28 replies to this topic

[rwac]

Neat. Ingestion of Methylene blue
1. Increased cognitive function and grip strength of old mice to nearly that of young mice.
2. reduces MAO activity, MAO activity increases in human brains with age.
3. Increases protein content in the brains of old mice.
4. Reduces the amount of water and food consumption in older mice.

After drinking 250 uM of MB in drinking water, brain concentration of MB was 128 nM, which is near the optimal concentration of 100nM.

It would have been fantastic to see if the same effects were seen in young mice, and to see whether there was a life-extending effect from MB.

Methylene Blue Induces Mitochondrial Complex IV and Improves Cognitive Function and Grip Strength in Old Mice

Authors: (Afshin Gharib, Hani Atamna, Children's Hospital Oakland Research Institute (CHORI), California, and others)

Abstract:
Methylene blue (MB) is very effective in delaying cellular senescence and enhancing mitochondrial activity of primary human embryonic fibroblasts. At nanomolar concentrations, MB increased the activity of mitochondrial cytochrome c oxidase (complex IV), heme synthesis, cell resistance to oxidants, and oxygen consumption. MB is the most effective among the many agents that has been are reported to delay cellular senescence. We extended these in vitro findings to the investigation of the effect of long-term intake of MB in old mice. We administered MB, in the drinking water (250 μM), to old mice for 90 days. In vivo, MB prevented the age-related decline in cognitive function and spatial memory. MB also prevented the age-related decline in grip strength. Interestingly, MB resulted in 100 % and 50 % increases in complex IV activities in the brains and hearts of old mice, respectively. The age-related decline in protein content of the brain was prevented by MB. We also found a 39 % decrease in brain monoamine oxidase (MAO) activity in old mice treated with MB while aging or MB did not affect the activity of brain NQO1. Our findings suggest that the in vitro model for cell senescence may be used for fast and reliable screening for mitochondria-protecting candidate agents before testing in animal models. The study also demonstrates simultaneous enhancement of mitochondrial function, improvement of the cognitive function, and improvement of grip strength in old mice by a drug. Since these are three major concerns in human aging, MB may be a useful agent for delaying neurodegeneration and physical impairments associated with aging.

https://www.novapubl...oducts_id=24925

[Ark]

Neat. Ingestion of Methylene blue
1. Increased cognitive function and grip strength of old mice to nearly that of young mice.
2. reduces MAO activity, MAO activity increases in human brains with age.
3. Increases protein content in the brains of old mice.
4. Reduces the amount of water and food consumption in older mice.

After drinking 250 uM of MB in drinking water, brain concentration of MB was 128 nM, which is near the optimal concentration of 100nM.

It would have been fantastic to see if the same effects were seen in young mice, and to see whether there was a life-extending effect from MB.

Methylene Blue Induces Mitochondrial Complex IV and Improves Cognitive Function and Grip Strength in Old Mice

Authors: (Afshin Gharib, Hani Atamna, Children's Hospital Oakland Research Institute (CHORI), California, and others)

Abstract:
Methylene blue (MB) is very effective in delaying cellular senescence and enhancing mitochondrial activity of primary human embryonic fibroblasts. At nanomolar concentrations, MB increased the activity of mitochondrial cytochrome c oxidase (complex IV), heme synthesis, cell resistance to oxidants, and oxygen consumption. MB is the most effective among the many agents that has been are reported to delay cellular senescence. We extended these in vitro findings to the investigation of the effect of long-term intake of MB in old mice. We administered MB, in the drinking water (250 μM), to old mice for 90 days. In vivo, MB prevented the age-related decline in cognitive function and spatial memory. MB also prevented the age-related decline in grip strength. Interestingly, MB resulted in 100 % and 50 % increases in complex IV activities in the brains and hearts of old mice, respectively. The age-related decline in protein content of the brain was prevented by MB. We also found a 39 % decrease in brain monoamine oxidase (MAO) activity in old mice treated with MB while aging or MB did not affect the activity of brain NQO1. Our findings suggest that the in vitro model for cell senescence may be used for fast and reliable screening for mitochondria-protecting candidate agents before testing in animal models. The study also demonstrates simultaneous enhancement of mitochondrial function, improvement of the cognitive function, and improvement of grip strength in old mice by a drug. Since these are three major concerns in human aging, MB may be a useful agent for delaying neurodegeneration and physical impairments associated with aging.

https://www.novapubl...oducts_id=24925

MB definitely causes a increases the overall energy department. ;-) in young rats

[maxwatt]

Methylene blue is used to treat priapism. It inhibits cMAP and nitric oxide synthesis. Sort of the opposite effect to Viaga. At the low, microgram doses I've seen recommended for life extension, I do not think this will be a problem.

