http://forums.phoenixrising.me/index.php?threads/glutathione-pro-con-arguments-confuse-me.21963/
Freddd said : Glutathione combines chemically with the
cobalamin, doesn't matter which one in this case. It's like
cyanide. It combines with it. For whatever the reason once the
glutathione combines with what appears to be about 100% of the
unbound b12 in the body and flushes it out through the urine, very
visiably if a person has any significant amount. The molecular mass
of MeCbl is about 1350 (several variations). The CH4 stripped off
is 1.3% of the mass , so the rest of the cobalamin is attached to
glutathione making glutathionyl cobalamin. If a person takes causes
1000mg of glutathione to be made that could destroy 5000mg or more
of MeCbl. Since a person has typically 1mg to 100mg in somebody
using a lot, there is vasrt overkill of glutathione regardless of
the exact amounts. When this b12 is swept from the body the person
goes onto methyltrap, in 2-3 hours if the dose of glutathione is
large enough. Now if the person is already in methyltrap, they
don't notice a thing except perhaps some relief from neurological
pain and whatever else the glutathione is doing. Glutathione, when
I was taking 30mg a day, had a coloration equal to 60mg in the
toilet bowl. The only thing comparable was taking multi hundred mg
doses by injection as far as the coloration goes. The difference
was that in that N=10 trial, was that everybody tjhat tried the
glutathione was already sucessfully healing and was out of methyl
block. Every one of us went back into methylblock in hours to a day
(whey was way slower). You can experiment for yourself. First tun
on healing. Start feeling pretty good for some months and then try
glutathione and you will feel yourself being cast back into the
pits of hell as symptoms return and getting worse by the day. In
six weeks a person can go from health to very sick. If you use
glutathione during methyltrap it will only make it worse but the
person can't feel it. I found the arguments strong enough to
convinve me to try it with 9 other people. I was very hopeful it
would work. I was looking what would fix me and others. The omne
thing I can tell you for sure. The people taking glutathione do not
get well as long as they are taking it. They may quibble about how
they feel. They do not largely heal in year. Healing does not turn
on while they are taking it. As some others found out who had never
had healing turn on when they discontinued the glutathione already
being taken at the same time as MeCbl etc they didn't heal until
some while after stopping glutathione and taking the reversal
doses.
Rich Vank said : The question of whether to supplement
glutathione in some way in conjuction with treatment of the partial
methylation cycle block in ME/CFS often comes up. There is some
recent research that appears to shed some light on this issue, so I
would like to review the status of at least my understanding of it.
As I see it currently, there are three groups of people with
respect to their response to adding glutathione to methylation
treatment: 1. There is a group who benefit from this addition, in
terms of their symptomatic response. 2. There is a group who
benefit initially, but as time goes on, it causes their symptoms to
worsen. 3. There is a group who experience immediate worsening of
their symptoms. I dont know what fraction of the ME/CFS population
is in each group. I would like to suggest what I think is going on
in each of these groups. I suggest that the first group have
inherited normal genotypes of their intracellular B12 processing
enzymes, and they also have normal status of vitamins B2 and B3. In
this group, the glutathione can be recycled at a normal rate when
it becomes oxidized by reactive oxygen species that are part of the
oxidative stress in ME/CFS, by the glutathione reductase reaction,
which requires both B2 and B3. Furthermore, glutathione is able to
play its normal roles with respect to the intracellular processing
of vitamin B12. In particular, the Cblc enzyme (also known as
MMACHC) uses glutathione to remove the upper ligand from incoming
forms of B12 (cyano-, methyl- or adenosyl-) by the formation of
glutathione conjugates of these ligands (PMID: 19801555). In
addition, it appears that glutathione also reacts with the
resulting aquocobalamin to form glutathionylcobalamin.
