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WOW! True life extension starts with benaGene?


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#1 ageless

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Posted 21 December 2006 - 03:33 PM


Any thoughts?


http://www.aor.ca/re...ch/benagene.php

#2 health_nutty

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Posted 21 December 2006 - 03:50 PM

If this helps your research the active ingredient is: 3-carboxy-3-oxopropanoic acid which is also known as oxaloacetic acid according to:

http://www.ebi.ac.uk...iId=CHEBI:30744

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#3 ageless

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Posted 21 December 2006 - 04:57 PM

thought this was interesting:

Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise.Lancha AH Jr, Recco MB, Abdalla DS, Curi R.
Physical Education School, Biodynamic Department, Sao Paulo University, Brasil.

The present study examined the effect of diet supplementation of oxaloacetate precursors (aspartate and asparagine) and carnitine on muscle metabolism and exercise endurance. The results suggest that the diet supplementation increased the capacity of the muscle to utilize FFA and spare glycogen. Time to exhaustion was about 40% longer in the experimental group compared to the control, which received commercial diet only. These findings suggest that oxaloacetate may be important to determine the time to exhaustion during a prolonged and moderate exercise.

#4 ageless

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Posted 22 December 2006 - 01:56 PM

Cool... just came across this website: http://www.benagene.org/home

Imagine a nutritional supplement proven to increase lifespan in multiple species by up to 36%.

Imagine a nutritional supplement proven to decrease the toxicity of neurotoxins and free radicals.

Imagine a nutritional supplement that allows for weight management.

Imagine a nutritional supplement that mimics the genomic profile seen in calorie restriction, without a reduction in calorie input.

Imagine a nutritional supplement composed of metabolic products already found in every living cell.

Imagine a nutritional supplement shown in clinical trials to reduce blood glucose levels.

Imagine no more. benaGene

#5 ageless

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Posted 22 December 2006 - 02:06 PM

This is fascinating stuff... just beginning to read more into benagene.

http://www.benagene....genomic_changes

I'm hoping to get my hands on benagene from AOR early in the new year if my own research satisfies these extraordinary claims... so I'll keep everyone posted on any noticeable changes... bad or good. Looking to lose a little fat from the waistline also so we'll see...

#6 curious_sle

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Posted 23 December 2006 - 06:34 PM

Duno, the page is a bit odd and the whois doesn't look too trustworthy...
http://who.godaddy.c...prog_id=godaddy
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#7 acash

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Posted 23 December 2006 - 07:11 PM

I will be glad to attempt to answer questions. We have been working on benaGene for about three years. We are just now sticking our toe in the murky world of commercial enterprise......

Regards,

Alan Cash
Terra Biological LLC
acash@ix.netcom.com

#8 curious_sle

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Posted 23 December 2006 - 10:24 PM

Well, welcome Mr Cash.

Um, are there any indications that supplementing with oxaloacetic acid is offering additional benefit when one takes resveratrol already? How much overlap is there in the mimicing of CR between Resveratrol and Oxaloacetic Acid?

I can see it wrong but i think your product is not something no one else can sell, how will you distinguish youselfs from future competition?

#9 DukeNukem

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Posted 24 December 2006 - 02:49 AM

Alan,

A.O.R. is selling beneGene. What sort of due diligence did they do on the product and your research behind it? Also, is there any relevant third-party research that supports your claims?

Scott

#10 Karomesis

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Posted 24 December 2006 - 03:01 AM

A.O.R. is selling beneGene.


AOR is one of the most reputable companies I can think of. when did they start to sell it?

#11 acash

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Posted 24 December 2006 - 03:04 PM

Hi,

On combining benaGene with resveratrol, we do not know if it has any benefit. One of the reasons for this lack of knowledge is the difficulty in detecting what resveratrol does in the body. As we understand it at this point (and subject to change at any point in time), resveratrol increases the rate that the Sirt1 protein reacts with it's substrate (affecting the Km), but does not necessarily increase either the transcription rate of the protein from the gene, nor the amount of protein in the cells. Thus, the effects are difficult to measure.

We have blocked the effect of the sir2 gene in worms with a compound call Splitomycin, and also fed them benaGene. The worms continued to live longer than the control group, but not as long as worms without the splitomycin. So there is a decrease when the sir2 gene is blocked, but only about a 1/3 decrease in the excess lifespan, indicating other genes are involved in the extension (at least in worms). There is also some controversy if Splitomycin is a good blocker for the sir2 gene, so we are looking closer at our results.

