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chris

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Nov 21, 1997, 3:00:00 AM11/21/97
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I've read this newsgroup on and off for many years now. I must say that
it certainly has gone downhill. Where are the real scientific issues?
Where are the novel ideas and thought provoking discussions?

Is this newsgroup really even about life extension anymore (real life
extension - not life extension in a bottle from GNC)? My apologies to
the few of you who post useful and informative things - you know who you
are.

It seems like this newsgroup has become a bunch of sheep jumping on the
new-supplement-of-the-day bandwagon. NEWSFLASH: Chances are Kombucha
tea isn't going to do much for you. Neither is Ginseng, Ma Huang, or
any other thing that sounds like a code word for parts of the male
anatomy.

Be a little scientific and have a little skepticism people. Don't you
think if any of these things really worked there would be
incontrovertible statistics on it? Some of these herbs have been in use
for THOUSANDS OF YEARS. Do you see any 300 year old Chinese people
running around?

Instead of worrying about supplements that have tenuous (and that's a
very generous word) claims of life extension (and could even end up
hurting you), you would be better off writing a letter to your
congressman to request more funding for the NIH, or volunteering to
particiapte in a research study, or picking up a book (for those
interested in theories of aging I would recommend Michael Rose's
Evolutionary Biology of Aging). The way real progress is going to be
made on these issues is through research - real research - not research
sponsored by people trying to sell you supplements.

John de Rivaz

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Nov 21, 1997, 3:00:00 AM11/21/97
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In article: <34753D...@ryley.com> chris <ch...@ryley.com> writes:
> Be a little scientific and have a little skepticism people. Don't you
> think if any of these things really worked there would be
> incontrovertible statistics on it? Some of these herbs have been in use
> for THOUSANDS OF YEARS. Do you see any 300 year old Chinese people
> running around?

no, but I think the problem is not with the products themselves, but the
fact that they are marketed over enthusiastically.

Arguably the best multi-vitamin in the world is called "Life Extension Mix",
(LEM) on the basis that it is formulated by The Life Extension Foundation
(LEF)

The LEF is aimed at doing the basic research you propose to extend maximum
lifespan, so its name is legitimate. And it is legitimate therefore to call
its flagship formulation after its actual name. However the formulation
is marketed in order to fund the research.

The LEM formulation does have a purpose, and that is to "square the curve".
Take it, and *statistically* you are less likely to suffer the dread
diseases of aging until you are older than those who do not take it. But you
will not live beyond 120 years as a result of taking it, and indeed *some
people* taking it will still perish in their seventies.

Professor Gordon McVie, the director general of the Cancer Research Campaign
is reported recently to have said that existing treatments for bowel cancer
in Britain fail in 63% of cases.

Nevertheless the treatment is offered and people get paid well for
providing it. Therefore if LEM and other supplements do not have success in
every case, it does not imply that they are worthless.

The test that needs to be done is to take ten thousand people and give half
LEM and half a placebo, and see the length and quality of their lives.
However this is neither practicable or of much use to those now living and
wondering whether to take LEM. They would be dead by the time the results
were known. The only thing that can be done is to extrapolate from shorter
term tests and make an informed chance.

--
*****************************************
Sincerely, * Longevity Report *
* http://www.longevb.demon.co.uk/lr.htm *
John de Rivaz * Fractal Report *
* http://www.longevb.demon.co.uk/fr.htm *
* Music I like - see homepage *
*****************************************
In the information age, sharing can increase world
wealth enormously, because giving information does
not decrease your information.
http://ourworld.compuserve.com/homepages/JohndeR
Fast loading, very few slow pictures

Rodney Reid

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Nov 22, 1997, 3:00:00 AM11/22/97
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Welcome to sci.life-extension Chris,

chris (ch...@ryley.com) wrote:
: I've read this newsgroup on and off for many years now. I must say that


: it certainly has gone downhill. Where are the real scientific issues?
: Where are the novel ideas and thought provoking discussions?

With the widespread use of dejanews and pubmed, a lot of the
repeated threads now go unrepeated. Thus more messages here are by
people who like to tell you about their newest product. Same all over
the net.

There is the longevity digest mailing list, for a higher
signal/noise ratio (although far less messages). It can be subscribed
to by sending email to list...@vm.ege.edu.tr with "subscribe
longevity-digest <your name>" in the body of the message.

bionet.molbio.ageing is another newsgroup with very sparse
messages, but worth checking every once in a while.

: Is this newsgroup really even about life extension anymore (real life


: extension - not life extension in a bottle from GNC)? My apologies to
: the few of you who post useful and informative things - you know who you
: are.

Here we get to the split between life extensionists here:

Do we poo-poo supplements and herbs, subscribing to the "calorie
restriction is the only thing that works in animal studies" school of
thought, hoping for unproven and farfetched remedies like telomere
modification, cloning, or (finally) cryonics down the road? Positive
thinking indeed!

Or (more practical I think) do we guard our own health today?
There are scientifically proven therapies against cancer and heart
disease, which to me means good levels of multiple types of antioxidants
(herbs, some foods, pills, minerals), aerobic-type exercise, low-cal
vegetable based diet, low stress (as possible), and my big detroit iron
with the seatbelt on when driving.

: It seems like this newsgroup has become a bunch of sheep jumping on the


: new-supplement-of-the-day bandwagon. NEWSFLASH: Chances are Kombucha
: tea isn't going to do much for you.

I believe you that Kombucha tea doesn't seem to be able to do
much. What about green tea (another HERB)? See:

Tohoku J Exp Med 1992 Apr;166(4):475-477
Mortality among female practitioners of Chanoyu (Japanese "tea-ceremony").
Authors: Sadakata S, Fukao A, Hisamichi S


: Neither is Ginseng, Ma Huang, or any other thing that sounds like a code


: word for parts of the male anatomy.

: Be a little scientific and have a little skepticism people.

Hmmm...scientific minds have written hundreds of articles showing benefits
of ginseng in rats and humans. You can take a view yourself by looking
them up on PubMed at http://www.ncbi.nlm.nih.gov/Entrez/medline.html

...Here is a recent one porporting age related changes in collagen
synthesis that are reversed with ginseng:

Biol Pharm Bull 1997 Mar;20(3):237-242
The preventive effect of ginseng with du-zhong leaf on protein metabolism
in aging.
Authors: Metori K, Furutsu M, Takahashi S


: Don't you think if any of these things really worked there would be


: incontrovertible statistics on it? Some of these herbs have been in use
: for THOUSANDS OF YEARS.

All of them have been in use for thousands of years. The science
you rely on to evaluate them has not been around this long, so it's taking
some time to get large amounts of decent scientific data on everything
that has historical life-extension claims.

: Do you see any 300 year old Chinese people running around?

No, but neither do I see any 300 year old telomere-modifying
scientists either. Nobody has been proven to have lived 300 years,
so why make this statement?


: Instead of worrying about supplements that have tenuous (and that's a


: very generous word) claims of life extension (and could even end up
: hurting you)

Prove your above statements with citations so we can see exactly
what you mean instead of this opinion. Everything and anything could
potentially hurt you. In which ways do you mean with what specific
supplements?

: you would be better off writing a letter to your


: congressman to request more funding for the NIH, or volunteering to
: particiapte in a research study, or picking up a book (for those
: interested in theories of aging I would recommend Michael Rose's
: Evolutionary Biology of Aging).

As far as picking up books, I would recommend Carol and Harris
Bernstein's book Aging, Sex, and DNA Repair (academic press 1991)
as another good book covering the basic issues of cellular aging, combined
with notes on their theories of sex as a hedge against continuous damage
on the genome.


: The way real progress is going to be


: made on these issues is through research - real research - not research
: sponsored by people trying to sell you supplements.

This is your opinion. I see benefits from reading all kinds of
legitimately done research. You imply by this last paragraph that
research on supplements is only done by people trying to sell me
something. This is not so (hell, many ARE done by the NIH!)


...Rodney


klin...@jlc.net

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Nov 23, 1997, 3:00:00 AM11/23/97
to

In article <34753D...@ryley.com>,

chris <ch...@ryley.com> wrote:
>
> It seems like this newsgroup has become a bunch of sheep jumping on the
> new-supplement-of-the-day bandwagon. NEWSFLASH: Chances are Kombucha
> tea isn't going to do much for you. Neither is Ginseng, Ma Huang, or

> any other thing that sounds like a code word for parts of the male
> anatomy.
>
> Be a little scientific and have a little skepticism people. Don't you

> think if any of these things really worked there would be
> incontrovertible statistics on it? Some of these herbs have been in use
> for THOUSANDS OF YEARS. Do you see any 300 year old Chinese people
> running around?
>

I don't know. A lot of Japanese seem to live a long time, some even
120 years. No one knows why. But the really exciting possibility is a
synergy between western science and herbal tradition, to find out the
pharmacological properties of herbs and how to use them more effectively
than in the past. The Herb Research Foundation supports real research on
herbs. Their website is www.herbs.org.

> Instead of worrying about supplements that have tenuous (and that's a
> very generous word) claims of life extension (and could even end up

> hurting you), you would be better off writing a letter to your


> congressman to request more funding for the NIH, or volunteering to
> particiapte in a research study, or picking up a book (for those
> interested in theories of aging I would recommend Michael Rose's

> Evolutionary Biology of Aging). The way real progress is going to be


> made on these issues is through research - real research - not research
> sponsored by people trying to sell you supplements.

I'm skeptical about more government funding - the war on cancer was a
disappointment. Tufts University has a lot of studies for people who wish
to participate.

Kate

-------------------==== Posted via Deja News ====-----------------------
http://www.dejanews.com/ Search, Read, Post to Usenet

Tom Matthews

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Nov 23, 1997, 3:00:00 AM11/23/97
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Rodney Reid wrote:

> Do we poo-poo supplements and herbs, subscribing to the "calorie
> restriction is the only thing that works in animal studies" school of
> thought, hoping for unproven and farfetched remedies like telomere
> modification, cloning, or (finally) cryonics down the road? Positive
> thinking indeed!

Hi Rodney,

I just want to make the point that one should not lump cryonics or even
perfected suspeneded animation (see http://www.prometheus-project.org/ )
with anti-aging or rejuvenation remedies. The purpose of the former is
not to "fix" the problem but simply to stabilize the patient and
transport him to a future time when the problem can be fixed. Thus,
cryonics and suspended animation have a quite different purpose than all
pro-health type activities and rely on those research activities
eventually bearing fruit.

Otherwise, a very good post.

--Tom
Tom Matthews

All personal comments do not represent the views of anyone from:
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-841-5433
A non-profit membership organization dedicated to the extension of the
healthy human lifespan through ground breaking research, innovative
ideas and practical methods.

james

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Nov 23, 1997, 3:00:00 AM11/23/97
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klin...@jlc.net wrote:

> I don't know. A lot of Japanese seem to live a long time, some even
> 120 years. No one knows why. But the really exciting possibility is a
> synergy between western science and herbal tradition, to find out the
> pharmacological properties of herbs and how to use them more effectively
> than in the past. The Herb Research Foundation supports real research on
> herbs. Their website is www.herbs.org.

This may be true. However, that in itself proves very little to
nothing. The Chinese also have a very different lifestyle than we do,
including diet and exercise habits. That probably contributes more to
mortality statistics than any other factor.
I wouldn't attribute much to herbs without large scale double-blind
placebo controlled studies. For the most part, we don't have these.

Brian Manning Delaney

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Nov 24, 1997, 3:00:00 AM11/24/97
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John de Rivaz wrote:
>
>In article: <34753D...@ryley.com>
>chris <ch...@ryley.com> writes:
>> Be a little scientific and have a little skepticism
>> people. Don't you think if any of these things really
>> worked there would be incontrovertible statistics on it?
>> Some of these herbs have been in use
>> for THOUSANDS OF YEARS. Do you see
>> any 300 year old Chinese people
>> running around?
>
> no, but I think the problem is not with the
> products themselves, but the fact that they are
> marketed over enthusiastically.