Glutathionylcobalamin is chemically more stable than the other
forms of B12, but Cbcl is normally able to retrieve cobalamin from
glutathionylcobalamin so that the cobalamin can be used to form
methylcobalamin and adenosylcobalamin in the amounts needed by the
cell (PMID: 21429294). Thus, glutathione appears to serve not only
as a reactant in the metabolism of B12, but also as a protector of
B12 from reactions with toxins, and a buffer to store B12 until it
is needed by the cell. I suggest that the second group have
inherited normal genotypes of their intracellular B12 processing
enzymes, but they have a deficiency in B2 or B3 or both, so that
the rate of the glutathione reductase reaction is too slow to keep
up with the oxidation of the glutathione. As a result, though the
supplemented glutathione is initially beneficial to them, over time
it becomes a detriment, because the ratio of reduced to oxidized
glutathione drops too low, and this worsens the oxidative stress of
the cells. I suggest that the third group has inherited an inborn
error of metabolism involving the Cblc enzyme. As a result of this,
when glutathione reacts with B12 to form glutathionylcobalamin,
their genotype of the Cblc enzyme is unable to retrieve the
cobalamin from the glutathione to use it to form methylcobalamin
and adenosylcobalamin. If glutathione is supplemented, this
situation is made worse for this group. In addition, this group is
unable to make use of hydroxocobalamin as their B12 supplement
(PMID: 21497120), because it is converted to glutathionylcobalamin
in their cells (even without supplementing glutathione) and is
therefore made inaccessible. I suggest that Freddd is in this
group, and this explains why he cannot tolerate supplementing
glutathione, why he cannot make use of cyanocobalamin or
hydroxocobalamin, and why he must use high dosages of
methylcobalamin and adenosylcobalamin, applied either sublingually
or by injection. This raises the concentration of these species in
the blood stream, and enough of them is able to diffuse into the
cells through their plasma membranes to be used directly without
intracellular processing, thus supplying the need of his cells for
methylcobalamin and adenosylcobalamin.
Freddd said : The one thing I will be clear about is that
aside from ignoring hypokalemia and calling it detox, the most
potentially damaging thing a person can do is take glutathione
above a certain unknown level and keep taking it. In 6 weeks it can
cause or worsen brain and cord damage in Subacute combined
degeneration and it's first cousin, MS is also likely rapidly
increased damage. It can cause high MCV and high MCH and half a
dozen other blood changes on the first 3 months (the problems
happen right away but blood cells stick around 3-4 months so it
takes a while ot see). Doing a risk assessment of this is probably
a good idea. A researcher I have spoken with who has approiached
these matters from a different direction told me, in person and on
the phone, that "There is probably no safe way to take
glutathione." The subjective benefits I too have felt. When there
is neurological pain, it reduces the neurological pain by damaoing
the nerves to numbness so even perveived benefit is dangerous and
damaging. That can be perceived in the first days, as I perveived
it, before the effects of methyltrap become felt. Those who are not
in methyltrap and are doing welll will be the ones who will feel
the worst onset of glutathione.
Rich Said :I suggest that the third group has inherited an
inborn error of metabolism involving the Cblc enzyme. As a result
of this, when glutathione reacts with B12 to form
glutathionylcobalamin, their genotype of the Cblc enzyme is unable
to retrieve the cobalamin from the glutathione to use it to form
methylcobalamin and adenosylcobalamin. If glutathione is
supplemented, this situation is made worse for this group.
Since Rich is basing this hypothesis on me, based on old
incorrect hypothses concerning my own supposed inborn error in the
CblC enzyme whic isabsolutely 100% wrong for me and all of the N=10
group, all logic flowing from this assumption is 100% wrong.
In addition, this group is unable to make use of
hydroxocobalamin as their B12 supplement.
This assumption is also 100% wrong concerning the people in the
N=10 group trial. Some of those were vegetarians. One man had such
amazingly good response to HyCbl that it got him out of a
wheelchair but the HyCbl could take it no further. He needed MeCbl
and AdoCbl to get rid of the walker frame and return to work.
because it is converted to glutathionylcobalamin in their
cells (even without supplementing glutathione) and is therefore
made inaccessible. I suggest that Freddd is in this group, and this
explains why he cannot tolerate supplementing glutathione, why he
cannot make use of cyanocobalamin or hydroxocobalamin, and why he
must use high dosages of methylcobalamin and adenosylcobalamin,
applied either sublingually or by injection. This raises the
concentration of these species in the blood stream, and enough of
them is able to diffuse into the cells through their plasma
membranes to be used directly without intracellular processing,
thus supplying the need of his cells for methylcobalamin and
adenosylcobalamin.
Again, all of this is based on assumptions that are 100%
WRONG!
it appears that glutathione also reacts with the resulting
aquocobalamin to form glutathionylcobalamin. Glutathionylcobalamin
is chemically more stable than the other forms of B12, but Cbcl is
normally able to retrieve cobalamin from glutathionylcobalamin so
that the cobalamin can be used to form methylcobalamin and
adenosylcobalamin in the amounts needed by the cell (PMID:
21429294).
