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Whisper9999



Joined: 16 Feb 2007
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Location: Sunny Southwest

PostPosted: Fri Jul 06, 2007 8:02 pm    Post subject: Reply with quote

drtodorov wrote:
Well, I've simply been theorizing as to what could explain the SOD increase that is allegedly much greater than SOD amount absorbed from Glisodin Iif that's indeed a real phenomenon). I am not saying it is necessarily due to reaction to gluten -- I could come up with other theories. But the point is that if this phenomenon is real, only actual studies can determine the cause. (Incidentally, does the manufacturer offer an explanation?).

In any case, people with gluten sensitivity should be careful with this supplement. Notably, gluten sensitivity is sometimes not obvious and may manifest, for example, as neuropathy rather than a GI syndrome.


The rep said they don't know. I printed off some of the studies that touch on this. One said "increased levels of serum IgE ahve been described in gliadin-intolerant patients; however, biological mechanism implicated in this immunoglobulin production remained unknown. In this study, we demonstrated that in vitro crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE production by human peripheral blood mononuclear cells (PBMC), indicating that the biological process related to gliadin intolerance anor allergy may lead to IgE production in vivo."

Can you translate that for me? :)
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drtodorov
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PostPosted: Fri Jul 06, 2007 8:25 pm    Post subject: Reply with quote

People with gluten intolerance often produce antibodies (IgE and IgG) to gliadin (part of gluten). This is well known and not very relevant because gluten intolerant patients should not take this supplement anyway.

This issue is what's going on in people w/o any known gluten intolerance when they take Glisodin.
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drtodorov
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PostPosted: Fri Jul 06, 2007 8:28 pm    Post subject: Reply with quote

People with gluten intolerance often produce antibodies (IgE and IgG, depending on whether it is immediate or delayed hypersensitivity) to gliadin, which is key protein in gluten. This is well known and not very relevant because gluten intolerant patients should not take this supplement anyway.

The issue is what's going on in people w/o any known gluten intolerance when they take Glisodin. (I presume they studied Glisodin and got those results in people who tested negative for gluten/gliadin intolerance. Otherwise, it would have been quite unwise...)
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Whisper9999



Joined: 16 Feb 2007
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Location: Sunny Southwest

PostPosted: Mon Jul 09, 2007 9:28 pm    Post subject: Reply with quote

drtodorov wrote:
Well, I've simply been theorizing as to what could explain the SOD increase that is allegedly much greater than SOD amount absorbed from Glisodin Iif that's indeed a real phenomenon). I am not saying it is necessarily due to reaction to gluten -- I could come up with other theories. But the point is that if this phenomenon is real, only actual studies can determine the cause. (Incidentally, does the manufacturer offer an explanation?).

In any case, people with gluten sensitivity should be careful with this supplement. Notably, gluten sensitivity is sometimes not obvious and may manifest, for example, as neuropathy rather than a GI syndrome.


I have browsed through the research on glisodin.org - and of course being a layman it could possibly be under my nose and I wouldn't recognize it - for your primary question: what is the immune response to a healthy person w/o gluten sensitivity? I see nothing that directly answers that question.

However, I did find one study that is related. Or at least I think it is. If Glisodin was eliciting an immune response of some sort, wouldn't we expect inflammation to increase? Well, here is another indication - I think anyway - that Glisodin actually decreases inflammation:

Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity

Ioannis Vouldoukisa, b, Dominique Lacanc, Caroline Kamatea, Philippe Costec, Alphonse Calendaa, Dominique Mazierb, Marc Contib and Bernard Dugas, , a, b
a Isocell Nutra SAS, 53 Bld du Général Martial Valin, 75015, Paris, France
b INSERM U511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié Salpétrière, Université Paris VI, 75013, Paris, France
c BIONOV sarl, 84911 Avignon, France
Received 18 February 2004; Revised 18 February 2004; accepted 19 April 2004. Available online 19 June 2004.


