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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    • 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
      • 1 yr 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
      • 1 yr ago
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      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
      • 1 yr ago
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      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
      • 1 yr 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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    • 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
      • 1 yr 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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    • 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
      • 1 yr 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
      • 1 yr 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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    • Peter H. Howe You go boy! 🥳🎈🙏

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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
      • 1 yr 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
      • 1 yr 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
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      JGC Did Sinclair mention if it caused any deformities?

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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
      • 1 yr 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
      • 6 mths 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
      • 9 mths ago
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      Larry Wonder how your experiment is going? Thanks!

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      • Fred Cloud
      • Fred_Cloud
      • 9 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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      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
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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
      • 6 mths 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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      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
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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
      • 6 mths 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
      • 6 mths 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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      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
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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
      • 6 mths 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
      • 6 mths 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
      • 6 mths 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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      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
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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
      • 6 mths 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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      • Jimmy2
      • Jimmy2
      • 6 mths ago
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      Chris Study on dietary and supplemental calcium says,

      " Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55)." 

      https://www.bmj.com/content/346/bmj.f228

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      • Chris
      • Chris.1
      • 6 mths ago
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      Jimmy2 Thanks!

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      • J Man
      • J_Man
      • 2 mths ago
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      Fred Cloud I agree that Rejuvant is too expensive. 

      In answer to your question the Rejuvant site (https://rejuvant.com/How-Rejuvant-Works) indicates that the product is "patent-pending sustained release combination of Calcium and Alpha-Ketoglutarate." I believe the men's formula may also contain vitamin A. From what I've read sustained-release may be a better approach to maintaining a constant level in the body.

      While doing a bit of research on this I found no other version of sustained-release except a product from Swanson Vitamins that is no longer in stock.  

      So, maybe this sustained-release aspect is why it costs so much more?  I certainly don't know.

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      • Fred Cloud
      • Fred_Cloud
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      Jay Orman Its the ca-akg that creates the sustained release, so just find a ca-akg from another supplier. AKG has been found to work also, so I think they just want something unique that they can patent so they can mark the price way up, that is the way things work in business. If it is a commodity they cant raise the price up as high. There are alot of gullible people who respond to marketing, it is what has made this country rich. So if you want to pay for marketing, go ahead. If not, buy generic ca-akg.

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      • J Man
      • J_Man
      • 2 mths ago
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      Fred Cloud Thanks for the information.  I didn't know that.  Do you have a source that talks more about the sustained release aspect of ca-akg?  

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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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      • JGC
      • JGC
      • 5 mths ago
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      Jimmy2 

          What's the evidence that "if you combine AKG with Metformin, it won’t reduce DNAm age" (but presumably will otherwise)?

          Fred Cloud said that AKG shows life extension effects because it inhibits Mtor and activates AMPK.  If it is acting like both Metformin and Rapamycin on the same life extension pathways, why would it have a different effect on epigenetic reprogramming (as indicated by DNAme age)?  What is the evidence, aside from the questionable Rejuvant sale pitch, that it does any epigenetic reprogramming at all?

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      • Jimmy2
      • Jimmy2
      • 5 mths ago
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      JGC I can’t go into detail, but watch Gordon Lithgow on AKG on the YouTube channel Modern Healthspan.  In it he says he test various combinations of drugs on worms.  Certain combination lower lifespan.  That’s why he is skeptical of people taking many supplements.  He’s part of the Buck Institute that tests CaAKG.  It’s only a hunch at this point.  That’s all I have.

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      • JGC
      • JGC
      • 5 mths ago
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      Jimmy2 

          OK, I have now read the Buck Institute AKG paper and watched two of the Lithgow interviews on Modern Healthspan.  I also watched some other videos on YouTube about the Buck Institute's AKG results.

          I gather from what Lithgow said that there is not likely to be much difference in the effects from Revuvant's time-release CaAKG versus the generally available Arginine AKG (Swanson @ $7.67 for 90 x 1,000 mg caps).  The Buck experimenters simply used CaAKG on their mouse subjects because that is what had been previously used on C. Elegans worms in similar studies.

          Alpha-ketoglutarate, in whatever form, is highly soluble in water, so there should be no bioavailability issues.  I did find a paper stating that in pigs, AKG remains resident in the bloodstream with a half-life of only about 5 minutes, so the time-release form of AKG should have added value.  However, since one wants the AKG in cells, not blood, the rapid absorption rate may not altogether bad.

          On the question of whether AKG can be expected to provide some level of epigenetic reprogramming, the Revuvant AKG promotion seems to be the only thing I could find that suggests this.  AKG does play a role in DNA methylation and de-methylation, but that cannot be taken as an indication that taking it produces epigenetic reprogramming.  Further, your experience indicates that it does not, at least in one case.