[rwac]

Just in case someone had doubts about the dosage, here's a patent by Dr. Atamna which suggests a dose of 5-500 μg/day of Methylene Blue.

http://www.google.co...AEBAJ&dq=atamna

[Sillewater]

What dose are you at now Rwac?

[rwac]

3mg but I'm going to cut back to about 450mcg.

Edited by rwac, 14 April 2011 - 05:39 AM.

[Sillewater]

What made you go up to 3mg?

[rwac]

I was basically playing with it. At somewhat higher concentrations, MB has anti-viral properties.

[sapentia]

Is there a high quality retailer for this yet?

[rwac]

Yes, I believe kingherbs provides this. you can mail them to ask.

[rwac]

MB definitely causes a increases the overall energy department. ;-) in young rats<

So are you talking about a pet or a human here ?

Edited by rwac, 14 April 2011 - 05:22 PM.

[Ark]

MB definitely causes a increases the overall energy department. ;-) in young rats<

So are you talking about a pet or a human here ?

No comment....

Edited by Ark, 30 May 2011 - 07:39 AM.

[jonathan_m]

Hi, I'm trying to work out a human equivalent dose to the one used in this study, and getting a larger answer than I expected (50mg a day, much higher than dosages in the patent by Dr Atama). I may be making some big error.

My workings:
weight of a mole of MB is about 320 grams http://en.wikipedia..../Methylene_blue
so 320g MB per litre is 1 molar http://en.wikipedia....r_concentration
divide by one million to get micromolar (uM) = 0.00032 grams per litre http://en.wikipedia....r_concentration
multiply by 250 to get 250 uM concentration = 0.08 grams per litre
divide by 1000 to get weight of MB per millilitre = 0.00008 grams per millilitre
multiply by water consumed millilitre per day per mouse (2.5) = 0.002 grams MB daily dosage to the mice
divide by mouse weight in grams (35) = 0.000005714285714 grams MB per day per gram of mouse
multiply by a human weight in grams (85000) = 0.485714 grams per day
divide by 10 for the faster metabolic rate of mice compared to humans = 0.0485714 grams per day

so I come up with 50 milligrams per day for a human equivalent dose...

[jonathan_m]

From this: http://www.mpasmb-ha...thyleneBlue.pdf

"As to the pharmacokinetics of MB, a typical daily dosage is 200 mg MB given orally (Table 1). The apparent half-life of MB in the human body is approximately 10 hours; the bioavailability is 􏰁73%. After the oral intake of 500 mg MB the concentration in blood peaks at 19 􏰅M; after i.v. administration of 50 mg MB the corresponding value is approximately 2.2 􏰅M (Walter-Sack et al., 2009); the di- verging data of Peter et al. (2000) and of other authors are discussed in the same report."

And from the old mouse paper above:

" The steady-state level of MB in the brain following treatment with MB is 128 nM (0.51 ± 0.25 pmols/mg protein) as measured by LC-MS-ESI [51]. As expected, no MB was detected in the brains of the control mice. Thus, although MB reaches the brain, the concentration is quite low. However, since it is within the 100 nM concentration range we found to be optimal for delaying cell senescence and protecting the mitochondria in cultured cells [17], it is reasonable to assume that MB is active in the brain at a nanomolar range concentration."

From these two sources, it seems reasonable (to me) that a 50mg daily dose could give 100 nM concentration in the brain, with a blood peak 20 times that (2 uM), and some difficulty entering the brain (from the second quote). This is in contrast to the 0.5mg daily dose from the patent.

[Krell]

Got 25g MB, what I thought was a lifetime supply, for $30 from
http://cgi.ebay.com/...g-/230578507923

Mixed 1.2 grams of MB powder with 1 liter of water to get 1.2mg/cc.