As to the competition, we do have some intellectual property filed, but we do expect that at least one of the key compounds goes generic soon. You can even order it from Sigma, and weigh it out yourself. If you do, however, please combine it with Vitamin C, as it effects the efficacy and safety. That is also part of our intellectual property.

On the other post as to due dilligence by AOR, they did an extensive review that primarily focused on safety and purity. Please note that the lifespan expansion in humans are not proven, and will not be for some time. But if you are a worm, a fly or a mouse, things look pretty good.... The glucose reduction effect has been proven in humans. The third party information is coming, but it takes awhile....

AOR is starting to sell benaGene now. Their webpage is currently being updated to reflect this.

Regards,

Alan Cash
Terra Biological LLC
acash@ix.netcom.com

#12 niner

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Posted 24 December 2006 - 06:23 PM

Alan, thanks for posting. Ageless's post above sounded so much like an advert out of eastern europe that I ignored your website. (Sorry Ageless, I guess you were just excited... It does look interesting.) So Alan, when do you think that preprints might be available, particularly of the phase I human data?

Thanks Much,
George

#13 ageless

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Posted 24 December 2006 - 07:40 PM

Alan, thanks for posting.  Ageless's post above sounded so much like an advert out of eastern europe that I ignored your website.  (Sorry Ageless, I guess you were just excited... It does look interesting.)  So Alan, when do you think that preprints might be available, particularly of the phase I human data?

Thanks Much,
George


LOl, yeah I do tend to get excited by these kinda things, but once you get to know me more you'll realize I tend to be honest and science-based in my expectations for supplement effectiveness... one reason why I love AOR so much.
I'm also glad I got this discussion going and Alan Cash's insight into benagene is greatly appreciated.
I can't help it, I love this stuff! That's why I'm here at imminst. [tung]

#14 curious_sle

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Posted 24 December 2006 - 07:57 PM

Well, it certainly looks quite promising. Still, 60$ for 60x200mg? Also, what would a sensible dose be per kg per day? etc etc... i guess in a year or so price and information will be much closer to where i like :-)

#15 opales

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Posted 25 December 2006 - 04:50 PM

Ok, I understood that the mechanism of BenaGene is increased NAD+:NADH ratio? Doesn't R-ALA likely also do that, does BenaGene have some additional benefits? Is there a danger of lactic acidosis as with high dose R-ALA (I am admittedly way over my expertise here but does not increased NAD+:NADH ratio lead to inceased lactate:pyruvate ratio too)?

#16 ageless

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Posted 25 December 2006 - 08:16 PM

Ok, I understood that the mechanism of BenaGene is increased NAD+:NADH ratio? Doesn't R-ALA likely also do that, does BenaGene have some additional benefits? Is there a danger of lactic acidosis as with high dose R-ALA (I am admittedly way over my expertise here but does not increased NAD+:NADH ratio lead to inceased lactate:pyruvate ratio too)?


I've never heard of a danger of lactic acidosis from high-dose R-ALA. Do you have a source for this Opales... I know that the phamaceutical metformin can and has caused lactic acidosis in rare circumstances.

Found this study by accident suggesting a 'decreased' ratio of NAD+/NADH lowers oxidative stress???

Mol Cells. 1999 Aug 31;9(4):429-35. Links
Alteration of the NAD+/NADH ratio in CHO cells by stable transfection with human cytosolic glycerol-3-phosphate dehydrogenase: resistance to oxidative stress.Hwang K, Jeong DW, Lee JW, Kim IH, Chang HI, Kim HJ, Kim IY.
Graduate School of Biotechnology, Korea University, Seoul.

