Greetings:

I ran across this article and was wondering if you both have ever used
or thought of supplementing with Glutathione.

[I have reviewed the possibility of supplementing glutathione (which LEF has
carried for some years) and have rejected it because of the apparent lack of
oral bioavailability. Even though we get our supplements without cost from LEF
(in lieu of payment for work done years ago), I try to order as sparingly as
possible and not to waste anything that I order from them. So no, neither I nor
Kitty have ever supplemented glutathione. --Paul]

[Some people may not realise that just because Paul gets supplements without
cost from LEF that does not mean he gets them for free. He gets the supplements
in exchange for the value he provided LEF for the several years he worked for
them, therefore he thinks of them as payment for past work rather than free
merchandise. He gave LEF a lot of value by working for them but the value he
gave them, and therefore the value LEF owes him, is not *unlimited*. This is an
important point, since if I know Paul correctly as a value trader he does not
like to receive any more value than he has rightfully earned. Therefore as he
has told me, sometime in the future he may evaluate that the value he has
received from LEF in the form of products is equal to the value he gave LEF by
working for them, and when that happens he will want to start to purchasing the
supplements himself rather than receiving them at no cost from LEF. Also if he
takes a supplement from LEF that turns out to be a waste of money the correct
way to think of it is that it is a waste of his own money not LEF's, since
everything of value he receives from LEF counts towards the total amount of the
limited value they owe him. -°Olafur]

[Although Olafur's explanation is mostly correct and well explained. I don't
remember ever saying that at some time in the future I might reevaluate and
consider that the value I had supplied to LEF was then paid and would then
proceed to purchase my supplements from them. I have stated many times that in
some ways I would rather not be getting supplements from LEF without cost
because I would then be "freer" to choose between the multitude of suppliers. If
I had a larger income then I would elect to do this, hopefully after
renegotiating with LEF for a lump sum payout.

[I made two mistakes in my writing above:
1) I see now that by placing the prefix "the" in front of the word "supplements"
in the sentence "he will want to start to purchasing the supplements himself", I
made the sentence sound like I thought he would take the same supplements if he
did not receive them without cost from LEF. But this was a mistake since I was
well aware of the fact that his choice of supplements would not be the same if
he were freer to choose between suppliers. My mistake for not phrasing the
sentence properly.
2) My second mistake involved putting words in Paul's mouth based on a hazy
memory of mine of a conversation we had. During my visit to them this past April
I'm pretty sure I remember Paul and Kitty mentioning to me in a conversation
that sometime in the distant future they may want to be more independent from
LEF. But I confess that I do not remember Paul directly saying what I wrote
above. I seem to have misunderstood some of our conversations, or maybe I'm just
mixing together some memories, I don't know. But I decided to write it anyway
even though I wasn't completely sure I was right since I knew Paul was going to
read over my comments before posting and would correct me if I were wrong. I
apologize for putting words in your mouth Paul and I will be more careful next
time. -°Olafur]

[No problem, Olafur. You also made some good points about value and I thought it
was best to leave the whole conversation in public to show how two
well-intentioned friends need not have any conflict as a result of such things,
but can in fact both benefit. --Paul]

I think that Olafur is also missing the fact that the value that I am collecting
from LEF is in two major parts.
1) An effective annuity (yearly "interest" payment) from an original failure of
LEF to pay for computer services rendered to them in 1996.
2) Royalty payments for the purchases of all those who are now LEF customers as
a result of my work on the Internet - which has actually continued since leaving
them as a paid consultant. (The "royalty payments" was an agreement with LEF
that such people would generate a continuing royalty to me from a small
percentage of their total purchases, but my method of promoting LEF on the
Internet made it impossible to tell just which purchasers actually came as a
result of my work.)

It is important to note that with respect to an annuity (and with respect to
purchases of customers - as long as they stay alive and keep purchasing), there
is no limit or end to the total amount of value. This is because all value is
discounted over time (also called "time preferencing").
Annuities are possible because the present value of a future payment of a given
amount is less than its numerical value in the future and since this gets
progressively smaller in proportion to the time interval into the future at
which payment is made, it is possible that the sum of the present values of all
that unending set of payments is still less than the current value which has
been supplied to purchase the annuity. This is related to the mathematical
notion of an unending series of terms which nevertheless add up to a finite
value, for example 1 + 1/2 + 1/4 + 1/8 + 1/16 + ... is always less than 2.