          I have just ordered several bottes of Arginine AKG  from Swanson.

      Like
      • Jimmy2
      • Jimmy2
      • 5 mths ago
      • Reported - view

      JGC Nice work on doing your own research.  Right now the evidence is based laboratory evidence on worms by the Buck Institute.  Also, Rejuvant has done pilot studies that shows it reduces epi-age.  The science community generally doesn't believe in pilot studies.  Also, Rejuvant has administered TruMe epi-age tests to many users of Rejuvant.  So, they actually have data to work with, but it's all internal evidence.  It just seems that Rejuvant doesn't work for everyone, and it affects people differently.  So, yes, we are reliant on one single company and their data.  The good news is an RCT trial is in progress, which is the gold standard of tests.  

      Like
      • Jimmy2
      • Jimmy2
      • 5 mths ago
      • Reported - view

      JGC By the way, I've tried AAKG but something about the arginine made me super alert.  Not sure about long term effects of arginine, either.

      Like
      • Jimmy2
      • Jimmy2
      • 5 mths ago
      • Reported - view

      JGC In this video, the CEO of Rejuvant explains that when berberine and AKG is combined it cancelled each other out: https://www.youtube.com/watch?v=fxNgfvOiHSM

      Like
      • JGC
      • JGC
      • 5 mths ago
      • Reported - view

      Jimmy2 

          Interesting point.  I suppose "cancelled each other out" means that something is up-regulated by one and down-regulated by the other.  I doubt that the "cancellation" applies to all of the AAKG effects.  I am currently taking both Berberine and AAKG but my wife is only taking AAKG.

      Like
  • I bought 180 500 mg AKG capsules for $15 on Amazon. Rejuvant's $110 monthly subscription price seems steep to me. I know my AKG from Amazon is not time release but in testing did the worms and mice get time release AKG? I think not.

    The Rejuvant people say that they have a patent but on exactly what? For better or for worse, I expect to see copy-cat type extended release AKG hitting the market.  

    Like 1
      • Fred Cloud
      • Fred_Cloud
      • 6 mths ago
      • 1
      • Reported - view

      Allen I did the same thing. The Rejuvant product is way overpriced. If someone still wants the ca-akg, they can buy generic version on amazon too for way cheaper.

      Like 1
      • JGC
      • JGC
      • 5 mths ago
      • 1
      • Reported - view

      Fred Cloud @allen_rosenberg

          I don't understand why you guys are continuing to buy and take AKG, when Jimmy2's self experiment (see above) indicated that taking the expensive Rejuvant's AKG-Ca for 4 months had no effect on his DNAme age, as measured by two independent labs  (mydnage and trume).   Are you doing the same thing and hoping for a different outcome?

          Jimmy2's results increase my suspicion that Rejuvant cherry-picked methylation sites that change with their treatment but have not much to do with bio-age.

      Like 1
      • Fred Cloud
      • Fred_Cloud
      • 5 mths ago
      • Reported - view

      JGC John, that was only one persons experience. Just because one person didnt get results doesn't mean the entire thing is useless. He may have also been taking something that cancelled it out such as metformin like he mentioned. I have heard from other people that did get results so all hope is not lost. So I wouldn't rush to judgement until you hear many other people not getting results.

      Like
      • aribadabar
      • aribadabar
      • 5 mths ago
      • Reported - view

      JGC I also have reports from people taking Kirkman's Ca-AKG product along with berberine who reported reduced methylation age as per their Trume results. So Jimmy2's results are not undisputed.

      Like
      • Jimmy2
      • Jimmy2
      • 5 mths ago
      • Reported - view

      JGC I am still taking Rejuvant, if though it didn't affect my biological age.  I think there is something else I am taking that is interfering with it.  I am going to adjust my stack and report back.  I do believe that it increases healthspan, if it doesn't decrease biological age for me, yet.  It also increases the oxygen carrying capacity of red blood cells so I can exercise for longer.

      Here is another study that also uses AKG along with many, many other interventions that reduced biological age: https://www.longevity.technology/wind-the-clock-back-three-years-in-just-eight-weeks/

      Research is still new so hopefully we can hone in on what is truly working.

      Like
      • JGC
      • JGC
      • 5 mths ago
      • 3
      • Reported - view

      Jimmy2 

          Maybe I'm just paranoid, but I think "trust but verify" is a good strategy when dealing with commercial bio-tech testing outfits.  In that context, I have a question about your DNAme age tests: Did you tell them your true calendar age when filling out the orders for the tests?

