SOD and ways to increase

I posted this at avant but thought relevant to post here also.

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--which if my fallible memory serves increase SOD. In addition there is:

http://www.enzymecompany.com

I discovered this place from an excellent holistic vet (they make people and animal products) and I think it likely that some of these products helped a friend's dog...essentially be cured from a nasty from of cancer (I think it was a sarcoma).

There is an interesting article on his using his products to help children recover from chernoble.

Ashwaganda increases SOD, GPX and CAT.

There is also "GliSODin" which is an orally bioavailable form of SOD.

1: Free Radic Res. 2004 Sep;38(9):927-32. Related Articles, Links
Click here to read
Influence of an orally effective SOD on hyperbaric oxygen-related cell damage.

Muth CM, Glenz Y, Klaus M, Radermacher P, Speit G, Leverve X.

Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum Ulm, D-89073 Ulm, Germany. claus-martin.muth@medizin.uni-ulm.de

In a prospective, double-blind, randomised placebo-controlled study, we tested the hypothesis that a new formulation consisting of wheat gliadin chemically combined with a vegetal (thus orally effective) preparation of superoxide dismutase (SOD) allows to prevent hyperbaric oxygen (HBO)-induced oxidative cell stress. Twenty healthy volunteers were exposed to 100% oxygen breathing at 2.5 ATA for a total of 60 min. DNA strand breaks (tail moments) were determined using the alkaline version of the comet assay. Whole blood concentrations of reduced (GSH) and oxidised (GSSG) glutathione and F2-isoprostanes, SOD, glutathione peroxidase (GPx) and catalase (Cat) activities and red cell malondialdehyde (MDA) content were determined. After HBO exposure the tail moment (p = 0.03) and isoprostane levels (p = 0.049) were significantly lower in the group that received the vegetal formulation. Neither SOD and Cat nor GSH and GSSG were significantly affected by this preparation or HBO exposure. By contrast, blood GPx activity, which tended to be lower in the SOD-group already before the HBO exposure (p = 0.076), was significantly lower afterwards (p = 0.045). We conclude that an orally effective SOD-wheat gliadin mixture is able to protect against DNA damage, which coincided with reduced blood isoprostane levels, and may therefore be used as an antioxidant.

PMID: 15621710 [PubMed - in process]

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Thanks Stellar.

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]

Knoll was not the only investigator to report on the LS benefits of deprenyl:


J Neural Transm Suppl. 1994;41:231-6.
Lifespan of immunosuppressed NMRI-mice is increased by deprenyl.
Freisleben HJ, Lehr F, Fuchs J.

Immunosuppressed NMRI-mice (nu/nu) were raised and kept under germ-reduced conditions and fed with a germ-reduced diet (14 animals = controls). For another 14 mice 4 mg of selegiline were admixed to 10 kg of the diet. The 50% survival rate of the latter group was 160% from birth or 220% from the beginning of the study. The survival rate in weeks finally reached 350%, and the area under the curve 250%. The last mouse in the control group died at the age of 5 months, 2.5 months after the study was started; the last mouse in the selegiline group died at the age of 14.5 months, 1 year after the beginning of the study.


Biochem Pharmacol. 1994 Apr 20;47(8):1333-8.
The effect of a long term (6 months) treatment with (-)deprenyl on antioxidant enzyme activities in selective brain regions in old female Fischer 344 rats.
Carrillo MC, Kitani K, Kanai S, Sato Y, Miyasaka K, Ivy GO.