Used medicine dropper @ 20 drops/ cc, so each drop has 1.2mg/20 = 0.060mg = 60ug.

Drink glass of water with one drop, three times per day - sometimes in tea or coffee.

Each glass has a faint blue tint with no taste to me.

No effects felt after 1 week @ 180ug MB. No improvement in tennis game.

If I need to go up to 50mg/day instead of 180ug/day (277.8x), then I should have bought the bigger bottle of MB!

Edited by Krell, 20 July 2011 - 05:01 PM.

[MrHappy]

Got 25g MB, what I thought was a lifetime supply, for $30 from
http://cgi.ebay.com/...g-/230578507923

Mixed 1.2 grams of MB powder with 1 liter of water to get 1.2mg/cc.

Used medicine dropper @ 20 drops/ cc, so each drop has 1.2mg/20 = 0.060mg = 60ug.

Drink glass of water with one drop, three times per day - sometimes in tea or coffee.

Each glass has a faint blue tint with no taste to me.

No effects felt after 1 week @ 180ug MB. No improvement in tennis game.

If I need to go up to 50mg/day instead of 180ug/day (277.8x), then I should have bought the bigger bottle of MB!

On another thread we seem to have converged on around 1mg / dose as a notable effect.

[Krell]

Got 25g MB, what I thought was a lifetime supply, for $30 from
http://cgi.ebay.com/...g-/230578507923

Mixed 1.2 grams of MB powder with 1 liter of water to get 1.2mg/cc.

Used medicine dropper @ 20 drops/ cc, so each drop has 1.2mg/20 = 0.060mg = 60ug.

Drink glass of water with one drop, three times per day - sometimes in tea or coffee.

Each glass has a faint blue tint with no taste to me.

No effects felt after 1 week @ 180ug MB. No improvement in tennis game.

If I need to go up to 50mg/day instead of 180ug/day (277.8x), then I should have bought the bigger bottle of MB!

On another thread we seem to have converged on around 1mg / dose as a notable effect.

Thanks, during the last two weeks I have increased from one drop to 5 of my drops (totalling ~0.3 mg) twice a day,
for a total of daily dose of ~0.6 mg/day. Still not much taste or immediate effects, good or bad.

However, I was able to move up to 5 reps @ 185 lb bench press this morning from my normal 3 reps.
Since I am an old mouse equivalent ( 66 yo), this might be the MB talking? But my tennis still stinks.

I generally take one of my MB doses just before bed, and I have not noticed any problems getting to sleep.

Edited by Krell, 15 August 2011 - 03:03 PM.

[niner]

Hi, I'm trying to work out a human equivalent dose to the one used in this study, and getting a larger answer than I expected (50mg a day, much higher than dosages in the patent by Dr Atama). I may be making some big error.

My workings:
weight of a mole of MB is about 320 grams http://en.wikipedia..../Methylene_blue
so 320g MB per litre is 1 molar http://en.wikipedia....r_concentration
divide by one million to get micromolar (uM) = 0.00032 grams per litre http://en.wikipedia....r_concentration
multiply by 250 to get 250 uM concentration = 0.08 grams per litre
divide by 1000 to get weight of MB per millilitre = 0.00008 grams per millilitre
multiply by water consumed millilitre per day per mouse (2.5) = 0.002 grams MB daily dosage to the mice
divide by mouse weight in grams (35) = 0.000005714285714 grams MB per day per gram of mouse
multiply by a human weight in grams (85000) = 0.485714 grams per day
divide by 10 for the faster metabolic rate of mice compared to humans = 0.0485714 grams per day

so I come up with 50 milligrams per day for a human equivalent dose...

There's a factor of ten error in the intermediate results, but the final answer is right. I'll change the human weight to the more standard 70 kg. From the paper, the old mice weighed 32g and drank 2.0ml/d, so using all these numbers I get:

250e-6m/L *(320g/m) * (1 L/1000ml) * (2.0ml/d) * (70000g human/32g mouse) = 0.35g/d; Dividing by 10 gives 35mg/day. Considering that the water volume, weights, and conversion factors are all semi-wild guesses, and that this is supposedly for a 24 hour period, it's probably not off by much more than a factor of ten. From my calculation in a different MB thread, using the volume of distribution measured for dogs, I got a dose of 1.8 mg, but that was probably only correct shortly after dosing. To maximize the period of time when you were in the 100nM region, you might need to double it, and redose every 6 hours of so. By that estimation, I would have a total daily dose of 14.4mg. I think starting low and titrating the dose to the way you feel is a non-crazy way of doing this.

