Gamma tocopherol, the liver ...
Quentin Grady
When supplement manufacturers turn out "natural" alpha tocopherol
they frequently have converted some gamma tocopherol to alpha
tocopherol. They are allowed to do this because their source of
tocopherol was natural. Of course you might ask why do they do this.
Alpha tocopherol is thought to have a higher efficacy than the other
tocopherols. Much of this supposed superiority is based on the
knowledge that most other tocopherols are removed on their first pass
through the liver. The usual assumption is that the other forms are
therefore largely a waste of packaging space. Assumptions though
depend on premises and some of them over time are updated.
If I am understanding a recent thread correctly oleic acid, the most
common mono-unsaturated fatty acid can cause liver damage and the way
to prevent it is to ensure the liver is getting sufficient Vit E. It
seems to me that alpha tocopherol which passes through the liver might
not in fact be the tocopherol of choice for protecting from oleic acid
overload.
For many people this might not matter at all but for T2 diabetics its
relevance is easy to see. Whether one follows the ADA guidelines or
not the one fat where there is the greatest degree of flexibility in
acceptable consumption levels is with mono-unsaturated fatty acids.
There are lots of good reasons to replace some carbs with MUFAs. The
question as always is how to get the benefits without the downside.
The simple questions that need answering are,
"Which forms of Vit E protect the liver best from high MUFA levels?"
"Are there other antioxidants that protect the liver better?"
--
Quentin Grady ^ ^ /
New Zealand, >#,#< [
/ \ /\
"... and the blind dog was leading."
Martin Banschbach
> The simple questions that need answering are,
>
> "Which forms of Vit E protect the liver best from high MUFA levels?"
>
> "Are there other antioxidants that protect the liver better?"
Vegetable oil intake can lead to fatty infiltration in rat liver.
There are many possibilities and the one I focused in on was free
radical damage with not enough E to protect.
Having oleic acid as a major factor in rat liver fat
infiltration was a shock for me. I did not have time
to pursue that. Gamma and alpha tocopherol appera to have different
actions and different absorption from the gut and use in the
liver.
One potential problem with rats is that they may be more
sensitive to fatty infiltration of the liver than humans.
Lipotrophic factors (inositiol and choline) are also known
to cause fatty infiltration in the liver if either is
deficient and I think that rat liver has a poorer choline
synthesis than human liver does.
The other issue is load, even with good formation of the
phospholipids that will be needed to off load fat from the
liver, this system can be overloaded. With a very strong
continuous push of glucose into the liver (type II diabetics)
fat may back up because it can't be off loaded fast enough.
For alcohol induced fatty infiltration of the liver both
increased fat formation and free radical damage appear to
be involved.
For rats, vitamin E may not be as important as I and others
once thought (why some oils cause fatty infiltration of rat
liver).
Once I get into work I'm going to try to get a handle on the
alpha, gamma tocopherols in terms of human liver function.
Steve Harris
> G'day G'day Folks,
>
> When supplement manufacturers turn out "natural" alpha tocopherol
> they frequently have converted some gamma tocopherol to alpha
> tocopherol. They are allowed to do this because their source of
> tocopherol was natural. Of course you might ask why do they do this.
> Alpha tocopherol is thought to have a higher efficacy than the other
> tocopherols.
COMMENT:
It does have higher vitamin activity. But that's not why manufacturers buy
alpha-tocopherol ("alpha-T") which has been converted from gamma-tocopherol
("gamma-T") to put into "Vitamin E" pills. The reason in the US (at least)
is because you're only allowed to report vitamin E activity on bottle labels
in IUs based on alpha-T content. Even though there is a perfectly good
conversion to IUs from gamma-T.
>Much of this supposed superiority is based on the
> knowledge that most other tocopherols are removed on their first pass
> through the liver. The usual assumption is that the other forms are
> therefore largely a waste of packaging space.
COMMENT
One wishes it were this sophisticated. You give the FDA too much credit.
Also, your facts are not in evidence.
Gamma-T in single doses in a healthy individual who is vitamin E replete,
does indeed get (mostly) metabolized almost immediately (within a day) and
go to metabolites which go off in the urine (things like
gamma-CEHC-gluconuride). However, please don't infer from that that this is
what happens to all gamma-T you take. There are pools of gamma-T in the body
which are doubtless MUCH slower, and there must be exchange in and out of
them. I know of no long term gamma-T supplementation studies in humans to
explore that, but in rats where you can supplement depleted animals, it
takes tissues stores several *weeks* to get to max gamma-T content. That
means gamma-T has a very slow compartment in rats. If it didn't in people
(and a much slower one than in rats, since our metabolisms are 1/5ths as
fast) I'd be very surprised, since gamma-T's distribution is very similar to
alpha-T.
Now, there are differences between alpha and gamma-T metabolism. Levels of
gamma-T in tissues run at much lower absolute levels (like a fifth of those
of alpha), due to the fact that the binding and transfer proteins for vit E
are specific to alpha-T, and store it by binding it, and sticking into
lipids preferentially. However, here again you could be fooled by even
alpha-T, if you just looked at plasma levels. For example, if you give
whopping doses of alpha-T to humans (this has been studied) for some time,
it takes maybe 5 days to hit max blood levels (about 2x normal at a dose of
10 RDIs), and then decays away in 2 weeks when you stop. However, levels of
alpha-T in fat tissues take more than a year equilibrate to a new dose,
implying half-times of many months, so you can see that the simple blood
picture isn't a good marker for metabolism or compartment half-times for
this vitamin. It probably isn't for gamma-T either, based on the repletion
studies.