The effect of long term treatment with (-)deprenyl (s.c. injection three times a week for 6 months) on superoxide dismutase (SOD) and catalase (CAT) in selective brain regions was examined in old (22 months) female Fischer 344 rats. The three doses of deprenyl used (0.1, 0.25 and 0.5 mg/kg/day) increased the activities of both enzymes in substantia nigra, striatum and cerebral cortices essentially in a dose dependent manner. However, for CAT activities in cerebral cortices, the smallest dose of 0.1 mg/kg/day was most effective, while the highest dose (0.5 mg/kg/day) had no effect. In contrast to these brain regions, there were no significant differences in enzyme activities between control and deprenyl-treated groups in the hippocampus and cerebellum. If the effect of deprenyl on the life span of female F-344 rats is causally related to its effect on antioxidant enzyme activities in selective brain regions as shown in this study, then a dose of 0.25 or 0.5 mg/kg/day appears to be most appropriate. Since this dose is much lower than the dose suggested by our previous short term (3 week) experiments, an even longer term experiment is necessary to determine the optimal dose of deprenyl to increase free radical scavenging and thus possibly extend lifespan.


Acta Physiol Hung. 1996;84(3):277-8.
Longevity treatment with (-)deprenyl in female rats: effect on copulatory activity and lifespan.
Dallo J, Koles L.

Six months old ovariectomized female rats (n = 9) were treated with (-)deprenyl in a dose of 0.25 mg/kg s.c. three times a week, and (n = 9) with physiologic saline (0.1 ml/100 g) till decay. It was found that control females (n = 9) decayed within the age of fifteen months while the members of the (-)deprenyl treated group were all alive at that age. Moreover three (-)deprenyl treated female rats reached 36 months of age. Sexual activity was quite absent in both groups. The data suggests that (-)deprenyl extended the lifespan of female rats only in total absence of gonadal hormones and sexual activity.




The other LS studies bear Knoll's name, but the investigative trends on selengine are now focused on more specific benefits, and these studies are numerous and have multiple sources.

All:

Knoll was not the only investigator to report on the LS benefits of deprenyl [1-3]:

First: note that (2) was not a lifespan study.

But re: (1,3): sorry, I should've been more explicit; I just have repeated it often enough in different forums that I unconsciously tend to assume that people know what I mean, even if I've never said as much to them. When I say "extension of max LS," I mean it precisely -- an extension of species maximum lifespan per se (as tenth-decile survivorship). The maximum lifespan for AL-fed wild-type laboratory mice is ~1200 days (4), whereas "The last mouse in the control group died at the age of 5 months... [and] the last mouse in the selegiline group died at the age of 14.5 months" in (1) (and again, this is single survivor, not tenth-decile, so the true maximum LS in the colony is lower); so brief a LS is not surprising, as NMRI mice are severely autoimmune.

Likewise, in (3), while they used the reasonably longevous F344 rat strain, they apparently weren't caring for them very well: "It was found that control females (n = 9) decayed within the age of fifteen months while the members of the (-)deprenyl treated group were all alive at that age. Moreover three (-)deprenyl treated female rats reached 36 months of age." Yet even if we constrain ourselves to the F344 strain rather than looking at true species maximum lifespan, this is actually an unusually short lifespan that is roughly normalized by deprenyl, not a true exension of LS that would be interesting for use in healthy people: AL females of this strain have an historical mean life span of 825.85 (27.52 months) ± 15.46; a median life span of 813.5 days; and a maximum LS of 1072 d (35.73 months).

So when I say that "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", I'm referring to this failure to extend the [i]normal, healthy organism's lifespan, not to the alleviation of premature mortality in short-lived strains or animals raised under poor husbandry. It's easy to reduce mortality by antioxidants in short-lived strains or chorts -- it's been done with any number of compounds, from Harnam on -- and deprenyl has certainly been reported to do this several times, although (again) it has also [i]increased mortality in others (eg (6)).

-Michael


1] J Neural Transm Suppl. 1994;41:231-6.
Lifespan of immunosuppressed NMRI-mice is increased by deprenyl.
Freisleben HJ, Lehr F, Fuchs J.

2. Biochem Pharmacol. 1994 Apr 20;47(8):1333-8.
The effect of a long term (6 months) treatment with (-)deprenyl on antioxidant enzyme activities in selective brain regions in old female Fischer 344 rats.
Carrillo MC, Kitani K, Kanai S, Sato Y, Miyasaka K, Ivy GO.