The intracellular level of the NAD+/NADH ratio plays a vital role in sustaining and coordinating the catabolic reaction of the cell, and reflects the redox state of cytosol. Antioxidants play a role to protect cytosol and membrane from free radicals. This role of antioxidants involves sustaining cell viability and the procedure is thought to be regulated by the equilibrium of the redox state of the cell. However, there is very little known about how the NAD+/NADH level is set and changed. To alter the ratio, human NAD-dependent glycerol-3-phosphate dehydrogenase (cGPDH) cDNA was transfected stably in CHO dhfr- cells. When compared to parental CHO cells, cGPDH activities of the transfected cells were increased 8-12 fold, but the NAD+/NADH ratio was decreased. Specific growth rate of the transfected cells was similar to or slight lower than that of wild type CHO cells. Cell viability of the stable transformants against H2O2 was increased without change of either catalase or glutathione peroxidase activity. However, the increase of cell viability was correlated with the decrease of NAD+/NADH ratio in transfectants. From these results, it is suggested that the overexpression of cGPDH changes the NAD+/NADH ratio toward a decrease, and by this change in the redox state the cell confers more resistance against H2O2.

#17 opales

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Posted 25 December 2006 - 08:42 PM

MR's supplement "guide" has some related discussion and few references, in discussion of combining R-ALA and metformin (potentially added risk for lactic acidosis):

http://www.cron-web....ts-guide-5.html

and for example Geronova lists on their R-PLUS description:
http://www.relentles...alog/r-plus.htm

Extremely high doses [of R- lipoic acid](over 6 gms/serving) may cause lactic acidosis.


Given this, would combining R-ALA and BenaGene be adviced against?

Edited by opales, 25 December 2006 - 09:16 PM.


#18 browser

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Posted 26 December 2006 - 03:33 AM

Hi,

On combining benaGene with resveratrol, we do not know if it has any benefit.  One of the reasons for this lack of knowledge is the difficulty in detecting what resveratrol does in the body.  As we understand it at this point (and subject to change at any point in time), resveratrol increases the rate that the Sirt1 protein reacts with it's substrate (affecting the Km), but does not necessarily increase either the transcription rate of the protein from the gene, nor the amount of protein in the cells.  Thus, the effects are difficult to measure.

We have blocked the effect of the sir2 gene in worms with a compound call Splitomycin, and also fed them benaGene.  The worms continued to live longer than the control group, but not as long as worms without the splitomycin. So there is a decrease when the sir2 gene is blocked, but only about a 1/3 decrease in the excess lifespan, indicating other genes are involved in the extension (at least in worms).  There is also some controversy if Splitomycin is a good blocker for the sir2 gene, so we are looking closer at our results.

As to the competition, we do have some intellectual property filed, but we do expect that at least one of the key compounds goes generic soon.  You can even order it from Sigma, and weigh it out yourself.  If you do, however, please combine it with Vitamin C, as it effects the efficacy and safety.  That is also part of our intellectual property.

On the other post as to due dilligence by AOR, they did an extensive review that primarily focused on safety and purity.  Please note that the lifespan expansion in humans are not proven, and will not be for some time.  But if you are a worm, a fly or a mouse, things look pretty good....  The glucose reduction effect has been proven in humans.  The third party information is coming, but it takes awhile....

AOR is starting to sell benaGene now.  Their webpage is currently being updated to reflect this.

Regards,

Alan Cash
Terra Biological LLC
acash@ix.netcom.com


You know, I searched and searched for sources of oxaloacetic acid. I asked a couple of suppliers of umm, "research" chemicals who are sponsoring members of ImmInst if they could get some oxaloacetic acid for me. I got the same response from each of them. No. It's too unstable. I've managed to UTFSE on a couple of websites which basically said the same thing. Yet Benagene contains it, guaranteed.
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#19 curious_sle

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Posted 26 December 2006 - 09:39 AM

Browser, i have thus far not seen a specification of the "proprietary blend" inuse in BenaGene but fromthe description it is fist of all probably not only oxaloacetic acid but a mix and second i would guess that the form in the supplement would be some buffered form.

Looks quite interresting. I don't use much ALA (except what little i get from 2 caps ortho-mind a day) so i see no problem there for me. Just, the thing is a wee but expensive and i have not seen a dose-response chart or anything like a decent sample size human trial (like, the averages are nice in the tables on the webpage but hey 15 people, one of em benefiting 1800% gives a excellent average... :-) )

#20 curious_sle

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Posted 26 December 2006 - 03:15 PM

ok AOR updated their page.

http://www.aor.ca/in...ts/benagene.php
http://www.aor.ca/in...ch/benagene.php

i wonder. the crmimic.ca guys state 200mg per cap... no specifics. AOR states 100mg vitamine C + 100mg oxaloacetic acid... that makes 200mg too... now do the crmimic.ca guys mean the same? Ah well...

