Rejuvant?

Has anyone heard of this?

https://rejuvant.com/Home

 

The speaker presented a talk indicating that users got substantial drop in DNA methylation age results - I seem to recall an average of 8 years after 6 months usage

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  • forgot to mention was presented in Longevity 2020 conference 5/1/20

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      • Fred Cloud
      • Fred_Cloud
      • 10 mths ago
      • Reported - view

      Paul Beauchemin Is there a video clip out there of this? I looked but didn't see it.

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  • I have not seen much information regarding Alpha-Ketoglutarate and its potential for agereversal - improving healthspan. But I have seen a lot of Alpha-Ketoglutarate in formulas that focus on improving physical peak perfromance in sport.

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  • Here’s a summary of CEO’s talk. Claims are quite impressive 

    https://www.longevity.technology/rejuvant-shows-positive-early-results-in-humans/

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    • Paul Beauchemin They use  calcium Alpha-Ketoglutarate monohydrate, 1000 mg daily. yes they report intresting resluts.

       

      Here is another report from a mice study.

      https://www.biorxiv.org/content/biorxiv/early/2019/10/04/779157.full.pdf

       

      it seems like the major effect is compressed morbidity and increased healthspan rather than increased lifespan.

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    • Paul Beauchemin I found this paper about CaAKG. Calcium-Alpha Ketoglutrate is to find. Have someone else here had better luck?

       

      https://www.sciencedirect.com/science/article/abs/pii/S1550413120304174

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      • David H
      • David_Hanson
      • 8 mths ago
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      Staffan Olsson I found this one with a google search:

      https://www.supplementplace.co.uk/calcium-akg/

      Free international shipping if you spend more than 50 pounds.

      Disclaimer:  I have never purchased from them.  Buyer beware as usual.

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    • David H Thank you David! Much appreciated.

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      • Iðunn
      • Iunn
      • 8 mths ago
      • Reported - view

      Staffan Olsson Does anyone have a copy of the full text of this paper? Would you please attach it to a post?

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      • Iðunn
      • Iunn
      • 8 mths ago
      • Reported - view

      Staffan Olsson Thanks. I was actually aware of that. That's of course the preprint, not the text as it was finally published (let alone the formatting changes); would anyone please post the final, published journal version?

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    • Iðunn AS far as know they published it yesterday in cell metabolism. But not the full paper. And it is not a free version.

       

      Cell-metabolism

      Short Article| Volume 32, ISSUE 3, P447-456.e6, September 01, 2020.

      https://www.cell.com/cell-metabolism/pdf/S1550-4131(20)30417-4.pdf

       

      I guess we have to keep looking for the full text.

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      • Iðunn
      • Iunn
      • 8 mths ago
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      Staffan Olsson That is the full text — but behind a pay-wall. I was hoping someone had access to a copy (university students and staff, etc). Thanks for following up.

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  • Paul. I found this one study on AKG antiaging effect.

    "In males, diets containing 10 mM AKG  increased maximum lifespan. Diet with 20 mM AKG shortened median lifespan and had no effect on maximum lifespan of males."

    http://ukrbiochemjournal.org/2018/11/effects-of-alpha-ketoglutarate-on-lifespan-and-functional-aging-of-drosophila-melanogaster-flies.html

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  • Paul Beauchemin I found this study. Now this is interesting AKG shows life extension because it inhibits Mtor and activates AMPK. So thats good news and bad news. Good news because it is acting like both metformin and rapamycin life extension pathways. However the bad news is that it doesn't seem to be working by rewinding the methylation clock.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629006/

    I will keep looking but I really don't see much. If this stuff is so great, shouldnt people be talking more about it and touting it for its antiaging properties?

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    • Fred Cloud lots of people talking about it now, including David Sinclair https://www.biorxiv.org/content/10.1101/779157v1.full.pdf

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      • Fred Cloud
      • Fred_Cloud
      • 8 mths ago
      • Reported - view

      Paul Beauchemin Interesting, thanks for posting this. I wonder if anyone here has confirmed methylation age reversal from taking it? They say it only take 6 months, I think we have been discussing it that long on here. Are you on it?

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      • Iðunn
      • Iunn
      • 8 mths ago
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      Fred Cloud I respect the hell out of Brian Kennedy and Gordon Lithgow, and the animal study is very interesting. However, the epigenetic age clock used in the PDLH "study" is really shoddy and has not been validated; I would ignore that part and wait for the human studies from Kennedy at the National University of Singapore or via PDLH at Indiana U.

