198 replies to this topic

[DanCG]

 

 

 

Problem is, its super acidic. TBH I think its borderline unsafe to sell it, coz some people dont use much water when swallowing the pills.

My guess is that taking Calcium Carbonate (Tums antacid) along with the acid would neutralize the acid. Once everything ionizes and equilibrates in solution, you have Ca-AKG. I see there are other vendors for the acid. I have no way of knowing whether these are more reliable than what I was already using. Any ideas out there?

[smithx]

With the retraction of that study I'd linked above, does anyone still feel there's enough evidence for the value of this compound as an anti-aging supplement?

 

If so, what do you feel is convincing about it (specific references appreciated)?

 

 

[DanCG]

With the retraction of that study I'd linked above, does anyone still feel there's enough evidence for the value of this compound as an anti-aging supplement?

 

If so, what do you feel is convincing about it (specific references appreciated)?

https://doi.org/10.1...arr.2020.101237

 

This is behind a paywall, but you can see the written and graphical abstracts for free. AKG is involved in so many ageing-related pathways that I don’t think that retraction of a single paper has much impact.

[smithx]

Yes I've seen that paper, thanks.

 

This particular quote did not make me feel more like taking AKG:

 

 

Due to influence on mitochondrial respiration, AKG can stimulate production of reactive oxygen species (ROS) by mitochondria.

 

Something that interferes with mitichondrial function and causes the production of free radicals doesn't seem particularly like a good thing to supplement all the time. Maybe once in a while?

 

[Michael]

All:
 

With the retraction of that study I'd linked above, does anyone still feel there's enough evidence for the value of this compound as an anti-aging supplement?
 
If so, what do you feel is convincing about it (specific references appreciated)?

 

Something that interferes with mitichondrial function and causes the production of free radicals doesn't seem particularly like a good thing to supplement all the time. Maybe once in a while?

The mTOR-related retraction should have no impact whatsoever on one's decision on whether to take Ca-AKG. All it means is that the reported effect on mTOR is not supported by this paper — which as I noted earlier actually resolves a tension in the literature, since Kennedy and Lithgow affirmatively report that it has no effect on mTOR in several tissues in mice. And the retracted paper originally claimed that AKG boosted mTOR activity, which if anything would have made people cautious about taking it, since mTOR inhibition is one of the most robustly supported means of retarding aging across the animal kingdom.
 
So now we appear to know that Ca-AKG's anti-frailty, bone anabolic, and (very slight) life-extension effects (in mice!) are not due to increasing mTOR activity. If anything, that's a bonus.
 
You shouldn't base your decision on whether to take supplement, or do anything, simply because of an effect on some putative mechanism, unless an effect on some mechanism is affirmatively reported that might be toxic and would not have surfaced in in vivo studies at the moment of evaluation.  You should make decision based on actual health and longevity benefits reported in vivo. "Activates SIRT1," "inhibits mTOR," "raises RBC NAD," etc are not benefits: they're potential explanations for benefits when such benefits are observed in vivo.
 
Now, an effect on ROS is obviously not neutral in the way that a non-effect on mTOR is. However, while the review correctly notes this effect has been reported in C. elegans, one should generally ignore anything that isn't reported in things with backbones. Indeed, the review goes on to say,
 

[Such a] moderate increase in ROS production could have beneficial effects due to induction of low intensity (mild) oxidative stress that triggers adaptive response to sufficient protection against any other stresses and thereby contributes to lessening functional decline of various processes with age (Lushchak, 2011, 2014a; Sies, 2015; Ristow and Schmeisser, 2014; Palmeira et al., 2019). In line with this, AKG supplement prevented an age-related increase in oxidative damage to biomolecules and modulated antioxidant defense in the aged mice (Niemiec et al., 2011) and aged yeasts (Burdyliuk and Bayliak, 2017). Finally, one should not ignore the fact, that AKG possesses antioxidant activity itself (Sokołowska et al., 2009; Fedotcheva et al., 2006; Bayliak et al., 2016b) and, hence, some beneficial effects of AKG can be caused by its direct antioxidant action.

