214 replies to this topic

[rfarris]

With dubious efficacy. Acetyl-l-carnosine appears to be a potent inhibitor of glycation, and seems useful for that purpose.

Are you suggesting, then, that it is more useful to take a-l-carnosine several times a day than a bolus once a day?

[maxwatt]

With dubious efficacy. Acetyl-l-carnosine appears to be a potent inhibitor of glycation, and seems useful for that purpose.

Are you suggesting, then, that it is more useful to take a-l-carnosine several times a day than a bolus once a day?

Umn, that is a natural inference, but I hadn't meant to imply it. the function of a-carnosine as an AGE-formation inhibitor is different than the use by body bulilder of l-carnosine, supposedly to build muscle and prevent exhaustion. For that purpose it is not terribly effective, any more than a steak dinner (which contains lots of carnosine.)

[acash]

Hello.

On the third party reveiws of benaGene, we are still working through the process. It takes quite awhile for peer review and to have third parties repeat some of the key experiments. Some good news on this front, the National Institute on Aging (part of the National Institute of Health) has written to us with the following statement,

"Your proposal to the NIA Interventions Testing Program (ITP) has been reviewed through a two-tier review and prioritization process, and was given a high priority for inclusion in the next round of testing."

NIA/NIH has some additional questions that we have to answer before we will know if benaGene is fully accepted into the program. It looks good so far....we should know in a month or so. It will generate quite a bit of data.

More on the Intervention Testing Program can be found at the following web site: http://www.nia.nih.g...tingProgram.htm

Most of our work will not be published because it deals with efficacy, stability and toxicity that was required in the permitting process. We do not wish to share this information with competitors at this time--we think parts of our blend will go generic soon enough without providing the information to our competitors.

Our work on life extension in animals should be reported within the next six months. So a good question is, "Why is benaGene being offered now? Why not wait six months?"

Once the product became legal to sell, we had a moral decision. Wait for the publications, or offer it for sale immediately. There was quite a bit of internal heated debate over this, and, as per most debates, both sides were right. We decided to offer benaGene for sale now, because the toxicity data indicates that it has about the same toxicity as a lemon (as would be expected from a Krebs cycle metabolite), and it may do significant good.....

Some other papers to consider:

Puntel, RL et al, "Krebs Cycle Intermediates Modulate Thiobarbituric Acid Reactive Species (TBARS) Production in Rat Brain In Vitro", Neurochemical Research, Vol. 30, No. 2 February 2005 pp. 225-235

Wood, JP et al, "Zinc and Energy Requirements in Induction of Oxidative Stress to Retinal Pigmented Epithelial Cells", Neurochemical Research, Vol. 28, No. 10, October 2003, pp. 1525-1533

Yamamoto, H, et al, "Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice" Toxicology Letters, 143 (2003) pp. 115-122

Desagher, S, et al, "Pyruvate Protects Neurons against Hydrogen Peroxide-Induced Toxicity", The Journal of Neuroscience, December 1, 1997 pp 9060-9067

There are others also.

Regards

[ageless]

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

My feelings are this is going to be a tad better than hedge trimmings.

[opales]

Alan (or anyone who knows), what do you think of this:

http://groups.google...a61547e347425e4

I interpret the above that carnosine depletes circulating krebs cycle intermediaries including *oxaloacetic acid*, and thus suffocates the mitochondrially mutated cells due lack of energy (they rely on pyruvate or possibly these intermediaries for energy). This, according to de Grey and Rae would probably be a good thing, in the long enhancing survival of other cells due reduced overall oxidative stress I presume.

Conversely, according to above (and my logic), extra oxaloacetic acid would enhance the survival of mitochondrially mutated cells.

Am I misunderstanding something? Does this challenge de Grey's MiFRA (Mitochondrial Free Radical Theory of Aging), usefulness of carnosine or maybe benaGene?

Edited by opales, 05 February 2007 - 07:51 PM.

[acash]

opales,

An interesting supposition, that adding oxaloacetic acid is preventing the death of "the evil 1%" of the cells that may move on to develop full blown tumors.

Expermentally, we have not seen this even a hint of this, but the opposite. Almost all laboratory mice die of cancer-- some are more prone to cancer than others, but in the end, cancer is the major cause of death (in the laboratory). Thus, mice are a fairly overstated predictor of the ability of compounds to cause cancer. In our experiments, we have seen an increase in lifespan in mice, which typically means allowing mice to live with their cancers or delaying the incidence of cancer. I believe it was Dr. Spindler that noted that under Calorie Restriction, the mice still get cancer....the cancer just grows slower or starts a bit later and kills them later. Thus, being somewhat pragmatic, I don't think the augument of "the evil 1% left" fits with what we are seeing. Genomically, it also does not seem to fit what is happing (at least in liver tissue), because we have seen an up-regulation of genes thought to be preventative of cancer, such as FOXO3.

