214 replies to this topic

[smithx]

How about the study I posted a few messages up, which concluded that the active ingredient in BeneGene does not extend the lifespan of mice at all?

It's my impression that people often seem to just ignore studies which show that their favorite supplements are not actually effective.

[niner]

I've noticed nothing with L-Carnosine that I can measure without blood tests and I'm not sure how anyone can really know especially if they are taking several supplements what is causing an effect or placebo. It seems too subjective and not well controlled. I have never heard anyone notice the effects of inhibiting glycation.

What effects do you see from carnosine? HbA1C?

[Kevnzworld]

What effects do you see from carnosine? HbA1C?

Given that most of us take a lot of supplements, it's hard to measure the affect of any single one. I take benfotiamine, p5p, and taurine as well as carnosine for glycation. My HbA1C went from 5.4 to 5.2. I take a few things to lower my glucose numbers, like metformin and coffee bean extract. I started limiting my desserts to sugar free only. Some of them actually taste like the real thing. I'm hoping my next HbA1C will be under 5. It could be hampered by my wine consumption however!

[Logan]

What effects do you see from carnosine? HbA1C?

Given that most of us take a lot of supplements, it's hard to measure the affect of any single one. I take benfotiamine, p5p, and taurine as well as carnosine for glycation. My HbA1C went from 5.4 to 5.2. I take a few things to lower my glucose numbers, like metformin and coffee bean extract. I started limiting my desserts to sugar free only. Some of them actually taste like the real thing. I'm hoping my next HbA1C will be under 5. It could be hampered by my wine consumption however!

How about just eating mostly a paleo style diet? Eliminate grains, bread, pasta, fruit juice, etc.

[Kevnzworld]

How about just eating mostly a paleo style diet? Eliminate grains, bread, pasta, fruit juice, etc.

I would never be able to do paleo or CR. I assume that Paleolithic people didn't consume wine either. I'm a foodie, so there is a limit to the amount of restriction I can endure. I do try to eat well, more of a Mediterranean diet. I also take a lot of CR mimic supplements.

[shermhead]

Is it just me or is there an infomercial on this forum

Sent from my SAMSUNG-SGH-I747 using Tapatalk 2

[niner]

Is it just me or is there an infomercial on this forum

Sent from my SAMSUNG-SGH-I747 using Tapatalk 2

My first thought when I read this was "An infomercial for SAMSUNG?" No, that's just a short ad. I guess it's not under your control, because I've seen the same thing from other Tapatalk posters. But then I realized you were talking about the title of this thread. Yeah, that's a little over the top, isn't it? The guy who started the thread did get hassled for that, back in the day when this thread was young.

[neuropill]

How about the study I posted a few messages up, which concluded that the active ingredient in BeneGene does not extend the lifespan of mice at all?

It's my impression that people often seem to just ignore studies which show that their favorite supplements are not actually effective.

I'm not sure if one study really concludes anything especially with a lifespan study. I'm more interested in the human research and anyone can test to determine if it's effective for them which is what is comes down to.

[niner]

How about the study I posted a few messages up, which concluded that the active ingredient in BeneGene does not extend the lifespan of mice at all?

It's my impression that people often seem to just ignore studies which show that their favorite supplements are not actually effective.

I'm not sure if one study really concludes anything especially with a lifespan study. I'm more interested in the human research and anyone can test to determine if it's effective for them which is what is comes down to.

When something is alleged to result in life extension in humans, a placebo-controlled, carefully run trial in mice that does not find any life extension isn't just one insignificant study. It's pretty close to Game Over for BenaGene, imho. Anyone can test a drug on themselves, and they are very likely to get a placebo response. That's why we go to all the trouble of placebo-controlled double blind studies.

[Alistair]

The Eurosymposium on Healthy Ageing [http://www.eha2012.org/] has now been and gone.

Has there been any meaningful update to the progress of Benagene?

Many thanks in advance,

Alistair

[Kevnzworld]

The Eurosymposium on Healthy Ageing [http://www.eha2012.org/] has now been and gone.

Has there been any meaningful update to the progress of Benagene?

Many thanks in advance,

Alistair

This is Spindler's recently reached conclusion ( posted by Mind ). It did find that oxaloacetate did extend lifespan, though not significantly.
http://m.youtube.com...h?v=uZLGYGjyX2U

It's interesting to note that in a partner study with Spindler, another scientist and a different strain of mice, Metformin's lifespan increase did reach statistical significance. Both lower blood glucose , and work through the AMPK pathway.