 
Absent an affirmative finding of a sustained increase in mtROS in mammals (ideally, resulting in accelerated accumulation of mtDNA mutations), I would ignore the putative effect reported in worms in light of the reported benefits and the somewhat contrary findings of Niemiec et al.

Edited by Michael, 09 September 2021 - 09:09 PM.

[TMNMK]

This isn't a salt or ester, but it is alpha-ketoglutaric acid — ie, H⁺AKG, or more likely H²⁺AKG (or IAC some such). I'm surprised it exists as a powder, but there are certainly other acids that exist in powders, including some dietary supplements. I see that DW do actually label it as "Alpha-ketoglutaric acid," and not "Alpha-ketoglutarate" or just "AKG," so I withdraw that objection to the labeling. But I still wouldn't buy from this company, for reasons aforesaid.

 

I can confirm that the acid is a solid, that's the original form I took it in, from a chem supplier not from a supplement provider. Someone mentioned acidity, you can dissolve in a large volume of water to dilute but probably not great for your teeth to drink regularly - somewhat like sucking on a lemon.

Edited by TMNMK, 19 September 2021 - 08:44 PM.

[Yosi]

I just found out about a product called Liposomal CaAKG claiming improved bioavailability.and am wondering if there's any proof to that? The research, AFAiCT, was done on regular CaAKG and I wonder if the liposomal product indeed provides any real benefits over the regular product?

[stockcarman]

I take AKG in a 12 oz bottle of water an drink through out the day just like the mice did it .

[Phoebus]

Yes I've seen that paper, thanks.

 

This particular quote did not make me feel more like taking AKG:

 

 

Something that interferes with mitichondrial function and causes the production of free radicals doesn't seem particularly like a good thing to supplement all the time. Maybe once in a while?

 

we have been conditioned to think of ROS as "bad" however more and more data suggest its not that simple 

 

 

Mitochondrial ROS (mtROS or mROS) are reactive oxygen species (ROS) that are produced by mitochondria.^[1][2][3] Generation of mitochondrial ROS mainly takes place at the electron transport chain located on the inner mitochondrial membrane during the process of oxidative phosphorylation. Leakage of electrons at complex I and complex III from electron transport chains leads to partial reduction of oxygen to form superoxide. Subsequently, superoxide is quickly dismutated to hydrogen peroxide by two dismutases including superoxide dismutase 2 (SOD2) in mitochondrial matrix and superoxide dismutase 1 (SOD1) in mitochondrial intermembrane space. Collectively, both superoxide and hydrogen peroxide generated in this process are considered as mitochondrial ROS.^[1]

Once thought as merely the by-products of cellular metabolism, mitochondrial ROS are increasingly viewed as important signaling molecules,^[4] whose levels of generation at 11 currently-identified sites vary depending on cellular energy supply and demand.^[5][6] At low levels, mitochondrial ROS are considered to be important for metabolic adaptation as seen in hypoxia.^[1] Mitochondrial ROS, stimulated by danger signals such as lysophosphatidylcholine and Toll-like receptor 4 and Toll-like receptor 2 bacterial ligands lipopolysaccharide (LPS) and lipopeptides, are involved in regulating inflammatory response.^[7][8] Finally, high levels of mitochondrial ROS activate apoptosis/autophagy pathways capable of inducing cell death.^[9]

 

that is from wikipedia 

 

tios study shows that ROS are an important part of defending the host against infection. Too much = bad. But also too little = bad. 

 

 

 

Mitochondria are inevitable sources for the generation of mitochondrial reactive oxygen species (mtROS) due to their fundamental roles in respiration. mtROS were reported to be bactericidal weapons with an innate effector function during infection. However, the controlled generation of mtROS is vital for the induction of efficient immune responses because excessive production of mtROS with mitochondrial damage leads to sustained inflammation, resulting in pathological outcomes such as sepsis. Here, we discuss the beneficial and detrimental roles of mtROS in the innate immune system during bacterial, viral, and fungal infections. Recent evidence suggests that several pathogens have evolved multiple strategies to modulate mtROS for their own benefit. We are just beginning to understand the mechanisms by which mtROS generation is regulated and how mtROS affect protective and pathological responses during infection.

https://www.frontier...2020.01649/full

[albedo]

Just seen today in Josh's blog (but I lack a reference/link to the publication)

"David Sinclair said his lab would be trying to duplicate the results of the following study in an interview.

