Re: Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways

[jw]

On Sep 2, 7:32 pm, ch...@my-deja.com wrote:
> On Aug 30, 12:55 am, "Les Shelley" <ksc...@mchsi.com> wrote:
>
> > Hmmm, not too enthusiastic about anything "homeopathic" but checked out the
> > Homeopathic Laboratories website and am confused by what is meant in
> > homeopathic terms when concentrations are expressed in units of 200c or
> > 200x.  How do these compare for instance to the dose that JC101 describes in
> > his (her?) regimen of ~200 mcg/day?
>
> ---------------------------------
>
> I got my little glass vial of blue-tinted Homeopathic Methylene Blue
> pellets from Hyland / Homeopathic Labs.
>
> They are 3x potency - (1x=1:10, 2x=1:100, 3x=1:1000)
>
> As you can see, the "x" potencies are in the "real" macro amount world
> (and these pills are pale blue! Forget any "c" potencies). Indeed,
> there are many simple herbal and mineral  OTC "1X" remedies that use
> the "homeopathic" designation - as opposed to a "supplement" one - so
> they could make specific medical claims. The traditional homeopathic
> indication of MB is for "rheumatism and spasms" and they recommend 3-6
> pills under the tongue 3-4 times /day.
>
> I don't know how the 1:1000 dilution in the small volume of the
> pellets translate into the dosages discussed here - the sublingual
> route may overcome some of the assimilation and brain barrier
> questions. I'm going the conservative route for now with 3/ once a
> day.
>
> I also got a box of Cognisure (Colostrinin) - which are also
> relatively small glazed tablets for chewing and holding in he mouth.
> They give a peculiar, staggered dose schedule on the box that I read
> they arrived at thru clinic testing. I also got some quality, water-
> soluble cinnamon extract too.
>
> I've just got these because I've recently became aware that I could be
> be a candidate for Lewy Body Dementia (perhaps w/ relatively young
> onset). While these items are promising for Alzheimer's Amyloids and
> Tau, rather than Lewy bodies, they also may help with Lewy's
> accompanying Parkinson's symptoms (Lewy bodies are also found in
> straight PD).
>
> I've recently read that either Cognisure (or MB/Rember?) is now being
> tested on Lewy bodies. Regardless, the MB and the Cognisure seem to
> have many other anti-aging benefits and are not very expensive
> considering the small amounts for chronic usage.

"3x potency" = ? mg or ug (micrograms) ??

[ch...@my-deja.com]

>
> "3x potency" = ? mg or ug (micrograms)  ??- Hide quoted text -

Well, unfortunantely it's apples and oranges :-)

The round, 1/8" lactose pellets are treated with MB/H2O solution of
1:1000. So there's no reliable way of extracting actual volume amount
of the MB in each.

Pellets were more convenient, but I guess I'll look next into an
actual water/grain alcohol solution bottle and assume each drop would
be approx 1mg of fluid containing the 1:1000 (3x) solution.

It's convenient, presumably sterile, and definately bluish!

[ch...@my-deja.com]

BTW, I took one additional pellet in the evening and couldn't sleep.
There could have been a few others reasons for this, but it was
definately unusual.

[cancu...@gmail.com]

On 30 ago, 22:22, RArmant <rarm...@sbcglobal.net> wrote:
> On Sat, 30 Aug 2008 10:17:12 -0700 (PDT), tellurian.l...@gmail.com
> wrote:
>
> >There is a concern I have regarding the studies in the news reports
> >and the dosing you describe. The Oakland Hospital research on cultured
> >cells translates in micro-grams of MB per day, however, the University
> >of Aberdeen research with Alzheimer's patients involved doses of milli-
> >grams per day. 60 milli-grams was the apparent optimal dosing revealed
> >from the phase II study. My concern is that these news stories are
> >using the letter "m" as in "mg" to represent micro-grams whereas if
> >taken literally, one would interpret the doses as in milligrams, i.e.
> >1000 times greater dose. Does anyone know what the doses in the
> >University of Aberdeen and TauRx really are? This is critical for
> >those amongst us that would take a risk and test MB on their own.
> >Unless MB is made a controlled substance, there is likely to be
> >widespread experimenting with the chemical.
>
> This post has some good information on rember.http://mfoundation.org/forums/showthread.php?p=4111#post4111
>
> A discussion of rember (MB) for alzheimer's can be found at --http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/3371094513