The transfer/binding protein for alpha-T makes it metabolize a bit like
vitamin A, where you only start seeing funny metabolism only after the
retinyl binding protein system has been saturated. When that happens for the
alpha-T binding proteins you start to see alpha-CEHC urine metabolites from
alpha-T that remind you a lot of the gamma-T paths. Again, though, just
because this doesn't happen with gamma-T, that doesn't mean all gamma-T is
immediately metabolized. It just means that overdoses or large doses are.
For alpha-T, by contrast, there's a buffer before you get spillover
metabolism to water-soluble metabolites. Your body's preferentially trying
to hold on to alpha-T, which probably tells you something.
There are suggestions in the literature that gamma-T might have some helpful
body function that alpha-T doesn't, but there's not much gross evidence for
it. Gamma-T's a much better anti-inflammatory, but that doesn't mean you
can't raise perfectly healthy animals on alpha-T alone, which live to ripe
old ages (they live as long as on mixed diets, which contain mostly
gamma-T). You can. Thus, there is no direct and strong evidence yet that
gamma-T is necessary for health.
You might wonder what happens when you try to raise animals on gamma-T alone
and no alpha-T, and the answer is that you can't do it. If you try, even
after many generations you get healthy animals, able to reproduce, whose
bodies contain some alpha-T (though not at normal levels). Evidently there
is a metabolic path, not yet elucidated, that turns gamma-T to alpha-T. So
(if they have to) animals are able to methylate the gamma up to alpha, just
like pharmaceutical companies do! Probably your own body can do this also.
Biochemically ones suspect for obvious reasons that this will turn out to be
yet one more B-12 dependent reaction.
SBH
--
I welcome Email from strangers with the minimal cleverness to fix my address
(it's an open-book test). I strongly recommend recipients of unsolicited
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Quentin Grady
>"Quentin Grady" <que...@paradise.net.nz> wrote in message
>news:gorv6uc5b0ci8u1e1...@4ax.com...
>> G'day G'day Folks,
>>
>> When supplement manufacturers turn out "natural" alpha tocopherol
>> they frequently have converted some gamma tocopherol to alpha
>> tocopherol. They are allowed to do this because their source of
>> tocopherol was natural. Of course you might ask why do they do this.
>> Alpha tocopherol is thought to have a higher efficacy than the other
>> tocopherols.
>
>COMMENT:
>
>It does have higher vitamin activity. But that's not why manufacturers buy
>alpha-tocopherol ("alpha-T") which has been converted from gamma-tocopherol
>("gamma-T") to put into "Vitamin E" pills. The reason in the US (at least)
>is because you're only allowed to report vitamin E activity on bottle labels
>in IUs based on alpha-T content. Even though there is a perfectly good
>conversion to IUs from gamma-T.
G'day G'day Steve,
Thanks that makes sense. In New Zealand we have Vit E from various
countries including of course the USA. I have noticed that Vit E with
the same numbers of IU can have different numbers of mg. Perhaps in
NZ we are allowed equivalents.
BTW, I really appreciate the detail with which you have answered this
question.
>>Much of this supposed superiority is based on the
>> knowledge that most other tocopherols are removed on their first pass
>> through the liver. The usual assumption is that the other forms are
>> therefore largely a waste of packaging space.
>
>COMMENT
>
>One wishes it were this sophisticated. You give the FDA too much credit.
>Also, your facts are not in evidence.
True.
I am not sure providing it would contribute anything worthwhile. Most
of it is from reading books which provide references which I haven't
checked out.
>Gamma-T in single doses in a healthy individual who is vitamin E replete,
>does indeed get (mostly) metabolized almost immediately (within a day) and
>go to metabolites which go off in the urine (things like
>gamma-CEHC-gluconuride). However, please don't infer from that that this is
>what happens to all gamma-T you take. There are pools of gamma-T in the body
>which are doubtless MUCH slower, and there must be exchange in and out of
>them. I know of no long term gamma-T supplementation studies in humans to
>explore that, but in rats where you can supplement depleted animals, it
>takes tissues stores several *weeks* to get to max gamma-T content. That
>means gamma-T has a very slow compartment in rats. If it didn't in people
>(and a much slower one than in rats, since our metabolisms are 1/5ths as
>fast) I'd be very surprised, since gamma-T's distribution is very similar to
>alpha-T.
In your opinion are these slow to equilibrate stores of gamma-T and
alpha-T important to health in people who haven't been forced into a
deprived nutrition status and are eeking out the supplies. To put it
another is there any evidence that the tocopherol in these reserves
does anything except wait if out for emergencies.
>Now, there are differences between alpha and gamma-T metabolism. Levels of
>gamma-T in tissues run at much lower absolute levels (like a fifth of those
>of alpha), due to the fact that the binding and transfer proteins for vit E
>are specific to alpha-T, and store it by binding it, and sticking into
>lipids preferentially. However, here again you could be fooled by even
>alpha-T, if you just looked at plasma levels. For example, if you give
>whopping doses of alpha-T to humans (this has been studied) for some time,
>it takes maybe 5 days to hit max blood levels (about 2x normal at a dose of
>10 RDIs), and then decays away in 2 weeks when you stop. However, levels of
>alpha-T in fat tissues take more than a year equilibrate to a new dose,
>implying half-times of many months, so you can see that the simple blood
>picture isn't a good marker for metabolism or compartment half-times for
>this vitamin. It probably isn't for gamma-T either, based on the repletion
>studies.