While this may be sort of correct in terms of normal amounts of
glutathione, in these much larger doses beiong taken, this is NOT
CORRECT. The glutathione combined dirrectly with AdoCbl and MeCbl
that is in serum or cells and changes there again and again faster
than the body can convert it back to usable forms, This is
demonstrable. No amount of injected MeCbl taken with large amounts
of glutathione survive to be used. The whole thing is based on a
first approximation understanding that upon more iuderstanding has
been proven totally wrong. Rich was unwilling to reconsider my
situation because it fit his theories so nicely. As everything he
thinks about my biochemistry as regards B12 and folates is wrong,
all of his suggestions and conclusions based on that are wrong.
This entire statement is too badly flawed to be any valid usage and
anybody basing what they do on it is at risk of doing unintentional
damage to themselves. That entire statement is so flawed that I'm
not sure any of it is salvagable.
I would like it much better if somebody knowledgeable could
write an understanding of it that isn't based on me as an example
and my presumed genetic characteristics and ignore entirely the
other 9 in the trial. I have been extremely specific about those
who tried it and found the reversal. FIRST they had to have
effectiveness of the Active B12 protocol. So whatever argument made
can't be about a specific set of rare genes because the people in
the N=10 are quite varied, including a vegetarian, using every
form. That every form of precursors were approximately as effective
as glutathione IV, including NAC alone in some people, shows that
it isn't difficult at all to get glutathione into the body. Any
explanation has to able to include the actual pragmatic examples
within a suitable hypothesis. You can't throw out every bit of
contrary information and form the hypothesis on wrong statements
and misunderstandings. The above fails that test. When all the
logic on who it happens to disappears and even reverses from his
statements, there is nothing valid there. It may be possible to
form a valid hypothesis from all this that supports glutatathion at
certain minimal doses for a short time in people who haven't
achieved methylation startup and who are still in methyltrap and
not yet achieved ATP startup. If Rich had been willing to discuss
this matter and revise his opinions about what is wrong with me
based on all the folate information he got me started on, this is
what I would have tried to work out with him. As he came to believe
that glutathione shouldn't generally be given in any case, he was
likely near to be willing to discuss. It was perhaps my
disappearing for some months that prevented that. You may not
understand how we were interacting. We exchanged information and
data. He brought to my attention a variety of flaws, all of which I
corrected. I brought flaws to his attention. SOme he considered and
made alterations. Some he ignored 100% despite repeated
explanation. His hypothesis appeared far more important to him than
mine is to me. For me what is important how to solve the probelm,
not the specific details of the solution. In order to get good
answers one must ask good questions. If there isn't some ancient
wisdom to that effect there should be. In the computer age it has
been summerized GIGO; Garbage In Garbage Out. That is logic based
on flawed assumptions and incorrect data doesn't yield valid
results except by accident. In computers if you do everything that
wrong the program doesn't run or gives lots of interesting and
weird errors. I'm playing "you bet your life" in this 100%. My life
is literally at stake in all this, as is yours. Rich was playing
science. He was a disinteresrted observer except for protecting his
theoretical turf. His life wasn't at stake. His theory was. "Old
scientists never die, they just loose track of their data". You
know, "Old gymnasts never die, they just can't remount in 30
seconds." I ask questions nobody else who hasn't lived through it
can ask. I have possible answers that require experienceto have .
In the end a valid hypothesis can explain you and me and Dan and
Dbkita et al and have each of us described accurately and
predictably. There is a lot to account for, not a lot to throw out
or ignore.
As far as understanding MeCbl better:
http://health101.org/art_methylcobalamin.htm and it has footnotes.
It was written before l-methylfolate and has some things that could
be changed. A sample paragraph.
The coenzyme form of vitamin B12 is known as methylcobalamin
or methyl B12.It's the only form of vitamin B12 which can directly
participate in homocysteine metabolism.In addition, converting
homocysteine to methionine via methyl B12 generates an increased
supply of SAMe (S-adenosyl methionine), the body's most important
methyl donor.Indeed, some of the benefits of methyl B12, such as
protection from neurotoxicity, appear to derive from increased
production of SAMe8, 9.Methyl B12 has also been reported to be
neurotrophic or growth-promoting for nerve cells10, 11, a property
which may help regenerate central and peripheral nervous tissues
damaged in disorders such as amyotrophic lateral sclerosis12 and
diabetic peripheral neuropathy13.
http://forums.phoenixrising.me/index.php?threads/glutathione-pro-con-arguments-confuse-me.21963/
![[​IMG]](http://blog.naturalhealthyconcepts.com/wp-content/berberine-post.png)