22 replies to this topic

[edward]

I am very interested in Benagene however as many have mentioned I cannot justify the price at this time, so here are some thoughts.

Malic acid converts directly to oxaloacetic acid (3-carboxy-3-oxopropanoic acid) the active ingredient of Benagene...

http://www.answers.c...ic/oxaloacetate
http://users.mrbean....last/HF5-2.html

It stands to reason that taking Malic Acid would be almost as effective as directly supplementing the Benagene compound... Malic Acid is very cheap and stable.

Any thoughts?

**********
benaGene™ contains a key intermediate in the Kreb's Cycle.

30 Vegi-Caps 200 mg 100% Vegetarian
_____________________________________________
SUPPLEMENT FACTS:
Serving Size: 1 Capsule
____________________________________________________
benaGene™ (3-carboxy-3-oxopropanoic acid) .......... 100 mg
Vitamin C .......................................................... 100 mg
____________________________________________________
*********

3-carboxy-3-oxopropanoic acid = oxaloacetic acid
http://www.ebi.ac.uk...iId=CHEBI:30744

again

oxaloacetic acid is produced by the oxidation of Malic Acid in the Krebs Cycle
http://www.answers.c...ic/oxaloacetate

[health_nutty]

I love posts like this. I used to take magnesium malate, but ever since starting high dosage resveratrol, I haven't been able to take much anymore.

Maybe I should try some regular malic acid caps.

[shadowrun]

It definately sounds very interesting and I have considered taking Benagene...but the cost is really prohibitive

I'm currently on resveratrol and I wonder these 2 substances would interact - Would it even be a smart idea to take them concurrently?

[edward]

There dosen't appear to be any negative interaction between Benagene and Resveratrol as they are working by different mechanisms.

Does anyone have any thoughts on the Malic Acid idea. My references and research back up my theory but no one that I know of has directly proposed the use of Malic Acid to boost 3-carboxy-3-oxopropanoic acid/oxaloacetic acid levels in the body since the Benagene product and research are so new.

Edited by edward, 07 May 2007 - 10:48 PM.

[maxwatt]

It definately sounds very interesting and I have considered taking Benagene...but the cost is really prohibitive

I'm currently on resveratrol and I wonder these 2 substances would interact - Would it even be a smart idea to take them concurrently?

Tintinet was taking both simultaneously, and reported peripheral neuropathy as a possible side effect, at a much lower dose of resveratrol than others are taking with no problem. Perhaps Benegene potentiates resveratrol's action, so 1 gram is like six grams. Perhaps not. No one really knows, but I would be cautious, and increase dosage only slowly.

[acash]

Hi Edward,

On the malate issue, one of the key issues is that benaGene turns NADH into NAD, not that the end product is malate (which won't hurt you). The change in the NAD/NADH ratio appears to be the switching mechanism (if held for more than 2.5 weeks) to start changing the expression of proteins from your DNA to a more favorable expression. The generation of malate is not the key issue....

For more on this, there are some publications you may want to look into:
http://dms.dartmouth...07_brenner.html
This press release shows that increasing NAD+ levels increases lifespan (if you are made out of yeast....)

Here is another one of interest:
http://www.jbc.org/c.../jbc.C700018200
This paper shows that increasing the rate of NAD generation from NADH increases the longevity of human cells by up to 70%. They do it by using a retrovirus and genetic engineering. Or you can use benaGene......

[edward]

acash,

I understand what you are saying but that is not the issue I am pointing out. I am pointing out that Malic Acid is converted in vivo to Oxaloacetic Acid (3-carboxy-3-oxopropanoic acid) which is the active ingredient in Benagene, therefore supplementing malic acid would accomplish the same thing as supplementing Benagene albeit much more cheaply (perhaps you would have to supplement a large amount of malic acid to ensure enough is converted, but that is no big deal as malic acid itself is good for you and even in high doses its still very cheap). Just like supplementing prohormones like Androsterone and DHEA to increase Testosterone by conversion, or taking beta carotene so that it converts in the body to vitamin A, its the same idea.

Edit: No offense acash, but you have a monetary interest in the sales of Benagene so although you may present some good information, it would be very negative to your business if say Malic Acid turns out to be a viable cheap alternative.

Edited by edward, 08 May 2007 - 02:56 AM.

[acash]

Edward,

Yes, I do have a monetary interest in the sales of benaGene, but taking malic acid does not change NADH to NAD, which is the real point (check your energy pathways)...not that malic acid is produced.

There are reasons to take malic acid supplements, especially if you have Fibromyalgia. We have no reason to suspect that malic acid increases lifespan at this time. Hey, but maybe I'll be surprised....

Regards,

Alan

[ganeshge]

acash,

Why not take NAD as a supplement. My guess would be, it should produce the same effect as Benagene.

