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-- Rivka
_________
Hi, Rivka.
Below are the abstracts of three papers that provide the basis for combining glutathione and
hydroxocobalamin.
The idea is that glutathione reacts with hydroxocobalamin to form glutathionylcobalamin. This
protects the hydroxocobalamin so that it can be used to form its coenzyme forms,
adenosylcobalamin and methylcobalamin, rather than reacting with toxins.
This normally happens inside the cells of the body, but when glutathione is depleted, as in CFS,
toxins build up because the detoxication system is not working well (Glutathione is responsible
for one of the Phase II detox pathways, as well as handling hydrogen peroxide that is produced
from superoxide, which in turn is produced by the Phase I CYP450 enzymes. So when
glutathione becomes depleted, the detox system does not function well, and toxins build up.)
Then, because the concentration of glutathione is low, while the concentrations of the toxins have
been allowed to rise, the toxins are able to compete successfully with glutathione to react with the
hydroxocobalamin. The hydroxocobalamin is thus not available to be converted to its coenzyme
forms. That's why I say that vitamin B12 is "hijacked" in CFS.
The ratio of 4 to 1 in mixing hydroxocobalamin with glutathione comes from the facts that these
substances react in a 1 to 1 mole ratio, but the molecular weight of hydroxocobalamin is 1346.37,
while the molecular weight of glutathione is 307.33. The ratio of these two numbers is 4.38. If
you mix these two substances at a ratio of 4 to 1, you will have excess glutathione with respect to
hydroxocobalamin, so that all the hydroxocobalamin will react with glutathione, and there will be
some glutathione left over.
I first heard about nebulizing glutathione together with hydroxocobalamin from Jim Seymour, a
pharmacist from Key Pharmacy in Kent, Washington, in a talk he gave to the Multiple Chemical
Sensitivity (MCS) workshop that was held at the DoubleTree Hotel in Burlingame, CA, near the
San Francisco airport, on August 4-6, 2006. He reported that Dr. Grace Ziem had been giving
glutathione and hydroxocobalamin separately by nebulizer as part of the protocol she and Prof.
Martin Pall had developed for MCS, and she decided to mix them together to speed up the
process. She found that when she did this, her patients experienced more benefit, so she
continued to do it. [RIVKA'S NOTE: I CALLED KEY PHARMACY AND THEY SELL THE
B12 AND GLUTATHIONE NEEDED TO DO THIS NEBULIZING. THO THEIR
GLUTATHIONE IS VERY PRICEY, AS THEY SEND IT OVERNIGHT ON ICE. INSTEAD,
SOME PEOPLE CHOOSE TO USE THE "REDUCED L-GLUTATHOINE WITH SODIUM
I was curious about this, dug into the literature, and found these papers. I concluded that mixing
the two together was protecting the hydroxocobalamin from toxins.
Please feel free to forward this email to your pharmacist, Dr., the CFS-Yasko group, and to
whomever else you think might be interested.
Best regards,
Rich
A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics.
major forms of vitamin B(12) isolated from mammalian cells, and high concentrations of
glutathione (1-10 mM) are also found in cells. We have now determined observed equilibrium
constants, K(obs)(GSCbl), for the formation of GSCbl from aquacobalamin and glutathione in the
pH range 4.50-6.00. K(obs)(GSCbl) increases with increasing pH, and this increase is attributed
to increasing amounts of the thiolate forms (RS(-)) of glutathione. An estimate for the equilibrium
constant for the formation of GSCbl from aquacobalamin and the thiolate forms of glutathione of
approximately 5 x 10(9) M(-1) is obtained from the data. Hence, under biological conditions the
formation of GSCbl from aquacobalamin and glutathione is essentially irreversible. The rate of
the reaction between aquacobalamin/hydroxycobalamin and glutathione for 4.50 < pH < 11.0 has
also been studied and the observed rate constant for the reaction was found to decrease with
increasing pH. The data were fitted to a mechanism in which each of the 3 macroscopic forms of
glutathione present in this pH region react with aquacobalamin, giving k(1) = 18.5 M(-1) s(-1),
k(2) = 28 +/- 10 M(-1) s(-1), and k(3) = 163 +/- 8 M(-1) s(-1). The temperature dependence of the
observed rate constant at pH 7.40 ( approximately k(1)) was also studied, and activation
parameters were obtained typical of a dissociative process (DeltaH++ = 81.0 +/- 0.5 kJ mol(-1)
and DeltaS++ = 48 +/- 2 J K(-1) mol(-1)). Formation of GSCbl from aquacobalamin is rapid; for
example, at approximately 5 mM concentrations of glutathione and at 37 degrees C, the half-life
for formation of GSCbl from aquacobalamin and glutathione is 2.8 s. On the basis of our
equilibrium and rate-constant data we conclude that, upon entering cells, any free (protein-
unbound) aquacobalamin could be rapidly and irreversibly converted to GSCbl. GSCbl may
indeed play an important role in vitamin B(12)-dependent processes.
PMID: 15476387 [PubMed - indexed for MEDLINE]
Biochem Biophys Res Commun. 1990 Jun 15;169(2):443-50.Links
Here is info on a ratio of B12 and glutathione and some info re: nebulizer….This one has an
additional mouthpiece (purchased separately, that closes the valve when you are not breathing,
saving medication.
THIS IS A STARTING POINT - Please search the archives for more recent posts but this is where
it stand at this point in time (March 2009)
Hi muralimanoharam,
I have made my numbers, and for maintaining the rate 1:1 moles in the
reaction: GSH+HB12=glutathionylB12, for each 10 mg of HydroxyB12 you
have to add 2.18 mg of GSH, so if you take 4 mg of HB12, you have only
to add 0.87 mg of GSH!!! this is a good news, since it is very cheaper!!
Sergio
_____________________
> the B 12 since I am pretty sure I have a load of toxins to deal with.
>
> Rich***Your dosages would amount to about 3 micromoles of
> hydroxocobalamin and about 200 micromoles of glutathione. Since they
> react in a one-to-one mole ratio to form glutathionylcobalamin, you
> have more than enough glutathione to take care of all the cobalamin.
> Once inside the body, no doubt some will become unbound because of
> the usual dynamic equilibrium in chemistry and because there will be
> competing reactants. But this should give it a good start."
>
> Hope this helps shed light on the question. Would love to hear your
> comments.
>
________________________
wasted etc. My choice was the Pari ProNeb Ultra II compressor with
the Sprint nebulizer. It comes with the Plus nebulizer but I asked to
get the Sprint as well because it is newer and faster. These
nebulizers only deliver medication when you inhale--a valve closes
when you exhale, so you don't waste medication.
They sell for a big range of prices for the same thing but after
searching through MANY pages on Google found this one for $42.95 at
http://www.bpimedicalsupply.com/mm5/merchant.mvc?
Screen=PROD&Store_Code=BP&Product_Code=PRP86F83LCPLUS&Category_Code=Ne
bulizers . The extra sprint nebulizer was $10. Some places want a
prescription for nebulizers, most don't. This one didn't. It you want
to get the Pari, be sure to order the II as it is newer and much
lighter. They also offer a smaller and lighte one for travelling but
it is much more expensive. Hope this is useful.
__________________
Susan
________________________
This message is from Jason after verifying with Rich regarding the ratio….
Rich was kind enough to respond already and explained what everyone else has been trying to
convince me of. You need 4 times the mass of hydroxocobalamin to 1 part of glutathione.
It still doesn't make sense to me, but neither does God and I believe in Him.
Thanks for letting me try to confuse everyone! I gave it my best without wanting to.
Take Care,
Jason R