What's your ratio?

[noos]

Is this a concern?

Biochem Pharmacol. 2003 Sep 1;66(5):777-84.
Generation of oxidant stress in cultured endothelial cells by methylene blue: protective effects of glucose and ascorbic acid.
May JM, Qu ZC, Whitesell RR.
Source

Abstract

The thiazine dye methylene blue has long been used to stimulate cellular redox metabolism. To determine the extent to which it also generates oxidant stress in cells, its effects in cultured human-derived endothelial cells were studied. As expected, low concentrations of the dye (2-20 microM) activated the pentose phosphate pathway and oxidized both NADPH and NADH. Methylene blue enhanced extracellular ferricyanide reduction, indicating that the reduced form of the dye was present outside the cells. This reduction was greater when ferricyanide was added just before rather than 15 min after methylene blue, confirming that the dye is at least initially reduced at the cell surface. In the absence of glucose, methylene blue at concentrations above 5 microM increased intracellular oxidant stress, as manifest by oxidation of dihydrofluorescein and cellular GSH. Inclusion of glucose protected against these effects. In cells that had been loaded with ascorbate, the dye caused progressive oxidation of ascorbate, even in the presence of D-glucose. Loading cells with ascorbate also partially prevented oxidation of dihydrofluorescein by methylene blue. These results suggest that concentrations of the dye above 5 microM generated intracellular reactive oxygen species that were scavenged by ascorbate and GSH. Further, although D-glucose enhanced reduction of methylene blue, it ameliorated the oxidant stress generated by the dye.
PMID: 12948858 [PubMed - indexed for MEDLINE]

[maxwatt]

@noos, I think this is no problem. We need 100 nano Mol for the effect we are seeking, and that takes a dose of about 1 or 2 mg at most. The oxidant stress was noted at levels of 5 micro mol. That is a higher concentration by a factor of 50 or so. Those taking 50 or 100 mg might be concerned, but doses that high have been used to treat malaria without adverse effects being nioted, at least in the short term.

[thedevinroy]

My understanding is that MB assists / induces COX IV not inhibits it?

!!

My bad, so totally sorry for that misinformation.

It DISINHIBITS and INCREASES Mitocondrial Complex IV by 30%. See here: http://www.ncbi.nlm....pubmed/17928358

Edited by devinthayer, 07 October 2011 - 07:27 PM.

[thedevinroy]

My understanding is that MB assists / induces COX IV not inhibits it?

Still...
The replacement with NADH/NAD+ is what I attribute most of its power. This effect seems to be more immediate.

Edited by devinthayer, 07 October 2011 - 07:28 PM.

[manic_racetam]

My understanding is that MB assists / induces COX IV not inhibits it?

!!

My bad, so totally sorry for that misinformation.

It DISINHIBITS and INCREASES Mitocondrial Complex IV by 30%. See here: http://www.ncbi.nlm....pubmed/17928358

Do you know the dosages used to attain the 30% ? Thanks

[thedevinroy]

My understanding is that MB assists / induces COX IV not inhibits it?

!!

My bad, so totally sorry for that misinformation.

It DISINHIBITS and INCREASES Mitocondrial Complex IV by 30%. See here: http://www.ncbi.nlm....pubmed/17928358

Do you know the dosages used to attain the 30% ? Thanks

The study was done in vitro. However, it was very small amount needed. 10nM is quite small and probably obtainable at even a very small dose of MB. Hard to say what dose exactly. You'll have to look back on the calculations in this thread for that. I suspect somewhere near 200mcg.

http://www.fasebj.or....expansion.html

[noos]

Which would be the human dose for this effect?

The brain metabolic enhancer methylene blue improves discrimination learning in rats.

Pharmacol Biochem Behav. 2007 Apr;86(4):712-7

Authors: Wrubel KM, Riha PD, Maldonado MA, McCollum D, Gonzalez-Lima F

Abstract
Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.