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  • Fred Cloud Brian Kennedy spoke at an online Longevity conference in London in March of this year. It was free to watch live but they charged for links to the replays and I did not buy the replay. His talk was featured along with top longevity scientists so it seems odd if this was a scam

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      • Fred Cloud
      • Fred_Cloud
      • 10 mths ago
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      Paul Beauchemin I see, well doesnt it seem odd no one is talking about this? Why the disconnect. A supplement that can rewind the methylation clock? That's huge news and the only one talking about it is the company promoting it. That seems strange. Everyone made a huge deal about Dr Katcher's breakthrough. This would be even bigger than Katchers announcement, as it is available now, no regulatory issues, just go down to the store and buy this supplement that has been sitting on the shelf for 30 years in health food stores and it can rewind your clock.

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      • Iðunn
      • Iunn
      • 10 mths ago
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      Paul Beauchemin 

      Paul Beauchemin said:
      Brian Kennedy spoke at an online Longevity conference in London in March

       Would you please link the website for this conference, and ideally the Kennedy video or related materials?

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  • How long did it take for Nicotinamide Riboside to become accepted?  Could this  be the newest supplement to take for longevity?

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  • This is strange and was in the FAQ on their website:  

     

    Can I take Rejuvant with multivitamins?

    Based on our data, taking multivitamins or other supplements that have many ingredients might not have additive effects. Because of this, we recommend taking Rejuvant apart from other supplements and vitamins.

     

    Do I really need to stop taking multivitamins?

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      • Iðunn
      • Iunn
      • 8 mths ago
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      Jim N There are a number of rodent lifespan studies and human epidemiological studies suggesting decreased rather than increased lifespan from multivitamins (especially high-dose multis like LE Mix); it seems best to target specific nutrients you need and not throw a huge load of every nutrient at everyone and then megadose something like AKG on top of that — and their results support that.

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    • Iðunn Could not disagree with you more on your  LEF multivitamin statement. I have been taking LEF multivitamin for 20 + years. Also follow LEF's recommendations on a number of supplements and hormones. You can always find a study or two which makes a false conclusion based on bad study design.

        I will be 80 in OCT. MY AI 2.0 and AI 3.0 were 25 and 29 years old respectively for a May, 2020 blood test. My Levine sspreadsheet for the same bloodwork calculated a Ptypic age of 73.42 and a DNAm of 71.8. 

      I had emergency bypass surgery based on angiogram over 26 years ago. The probability of my being here 26 years later is less than 5 %. 

      Thank you LEF

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  • Lifespan IO talked about it yesterday. I'll wait for better studies. 

    https://www.lifespan.io/news/pilot-study-results-suggest-epigenetic-age-reversal/

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    • Paul Beauchemin

      Thank you for the links. The you tube interview was great. I think they don't recommend taking AKG with multivitamins since the combination might cancel out each other's positive effects. At least that is how I interpreted what he said. They have seen that happen when they have tried to combine other products. Products that on their own had positive effects but when taken together the positive effects of both products vanished. 

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  • Questionable 13-Site DNAm Clock?

       On fightingaging.org, Reason says the following:

    "The important point to consider here is that the TrueMe Labs assay is not a relabeling of any of the more established epigenetic clocks, those with significant research associated with their behavior. It is is its own beast, an independently developed test. It uses only 13 DNA methylation sites, and so it is very possible that it is much more sensitive to some interventions than others, in comparison to, say, the original Horvath clock, depending on which mechanisms influence those sites. Thus one cannot take any of the established research into the better studied clocks and use it to inform expectations as to how the TrueMe Labs assay will behave. 8.5 years might sound like a large effect size, but it is impossible to say whether or not that is the case."

        In other words, the Rejuvenant claim about producing a DNAm clock reset is very questionable, because they used a nonstandard clock, possibly tailored to show a maximum effect.  It would be a real service to the anti-aging enterprise if someone or some group would demonstrate, either systematically with mice or anecdotally with humans, that Calcium Alpha-ketoglutarate intervention actually significantly lowers the methylation age indicated by the Horvath clock.

         Also, I note that there is a load of misinformation about DNA methylation on the Rejuvenant site.  It characterizes DNA methylation as age-accumulated "rust" that randomly builds up with age.  As I understand it, the correct picture is that genes are silenced by methylation, mainly by methylating sites in the promoter regions of DNA coding for making mRNA leading to protein production.  Even infants have many methylated regions silencing genes that are not needed.  As aging progresses, epigenetic programming silences some genes and activates others, and the methylation pattern shifts.  Horvath's clock specifically selects hundreds of methylation sites that are best (positively or negatively) correlated with aging from 450,000 sites on an analysis chip.  I'm not impressed by the results of a 13-site analysis.