I don't think there's a huge difference there. A product, as
opposed to a chemical or substance, is, in part, that for
which it was produced, like the prevention of cancer, or the
retardation of aging. In other words, I don't think Chris is
calling for skepticism about vitamin C, for example. What
would that even look like? Vitamin C is vitamin C.
Skepticism is called for about the claims made for it, by
those who market it or not.


> Arguably thebest multi-vitamin in the world is


> called "Life Extension Mix", (LEM) on the basis
> that it is formulated by The Life Extension
> Foundation (LEF)

I agree strongly the LEM is probably the best
multi-vitamin/-mineral/-etc. formulation available, but that
doesn't say all that much, since so little research (close
to none) has been done on supplements taken in combination.

> ... The only thing that can be done is to


> extrapolate from shorter term tests and make an
> informed chance.

I think our decisions about these matters are far less
informed than many tend to think. John, do you know of any
tests of multivitamins, or tests of commonly used
supplements in combinations of more than three or four, that
look at health endpoints (as opposed to looking at
absorption, safety, etc.), health endpoints that would be of
interest to the typical person interested in life-extension
(cancer-prevention, etc.)?

Brian
--
Brian Manning Delaney
My email address is here:
http://xyz.uchicago.edu/users/bmdelane/email.htm
[Wrists: "Leave unambiguous typos."]
Note: All statements in this article are in jest; they
are not statements of fact.
"Mein Genie ist in meinen Nuestern." -Nietzsche.
** Please do not CC your Usenet articles to me. I'll find
them.

Brian Manning Delaney

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Nov 24, 1997, 3:00:00 AM11/24/97
to

Rodney Reid wrote:

> chris (ch...@ryley.com) wrote:
>
> Here we get to the split between life extensionists
> here:
>
> Do we poo-poo supplements and herbs, subscribing
> to the "calorie restriction is the only thing
> that works in animal studies" school of thought,
> hoping for unproven and farfetched remedies like
> telomere modification, cloning, or (finally)
> cryonics down the road? Positive thinking
> indeed!

Rodney, do you know any life-extensionist who fits the above
description? I know a few NON-life-extensionist research
gerontologists whose thought you've described, but a
life-extensionist is someone interested in living longer, so
whatever works is worth taking seriously. This will include,
above all, Calorie restriction, to be sure, but also, for
many people, cryonics; and, of less significance, but still
quite important, whatever interventions have evidence of
health benefits behind them: green tea, certain supplements
taken in isolation, seat belts, etc.

> Or (more practical I think) do we guard our own
> health today?

?! I think your division sounds more like researchers vs.
life-extensionists.

Ahh, wait, I see, it's the old maximum life span vs. average
life span split? (or are you getting at the me vs. Tom
Matthews diff.? If so, I think you've missed it entirely)
-->

> There are scientifically proven
> therapies against cancer and heart disease,
> which to me means good levels of multiple types
> of antioxidants (herbs, some foods, pills,

> minerals)....

Show me some scientific proof that _multiple_ types of
anti-oxidants (beyond the beta-carotene, Se, etc. studies --
I mean studies with the larger numbers of supplements I
think
you're advocating) are helpful.

> and my big detroit iron....

Extend your life, and others' death! Well, it depends on
where you live, of course.

> I believe you that Kombucha tea doesn't
> seem to be able to do much. What about green
> tea (another HERB)?

There is a lot of evidence that green tea has numerous
health benefits, but, of course, it has not been tested in
combo with much else typically consumed/practiced by
life-extensionsts.

Best,
Brian.

klin...@jlc.net

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Nov 25, 1997, 3:00:00 AM11/25/97
to

In article <3478FF...@ryley.com>,

Of course, the presence of 120 year old Japanese does not prove that
herbs work. But the absence of 300 year old Chinese does not prove that
they DON'T work, as Chris implied. I was responding to his comment about
why we don't see 300 year old Chinese.

Kate

John de Rivaz

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Nov 25, 1997, 3:00:00 AM11/25/97
to

I think that the Life Extension Foundation would like to run such tests, but
there are problems with time over this. One of the main problems I see is
that LEM is changed relatively frequently to reflect current findings, and a
contant formulation would be needed to be fed to test subjects (presumably
short lived animals that are a reasonable model for humans) over a period
large compared to the product life of a particular LEM formulation.

Nevertheless, I think it would be well worthwhile from a business point
of view for an insurance company or even a government health agancy to run
such tests using the changing LEM over a period of say ten years and see if
there are any economic advantages in sponsoring its subjects' use of the
product. If there is, then it is highly likey that the product is giving a
quality of life improvement as well. (one assumes that the product does not
shorten lifespan drastically - this may improve the economic poerformance of
insurance programs as well).

In article: <347A2CF3...@notarealaddr.ess> Brian Manning Delaney

<bmde...@notarealaddr.ess> writes:
> I agree strongly the LEM is probably the best
> multi-vitamin/-mineral/-etc. formulation available, but that
> doesn't say all that much, since so little research (close
> to none) has been done on supplements taken in combination.
>
> > ... The only thing that can be done is to
> > extrapolate from shorter term tests and make an
> > informed chance.
>
> I think our decisions about these matters are far less
> informed than many tend to think. John, do you know of any
> tests of multivitamins, or tests of commonly used
> supplements in combinations of more than three or four, that
> look at health endpoints (as opposed to looking at
> absorption, safety, etc.), health endpoints that would be of
> interest to the typical person interested in life-extension
> (cancer-prevention, etc.)?
>

Tom Matthews

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Nov 25, 1997, 3:00:00 AM11/25/97
to

Brian Manning Delaney wrote:

> I agree strongly the LEM is probably the best
> multi-vitamin/-mineral/-etc. formulation available, but that
> doesn't say all that much, since so little research (close
> to none) has been done on supplements taken in combination.

Unfortunately this is quite true and not likely to be soon rectified.
The major problem is the vast number of combinations of both specific
supplements and different dosages of them. It is hard enough to even get
experiments done with sufficiently wide dosage ranges of single
supplements. The result has been that many experiments have returned
negative or inconclusive results because they were testing the vitamin
or nutrient at a suboptimal (more often than superoptimal) dosage level.

However, others have returned negative results because they were testing
in isolation and certain other nutrients were later found to be needed
at the same time to show a beneficial effect (or even to prevent a
harmful effect).

With respect to combinations of supplements in general, there are
biochemical relationships between some nutrients which imply that one
should be increased when another is. Until research studies are done, I
believe that it is reasonable to use our biochemical knowledge of
nutrient use by the body (such as it is) to make decisions about the
amounts of various individually beneficial vitamin/mineral/nutrients to
combine together.

> I think our decisions about these matters are far less
> informed than many tend to think.

I would agree that no one's decisions about these matters are well based
on experiments showing health benefits of specific multi-nutrient
combinations since there have been few such experiments done. However, I
think that there are other ways of making "informed" decisions. Many
individual nutrients have not only been proven to be beneficial in
studies but their mechanisms of action have also been fairly well
elucidated. By combining all the mechanisms and studying the
interactions and the potential results, I believe that one can make a
reasoned decision that taking a certain combination of nutrients will be
beneficial to one's health.

I believe that is it far better to take a carefully considered chance on
extending one's lifespan and one's healthy vital years into an era of
potential anti-aging breakthroughs, than is it to simply accept a normal
lifespan with the enormous reduced quality of life during its last many
years caused by the debilitation of normal aging.

It is true that calorie restriction is another alternative that has more
solid evidence for life-extension in animal models than does the use of
supplements. However, CR is not proven in complex humans living in the
real world and for most people its application implies such a reduced
quality of life that their overall life-happiness is thereby reduced.
Furthermore, as someone pointed out on another thread, if CR was shown
to not only shift the mean and maximum lifespan higher but also to
narrow the standard deviation, then is would be more acceptable. Since
it does not do this, it is logical that one's concern in pursuing CR may
be that oneself may be the individual who will drop out of the study
early (by death) due to an individual biochemistry which is not
compatible with life-extension by CR.

IMO, while showing less extension of maximum lifespan than CR, most
nutrient studies that have shown an increase of mean lifespan have also
shown a better standard deviation reducing effect (only in animals
again, of course).

Finally BTW, with respect to several remarks about the possible status
of my liver on other threads, please be informed that my liver enzymes
have always tested in the low normal range. This may be partly because I
also take a number of things (eg NAC, silymarin) which are liver
strengthening.

Tom Matthews

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Nov 25, 1997, 3:00:00 AM11/25/97
to

Brian Manning Delaney wrote:

> Rodney Reid wrote:

> > There are scientifically proven
> > therapies against cancer and heart disease,
> > which to me means good levels of multiple types
> > of antioxidants (herbs, some foods, pills,

> > minerals)....
>
> Show me some scientific proof that _multiple_ types of
> anti-oxidants (beyond the beta-carotene, Se, etc. studies --
> I mean studies with the larger numbers of supplements I
> think you're advocating) are helpful.

If certain nutrients a,b,c have been proven to be beneficial together,
and certain others d,e,f,g have separately been shown also to be
beneficial in some other way, and furthermore there are no studies or
known biochemical mechanisms which suggest that taking a,b,c,d,e,f,g
together would be harmful, then I think the onus is the person making
the assertion of potentil harm to provide such evidence. Without any
such evidence to the contrary, I believe that it is very reasonable to
assume that one will get both the benefits from the a,b,c group *and*
the d,e,f,g group by taking a,b,c,d,e,f,g together.

Message has been deleted

Brian Manning Delaney

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Nov 26, 1997, 3:00:00 AM11/26/97
to

Tom Matthews wrote:
> Brian Manning Delaney wrote:
>
>> Rodney Reid wrote:
>>
>> > There are scientifically proven
>> > therapies against cancer and heart disease,
>> > which to me means good levels of multiple types
>> > of antioxidants (herbs, some foods, pills,
>> > minerals)....
>>
>> Show me some scientific proof that _multiple_ types of
>> anti-oxidants (beyond the beta-carotene, Se, etc. studies --
>> I mean studies with the larger numbers of supplements I
>> think you're advocating) are helpful.
>
> If certain nutrients a,b,c have been proven to
> be beneficial together, and certain others d,e,f,g
> have separately been shown also to be beneficial
> in some other way, and furthermore there are no
> studies or known biochemical mechanisms which
> suggest that taking a,b,c,d,e,f,g together would
> be harmful, then I think the onus is the person
> making the assertion of potentil harm to provide
> such evidence....

I agree. But what I was asking for was evidence not of harm,
but of benefit. Questioning the presence of benefit isn't
the same as asserting the presence of harm.

> ... Without any such evidence to the


> contrary, I believe that it is very reasonable
> to assume that one will get both the benefits
> from the a,b,c group *and* the d,e,f,g group by
> taking a,b,c,d,e,f,g together.

Rodney said, "There are scientifically proven therapies
against cancer and heart disease, [therefore it is good to
take] good levels of multiple types of antioxidants (herbs,
some foods, pills, minerals)." I'm saying that that (whole)
statement is wrong. The consequent may be correct, but it
doesn't follow from evidence based on studies of supplements
in isolation. Does that mean we wait for studies of
combinations of supplements before taking supplements in
combination? Not in my view. But the extent to which our
knowledge of "biochemical mechanisms" allows us to make
reasonable guesses, I contend, is more limited than you,
Tom, seem to think. We've been through that one before. The
relevant point here, though, with respect to the original
question, whether The Life Extension Foundation's multi is
the best one available, is simply that no strong claim about
the superiority of one multi over another can be made, since
all of them are untested, and supplement combining in
general involves so much guesswork.