[renwosing]

Anybody knows if oxaloacetic acid is available in injectable form? And what is the suggested dose?

Would be interested in injecting both resveratrol and oxaloacetic acid...and observe any health benefits outa it...

[niner]

Anybody knows if oxaloacetic acid is available in injectable form? And what is the suggested dose?

Would be interested in injecting both resveratrol and oxaloacetic acid...and observe any health benefits outa it...

I think oxaloacetate would have pretty good bioavailability orally, so I'm not sure if injecting would be necessary. Resveratrol is a tougher problem, because it's difficult to get it to dissolve in media that are compatible with blood. Maybe a cyclodextrin complex? I think this is going to be a tough one.

[cATsE]

I know this is a rather old topic, but could someone please tell me if this is the same substance?

http://www.bulletpro...-aging-formula/

Edited by cATsE, 22 May 2013 - 06:43 PM.

[niner]

I know this is a rather old topic, but could someone please tell me if this is the same substance?

http://www.bulletpro...-aging-formula/

It appears to be about the same; 100mg of oxaloacetate and 150mg of vitamin c (benagene has 100 of each). Whether either of them are worth it for healthy people is questionable, but it might (or might not...) have value for diabetics.

See Spindler's take above.

Edited by niner, 22 May 2013 - 09:21 PM.

[cATsE]

Thanks niner. It's not as expensive as I thought.

Anyway, it's not for myself, have no real use for it as far as I can tell, but a friend who's very worried about getting diabetes eventually since it runs in his family (or should I say his genes) wanted to try it.

[jolly]

I know this is a rather old topic, but could someone please tell me if this is the same substance?

http://www.bulletpro...-aging-formula/

 

Yep, its the same.  

 

I believe it should have benefits on glucose levels.

[resveratrol_guy]

Here is a great YouTube podcast interview with Alan Cash, starting at 5:50.

 

Executive summary: (1) caloric restriction causes 10% of your epigentic profile to toggle its expression; (2) in rodents, after 3 months, there is a 99% correlation between calorie restriction and oxaloacetate-without-CR genetic expression; and (3) human doses effective against type 2 diabetes were in the range of 100 mg to 1 g/d for several weeks. (So I take it that 90% of the epigenetic states are identical vs. ad libidum controls, and 90% of the remaining 10% matches CR.) In other words, it sounds like you can activate 90% of the epigenetic profile changes of CR merely by taking enough oxaloacetate.

 

At present, 100 mg is about $1.10.

 

Edited by resveratrol_guy, 02 September 2015 - 11:35 AM.

[docmaas]

Having just gone through the entire thread and discovering that Spindler showed only moderate impact and that the NIH study found none at all I think that what Spindler said here:   namely that both fruitflies and worms lead to more false positives because they in general test more successfully than mice is sort of a bottom line warning to both experimenters and consumers.  He also said that what is successful in mice generally turns out to be successful in fruitflies but the opposite is not true.  

 

Given this and it is his intimation as well, perhaps fruitflies and worms should be first level differentiators for viable candidates but subsequent testing with mice is a better standard for assessing possible usefulness in humans.   As I recall the initial and most of the subsequent evidence for oxaloacetate aside from the blood sugar reports was worm based.  I also find the way the blood sugar numbers were presented with widely varying results and dosages looks much more like a collection of anecdotes than a serious trial.

 

I have diabetes type 2 and am constantly on the lookout for the miracle we all hope will be found.  Oxaloacetate really looked like a good candidate for awhile.  

 

Right now I'm focussed on glycine due to two different trials that showed very positive effects from doses from 5 to @20gm per day.  It does seem to be helping in that the peaks are lower and the recoveries quicker resulting in less time under the curve defined by the beginning of an arbitrary number through its elevation and return to that same number resulting in less damage and hopefully a lower a1c.  This may not change the fasting glucose level at all though.  The whole thing could just as easily be a concatenation of sampling errors though with only one interested participant/observer.  

 

Mike

[tintinet]

Here is a great YouTube podcast interview with Alan Cash, starting at 5:50.

