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Alpha-Ketoglutarate

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#1 SearchingForAnswers

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Posted 17 September 2019 - 06:35 PM


Has anybody tried Alpha-Ketoglutarate?

 

I see this company advertising the product, but I can't find anecdotes of anybody taking it. Going by the name of rejuvant, and others, I believe.

 

It's quite expensive so I wouldn't want to try it without reading somebody elses' experience first.



#2 Oakman

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Posted 19 September 2019 - 01:07 AM

If you're speaking of Arginine Alpha Ketoglutarate (AAKG), then I do take that for its nitric oxide production potential, along with several other compounds. BTW, it's quite inexpensive, such as here.



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#3 brosci

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Posted 19 September 2019 - 07:15 PM

I've been on the lookout for Glycine-AKG but haven't come across it.

 

https://www.ergo-log...supplement.html



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#4 SearchingForAnswers

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Posted 15 October 2019 - 04:29 PM

The ingredient is listed as calcium alpha-ketoglutarate monohydrate.



#5 TMNMK

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Posted 16 October 2019 - 07:32 PM

I've been trying it out but not as the salt: https://www.longecit...ivate-autophagy (few posts down) both topically and by dissolving in water and drinking. Nothing shocking to report yet. It's pretty water soluble so I don't know what is the advantage of the calcium salt beyond perhaps stability or taste. Although there is  one paper that describes sodium vs calcium salt.



#6 TMNMK

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Posted 29 October 2019 - 01:19 AM

I'm stupefied as to how people are ignoring α-ketoglutarate here on this site (if you're google scholar-ing, it is the conjugate base of α-ketoglutaric acid, aka AKG sometimes written αKG or α-KG). There's a lot of very interesting literature on it, the more I dig the more I'm impressed. And it is super cheap, no need to buy it from that vendor mentioned above unless you dig fancy packaging or have issues with measuring dosage.

 

People, YO!

 

 

 

Alpha-ketoglutarate (AKG), an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. It functions as an energy donor, a precursor in the amino acid biosynthesis, a signalling molecule, as well as a regulator of epigenetic processes and cellular signalling via protein binding. AKG is an obligatory co-substrate for 2-oxoglutarate-dependent dioxygenases, which catalyse hydroxylation reactions on various types of substrates. It regulates the activity of prolyl-4 hydroxylase, which controls the biosynthesis of collagen, a component of bone tissue. AKG also affects the functioning of prolyl hydroxylases, which, in turn, influences the function of the hypoxia-inducible factor, an important transcription factor in cancer development and progression. Additionally, it affects the functioning of enzymes that influence epigenetic modifications of chromatin: ten–eleven translocation hydroxylases involved in DNA demethylation and the Jumonji C domain containing lysine demethylases, which are the major histone demethylases. Thus, it regulates gene expression. The metabolic and extrametabolic function of AKG in cells and the organism open many different fields for therapeutic interventions for treatment of diseases. This review presents the results of studies conducted with the use of AKG in states of protein deficiency and oxidative stress conditions. It also discusses current knowledge about AKG as an immunomodulatory agent and a bone anabolic factor. Additionally, the regulatory role of AKG and its structural analogues in carcinogenesis as well as the results of studies of AKG as an anticancer agent are discussed.

 

 

 

Alpha-ketoglutarate is a precursor of glutamine which contributes to muscle repair, prevents protein catabolism, improves nitrogen retention, functions as an immunomodulatory molecule, and takes part in proper function of intestines. AKG is also involved in cell protection against oxidative stress and cyanide poisoning. It can also influence bone strength and density and inhibit carcinogenesis induced by oncometabolites or hypoxia by activating enzymes from the 2-OGDD family (2-oxoglutarate-dependent dioxygenases). Their action involves epigenetic regulation such as histone and DNA demethylation carried out by KDM 2–7 (Jumonji C domain containing lysine demethylases) and TET 1–3 (10–11 translocation hydroxylases), respectively, and non-epigenetic regulation, which includes activation of prolyl hydroxylases: P4H (prolyl 4-hydroxylase) involved in type I collagen biosynthesis and PHD2 (prolyl hydroxylase domain-containing protein 2) responsible for hydroxylation and thus inactivation of HIF-1α (hypoxia-inducible factor). Other cofactors for the 2-OGDD enzymes are Fe2+, O2, and ascorbate while their inhibitors known as oncometabolites include succinate, fumarate, and 2-HG (R(−)-2-hydroxyglutarate)

 

Also inhibits mTOR and has allowed some lucky mature mice (from what I've read) to date well out of their league.


Edited by TMNMK, 29 October 2019 - 02:07 AM.


#7 TMNMK

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Posted 29 October 2019 - 02:53 AM

Also, Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

 

So not just worms fortunately.


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#8 Oakman

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Posted 29 October 2019 - 01:38 PM

Amino Acid Alpha-Ketoglutarates are amino acids with an alpha-ketoglutaric acid (AKG) molecule attached. This AKG transport molecule helps the amino acid bypass the gut and enter the muscle cell directly giving you superior absorption. Unlike L- form amino acids, AKGs are shuttled directly to the muscle cells rather than being absorbed and used by the small intestines for nucleotide synthesis. This makes AKG aminos the perfect choice if your goal is building muscle, but maybe not the best choice if you have more generalized health goals. AKG drives the amino acid into muscle cells creating a pro-anabolic environment.

 

https://www.nutrabio.../aminoacid-akg/

 

This above seems to lead to using pure AKG rather than the protein or salt forms if interested in some of the additional benefits of AKG mentioned in TMNMK's link, rather than focusing on muscle. While not as popular as the other forms, pure AKG (example), is also fairly expensive vs. the other forms.


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#9 TMNMK

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Posted 29 October 2019 - 02:03 PM

Ah good info, thanks Oakman I wasn't entirely sure what the reason was for that combination. I purchased mine from a chemical supplier instead of a supplement maker so it was much cheaper. But that raises a very important point. It should not be recommended that people eat chemicals that are sent to them from a chemical supplier (not a supplement provider), so forgive me I'm going to walk back that statement entirely.

 

The good news is that once the supplement providers start getting calls for this, the price should drop. I purchased 100g for ~50 USD including shipping iirc (from a re-packager, not even from a direct supplier).


Edited by TMNMK, 29 October 2019 - 03:00 PM.


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#10 Andey

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Posted 19 November 2019 - 01:09 PM

Looks like people using pure AKG with Deanna protocol for ALS.

 

https://www.simplesa...osing-Guide.pdf

One 300mg capsule every waking hour plus 9 gr of AAKG.

 



#11 TMNMK

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Posted 19 November 2019 - 02:02 PM

Nice find Andey, and in addition to arginine α-ketoglutarate (AAKG), indeed it looks like they also have the free α-ketoglutaric acid (α-KG) in a mixture with caprylic acid as part of that protocol also along with glutathione and some other things. I had not heard of this treatment for ALS.


Edited by TMNMK, 19 November 2019 - 02:02 PM.


#12 Andey

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Posted 19 November 2019 - 02:40 PM

Nice find Andey, and in addition to arginine α-ketoglutarate (AAKG), indeed it looks like they also have the free α-ketoglutaric acid (α-KG) in a mixture with caprylic acid as part of that protocol also along with glutathione and some other things. I had not heard of this treatment for ALS.

 

 am I right that this topic is about free α-ketoglutaric acid?

 

AAKG is abundant in bodybuilding and if it is substantially beneficial for longevity we would heard about it already. 

if I understand the study for this Deanna protocol correctly, they use AAKG at max dosage as it shown to increase AKG levels.

https://www.ncbi.nlm...les/PMC4111621/

Study that shows that "AAKG at max dosage as it shown to increase AKG levels" is not available though (reference #18)

 

Then in a human protocol they increase AKG levels even more with direct AKG. 


Edited by Andey, 19 November 2019 - 02:46 PM.


#13 TMNMK

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Posted 19 November 2019 - 02:56 PM

 am I right that this topic is about free α-ketoglutaric acid?

 

AAKG is abundant in bodybuilding and if it is substantially beneficial for longevity we would heard about it already. 

if I understand the study for this Deanna protocol correctly, they use AAKG at max dosage as it shown to increase AKG levels. Then they increase it even more with direct AKG.

https://www.ncbi.nlm...les/PMC4111621/

Study that shows that "AAKG at max dosage as it shown to increase AKG levels" is not available though (reference #18)

 

Well maybe that's for the OP but personally I'm open o discussing any formulation or salt. Different salts apparently have different results in the literature - calcium, disodium, etc. Also there's arginine, ornithine, and others I believe in the literature.

Going to have to research the Deanna protocol more, very interesting!


Edited by TMNMK, 19 November 2019 - 03:09 PM.


#14 mkp6019

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Posted 21 November 2019 - 01:27 PM

This newly packaged supplement is interesting but at $150 a month is quite the leap of faith IMO. I would be curious to see if one of you guys can nail down a cheaper formulation at the right dose and at  right price to make this worth experimenting with. I am tempted to try a 30 day trial and see if I feel anything beyond subtle.



#15 albedo

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Posted 23 January 2020 - 12:09 PM

There are new results being published (on mice models only), could not find info on different forms, probably in the reference list, sorry if  am overlooking. Tempted to try as several folks here ...

 

"...Interestingly, in humans plasma AKG levels decline 10 folds between the ages of 40 and 80 [28]. The molecule is not available in the human diet, making direct supplementation the only feasible route to restore levels. AKG has been used in human clinical studies linked to diseases without associated adverse effects [29-31]. More studies will be needed to determine whether chronic AKG consumption can affect other parameters of aging. Given its GRAS status and human safety record, our findings point to a potential safe human intervention that may impact important elements of aging and improve quality of life in the elderly population..."

  • AKG extends lifespan and decrease mortality
  • AKG treatment extends health span and alleviates age-associated frailty
  • Compression of morbidity by AKG treatment
  • AKG reduces inflammation and lowers the proinflammatory SASP without preventing the senescence growth arrest

Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

Azar Asadi Shahmirzadi, Daniel Edgar, Chen-Yu Liao, Yueh-Mei Hsu, Mark Lucanic, Arash Asadi Shahmirzadi, Christopher Wiley, Rebeccah Riley, Brian Kaplowitz, Garbo Gan, Chisaka Kuehnemann, Dipa Bhaumik, Judith Campisi, Brian K Kennedy, Gordon J. Lithgow

doi: https://doi.org/10.1101/779157


Edited by albedo, 23 January 2020 - 12:19 PM.

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#16 QuestforLife

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Posted 06 February 2020 - 10:31 AM

The ingredient is listed as calcium alpha-ketoglutarate monohydrate.

 

I believe the reason the Rejuvant guys are using the calcium salt (and also adding pure calcium to the supplement), is to make it slow release. You get a gram of the alpha-keto-glutarate salt and another 190mg of calcium. 

 

I'm not sure if you could say take more arginine with arginine-AKA and make it slower release,or take more, smaller doses of AAKA throughout the day to get the same effect as a slow release version.

 

If the early reported human anecdotes are true, its astonishing. The are so confident the supplement with reduce methylation age, they even supply a DNA methylation test with it. 

 

Might be hard to patent though (good for us).


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#17 QuestforLife

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Posted 07 February 2020 - 06:11 PM

I purchased this product, which is a mix of calcium and magnesium ketoglutarate. It should be as effective as the far more expensive Rejuvant.

Alpha-Ketoglutaric Acid 300 mg -... https://www.amazon.c...op_mob_ap_share

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#18 ta5

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Posted 08 February 2020 - 04:42 AM

Aside from AAKG and other products mentioned above...

 

PureBulk sells Glutamine AKG, and recently back in stock:

https://purebulk.com...a-ketoglutarate

 

JoMarLabs used to sell plain AKG, but it's been out of stock for a long time:

https://www.jomarlab...taric-acid.html

 

You used to be able to get Creatine AKG a few places. I haven't seen that for awhile either.

 

I posted some old studies here:

https://www.longecit...ndpost&p=663005

 


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#19 QuestforLife

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Posted 09 February 2020 - 01:40 PM

You get a gram of the alpha-keto-glutarate (calcium) salt and another 190mg of calcium.


Sorry this is wrong.Two calcium molecules are added to the AKG molecule and there is no other calcium.

Given other supplement manufacturers make this, I don't see how this is patentenable.





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