Edited by niner, 15 August 2011 - 04:46 PM.

[noos]

Hi, I'm trying to work out a human equivalent dose to the one used in this study, and getting a larger answer than I expected (50mg a day, much higher than dosages in the patent by Dr Atama). I may be making some big error.

My workings:
weight of a mole of MB is about 320 grams http://en.wikipedia..../Methylene_blue
so 320g MB per litre is 1 molar http://en.wikipedia....r_concentration
divide by one million to get micromolar (uM) = 0.00032 grams per litre http://en.wikipedia....r_concentration
multiply by 250 to get 250 uM concentration = 0.08 grams per litre
divide by 1000 to get weight of MB per millilitre = 0.00008 grams per millilitre
multiply by water consumed millilitre per day per mouse (2.5) = 0.002 grams MB daily dosage to the mice
divide by mouse weight in grams (35) = 0.000005714285714 grams MB per day per gram of mouse
multiply by a human weight in grams (85000) = 0.485714 grams per day
divide by 10 for the faster metabolic rate of mice compared to humans = 0.0485714 grams per day

so I come up with 50 milligrams per day for a human equivalent dose...

You have to correct to different metabolism.

Edited by noos, 11 October 2011 - 12:30 AM.

[niner]

divide by 10 for the faster metabolic rate of mice compared to humans = 0.0485714 grams per day

so I come up with 50 milligrams per day for a human equivalent dose...

You have to correct to different metabolism.

That's what he was doing when he divided by 10. You could argue that that number should be higher. I think 12 is often used; If you use the numbers that I used in the previous post, but divide by 12 instead of ten, you get 29mg. That's within a factor of ten of what we're using, which isn't bad for biology.

[noos]

That's what he was doing when he divided by 10. You could argue that that number should be higher. I think 12 is often used; If you use the numbers that I used in the previous post, but divide by 12 instead of ten, you get 29mg. That's within a factor of ten of what we're using, which isn't bad for biology.

Sorry, I did not notice it was in the last line. It shows MB does not work for me

[Skypp]

Methylene blue is used to treat priapism. It inhibits cMAP and nitric oxide synthesis. Sort of the opposite effect to Viaga. At the low, microgram doses I've seen recommended for life extension, I do not think this will be a problem.

Ummmm, been giving MB to my husband for brain fog and slight depression. Let's just say it hasn't hurt him one bit in other areas. Maybe because his mood is much brighter? All good here!

Edited by Skypp, 28 December 2013 - 11:02 PM.

[xks201]

The stuff turns my pee blue and makes me smell funny. Not joking.

[Adamzski]

I will have another go at 1mg per day of MB, I seen that they were saying in the ebay listing that the MB is made in Korea so I searched gmarket here and you can buy much smaller than 30 year supplies. http://gsearch.gmark...=Methylene Blue has the same brand as the ebay listing and most of these places here ship worldwide

[AgeVivo]

of note, the ITP tested Methylene Blue on mouse lifespan and recently published results: http://www.ncbi.nlm....pubmed/24245565 ("Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males")

the life extension they found with methyleneblue was very small:

MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P = 0.004) increase in female maximum lifespan

[dunbar]

Is MB safe for humans? The name alone sounds very chemical and very unhealthy. I'd be scared to take stuff like that.

[Jeoshua]

Dihydrogen Monoxide is a really scary word, too...

And you're like 90% made of it.

[dunbar]

Dihydrogen Monoxide is a really scary word, too...

And you're like 90% made of it.

90%? How's this possible. I am made of at least 25% fat.

Edited by dunbar, 03 January 2014 - 06:29 PM.

[Ali Ismail]

Hi Guies,

 

Has anyone here used MB for brain atropy or know anyone who has and seen any benefit ?

 

Best Regards