          My wife and I recently did DNAme Age tests with EpiAging.  In placing the orders, I avoided divulging our calendar ages (even though they asked for them.)  The results (see LINK) came back with my DNAme age less than my calendar age by 23.6 years and hers less by 14.3 years.  It is devoutly to be hoped that our use of anti-aging supplements (metformin, rapamycin, resveratrol, curcumin, spermidine, GLA, ...) and our periodic D+Q+F+P senolytic sessions have actually made us biologically younger by those spectacular amounts, but I'm skeptical.  I wonder if it could be that some or all of the DNAme testing laboratories are "dry-lab-ing" their results to put them within a few years of calendar age, if it is known.  I think that when doing such tests, one should give the testing lab as little age information as possible.

      Like 3
      • Jimmy2
      • Jimmy2
      • 5 mths ago
      • 1
      • Reported - view

      JGC Good point.  For my next DNA test I will create a new identity and avoid revealing my age.

      Like 1
    • JGC As I reported earlier, my EPIAGEING DNAme age test  was 22 years younger than my calendar  age (80) and I did provide them with my calendar age. I did have some issues with their bookkeeping,  but do not know if these issues extend to the laboratory.

      Like
      • Allen
      • Allen_Rosenberg
      • 5 mths ago
      • Reported - view

      JGC At this point, I think the scientific evidence outweighs an anecdotal report. Excluding Rejuvant, the cost of AKG is low so why not give it a try?

      Like
      • Fred Cloud
      • Fred_Cloud
      • 5 mths ago
      • 1
      • Reported - view

      JGC I felt the same exact way when I ordered my methylation test from mydnage.

      They asked my age before the test and that screamed red flag for the same reason you expressed, I thought what is to prevent them from dry labbing the result close to your age and pocketing the money? So I told them I was 99 years old, they called me in a panic when my result came back in the 50's. I told them there was no way I was giving them my real age before they gave me the result, they were so confused, they couldnt even understand the concern. I sent several emails to their execs, and they couldnt understand my concern. It was very strange.

      Like 1
    • Allen My wife had ocular shingles and traced it to the arginine supplements she was taking for growth hormone release.   Young body builders are coming down with shingles by over doing arginine supplementation.   So  there is AAKG and AKG.  Does AKG have any arginine in it?

      Like
    • Robert Olin

      "Arginine bioavailability is absolutely necessary for the replication of herpes simplex virus, which causes cold sores/genital herpes. When arginine is not available, herpes viruses in cells are unable to complete a single replication cycle and cell damage is evident in infected cells".

      "Herpes zoster ophthalmicus is reactivation of a varicella-zoster virus infection (shingles) involving the eye"

      But Calcium AKG doesnt seem to cause such problems.

      Like
    • chuck stanley    The product we have is Double Wood  Supplements   AKG.   There is no mention of calcium or arginine.    If it had arginine wouldn't it say AAKG?

      Thanks.

       

      Bob

      Like
    • Robert Olin  I dont see arginine anywhere in their ingredients list. I cant think of  any reason that arginine would be produced by any other form of AKG. But I'm only familiar with the Ca AKG which if I recall was the product used in the studies, so thats the one I use. Since virtually all or nearly all of us have some sort of herpes virus living in us, I expect we would have heard of any adverse reactions to the Ca AKG.

      I was curious so I contacted Doublewood and the rep wasnt able to tell me the source of the AKG. I hope to get an email response. At this point, since she did tell me the AKG was not from Ca AKG, I would assume it is from the arginine- AKG.

      Like
    • chuck stanley   Thanks so much.   So it appears then, that AKG comes in one of two forms - calcium and arginine.    I've heard that if you do take arginine you should also take lysine to balance it.

      Like
    • Robert Olin interesting point. If you are supplementing with arginine for its benefits you probably wouldnt want any extra lysine competing with it.

      Like
    • chuck stanley If the Double Wood AKG has arginine my wife can't take it but I can, however, the lysine might help.   I've never had shingles but my God it can be painful and leave you with lasting nerve pain.   I've scanned the net and can find nothing that repairs the damaged nerves.   My wife has to take seizure medicine to live with it.  It's driven some people to suicide.  

      Like
    • Robert Olin well, it might not have arginine in it after all.

      Here is what it says on Amazon about the product: "Different than AAKG - AKG is not be confused with AAKG. AAKG is a combination of Arginine and Alpha Ketoglutarate which AKG is pure Alpha Ketoglutarate." So according to that statement, its not the salt, but the  pure AKG.