 

Executive summary: (1) caloric restriction causes 10% of your epigentic profile to toggle its expression; (2) in rodents, after 3 months, there is a 99% correlation between calorie restriction and oxaloacetate-without-CR genetic expression; and (3) human doses effective against type 2 diabetes were in the range of 100 mg to 1 g/d for several weeks. (So I take it that 90% of the epigenetic states are identical vs. ad libidum controls, and 90% of the remaining 10% matches CR.) In other words, it sounds like you can activate 90% of the epigenetic profile changes of CR merely by taking enough oxaloacetate.

 

At present, 100 mg is about $1.10.

 

100 mg from what source?

 

Thanks!

[docmaas]

NIH test of benagene led to no increase in life span of mice.  In one of Cash's youtube presentations ( at 12:57) he alludes to the fact that "we", probably his company, asked the NIH to send them a sample of the chow containing oxaloacetate and they had it tested and found no oxaloacetate and he then concludes the test was a comparison of two controls against one another.  However the NIH results say nothing about this event here:  http://www.ncbi.nlm....les/PMC3598361/ where they do say it had no impact at all on lifespan and also go into significant detail about the preparation and testing of the chow to which the oxaloacetate was added.

 

There should be a corrective from the NIH if what Cash says is true.  Where is it?

 

In the absence of significant results from both the NIH and from Spindler why is anyone even seriously considering this drug right now? 

 

Mike

[docmaas]

Here's a pdf of the 1968 Japanese paper:

 

The actual 1968 paper can be found here:  https://www.jstage.j...2/96_2_127/_pdf

 

Just one comment.  It turned out to only work well for 5 of 11 type 2 diabetics, ok for 1 more and failed for 5 of 11 for a success rate of just over 50%.  That could be for a number of reasons.  The first two that come to mind for me is that the failed were the obese, older and longer diseased subjects and they might have very well burned out their pancreatic potential as does happen in advanced type 2, the second is that there may be a significant gene issue.  In the case of pancreatic burnout one wonders why it would work for type 1 so well, 10/10 excellent response.

 

Perhaps some others will have some additional thoughts after reading the paper.

 

I think I will get some benagene and compare it to my glycine results using the same methodology.  

 

​The Japanese research used a sodium salt of oxaloacetate.  

 

I'm also wondering if anyone has thought about the oxalic acid impact of some green vegetables as regards this compound.

 

Mike

 

Mike

[resveratrol_guy]

Notwithstanding the above criticisms, I still think there's more to oxaloacetate than it would appear. In particular:

1. According to the full text of the study provided in 2012 above by smithx, the highest concentration of oxaloacetate used in the chow was 3.5 mg per kg of chow (see "Measurement of Oxaloacetic Acid in Lab Chow", wherein they equivalently refer to ug per mg of chow). This is far less than the minimum dietary concentration required in humans, which according to Spindler's video comments above, should be expected to be roughly an order of magnitude greater than what would be required in mice. (@ tintinet: According to Cash, he concluded from the Japanese study that 100 mg/d would be the minimum clinically effective human dose, with 1 g/d being perhaps the maximum. This was in an audio interview on YouTube. I haven't verified this, but in any event, that would be maybe 30-50 mg per kg of human food -- not 3.5, let alone 0.35.) Furthermore, oxaloacetate is notoriously unstable, which is why Benagene and Upgraded Aging come stabilized with vitamin C. If they just bought some oxaloacetate from Sigma Chemical, mixed it with chow, and then immediately HPLCed it, then they weren't accurately estimating what the mice actually ingested, besides the fact that in the best of circumstances, the concentration would have been negligible.

2. Even if the above study actually tested oxaloacetate properly, we would still need to define what we mean by "life extension". As I recall from the studies of resveratrol in mice, the extension effect is statistically significant in (1) mice already on caloric restriction (every-other-day feeding) and (2) mice whose lives would otherwise have been truncated due to excessive caloric intake. Normocaloric mice did not obtain a life extension benefit. So does this mean that resveratrol is ineffective for the treatment of the murine aging process? No. It just means that it's selectively effective. I suspect that an analogous partitioning may occur with oxaloacetate. From the (admittedly short term) Japanese study, it seems like oxaloacetate is actually more effective in less diabetic patients. That's counterintuitive, but offers some hope for the healthier segment of the population, above and beyond the value of healthy eating.

3. The Japanese study above says right up front: "A long-term administration of OAA-sodium induced hyperplasia and proliferation of the islet cells of the pancreas in rats, but no mentionable changes were found in other organs."