One practical conclusion: let's support research into this
and related questions. There is a difference between aging
research and anti-aging research. Very little of the latter
has been done (aside from that which is the former construed
as _ultimately_ the latter...). What happens when people
take huge doses of many types of supplements? What happens
when people practice Calorie restriction and take
supplements? What happens when people change their
life-extension regimen many times over the course of their
life? We need to know the answers to these questions.

klin...@jlc.net

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Nov 26, 1997, 3:00:00 AM11/26/97
to

In article <347B76...@ryley.com>,

james <ja...@ryley.com> wrote:
>
> > Of course, the presence of 120 year old Japanese does not prove that
> > herbs work. But the absence of 300 year old Chinese does not prove that
> > they DON'T work, as Chris implied.
>
> I must disagree with this. That is EXACTLY what it means. If you have
> millions and millions of people that take these herbs on a regular
> basis, and (once you account for dietary, medical care, and other
> differences) you don't see a stastical increase in life span, that's
> about as close as you can come to showing that they don't work. Of
> course, you can't ever prove a negative, but that's pretty damning
> evidence.
>

What statistical analysis are you referring to? Chris didn't cite a
statistical study, he referred to 300 year life spans. No one claims
that much for even caloric restriction.

> Regardless, why should anyone be trying to prove they don't work?
> That's not the way science is generally conducted.

If they claim to have proved that herbs don't work, that's a claim
itself,and its appropriate for others to challenge it..

> Unless studies can
> prove that herbs/supplements DO work to extend lifespan, the assumption
> is that they do not.

The Herb Research Foundation does report plenty of studies supporting
benefits for herbs. They include in vitro studies, animal studies,
clinical studies and small scale double blind studies. At the current
time, there are very few large scale double blind studies, so its not
proof. But there is enough evidence to suggest that it is a fruitful
area for research in the future. As far as aging goes, my attitude is
maybe, lets wait and see

BTW, a large scale study of echinacea is starting up at Bastyr
University Research Institure( 206-365-3130 ),

Kate .

Tom Matthews

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Nov 28, 1997, 3:00:00 AM11/28/97
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Brian Manning Delaney wrote:
>
> Tom Matthews wrote:
> > Brian Manning Delaney wrote:
> >
> >> Rodney Reid wrote:
> >>
> >> > There are scientifically proven
> >> > therapies against cancer and heart disease,
> >> > which to me means good levels of multiple types
> >> > of antioxidants (herbs, some foods, pills,
> >> > minerals)....
> >>
> >> Show me some scientific proof that _multiple_ types of
> >> anti-oxidants (beyond the beta-carotene, Se, etc. studies --
> >> I mean studies with the larger numbers of supplements I
> >> think you're advocating) are helpful.
> >
> > If certain nutrients a,b,c have been proven to
> > be beneficial together, and certain others d,e,f,g
> > have separately been shown also to be beneficial
> > in some other way, and furthermore there are no
> > studies or known biochemical mechanisms which
> > suggest that taking a,b,c,d,e,f,g together would
> > be harmful, then I think the onus is the person
> > making the assertion of potentil harm to provide
> > such evidence....
>
> I agree. But what I was asking for was evidence not of harm,
> but of benefit. Questioning the presence of benefit isn't
> the same as asserting the presence of harm.

Brian, when I reply to a post, I don't reply just to the one thing that
was being said in that message but to the sum total of what that person
and others have been saying about the issue in many messages. My purpose
in posting is generally *never* to make points *against* or even
*related* to another poster, but instead to convey information, analysis
and other correct ways of thinking about the subject at hand.
Occasionally, I do get drawn into a "debate" as earlier between you and
I. If I do then I soon quit because, as I have stated, in my view such
"debates" are a juvenille and unproductive method of discussing
information and trying to understand it better.

In rereading the above quote, I realize that I actually meant to write
"I think the onus is on the person making the assertion of the lack of
multiple benefit, or even of potential harm to provide such evidence". I
think that I *did* imply that when I went on to state:

>> Without any
>> such evidence to the contrary, I believe that it is very reasonable to
>> assume that one will get both the benefits from the a,b,c group *and*
>> the d,e,f,g group by taking a,b,c,d,e,f,g together.

something which your "selective quoting" masked from view in your reply.
(Although, you did quote it further down.)

Several people on these lists (including you, I believe) have previously
stated that while they agreed that a certain few supplements had been
shown to be individually beneficial to health for certain limited
purposes, they believed that taking multiple supplements could very well
be harmful. In particular, some posters have stated the *I* was most
likely shortening my life, causing liver damage, etc. by doing so. I
believe those statements to be just so much garbage and I intend to make
that quite clear before I am through. My statement above about the
reasonableness of additive benefits from taking both sets of
supplements, each set of which are beneficial in some reasonably
independent way, is a step in that direction.

If you, specifically, have not made or implied such statements about me
then I apologize for any implication that my response was directed to
you personally. As I stated, you should look at all my posts as directed
toward issues and thinking, *not* directed towards specific people.

> > ... Without any such evidence to the
> > contrary, I believe that it is very reasonable
> > to assume that one will get both the benefits
> > from the a,b,c group *and* the d,e,f,g group by
> > taking a,b,c,d,e,f,g together.
>
> Rodney said, "There are scientifically proven therapies
> against cancer and heart disease, [therefore it is good to
> take] good levels of multiple types of antioxidants (herbs,
> some foods, pills, minerals)." I'm saying that that (whole)
> statement is wrong. The consequent may be correct, but it
> doesn't follow from evidence based on studies of supplements
> in isolation.

But, in fact, the synergy of several groupings of supplements *is* quite
well proven, even if not necessarily in particular disease prevention
studies. (See examples below.)

> Does that mean we wait for studies of
> combinations of supplements before taking supplements in
> combination? Not in my view.

Well this at least is positive. The most positive thing that I have
heard you say about supplements, I believe :)

> But the extent to which our
> knowledge of "biochemical mechanisms" allows us to make
> reasonable guesses, I contend, is more limited than you,
> Tom, seem to think. We've been through that one before. The
> relevant point here, though, with respect to the original
> question, whether The Life Extension Foundation's multi is
> the best one available, is simply that no strong claim about
> the superiority of one multi over another can be made, since
> all of them are untested, and supplement combining in
> general involves so much guesswork.

And I believe that there is a lot less guesswork than *you* think. It is
true that we cannot tell much different between too multi vitamin
formula which are generally of the same caliber (numbers and amounts of
ingredients). But difference between the value of Life Extension Mix and
some one-a-day complete RDA Walmart special is as between night and day.
And clear supporting documentation can be produced to show those
differences.

> One practical conclusion: let's support research into this
> and related questions. There is a difference between aging
> research and anti-aging research. Very little of the latter
> has been done (aside from that which is the former construed
> as _ultimately_ the latter...). What happens when people
> take huge doses of many types of supplements? What happens
> when people practice Calorie restriction and take
> supplements? What happens when people change their
> life-extension regimen many times over the course of their
> life? We need to know the answers to these questions.

You certainly haven't got any arguement from me about this. However, I
believe that practicalities of the research situation and the enormous
complexity of the task, and possibly the lack of proper (ie meaningful)
animal models for such a process are going to prevent this from
happening. So we must develop reasonable methods to do the best we can
without it. Also as I have always stressed, we are all aging and getting
more unhealthy and more debilitated every day, so we must make decisions
right now about what to do before all the evidence that we need is
available. All that I am trying to do is to show that some reasonably
sound decisions *can* already be made. I have *never* suggested that we
have all the evidence that we need.

I did a medline search for "vitamins synergy" and got the following
pertinent references:

J Biol Chem 1996 Aug 23;271(34):20650-20654
Competition for a unique response element mediates retinoic acid
inhibition of vitamin D3-stimulated transcription.

Lipids 1992 Jul;27(7):543-550
Ascorbate and phenolic antioxidant interactions in prevention of
liposomal oxidation.

Ann Chir 1990;44(7):512-520
[Improvement in the healing of colonic anastomoses by vitamin B5 and C
supplements. Experimental study in the rabbit].

Arthritis Rheum 1989 Jan;32(1):31-36
1,25-dihydroxyvitamin D3 potentiates the in vitro inhibitory effects of
cyclosporin A on T cells from rheumatoid arthritis patients.

Vopr Pitan 1987 Jan;1:39-43
[Effect of combined vitamin D and E deficiencies on calcium metabolism
and bone tissue of the rat].

Cancer Treat Rep 1986 Dec;70(12):1433-1435
In vivo synergy of vitamin K3 and methotrexate in tumor-bearing animals.

*And here an exceptionally interesting one which provides evidence that
exogenous enzymes do survive digestion *and interact synergistically
with endogenous enzymes.

Med Hypotheses 1994 Jun;42(6):355-362
On the synergistic effects of enzymes in food with enzymes in the human
body. A literature survey and analytical report.
Prochaska LJ, Piekutowski WV

Recently, a theory has been postulated that suggests that vital enzymes
in ingested food interact synergistically with enzymes within the human
body and more specifically with enzymes in the digestive tract.
Alterations in food enzymes induced by bulk processing including heating
and irradiation and also the addition of chemical additives have been
proposed to create a decrease in metabolic availability of nutrients,
with the long-term consequence being disease. This review of the medical
literature provides evidence that enzymes in food do in fact survive
during digestion and can indeed, add significantly to the nutritive
value of ingested foodstuffs. Examples of enzyme synergy in human
nutrition are provided in whole grains, milk and dairy products, beans
and seeds, and meat products. A bibliography on this interesting finding
is included as well as concluding remarks on enzyme synergy and its
putative interaction with cell metabolism. Finally, the interaction of
enzyme synergy with disease is discussed.

Under "multiple vitamins" I found:

Aging (Milano) 1997 Aug;9(4):241-257
Role of homocysteine in age-related vascular and non-vascular diseases.

which make a good case for supplementing B-12 and folate together.
And for women who want twins :), I turned up the following two:

Am J Med Genet 1997 Jul 11;71(1):93-96
Multivitamin supplementation and multiple births.

Orv Hetil 1996 Oct 27;137(43):2401-2405
[Peri-conceptional multivitamin administration may result in higher
frequency of twin pregnancies].

And here's another excellent case for B-12 and folate:

Mutat Res 1997 Jun 9;377(1):125-135
'Spontaneous' genetic damage in man: evaluation of interindividual
variability, relationship among markers of damage, and influence of
nutritional status.

and B6 in addition to B-12 and folate

Circulation 1996 Dec 1;94(11):2743-2748
Hyperhomocysteinemia confers an independent increased risk of
atherosclerosis in end-stage renal disease and is closely linked to
plasma folate and pyridoxine concentrations.

And here are several positive results for supplementation with multiple
vitamins:

Arch Intern Med 1997 Jan 27;157(2):169-177
Nutritional management of cardiovascular risk factors. A randomized
clinical trial.

Nutr Cancer 1997;27(1):41-47
Evaluation of multiple micronutrient supplementation in the management
of oral submucous fibrosis in Karachi, Pakistan.

Am J Epidemiol 1996 Apr 1;143(7):658-664
Lowered risks of hypertension and cerebrovascular disease after
vitamin/mineral supplementation: the Linxian Nutrition Intervention
Trial.