So short term studies of the efficacy of supplementation of alpha-T or
gamma-T could be quite misleading.
>The transfer/binding protein for alpha-T makes it metabolize a bit like
>vitamin A, where you only start seeing funny metabolism only after the
>retinyl binding protein system has been saturated. When that happens for the
>alpha-T binding proteins you start to see alpha-CEHC urine metabolites from
>alpha-T that remind you a lot of the gamma-T paths. Again, though, just
>because this doesn't happen with gamma-T, that doesn't mean all gamma-T is
>immediately metabolized. It just means that overdoses or large doses are.
>For alpha-T, by contrast, there's a buffer before you get spillover
>metabolism to water-soluble metabolites. Your body's preferentially trying
>to hold on to alpha-T, which probably tells you something.
I think that is the general message I have absorbed over the years.
The body works hard to preserve alpha-T but seems to waste gamma-T.
Then I wondered if I was looking at it from the right perspective. The
fact that alpha-T has a buffer system to prevent spill over to water
soluble metabolites seems to suggest an evolutionary investment in
alpha-T.
>There are suggestions in the literature that gamma-T might have some helpful
>body function that alpha-T doesn't, but there's not much gross evidence for
>it. Gamma-T's a much better anti-inflammatory, but that doesn't mean you
>can't raise perfectly healthy animals on alpha-T alone, which live to ripe
>old ages (they live as long as on mixed diets, which contain mostly
>gamma-T). You can. Thus, there is no direct and strong evidence yet that
>gamma-T is necessary for health.
I damaged a foot many years ago in a freak high jumping accident.
That foot frequently swells and adds to the complications of having
some peripheral neuropathy in my feet. It is just something I live
with and deal with. It is useful to know that gamma-T has some
anti-inflammatory effects.
It is not something I would have thought of.
>You might wonder what happens when you try to raise animals on gamma-T alone
>and no alpha-T, and the answer is that you can't do it. If you try, even
>after many generations you get healthy animals, able to reproduce, whose
>bodies contain some alpha-T (though not at normal levels). Evidently there
>is a metabolic path, not yet elucidated, that turns gamma-T to alpha-T. So
>(if they have to) animals are able to methylate the gamma up to alpha, just
>like pharmaceutical companies do! Probably your own body can do this also.
>Biochemically ones suspect for obvious reasons that this will turn out to be
>yet one more B-12 dependent reaction.
FWIIW I have B-12 levels 50% above lab normal. If that is the only
condition required for conversion of gamma-T to alpha-T chances are I
am making the conversion successfully.
>SBH
If you had to choose an antioxidant to protect LDL etc from oxidation
what would you choose?
Quentin Grady
wrote:
>Quentin Grady <que...@paradise.net.nz> wrote in message
>
>> The simple questions that need answering are,
>>
>> "Which forms of Vit E protect the liver best from high MUFA levels?"
>>
>> "Are there other antioxidants that protect the liver better?"
>
>Vegetable oil intake can lead to fatty infiltration in rat liver.
>There are many possibilities and the one I focused in on was free
>radical damage with not enough E to protect.
>
>Having oleic acid as a major factor in rat liver fat
>infiltration was a shock for me.
No kidding me too. In the couple of years I have been diagnosed as a
T2 most of it has been a boring process of getting better and better
lab results. The one minor hiccup was a slightly abnormal liver
function test that soon cleared up. Whatever. It was enough to make
me check rather than assume I had my strategy correct.
>I did not have time
>to pursue that. Gamma and alpha tocopherol appear to have different
>actions and different absorption from the gut and use in the
>liver.
I think they are also different where LDL is concerned.
>One potential problem with rats is that they may be more
>sensitive to fatty infiltration of the liver than humans.
OK. That is helpful to know. They are also more sensitive to
fructose. Fructose and fats seem to challenge T2s and rats.
>Lipotrophic factors (inositiol and choline) are also known
>to cause fatty infiltration in the liver if either is
>deficient and I think that rat liver has a poorer choline
>synthesis than human liver does.
I have been looking at the combination of inositol and choline in
conjunction with weight loss. I lost 20 kg then quite suddenly
stopped. I like to lose a few more kilos. At the moment I am doing
weight and getting better posture but very little weight loss.
>The other issue is load, even with good formation of the
>phospholipids that will be needed to off load fat from the
>liver, this system can be overloaded. With a very strong
>continuous push of glucose into the liver (type II diabetics)
>fat may back up because it can't be off loaded fast enough.
A good reason to keep blood glucose levels down.
>For alcohol induced fatty infiltration of the liver both
>increased fat formation and free radical damage appear to
>be involved.
>
>For rats, vitamin E may not be as important as I and others
>once thought (why some oils cause fatty infiltration of rat
>liver).
Oh, how is that?
>Once I get into work I'm going to try to get a handle on the
>alpha, gamma tocopherols in terms of human liver function.
IMHO there are other supplements with antioxidant properties that
might be relevant eg turmeric and milk thistle.
Martin Banschbach
> >once thought (why some oils cause fatty infiltration of rat
> >liver).
>
> Oh, how is that?
Vitamin E is not one compound, its' 8 different compounds each with
a different structure and different biological activity both in vivo
and in vitro. "Molecular mechanism of cellular uptake and
intracellular
translocation of alpha-tocopherol:role of tocopherol-binding
proteins."
Food Chem Toxicol 1999 Sep-Oct;37(9-10:967-971.