As to the challenge to de Grey's MiFRA, I don't think there is any challenge. Oxaloacetic Acid is a powerful anti-oxidant. (See Puntel, RL et al, "Krebs Cycle Intermediates Modulate Thiobarbituric Acid Reactive Species (TBARS) Production in Rat Brain In Vitro", Neurochemical Research, Vol. 30, No. 2 February 2005 pp. 225-235). I personally don't think that the additional lifespan we have seen is due to antioxidant activity, but due to changes in genomic expression. So far, I am not aware of any anti-oxidants that have increased maximal lifespan-- only genomic changes seem to work, whether by genetic engineering or causing the cells to change the genomic profile itself (such as in calorie restrion or by using my favorite compound). Anti-oxidants may, however, increase average lifespan by reducing the risk of various disease states. They also may interact with kreb cycle metabolites, which makes life more complicated....Vitamin C certainly does with pyruvate and oxaloacetic acid.

Regards,

Alan Cash

[tintinet]

Hi Alan-

The question of the actual contents of CR Mimic caps (200 mg), has been raised several times in this thread. Can you tell us if it's 100 mg 3-carboxy-3-oxopropanoic acid plus 100 mg vitamin C (AOR's formulation) , or 200 mg 3-carboxy-3-oxopropanoic acid, or other formulation?

Also, on what basis are you recommending 1 cap/day?



Thanks!

[acash]

The CR Mimic caps are the same formulation as the AOR caps, 100 mg 3-carboxy-3-oxopropanoic acid plus 100 mg vitamin C.

The basis for recommending 1 cap/day took into consideration several factors. They are as follows:

1. Safety. In the USA, this is currently working it's way through the FDA as a "New Dietary Ingredient" or NDI. The ingredients in the capsules are consumed every day by everyone (as long as you eat, CR society personnel possibly exempted...). However the amount of the supplement in the food is very low. We had to show FDA a possible diet that contains the same amount of our NDI as can be found in the food supply in order to obtain our NDI certification (which we expect in the USA by the end of the year), which limited the maximum amount of ingredients we could place in the capsules.
2. Safety. We wanted a product that if the entire bottle was consumed in one event, such as by a child by mistake, that there would be little risk of major injury. Our calculations are based on maximal does tolerated by mice with out ill effect (we have not tried to find and LD50 in humans....)
3. Safety. We wanted a product that simulated calorie restriction, but made with human metabolic products to lower overall risk of rare adverse reactions. Our components are already in every cell of everybody, which lowers the risk of the 1 in 1,000,000 type of problem which occationally occurs with the introduction of new compounds. As an example of this, peanuts contain resveratrol, and many people can eat large amounts of peanuts to obtain their resveratrol fix, but for some rare individuals with a peanut allergy, they can be deadly...... As an NDI, we have to think of things like this.
4. Safety. We selected the lowest dose in the human clinical trials that was shown to have an effect on fasting glucose levels. Our thinking is that lowering glucose levels is very much like eating less.....which is kind of like calorie restriction.....which is kind of a simple thought, but we like simple. It is interesting that other glucose reduction compounds seem to also have the ability to change the genomic response of the organism, like metformin, and also has been shown to increase lifespan in mice.

Hope this helps.

Regards,

Alan Cash

[DukeNukem]

Alan,

Who is the cheapest supplier of beneGene currently?

[tintinet]

So, is this a homeopathic dose?

Resveratrol from peanuts?

Are you serious?

The CR Mimic caps are the same formulation as the AOR caps, 100 mg 3-carboxy-3-oxopropanoic acid plus 100 mg vitamin C.

The basis for recommending 1 cap/day took into consideration several factors.  They are as follows:

1.  Safety.  In the USA, this is currently working it's way through the FDA as a "New Dietary Ingredient" or NDI.  The ingredients in the capsules are consumed every day by everyone (as long as you eat, CR society personnel possibly exempted...).  However the amount of the supplement in the food is very low.  We had to show FDA a possible diet that contains the same amount of our NDI as can be found in the food supply in order to obtain our NDI certification (which we expect in the USA by the end of the year), which limited the maximum amount of ingredients we could place in the capsules.
2. Safety.  We wanted a product that if the entire bottle was consumed in one event, such as by a child by mistake, that there would be little risk of major injury.  Our calculations are based on maximal does tolerated by mice with out ill effect (we have not tried to find and LD50 in humans....)
3. Safety.  We wanted a product that simulated calorie restriction, but made with human metabolic products to lower overall risk of rare adverse reactions.  Our components are already in every cell of everybody, which lowers the risk of the 1 in 1,000,000 type of problem which occationally occurs with the introduction of new compounds.  As an example of this, peanuts contain resveratrol, and many people can eat large amounts of peanuts to obtain their resveratrol fix, but for some rare individuals with a peanut allergy, they can be deadly......  As an NDI, we have to think of things like this.
4.  Safety.  We selected the lowest dose in the human clinical trials that was shown to have an effect on fasting glucose levels.  Our thinking is that lowering glucose levels is very much like eating less.....which is kind of like calorie restriction.....which is kind of a simple thought, but we like simple.  It is interesting that other glucose reduction compounds seem to also have the ability to change the genomic response of the organism, like metformin, and also has been shown to increase lifespan in mice. 

Hope this helps.

Regards,

Alan Cash

[acash]

Tintinet,

Resveratrol is found in peanuts, but that was used as an example because of the extremely toxic nature of some plants to very small percentages of people. Just because something is a "natural" product, it does not mean it is not dangerous to a small group. We wish to minimize this risk by using a metabolite already found in people. That was the point I was trying to get at, not that you should eat peanuts because of their resveratrol content.

The term "homeopathic dose" seems to have a variety of meanings, depending upon which practitioner you favor. We did the dosage based on the above thread.

Regards,

Alan

Duke Nukem,

I am not quite sure which distributor has the lowest price at any one point in time. I am not involved in that side of things.

Alan

[tintinet]

Tintinet,

Resveratrol is found in peanuts, but that was used as an example because of the extremely toxic nature of some plants to very small percentages of people.  Just because something is a "natural" product, it does not mean it is not dangerous to a small group.  We wish to minimize this risk by using a metabolite already found in people.  That was the point I was trying to get at, not that you should eat peanuts because of their resveratrol content. 

The term "homeopathic dose" seems to have a variety of meanings, depending upon which practitioner you favor.  We did the dosage based on the above thread.

Regards,

Alan

Duke Nukem,

I am not quite sure which distributor has the lowest price at any one point in time.  I am not involved in that side of things.

Alan

Alan,

Please excuse my prior exasperated comments.

AFAIK, the amount of found in peanuts contain relatively minuscule quantities of resveratrol, thus the idea of consuming mass quantities of peanuts (massively high in calories, obviously) to attain resveratrol. strikes me as a ludicrous proposition.

If you have a peanut allergy, you don't buy Jif. You don't just buy a little Jif.

Has this dose of Benegene been clinically tested in humans? ISTM the clinical results posted for it used those terrible larger doses.

Homeopathic dose. Yes, it varies- from almost zilch to 0 plus zilch plus nada. Sorry, I didn't mean to be taken literally there.

[acash]

Hi Tintinet,

I see your point on the peanuts.

On the clinically testing, there was a range given from 100 mg per day to up to 1,000 mg per day. No adverse side effects were noted. We have elected to start with the lower doses for the reasons stated above.

As an interesting side note, dosing rats was also part of the study. At very high doses the rats did not die, but their pancreas began to increase the number and size of the beta cells. The beta cells produce insulin. It has been speculated that this is the reason that the test in Type 1 diabetics was positive. At lower doses in the rats this was not seen. Even more interesting is that there was a study that overexpression of Sirt1 in the pancreas increases glucose tolerance. Somehow, this is all tied together, but we are still looking into this.

Regards,

Alan

[tintinet]

Thanks Alan.

Are there any results for humans with restriction of dose to 100 mg QD only?

Pancreatic hypertrophy with islet cell hyperplasia? Were insulin levels increased at higher levels of intake of Benegene? Lower levels? Any development of neuroendocrine neoplasia?

Thanks!

[acash]

Tintinet,

No neoplasias noted in the necropsies.

As safety is our number 1 concern, our animal testing was done a "overdose" levels as seen below:

The rat study was done with 40 Wistar rats initially given 5mg per day orally for 40 days. The pancreas of the rats demonstrated proliferation and hyperplasia of the islet cells (i.e. an increase in the number and size of the the islet cells). Note that 5 mg/day in these rats is about 50 mg/kg body weight, or in humans a dosing of about 5,000 mg, or about 1 and 1/2 BOTTLES of benaGene per day for 40 days.

In another test, 40 rats were given 10 mg per day (about 3 Bottles per day in human dosage terms) for 40 days. In these rats there were some changes in the pancreas. Some islets were decrease in size and hyperemic, alpha cells being atrophic, while beta cells were hypertrophic and stained densely. The liver, hypophysis, adrenals and gonadal glands showed no particular changes.