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  • JGC said:
    the Rejuvenant claim about producing a DNAm clock reset is very questionable, because they used a nonstandard clock, possibly tailored to show a maximum effect.  It would be a real service to the anti-aging enterprise if someone or some group would demonstrate, either systematically with mice or anecdotally with humans, that Calcium Alpha-ketoglutarate intervention actually significantly lowers the methylation age indicated by the Horvath clock.

     Yes: I pointed this out earlier in this topic. I doubt they intentionally "hacked" it to turn out favorably for their product: the problem is that it's sloppy and not validated, not that it's intentionally pushed in one direction or the other.

     

         Also, I note that there is a load of misinformation about DNA methylation on the Rejuvenant site.  It characterizes DNA methylation as age-accumulated "rust" that randomly builds up with age.  As I understand it, the correct picture is that genes are silenced by methylation, mainly by methylating sites in the promoter regions of DNA coding for making mRNA leading to protein production.  Even infants have many methylated regions silencing genes that are not needed.  As aging progresses, epigenetic programming silences some genes and activates others, and the methylation pattern shifts.  Horvath's clock specifically selects hundreds of methylation sites that are best (positively or negatively) correlated with aging from 450,000 sites on an analysis chip.  I'm not impressed by the results of a 13-site analysis.

    So they're actually kind of right about this, though they've oversimplified. When you're developing from a zygote to a newborn and go through development to become an adult, your cells undergo regulated methylation under a developmental program aimed to turn you eventually into a functioning adult with all your cells doing what they're supposed to do. What happens in aging is very different: not an unfolding preprogrammed process, but a series of events all somehow involving damage that changes the epigenome in dysfunctional ways. This is a mixture of a very small number of stochastic events that methylate or demethylate genes that should stay as they are (direct epigenetic "rust") and regulated changes in cells as they have to adapt to an environment that has been changed by stochastic aging damage (what we might call secondary or downstream epigenetic "rust response").

    Also, everyone keeps talking about "the Horvath clock." It's important to understand that there are now dozens of epigenetic aging clocks, including at least six developed by or with the involvement of Horvath, each of which is more or lesss good at different things. His original clocks were good at predicting calendar age, but not very good at predicting risk of age-related disease and death (biological age); the newer Levine "DNAm PhenoAge" is better at that (and the underlying PhenoAge clock is even better), and the "DNAm GrimAge" is at least as good and maybe better, though it "cheats" a bit by building smoking status into the clock.

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      • JGC
      • JGC
      • 8 mths ago
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      Iðunn 

           About your "stocastic events": there is likely some random methylation that happens to DNA in particular cells, but that should be extremely unlikely to effect all  DNA, so that it would show up in an overall methylation assay for a clock estimate.  Or perhaps you had in mind random epigenetic reprogramming events from some feedback mechanism that went astray.  I don't know of any information about that.

          I also note that the Rejuvenant site also says:  "Methyl groups are chemical tags, that in effect block our DNA from doing its job when it comes to making ideal copies of itself ..."   That's wrong.  In cell division the methylation pattern is copied along with the rest of the DNA structure.  Otherwise epigenetic programming to determine cell function wouldn't work.

           Finally, I wonder how TrueMe Labs picked their selected 16 methylation sites, if it wasn't done to optimize their age-reduction effect.  As I said, if you use the right chip, there are hundreds of thousands of methylation sites to choose from.

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      • JGC
      • JGC
      • 8 mths ago
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      Iðunn 

           On the matter of bio-clocks, in his 2020 ARDD Meeting talk on Friday, David Sinclair presented evidence from his mouse-based experiments that when his OSK cocktail of Yamanaka factors is used to reset the DNA methylation clock of aged mice, it also resets the gene expression to a profile characteristic of young mice.   In other words, resetting the DNAm clock (at least using OSK) also resets the biological age.  I consider that to be very good news.

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      • Jimmy
      • Jim_N
      • 8 mths ago
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      JGC Did Sinclair mention if it caused any deformities?

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      • Fred Cloud
      • Fred_Cloud
      • 8 mths ago
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      Jim N well sure you may grow an extra toe, but thats the price you have to pay to live past 100.

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      • JGC
      • JGC
      • 8 mths ago
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      Jim N 

           Next week you should be able to view the recording of his talk yourself on the ARDD site.  From my understanding and memory, what his group did was this: (1) injure a mouse in a particular way; (2) show from DNAme testing that the methylation pattern had been modified in the injured tissue to map into that of an aged mouse; (3) apply a virus that implanted OSK-generating genes in the damaged tissue only; (4) demonstrate that the damaged tissue had recovered its function; (5) demonstrate that the DNAm methylation pattern of the tissue had been restored to its former youthful profile.