I could find only 1 published paper where the gamma form was
examined in rats given alcohol to produce fatty infiltration of the
liver.
"Effect of chronic ethanol feeding on hepatic and extrahepatic
distribution of vitamin E in rats" Alcohol Clin Exp Res 1991
Oct;15(5):771-774.
With 36% of total calories coming from alcohol a very nice increase in
liver weight was seen (fatty infiltartion of the liver) after just 3
weeks.
Alpha levels in the serum were not affected but gamma levels doubled.
In the liver, no change in alpha was seen (after correcting for the
weight
increase of the liver) but gamma went up 2.5 times over what was seen
for control rats (no ethanol).
Alcohol also changes the tissue distribution of alpha and gamma. Both
went up in the testis, only gamma went up in lung tissue.
If alpha or gamma were really protecting the rat liver from
free radicals produced by ethanol, both should have gone down. Not
only
did gamma not go down, it went up!
I could not find any papers where gamma was examined in oil induced
fatty infiltration of rat liver in vivo but I did find one for
cultured hepatocytes (cited below). Many studies have been done in
rats
using oils to give fatty infiltration of the liver and most of them
say it's malondialdehyde that's doing it. "High peroxidative
susceptibility of fish oil polyunsaturated fatty acid in cultured rat
hepatocytes." Toxicol Appl Pharmacol 1994 May;126(1):124-128.
Rank for production of malondialdehyde:
1. Docosahexaenoic acid
2. EPA
3. Arachidonic acid
4. Alpha-linolenic acid = Gamma-linolenic acid
5. Linoleic acid
6. Oleic acid
Biggest effect is a loss of glutathione (GSH) and protein thiols
in the hepatocytes. Drugs that deplete GSH greatly increased
malondialdehyde
formation. Iron chelation greatly reduced malondialdehyde formation.
The only other approach that greatly decreased the formation of
malondialdehyde when the rat liver cells were challenged with
different
kinds of unsaturated fatty acids was gamma-tocopherol.
This study also measured LDH (cells that are damaged will leak this
enzyme).
Even with docosahexaenoic acid challenge, iron chelation or
gamma-tocopherol would completely stop LDH from leaking out into the
culture media.
> IMHO there are other supplements with antioxidant properties that
> might be relevant eg turmeric and milk thistle.
You are absolutely right Quentin, there are many natural chemicals
that
appear to protect the liver from free radical damage. For alcohol and
polyunsaturated fatty acid free radical damage, vitamin E has always
been thought to have a major role. I spent quite a bit of time last
night going through published medicine to try to get a better
handle on gamma-tocopherol. In humans and rats, alpha appears to
be handled very differently from gamma with specific alpha transport
proteins being produced in both the gut and the liver.
Gamma is considered to be the better protector of lipids from
peroxidation in both the liver and LDL. While there is a tremendous
variation in the level of alpha and gamma in plant food, gamma
dominates
as far as the human diet is concerned.
"Gamma-tocopherol, the major form of vitamin E in the U.S. diet,
deserves more
attention." Am J Clin Nutr 2001 Dec;74(6):714-722. This paper points
out
that gamma is a much more effective lipophilic free radical trap than
is alpha.
Lipophilic is lipid and this means unsaturated fatty acid
peroxidation.
Gamma inhibits cyclooxygenase but alpha does not. The self
destruction product
of gamma has natriuretic activity in the human kidneys but the self
destruction
product of alpha does not have this action in human kidneys.
Now that gamma is being measured in human serum, we are starting to
see a very
strong inverse correlation between gamma levels and prostate cancer
and cardiovascular disease. To my knowledge, no clinical trial has
yet been done
using gamma supplementation to try to decrease the chance of having a
second
heart attack.
The paper I cited above also points out that alpha supplementation
will block
gamma absorption and deplete serum gamma levels in humans.
Alpha appears to have two separate absorption processes in the human
gut, 1
uses a specific alpha binding protein and the other is passive for
lipid material. This passive system takes up all 8 forms of E and the
carotenoids.
Beta-carotene supplementation will also decrease gamma absorption in
the human
gut and lower gamma levels in the serum of humans.
What I thought was fairly simple turns out to be extremely complex.
Neither alpha nor gamma appear to help with alcohol induced liver
damage in rats.
Gamma appears to be the most important kind of E in protecting rat
liver from lipid peroxidation damage.
Using supplements (alpha-tocopherol or beta-carotene) can destroy the
role of gamma in human health. I deep fryed some trout that I had
caught this past weekend and added alpha-tocopherol to the canola oil.
Even though the natural
mixed tocopherols are much more expensive, I think that I am going to
use the natural E mix the next time I fry fish.
Martin Banschbach PhD
> The body works hard to preserve alpha-T but seems to waste gamma-T.
> Then I wondered if I was looking at it from the right perspective. The
> fact that alpha-T has a buffer system to prevent spill over to water
> soluble metabolites seems to suggest an evolutionary investment in
> alpha-T.
Quentin,
You have spent more time looking at E than I have. And I know that Steve
has spent more time looking at it too.
To me, E was always very simple. The major player was d-alpha-tocopherol.
Liver and gut would never have invested considerable metabolism to produce a
d-alpha-tocopherol binding protein if this was not important for human
health. But the kicker was always little or no impact in humans deprived of
any vitamin E.
The early days of TPN had no alpha-linolenic acid and no E. About the only
bad thing you see with no E is a shortened life span for red blood cells.