Study was just published a few days ago:

Rejuvant®, a potential life-extending compound formulation with
alpha-ketoglutarate and vitamins, conferred an average 8 year reduction
in biological aging, after an average of 7 months of use,
in the TruAge DNA methylation test"

https://joshmitteldo...rough/#comments

[Harkijn]

Just seen today in Josh's blog (but I lack a reference/link to the publication)

"David Sinclair said his lab would be trying to duplicate the results of the following study in an interview.

Study was just published a few days ago:

Rejuvant®, a potential life-extending compound formulation with
alpha-ketoglutarate and vitamins, conferred an average 8 year reduction
in biological aging, after an average of 7 months of use,
in the TruAge DNA methylation test"

https://joshmitteldo...rough/#comments

On sound of it it is the same rather disappointing study that was discussed in the various longevity media some weeks ago.

 

https://www.longecit...in-human-study/

 

It would be great if dr. Sinclair or anyone else replicates as well as improves....

[Kevnzworld]

@ Harkjin. 
disappointing?  In what way?  
This was the result of a small initial study.   Currently BK is conducting 

a much more robust clinical study of AKG with measurements of many more 

markers than epigenetic age. 
l take AKG personally.  

[Harkijn]

I use some AAKG myself and by nature I am inclined to see the bright side but the limitations  Steve H listed in the article above make that a bit difficult in this case. I perused the publication at the time and was inclined to agree with Reason's somewhat harsher verdict:

https://www.fightagi...vides-no-value/

 

That said AKG remains highly interesting and  the study  achieves a lot if it inspires dr. Sinclair to dive deeper into the matter.

[Harkijn]

I happened to come across this  recent video where dr. Sinclair seems to address  this study.

 

He seems to me more interested in AKG in general and not specifically in Ca-AKG. What do you think?

[stockcarman]

Calcium Alpha Ketoglutarate is very exspensive to buy but could you just Take regular AK with some calcium . Would that be just as good ? You are still getting both supplements .

[ironfistx]

On this thread they are saying do not take Berberine and CaAKG together because they nullify each other:

 

https://www.fightagi...-age-in-humans/

 

Somewhere else in that thraed it says people can't take AAKG or OAKG long term but the reasons are not given.

 

Are we agreeing that HERBMAXX brand is no good?  I read in another thread their NMN is no good either (contaminated with something).  How does one find a good CaAKG?  DoNotAge has one but it's a minimum order of 366 caps and it's like $250 or something.  Rejuvant is expensive.  There are a few other manufacturers.  What is the consensus on the AKG stuff that has no mineral or pair listed?

[ironfistx]

Does anyone else think it's bizarre that a company selling this product is selling the tests?

 

Do you think they are going to log your name and then send you a better result in 7 months to "prove" their vitamin works?

[Brian Valerie]

Regarding the purported mutually cancelling effects of berberine taken with CaAKG, in just a single evidently unpublished mouse study, that combination did not extend lifespan beyond that of the control group.  Rejuvant CEO Tom Weldon mentions this in his "Modern Healthspan" YouTube video.  I've decided to take my CaAKG in the morning and my berberine in the evening, as well as regularly cycling off of each compound on different days, just in case there is some actual contraindication, but one unpublished and probably small sample sized mouse study does not persuade me to discontinue either supplement, both of which seem to have significant potential benefits.  I believe in cycling a weekly day or more off from virtually all of my supplements anyway, in the hope of diminishing any homeostatic tolerance effect and also to allow my body to respond to any potential build up of possibly deleterious metabolites. 

 

I am able to inform those interested that Simplesa sells 360 caps of 300 mg CaAKG (with 50 mg caprylic acid) for $60, but I know nothing more about them or their product reliability.

 

Hope that helps! 

[ironfistx]

Regarding the purported mutually cancelling effects of berberine taken with CaAKG, in just a single evidently unpublished mouse study, that combination did not extend lifespan beyond that of the control group.  Rejuvant CEO Tom Weldon mentions this in his "Modern Healthspan" YouTube video.  I've decided to take my CaAKG in the morning and my berberine in the evening, as well as regularly cycling off of each compound on different days, just in case there is some actual contraindication, but one unpublished and probably small sample sized mouse study does not persuade me to discontinue either supplement, both of which seem to have significant potential benefits.  I believe in cycling a weekly day or more off from virtually all of my supplements anyway, in the hope of diminishing any homeostatic tolerance effect and also to allow my body to respond to any potential build up of possibly deleterious metabolites. 

 

I am able to inform those interested that Simplesa sells 360 caps of 300 mg CaAKG (with 50 mg caprylic acid) for $60, but I know nothing more about them or their product reliability.

 

Hope that helps! 

 

So CaAKG and Berberine did not extent lifespan beyond that control group of mice?

 

Were mice given CaAKG alone able to live longer?

 

Does Berberine inhibit the CaAKG then?

 

Does Berberine alone give longer life?

 

I don't even know the purpose of Berberine?

[ironfistx]

To continue from the previous post of mine up there, I remember reading somewhere that HERB MAXX was not good, but it wasn't for NMN as I stated, because they don't sell NMN.

 

I cannot find the post.  I searched everything I could think of and can't find it.

[Michael]

To continue from the previous post of mine up there, I remember reading somewhere that HERB [Brand XX] was not good, but it wasn't for NMN as I stated, because they don't sell NMN.

 

I cannot find the post.  I searched everything I could think of and can't find it.

 

I believe you're referencing this post:

https://www.longecit...ndpost&p=898613

[Michael]

Regarding the purported mutually cancelling effects of berberine taken with CaAKG, in just a single evidently unpublished mouse study, that combination did not extend lifespan beyond that of the control group.

 

Well, the evidence that Ca-AKG (slightly) extends lifespan and protects against frailty also comes from a single mouse study. It's published, unlike the berberine combo study — but the latter is by the same scientists (Kennedy, Lithgow, et al) and was perforned with the sae kind of mice in the same facility. So I would be highly reluctant to dismiss it and would not do so without contravening evidence.
 

[Brian Valerie]

Thank you for sharing your knowledge (and wisdom!), Michael.  I agree that even a single mouse study should not be dismissed out of hand, and have decided to further separate my ingestion of berberine and CaAKG.  Instead of separating the time of my ingestion of berberine and CaAKG by a mere 12 hours, I'm now initiating a weekly cycling protocol, alternating the on and off weeks of each compound.  I'll also reread the research on both substances to help me decide if it might be wiser to discontinue either of them at this time.

 

For those readers who have been concerned about the preference of CaAKG versus other AKG compounds, Rejuvant CEO Tom Weldon stated that calcium was selected simply for its buffering effect on the highly acidic AKG.   

[ironfistx]

I believe you're referencing this post:

https://www.longecit...ndpost&p=898613

The one I remembered said something about a quality test showing the amount of lead(?) and it said it was bad because it was listed in ppm and lead is supposed to be ppb, so the results were one thousand times worse than they should be.  That wasn't in the post you linked to.  Frustratingly, I cannot find this post despite all permutations of searching for things of "maxx herb nmn ppm ppb" "maxxherb nmn ppm ppb" etc.

[ironfistx]

Thank you for sharing your knowledge (and wisdom!), Michael.  I agree that even a single mouse study should not be dismissed out of hand, and have decided to further separate my ingestion of berberine and CaAKG.  Instead of separating the time of my ingestion of berberine and CaAKG by a mere 12 hours, I'm now initiating a weekly cycling protocol, alternating the on and off weeks of each compound.  I'll also reread the research on both substances to help me decide if it might be wiser to discontinue either of them at this time.
 
For those readers who have been concerned about the preference of CaAKG versus other AKG compounds, Rejuvant CEO Tom Weldon stated that calcium was selected simply for its buffering effect on the highly acidic AKG.

Based on what I read, AAKG would provide an unhealthy amount of arginine when using in doses to get you the right about of AKG.
 