Recent research revealed the use of NAD to extend the lifespan of yeast (link to the article is mentioned below)

http://www.news-medical.net/?id=24758

[edward]

As you can see (acash, here is the metabolic pathway). Malic Acid converts directly to oxaloacetic acid (benagene), therefore enough malic acid being converted in this way should boost oxaloacetic acid levels in turn modifying NADH to NAD just like directly supplementing oxaloacetic acid (benagene). I don't know how much clearer I can be.

[ganeshge]

Edward,

It would be interesting to check literature on the use of Malic acid for lifespan extension. Malic acid also seem to be a good chealting agent which would help in maintaing the longevity of the cell.

Any thoughts on using NAD (may be sublingual) as a supplement (refer to my previous post)?

[luv2increase]

It seems feasible to me!

You got your theory down, now test it out. The hard part will be finding a way to go about that. Good luck!

[krillin]

acash, 

Why not take NAD as a supplement. My guess would be, it should produce the same effect as Benagene.

SLE thread

> > I have concerns about possible deleterious
> > effects of high-dose NAD, related to the PMOR, which seems (in vitro) to
> > make extracellular superoxide far faster from extracellular NAD than from
> > cytosolic NAD (see the O'Donnell and Azzi ref).

> Um, do you mean NADH? Are you reading my "NAD" as "reduced NAD," because
> of the absence of the "+"? If not: why would increased NAD+ generate any
> extra superoxide unless more electrons were shuttled into it? If caloric
> content is content, then elevating NAD+ shouldn't result in significantly
> more NADH to be fed into PMOR, ETS, or whatever -- should it?

I was reading your "NAD" as "NADH and/or NAD+", which is what it normally
denotes. Good point, potentially, but in fact the O'Donnell work (yes that
is the right reference) cannot be extrapolated quite so faithfully as you're
doing to the in vivo case: in the circulation, redox-active compounds such as
ascorbate are kept extremely reduced, so any NAD that did get into the blood
stream would (I expect) be mostly NADH very quickly.

[ageless]

acash,

I understand what you are saying but that is not the issue I am pointing out. I am pointing out that Malic Acid is converted in vivo to Oxaloacetic Acid (3-carboxy-3-oxopropanoic acid) which is the active ingredient in Benagene, therefore supplementing malic acid would accomplish the same thing as supplementing Benagene albeit much more cheaply (perhaps you would have to supplement a large amount of malic acid to ensure enough is converted, but that is no big deal as malic acid itself is good for you and even in high doses its still very cheap). Just like supplementing prohormones like Androsterone and DHEA to increase Testosterone by conversion, or taking beta carotene so that it converts in the body to vitamin A, its the same idea.

Edit: No offense acash, but you have a monetary interest in the sales of Benagene so although you may present some good information, it would be very negative to your business if say Malic Acid turns out to be a viable cheap alternative.

Well as you should know, conversion processes are often imperfect and weak when it comes to many things... ie.. androstendione and dhea to test, ala from flax to DHA/EPA. I don't think you're totally being fair here, but I'm not saying you don't bring up a interesting point nonetheless.

[acash]

The size, complexity and shape of the Nicotinamide Adenine Dinucleotide (NAD) molecule makes the transport of the molecule to the cells, and then into the cells-- difficult. The molecular formula is C21H27N7O14P2 See a picture of the molecule at:

http://en.wikipedia....ne_dinucleotide

The very small molecule we use is able to enter the cells and converts the NADH to NAD+ in the cytoplasm.

There may be other ways to increase NAD+ and decrease NADH.... we looked at several methods, but liked the current benaGene method because of simplicity and the greatly reduced risk of using a citric acid cycle metabolite to effect the change. We like simple and safe......

Regards,

Alan

[edward]

[quote]Edward,

It would be interesting to check literature on the use of Malic acid for lifespan extension. Malic acid also seem to be a good chealting agent which would help in maintaing the longevity of the cell.

Any thoughts on using NAD (may be sublingual) as a supplement (refer to my previous post)?
[/quote]

Seems logical that supplementing NAD would increase the NAD+/NADH ratio (if one could get enough absorbed) , the supposed mechanism behind benagene's effectiveness. Also I've looked for life extension studies on Malic Acid and I can't find any testing of it for this purpose, though there are numerous studies of other health benefits.


[quote]It seems feasible to me!

You got your theory down, now test it out. The hard part will be finding a way to go about that. Good luck![/quote]

Sadly I am not equiped to test out such a theory as I work in the business side of healthcare not as a researcher. Although I am planning a career change (at the age of 29 lol) and will be taking Microbiology and Anatomy/Physiology this summer, so I will have access to a lab and maybe could do a study, I will have to see. I start class at the end of this month.