To me that said that other antioxidants are able to do what E does. But the
DNA interaction for alpha is really throwing me for a loop. I've almost
come to the same conclusion, retinoic acid, selenium or zinc may also be
able to take over what E does for the regulation of gene expression.
When we put the space shuttle together we used redundant systems to improve
safety. I'm beginning to believe that the human body figured out that
redundant systems would be useful in human survival.
--
Marty B. "You are what you eat."
http://centernet.okstate.edu/nutrition/index.html
The above website is for educational purposes
only. Material in this website and posted material
represents the opinion of Martin Banschbach,
Ph.D. and does not reflect Oklahoma State
University policy or position on nutrition.
Issues regarding the diagnosis and treatment
of human disease can not be addressed
by material in the above website or by
Martin Banschbach, Ph.D.
Any comments made by Martin
Banschbach, Ph.D. are invalid unless
confirmed by your personal physician.
Quentin Grady
wrote:
>Many studies have been done in rats using oils to give fatty
>infiltration of the liver and most of them
>say it's malondialdehyde that's doing it. "High peroxidative
>susceptibility of fish oil polyunsaturated fatty acid in cultured rat
>hepatocytes." Toxicol Appl Pharmacol 1994 May;126(1):124-128.
>
>Rank for production of malondialdehyde:
>1. Docosahexaenoic acid
>2. EPA
>3. Arachidonic acid
>4. Alpha-linolenic acid = Gamma-linolenic acid
>5. Linoleic acid
>6. Oleic acid
G'day G'day Martin,
The obvious but awful question is what about stearic, palmitic,
elaidic, vaccinic acids?
Is there no data for them or are the saturated fatty acids and trans
fats less likely to cause malondialdehyde?
Could it be that Atkins was on to something when he poo pooed the
dangers of saturated fats?
Martin Banschbach
> >Rank for production of malondialdehyde:
>
> >1. Docosahexaenoic acid
> >2. EPA
> >3. Arachidonic acid
> >4. Alpha-linolenic acid = Gamma-linolenic acid
> >5. Linoleic acid
> >6. Oleic acid
>
> G'day G'day Martin,
>
> The obvious but awful question is what about stearic, palmitic,
> elaidic, vaccinic acids?
>
> Is there no data for them or are the saturated fatty acids and trans
> fats less likely to cause malondialdehyde?
>
> Could it be that Atkins was on to something when he poo pooed the
> dangers of saturated fats?
Saturated fatty acids are not going to produce malondialdehyde. Trans
fatty acids probably would. It would be interesting to know if trans
fatty acids actually produce more malondialdehyde than their identical
cis conterparts. This rat liver cell culture was a gold mine for
getting a really good feel for how rat liver handles each *specific*
fatty acid that has double bonds in it.
There are an awful lot of ways that the fatty acid profile in humans
alters human metabolism. Malondialdehydehyde production is just one
of these ways. The nice thing about malondialdehydehyde is that it
can be measured and it's pretty specific for fatty acid peroxidation
(fatty acids with double bonds getting themselves into trouble).
While alpha does not appear to save them as well as was once thought,
gamma saves them very well. But even with no gamma, other
antioxidants can stop lipid peroxidation (slow it down, you can never
stop it completely).
For every free radical that has been identified in human tissues, more
than 1 antioxidant can handle it. However, a single anti-oxidant can
not handle them all. Because of what Steve Harris said about vodka
drinkers I decided to play around in published medicine last night
until about 1:30 am.
I've seen suggestions that even straight ethanol could have a health
benefit in humans but it's certainly not as strong as what you see for
red wine. I have convinced myself that sulfur holds the key to human
health and longivity.
I'm pretty sure that the human liver will sulfate ethanol but I have
not been able to prove it yet using published medicine. If you look
at mercaptoethanol you are going to get a tremendous number of hits
because this is a chemical that is often used during isolation of
material to keep sulfur reduced (keep disulfide bonds from forming).
I have always had an interest in ageing research because just like
everyone else, I'm going to die sometime. Nothing really works all
that well in animals except for calorie restriction. While playing
around with mercaptoethanol last night I came across some very
interesting papers. Calorie restriction may not work the way most of
us (by us I mean people who have been trained in the area of science)
think it works. The lower oxygen intake may not be all that
important. The lower intake of glucose may be the key.
Even in a person who does not have diabetes, glucose will always
glycosalate proteins. This happens both in the blood and inside
cells. Lipoic acid really does not do a good job of stopping this
(although in diabetics it does appear to help). I learned something
that I did not know. Mercaptoethanol is a monothiol while lipoic acid
is a dithiol (I guess I knew it but it never seemed to be very
important). Mercaptoethanol will get all of the glucose off proteins
but lipoic acid can not do this.
The paper that still burns in my memory banks looked at glycosalation
of rat brain protein. Giving the rats mercaptoethanol took off almost
all of the glucose from the rat brain proteins (I think that this
means that sulfur in the protein was what got hit with the glucose).
The paper said that this process of gradually accumulating
glycosalated protein in the brain over time may be what causes brain
ageing. Before you get too excited, you can not get mercaptoethanol
as a supplement (that I know of). But it's widely available as a
chemcial because research labs use it all of the time. I also found
the first reported human death caused by ingesting mercaptoethanol. I
guess that somebody was reading the anti-ageing literature and decided
to order some mercaptoethanol and try it. This chemical is just like
DMSO, it has substantial toxicity. I am going to continue my hunt for
proof that human (or animal for that matter) liver can form
mercaptoethanol upon exposure to ethanol.