Abstract

The present study was conducted to evaluate in vitro and in vivo the antioxidant and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity. Peritoneal macrophages were pre-activated in vitro with 300 IU of interferon-γ (IFN-γ) and were then challenged in culture with IgGl/anti-IgG1 immune complexes (IgG1IC) in presence of various CME extracts. The subsequent production of free radicals (superoxide anion, nitric oxide, and peroxynitrite) and of pro-(TNF-α) and anti-(IL-10) inflammatory cytokines was evaluated. The CME inhibited in a dose-dependent manner the production of superoxide anion with a maximal effect at 100 μg/ml. This inhibitory effect of CME appeared to be closely linked to the SOD activity because it was dramatically decreased after heat inactivation of the SOD activity (HI-CME). In addition, the CME inhibited the production of peroxynitrite strengthening the antioxidant properties of this CME rich in SOD activity. The production of the pro- and anti-inflammatory cytokines, namely TNF-α and IL-10, being conditioned by the redox status of macrophages we also evaluated the effect of CME and HI-CME on the IgG1IC-induced cytokine production. When the SOD activity was present in the CME it promoted the IgG1IC-induced production of IL-10 instead of TNF-α. These data demonstrated that, in addition to its antioxidant properties, the anti-inflammatory properties of the CME extract were principally related to its capacity to induce the production of IL-10 by peritoneal macrophages. The particular properties of wheat gliadin (Triticum vulgare, Poaceae) for the oral delivery of functional proteins led us to test it in a new nutraceutical formula based on its combination with the CME thus monitoring the SOD activity release during the gastro-intestinal digestive process. In these experiments C57BL/6 mice were supplemented orally everyday during 28 days with: (1) the placebo, (2) the CME extract alone, (3) the gliadin, (4) the CME/gliadin combination, or (5) the HI-CME/gliadin combination (SOD inactivated). At the end of the supplementation period all the animals were injected intra-peritoneal (i.p.) with the pro-inflammatory cytokine IFN-γ (300 IU) and peritoneal macrophages were harvested 24 h after to test their capacities to produce free radicals, TNF-α and IL-10 after triggering with IgG1IC. We demonstrated that animals supplemented during 28 days with the CME/gliadin combination were protected against the pro-inflammatory properties of IFN-γ while the other products were inefficient. These data did not only indicate that the SOD activity is important for the antioxidant and anti-inflammatory properties of the CME extract, but also demonstrated that when the SOD activity is preserved during the digestive process by its combination with wheat gliadin it is possible to elicit in vivo the pharmacological effects of this antioxidant enzyme.

Author Keywords: Superoxide dismutase; Cucumis melo; Antioxidant; Inflammation
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Whisper9999



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PostPosted: Mon Jul 09, 2007 9:37 pm    Post subject: Reply with quote

I think I found something that is actually directly related. In the study below they took some normal cells and found that gliadin alone would increase IgE production. However, when SOD was delivered into the cells (from the bonded SOD of course), it dampened this effect and IgE levels were acceptable. That's my layman's interpretation so if you get a chance to let me know if I"m on track, I'd apprecaite it.

hytoned . com / WheatGliadin2003.pdf

You need the world wide web at the beginning.
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drtodorov
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PostPosted: Mon Jul 09, 2007 9:57 pm    Post subject: Reply with quote

It is interesting but not directly relevant because this is a tissues culture study and, besides, they ensured intracellular delivery of SOD. Glisodin effects are in vivo and we don't know how much of their SOD ends up inside immune cells. Furthermore, even if this effect occurs in vivo with Glisodin, it still does not explain the alleged dramatic stimulation of endogenous SOD production by Glisodin.

But it is an interesting study. Thanks for posting it.
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Whisper9999



Joined: 16 Feb 2007
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Location: Sunny Southwest

PostPosted: Tue Jul 10, 2007 12:25 am    Post subject: Reply with quote

drtodorov wrote:
It is interesting but not directly relevant because this is a tissues culture study and, besides, they ensured intracellular delivery of SOD. Glisodin effects are in vivo and we don't know how much of their SOD ends up inside immune cells. Furthermore, even if this effect occurs in vivo with Glisodin, it still does not explain the alleged dramatic stimulation of endogenous SOD production by Glisodin.

But it is an interesting study. Thanks for posting it.


As an fyi, the (according to my impression) American distributor PL Thomas put out this web site

w cubed . glisodin . info

which boldly states

"Simply put, GliSODin® is the only supplement that stimulates the body’s own built-in antioxidant defense system. GliSODin® acts as a catalyst, stimulating the body’s production of its own internal antioxidants, the most powerful of which is known as SOD (Superoxide Dismutase)."

So they're not shy about the fact that it is not a direct delivery system...
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Whisper9999



Joined: 16 Feb 2007
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Location: Sunny Southwest

PostPosted: Tue Jul 10, 2007 1:23 am    Post subject: Reply with quote

drtodorov wrote:
It is interesting but not directly relevant because this is a tissues culture study and, besides, they ensured intracellular delivery of SOD. Glisodin effects are in vivo and we don't know how much of their SOD ends up inside immune cells. Furthermore, even if this effect occurs in vivo with Glisodin, it still does not explain the alleged dramatic stimulation of endogenous SOD production by Glisodin.

But it is an interesting study. Thanks for posting it.