The next one I quote in whole because of its strong conclusion:

Nutr Cancer 1996;26(1):11-19
Effect of individual and multiple antioxidant vitamins on growth and
morphology of human nontumorigenic and tumorigenic parotid acinar cells
in culture.
Prasad KN, Kumar R

The effects of individual and multiple antioxidant vitamins on growth
and morphology of human nontumorigenic (2HPC8) and tumorigenic (2HP1G)
parotid acinar cells in culture have not been investigated. Our study
showed that tumorigenic acinar cells were more sensitive than
nontumorigenic acinar cells to individual vitamins such as vitamin C,
beta-carotene (BC), d-alpha-tocopheryl succinate (alpha-TS), and
retinoic acid (RA) and a mixture of four vitamins (vitamin C, BC,
alpha-TS, and RA). The effect of individual vitamins on tumorigenic
acinar cells depended on the dose and the type of vitamins. Vitamin C at
a low concentration stimulated growth, but at a high concentration it
inhibited growth. BC was most effective in reducing growth, and it alone
caused extensive morphological changes in tumorigenic acinar cells. A
mixture of four vitamins at
appropriate doses was more effective than a mixture of two or three
vitamins at the same doses in reducing the growth of tumorigenic acinar
cells. The extent of growth inhibition depended on the dose and the type
of vitamins.
***Our results suggest that the use of multiple antioxidant ***
***vitamins is essential for a maximal reduction in cancer ***
***incidence among a high-risk population. The use of one or***
*** two vitamins may be ineffective or even harmful. ***

Ann Epidemiol 1996 Jan;6(1):41-46
Food and nutrient intake and risk of cataract.
Tavani A, Negri E, La Vecchia C

The relationship between cataract extraction and diet was considered in
a case-control study conducted in northern Italy. A total of 207
patients who had cataract extraction and 706 control subjects....
Thus, this study indicates that diet plays a considerable role in the
risk of cataract extraction in this Italian population, with a
protective action played by some vegetables, fruit, calcium, folic
acid,and vitamin E, and an increased risk associated with elevated salt
and fat intake.

Am J Clin Nutr 1995 Dec;62(6 Suppl):1477S-1482S
Possible immunologic involvement of antioxidants in cancer prevention.

*The next one found that carotenoids, C and E produced more melanin
which would be protective against skin cancer.

Biochem Mol Biol Int 1997 Aug;42(5):1023-1033
Evidence for antioxidant nutrients-induced pigmentation in skin: results
of a clinical trial.

J Trauma 1996 Jan;40(1):103-109
Copper, selenium, and zinc status and balances after major trauma.
... Considering the importance of Se and Zn in free radical scavenging,
anabolism, and immunity, current recommendations for TE supplements in
severely traumatized patients ought to be revised.

J Urol 1994 Jan;151(1):21-26
Megadose vitamins in bladder cancer: a double-blind clinical trial.

...A total of 65 patients with biopsy confirmed transitional cell
carcinoma of the bladder enrolled in a randomized comparison of ...
therapy with multiple vitamins in the recommended daily allowance (RDA)
versus RDA multivitamins plus 40,000 units vitamin A, 100 mg. vitamin
B6, 2,000 mg. vitamin C, 400 units vitamin E and 90 mg. zinc. ... The
5-year estimates of tumor recurrence are 91% in the RDA arm and 41% in
the megadose arm (p = 0.0014, Mantel-Cox). Overall recurrence was 24 of
30 patients (80%) in the RDA arm and 14 of 35 (40%) in the high dose arm
(p = 0.0011, 2-tailed Fisher's exact test).
*** Megadose vitamins A, B6, C and E plus zinc decrease bladder***
*** tumor recurrence in patients receiving BCG immunotherapy. ***

Rheum Dis Clin North Am 1991 May;17(2):203-212
Nutrients and immune responses.

A wide spectrum of nutritional deficiencies, ranging from trace elements
to protein, can impair normal immunologic functions. Repletion of
deficient nutrients generally will restore the immune response. ...
Adequate nutrition is essential for maintaining the integrity of the
immune system.

Biochem Soc Trans 1990 Dec;18(6):1041-1045
The antioxidant hypothesis of cardiovascular disease: epidemiology and
mechanisms.
... This finding is consistent with the hypothesis of the prevention of
arteriosclerosis by antioxidant protection against peroxidative
lipoprotein modification, but does not exclude additional effects of
antioxidant vitamins, e.g. on the cellular or immunological level.

Tom Matthews

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Nov 28, 1997, 3:00:00 AM11/28/97
to

Just to let you know that I was far from finished with that message. I
wasn't intending to send yet, but I guess my tired brain made me hit
send early :-) So will take the hint from my body and quit for now.

Brian Manning Delaney

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Nov 28, 1997, 3:00:00 AM11/28/97
to

I think this is ultimately incoherent, but that's a
philosophical question, which I'm content not to pursue. In
any event, your view is noted.

> Several people on these lists (including you, I
> believe) have previously stated that while they
> agreed that a certain few supplements had been
> shown to be individually beneficial to health
> for certain limited purposes, they believed that
> taking multiple supplements could very well be
> harmful.

My main point was that evidence of synergy was minimal,
though I added that it's conceivable that mega-doses of
multiple supplements is harmful. I meant to suggest that
it's a fairly small possibility.

> In particular, some posters have stated
> the *I* was most likely shortening my life,
> causing liver damage, etc. by doing so.

For the record, I think it's very unlikely that you're
shortening the life you would live with no supplementation
at all, and, further, believe that the risks aren't
primarily about liver damage. (Since your relation to you
interlocutors is unusually "diffuse", let us say, note that
I'm just stating this for the record, and not saying you're
attributing such a view to me, or that you [think you]
care.)

>> Rodney said, "There are scientifically proven therapies
>> against cancer and heart disease, [therefore it is good to
>> take] good levels of multiple types of antioxidants (herbs,
>> some foods, pills, minerals)." I'm saying that that (whole)
>> statement is wrong. The consequent may be correct, but it
>> doesn't follow from evidence based on studies of supplements
>> in isolation.
>
> But, in fact, the synergy of several groupings
> of supplements *is* quite well proven, even if
> not necessarily in particular disease prevention
> studies. (See examples below.)

My point was about something else. There is a common
assumption among pop life-extensionists that individual
studies of isolated supplements ALONE allow one to conclude
that these supplements taken in combination will have an
effect that is the sum of the individual effects (or that is
even more than the sum). This is false. But that doesn't
mean that supplements in combination aren't additive in
their effects, as I tried to make clear. The point is that
we need studies of the supplements in combination.

You've pointed to some studies that look at pairs of
high-dose vitamins, and in a few cases, more than two or
three vitamins (but not in mega-doses). This is a beginning,
but doesn't bear more than minimally on the question of 1)
mega-doses of 2) dozens of different supplements. (One
exception, the A, B6, C and E plus zinc mega-dose study. But
this was a study of people who HAVE cancer, AND are
receiving BCG immunotherapy. Why should the study have
anything to do with the vast majority of people taking
multi- mega-supplements?)

>> Does that mean we wait for studies of
>> combinations of supplements before taking supplements in
>> combination? Not in my view.
>
> Well this at least is positive. The most
> positive thing that I have heard you say about
> supplements, I believe :)

Tom, you haven't been in this newsgroup for very long. I was
in it at the beginning (I created it). If you'd been around
for the last four or five years, you would have observed
some _very_ positive statements about supplements from me.
Hard to believe, I'm sure :) but true. I just think blanket,
or quasi-blanket statements about supplements have little
merit, as things stand now.


[....]

> But difference between the value of Life
> Extension Mix and some one-a-day complete RDA
> Walmart special is as between night and day. And
> clear supporting documentation can be produced
> to show those differences.

At this point, one way we can try to advance this discussion
is with more specifics. Something I would love to see -- as
would most people reading this group, if the email pulse is
representative -- is a detailed justification of The Life
Extension Foundation's Life-Extension Mix (TM): "clear
supporting documentation." This would be very helpful.

There are a lot of ingredients in LEM, but for the
well-known ones, I wouldn't expect citations of studies. I
mean a justification for LEM geared towards people who know
the life-ext. literature well. We know vitamin E reduces
risk of heart disease, probably cancer, possibly
Alzheimer's, etc., etc. I just mean: 1) justification for
the less well-known nutrients, and 2) justification of the
doses, and 3) justification for the claim of efficacy of the
substances in combination.

Please don't take this request as agonistic in any way. I'm
authentically curious, and think it would help advance this
discussion tremendously to have something in writing about
how The Life Extension Foundation came to the decisions they
did about the (current) formulation for the LEM. Maybe some
of this is already in writing, in the form of notes at
meetings, missives, etc.


>> One practical conclusion: let's support research into this
>> and related questions.

[....]

> You certainly haven't got any arguement from me
> about this. However, I believe that
> practicalities of the research situation and the

> enormous complexity of the task...

I don't know what you mean here. Give lab animals or people
LEM and follow them for a few years. What's the prob with
that?

> ...and possibly


> the lack of proper (ie meaningful) animal models
> for such a process are going to prevent this
> from happening.

How so? You continually cite studies using standard lab
rodents to support other claims you've made. Is it just that
things like DHEA (is this in the Life-Extension Mix?) can't
be tested in rodents, since they don't produce it naturally?
That's true, but for almost all substances in LEM, this
isn't true.

> Also as I have always stressed, we are all aging and
> getting more unhealthy and more debilitated
> every day, so we must make decisions right now
> about what to do before all the evidence that we
> need is available.

Of course.

I await the rationale for the Life Extension Mix.

-Brian.

Rodney Reid

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Nov 28, 1997, 3:00:00 AM11/28/97
to

James, are there any large scale double blind placebo controlled studies
for any supposed life-extension techniques proposed here? Not that I know
of, CR or chemical/herbal. Why not?


james (ja...@ryley.com) wrote:

: I wouldn't attribute much to herbs without large scale double-blind

Rodney Reid

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Nov 28, 1997, 3:00:00 AM11/28/97
to

Brian Manning Delaney (bmde...@notarealaddr.ess) wrote:

: life-extensionist is someone interested in living longer, so


: whatever works is worth taking seriously. This will include,
: above all, Calorie restriction, to be sure, but also, for
: many people, cryonics; and, of less significance, but still
: quite important, whatever interventions have evidence of
: health benefits behind them: green tea, certain supplements
: taken in isolation, seat belts, etc.

Brian,

I do not believe cryonics is a life-extension technique... I
certainly wouldn't place it above prevention of debilitating disease with
researched herbs/supplements, or taking measures to avoid accidental
death.

Calorie Restriction seems to work in animals, and possibly in
humans too.... I am especially interested in Roy Walford's current work
relating CR to mammalian hibernation.


: > There are scientifically proven


: > therapies against cancer and heart disease,
: > which to me means good levels of multiple types
: > of antioxidants (herbs, some foods, pills,

: > minerals)....

: Show me some scientific proof that _multiple_ types of
: anti-oxidants (beyond the beta-carotene, Se, etc. studies --
: I mean studies with the larger numbers of supplements I
: think you're advocating) are helpful.

You've already had this debate with Tom Matthews in the past,
which I read with interest. His recent posts to this thread are
more justice than I could do to the subject.

: > and my big detroit iron....

: Extend your life, and others' death! Well, it depends on
: where you live, of course.

Explain this to me.

: There is a lot of evidence that green tea has numerous


: health benefits, but, of course, it has not been tested in
: combo with much else typically consumed/practiced by
: life-extensionsts.

Of course. Green tea hasn't been tested for efficacy with, say
vegetarians vs. non-vegetarians either, or people on high-calorie vs.
low-calorie diets. It does seem to confer more health benefits than
other popular drinks though, which is reason enough to me to reach
for my tea jar than a soda or coffee.


...Rodney

Brian Manning Delaney

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Nov 28, 1997, 3:00:00 AM11/28/97
to

Rodney Reid wrote:

> I do not believe cryonics is a life-extension
> technique... I certainly wouldn't place it
> above prevention of debilitating disease with
> researched herbs/supplements, or taking measures
> to avoid accidental death.

Well, this is a difficult question. We'd have to have good
estimates of the likelihood of success of cryonics, and the
expected number of added years with cryonics' success. The
former is probably very low, but the latter is probably
very, very high. Who knows. But, yes, I shouldn't so
squarely put it above wearing seatbelts and such.



> Calorie Restriction seems to work in animals,
> and possibly in humans too.... I am especially
> interested in Roy Walford's current work
> relating CR to mammalian hibernation.