Your concern is a great concern.. most of the articles are stating
60mg (60/ thousanths of a gram) three times daily and the 100 mg was
ineffective.. Correctly it should be micrograms or 60/millionth of a
gram! So anyone who is ingesting 60mg is getting an ineffective 1000
time overdose. from what I gather, a popular "ich" fish methylene blue
is 2.303% w/v so that is 2.303 grams in 100cc of distilled purified
water. Take a ml or 1/100th = 23 mg / ml (1ml = 1 dropperful) .. Take
2 ml or 2 dropperfuls = 46mg , place it in 30ml water and you get a
dilution of 1.53 mg /ml. There 20 drops to a ml in a medicine
dropper, so 1.53 mg divided by 20 = .075 mg which is 75 microgram- we
only want 60mcg, so let's go back to the 2 dropperfuls X 60mcg/75mcg =
1.6 dropperful in 30 ml medicinal dropper bottle and qs to 30ml which
now gives the 60mcg per DROP! three times daily. So if no one reads
this blog there are going to be a lot of people taking and ineffective
overdose. I guess that is why they make pharmacists. I have tried to
correct this on a few articles but you have to register and that is
blocked. so what do they say caveat emptor .. beware the buyer.

CLAYTON TOM, Reg. Pharmacist, UCSF School of Pharmacy '60. THIS IS
FREE. I WILL BE CHARGING $10 FOR THIS ON MY WEBSITE www.4mRx where I
will be giving pharmaceutical advise on off label uses. still under
construction. make a note and check back later. in the meantime...
4meR...@gmail.com / cancu...@gmail.com

[dock...@aol.com]

On Tuesday, October 16, 2012 at 2:48:53 PM UTC-4, laurad...@gmail.com wrote:
> On Sunday, August 24, 2008 8:05:23 AM UTC-7, windwatcher wrote:
> > methylene blue eye whites - sounds like something from Dune. The spice
> > extended life and gave those who used it blued overall eyes. Sci fi
> > predicts the future? If it extends life, everyone would use it.
>
> Using minimum 1000mg of vitamin C will stop the blue pee and eyes.

Urolene is prescription methylene blue that comes in both oral and IV formulations. The Rember trial referenced used dosages in MGS not micrograms. Oral Urolene is dosed at 60 mg 2-3 times a day for UTI's.I don't know how "pure" the methylene blue at the 2.3% solution used in aquariums is, but the amount of MB would be 23 mg/ml; 3 ml three times a day would be an equivalent dose to the median dose used in the study. A "reformulated" Rember is now being used in clinical trials throughout the US; the dosage used in the studies does turn your urine blue (as well as the placebo which is just a much lower dose of the study drug). MB is relatively safe assuming you're not on an MAOI or SSRI; MB is also contraindicated if one is on some other medications or has certain medical conditions.

[Taka]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC49605/

[RArmant]

FASEB J. 2008 Mar;22(3):703-12. Epub 2007 Oct 10.

Methylene blue delays cellular senescence and enhances key
mitochondrial biochemical pathways.

Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN.