I also came across a very recent publication where MSM levels in human
brain was examined. For people not using MSM, there is basically
none. For people using this supplement there is a very large amount.
The paper pointed out that this was the first documentation that MSM
will cross the human blood-brain barrier and that the brain function
that was examined was not altered by the high MSM levels. They
conclude that MSM is probably safe but there is no evidence that it
offers any protection from ageing in the human brain. MSM is not
active sulfur. It really can not do much until the liver converts it
to active sulfur.
Quentin,
I answered your question but I know that I moved into an area where
you personally probably have more questions than I can probably answer
right now. I have been looking at mercaptoethanol and
mercaptoethanolamine for a very long time. In the early 1980's I had
to clean out the offfice and lab of a biochemist who died in a hunting
accident. He was an organic chemist doing work for the U.S. Army
synthesizing various sulfur containing compounds to be screened for
radioprotectant properties. Many of his papers were classified and I
had to shred them but I could not help reading them before I shredded
them.
When ionizing radiation hits human tissue hydroxyl free radicals are
generated. If the DNA damage does not kill immediately, radiation
sickness from all of these hydroxyl free radicals will usually kill in
a few days to a few weeks. The Army needs drugs to try to protect
it's troops from radiation. Monothiolamines are the very best class
of drugs developed to date and I did actually finally find some papers
in published medicine last night that confirms what I read many years
ago. Those classified Army documents indicated that as part of
determining what mercaptoethanolamine would do to rats and mice, they
determined an LD50 and also took some mice and rats out to their
maximum lifetime with low levels constantly present in their diet. A
doubling or tripling of maximum lifespan was reported depending on the
dose used. I have searched all these years in published medicine to
try to confrim this but to date I have come up empty. Again, to my
knowledge mercaptoethanolamine can not be obtained as a supplements
but even if you could get your hands on it, it has a higher LD50 than
mercaptoethanol does. Again, I think that the liver can form this if
it is exposed to ethanol but proving it is a different matter. While
mercaptoethanol generates thousands of hits, mercaptoethanolamine only
generates 3 hits.
If anyone made it this far, my message is that the health benefit of
ethanol in humans may be tied to the sulfur status of the human liver.
Alcohol is both vilifiled in the Bible and praised in the Bible. If
I understand Earth histroy correctly there apparently was a time when
clouds covered the Earth all of the time and the sulfur content in the
clouds was very high. If the plants had more sulfur and regular
intake of ethanol occured, then maybe the human lifespan was 2 to 3
times what it is now.
I like to try to use my mind once in awhile to seek out really weird
stuff. This is by far the wierdest that I've let my brain go so far.
Pauling fixated on vitamin C. I'm fixated on sulfur, the stuff that
hell (fire and brimstone)is made of. Until I can prove that liver can
take ethanol to mercaptoethanol and mercaptoethanolamine, this is just
a fairy tale. Both of these chemicals are far too toxic for anybody
to be playing around with. But with a good sulfur status, the liver
may give just enough each day if ethanol is coming in each day in
small amounts to really slow down the ageing process in humans.
I can get both of these chemicals from research lab chemical
suppliers. If I were Pauling, maybe I'd buy them. But I'm not
Pauling and I do no think that anyone should ever buy either of these
chemicals. If they are formed in the human body from ethanol, I say
let the process occur naturally.
Alf Christophersen
wrote:
>There are an awful lot of ways that the fatty acid profile in humans
>alters human metabolism. Malondialdehydehyde production is just one
>of these ways. The nice thing about malondialdehydehyde is that it
>can be measured and it's pretty specific for fatty acid peroxidation
>(fatty acids with double bonds getting themselves into trouble).
Has anyone corrected the data for the binding of taurine to
malondialdehyde ??
It reacts quite good with it, I have seen some data showing that.
Martin Banschbach Ph.D.
>malondialdehyde ??
>It reacts quite good with it, I have seen some data showing that.
Since I do not have the paper I can't look at the methods section. It was a
fairly recent paper but that does not really mean anything if they did not know
that taurine might mask some of the malondialdehyde that the cultured rat liver
cells were cranking when each different fatty acid was added to the culture
medium. Taurine would not have affected the ranking that they developed but it
certainly could have affected the point a which they were seeing LDH come out.
Marty B "You are what you eat"
Quentin Grady
wrote:
>Quentin Grady <que...@paradise.net.nz> wrote in message
The Okinawans eat about 100 grams of sea food per day. My guess is
they are getting plenty of DHA and EPA. Since they cook with rapeseed
oil and eat pork regularly chances are they get plenty of oleic acid
in the fatty acid mix. Those in the longevity survey average about
25% fats, 22% protein and 53% carbs so they are not as low fat as some
other Asian countries. A significant fact that might be relevant to
this discussion is that they regularly include turmeric in their
cooking. They also include some relative of lemon grass.
>For every free radical that has been identified in human tissues, more
>than 1 antioxidant can handle it. However, a single anti-oxidant can
>not handle them all. Because of what Steve Harris said about vodka
>drinkers I decided to play around in published medicine last night
>until about 1:30 am.
>
>I've seen suggestions that even straight ethanol could have a health
>benefit in humans but it's certainly not as strong as what you see for
>red wine. I have convinced myself that sulfur holds the key to human
>health and longivity.