Yes, this is fascinating research. It may be that induced
hibernation may achieve something like what Paul Wakfer is
trying to achieve with The Prometheus Project
(http://www.prometheus-project.org/), though on a smaller
scale.

>: > and my big detroit iron....
>
>: Extend your life, and others' death! Well, it depends on
>: where you live, of course.

> Explain this to me.

Sorry, I was being flippant. I'd just driven across the U.S.
in my small Toyota, and was feeling annoyed at the people
bearing down on me in large cars, seemingly concerned only
with their own safety. Everyone driving big cars is better
than everyone driving small cars, from a very short-term
perspective. Maybe that's what you were thinking of.

Best,

Tom Matthews

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Nov 29, 1997, 3:00:00 AM11/29/97
to

Brian,

Let me state right off, that I appreciate your tactful reply and I will
in turn attempt to be cordial and not say thinks in a way which might
offend you.

Brian Manning Delaney wrote:

> Tom Matthews wrote:

> > Brian, when I reply to a post, I don't reply
> > just to the one thing that was being said in
> > that message but to the sum total of what that
> > person and others have been saying about the
> > issue in many messages. My purpose in posting is
> > generally *never* to make points *against* or
> > even *related* to another poster, but instead to
> > convey information, analysis and other correct
> > ways of thinking about the subject at hand.

> I think this is ultimately incoherent, but that's a
> philosophical question, which I'm content not to pursue. In
> any event, your view is noted.

Thanks for your tact here. But I believe it is not a philosophical
question but more of a question of fidelity and comprehensibility of
information. I don't think that it will necessarily be incoherent if one
makes it clear this is what one is doing and states up front what issues
and viewpoints one is addressing. Perhaps I have been negligent in doing
so. I will try to be more careful about this in future.

> > Several people on these lists (including you, I
> > believe) have previously stated that while they
> > agreed that a certain few supplements had been
> > shown to be individually beneficial to health
> > for certain limited purposes, they believed that
> > taking multiple supplements could very well be
> > harmful.
>
> My main point was that evidence of synergy was minimal,

There are a few combinations where such evidence is quite good. Off the
top of my head, E with Selenium and C, E, Beta-carotene, and lipoic
acid (antioxidant replenishment of each other), and folate and B-12 (and
ascorbate in turn protects folate from oxidative destruction) come to
mind. I will try to dig up more.

> though I added that it's conceivable that mega-doses of
> multiple supplements is harmful. I meant to suggest that
> it's a fairly small possibility.

Actually, I admit that this is a distinct possibility and has even been
the case (I found a couple of papers on this). However, in every case I
have looked at where this happened, it was because of a clear overdose
of one or more of the vitamins/nutrients (possibly only for the
particular individual at hand, or some other nutritionally well known
need for an increase of one nutrient when more of another zinc impairs
copper retention, etc. I my view, all that has ever been shown, is that
when mega-dosing (defined as taking
levels many times more than the RDA), one must know what one is doing
and be careful to "balance" things.
But then as always "a little bit of knowledge is a dangerous thing".
Nothing new about that!

> > In particular, some posters have stated
> > the *I* was most likely shortening my life,
> > causing liver damage, etc. by doing so.
>
> For the record, I think it's very unlikely that you're
> shortening the life you would live with no supplementation
> at all, and, further, believe that the risks aren't
> primarily about liver damage.

But I remember you appearing to agree with Mark Thorson on a
sci.med.nutrition thread concerning the potiential state of my liver.



> (Since your relation to you
> interlocutors is unusually "diffuse", let us say, note that
> I'm just stating this for the record, and not saying you're
> attributing such a view to me, or that you [think you]
> care.)

Point accepted and understood.

> >> Rodney said, "There are scientifically proven therapies
> >> against cancer and heart disease, [therefore it is good to
> >> take] good levels of multiple types of antioxidants (herbs,
> >> some foods, pills, minerals)." I'm saying that that (whole)
> >> statement is wrong. The consequent may be correct, but it
> >> doesn't follow from evidence based on studies of supplements
> >> in isolation.
> >
> > But, in fact, the synergy of several groupings
> > of supplements *is* quite well proven, even if
> > not necessarily in particular disease prevention
> > studies. (See examples below.)
>
> My point was about something else. There is a common
> assumption among pop life-extensionists that individual
> studies of isolated supplements ALONE allow one to conclude
> that these supplements taken in combination will have an
> effect that is the sum of the individual effects (or that is
> even more than the sum). This is false.

Although your next sentence implies it. You weren't clear here that your
"this is false" statement only applies to the synergy part.

> But that doesn't
> mean that supplements in combination aren't additive in
> their effects, as I tried to make clear.

In support of this statement, I will even make a stronger one. If the
effects of the individual nutrients are not by quite independent
mechanisms of action, the effects will *not* be additive and there may
be hardly any benefit at all from taking one if several others are
already being taken.

> The point is that
> we need studies of the supplements in combination.
>
> You've pointed to some studies that look at pairs of
> high-dose vitamins, and in a few cases, more than two or
> three vitamins (but not in mega-doses). This is a beginning,
> but doesn't bear more than minimally on the question of 1)
> mega-doses of 2) dozens of different supplements. (One
> exception, the A, B6, C and E plus zinc mega-dose study. But
> this was a study of people who HAVE cancer, AND are
> receiving BCG immunotherapy. Why should the study have
> anything to do with the vast majority of people taking
> multi- mega-supplements?)

This is a reasonable question and, in fact, in most of the studies which
I cited and for others which can be found, the nutrients, multiple or
not, were being taken in an attempt to ameliorate some disease process.
My view of this is that any combination of vitamins which does
ameliorate some disease process is quite likely (not necessarily, but
reasonably likely) to be beneficial to those which do not have that
disease process either to prevent them from getting that specific
disease or for other general health purposes. I find it hard to imagine
any mechanisms of action which would work against this. The only one
which I can think of at the moment which might have to do with
autoimmune conditions where it would be unwise to take general immune
system enhancers, although some specific immune system enhancers might
be beneficial. So again while there are special cases where some
specific type of supplementation may not be beneficial these are clear
and well known.

> > But the difference between the value of Life


> > Extension Mix and some one-a-day complete RDA
> > Walmart special is as between night and day. And
> > clear supporting documentation can be produced
> > to show those differences.
>
> At this point, one way we can try to advance this discussion
> is with more specifics. Something I would love to see -- as
> would most people reading this group, if the email pulse is
> representative -- is a detailed justification of The Life
> Extension Foundation's Life-Extension Mix (TM): "clear
> supporting documentation." This would be very helpful.

A bit of this was done in the sci.med.nutrition and
misc.health.alternative ngs several months ago when I and others were
involved with a comparison table of several major mega-vitamin mixes.
The decisions made with respect to LE Mix have been evolving over the
years (it appears to change formula every couple of years) and I expect
several people have had a hand in those decisions. Certainly, I have
not. I believe that the main decision maker has been Bill Faloon. I will
proceed on this request be doing two things. First, I will query LEF
about who and how the decisions are made. And secondly I will start
producing abstracts supporting ingredients, ratios, etc in the mix. This
will be a long but worthwhile and interesting exercise. Who knows, the
result may be a still superior mix which we will all understand the
reasons for.

> There are a lot of ingredients in LEM, but for the
> well-known ones, I wouldn't expect citations of studies. I
> mean a justification for LEM geared towards people who know
> the life-ext. literature well. We know vitamin E reduces
> risk of heart disease, probably cancer, possibly
> Alzheimer's, etc., etc. I just mean: 1) justification for
> the less well-known nutrients, and 2) justification of the
> doses,

Yes, we can approach it that way.

> and 3) justification for the claim of efficacy of the
> substances in combination.

I don't understand you again here. You know that we will "not" find any
such studies in general. That best that we can hope to do is to find
studies that each nutrient has a key biochemical role which can be
enhanced by supplementing it and that the biochemical mechanisms of two
nutrients are sufficiently independent that it is reasonable that the
effects will be nearly additive. Is not this sufficient to justify "the
claim of efficacy of the substances in combination"?



> Please don't take this request as agonistic in any way. I'm
> authentically curious, and think it would help advance this
> discussion tremendously to have something in writing about
> how The Life Extension Foundation came to the decisions they
> did about the (current) formulation for the LEM. Maybe some
> of this is already in writing, in the form of notes at
> meetings, missives, etc.

I will ask. (In fact, I will forward part of your message to Bill Faloon
and Saul Kent.)



> >> One practical conclusion: let's support research into this
> >> and related questions.
> [....]
>
> > You certainly haven't got any arguement from me
> > about this. However, I believe that
> > practicalities of the research situation and the
> > enormous complexity of the task...
>
> I don't know what you mean here. Give lab animals or people
> LEM and follow them for a few years. What's the prob with
> that?

Of course, this would be possible, but only LEF would be willing to
finance it. I meant general studies of general multiple combinations of
vitamins by disinterested scientists.

> > ...and possibly
> > the lack of proper (ie meaningful) animal models
> > for such a process are going to prevent this
> > from happening.
>
> How so? You continually cite studies using standard lab
> rodents to support other claims you've made.

Actually, I believe that you are mistaken. I don't do that very much. I
generally look only for human studies. Only when I can't find any do I
look at animal studies for some evidence. That one of the problems that
I have with the studies about CR. Animal studies for CR certainly give
better life-extension results than do animal or human studies for
supplementation. However, if one restricts oneself to only human
studies, there is far more health beneficial evidence for
supplementation that there is for CR. Animal studies are extremely
important for assessing things and supplying indications for humans, but
humans are much more complex and live in a much more complex
environment. I, therefore, generally require human studies before I am
really "sold" on something, unless the biochemical mechanisms are very
clear.

> Is it just that
> things like DHEA (is this in the Life-Extension Mix?)

No, it is not. Neither is pregnenolone or melatonin, etc. If you do a
Dejanews search you will find the threads which I mentioned above where
LE mix was discussed and all ingredients and their amounts were posted.
I can dig it up and re post if you like. However, I think they are now
all on-line at http://www.lef.org



> can't
> be tested in rodents, since they don't produce it naturally?
> That's true, but for almost all substances in LEM, this
> isn't true.

As stated above, to me, rodent studies are only the beginning of the
evidential process.

> > Also as I have always stressed, we are all aging and
> > getting more unhealthy and more debilitated
> > every day, so we must make decisions right now
> > about what to do before all the evidence that we
> > need is available.
>
> Of course.
>
> I await the rationale for the Life Extension Mix.

It's going to take some time.

Tom Matthews

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Nov 29, 1997, 3:00:00 AM11/29/97
to

Rodney Reid wrote:
>
> Brian Manning Delaney (bmde...@notarealaddr.ess) wrote:
>
> : life-extensionist is someone interested in living longer, so
> : whatever works is worth taking seriously. This will include,
> : above all, Calorie restriction, to be sure, but also, for
> : many people, cryonics; and, of less significance, but still
> : quite important, whatever interventions have evidence of
> : health benefits behind them: green tea, certain supplements
> : taken in isolation, seat belts, etc.
>
> Brian,
>
> I do not believe cryonics is a life-extension technique... I
> certainly wouldn't place it above prevention of debilitating disease with
> researched herbs/supplements, or taking measures to avoid accidental
> death.

Technically, Rodney is correct here. I, too, was going to object to
Brian's
relating and comparing of cryonics to other life extension methods.
I believe that some cyronicists themselves make this mistake too much
and a
few of them give no care or thought to extending their current life
"cycle".
Viewed correctly cryonics or even perfected suspended animation (as with
the
Prometheus Project) is nothing more than a preservation and
stabilization
method to transport you to a time when anti-aging, rejuvenation, and
disease
curing breakthroughs will have been achieved. In its present very poor
state
(highly damaging cryopreservations and small unstable societies),
cryonics
cannot be relied upon to give you a reasonable chance of being recovered
and
repaired in the future (even if your memories survive the process which
no
one can say for sure at this time).