Nutrition & Metabolism Center, Children's Hospital Oakland Research
Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA.
Methylene blue (MB) has been used clinically for about a century to
treat numerous ailments. We show that MB and other diaminophenothiazines
extend the life span of human IMR90 fibroblasts in tissue culture by >20
population doubling (PDLs). MB delays senescence at nM levels in IMR90
by enhancing mitochondrial function. MB increases mitochondrial complex
IV by 30%, enhances cellular oxygen consumption by 37-70%, increases
heme synthesis, and reverses premature senescence caused by H2O2 or
cadmium. MB also induces phase-2 antioxidant enzymes in hepG2 cells.
Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to
leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB.
Experiments on lysates from rat liver mitochondria suggest the ratio
MB/cytochrome c is important for the protective actions of MB. We
propose that the cellular senescence delay caused by MB is due to
cycling between MB and MBH2 in mitochondria, which may partly explain
the increase in specific mitochondrial activities. Cycling of MB between
oxidized and reduced forms may block oxidant production by mitochondria.
Mitochondrial dysfunction and oxidative stress are thought to be key
aberrations that lead to cellular senescence and aging. MB may be useful
to delay mitochondrial dysfunction with aging and the decrease in
complex IV in Alzheimer disease.

PMID: 17928358

[Manfred Bartz]

hmm, sounds interesting, but what reaction would one get with the
white of the eyes turned blue....? ;-)

[windwatcher]

[telluri...@gmail.com]

I wonder if the extremely diluted MB they describe is really what they
used in their experiments. This could have been stated in order to
prevent ordinary citizens from going out and buying MB and trying it
out. At such diluted levels as described in their paper, no one is
going to hurt themselves. And certainly, no one is going to end up
with blue eyed eyeballs at such an extremely low concentration.

The concentrations as described in the Science Daily article - a few
rain drops diluted in two olympic sized pools, are what apparently was
applied to the "petri dish" samples of living cells. In order to gain
such a concentration in one's blood stream, one would obviously need a
higher ingested concentration. How much so I do not know. Anyone have
an idea? if one weighs 70kg and a human is 60% water by weight, then
there is 42 liters of water in one's body. This could be used to reach
a rough estimate of what one would need to ingest to reach the
concentrations described in the paper, however, the MG would not
necessarily be distributed evenly throughout the 42 liters of water
within one's body.

[telluri...@gmail.com]

First question to ask - is this quackery that was reported in Science
Daily? Who are these reserachers? Reputable or is this a biomedical
instance of Cold Fusion research?

[jc101]

I've used this for quite a while. Dosage :
Mix 0.1cc scoop (~40 mg) methylene blue in 30 ml (1 oz) dropper bottle
of water. Delivers
~50 mcg/drop.
I mix one drop in each of my three tea drinks, and one in the morning
early - so 200 mcg/day total.
Patent app info and excerpts follows.
JLC

http://tinyurl.com/5nmrva
US Patent Application 20060188866
Atamna; Hani ; et al. August 24, 2006

Diaminophenothiazine compositions and uses thereof

In one embodiment, the dosage is between 0.1-10.0 mcg/kg body weight/
day. In
a preferred embodiment, the dosage achieves a blood concentration of
about
1.0 to 100 nM of the diaminophenothiazine. In another embodiment, the
dosage
achieves a brain concentration of about 1.0 to 100 nM of the
diaminophenothiazine. For a human weighing about 160 lbs and having
about 5
liters of blood, the daily dose of methylene blue (mol. wt.=319)
needed to
achieve this concentration is about 1.6 to 160 mcg. The oral dosage is
typically given one to three times daily for prolonged periods,
usually for
at least 30 days. In some cases, the oral dosage is administered
chronically, i.e. regularly over a period of at least 3, preferably at
least
6, more preferably at least 12 months, wherein the regularity is at
least
once, preferably at least 2-3 times, more preferably at least 7 times
(daily) per week.

Long-Term Administration of diaminophenothiazines Improve Skin
Elasticity
and Activity Levels in Patients over 50.