This sounds like: "Oxaloacetate increases the probability of hyperinsulinemic neuroendocrine tumors of the pancreas." Such tumors have a 50% 5-year survival rate. However, they are slow-growing as compared to pancreatic adenocarcinoma, and may be preventable with annual abdominal MRIs, unlike more common forms of pancreatic cancer.

But secondly, there is a form of pancreatic ductal adenocarcinoma  mediated by KRAS mutations. Unlike almost all other malignant tumors, this species involves OXPHOS as opposed to glycolysis, which is evidently enhanced by oxaloacetate as derived from glutamine  and actually involves a decrease in ROS signalling. One proposed treatment is suffocation of the cancer, which sounds like it might result in unrelated malignancies even if it succeeded.

Preventing KRAS-mediated pancreatic cancer may involve, among other things (e.g. low-dose aspirin), the ingestion of adequate delta-tocotrienol (not to be confused with delta-tocopherol, which is a related vitamin E species). The only significant dietary source is annatto, although a number of supplements are available. In fact, there is a phase 1 clincal trial testing much higher doses (about 100X what's available in a spoonful of anatto) in healthy individuls, with the goal of using those doses in cancer patients in order to enhance the effectiveness of chemotherapy.
 

4. What is the weight of the evidence? It sounds, from the large body of research on oxaloacetate (for example this and this and the Japanese study), that it supports brain health and glucose control, even if it doesn't extend life in humans. OTOH, it sounds like it would support the above forms of pancreatic cancer. (Perhaps the antidiabetic effect is due as much to islet cell proliferation as citric acid cycle acceleration, frankly.) But I see no evidence that it causes cancer, absent the required nuclear mutations; hyperplasia and proliferation is not equivalent to malignancy. At the end of the day, there's no silver bullet. Trading a lower rate of dementia and diabetes for a theoretically higher rate of an uncommon cancer might be worthwhile, especially if we can appreciate the risk and take steps to avoid it.

 

Edited by resveratrol_guy, 17 September 2015 - 04:02 PM.

[resveratrol_guy]

So continuing with the theory that oxaloacetate should best be consumed along with a sufficient amount of annatto extract (norbixin), I decided to investigate the potential toxicity of the latter. I found one study which appeared to indicate that it might become toxic at doses exceeding 69 mg/kg/d in rats (and perhaps less in humans). But the resulting "toxicity" is indicated as:

 

"Hepatocyte hypertrophy was evident and an additional electron microscopic examination demonstrated this to be linked to abundant mitochondria after exposure to a dietary level of 0.9% annatto extract for 2 weeks."

 

Abundant mitochondria? As in, the hepatocytes were swelling because they contained too many mitochrondria? That would require a lot of extra mitochondria.

 

But this sounds like exactly what we want, especially in the liver. I wonder if (1) I'm understanding this in the absence of the full text and (2) it works in humans.

 

To be clear, norbixin is not delta-tocotrienol, but this obviously matters if we contemplate an oxaloacetate-annatto pill.

 

Edited by resveratrol_guy, 21 September 2015 - 01:00 AM.

[docmaas]

I think your numbers may be wrong as concerns the chow:

 

"Control and Experimental Diets

TestDiet, Inc., a division of Purina Mills (Richmond, IN), prepared batches of Purina 5LG6 food containing each of the test substances, as well as control diet batches, at intervals of approximately 4 months, and shipped each batch of food at the same time to each of the three test sites. RES was purchased from Lali Lab (Durham, NC) and was mixed with chow at a concentration of 300 mg of RES per kilogram of food (300 ppm). Curcumin was a gift from Sabinsa Corporation (East Windsor, NJ) and used at a dose of 2000 mg of curcumin per kilogram of food. Green tea extract (GTE) was obtained from LKT Laboratories, Inc. (St Paul, MN, catalog #G6817) and used at a dose of 2000 mg of GTE per kilogram of food. Medium-chain triglyceride oil (MCTO) was obtained from Life Enhancement Products, Inc. (Petaluma, CA; Functional Gourmet MCT Oil) and used at 60,000 mg/kg of diet. Oxaloacetic acid (OAA) was obtained from Sigma-Aldrich Co. LLC (St Louis, MO, catalog #O4126-100G) and incorporated into the food at a concentration of 2200 mg/kg of food. On the assumption that each mouse weighs 30 g and consumes 5 g food/day, the estimated daily doses of these agents would be: RES 50; curcumin 333; GTE 333; MCTO 10,000; and OAA 367 mg/kg body weight/day."