Therefore, even if one has enrolled for cryonics, and I certainly urge
anyone
who is seriously interested in saving his life, to buy life insurance
funding
and to do so (it does not work to think that you can wait until you
become
terminal), it is also enormously important to do everything that you can
to prolong your current healthy lifespan.

Even when/if we achieve perfected suspended animation, is will still not
be
100% successful even as current major operations at the best hospitals
are not.
As cryonicists say, only half jokingly. "being cryopreserved is the
second
worst thing that can happen to you". The worst being dying and *not*
being
cryopreserved ie. being *obliterated* by burning or the total decay of
burial.
As it is practiced today, cryonics is very damaging even though, if you
are
teriminal, it is the only hope that you have. By keeping yourself as
healthy
as possible and your aging rate as low as possible, you benefit in two
ways:

1. The longer you stay alive the larger and more stable will cryonics
become
and the less damaging will be their methods. If the Prometheus Project
is
successful there will be virtually no damage at all. So if you can live
another 20 years (and maybe help it become a success by then or sooner),
you
may be able to be preserved, probably before the agonal damage of a
terminal
disease process, in a manner which will give a *very* high probability
of
successful restoration however many years later is required before your
terminal "problems" are fixable.

2. If anti-aging research progresses at the rate that some people think
it
will (I wish I could be that optimistic), then within 50 years or so (if
you
can make it that far) we will be able to stop aging for most people and
even
to rejuvenate them. In this case, you will be able to stave off needing
cryonics (or perfected suspended animation) until and unless some other
terminal condition is about to "get" you.

Rodney Reid

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Nov 29, 1997, 3:00:00 AM11/29/97
to

Brian Manning Delaney (bmde...@notarealaddr.ess) wrote:

: Yes, this is fascinating research. It may be that induced


: hibernation may achieve something like what Paul Wakfer is
: trying to achieve with The Prometheus Project
: (http://www.prometheus-project.org/), though on a smaller
: scale.

I will check it out.

: >: > and my big detroit iron....


: >
: >: Extend your life, and others' death! Well, it depends on
: >: where you live, of course.

: > Explain this to me.

: Sorry, I was being flippant. I'd just driven across the U.S.
: in my small Toyota, and was feeling annoyed at the people
: bearing down on me in large cars, seemingly concerned only
: with their own safety. Everyone driving big cars is better
: than everyone driving small cars, from a very short-term
: perspective. Maybe that's what you were thinking of.

Very well then. I had a chevette until 4 months ago, so I know
the joy of being surrounded by cars larger than me. Unfortunately, now
that my work is farther away, I seem to take a route with a lot of semi
trailers (which would still make mincemeat of my car, but even moreso).
Can't win.

...Rodney


Brian Manning Delaney

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Nov 29, 1997, 3:00:00 AM11/29/97
to

Tom Matthews wrote:

[....]


>> > In particular, some posters have stated
>> > the *I* was most likely shortening my life,
>> > causing liver damage, etc. by doing so.
>>
>> For the record, I think it's very unlikely that you're
>> shortening the life you would live with no supplementation
>> at all, and, further, believe that the risks aren't
>> primarily about liver damage.
>
> But I remember you appearing to agree with Mark
> Thorson on a sci.med.nutrition thread concerning
> the potiential state of my liver.

Hmm.. I don't think so. If I did so, I retract it (not that
I think your liver is in good shape; rather, I wouldn't
argue it's in bad shape).

I, Brian, wrote:
>> The point is that
>> we need studies of the supplements in combination.

Let me add what I normally add here: we need studies of the
supplements in combination, OR a radically improved
knowledge of human physiology, improved in such a way that
we can deduce what effect supplements in combination would
have. The studies are much, much easier to pull together
quickly, that's why I usually stress the direct empirical
evidence approach to questions like these.

>> You've pointed to some studies that look at pairs of
>> high-dose vitamins, and in a few cases, more than two or
>> three vitamins (but not in mega-doses). This is a beginning,
>> but doesn't bear more than minimally on the question of 1)
>> mega-doses of 2) dozens of different supplements. (One
>> exception, the A, B6, C and E plus zinc mega-dose study. But
>> this was a study of people who HAVE cancer, AND are
>> receiving BCG immunotherapy. Why should the study have
>> anything to do with the vast majority of people taking
>> multi- mega-supplements?)
>
> This is a reasonable question and, in fact, in
> most of the studies which I cited and for others
> which can be found, the nutrients, multiple or
> not, were being taken in an attempt to
> ameliorate some disease process. My view of this
> is that any combination of vitamins which does
> ameliorate some disease process is quite likely (not
> necessarily, but reasonably likely) to be
> beneficial to those which do not have that
> disease process either to prevent them from
> getting that specific disease or for other
> general health purposes.

I disagree very strongly with this view, especially if you
expand it to include more than just vitamins. One obvious
example where this is false is where a disease is caused by
a deficiency of a vitamin (most vitamins). Giving someone
more than enough B-12 to prevent the B-12 deficiency
associated diseases isn't going to improve their health
beyond the improvement that would come with the amelioration
of existing deficiency conditions (if there had been a
deficiency). Thinking otherwise is the classic 1970's
life-extensionist fallacy: less than "normal" is bad,
therefore more than normal is good. It's not true (the whole
statement).

>> At this point, one way we can try to advance this discussion
>> is with more specifics. Something I would love to see -- as
>> would most people reading this group, if the email pulse is
>> representative -- is a detailed justification of The Life
>> Extension Foundation's Life-Extension Mix (TM): "clear
>> supporting documentation." This would be very helpful.

> ... First, I will query LEF about who and how


> the decisions are made. And secondly I will
> start producing abstracts supporting ingredients,
> ratios, etc in the mix. This will be a long but
> worthwhile and interesting exercise. Who knows,
> the result may be a still superior mix which we
> will all understand the reasons for.

That would be great. I wouldn't, though, expect you to put
any time into posting abstracts supporting well-known
nutrients taken in isolation, since that would be a huge
undertaking. (Take "well-known" as you want; you'll probably
be right enough.)

>> There are a lot of ingredients in LEM, but for the
>> well-known ones, I wouldn't expect citations of studies. I
>> mean a justification for LEM geared towards people who know
>> the life-ext. literature well. We know vitamin E reduces
>> risk of heart disease, probably cancer, possibly
>> Alzheimer's, etc., etc. I just mean: 1) justification for
>> the less well-known nutrients, and 2) justification of the
>> doses,

> Yes, we can approach it that way.

>> and 3) justification for the claim of efficacy of the
>> substances in combination.

> I don't understand you again here. You know that
> we will "not" find any such studies in general.

We've run into this problem before, the problem of
understanding what we mean by "justification," or even
"reasons." Justification doesn't require a strictly
empirical approach; indeed, such an approach is impossible
(deduction and interpretation are both always required).

I just mean an answer to the question: What are the reasons
for thinking that evidence of the efficacy of the substances
that comes from studies of their use in isolation (or pairs
or other small numbers of them) still operates when all
these substances are used in combination? (You know,
"justify": to make "justus," to make just, right. The _quid
juris_ question, etc.)

The answer I'd expect would be, perhaps, of the form: "Well,
we have studies in humans with vitamin E, beta carotene, and
selenium, and the results were positive. Now, we add vitamin
C into the mix, and we believe this is good because vitamin
C works on system Z, and E and the others work on W, X, Y,
respectively, and we believe these systems are sufficiently
independent, in the following ways, for the following
reasons.... Onto gingko: Gingko effects blood vessel wall
health in a way that would not be interfered with by
vitamins C or E or...."

Something like that.

> That best that we can hope to do is to find
> studies that each nutrient has a key biochemical
> role which can be enhanced by supplementing it
> and that the biochemical mechanisms of two
> nutrients are sufficiently independent that it
> is reasonable that the effects will be nearly
> additive. Is not this sufficient to justify "the
> claim of efficacy of the substances in
> combination"?

It might well be, but I'd have to see the details -- above
all, the reasons for believing that the nutrients' modes of
action are independent.

>> >> One practical conclusion: let's support research into this
>> >> and related questions.
>> [....]
>>
>> > You certainly haven't got any arguement from me
>> > about this. However, I believe that
>> > practicalities of the research situation and the
>> > enormous complexity of the task...
>>
>> I don't know what you mean here. Give lab animals or people
>> LEM and follow them for a few years. What's the prob with
>> that?
>
> Of course, this would be possible, but only LEF
> would be willing to finance it. I meant general
> studies of general multiple combinations of
> vitamins by disinterested scientists.

Last time I talked with Saul Kent about this (two or three
years ago), he said LEF was indeed willing to finance this.

>> > ...and possibly
>> > the lack of proper (ie meaningful) animal models
>> > for such a process are going to prevent this
>> > from happening.
>>
>> How so? You continually cite studies using standard lab
>> rodents to support other claims you've made.
>
> Actually, I believe that you are mistaken. I
> don't do that very much. I generally look only
> for human studies. Only when I can't find any do
> I look at animal studies for some evidence. That
> one of the problems that I have with the studies
> about CR. Animal studies for CR certainly give
> better life-extension results than do animal or
> human studies for supplementation. However, if
> one restricts oneself to only human studies,
> there is far more health beneficial evidence for
> supplementation that there is for CR.

Oh, I disagree, but we can get into that later, after more
of a breather from the last round.

>> I await the rationale for the Life Extension Mix.
>
>It's going to take some time.

Understood.


<> Non-Science Issue.

>Brian Manning Delaney wrote:
>> Tom Matthews wrote:
>> > Brian, when I reply to a post, I don't reply
>> > just to the one thing that was being said in
>> > that message but to the sum total of what that
>> > person and others have been saying about the
>> > issue in many messages. My purpose in posting is
>> > generally *never* to make points *against* or
>> > even *related* to another poster, but instead to
>> > convey information, analysis and other correct
>> > ways of thinking about the subject at hand.
>
>> I think this is ultimately incoherent, but that's a
>> philosophical question, which I'm content not to pursue. In
>> any event, your view is noted.
>
> Thanks for your tact here. But I believe it is
> not a philosophical question but more of a
> question of fidelity and comprehensibility of
> information.

I just meant that the idea that information is neither for
nor against is incoherent. But maybe you just mean that your
for's and against's shouldn't be taken to be about
particular Usenet posters, but about larger positions in
general. If so, that's certainly not incoherent.

Tom Matthews

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Nov 29, 1997, 3:00:00 AM11/29/97
to

Brian Manning Delaney wrote:

-> >> You've pointed to some studies that look at pairs of
-> >> high-dose vitamins, and in a few cases, more than two or
-> >> three vitamins (but not in mega-doses). This is a beginning,
-> >> but doesn't bear more than minimally on the question of 1)
-> >> mega-doses of 2) dozens of different supplements. (One
-> >> exception, the A, B6, C and E plus zinc mega-dose study. But
-> >> this was a study of people who HAVE cancer, AND are
-> >> receiving BCG immunotherapy. Why should the study have
-> >> anything to do with the vast majority of people taking
-> >> multi- mega-supplements?)
-
-> > This is a reasonable question and, in fact, in
-> > most of the studies which I cited and for others
-> > which can be found, the nutrients, multiple or
-> > not, were being taken in an attempt to
-> > ameliorate some disease process. My view of this
-> > is that any combination of vitamins which does
-> > ameliorate some disease process is quite likely (not
-> > necessarily, but reasonably likely) to be
-> > beneficial to those which do not have that
-> > disease process either to prevent them from
-> > getting that specific disease or for other
-> > general health purposes.

> I disagree very strongly with this view, especially if you
> expand it to include more than just vitamins.