      That statement by itself would be reassuring, but it also says: "Nitric Oxide Booster; AKG may act as a precursor for both arginine and nitric oxide to help boost levels of both" Sounds pretty ominous. I'd be afraid of it myself.

      Maybe the Ca AKG is a form that doesnt have that effect.

      If I get an answer from the manufacturer I'll post it.

      Like
      • Allen
      • Allen_Rosenberg
      • 5 mths ago
      • Reported - view

      Robert Olin I knew someone years ago who committed suicide because of shingles. He was young, maybe not even 30.  

      Like
    • JGC does the p in d+q+f+p stand for piperlongumine?

      Like
      • JGC
      • JGC
      • 5 mths ago
      • 1
      • Reported - view

      Chuck Frasher 

          The P stands for Piper Nigrum in the form of Swanson BioPerine ($2.86 for 60 x 10 mg caps).  It is intended to increase bioavailability of flavenoids like Fisetin and Quercetin  by suppressing the presence of P-glycoprotein in the small intestine.  We take it an hour before the other items in D+Q+F+P to give it a  chance to do that.

          See https://www.isotrope.com/bioperine/ .  It says that: "P-glycoprotein is a protein the body uses to break down exogenous compounds found in the body. This protein inhibits the action of many medications, and also regulates the degree to which certain nutrients are absorbed by the body. This protein actively controls the permeability of the blood-brain barrier, which directly impacts the overall effects seen by many compounds such as curcumin—the active compound found in Turmeric. Piperine inhibits the action of this protein."

      Like 1
    • JGC That sounds like a good protocol. I’ve read about bioperine from LEF. I don’t have access to Dasatinib yet but I did take Fisetin, Quercetin, Resveratrol, with some milk thistle and coconut oil for the first three days of a 5 day fast recently. I did also take some piperlongumine as well. I thought I might get a better effect while fasting. Thanks so much for the tip. I’m going to give it a try.

      Like
    • Fred Cloud 

      One way to interpret information about AKG-rejuvant is that epigenetic age can be reversed in some tissues and in some organs and that the tissue specific rejuvenation and the reduction of epigenetic age of tissues and organs does not translate into a reduction of the epigenetic age of the whole organism.  In other words, the reversed epigenetic age of tissues does not correlate with a reversal of the epigenetic age of the person.

       

      If AKG achieves a tissue specific rejuvenation that makes a human body healthier and less prone to the diseases and the frailty that comes with old age then the result is a healthier body but not a longer lifespan (or maybe only a modest gain in average lifespan).

       

      AKG might compress morbidity and make some tissues/organs healthier and rejuvenated to a younger state. If the epigenetic clock rejuvant use “catch” some tissue specific rejuvenation then I know  what I can expect from AKG. A healthier body but not an expanded lifespan. 

       

      Not all epigenetic clocks are the same, some are good at measuring the biological age of the human body. Others are better at measuring the biological age of organs/tissues and disease related phenotypes. I don’t know which clock Rejuvant used. As far as I have learned, Kennedy himself and rejuvant speaks more about increased healthspan and compressed morbidity than of increased lifespan.

       

      Michael Lustgarten, made a short video about the pros and cons of different epigenetic clocks. Some clocks are better in measuring the general biological ageing vs chronological ageing, Other epigentic clocks are better at measuring disease related changes.

       

      https://www.youtube.com/watch?v=iNnvF1Eh7VE

       

      AKG is a key metabolite in the krebs cycle and by manipulating it we might delay age related diseases and some organ dysfunctions. If this is the case then I know what to expect from it and I keep AKG in my regimen. I guess the choice I have to make is between wait for more data and till then take a leap of faith based studies on mammals or wait for more data and till that arrives stay away from AKG. I stay with AKG for now.  

       

      https://www.lifespan.io/news/a-summary-of-alpha-ketoglutarate/

      Like 1
      • JGC
      • JGC
      • 5 mths ago
      • 3
      • Reported - view

      Staffan Olsson 

          You wrote: "I don’t know which clock Rejuvant used."  The Rejuvant clock used only 13 methylation sites, while Horvath-based clocks use several hundred.  That suggests that the Revjuvant clock was "cherry-picked" to show evidence of epigenetic reprogramming, and that, as you suggest, actually only a few cell-types were affected.

          I note that in an N=1 self-experiment, jimmy2 did a before/after clock comparison involving taking the Rejuvant product for 6 months.  Using two different commercial DNAme clocks, he found no evidence of epigenetic reprogramming.