 

According to the product sheet:  https://www.sigmaald.../2/o4126pis.pdf

oxaloacetic acid is stable dry but unstable in a water solution and must be kept on ice.  The chow is dry until it is consumed.  Not sure if this is an issue or not and the Japanese researchers did use a salt.

 

On the beta and alpha cells hyperplasia on the beta and atrophy on the alpha it makes me inclined to think that oxaloacetate is overriding the normal alpha beta paracrine feedback system at the expense of the alpha glucagon side.  This is somewhat supported by how well it worked for type 1 diabetics since they are insulin dependent because they can't make their own but seem to have done so with oxaloacetate.  I have no idea what this might mean and how other medications might be more or less similar.

From the reading I've been doing today though I'd guess that glycine is a bit more moderate in the way it works.  Oxaloacetate sounds like a sledgehammer in this respect.  

 

In fact given this admittedly hypothetical understanding I don't think I'll be trying benagene without a deeper understanding.

Notwithstanding the above criticisms, I still think there's more to oxaloacetate than it would appear. In particular:

1. According to the full text of the study provided in 2012 above by smithx, the highest concentration of oxaloacetate used in the chow was 3.5 mg per kg of chow (see "Measurement of Oxaloacetic Acid in Lab Chow", wherein they equivalently refer to ug per mg of chow). This is far less than the minimum dietary concentration required in humans, which according to Spindler's video comments above, should be expected to be roughly an order of magnitude greater than what would be required in mice. (@ tintinet: According to Cash, he concluded from the Japanese study that 100 mg/d would be the minimum clinically effective human dose, with 1 g/d being perhaps the maximum. This was in an audio interview on YouTube. I haven't verified this, but in any event, that would be maybe 30-50 mg per kg of human food -- not 3.5, let alone 0.35.) Furthermore, oxaloacetate is notoriously unstable, which is why Benagene and Upgraded Aging come stabilized with vitamin C. If they just bought some oxaloacetate from Sigma Chemical, mixed it with chow, and then immediately HPLCed it, then they weren't accurately estimating what the mice actually ingested, besides the fact that in the best of circumstances, the concentration would have been negligible.

2. Even if the above study actually tested oxaloacetate properly, we would still need to define what we mean by "life extension". As I recall from the studies of resveratrol in mice, the extension effect is statistically significant in (1) mice already on caloric restriction (every-other-day feeding) and (2) mice whose lives would otherwise have been truncated due to excessive caloric intake. Normocaloric mice did not obtain a life extension benefit. So does this mean that resveratrol is ineffective for the treatment of the murine aging process? No. It just means that it's selectively effective. I suspect that an analogous partitioning may occur with oxaloacetate. From the (admittedly short term) Japanese study, it seems like oxaloacetate is actually more effective in less diabetic patients. That's counterintuitive, but offers some hope for the healthier segment of the population, above and beyond the value of healthy eating.

3. The Japanese study above says right up front: "A long-term administration of OAA-sodium induced hyperplasia and proliferation of the islet cells of the pancreas in rats, but no mentionable changes were found in other organs."

This sounds like: "Oxaloacetate increases the probability of hyperinsulinemic neuroendocrine tumors of the pancreas." Such tumors have a 50% 5-year survival rate. However, they are slow-growing as compared to pancreatic adenocarcinoma, and may be preventable with annual abdominal MRIs, unlike more common forms of pancreatic cancer.

But secondly, there is a form of pancreatic ductal adenocarcinoma  mediated by KRAS mutations. Unlike almost all other malignant tumors, this species involves OXPHOS as opposed to glycolysis, which is evidently enhanced by oxaloacetate as derived from glutamine  and actually involves a decrease in ROS signalling. One proposed treatment is suffocation of the cancer, which sounds like it might result in unrelated malignancies even if it succeeded.

Preventing KRAS-mediated pancreatic cancer may involve, among other things (e.g. low-dose aspirin), the ingestion of adequate delta-tocotrienol (not to be confused with delta-tocopherol, which is a related vitamin E species). The only significant dietary source is annatto, although a number of supplements are available. In fact, there is a phase 1 clincal trial testing much higher doses (about 100X what's available in a spoonful of anatto) in healthy individuls, with the goal of using those doses in cancer patients in order to enhance the effectiveness of chemotherapy.
 