Well we do need a common term which stands for all the things, possibly
excepting hormones, which one normally supplements. My preferred term is
"nutrient", but I realize that's actually too broad since is includes
all foods as well. But then often, foods too are taken in concentrated
supplemental pill form. I will try to stick to just using the term
"nutrient" unless I specifically mean the defined vitamins.

> One obvious
> example where this is false is where a disease is caused by
> a deficiency of a vitamin (most vitamins). Giving someone
> more than enough B-12 to prevent the B-12 deficiency
> associated diseases isn't going to improve their health
> beyond the improvement that would come with the amelioration
> of existing deficiency conditions (if there had been a
> deficiency). Thinking otherwise is the classic 1970's
> life-extensionist fallacy: less than "normal" is bad,
> therefore more than normal is good. It's not true (the whole
> statement).

Well, I understand what you are saying and you are right that in certain
cases, more will not be better and in fact may be worse. However, with
respect to vitamin deficiency conditions, I believe that you are wrong.
It doesn't make sense that the amount necessary to stop the deficiency
symptoms will also be the optimal amount to stop various unseen, hard to
detect, subclinial physiological or biochemical "weaknesses" which a
higher, "optimal" amount would overcome. So what I am saying is that in
general more beyond the RDA *will* be better up to the point at which it
gets worse. I believe that the point at which raising a particular
vitamin dosage starts to have detrimental effects depends strongly on
the dosages of other certain other nutrients which are related to it.

As for the "classic 1970's life-extension fallacy", it is always easy
for those who weren't mature (or even born) at a certain time in the
past to look back and see the era in a stereotyped way. However, I
believe there were lots of people around then who also did not simply
think that more was always better. At least, I know I didn't. The people
of the past were not as dumb as history generally paints them to be. And
the people of the present aren't that much more brilliant either, they
simply have a little more research knowledge to work from.

But, Brian, this is where you seem to keep changing your tune
(seriously, no offense intended, I am honestly very confused as to what
you will or will not accept). When I and others have before suggested
that we can effectively make the kind of reasoning which you just
illustrated to make decisions, you have continually stated that we can't
or that such arguments aren't nearly as strong as we thing they are. At
least, that is how what you have been saying appears to me. This type of
reasoning you have just described is precisely what I say we *can* use
to make good decisions for multiple combinations from the limited single
studies and the knowledge of biochemical/physiological mechanisms which
we have.

> > That best that we can hope to do is to find
> > studies that each nutrient has a key biochemical
> > role which can be enhanced by supplementing it
> > and that the biochemical mechanisms of two
> > nutrients are sufficiently independent that it
> > is reasonable that the effects will be nearly
> > additive. Is not this sufficient to justify "the
> > claim of efficacy of the substances in
> > combination"?

> It might well be, but I'd have to see the details -- above
> all, the reasons for believing that the nutrients' modes of
> action are independent.

Well, we seem to getting somewhere here!

> >> >> One practical conclusion: let's support research into this
> >> >> and related questions.

> >> > You certainly haven't got any arguement from me

Ok. Thanks for your forbearance, that's an admirable quality.

That's precisely what I meant!
Hey! maybe we are starting to understand each other :-)

Tom Matthews

unread,
Nov 30, 1997, 3:00:00 AM11/30/97
to

In response to my forwarding of Brian Delaney's message re suppor for
multiple supplement use and testing the Life Extension Mix formulation
to Bill Faloon and Saul Kent founders of LEF, I received the following
replies:

From Bill Faloon:

>Dear Tom,
>
>Please be advised that the original Life Extension Mix formula was based on
>the recommendations made by Durk Pearson and Sandy Shaw in the 1982 book
>Life Extension.
>
>Since then, new evidence has prompted us to change the formula eleven times
>to reflect new research data.
>
>We extrapolate from animal studies and human epidemiological studies when
>determining the potency of any single ingredient in the formula.
>
>We could fund studies using Life Extension Mix, but the objective of our
>studies is to find new methods of extending lifespan. Life Extension Mix
>relies on existing research showing disease risk reduction when the
>nutrients contained in the formula are consummed on a regular basis. The
>aging process meanwhile continues unabated.
>
>As our research budget expands, we intend to do a lifespan study on Life
>Extension Mix, but for now, we have thousands of published studies backing
>up the individual ingredients in the product.
>
>We need to go well beyond the efficacy of the Life Extension Mix
>ingredients if we are to significantly increase lifespan.

And from Saul Kent:

> Tom. Yes, Bill knows the most about the rationale for the LE Mix
>formula. We pay far more attention to research in formulating and
>re-formulating LE Mix than most other companies do for their
>multi-nutrient formulas.

> The reason we didn't include LE Mix in the lifespan studies is because
>we were looking to test substances we thought had the best chance of
>extending maximum lifespan based on the most commonly advanced theories
>of aging. Traditionally, such studies include only a single agent. In our
>studies, we have several groups where there is a combination of agents.
>This is highly unusual in itself. A 52-ingredient formula such as Life
>Extension Mix would have many confounding variables. I think it is highly
>unlikely that *any* of these studies will lead to a significant extension
>of maximum lifespan, however, if one of them does, it will be a monumental
>discovery. My assumption is that we will have to do a great many lifespan
>studies over many years to find something that can extend maximum lifespan,
>unless and until we have better clues from basic research about agents most
>likely to extend maximum lifespan.
>
> We do have about 15 years of extensive human use of LE Mix, with
>considerable anecdotal evidence for its benefits and little or no evidence
>of adverse side effects.

> A clinical study will soon begin among union members in the Boston
>area in conjunction with an HMO and Tufts Medical School to assess the
>affects of a multi-nutrient supplement similar (but not identical to) Life
>Extension Mix. This should provide more controlled evidence in a couple of
>years.

Here are the nutrients and combinations for which the Life Extension
Foundation currently has lifespan studies underway.
For details, see the August 1997 issue of Life Extension Magazine at
http://www.lef.org

By Richard Weindruch at the University of Wisconsin at Madison

1. Alpha lipoic acid
2. Alpha lipoic acid & procysteine & vitamin E & lycopene
3. Coenzyme Q10
4. Coenzyme Q10 & acetyl-l-carntine and alpha lipoic acid & NADH

Conrols:
5. 40% Calorie restricted
6. ad libitum, no supplements


By Stephen R Spindler at the University of California at Riverside

1. Pregnenolone
2. Pregnenolone & melatonin
3. Aminoguanidine
4. Aminoguanidine & alpha lipoic acid
5. aminoguanidine & alpha lipoic acid & pregnenolone & coenzyme Q10

Controls:
6. ad libitum, no supplements

I would like to add that my current supplement regimen already includes
everything being tested here except "procysteine" (I take n-acetyl
cysteine instead). And I am moderately calorie restricted as well.

From the same issue of Life Extension Magazine:

Strategies Tested in Mice, Rats, and Hampsters for effects on Lifespan

Type of Intervention Reference

Nutritional:
-Caloric restriction Weindruch and Walford 1988; Weindruch 1996
-Protein level Nakagawa et al 1974; Feldman et al 1982
-Fat level French et al 1953; Birt et al 1982
-Carbohydrate level Dalderup and Visser 1969
-Source of protein, Fat Iwasaki et al 1988a; Kaunitz & Johnson 1975
or carbohydrate Durand et al 1968; Murtagh-Mark et al 1995
-Vitamin level (overall) Kokkonen and Barrows 1985
-Vitamin E Blackett and Hall 1981
-Mineral level (overall) Iwasaki et al 1988b
-Selenium Schroder and Mitchner 1971
-Self-selection among Ross et al 1976
different diets

Drugs, Hormones, and Metabolic Factors:
-Antioxidants Harman 1968; Khon 1971
-Melatonin Pierpaoli and Regelson 1994
-Centrophenoxine Hochschild 1973
-L-dopa Cotzias et al 1977
-Gerovital H3 Verzar 1959
-Beta-aminopropionitrile (BAPN) LaBella and Viven 1975
-Anterior pituitary Robertson and Ray 1919
-Prednisolone Bellamy 1968 "Surgery"
-Removal of pituitary gland Everitt et al 1980
-Immunologic reconstruction Walford et al 1977
-Parabiosis Ludwig and Elashoff 1972
-Castration (males) Drori and Folman 1976

Exercise: Holloszy et al 1985
Ambient temperature: Kibler and Johnson 1966

I would like to add that I have *not* done ALL the things from this long
list, and don't intend too! :-)

Tom Matthews

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Nov 30, 1997, 3:00:00 AM11/30/97
to

Here is another reference I just turned up, showing an additive, if not
synergistic, effect of multiple supplements.

Anticancer Res 1997 Mar;17(2A):1099-1106
Effects of conjugated dienoic derivatives of linoleic acid and
beta-carotene in modulating lymphocyte and macrophage function.

"When present together, CLA and beta-carotene interacted in an additive
manner to further enhance lymphocyte cytotoxicity and spontaneous
lymphocyte proliferation. In addition, beta-carotene was able to negate
the inhibitory action of CLA on the phagocytic activity of macrophages.
Also, CLA and beta-carotene together seemed to suppress mitogen-induced
lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
concert, act to modulate different aspects of cellular host defense."

Brian Manning Delaney

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Nov 30, 1997, 3:00:00 AM11/30/97
to

<> Terminology

Tom Matthews wrote:
: Well we do need a common term which stands for


: all the things, possibly excepting hormones,
: which one normally supplements. My preferred
: term is "nutrient", but I realize that's
: actually too broad since is includes all foods
: as well. But then often, foods too are taken in
: concentrated supplemental pill form. I will try
: to stick to just using the term "nutrient"
: unless I specifically mean the defined vitamins.

"Nutrient" is a good general term (I think it ultimately
comes from the Latin _nutrire_, to feed, which is, in a
sense, all we're talking about here), but it's not great,
since it presupposes that the substances in question
actually do nourish. Maybe "purported nutrients" or
something like that would be better. I prefer "substance."
But I'll know what you mean when you say nutrient.

<> Miscellaneous.

[....]
: > > My view of this
: > > is that any combination of vitamins which does
: > > ameliorate some disease process is quite likely (not
: > > necessarily, but reasonably likely) to be
: > > beneficial to those which do not have that
: > > disease process either to prevent them from
: > > getting that specific disease or for other
: > > general health purposes.
:
:
: Brian Manning Delaney wrote:
: > I disagree very strongly with this view, especially if


you
: > expand it to include more than just vitamins.

: >
: > One obvious


: > example where this is false is where a disease is caused
by
: > a deficiency of a vitamin (most vitamins). Giving
someone
: > more than enough B-12 to prevent the B-12 deficiency
: > associated diseases isn't going to improve their health
: > beyond the improvement that would come with the
amelioration
: > of existing deficiency conditions (if there had been a
: > deficiency). Thinking otherwise is the classic 1970's
: > life-extensionist fallacy: less than "normal" is bad,
: > therefore more than normal is good. It's not true (the
whole
: > statement).
:
: Well, I understand what you are saying and you
: are right that in certain cases, more will not

: be better and in fact may be worse....

That's not what I'm getting at. I put in the parenthetical
comment to stress that I'm disagreeing with a particular
line of reasoning which argues: IF less is bad, THEN more is
good (more is better than normal; normal =
"deficiency"-avoidance levels). I believe that more is
indeed good, very good, in particular cases. Example:
there's evidence that folic acid far above levels that
prevent anemia is beneficial. But we don't know if the extra
folic acid is beneficial in ways that have much to do with
its RDA-level functioning. It might not be at all. (There
are many other exs.; vitamin C is also a good case.)

Does B-12 beyond RDA levels do anything special? Vitamin K?
Copper? Manganese? Iodine?, etc.

: ... However,


: with respect to vitamin deficiency conditions, I
: believe that you are wrong. It doesn't make
: sense that the amount necessary to stop the
: deficiency symptoms will also be the optimal
: amount to stop various unseen, hard to detect,
: subclinial physiological or biochemical "weaknesses"
: which a higher, "optimal" amount would overcome.