#21 browser

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Posted 26 December 2006 - 05:45 PM

ok AOR updated their page.

http://www.aor.ca/in...ts/benagene.php
http://www.aor.ca/in...ch/benagene.php

i wonder. the crmimic.ca guys state 200mg per cap... no specifics. AOR states 100mg vitamine C + 100mg oxaloacetic acid... that makes 200mg too... now do the crmimic.ca guys mean the same? Ah well...


Look at the dosages given at http://www.benagene....ucose_reduction . The doses are all over the place and though I haven't bothered to graph response to dosage, by eyeballing it, it looks like the dosage has little to do with the response. Of course we're dealing with ages and physical conditions which vary all over the place.

Notice at http://www.benagene....genomic_changes the Sirt1 and Sirt2 genes are left out. The Sert1 gene is the one upgregulated by resveratrol.

With respect to the price, well, USD 60/30 days is steep for the average supplement. Two things here. First off, this, if it turns out to be genuine, it is no ordinary supplement. It's sort of the Holy Grail we've been looking for. We should expect to pay extra for Holy Grails. I am not part of Tom/Paul Mathews/Wakfur bulk buy of resveratrol, but I do know that if you tried to mimic this sort of thing with resveratrol by buying lots of Longevinex (which will be shipping 100 mg. resveratrol in the new batch of capsules) or other sources, you'd be paying at least USD 2/day and probably quite a bit more if you wanted the resveratrol version of CR mimics. You'd be taking large doses of resveratrol, which has been /tested for toxicity/ in rats but it's something we don't really know the long term effects of in very large quantities. Myself, I /can/ afford this stuff, but /am/ suspicious. If there are some real clinical trials of this stuff in humans and the mechanism by which this stuff works gets explained to my satisfaction (e.g. why go after this particular part of the Krebs/Citric Acid Cycle?) then I'd be a buyer. As far as the price, competition can enter the market and it would be easy for others to offer a "me too" version of this, sans the Vitamin C, just as you can go most anywhere these days, buy R-ALA and ALCAR separately and take them together, thereby avoiding having to pay royalties to Ames.

If we get some more proof that this is the real deal, I would buy perhaps a couple years' supply of the Benagene product from AOR or whomever because I feel both an ethical obligation and an obligation to the spirit of discovery and research to pay the piper. The developers/people paying for the clinical trials deserve to be compensated for their efforts. I don't feel the same way about Ames' patent (though I cannot take R-ALA nor ALCAR because they make me too speedy and instantly insomniac) because I feel a different obligation to a researcher in education who's research is already funded.



What I am very excited about is that the Gaia effect (people interested and sometimes making independent but identical discoveries in different parts of the world has hit CR and weight management). There was the proposition made on sci.life-extension which there seemed to be agreement on that

"How does Sinclair know that the OPCs found in grape seed extract, for example, aren't far more effective than resveratrol in extending lifespan? Or how does he know pomegranate extract or rhubarb extract or citrus bioflavonoids like nobiletin aren't more effective? There are enough clues in the literature to suggest to any reasonable, informed person, that some of these compounds will extend lifespan."

The consensus was that Sinclair's research would prevent research on other approaches. I didn't believe that to be true, and thankfully it looks like I was right. The other exciting thing is the recent announcement of the research that's going to be published in Nature that there's a definite profile of bacteria found in the stomach of obese versus lean rats and humans. The study involved transferring the bacteria in the stomachs of obese rats to those of lean rats. The lean rats got fat. It was observed in humans that the profile of bacteria in the stomachs of obese people got closer and closer to the profile of bacteria in lean people as they dieted and lost weight. Now of course this is just an interesting study that needs to be repeated and has already been attacked as being pretty much useless with respect to the human obesity epidemic because that is caused by junk food and sloth, not bacteria. Nonetheless, I'm excited. I have this intuitive faith that Nature has kept things simple. We just need to find the little trick, like for example, discovering the value of NO (and thereby winning a Nobel Prize), that stomach ulcers are caused by a bacteria cured by an antibiotic and not the result of emotional makeup. I'm excited the way things are moving. I'm expecting someone to discover that things like BHP and baldness aren't caused by DHT afterall. That there's a much more simple explanation and preventative (maybe even cure?) and that DHT and all the complicated mechanisms being researched are just features (like stress in ulcers) that are throwing people off from discovering the truth. BTW, the active ingredients in Benagene, according to the AOR website, are found in abundance in red apples.