There was no mortality in the group despite taking the equivalent of 3 bottles of benaGene a day for 40 consecutive days. We don't recommend this dosage, however, of course......

Regards,

Alan Cash

[xanadu]

We are starting to see the negative side of res at high dosages. No doubt there will be other things to turn up. I've always said to avoid megadoses and as usual that seems to be the case once again. Shoot for the lowest effective dose, not the highest you can stand.

[tintinet]

We are starting to see the negative side of res at high dosages. No doubt there will be other things to turn up. I've always said to avoid megadoses and as usual that seems to be the case once again. Shoot for the lowest effective dose, not the highest you can stand.

So far, I've not seen mention of a negative side of resveratrol, although I expect, at some dose, some negative effects must emerge. Do you know specifics and dose levels? Thanks!

[xanadu]

tin, take a look at the previous few posts and read them "At very high doses the rats did not die, but their pancreas began to increase the number and size of the beta cells" This is not normal.

[curious_sle]

Alan,

Who is the cheapest supplier of beneGene currently?

crmimic, they charge like 30$ for a at recomended dose one onth supply. The AOR PRoduct i've seen so far was like 60$ (wow :-) me not buying). I'll wait till summer or so when there is more to read and when hopefully (sorry Mr. Cash :-) ) there is some more cost efficient way to get it. I guess my break-even is at like 20$/month or so. And i'd like more then 100mg... ah well...

[curious_sle]

tin, take a look at the previous few posts and read them "At very high doses the rats did not die, but their pancreas began to increase the number and size of the beta cells" This is not normal.

Um, did i miss something? this is about oxaloacetic acid right? Where is resveratrol beeing adressed exactly?

ps: hat tip to Mr Cash for beeing helpfull :-)

[checkinguy]

I see it for 45 $Can.

http://www.feelgreat...ct.php?p=25406#

(This is where I buy my AOR OrthoMind)

I think that I'll buy some and try a conservative dose, like 1 per week and check for reactions.
Maybe more news will trickle out to make me more confident.

[tintinet]

tin, take a look at the previous few posts and read them "At very high doses the rats did not die, but their pancreas began to increase the number and size of the beta cells" This is not normal.

Sorry, I thought you also made a statement regarding side effects of resveratrol. I did understand the effects of high dose Benegene, according to Alan, resulted in pancreatic abnormalities.

[acash]

Hi,

For clairity, I need to note that the doses of benaGene that resulted in changes to the pancreas in rats were very, very, very, very high over an extended period of time.

In separate tests, we determined that the LD50 for a single dose exceeded 5,000 mg/kg. Many people would consider this as "non-toxic".

As perhaps a better way to picture this, and to give some perspective here, imagine taking a similar sized mega dose with something else, like asprin. 3 bottles of asprin per day for 40 days..... not a pretty thought.....

[tintinet]

Thanks, Alan. Your input here WRT clear evaluation of Benegene is invaluable.

[health_nutty]

We are starting to see the negative side of res at high dosages. No doubt there will be other things to turn up. I've always said to avoid megadoses and as usual that seems to be the case once again. Shoot for the lowest effective dose, not the highest you can stand.

The question is: what is the minimum effective dose to maximize the health potential from resveratrol? 400mg-1000mg may seem like megadosing but it's really just a matter of perception of what is large and what is small (is 1g of vit c megadosing?). Based on the mice studies the minimum effective human *seems* to be at least 5mg/kg/d. My only point is it is too early to know what are megadoses and what are not. I certainly understand the value of waiting until we know for sure.

Edited by health_nutty, 08 February 2007 - 08:43 PM.

[tintinet]

On n'est jamais sûr de rien.

[xanadu]

OK, I seem to have read the part about high doses and thought he was talking about rsv causing the abnormalities but it was benagene he was talking about.

[cellfighter]

I just bought my AOR Benegene from a US source at a great price! US $34.99. I plan to take 2 capsules daily. Should I take a higher dose?

Edited by cellfighter, 10 February 2007 - 02:01 AM.

[tintinet]

'K: Whereat, please?

Or is this type of discussion relegated to PMs only?

[curious_sle]

Yeah, still no froogleable shop that features benagene... 35$ is getting close to reasonable... still, cellfighter: 70$ per month? are you shure it is worth it? I mean within 12 months or so cost will be a whole lot lower and I am not shure it makes that much difference, i mean even if it slows aging :-) down 10% that'd be like a bit more then a month in that year and you'd have spent like 840$ on that... nah...