Substances ("nutrients") do _qualitatively_ different things
at different doses. Claims about zinc are an instance of the
1970's life-extensionist fallacy: zinc is needed for proper
immune function, THEREFORE more zinc gives even BETTER
immunity. This is wrong (both the full statement, AND the
idea itself that more than RDA zinc improves immunity, as
far as research currently shows -- there may be exceptions
-- the elderly, for ex.).

Extra zinc, may, under certain conditions, be useful for
certain disease conditions, but thoughts and experiments
about this should be -- or, certainly, shouldn't not at all
be -- decoupled from what we know of its RDA-level role.

: As for the "classic 1970's life-extension fallacy",


: it is always easy for those who weren't mature (or
: even born) at a certain time in the past to look
: back and see the era in a stereotyped way.
: However, I believe there were lots of people
: around then who also did not simply think that
: more was always better. At least, I know I didn't.

Absolutely. I'm referring only to what appeared in a lot of
pop books, and to that which was believed by a lot of people
in general.

[....]

: > >> and 3) justification for the claim of efficacy of the

I think reasoning of this form -- reasoning that purports to
work like computer drug-testing models -- tends to be weak.
Sometimes it's all we have to go on, though. Either way,
what I said was "The answer I'd expect would be, perhaps, of
the form:...." I didn't say that would be a good answer. But
it appears to be all you and The Life Extension Foundation
have. This is understandable, since the direct empirical
studies haven't been done.

I can't pass any final judgements on the reasoning until I
get details.

(Ah, just noticed your recent posts -- more on those soon.)

Best,

Mark Thorson

unread,
Dec 1, 1997, 3:00:00 AM12/1/97
to

In article <348226...@netcom.ca>, Tom Matthews <tma...@netcom.ca> wrote:
>
>"When present together, CLA and beta-carotene interacted in an additive
>manner to further enhance lymphocyte cytotoxicity and spontaneous
>lymphocyte proliferation. In addition, beta-carotene was able to negate
>the inhibitory action of CLA on the phagocytic activity of macrophages.
>Also, CLA and beta-carotene together seemed to suppress mitogen-induced
>lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
>concert, act to modulate different aspects of cellular host defense."

So one nutrient suppresses the immune response, while another
mitigates the suppression. How do you know how much of either
to take, or even whether you should take either one at all?

People who wouldn't even consider taking a screwdriver and
adjusting the carburator of their car should be screwing
around with their immune system?

Oh, but hey, I NEED my car.


Brian Manning Delaney

unread,
Dec 2, 1997, 3:00:00 AM12/2/97
to

Tom Matthews wrote:
:
: In response to my forwarding of Brian Delaney's

: message re suppor for multiple supplement use
: and testing the Life Extension Mix formulation
: to Bill Faloon and Saul Kent founders of LEF,
: I received the following replies:
:
: From Bill Faloon:
:
: >Dear Tom,
: >
: >Please be advised that the original Life Extension
: >Mix formula was based on the recommendations
: >made by Durk Pearson and Sandy Shaw in the 1982 book
: >Life Extension.

[....]

: >We extrapolate from animal studies and human


: >epidemiological studies when determining the
: >potency of any single ingredient in the formula.

[....]

: >As our research budget expands, we intend to do


: >a lifespan study on Life
: >Extension Mix, but for now, we have thousands
: >of published studies backing
: >up the individual ingredients in the product.


: And from Saul Kent:
:

[....]

: > We do have about 15 years of extensive


: >human use of LE Mix, with considerable anecdotal
: >evidence for its benefits and little or no evidence
: >of adverse side effects.

Tom, the info in your post from Saul and Bill is probably
useful to many people reading this, so thanks for passing it
on. But I still don't see an answer for the third of my
requested justifications -- the three being, again:

1) justification for the less well-known nutrients

2) justification of the doses


3) justification for the claim of efficacy of
the substances in combination.

except for the evidence Saul pointed to: the 15 years of
anecdotal evidence. Anecdotal evidence is not worthless in
my view, but I'd like to see something of what I was
expecting -- detailed thought about likely or possible
interactions among the various components of LEM.

Here's another thought. We might be able to make the
evidence stronger than merely anecdotal. Wait, I'll put this
in a different post. (I'll post this other post only to
sci.life-extension, for those reading in a cross-posted
group.)

But I do want to see some details on the question of
interaction of the components of the Mix.

Tom Matthews

unread,
Dec 2, 1997, 3:00:00 AM12/2/97
to

Brian Manning Delaney wrote:

> I believe that more is
> indeed good, very good, in particular cases. Example:
> there's evidence that folic acid far above levels that
> prevent anemia is beneficial. But we don't know if the extra
> folic acid is beneficial in ways that have much to do with
> its RDA-level functioning. It might not be at all. (There
> are many other exs.; vitamin C is also a good case.)

Well I agree with you here, but all this suggests to me is that the RDA
deficiency disease caused by the lack of a vitamin is a very poor
indicator of its many possible biochemical uses and, therefore, of its
potential for benefiting (or harming) health. Vitamin E in its various
forms in another good example. From the studies that have been done it
appears as if E succinate should be classified as a separate nutrient to
unesterfied tocopherol or tocopherol acetate.
RDA levels should simply be viewed as what they are the level above
which most people do not get the specific deficiency disease. But we do
not take more than the RDA of say, Vitamin C so that we will get a
"negative amount" of scurvy, we take it because it has other major
benefits, the harmfulness of which is not so simple to detect and
classify as is scruvy. I would suggest that this potential for action at
many levels, in many biochemical ways and at many physiological sites is
probably the norm for most nutrients. In fact, a nutrient may even have
different U-shaped dose/response curves for each of its different
biochemical uses and these dose/response curves may vary quite a lot
between genetically determined biochemical variations of different
individuals. I have never said that working out optimal doses would be
easy!
=

> Does B-12 beyond RDA levels do anything special?

Yes, when combined with folate. As well as possibly being necessary.

Call for endorsement of a petition to the Food and Drug Administration
to always add vitamin B-12 to any
folate fortification or supplement. (Herbert V; Am J Clin
Nutr, 1997 Feb)

> Vitamin K?

Yes, if you are newborn at risk for hemorrhagic disease. =


Prevention of vitamin K deficiency bleeding: efficacy of different
multiple oral dose schedules of vitamin K.
(Cornelissen M; Eur J Pediatr, 1997 Feb)

Both more often (for those with a tendency to blood clots) it may be
harmful, although more supplemented generally just gets excreted.

>Copper?

Yes, if you are taking lots of zinc, ascorbate or cysteine, but
generally extra copper is a free radical producer almost as bad as iron.

The resistance of low density lipoprotein to oxidation promoted by
copper and its use as an index of
antioxidant therapy. (O'Leary VJ; Atherosclerosis, 1996 Jan
26)

>Manganese?

Yes, it you have AIDS:

Effects of manganese salts on the AIDS-related pathogen, Cryptosporidium
parvum in vitro and in vivo.
(Nesterenko MV; Biol Trace Elem Res, 1997 Mar)

Or if you are eating lots of fat and iron:

Increasing dietary lipid and iron content decreases manganese superoxide
dismutase activity in colonic
mucosa. (Kuratko CN; Nutr Cancer, 1997)

> Iodine?

It may lower calcium and magnesium excretion

[Changes in urinary calcium and magnesium levels during supplementation
with iodine and selenium]
(Simeckov=E1 A; Vnitr Lek, 1996 Nov)

The main point, however, that I would make with all of your examples
(except K and copper), is that quite a lot more than the RDA has well
been shown to be not harmful. Therefore, I believe that it would be
reasonable (because is might be beneficial and is highly unlikely to be
harmful) to take an amount more than the RDA but still substantially
less than any know toxic amount, possibly even many times more if there
is no known toxicity at all. =


> : ... However,
> : with respect to vitamin deficiency conditions, I
> : believe that you are wrong. It doesn't make
> : sense that the amount necessary to stop the
> : deficiency symptoms will also be the optimal
> : amount to stop various unseen, hard to detect,
> : subclinial physiological or biochemical "weaknesses"
> : which a higher, "optimal" amount would overcome.

> =

> Substances ("nutrients") do _qualitatively_ different things
> at different doses.

I don't disagree with this. I said the same thing above.

> Claims about zinc are an instance of the
> 1970's life-extensionist fallacy: zinc is needed for proper
> immune function, THEREFORE more zinc gives even BETTER
> immunity. This is wrong (both the full statement, AND the
> idea itself that more than RDA zinc improves immunity, as
> far as research currently shows -- there may be exceptions
> -- the elderly, for ex.).

Don't forget the RDA (12-15mg) is the amount necessary to stop the
deficiency disease (poor wound healing, lowered immunity and retarded
growth in children) in *most* people. To be safe, I think it would be
wise to take a bit more, say 30mg, since the toxic dose is a few hunderd
mg (and then you will know it form having cramps or vomiting) it would
be wise to keep the dose below 100mg and if you are about 30mg you
should take extra copper and make sure you have adequate calcium.

Anyway, again zinc as with so many other nutrients has more uses than
just one (immunity enhancement). Here's as study which showed great
benefit from supplementing with 25mg daily.

Zinc supplementation and plasma lipid peroxides in an elderly
population. (Fortes C; Eur J Clin Nutr, 1997
Feb)

Furthermore, here's an abstract which suggests to me that additional
zinc beyond the RDA may well increase immunity also.

Competitive reverse transcriptase-polymerase chain reaction shows that
dietary zinc supplementation in
humans increases monocyte metallothionein mRNA levels.
(Sullivan VK; J Nutr, 1997 May)
=

> Extra zinc, may, under certain conditions, be useful for
> certain disease conditions, but thoughts and experiments
> about this should be -- or, certainly, shouldn't not at all
> be -- decoupled from what we know of its RDA-level role.

Quite so. The RDA is only one facit of its potential. It is especially
true with nutrients such as zinc, where there is no clear-cut single RDA
deficiency disease, that there are many clear possibilities for benefit
by taking more than the RDA. =


More later,

--Tom =

Tom Matthews
=

All personal comments do not represent the views of anyone from:

The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-841-5433 =

A non-profit membership organization dedicated to the extension of the =

healthy human lifespan through ground breaking research, innovative =

ideas and practical methods.

Tom Matthews

unread,
Dec 2, 1997, 3:00:00 AM12/2/97
to

Mark Thorson wrote:
>
> In article <348226...@netcom.ca>, Tom Matthews <tma...@netcom.ca> wrote:
> >
> >"When present together, CLA and beta-carotene interacted in an additive
> >manner to further enhance lymphocyte cytotoxicity and spontaneous
> >lymphocyte proliferation. In addition, beta-carotene was able to negate
> >the inhibitory action of CLA on the phagocytic activity of macrophages.
> >Also, CLA and beta-carotene together seemed to suppress mitogen-induced
> >lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
> >concert, act to modulate different aspects of cellular host defense."
>
> So one nutrient suppresses the immune response, while another
> mitigates the suppression. How do you know how much of either
> to take, or even whether you should take either one at all?

Mark, you seem to be under the misguided impression that the immune
system is all good. That any lowering or modifying of it in any way must
be bad. This is far from the truth as shown buy the many forms of
autoimmune diseases which are around us (which properly looked at are
*distorted* immune systems rather than just too much generally
immunity). Furthermore, as a science news article that I was just
reading today pointed out the immune system and markers of the potential
problem are now clearly implicated in atheroscelosis many years prior to
what were thought to be the standard risk factors. Both CLA and
beta-carotene (make sure to take lots of other carotenoids as well) have
been shown to be highly beneficial for various things. The study that I
cited simply showed that there effect was additive for one particular
purpose. That's all that I was using it to illustrate.

> People who wouldn't even consider