#22 ageless

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Posted 26 December 2006 - 06:24 PM

Nice, inspiring post browser!
I too noticed the red apples statement and it instantly reminded me of my grandparents who only recently passed away in their 90's... they owned a apple orchird for many years and my grandmother was fond of incorporating these organic apples into many dishes. Myself, I liked the taste of a freshly picked apple straight from the tree.
Despite a high fat/salt diet and decades of smoking both lived tremendous-rich lives with amazing mental/physical stamina that lasted into their final decade.
Could it have been the apples all along... I have begun to wonder.


ok AOR updated their page.

http://www.aor.ca/in...ts/benagene.php
http://www.aor.ca/in...ch/benagene.php

i wonder. the crmimic.ca guys state 200mg per cap... no specifics. AOR states 100mg vitamine C + 100mg oxaloacetic acid... that makes 200mg too... now do the crmimic.ca guys mean the same? Ah well...


Look at the dosages given at http://www.benagene....ucose_reduction . The doses are all over the place and though I haven't bothered to graph response to dosage, by eyeballing it, it looks like the dosage has little to do with the response. Of course we're dealing with ages and physical conditions which vary all over the place.

Notice at http://www.benagene....genomic_changes the Sirt1 and Sirt2 genes are left out. The Sert1 gene is the one upgregulated by resveratrol.

With respect to the price, well, USD 60/30 days is steep for the average supplement. Two things here. First off, this, if it turns out to be genuine, it is no ordinary supplement. It's sort of the Holy Grail we've been looking for. We should expect to pay extra for Holy Grails. I am not part of Tom/Paul Mathews/Wakfur bulk buy of resveratrol, but I do know that if you tried to mimic this sort of thing with resveratrol by buying lots of Longevinex (which will be shipping 100 mg. resveratrol in the new batch of capsules) or other sources, you'd be paying at least USD 2/day and probably quite a bit more if you wanted the resveratrol version of CR mimics. You'd be taking large doses of resveratrol, which has been /tested for toxicity/ in rats but it's something we don't really know the long term effects of in very large quantities. Myself, I /can/ afford this stuff, but /am/ suspicious. If there are some real clinical trials of this stuff in humans and the mechanism by which this stuff works gets explained to my satisfaction (e.g. why go after this particular part of the Krebs/Citric Acid Cycle?) then I'd be a buyer. As far as the price, competition can enter the market and it would be easy for others to offer a "me too" version of this, sans the Vitamin C, just as you can go most anywhere these days, buy R-ALA and ALCAR separately and take them together, thereby avoiding having to pay royalties to Ames.

If we get some more proof that this is the real deal, I would buy perhaps a couple years' supply of the Benagene product from AOR or whomever because I feel both an ethical obligation and an obligation to the spirit of discovery and research to pay the piper. The developers/people paying for the clinical trials deserve to be compensated for their efforts. I don't feel the same way about Ames' patent (though I cannot take R-ALA nor ALCAR because they make me too speedy and instantly insomniac) because I feel a different obligation to a researcher in education who's research is already funded.



What I am very excited about is that the Gaia effect (people interested and sometimes making independent but identical discoveries in different parts of the world has hit CR and weight management). There was the proposition made on sci.life-extension which there seemed to be agreement on that

"How does Sinclair know that the OPCs found in grape seed extract, for example, aren't far more effective than resveratrol in extending lifespan? Or how does he know pomegranate extract or rhubarb extract or citrus bioflavonoids like nobiletin aren't more effective? There are enough clues in the literature to suggest to any reasonable, informed person, that some of these compounds will extend lifespan."