3. Acta Physiol Hung. 1996;84(3):277-8.
Longevity treatment with (-)deprenyl in female rats: effect on copulatory activity and lifespan.
Dallo J, Koles L.

4. Miller RA, Harper JM, Dysko RC, Durkee SJ, Austad SN.
Longer life spans and delayed maturation in wild-derived mice.
Exp Biol Med (Maywood). 2002 Jul;227(7):500-8.
PMID: 12094015

5. Holmes DJ.
F344 Rat.
Sci. SAGE KE. 2003 Sep 10;36:as2.
[DOI: 10.1126/sageke.2003.36.as2]

6. Gallagher IM, Clow A, Glover V.
Long-term administration of (-)-deprenyl increases mortality in male Wistar
rats.
J Neural Transm Suppl. 1998;52:315-20.
PMID: 9564632 [PubMed - indexed for MEDLINE]

Unfortunately, one can interpret and present for support the literature in almost any way one sees fit. For the purpose of those who are considering deprenyl as an antiaging supplement, however, why don't you summarize for them the benefits, if any, of using it and the unwanted effects and interactions. I think that is what they are really interested in.

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

Perhaps a bit off-topic, but that might explain something I never could quite swallow in (1). de Grey argued that the ratio of SOD to superoxide was all that mattered, and thus a reduction in superoxide production should require a lower level of SOD. But as far as I remember from high school chemistry, it's not the ratio that's the key, because the rate of the reaction is proportional to the concentration of each chemical multipled together. So a 90% reduction in superoxide production will lead to a 90% reduction in the reaction rate, and hence the lifetime of the superoxide (the "potency" factor, as de Grey called it) would not diminish, even if we maintained the same level of SOD. Reducing SOD concentrations would actually increase the lifetime of superoxide. For example, a 90% reduction in superoxide and a 90% reduction in SOD should yield a 99% reduction in the reaction rate. Or, more intuitively, reducing to 10% the superoxide concentration, and to 10% the SOD concentration, should yield a 1% reaction rate compared to the original rate. 1% reaction rate acting on 10% of the superoxide leads to a 10 times longer lifetime, if no other mechanisms for quenching superoxide existed. Sadly, other such mechanisms exist, namely conversion to more toxic ROS, and oxidation reactions with macromolecules.

A minor issue, except that it was a weak point to begin with in explaining the negative correlation (metabolic inefficiency of producing excess enzymes is not going to reduce lifespan by an appreciable percentage, not compared to something inherently toxic). However, a negative consequence of SOD levels being too high (indirect toxicity) makes a much better explanation for the negative correlation.

An interesting idea here then is that there is a point of diminishing returns of increased SOD levels, and that there is inherent toxicity that increases, perhaps linearly or superlinearly, with SOD levels, and that the crossover point of benefit/cost varies proportionally to superoxide production rates (i.e. cut the superoxide production rate in half, and expect half the SOD level to be the crossover point). An interesting project for a graduate student to undertake. I'd like to see more validation of de Grey's theories, as an invalidation might have negative consequences for... er, certain speculative therapies based on his understanding of mitochondrial mtDNA damage dynamics.

(1) de Grey ADNJ.
The non-correlation between maximum longevity and enzymatic antioxidant levels among homeotherms; implications for retarding human aging.
J Anti-Aging Med 2000; 3(1):25-36.

This is an excellent topic worth a bump.

Chyavanprash

http://www.banyan-bo...aitem=1&mitem=1

Where can I find injectable SOD?

Renwosing

Where can I find injectable SOD?

Renwosing

 

Why would you want this?   Supplemental SOD is shown in the literature to lower endogenous SOD levels by *more* than the amount you supplement.   It's a poor strategy for increasing overall SOD levels.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

rooibos significantly increases SOD levels. There is a thread on this forum about it.