>
>I'm pretty sure that the human liver will sulfate ethanol but I have
>not been able to prove it yet using published medicine. If you look
>at mercaptoethanol you are going to get a tremendous number of hits
>because this is a chemical that is often used during isolation of
>material to keep sulfur reduced (keep disulfide bonds from forming).
>
>I have always had an interest in ageing research because just like
>everyone else, I'm going to die sometime. Nothing really works all
>that well in animals except for calorie restriction. While playing
>around with mercaptoethanol last night I came across some very
>interesting papers. Calorie restriction may not work the way most of
>us (by us I mean people who have been trained in the area of science)
>think it works. The lower oxygen intake may not be all that
>important. The lower intake of glucose may be the key.
The TV version of the low energy intake connection with longevity
related it to lowered production of free radicals.
>Even in a person who does not have diabetes, glucose will always
>glycosalate proteins.
So will fructose, galactose and probably some other simple sugars.
Glucose gets more attention because diabetics measure glucose levels.
>This happens both in the blood and inside
>cells. Lipoic acid really does not do a good job of stopping this
>(although in diabetics it does appear to help).
Slow release is supposed to work better because alpha lipoic acid has
a very limited half life in the body.
>I learned something
>that I did not know. Mercaptoethanol is a monothiol while lipoic acid
>is a dithiol (I guess I knew it but it never seemed to be very
>important). Mercaptoethanol will get all of the glucose off proteins
>but lipoic acid can not do this.
Perhaps we need a diet that encourages the production of the right
enzyme...
>The paper that still burns in my memory banks looked at glycosalation
>of rat brain protein. Giving the rats mercaptoethanol took off almost
>all of the glucose from the rat brain proteins (I think that this
>means that sulfur in the protein was what got hit with the glucose).
>The paper said that this process of gradually accumulating
>glycosalated protein in the brain over time may be what causes brain
>ageing. Before you get too excited, you can not get mercaptoethanol
>as a supplement (that I know of). But it's widely available as a
>chemcial because research labs use it all of the time. I also found
>the first reported human death caused by ingesting mercaptoethanol. I
>guess that somebody was reading the anti-ageing literature and decided
>to order some mercaptoethanol and try it. This chemical is just like
>DMSO, it has substantial toxicity. I am going to continue my hunt for
>proof that human (or animal for that matter) liver can form
>mercaptoethanol upon exposure to ethanol.
It might also smell. Aren't the mercaptans famous?
Perhaps garlic flavoured vodka would give a mercaptoethanol rush?
<grin>
Overdosing on garlic and vodka simultaneously would lead to a life
that would seem longer ... or at least one filled with loneliness.
>I also came across a very recent publication where MSM levels in human
>brain was examined. For people not using MSM, there is basically
>none. For people using this supplement there is a very large amount.
>The paper pointed out that this was the first documentation that MSM
>will cross the human blood-brain barrier and that the brain function
>that was examined was not altered by the high MSM levels. They
>conclude that MSM is probably safe but there is no evidence that it
>offers any protection from ageing in the human brain. MSM is not
>active sulfur. It really can not do much until the liver converts it
>to active sulfur.
Do the metabolites cross the brain barrier?
The major problem with extra sulphur in the diet that modern diets are
already reputed to be rich in sulphur. There was a report in New
Scientist a while back of research on smelly farts. The major culprit
in modern diets was sulphates left behind from the use of sulphur
dioxide as a preservative.
Best wishes, and thanks of the entertaining lines of enquiry.
Martin Banschbach
> >I also came across a very recent publication where MSM levels in human
> >brain was examined. For people not using MSM, there is basically
> >none. For people using this supplement there is a very large amount.
> >The paper pointed out that this was the first documentation that MSM
> >will cross the human blood-brain barrier and that the brain function
> >that was examined was not altered by the high MSM levels. They
> >conclude that MSM is probably safe but there is no evidence that it
> >offers any protection from ageing in the human brain. MSM is not
> >active sulfur. It really can not do much until the liver converts it
> >to active sulfur.
>
> Do the metabolites cross the brain barrier?
>
> >Quentin,
MSM gets into the human brain in very good amounts. I don't know if sulfate
does though. Taurine will get in and since MSM is going to give some
methionine and cysteine there may be a little better production of taurine
but if there is, I doubt if it's that significant.
From what I understand, the best brain protectant is taurine.
Alf Christophersen
wrote:
>MSM gets into the human brain in very good amounts. I don't know if sulfate
>does though. Taurine will get in and since MSM is going to give some
>methionine and cysteine there may be a little better production of taurine
>but if there is, I doubt if it's that significant.
Fish and seafoods are some of the main sources for taurine, and high
intake of that mean lots of taurine in your body. Eating lots of other
antioxidants maybe protect cells against taurine loss due to
overshooting of the taurine release mechanism that are most possibly
triggered by several harmful attacks against cells that involve cell
membrane damages (leakage) or cell swelling or sorbitol formation from
glucose by oxidative stress induced aldose reductase (expressed
through activation of amongst other, NFkappa-B..
Quentin Grady
wrote:
>Quentin Grady <que...@paradise.net.nz> wrote in message
G'day G'day Martin,
Another antioxidant that is supposed to cross the brain barrier is
astaxanthin from salmon. I often wondered what colour salmon eaters
brains would eventually become. Would they literally be "in the
pink?"
Quentin Grady
G'day G'day Alf,
Martin produced a list showing DHA and EPA at the top for inducing
free radical damage in the liver. At least that is what I think it
was showing.
Could it be that those people who eat fish instead of taking fish oil
capsules basically avoid this risk because of their increased intake
of taurine?
