7 replies to this topic

[doug123]

From here:

http://www.imminst.o...t=0

All:

I had run across SOD and increasing it a while back and.... I've forgotten which ones, but if you google SOD you'll pop up the names of some familiar herbs and possibly a nootropic as well

The question is whether it's a good thing to increase SOD. Antioxidant enzymes are NEGATIVELY correlated with species max LS (1,2); expressing extra SOD without extra CAT could actually INCREASE free radical stress by converting minimally-toxic superoxide into more-toxic hydrogen peroxide without the capacity to break it further down to water; SOD knockouts fail to show accelerated mortality except under artificially-indduced high oxidative stress; Down's syndrome is characterized by high SOD activity; etc.

"Superoxide dismutase mimetics [EUK-134 or EUK-8] elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans" despite the fact that they protect against hihg-level oxidative stress and prevent brain damage after a stroke or induced seizure (3).

Most notably, "Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice" (4), despite the fact that increased SOD in this model also leads to increased CAT.

Deprenyl is often cited as a counterexample, but it really isn't. Yes, Knoll made an exciting single report (and repeated it in several journals), but he's the ONLY person to report an extension of max LS: lots of others show increases in av'g bu t not max, no extension at all, or even *increased* mortality. Flat ad hominem: Knoll had the patent on the stuff. See the desperate attempts to reconcile the data between different studies on pp. 3-8, esp. the lifespan discussions on pp 7-8, of (1). Much of this info (but without, alas, the unpublished stuff sumarized in (1)) is put in a tabular form in (2), which makes the fundamental lack of anything like a logical pattern in the results clear. IMO, this shows pretty clearly that even if you believe there's something to it as a life-extension drug, there is just no way that one can rationally USE it as such at this time as there is no basis upon which to reasonably extrapolate a dose which can be expected to consistently extend even AV'G LS in humans.

There are no trials in normal, healthy humans, & the studies in both early and late PD are in sum quite inconclusive on the safety of deprenyl. See:

http://groups.google.....4A@aimnet.com
http://groups.google.....BC@aimnet.com
http://groups.google.....84@aimnet.com

http://bmj.com/cgi/c...ll/317/7153/252
http://bmj.com/cgi/c...l/316/7139/1191
http://groups.google...m&output=gplain

(The first 3 largely go over the same ground, albeit from slightly
different angles; the others cover newer material).

A recent editorial comment on the study from which the last post is
abstracted:

http://www.neurology...s/55/12/1785#29

"Laboratory studies suggest that selegiline has properties that
theoretically could confer neuroprotection; however, evidence for this
in clinical trials is unfortunately lacking. ... Prescribing
medications such as selegiline on faith, with little evidence-based
efficacy, ignores the negative side of this practice, including
unnecessary expense to the patient, and the potential of deleterious
drug interations. (ref. 14)." The comment seems especially relevant in
the present discussion.

It doesn't appear to give any reliable benefits in animal systems; it seems to kill the folks it's designed to TREAT; I just do not see how the risk:benefit calculation can be fudged to make it come out in favor of use by young, healthy people.

-Michael

1. Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC.
Why (--)deprenyl prolongs survivals of experimental animals: increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects.
Mech Ageing Dev. 2002 Apr 30;123(8):1087-100. Review.
PMID: 12044958 [PubMed - indexed for MEDLINE]

2. Kitani K, Kanai S, Ivy GO, Carrillo MC.
Assessing the effects of deprenyl on longevity and antioxidant defenses in
different animal models.
Ann N Y Acad Sci. 1998 Nov 20;854:291-306. Review.
PMID: 9928438 [PubMed - indexed for MEDLINE]

3. Keaney M, Matthijssens F, Sharpe M, Vanfleteren J, Gems D.
Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but
do not retard aging in the nematode Caenorhabditis elegans.
Free Radic Biol Med. 2004 Jul 15;37(2):239-50.
PMID: 15203195 [PubMed - indexed for MEDLINE]

4. Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ.
Ubiquitous overexpression of CuZn superoxide dismutase does not extend life
span in mice.
J Gerontol A Biol Sci Med Sci. 2000 Jan;55(1):B5-9.
PMID: 10719757 [PubMed - indexed for MEDLINE]

[Shepard]

How many folks on here take it specifically for life extension purposes? I know Duke does, but from a lot of the posts it seems that some of the folks take it for other reasons.

[doug123]

I got to type this quick, as I got to do my homework.

I disagree with the statement: "Posting just negative stuff you can make a killer out of any supplement/drug." Please try to support this argument so we can perhaps be convinced.

I kindly request for you to present any evidence that R-alpha-lipoic acid or Acetyl-L-carnitine (at clinically revelant dosages) are in any, way, shape, or form a "killer."

Deprenyl can be an effective treatment for Parkinsons, Alzheimers, ADD/ADHD (in some cases), and may have some indications to substantitate its use as an anti-depressant.

But as a life-extension drug, there is no real evidence suggesting it is effective -- in fact, some data seems to indicate deprenyl might even cause a premature death.

There are no trials in normal, healthy humans, & the studies in both early and late PD are in sum quite inconclusive on the safety of deprenyl.

Peace.

[Shepard]

You think FDA would approve selegiline as antidepressive even for young people if there weren't studies confirming it's safety?

Depends on how much money was involved.

[doug123]

"There are no trials in normal, healthy humans, & the studies in both early and late PD are in sum quite inconclusive on the safety of deprenyl."

You think FDA would approve selegiline as antidepressive even for young people if there weren't studies confirming it's safety?

Currently i have no time to go thru studies and look for information. But FDA approval for both Parkinson and depression is good enough for me for safety issue. Does it really extends life is another question and probably the one we're not going to get answer anytime soon.

I said it too harsh "killer", but i meant something that's bad for you. Selegiline is not dangerous drug as one could conclude from quoted text in first post. Neither is ALCAR. But, in fact ALCAR itself could be more dangerous than selegiline because of it's pro oxidant effects. Take few gr of ALCAR all your life without additional antioxidants and you'll probably shorten your lifespan a lot.

FDA has approved Ritalin, Adderall, Celebrex, and all can be dangerous. So just because FDA approved it does not automatically mean it's safe.

If you want your arguments to be taken seriously, I suggest you find the time to support them with some relevant data. I can usually find data to support my arguments in less than a minute (whether or not they are about effectiveness or safety of drugs). If you would like me to share my methodology, I'd be happy to.

Peace.