4. What is the weight of the evidence? It sounds, from the large body of research on oxaloacetate (for example this and this and the Japanese study), that it supports brain health and glucose control, even if it doesn't extend life in humans. OTOH, it sounds like it would support the above forms of pancreatic cancer. (Perhaps the antidiabetic effect is due as much to islet cell proliferation as citric acid cycle acceleration, frankly.) But I see no evidence that it causes cancer, absent the required nuclear mutations; hyperplasia and proliferation is not equivalent to malignancy. At the end of the day, there's no silver bullet. Trading a lower rate of dementia and diabetes for a theoretically higher rate of an uncommon cancer might be worthwhile, especially if we can appreciate the risk and take steps to avoid it.

 

Edited by docmaas, 21 September 2015 - 08:54 AM.

[resveratrol_guy]

 

I think your numbers may be wrong as concerns the chow:

 

"Control and Experimental Diets

TestDiet, Inc., a division of Purina Mills (Richmond, IN), prepared batches of Purina 5LG6 food containing each of the test substances, as well as control diet batches, at intervals of approximately 4 months, and shipped each batch of food at the same time to each of the three test sites. RES was purchased from Lali Lab (Durham, NC) and was mixed with chow at a concentration of 300 mg of RES per kilogram of food (300 ppm). Curcumin was a gift from Sabinsa Corporation (East Windsor, NJ) and used at a dose of 2000 mg of curcumin per kilogram of food. Green tea extract (GTE) was obtained from LKT Laboratories, Inc. (St Paul, MN, catalog #G6817) and used at a dose of 2000 mg of GTE per kilogram of food. Medium-chain triglyceride oil (MCTO) was obtained from Life Enhancement Products, Inc. (Petaluma, CA; Functional Gourmet MCT Oil) and used at 60,000 mg/kg of diet. Oxaloacetic acid (OAA) was obtained from Sigma-Aldrich Co. LLC (St Louis, MO, catalog #O4126-100G) and incorporated into the food at a concentration of 2200 mg/kg of food. On the assumption that each mouse weighs 30 g and consumes 5 g food/day, the estimated daily doses of these agents would be: RES 50; curcumin 333; GTE 333; MCTO 10,000; and OAA 367 mg/kg body weight/day."

 

According to the product sheet:  https://www.sigmaald.../2/o4126pis.pdf

oxaloacetic acid is stable dry but unstable in a water solution and must be kept on ice.  The chow is dry until it is consumed.  Not sure if this is an issue or not and the Japanese researchers did use a salt.

 

On the beta and alpha cells hyperplasia on the beta and atrophy on the alpha it makes me inclined to think that oxaloacetate is overriding the normal alpha beta paracrine feedback system at the expense of the alpha glucagon side.  This is somewhat supported by how well it worked for type 1 diabetics since they are insulin dependent because they can't make their own but seem to have done so with oxaloacetate.  I have no idea what this might mean and how other medications might be more or less similar.

From the reading I've been doing today though I'd guess that glycine is a bit more moderate in the way it works.  Oxaloacetate sounds like a sledgehammer in this respect.  

 

In fact given this admittedly hypothetical understanding I don't think I'll be trying benagene without a deeper understanding.

 

 

Thanks for pointing this out. I think the sentence that threw me off was: "To quantify oxaloacetic acid in each sample, the peak area of oxaloacetic acid was compared against a linear regression of peak areas of oxaloacetic acid in lab chow samples spiked with 0, 0.5, 1.5, 2.5, and 3.5 μg/mg lab chow." This makes it sound as though they were verifying various oxaloacetate concentrations against an HPLC standard, with the greatest being 3.5 mg/kg chow. That's a little odd, considering what you quoted above. 367 mg/kg body/d is a huge dose.

 

We're still left with the question as to whether either CRed or overfed mice might experience life extension, as they did in the original resveratrol study.

 

Superficially it sounds like oxaloacetate works as you said, mainly by acting like a pancreatic beta cell steroid. OTOH, Alan Cash claims that it's 99% epigenetically identical to CR in certain rodents. I don't have the data to back that up, but I can't refute it, either. It might be true because oxaloacetate is embedded in the citric acid cycle, which ostensibly has more to do with NAD+ than anything pancreatic. So I feel like there are a lot of important questions here, but I'm not ready to dismiss what might be an imperfect but significant breakthrough, especially at much lower doses than 367/mg/kg body/d.