There are also other values that I have given to cryonics and particularly to
21st Century Medicine (of which LEF is essentially the owner at this time). Bill
Faloon (and Saul Kent) is well aware of all these things and the continuing
value to LEF of my website MoreLife (in which I have many links to LEF without
gaining any direct royalty remuneration as any kind of LEF "agent"). And since
there is no formal contract at all between us, LEF could easily at any time
decide to stop providing me with supplements at no cost (they already extended
the arrangement to include Kitty after beginning only with me). Since Bill
chooses not to stop this arrangement, I can reasonably assume that he thinks
that LEF has gained and still gains sufficient value for it to be worthwhile
continuing. Thus, if I unilaterally decided to stop taking this value offered to
me, I would actually be refusing to accept what I was earning. That is why, as I
said above, even if I did ever decide to terminate the arrangement, I would ask
for some payment in cash instead. The only reason why I have not done so to date
is that not everyone in this world is rational enough to be able to fully
address such changes in a situation that is not fully detailed and is very
likely understood differently by each party involved. --Paul]

[Thanks for making this clear Paul, I was not well informed about the exact
arrangement you had with LEF. I will have to talk to you more about your past
next time I visit you and Kitty. -°Olafur]


Here is a link to the article by Ward Dean, MD at VRP:
http://www.vrp.com/art/1181.asp

I know from readings at morelife.com that R+ Lipoic Acid can mediate
the age related decline of Glutathione somewhat
(http://morelife.org/supplements/RLA.html), but wonder if
supplementation might be useful.

I noted that under the additional Reading section of the above
morelife referenced page that Glutathione (not sure which paper is
cited in this section) "cannot be directly administered, whereas
alpha-lipoic acid can." (http://morelife.org/supplements/RLA.html)

[That quote is from the abstract of PMID: 8958163 of which the full paper is
available in the MoreLife Library at:
http://morelife.org/references/full_papers/8958163.pdf The paper is written by
Lester Packer who I fully expected would write only true statements regarding
antioxidants and besides that statement (in the form "would be ineffective if
administered orally") completely agreed with my previous readings and
understandings. The same statement is made by the authors in the introduction
section of the full paper, but they give no reference for their statement (which
is normal for a statement which is universally known to be true, else all papers
would need to be of book length in their references). As with the absorption of
many peptides (glutathione is a tripeptide), those with unhealthy digestive
systems will undoubtedly absorb some (and the smaller the peptide and the more
unhealthy the digestive system, the more such persons will absorb). However, I
will examine and comment on the references to the contrary that you cite below.
In the past I have found Ward Dean and many other supplement promoters to be
*convinced* of things on much less evidence than I and others are. --Paul]


However Dr. Dean from VRP states:
"I used to think that oral glutathione was destroyed in the stomach,
and was not effective in raising glutathione concentrations. However,
Dr. Steve Edelson, of the Edelson Center for Environmental and
Preventive Medicine in Atlanta, Georgia, kindly sent me a number of
articles that convinced me otherwise. These articles demonstrated that
about 80 percent of oral glutathione is absorbed intact, and that the
blood levels remain elevated for about three hours (Fig. 6).23-26"
(http://www.vrp.com/art/1181.asp)

23. Hagen, T.M., Aw, T.Y., and Jones, D.P. Glutathione uptake and
protection against oxidative injury in isolated kidney cells, Kidney
International, 1988, 34:74-81. PMID: 3172638

[Here is the abstract:

"Analysis with radiotracer and high performance liquid chromatography
techniques showed that glutathione (GSH) is transported intact into
cells primarily of proximal tubule origin. Characteristics of GSH
uptake were the same as previously reported for basal-lateral membrane
vesicles, namely, uptake was Na+-dependent, inhibited by gamma-glutamylglutamate
and/or probenecid, and not inhibited by
cysteinylglycine or the constituent amino acids. Studies with inhibitors of
gamma-glutamyltransferase (acivicin) and
gamma-glutamylcysteine synthetase (buthionine sulfoximine) showed that
GSH uptake, degradation and resynthesis are independent processes. The
GSH uptake rate with 1 mM GSH was approximately three-fold greater
than the GSH synthetic rate with 1 mM amino acids. To examine whether
uptake of GSH can supplement synthesis to protect against injury, we
incubated cells with a toxic concentration of t-butylhydroperoxide
with or without GSH or its constituent amino acids. Although amino
acids provided significant protection, GSH provided greater protection
(cells with t-butylhydroperoxide plus GSH were not significantly
different from cells alone). This protection by GSH was eliminated by
gamma-glutamylglutamate or probenecid, indicating that GSH uptake was
required for the protection seen. Protection was also eliminated when
the GSSG reductase/GSH peroxidase system was inhibited by
bischloronitrosourea (BCNU), indicating that GSH transport affords
protection by maintaining GSH levels in the cell. Thus, intact GSH is
transported into isolated proximal tubule cells by a Na+-dependent
system, and this transported GSH can be used to supplement endogenous
synthesis and GSSG reduction to protect cells against oxidative
injury."