A double blind, randomized, vehicle controlled study is conducted in
160
subjects ranging in ages from 50 to 65. Treatment groups are
prescribed 25
mcg diaminophenothiazine (azure A, azure B, azure C, thionine,
toluidine
blue, methylene blue, new methylene blue, or 1-9-dimethyl methylene
blue)
tablets taken orally with meals 3 times daily. Clinical monitoring,
subjective self assessment, objective measurement methods of skin
elasticity, epidermal hydration and skin surface lipids are used to
determine effects of each treatment at four visits during 24 weeks.
Clinical
monitoring includes wrinkle counts, measurement of wrinkle depth
around the
right eye, and nasolabial fold depth. Results demonstrate consistent
efficacy of diaminophenothiazine treatment over placebo in
counteracting
different signs of aging in the skin and improving overall energy
levels.

[telluri...@gmail.com]

I'm assessing the concentrations you state. Lets start with the first
one below. A Standard medical "Drop" is about 83 micro-liters. Divide
that drop by 30 milli-liters and then multiply by 40 mg and the result
is 110 mcg of M-B per drop. This is twice the concentration you state.
Please review and restate the calculation if in error. Using 60 micro-
liters per drop results in delivery of 80 mcg of MB per drop. Even
that is 50% more than what you state.

[jc101]

> > JLC- Hide quoted text -
>
> - Show quoted text -

Every drop size is different depending on the viscosity of the fluid
and size of the orifice. I measured 26 drops per ml from my dropper
with this solution. Your mileage may vary.

40000 mcg divided by 30 ml divided by 26 drops per ml equals 51 mcg/
drop.
JLC

[cancu...@gmail.com]

Hello I just read your article pertaining to Methylene blue delaying
senescence in the Mitochondria.. I am a registered Pharmacist ..
UCSF.. Do you have more information, and what dose, how many drops
would an average person of 70 kg take daily? Sincerely, Clayton Tom,
RPh

[telluri...@gmail.com]

Well that is a pretty small drop in comparison to what the wiki page
for a drop states. The wiki page lists several defined drop sizes
ranging from 50 to 80-odd micro-liters. I'll have to measure my
droppers drop size to determine the concentration to match the dosage
you state.

Presently MB is very inexpensive (that could change but apparently its
production is not expensive and suppliers could adapt to demand). I do
not know if there is a difference in purity between MB sold by lab
material supplier intended as a dye, and MB meant for human
consumption such as for treatment of methemoglobinemia. Do you have
any idea if there is a difference and what impurities would exist in a
"lower grade" MB? And would you recommend not using MB sold as a lab
stain?

A 1 fluid oz bottle at 1% (w/v) would need to be diluted by a factor
of about 7. The MB is at a low concentration. Any impurities would be
at a lower level. The toxicity of MB alone, using the Wikipedia
reference, appears to be on the order of 5 mg/kg of body weight. Such
a dosage is 5,000 times greater than what is stated in this
discussion.

If the efficacy of MB at this dosage were to hold true, a 1 fluid
ounce bottle of MB at 1%(w/v) would provide sufficient MB at the
concentration we are discussing for 3 doses taken daily for 5 years.
The cost for that 1 fluid ounce (1 %) of MB sold as a Lab stain is $4.
A medical prescription of MB, the same quantity costs $30. Either way
MB would be an extremely cheap treatment for dementia, parkinsons or
increasing one's longevity. Justifying MB to acquire a prescription
would involve jumping through some hoops with one's doctor (a touchy
matter). There will be those that will buy MB lab stain to avoid the
trouble.

Frankly, it is totally astounding to imagine that such a relatively
simple and inexpensive chemical could have such a profound effect on
human physiology.

[ch...@my-deja.com]

I guess everyone knows that a varient of Methylene blue is what makes
up the apparently promising new UK Alzheimer’s drug, "Rember."

"...the aggregation of tau protein is autocatalytic: once it gets
going, it's a cascade. They believe that methylene blue disrupts the
aggregation, and even helps to dissociate existing aggregates. Once
they're out in their monomeric forms, the helical tau fragments are
degraded normally again, and the whole tau backup starts to clear out"

http://pipeline.corante.com/archives/2008/07/31/rember_for_alzheimers_methylene_blues_comeback.php

[LokiRagnor]

And how exactly does one acquire methylene blue for personal use??