[resveratrol_guy]

Also, Bryan_S mailed me with some hazards that he found regarding norbixin. His expertise is with nicotinamide riboside, which he prefers over oxaloacetate. Personally, I suppose I will quit dosing Benagene when my bottle is done, as it looks like annatto isn't as clean as I thought. But I still like both compounds, and might change my mind, given sufficiently compelling data

 

He wrote, of norbixin:

I could push my search further but cell damage was established and is confirmed. Now as far as safety since the use of this substance does not approach the dosages they used in the following studies it looks relatively safe at low dose but you also don't get the effect. The damage seemed to be from the mitochondria increase crowding out other cell organelles. It appears this result was dose dependent. The active ingredient appears to be Bixin but thats a guess and it is mentioned in some studies. Here was a positive result on Bixin 

http://www.biolres.com/content/47/1/49 [I don't know whether bixin and norbixin are bioequivalent.]

 

Damage

http://www2.ibb.unes...aper_2004_4.pdf

"Nevertheless, extensive damage in mitochondria and endoplasmatic reticulum of liver and pancreas cells has been observed in Mongrel dogs, when pure bixin, dissolved into 40% ethanol, was orally administered at single dose of 0.06 g/kg/body wt (Morrison et al., 1991)."

 

Damage

https://www.ncbi.nlm.../pubmed/1750113

"This purified substance was demonstrated, in anaesthetised mongrel dogs, to cause hyperglycaemia. Concomitant electron microscopy of tissue biopsies, revealed damage to mitochondria and endoplasmic reticulum mainly in liver and pancreas."

 

So personally as I weigh this out since NAD boosting promotes mitochondrial biogenesis anyway, I'll stick to the safe path. If this property is what your interested in you're already there without the [mitochondrial] overcrowding.

 

Edited by resveratrol_guy, 22 September 2015 - 03:40 AM.

[docmaas]

bixin looks useful but I have my hands more than full trying to get a handle on glycine.  Both Taurine and Cysteine have been mentioned with Glycine and appear to have been helpful.  I'll be posting some more experimental results on the glycine thread.  

 

Here is a positive article for bixin and blood glucose though: http://www.medicalex...ellitus-in-rats

and a couple more:  http://www.hindawi.c...je/2014/839095/  http://omicspace.riken.jp/PosMed/search#doc

 

One more comment on the Japanese paper.  All the subjects had urinary sugar and the mark of failure as judged by the experimenters appears to have been based on minimal changes in urinary sugar levels rather than blood sugar levels.  I suppose that monkeying around with the numbers one could probably come up with a close approximation of what they considered to be a failure in terms of both urinary sugar and blood sugar and thereby gain some insight as to what they considered to be the mark of success.  I think it is incumbent on Cash to look over this data more carefully and give a fuller explanation.  Using only the blood sugar numbers in the face of the other data available seems to be misrepresentation by data exclusion.  What I really think he should do is replicate the test himself and use those numbers.  

 

I'm just not comfortable with his whole approach to oxaloacetate but he probably has little choice having put millions of Cash's cash into the project.  

 

Mike 

Edited by docmaas, 24 September 2015 - 06:10 AM.

[docmaas]

Possibly more illumination on the Japan study and T1 diabetes.  In that study there was a 100% success rate for T1 and just slightly better than 50% for T2.  In addition there was significant proliferation in the beta cells of treated mice and atrophy in the alpha cells.

 

http://www.pubfacts....-transaminase-G

 

"Abstract

Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1–20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic β cells and results in type 1 diabetes."

Looks to me like Benagene, or some other interested party, might want to focus on type 1 as opposed to type 2.  

Mike

 

[resveratrol_guy]

Getting back to the original Japanese study, I just noticed that the last few pages are photos depicting the alpha and beta cell issues that we've been discussing.

 

I think it's worth considering the tradeoff between these problems and the data showing health benefits in animals (and life extension in C. elegans), particularly since we now have a large number of ways to thwart pancreatic cancer. The specter of pancreatic cancer is certainly not a trivial one, but neither is the prospect of living a long and productive life without the necessity for caloric restriction.

 

I stopped after 100 mg/d for a month, but I must admit, I do miss that mental energy boost.

 

Edited by resveratrol_guy, 13 October 2015 - 04:25 PM.