           There were no deformities, but one would not expect any.  Sinclair did say when introducing discussion of the experiment that if you simply dosed yourself with OSK, it would kill you.   Here's his slide showing the DNAme comparison:

       

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    • JGC What is the dosage with OSK? What does O, S and K mean?

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      • JGC
      • JGC
      • 2 wk ago
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      Pablo Reinaldos López 

          OSK stands for three of the four  "Yamanaka Factors", four proteins designated by the acronyms OCT4, SOX2, KLF4, and c-MYC (OSKM).  There is no "dosage" involved.  The researchers genetically modified a strain of mice using a virus that implanted a "cassette" in their DNA.  This produced a setup in which, when a certain exotic antibiotic was present, the cassette would switch on the expression of OCT4, SOX2, and KLF4.  (They omitted c-MYC because there was some evidence that it causes tumors.)

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  • I ordered some this week. I’ll tell you in four months if I see anything. I also take rapamycin weekly, do you thinks it’s a bad idea to combine the two?

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      • Gokhan
      • Gokhan
      • 3 mths ago
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      Larry Wonder how your experiment is going? Thanks!

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      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
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      Larry who knows, it might have some great synergy.

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    • Larry I"ve been using Rejuvant and Rapamycin for the past 4 months... no issues.  But would be really nice to see all the permutations and combinations of common age-mitigation drugs and supplements tested ... sample size n=1 is a lousy way to live our lives :-)

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  • Hi, I noticed many available akg supplements available in ~300mg caps-  is this what an “effective “ daily amount should be to start? 

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  • New rejuvant user here. I think it's amazing (as far as my exercise performance goes :P ). I'm combining it with 6mg weekly rapamycin, 500mg x 2 metformin, 5mg rosuvastatin, 500mg x 2 vit c, daily celery juice, garlic powder/AGE, magnesium, fiber, vit D... No issues to report after 4-5 days of use... except having a lot of energy to exercise :) We'll see how my bloodwork will be affected over time. 

    Life extension studies are solid (mice, worms, flies). Mice life extension is there (maybe ~3-4% on avg). Health extension is very significant. Turns hair darker ("better fur" :))... also reported by a forum member. Reduces ischemia in humans. There's some evidence AKG is an anti-cancer compound (works agains several cancer lines in cell and mice studies); reduces hypoxia. Human studies are limited, but that's ok as this compound has been on the market for decades and it hasn't harmed anyone. Safe to test N=1, imho. 

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  • I have taken 2 different DNAm tests and after 6 months of Rejuvant it did not lower my epigenetic age in either test.  I'm debating on whether to continue taking Rejuvant...

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    • Jimmy2 Well thats a bummer. Did you use their recommended lab trueme or a different dna age test?

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      • Jimmy2
      • Jimmy2
      • 2 wk ago
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      Fred Cloud I used mydnage.com at 4 months and their test at 6 month. No significant changes in epi age. I'm disappointed.

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    • Jimmy2 Did you take a before test or just at 4 months? I took the mydnage test before and will retest at 6 months. I am not taking rejuvant though, I just went out and bought the same active ingredient, ca-akg for a fraction of the price as rejuvant.

      Is there a reason you are paying so much money for rejuvant brand of ca-akg versus just buying generic ca-akg?

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      • Jimmy2
      • Jimmy2
      • 2 wk ago
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      Fred Cloud 

      mydnage:

      • 10/01/2021
        • 41 Calendar Age
        • 39 years DNAm age
        • -2.3 years
      • 1//27/2021
        • 41 Calendar Age
        • 28 DNAm age
        • -2.5 years
          • In this test I got barely younger.
          • Could be in error range.

      trume: 

      • 11/23/2020
        • 39.6 Calendar age
        • 41.3 DNAm age
        • -1.7 years
      •   4/29/2021
        • 41.9 Calendar age
        • 40.6 DNAm age
        • -1.3 years
          • So I got older faster, but just barely.
          • Could be in error range.
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      • Jimmy2
      • Jimmy2
      • 2 wk ago
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      Fred Cloud Rejuvant is what I consider a premium supplment.  Dr. Brian Kennedy runs the Buck Institute.  He is somewhat involved with the creation of Rejuvant.  That's the reason I am paying a premium.  Is it worth it?  Maybe.