PMID: 17428524 [PubMed - indexed for MEDLINE]
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Edited by noos, 12 October 2011 - 03:37 PM.

[manic_racetam]

Which would be the human dose for this effect?

It would be roughly a 15mg injection for a 70kg person. Keep in mind that this is a study on rats, so it's really difficult to deduce a human dose without adequate testing in humans. You can use this online allometric scaling calculator for estimating these types of dosages.

What would the equivalent oral dose be to achieve the same plasma levels as an intravenous injection? I really don't know, but I wouldn't suggest injecting this stuff.

[chrono]

Which would be the human dose for this effect?

It would be roughly a 15mg injection for a 70kg person. Keep in mind that this is a study on rats, so it's really difficult to deduce a human dose without adequate testing in humans. You can use this online allometric scaling calculator for estimating these types of dosages.

The BSA calculation gives a number of 11.3mg instead (I just wrote a rather lengthy post about why I think BSA method is easier and more accurate than this exponential calculator). I seem to recall a mention in the MAOI conversation that oral dosing resulted in 10x lesser plasma levels? Haven't been taking notes, though.

I think the key question, which is unclear from the abstract, is whether this was the lowest dose which produced the effect, or simply the nice round number they chose to test. Sounds like the latter.

Edited by chrono, 12 October 2011 - 11:56 PM.

[noos]

thanks manic, chrono

[Baten]

"Severe, immediate reduction in sperm motility after exposure to undiluted standard solutions of methylene blue"

this shouldn't have any permanent effects using diluted MB dosing from 60mcg to 2mg, right?

[MrHappy]

Not unless you are injecting it into your scrotum.

[wolfeye]

METHYLENE BLUE INHIBITS SEROTONIN TRANSPORTER FUNCTION.


Background and purpose. Methylene Blue (MB) is commonly employed as a therapeutic tool for methemoglobinemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause serotonin (5-HT) toxicity, when administered with a serotonin reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB upon SERT. Experimental approach. Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+) ), [(3) H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. Key results. In EM4 cells expressing GFP-tagged human SERT (hSERT) MB produced a concentration-dependent inhibition of ASP(+) accumulation (IC(50) : 1.4 ± 0.3 µM). A similar effect was observed in N2A cells. Uptake of [(3) H]5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT evoked ion currents. 8-Br-cGMP pretreatment did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca(2+) levels remained unchanged during MB applications. Further experiments revealed that ASP(+) binding to cell surface hSERT was reduced after MB treatments. In whole-cell radioligand experiments, MB treatment (10 µM; 10 min) did not alter surface binding of the SERT ligand, [(125) I]RTI-55. Conclusions and implications: These results demonstrate that MB modulates SERT function and suggest that SERT may be an additional target upon which MB acts to produce 5-HT toxicity.

PMID: 21542830

Edited by wolfeye, 14 October 2011 - 01:05 PM.

[MrHappy]

Thanks, Wolfeye!

[Sartac]

Are any of the experimenters having their methemoglobin levels tested? This appears to be the primary concern when administering to mammals. Surely the effects have been discussed on here somewhere. Could someone link to relevant info? Otherwise ill take a better look when not on a mobile device.

http://docs.google.c...ates/60pg42.pdf

Edit: ah, yes, here http://www.longecity...__1#entry323240

Edited by sartac, 15 October 2011 - 03:53 AM.

[noos]

by physicus007@M&M

PodcastDirectory | Episode: Super Human Radio Show # 529 - BEST OF - 100 Yr Old Dye Reverses Brain Aging And May Cure Alzheimer's Disease Podcas

http://www.podcastdi...odshows/8248518

# 529 - BEST OF - 100 Yr Old Dye Reverses Brain Aging And May Cure Alzheimer's Disease :: Guest: Guest: Dr. Bruce Ames :: Just a little over 100 years ago the first synthetic dye used in the lab was formulated - Methylene Blue. Research has shown that this compound may possess far greater benefits than highlighting a specimen. ::