Okay, I think I may have found a study that actually directly, if you consider a mice study direct, deals with your question. It is on p. 8 of the following (and you have to add the world wide web at the beginning):

glisodininfo . com /documents/GliSODin%20Monograph%205.17.pdf

First of all, mice were supplemented with Glisodin and the spleen cells isolated and studied. As a side note, those supplemented with GliSodin had "increased production of type1 helper T lumphocytes (Th1) and INF-y and IL-4". Of course, that's a positive immune response but doesn't answer your question about the immunoglobulins. As it turns out, they found out that IgE was only marginally effected while IgG was stimulated, all of which is good.

One researcher, Vouldoukis, "proposed that the mechanism behind these effects was due to an activation of antigen presenting cells (APC), which results in the production of hydrogen peroxide (H2O2) and nitric oxide (NO), both of which are reactive oxygen species and upset the oxidant-anitoxidant balance. In response to this, production of the antioxidant enzymes catalase and glutathione peroxidase is induced. This results in a polarized adaptive immune system..."

Again, I realize that I know just enough to be dangerous. So you'll have to let me know if all of this has any significance if you get the chance...
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Whisper9999



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PostPosted: Tue Jul 10, 2007 1:26 am    Post subject: Reply with quote

One q I do have is "how can activation of some nasty oxidizers be a good thing"? Are glutathione and SOD really potent enough to take these bad boys immediately before they do any damage or could this be like when researchers found Acetyl-L-Carnitine needed ALA to protect the increased mitochondrial activity?
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drtodorov
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PostPosted: Tue Jul 10, 2007 2:09 am    Post subject: Reply with quote

Well, if your synopsis is correct, then Vouldoukis proposed exactly the mechanism I hypothesized in my initial reply, i.e. glisodin triggers an immune response and activation of certain types of immune cells, which triggers the release of free radicals (a.k.a. ROS) because free radicals is how some immune cells kill invaders. ROS, in turn, are known to activate SOD, catalase, glutathione persoxidase, i.e the body's antioxidant defences (just like a wound would active defensive release of growth factors and synthesis of scar tissue).

The question is whether the net effect of all this is negative or positive over the long run. That one vascular study seems to indicate that it might be positive for atherosclerosis. But whether it is positive for the body as a whole remains to be seen.

Also, it could be that simply ingesting highly absorbable forms of gliadin alone (w/o exogenous SOD) could have the same effect as glisodin.

Did they do any lifespan studies in mice with Glisodin by any chance?
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Whisper9999



Joined: 16 Feb 2007
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PostPosted: Tue Jul 10, 2007 10:15 am    Post subject: Reply with quote

drtodorov wrote:
Well, if your synopsis is correct, then Vouldoukis proposed exactly the mechanism I hypothesized in my initial reply, i.e. glisodin triggers an immune response and activation of certain types of immune cells, which triggers the release of free radicals (a.k.a. ROS) because free radicals is how some immune cells kill invaders. ROS, in turn, are known to activate SOD, catalase, glutathione persoxidase, i.e the body's antioxidant defences (just like a wound would active defensive release of growth factors and synthesis of scar tissue).

The question is whether the net effect of all this is negative or positive over the long run. That one vascular study seems to indicate that it might be positive for atherosclerosis. But whether it is positive for the body as a whole remains to be seen.

Also, it could be that simply ingesting highly absorbable forms of gliadin alone (w/o exogenous SOD) could have the same effect as glisodin.

Did they do any lifespan studies in mice with Glisodin by any chance?


That's what I was afraid you were going to say. When I saw that it increased ROS output, it got me a little worried. But I do have to say that anything that it does a lot of things remarkably well: deceasing many types of inflammation, lowering IMT, decreasing oxidative stress, etc.

Anyway, your caution is a good one: I hadn't really thought about it, but it might end up being analagous to statins which help cardiovascular profiles but probably worsen other conditions leading to no net gain. (The "Acetyl-L-Carnitine w/o the ALA" isn't the best example because SOD is kind of the ALA.)

One more question: I am probably safe taking pomegranate juice everyday, right? (There was a study that showed that it decreased IMT and blood pressure as well.) Surely it does not work by causing a flood of free radicals but rather by pure antioxidant activity on LDL molecules as the authors of the study suggest?

Also, I haven't seen anything on lifespan studies so I don't think that those are there. Furthermore, their research plan doesn't include it as far as I know. But if I find something, I'll post it for everyone...
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drtodorov
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PostPosted: Tue Jul 10, 2007 12:17 pm    Post subject: Reply with quote

Pomegranate should be fine - as far as I know.
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