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    • Jimmy2 I looked into it. Ca-akg is ca-akg, they probably get it from the same exact manufacturer. Aminos all have high purity, so there isnt a difference between suppliers as they are all basically commodities of the same quality. So there is no valid reason to pay a premium for Rejuvant.

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      • Jimmy2
      • Jimmy2
      • 2 wk ago
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      Fred Cloud Without a third party test who knows which is more pure.  It’s like buying generics versus the original.  Rejuvant was first to sell CaAKG.  Before there were other forms for body building.

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      • Jimmy2
      • Jimmy2
      • 2 wk ago
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      Jimmy2 I meant to say 38 DNAm age above for 1/27.  Not sure how to edit.

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      • Chris
      • Chris.1
      • 2 wk ago
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      Jimmy2  Does it have to be the calcium AKG?  How much calcium is in a serving?  

      Can one use the AAKG instead?

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    • Chris All the studies on AKG in longevity have been done only with Ca-AKG, so nobody knows if any of the other versions work. I wouldn't waste my money on the other versions until more studies come out. Listen to the lead researcher on this issue: https://www.youtube.com/watch?v=rPuHXjZIaAc

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    • Brin Chikovski If you want ca-akg then buy the generic brand that costs a fraction of Rejuvant.

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      • Chris
      • Chris.1
      • 2 wk ago
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      Brin Chikovski Thanks! I'm just concerned on how much calcium is in a serving, do you know?

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    • Chris In the Rejuvant product its 190mg of Calcium per 1,000 mg of AKG.  I suspect its close to the same for all the Ca-AKG products.  I've emailed MaxxHerb to ask them about their Calcium levels.  Fundamentally - its a small amount, so I wouldn't worry about it.    The RDA for Calcium is 1,000 mg / day.

      https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Alpha-ketoglutarate-Cognitive-Vitality-For-Researchers.pdf

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    • Brin Chikovski Rejuvant website indicates the Buck institute used their sustained release product in their studies. Do we know if it is particularly important that the product be sustained release AKG?

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    • chuck stanley I think the Rejuvant website may be misleading here.  In this video:

      https://www.youtube.com/watch?v=rPuHXjZIaAc&t=9s

      Gordon Lithgow says that they used the CA-AKG version of the molecule in mice because that is what had proven effective in worms in earlier studies.  

      I believe they just used the time release version of CA-AKG in the mouse studies that were published in this paper (not the full rejuvant formula that includes some other supplement ingredients):

      https://www.biorxiv.org/content/10.1101/779157v1.full.pdf

      And I seem to remember in one video interview with Gordon Lithgow - he mentioned that PDLH then took the CA-AKG and added some other supplements to the mix as they made their version of AKG and also male and female specific versions of ca-AKG (but again, these were not part of the studies completed by the Buck).  

      Now - I believe there are other new studies being done with the Rejuvant in humans using the new Rejuvant commercial product - as is discussed here, and this may be what the PDLH / REjuvant website is talking about:

      https://www.youtube.com/watch?v=ctrfZ3QoqTI&t=585s

      Brian Kennedy does mention in one of his interviews - perhaps this one:

      https://www.youtube.com/watch?v=5Jg6jexruZ4&t=518s

      That Ca-AKG does have a short half-life of a few hours so if you aren't taking the time-release version (i.e. just the generic CA-AKG powder) you need to take it more often.  

      Given the cost difference - I'm ok with that.

      Price of Rejuvant is $110 to $150 for a 30 day supply (taking two tablets with a total of 1,000mg / 1 gram of CA-AKG per day.  Cost per gram of CA-AKG is in the $3 to $5 per gram range,

      Price of MAXXherb Ca-AKG powder is in the range of $42 to $46 per 100 grams, so approx. $0.42 to $0.46 per gram for the same thing.

      S0, you're paying a 600% to 1,000% higher price for the Rejuvant for time release.  Seems like too high a premium to me.

      I've used Rejuvant for 4 months, and then switched to MaxxHerb.  I can't tell the difference.  

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  • Guys, Rejuvant is extended (slow release), whereas other AKG formulations on the market are immediate release (as of 04/2021). I believe AKG is metabilized fast, and to get the same effect, one has to consume immediate-release AKG every 4 hours. I'm sure Rejuvant went through stringent quality checks as well, given the premium price and the brand they're building. 

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  • Don’t know how true this is but I’ve read some “reliable” sources that AKG can reduce DNAm age.  However, if you combine it with Metformin it won’t reduce DNAm age.  Although there could be other beneficial effects.  🤷🏻‍♂️  I’m still undecided.  I’m sure more papers will come out on this, hopefully sooner than later.

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