The consensus was that Sinclair's research would prevent research on other approaches. I didn't believe that to be true, and thankfully it looks like I was right. The other exciting thing is the recent announcement of the research that's going to be published in Nature that there's a definite profile of bacteria found in the stomach of obese versus lean rats and humans. The study involved transferring the bacteria in the stomachs of obese rats to those of lean rats. The lean rats got fat. It was observed in humans that the profile of bacteria in the stomachs of obese people got closer and closer to the profile of bacteria in lean people as they dieted and lost weight. Now of course this is just an interesting study that needs to be repeated and has already been attacked as being pretty much useless with respect to the human obesity epidemic because that is caused by junk food and sloth, not bacteria. Nonetheless, I'm excited. I have this intuitive faith that Nature has kept things simple. We just need to find the little trick, like for example, discovering the value of NO (and thereby winning a Nobel Prize), that stomach ulcers are caused by a bacteria cured by an antibiotic and not the result of emotional makeup. I'm excited the way things are moving. I'm expecting someone to discover that things like BHP and baldness aren't caused by DHT afterall. That there's a much more simple explanation and preventative (maybe even cure?) and that DHT and all the complicated mechanisms being researched are just features (like stress in ulcers) that are throwing people off from discovering the truth. BTW, the active ingredients in Benagene, according to the AOR website, are found in abundance in red apples.



#23 curious_sle

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Posted 26 December 2006 - 08:25 PM

Well, i for one have been positively surprised that already now (relatively speaking) there is a supplement out that works on shifting nah+/nadh ratio, something that has extensively been researched and where there is tantalizing indication that influencing can have very positive outcomes in "aging". Could it be i should be cautiously more optimistic about life extension? Maybe really the time has come for robust moderate life extension (say, 20% if begun in your 30ies) in this decade already? I certainly hope so!

2$/day or more for Resveratrol. Well, since i lost weight on very :-) moderate CR i need fairly little to achieve a decent mg/kg ratio so i spend less on Resveratrol but invest the remainder in cardiovascular stuff like ellagitanin/pomegranate extract and asthaxantin etc :-). So yes i would rather like a recomendation as to what aprox would be the mg/kg/d ratio in humans. The trial data on their website is erm, minimal :-) and does not allow for too much insight there. (others care to point out what i've overlooked perhaps?)

#24 renwosing

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Posted 27 December 2006 - 06:04 PM

Will Benegene be benefit for recovering stroke patient?

I am looking for every possibility.

Anybody would like to comment on it?

Thanks.

Later,

Renwosing

#25 VP.

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Posted 28 December 2006 - 04:40 AM

Where are the published, peer reviewed studies on Benegene? If AOR says it's true does that make it Gospel? I smell a rat, and I don't mean a double blind placebo controlled rat.

#26 FunkOdyssey

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Posted 28 December 2006 - 07:05 AM

Where are the published, peer reviewed studies on Benegene?

Now we're asking the right question.

#27 browser

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Posted 29 December 2006 - 12:02 AM

ok AOR updated their page.

http://www.aor.ca/in...ts/benagene.php
http://www.aor.ca/in...ch/benagene.php

i wonder. the crmimic.ca guys state 200mg per cap... no specifics. AOR states 100mg vitamine C + 100mg oxaloacetic acid... that makes 200mg too... now do the crmimic.ca guys mean the same? Ah well...


I was thinking the same thing. Yes, it's not clear, but I suspect because Vitamin C is a necessary part and parcel of the preparation/delivery, when they say 200 mg in the research they mean 100+100 mg.

#28 maxwatt

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Posted 29 December 2006 - 02:40 AM

I would be pleasantly surprised when/if benegene actually works out. My observation is that it's too simplistic to try to overload one element of a chemical cycle as this substance is claimed to do. The body's exquisitely tuned feedback mechanisms simply adjust endogenous production and maintain homeostasis. The attempt fails. Years ago they tried to do something like this with NAD and NADH supplements. The gullible put them in their gullets. It didn't work. While I hope this one is different, I am dubious. All the more so because there are no published papers. Usually there is at least a hint to be found in pub med.

I look forward to users' reports on this supplement, but one Dr. Colgan once said "You can put hedge trimmings in capsules and sell them", [and the placebo effect guarantees enough people will swear it works that you'll make money.]

Richard

#29 rfarris

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Posted 29 December 2006 - 03:21 PM

What about Carnosine? Supposedly it overloads one of the cycles, too.

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#30 maxwatt

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Posted 29 December 2006 - 04:44 PM

What about Carnosine?  Supposedly it overloads one of the cycles, too.


With dubious efficacy. Acetyl-l-carnosine appears to be a potent inhibitor of glycation, and seems useful for that purpose. As for Benagene, I await the peer-reviewed studies. The putatuve mechanism of action is plausible but unconvincing.




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