"jc101" <uniquep...@comcast.net> wrote in message
news:9fc0a6fe-ef61-4c8b...@r15g2000prd.googlegroups.com...

[LokiRagnor]

I suppose it could be purchased at a pet store since it is used as an
antifungal tx for tropical fish. This would, of course, necessitate careful
attention to concentration, etc. And who's to say the stuff sold in pet
stores isn't simple the industrial dye version...

<telluri...@gmail.com> wrote in message
news:6bf2a2f1-d1ba-467e...@s50g2000hsb.googlegroups.com...

[Unknown]

LokiRagnor wrote:
> And how exactly does one acquire methylene blue for personal use??

well, a quick web search came up with this, for example
http://www.sciencestuff.com/prod/Chem-Rgnts/C2100

[ch...@my-deja.com]

FWIW, if you google around, you can find "homeopathic" MB in
relatively "high" concentrations of 3x or so.

[Les Shelley]

Hmmm, not too enthusiastic about anything "homeopathic" but checked out the
Homeopathic Laboratories website and am confused by what is meant in
homeopathic terms when concentrations are expressed in units of 200c or
200x. How do these compare for instance to the dose that JC101 describes in
his (her?) regimen of ~200 mcg/day?

Loki

<ch...@my-deja.com> wrote in message
news:dafcc55d-47cd-4359...@c58g2000hsc.googlegroups.com...

[telluri...@gmail.com]

[RArmant]

On Sat, 30 Aug 2008 10:17:12 -0700 (PDT), telluri...@gmail.com
wrote:

This post has some good information on rember.

[harpersnotes]

Methylene Blue Oral listing at web MD as
agent against urinary tract infections:

http://www.webmd.com/drugs/drug-8812-Methylene+Blue+Oral.aspx?drugid=8812&drugname=Methylene+Blue+Oral

Listing of the side effects there:

---cut and pasted----
Nausea, stomach upset, diarrhea, vomiting, or bladder irritation may
occur. If any of these effects continue or become bothersome, tell
your doctor.

This medication may cause your urine or stool to turn green-blue. This
effect is harmless and will disappear when the medication is stopped.

Remember that your doctor has prescribed this medication because he or
she has judged that the benefit to you is greater than the risk of
side effects. Many people using this medication do not have serious
side effects.

Tell your doctor immediately if any of these rare but very serious
side effects occur: dizziness, fainting, high fever, fast/irregular/
pounding heartbeat, pale/blue skin color, unusual tiredness.

Seek immediate medical attention if this rare but very serious side
effect occurs: chest pain.

A very serious allergic reaction to this drug is rare. However, seek
immediate medical attention if you notice any symptoms of a serious
allergic reaction, including: rash, itching, swelling, severe
dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice
other effects not listed above, contact your doctor or pharmacist.
---- end of cut and pasted ----

The information at the following link seems possibly suggestive
that methylene blue occurs naturally with belladonna alkaloids??

http://www.drugs.com/cdi/belladonna-alkaloids-methenamine-methylene-blue-phenyl-salicylate.html

harpersnotes

[ch...@my-deja.com]

On Aug 30, 12:55 am, "Les Shelley" <ksc...@mchsi.com> wrote:

> Hmmm, not too enthusiastic about anything "homeopathic" but checked out the
> Homeopathic Laboratories website and am confused by what is meant in
> homeopathic terms when concentrations are expressed in units of 200c or
> 200x. How do these compare for instance to the dose that JC101 describes in
> his (her?) regimen of ~200 mcg/day?

---------------------------------

[laurad...@gmail.com]

On Sunday, August 24, 2008 8:05:23 AM UTC-7, windwatcher wrote: