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Alpha-Ketoglutarate as an Anti-Aging, Anti-Frailty Compound

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#181 timedilation

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Posted 05 March 2023 - 11:14 PM

General question: A fair amount of the longevity benefit of AKG is attributed to its DNA/histone demethylation effects, which are associated with reductions in epigenetic age.  Separately, there is a fair amount of interest in restoring methylation through the use of TMG, methyl-cobalamin, etc., particularly for individuals with MTHFR.  Are these two goals contradictory, or are they completely separate and noninteracting methylation targets?  Could other interventions that use up methyl groups (e.g., I've heard NAD+ has that effect) lead to a slow down of epigenetic aging?  Could the consumption of excessive methyl groups speed up epigenetic aging?


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#182 osris

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Posted 10 March 2023 - 03:04 PM

I asked Dr Kennedy this question above re: CA-AKG vs. AAKG, and he said, as in the video already posted, that he didn't want to introduce so much protein. He also mentioned that it would be interesting to try AAKG, although they had not. So no special reasoning for CA-AKG other than the one mentioned.

 

This is a good point.

 

Maybe AAKG is a better alternative to the more expensive CA-AKG.



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#183 osris

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Posted 10 March 2023 - 03:29 PM

Here's another calcium AKG source.

https://www.simplesa...0-capsules.html

 

It certainly is cheaper, and you get a year's supply. But the dosing recommendation says to take one 300 mg capsule a day. That dosage sounds a bit low, given that a gram is usually suggested for CA-AKG supplements. 

 

There is enough in the container though to take more capsules, but that would no longer make it a year's supply.

 

Also, I see that dextrose is uses as a capsule filler. That seems a bit odd... sugar as filler.


Edited by osris, 10 March 2023 - 03:33 PM.


#184 osris

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Posted 10 March 2023 - 03:58 PM

New rejuvant user here. 1 tablet/day seems to do the trick for me. I experienced significant improvement in exercise performance. Am encouraged by a forum-member reporting their hair turning darker after ~6 months. Also reports of significant decrease in epigenetic age (outside of company claims). Also encouraging: This compound has anti-cancer effects. IMO, this differentiates it from the likes of NR/NMN, which have some worries regarding encouraging cancer growth.

 

 

 

What is the source of your claim about NR/NMN and cancer growth?



#185 osris

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Posted 10 March 2023 - 04:08 PM

There were some first adopters to this product. Still using it? I would appreciate to learn about experiences or test results.

 

 

I'd also like to know this.



#186 Harkijn

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Posted 13 March 2023 - 09:12 AM

I posted the same question in other forums. No one has stepped forward...



#187 ta5

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Posted 23 April 2023 - 10:19 PM

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. 

 

On the Part II video there's this comment:

D Dutton
Interference between AKG and metformin and berberine. Metformin, berberine, apigenin and others inhibit AKT signaling. In the paper I mentioned they show that epigenetic reprogramming was driven by increasing AKT signaling. The paper is very technical but the abstract is readable. Sirtuins, NAD+ boosters, rapalogs and others activate AKT.

 

I wonder why their own patent says the combination of Berberine and Ca-AKG has beneficial effects in C. elegans and mice?

1. A method of extending lifespan in a subject in need thereof comprising administering to the subject a therapeutically effective amount of berberine, a vitamin A compound, and a-ketoglutarate (AKG).

...and other similar claims 

[0030] FIG. 1 shows the lifespan effects of indicated compounds on C. elegans aging. Compound 1 is Ca-AKG. Compound 2 is retinoic acid (RA), a metabolite of vitamin A that mediates its functions. Compound 3 is berberine. Both Ca-AKG+RA and the combination of all three compounds have robust effects on longevity.
[0031] FIG. 2 shows the effect of the combination of berberine, Ca-AKG, and retinoic acid (RA) has on survival in female mice compared to control female mice. (Cohort 1)
[0032] FIG. 3 shows the effect of the combination of berberine, Ca-AKG, and vitamin A has on frailty scores in female mice (bottom line) compared to control female mice (top line). (Cohort 1)
[0033] FIG. 4 shows the effect of berberine, control, or retinoic acid (RA) on female mice lifespan. (Cohort 1)
[0034] FIG. 5 shows the effect of the combination of berberine, Ca-AKG, and retinoic acid (RA) (triple) and the combination of Ca-AKG and berberine (double) on female mice lifespan. (Cohort 1)

 

 

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#188 DanCG

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Posted 28 April 2023 - 10:40 PM

 

 

I wonder why their own patent says the combination of Berberine and Ca-AKG has beneficial effects in C. elegans and mice?

.1. A method of extending lifespan in a subject in need thereof comprising administering to the subject a therapeutically effective amount of berberine, a vitamin A compound, and a-ketoglutarate (AKG).

 

..and other similar claims 

 

 

This was the original claim 1. You can find the prosecution history of the patent application here. The applicant amended the claims before it reached an examiner. For reasons unknown to us, they canceled claims for the combination of berberine and AKG, and instead went ahead with claims for either vitamin A plus AKG or vitamin D plus AKG.

We can only speculate on why they chose to drop the berberine claims before the US examiner had even expressed an opinion about them. In Global Dossier, we find that they took the same strategy in the European Patent Office and in Japan (probably others too, I didn’t look).

 

Don’t read too much into the claims for combinations. It may only be a patent strategy and not really that important scientifically. AKG by itself would not be patentable because it is an unmodified natural product and because of prior art. Combining AKG with other things has a chance of being patentable if the combination is not obvious.

 

We can see how the strategy has played out so far.

The US examiner required them to choose either vitamin A plus AKG or vitamin D plus AKG for further examination. (This is a common practice; the applicant can go for the things they did not choose in a separate application later). They chose vitamin D plus AKG. So far, the US examiner doesn’t seem to think that using AKG to extend healthspan was really a new idea at the time the application was filed. The examiner is also not convinced that there is anything special about the combination of vitamin D plus AKG. Of course that is just one person’s opinion, which could be overcome with further argumentation or it may be overturned on appeal.

 

I suspect that they dropped the berberine claims because both berberine and AKG were previously known or suspected to be beneficial for aging and, therefore, by patent legal precedent, the examiner could argue that it would be obvious to combine them. Maybe they wanted to avoid that argument for now. So their strategy of foregoing the berberine claims says nothing about whether the combination actually works. Scientifically though, the actual data in the application does seem to support their use in combination.


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#189 ironfistx

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Posted 29 April 2023 - 06:54 PM

Can we take alpha ketoglutaric acid instead or must it be cakg? I ask because longevity companies appear to be a little unscrupulous.

Would it be the akg helping or the ca that is connected to it?

I don't know. Like how I don't know how taking magnesium and taurine concurrently is any different than taking magnesium taurate.
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#190 MikeDC

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Posted 20 May 2023 - 01:27 PM

From Sinclair, AKG can activate OSK factors and make cells and tissues younger
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#191 Fafner55

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Posted 20 May 2023 - 03:24 PM

From Sinclair, AKG can activate OSK factors and make cells and tissues younger

 

Could you cite a reference?



#192 MikeDC

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Posted 20 May 2023 - 05:40 PM

Could you cite a reference?


https://youtu.be/n5XjNdAudss
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#193 bhoffman

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Posted 09 June 2023 - 02:45 AM

I am taking it but cannt tell if any of the health benefits I have have been from CA-AKG or other supplements, I am trusting the studies and research 


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#194 ironfistx

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Posted 24 June 2023 - 07:11 PM

This is a good point.

 

Maybe AAKG is a better alternative to the more expensive CA-AKG.

 

From what I read somewhere else, AAKG requires too much A in order to get proper doses of AKG.



#195 ironfistx

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Posted 24 June 2023 - 07:14 PM

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


Edited by ironfistx, 24 June 2023 - 07:15 PM.

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#196 ironfistx

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Posted 24 June 2023 - 07:23 PM

From Sinclair, AKG can activate OSK factors and make cells and tissues younger

Can we trust this salesman?



#197 MikeDC

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Posted 24 June 2023 - 07:40 PM

From what I read somewhere else, AAKG requires too much A in order to get proper doses of AKG.


A is heavier than Ca by a factor of 4. But AAKG is cheaper and A is harmless.

Can we trust this salesman?


Sinclair has not been very honest to say the least. But this thing
Seems to have scientific bases.

#198 MikeDC

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Posted 24 June 2023 - 07:43 PM

I am taking it but cannt tell if any of the health benefits I have have been from CA-AKG or other supplements, I am trusting the studies and research


One will probably need high doses of AKG and longer term supplementation to see significant results.
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#199 MikeDC

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Posted 20 August 2023 - 04:01 PM

I asked Dr Kennedy this question above re: CA-AKG vs. AAKG, and he said, as in the video already posted, that he didn't want to introduce so much protein. He also mentioned that it would be interesting to try AAKG, although they had not. So no special reasoning for CA-AKG other than the one mentioned.

I have been using AAKG for a couple of weeks. About 5-6g per day. I am getting similar effects as Tru Niagen initially. I get very smooth skins. I get less sleep using Tru Niagen. But much better sleep with AAKG because of the arginine. I think AKG will be proven to be the best anti aging supplement. Much better than NR and NMN.
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#200 Florin

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Posted 09 November 2024 - 10:36 PM

First: a new Ca-AKG supplement has become available from a vendor I consider generally reliable that is both cheaper and higher-dose than the Kirkman product that a number of people are using.

 

Is anyone concerned about arsenic contamination from the rice flour filler contained in this ProHealth Ca-AKG supplement?

 

There's another thread discussing arsenic-containing, supplement fillers, but it hasn't gotten much attention.



#201 MikeDC

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Posted 19 November 2024 - 11:34 PM

27.5% AKG in AAKG.
32.7% AKG in OAKG.

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#202 MikeDC

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Posted 19 November 2024 - 11:38 PM

I posted an AKG mice study under the NAD+ section. The study showed AKG increases NAD+, NAD+/NADH, Sirt1.
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