Alf Christophersen
<que...@paradise.net.nz> wrote:
> Martin produced a list showing DHA and EPA at the top for inducing
>free radical damage in the liver. At least that is what I think it
>was showing.
>
>Could it be that those people who eat fish instead of taking fish oil
>capsules basically avoid this risk because of their increased intake
>of taurine?
Maybe, but fish also contain other natural antioxydants. Some of these
contain eg. trimethylamineoxide which is a very strong antioxidant.
Some fat fish contain it, especially capelin.
Martin Banschbach
> >From what I understand, the best brain protectant is taurine.
>
> G'day G'day Martin,
>
> Another antioxidant that is supposed to cross the brain barrier is
> astaxanthin from salmon. I often wondered what colour salmon eaters
> brains would eventually become. Would they literally be "in the
> pink?"
You can add creatine to the list of brain protectants. A 2002 paper
just showed that it's a very good antioxidant with levels in brain
as high or even higher than in muscle. It gets into mitochondria
and may actually be better than either acetyl-carnitine or lipoic
acid in protecting mitochondria. It has shown great promise
in experimental ALS and Hunginton's lab animals for protecting against
the damage that these two diseases cause to brain tissue. I think
that we are going to look at it in Alzheimer's patients.
Quentin Grady
Thanks Alf,
There doesn't appear to be an capelin locally, at least not by that
name at the fish mongers/wholesalers. It seems unlikely they are the
only fish to produce it in their fat.
Is there something else about capelin ... are they deep sea or
pelagic?
Its buy a clue time as I am keen to eat a range of sea foods with a
variety of benefits.
Some local fish eg snapper are high in selenium though NZ is generally
selenium deficient. Some shellfish are high in Vit 12 though other
aren't. The variations always puzzle me. The variance is also so
wide it challenges the idea that people can attribute physiological
changes to say eating fish three times a week, without specifying
which fish.
Quentin Grady
wrote:
>Quentin Grady <que...@paradise.net.nz> wrote in message
Should make body builders regular Einsteins in their old age. <grin>
DB
(...)
> Some local fish eg snapper are high in selenium though NZ is generally
> selenium deficient. Some shellfish are high in Vit 12 though other
> aren't. The variations always puzzle me. The variance is also so
> wide it challenges the idea that people can attribute physiological
> changes to say eating fish three times a week, without specifying
> which fish.
Good point. But I think that most benefits that a person actually notices
from fish is most likely due to the omega 3's and their effect on the brain.
Dave
Quentin Grady
Most people associate the effects of coffee with the compound
caffeine. However when trials were done on about a dozen symptom
attributed to the caffeine in coffee some 80% of them remained with
decaffeinated coffee. At the moment I have not reason to believe
anything other than that your reasons are based on short-circuit
logic.
The number of active ingredients associated with fish is large eg
trimethylglycine, taurine, squalene, alkoxyglycerols, phospholipids,
various sterols,wax esters, besides DHA, EPA
Alf Christophersen
<que...@paradise.net.nz> wrote:
> There doesn't appear to be an capelin locally, at least not by that
>name at the fish mongers/wholesalers. It seems unlikely they are the
>only fish to produce it in their fat.
>
>Is there something else about capelin ... are they deep sea or
>pelagic?
Fresh capelin is almost sold exclusively to Japan (as fresh capeline).
In Norway ti was used for fish meal (for industry) but now it is only
Iceland that do fish it. It is the smallest member of the salmon
famoly
>Some local fish eg snapper are high in selenium though NZ is generally
>selenium deficient. Some shellfish are high in Vit 12 though other
>aren't. The variations always puzzle me. The variance is also so
>wide it challenges the idea that people can attribute physiological
>changes to say eating fish three times a week, without specifying
>which fish.
To my knowledge cleaning of phosphor sources for arsenicals are the
main reason why you are deficient in selenium. The raw phosphate was
the main source for selenium in agriculture before purification of raw
phosphate started.
Many of the compounds mentioned are used as osmolytes to counteract
the effects of high salinity and content may thus vary depending on
salinity of the layer in water where they are catched. If low
salinity, osmolytes are skipped and content lowered, and vice versa.
How much this affecting composition in each fish, I do not know, but
guess it may explain some of the variations observed.
John De Hoog
Alf Christophersen wrote:
> Fresh capelin is almost sold exclusively to Japan (as fresh capeline).
> In Norway it was used for fish meal (for industry) but now it is only
> Iceland that do fish it. It is the smallest member of the salmon
> family
I looked this up and found that it is what we call *shishamo* (or karufuto
shishamo) in Japan. The most common way of eating it is by skewering several
dried ones and braising them over fire. It's a staple for breakfast at
Japanese inns and in many households.
The scientific name is Mallotus villosus.
--
John De Hoog
http://dehoog.org
John De Hoog
question, since "karafuto" is not in the Bering Sea but above Japan. I
wonder if they are really the same, despite sharing the same scientific
name.
> I looked this up and found that it is what we call *shishamo* (or karufuto
> shishamo) in Japan.
--
John De Hoog
really Spirinchus lanceolatus, although it is not uncommon for look-alike
fish to be sold here under the same general name.
Alf Christophersen
<que...@paradise.net.nz> wrote:
>The number of active ingredients associated with fish is large eg
>trimethylglycine, taurine, squalene, alkoxyglycerols, phospholipids,
>various sterols,wax esters, besides DHA, EPA
And also inositol, choline and many others.