This was mentioned in the post I linked to on another forum.  But maybe I didn't do that, because apparently I am misremembering everything in this thread.  Like, I just checked, and it's in the thread on fightaging.org above.  Here's the comment: "Definitely do not take AAKG because the arginine gives you a massive vascular dilation boost that in the long term is deleterious but in the short term makes you feel like superman.
The Ca-AKG gives you the opposite of a boost - at least mentally - and that's what you want. autophagy etc. I feel like NOT working out (I am 73) after Ca-AKG and my maximum strength is a bit lower - no energy feeling. BUT BUT BUT I noticed I can do MORE press ups even though I feel low. That "low" feeling, IMO, is a ketogenic feeling, and actually the body is doing better.
I am off-and-on carnivore so I know all about ketogenesis.
One thing I am worried about - could the Ca-AKG I have (from two sources) have ISOMER issues?
Noticed maybe diarrhoea if I take a lot of one of them - that to me, indicates the body rejecting ENANTIOMER version of Ca-AKG. Or maybe I'm wrong here - hopes so."

Edited by ironfistx, 16 January 2023 - 04:13 AM.

[ironfistx]

So, let's mention places that sell CaAKG.

 

I have found:

 

DoNotAge.  They only sell like 266 capsule jars though for $200+.

Maxx Herb:  Powder.  But in another page here someone says it's a shady company.

Renuebyscience: They sell it in lipo pill form, so instead of 1,000mg, the dose is 300mg.  I'm not sure about lipo forms.  Everyone says they're "better" but none of the research uses these. 

[ironfistx]

Pro Health sells it, too.  But their page rubs me the wrong way.  Let me explain:

 

If you choose bulk supplements at the top, you get taken to a page which lists supplements.  On the left are like 50 categories of supplements, and they basically list every supplement in every category.  This is frustrating marketing.

 

Their NMN is Uthever.  According to a paper, their NMN is legit.  However, according to this site, Uthever NMN doesn't work.  So, trying too hard to sell everything + selling a version of NMN that may not even work, I am suspicious of them.

 

And, their purity tests (which, again, I believe are true because even Chroma Dex's paper who tested 23 NMN brands said at least one of their products was real) only show purity, but not heavy metal or bacteria.

 

I've only seen one company which shows all those things in their lab tests (Renue By Science).

 

This is the analysis for MAXX HERB Calcium Alpha Ketoglutarate:

 

https://cdn.shopify....pg?v=1668800874

 

I have no idea who did it, it has their own logo in the top.

 

It doesn't even say how much Alpha Ketoglutarate is in it.

 

Being honest, I have no idea how to even read one of these.  I made a thread about it but it has zero replies so far.

 

I mean, someone could have made that in Excel.  I have no idea if it even came from a real lab.

 

Some company called Youth & Earth sells it, but I've never heard of them and there's no testing papers:

 

https://youthandeart...=43022639169749

 

Update - It would be nice if Pro Health turned out to be legit.  iHerb sells it for a good price ($19 for 1,000mg x 30 servings) so that's like $20 for 30g.  The powder stuff from Maxx Herb is $50 for 100g.  The Liposomal stuff from Renue By Science is like $49 for 90 x 300mg capsules (so that's like $50 for 27g).  This is the liposomal version, though, so who knows what it's compared to.

 

 

Edited by ironfistx, 16 January 2023 - 06:10 AM.

[Harkijn]

In this thread Arginine has a very 'bad'reputation. Interesting to note that  the perspective on it is totally different here:

 

https://www.longecit...sk/#entry921071

[timedilation]

I have also seen a product with ornithine alpha-ketoglutarate.  How would that compare to AAKG?

[ironfistx]

For those of you wondering about calcium alpha ketoglutarate, I spoke to Twin Arbor Analysis about their results for Pro Health, and I spoke to MAXX HERB about why there is no company information on their COA.

 

The results are in this thread:

 

https://www.longecit...st-certificate/

 

Summary:

 

Pro Health's test results are legit, as verified by the lab, whom I spoke to on the phone

 

Maxx Herb is playing the secretive game and their COA looks fake AF and there's no way to verify it was even tested.

 

The other brands are:

 

Renue by Science: Liposomal version.  I know nothing about this.

Rejuvant: ultra expensive.  Likely real.