Comment: This paper simply shows that GSH can be absorbed through the membranes
of cells to supplement the endogenous production (within the cells). Therefore,
injecting GSH may be a helpful therapy. This does not imply that oral GSH
supplementation will enable GSH to be available for cellular uptake. --Paul]


24. Hagen, T.M., Wierzbicka, G.T., Sillau, A.H., Bowman. B.B., and
Jones, D.P. Bioavailability of dietary glutathione: Effect on plasma
concentration, Am. J. Physiol, 1990a, 259: G524-G529. PMID: 2221062

[I do not have access to the full text of this without paying $8, but here is
the abstract:

"Plasma glutathione (GSH) concentration in rats increased from
approximately 15 to 30 microM after administration of GSH either as a
liquid bolus (30 mumol) or mixed (2.5-50 mg/g) in AIN-76 semisynthetic
diet. GSH concentration was maximal at 90-120 min after GSH
administration and remained high for over 3 h. Administration of the
amino acid precursors of GSH had little or no effect on plasma GSH
values, indicating that GSH catabolism and resynthesis do not account
for the increased GSH concentration seen. Inhibition of GSH synthesis
and degradation by L-buthionine-[S,R]-sulfoximine and acivicin showed
that the increased plasma GSH came mostly from absorption of intact
GSH instead of from its metabolism. Plasma protein-bound GSH also
increased after GSH administration, with a time course similar to that
observed for free plasma GSH. Thus dietary GSH can be absorbed intact
and results in a substantial increase in blood plasma GSH. This
indicates that oral supplementation may be useful to enhance tissue
availability of GSH."

My comment is below. --Paul]


25. Hagen, T.M., Wierzbicka, G.T., Sillau, A.H., Bowman. B.B., Aw,
T.Y., and Jones, D.P. Fate of dietary glutathione: Disposition in the
gastrointestinal tract, Am. J. Physiol, 1990b, 259: G530-G535. PMID:
2221063

[Again, I do not have access to the full text of this without paying $8, but
here is the abstract:

"Studies were performed in rats that had been fasted 24 h, fed a
glutathione (GSH)-free semisynthetic diet (AIN-76), and fed the same
diet supplemented with GSH. The results from the fasted rats and those
fed GSH-free diet showed that the duodenum and jejunum contained
0.2-0.5 mumol of GSH/gram wet wt of luminal contents. The GSH contents
of biliary juice was sufficient to maintain this amount of GSH in the
intestinal lumen. Other analyses showed that cell sloughing, bacterial
GSH content, and GSH secretion by epithelial cells of the jejunum were
not sufficient to account for this content. GSH concentrations
following consumption of a GSH-supplemented diet (5-50 mg/g AIN-76)
showed a rapid increase in all regions of the small intestine and
indicated that removal occurred primarily in the jejunum. However, the
combined activities of brush-border gamma-glutamyltransferase and GSH
uptake systems were not sufficient to remove all of the ingested GSH.
Results from in situ vascular perfusions of small intestine showed
that the upper jejunum is a principal site of GSH absorption.
Measurements of the GSH-to-glutathione disulfide (GSSG) ratio in the
lumen after ingestion of GSSG (5 mg/g diet) indicated that the upper
small intestine also has a mechanism for reducing GSSG to GSH. The
results therefore indicate that GSH is present in the lumen of the
small intestine of rat under most if not all conditions. Although the
physiological importance of luminal GSH remains unclear, it could
potentially be used to detoxify reactive electrophiles in the diet or
be absorbed for intracellular detoxication reactions."

My comment is below. --Paul]


26. Vincenzini, M.T., Favilli, F., and Iantomasi, T. Intestinal uptake
and transmembrane transport systems of intact GSH: Characteristics and
possible biological role. Biochimica et Biophysica Acta, 1992,
1113:13-23. PMID: 1550859

[This paper has no abstract and access to the full paper would cost $30.

Final comment: Although the abstracts of the papers referenced as 24 and 25
above certainly provide evidence that GSH is orally bioavailable, without the
chance to examine the full papers I still think that this is generally not valid
because of the general breakdown of all proteins and peptides by the digestive
system (except a very few special enzymes) and because so many other
knowledgeable authors are apparently convinced that GSH is not orally
bioavailable. Still I am now far less certain and because I get my supplements
without cost from LEF, I may decide to order and take a small amount of
glutathione orally. --Paul]


Erich Brueschke