[quote][quote]acash,

Well as you should know, conversion processes are often imperfect and weak when it comes to many things... ie.. androstendione and dhea to test, ala from flax to DHA/EPA. I don't think you're totally being fair here, but I'm not saying you don't bring up a interesting point nonetheless.[/quote]

Good point, I was thinking the same thing, the conversion occurs, that is obvious, just like Andro to Test or Beta Carotene to Vit A or as you pointed out ala to DHA/EPA, not all of the original substance gets converted so one would have to figure out how much does and what oral dosage this translates to.

Edited by edward, 08 May 2007 - 10:02 PM.

[acash]

Oh, by the way,

benaGene reacts in the cytosol because of favorable Gibbs Free Energy dynamics, rather than in the "Citric Acid Cycle" in the mitochondria shown in the picture above.

Regards,

Alan

[edward]

Oh, by the way,

benaGene reacts in the cytosol because of favorable Gibbs Free Energy dynamics, rather than in the "Citric Acid Cycle" in the mitochondria shown in the picture above. 

Regards,

Alan

That is not what is implied by the Benagene Label (benaGene™ contains a key intermediate in the Kreb's Cycle). Even if that is the case Malic Acid is still converted to the active ingredient of Benagene in the Krebs/Citric Acid Cycle so therefore enough of it will boost the levels of the 3-carboxy-3-oxopropanoic acid/oxaloacetic acid (benagene) so it doesn't matter where it is coming from, again not the point. Analogy: If compound Y influenced say arterial flexibility but this compound was converted from compound X in the liver to compound Y which then affected arterial flexibility throughout the body it wouldn't matter where the compound came from. The point is taking Malic Acid to boost in vivo concentrations of its metabolite 3-carboxy-3-oxopropanoic acid/oxaloacetic acid (benagene)

[acash]

Hi Edward,

I do get your point, and agree that the malic acid supplement can go into the mitochondria and can produce more oxaloacetic acid. But that is not the whole story.....

Check out http://en.wikipedia....i/Image:TCA.svg (don't you just love wikipedia?)

In the citric acid cycle, malic acid does turn to oxaloacetic acid, but you will also notice that at the same time it also changes NAD+ to NADH, thus lowering the NAD+/NADH ratio-- the opposite of what we are trying to achieve-- more NAD+ in the cytosol.

So your next question should be, if benaGene creates malate, why does the NAD+/NADH ratio stay high, and why is it not knocked down by the malate returning to oxaloacetic acid in the mitochondria?

The answer to this question is in the energy dynamics. The Gibbs Free Energy of Oxaloacetate to Malate is Negative 29.7 kJ/mol. This highly negative energy means that the reaction is very favorable. It takes place in the cytosol because the inner mitchondrial membrane is not very permeable to oxaloacetic acid. The malate that is formed floats around the cytosol, and some of it enters the mitochondria (it is not blocked by the inner mitochondrial membrane). The malate that does enter into the mitochondria has to have considerable energy to react back into Oxaloacetate (Positive 29.7 kJ/mol) and this energy is not freely available in the mitochondria. So the reaction takes place slowly, leaving the cells in a different Redox state (similar to cells that are calorie restricted).

By the way, the only reason that the citric acid cycle goes around is that the overall energy of the entire cycle is Negative 115 kJ/mol.

Hope this helps.

Regards,

Alan

[edward]

I both love and hate wikipedia (collective group think references, like wikipedia and lol blogs can be good and bad). Here is a better chart http://www.biocarta....krebPathway.asp

And yes I see your point, the conversion of Malic Acid to Oxaloacetic Acid appears to require NAD+ with a byproduct of NADH which could potentially negatively affect the NAD+/NADH ratio. Although the conversion of oxaloacetic acid back to malic acid will also have this effect as I am sure does occur with oxaloacetic acid supplementation. I am not well versed in thermodynamics so at this point I am not prepared to discuss the Gibbs Free Energy issue. It seems however that introduction of malic acid in turn converted to oxaloacetic acid and in turn as you say slowly converted back to malic acid would still leave the cells in a redox state. I think it is definitely worth looking at and a study of malic acid and lifespan would be very interesting.

[AgeVivo]

I think it is definitely worth looking at and a study of malic acid and lifespan would be very interesting.

Edward/other, any news concerning malic acid and lifespan?
Not sure whether this is a guide: Late onset of dietary restriction reverses age-related decline of malate-aspartate shuttle enzymes in the liver and kidney of mice.(Biogerontology 2008)
Since benaGene is not stable is the water, malic acid would be a good alternative for MPrize @ home.

Edited by AgeVivo, 03 May 2009 - 06:59 PM.

[tunt01]

pretty interesting thread. wonder why i've not seen more people supplementing with Benagene or oxaloacetate.

Aubrey said there was a peer reviewed submission to a journal on the way in May 2008... maybe someone has time to poke around and dig into this issue.

http://www.methusela...hread.php?t=715

[Sillewater]

I hope malic acid works. Because my magnesium malate has malic acid in it.