          The Rejuvant web site contains lots of misinformation about the DNA methylation process.  Whatever their internal expertise, I suspect that they have some snake-oil salesmen on their payroll, and I would regard any claims about general epigenetic reprogramming with suspicion.  However, the Buck Institute work does indicate some significant AMG benefits (at least for worms an mice), and I plan to add the Swanson version of AMG to my evening supplements  when my order arrives.

      Like 3
      • Fred Cloud
      • Fred_Cloud
      • 5 mths ago
      • 1
      • Reported - view

      Staffan Olsson Various tissues could be rejuvenated at different rates and you would never know because the DNA tested and used for the popular blood based methylation age test like mydnage is only white blood cells.

      So it doesnt look at the various tissues throughout the body. Sometimes it can be misleading when a test says they use 11 sites or 200 sites or thousands of sites, it isnt sites in various tissues in the body, it is sites on the dna of one type of cell, in this case white blood cell.

      Trueme which is what rejuvant uses  is a saliva based test, so I assume they are using cells from your cheek but I would have to verify that.

      Like 1
      • JGC
      • JGC
      • 5 mths ago
      • 1
      • Reported - view

      Fred Cloud 

          I don't recall the venue (maybe ARDD?), but I do recall a talk by Steve Horvath in which he reported on the DNAm clock readings for various tissue samples from the same human individual.  I think he said that, in general, tissues age at about the same rate.  The exception was the tissue of women's breasts, which age faster than other tissue.   So it is possible to do differential tissue aging studies (but maybe only after an autopsy ☹️).

          I note that one can get DNAm tests done based on saliva or urine (as well as blood), so the those probably do not use white blood cells.

      Like 1
      • Chris
      • Chris.1
      • 5 mths ago
      • Reported - view
      • aribadabar
      • aribadabar
      • 5 mths ago
      • Reported - view

      JGC What is your rationale for taking AKG in the evening?

      FWIW I take it first thing in the morning , on an empty stomach. Reason being, better absorption.

      Like
    • aribadabar Just heard that the calcium acts as a buffer to counter it's acidity ie taking on an empty stomach.

      Like 1
  • AKG researcher, Dr. Gordon Lithgow was recently interviewed by Modern Healthspan. He doesn't seem to think that the CA from of AKG is superior. Another AKG researcher, Dr. Brian Kennedy was recently interviewed by the Skeekey Science Show. He stated that he saw no advantage of the CA form of AKG. 

    Kennedy has said that maybe the time release form is superior but tests are still being run to determine that. 

    Like 1
  • I'm on my last 5miligrams of rapamycin and have just become aware of AKG.   Anyone know if they can be taken together?   Just out of caution I thought I'd wait until my 1.25 month rapamycin cycle is through before tanking AKG.    Also, my wife had a horrible case of ocular shingles after supplementing with arginine.  She worries that AKG might set it off again but it seems that would be AAKG not AKG?   Comments.

    Like
      • Allen
      • Allen_Rosenberg
      • 5 mths ago
      • Reported - view

      Robert Olin I believe that AKG does contain arginine. I would think that anyone prone to shingles should avoid it. As fast as this field is evolving, there is and will be many other options to choose.

      Like
    • Allen Thanks.   She will avoid it.   She still suffer really bad nerve pain.   Is calcium AKG arginine free?

      Like
      • Allen
      • Allen_Rosenberg
      • 5 mths ago
      • Reported - view

      Robert Olin I called Kirkman Labs. They sell CA-AKG and they told me it is Arginine free. It does cost a little more than AKG, but it's still much less expensive than Rejuvant. However, if extended release is important to you, Rejuvant is currently the only option I know of.

      Like
      • aribadabar
      • aribadabar
      • 5 mths ago
      • Reported - view

      Allen AKG does NOT contain arginine. AAKG is the arginine-containing one.

      Like
      • Allen
      • Allen_Rosenberg
      • 5 mths ago
      • Reported - view

      aribadabar I was referring to what it by far the most common form in use. That is of course, the arginine containing one. But yes, I should have been clearer. 

      Like
  • Thanks to all of you for the valuable information.  

    Bob

    Like
  • Fred Cloud said:
    Its the ca-akg that creates the sustained release,

     This is incorrect. Ca-AKG is just an AKG salt; it has negligible effects on pharmacokinetics. Rejuvant was formulated for extended-release characteristics.

     

    Fred Cloud said:
    AKG has been found to work also, so I think they just want something unique that they can patent so they can mark the price way up,

    This is fairly obviously not correct: I'm sure they  "want something unique that they can patent so they can mark the price way up," but there's nothing unique about Ca-AKG, and it's certainly not patentable: lots of other people sell it at much lower prices. Rejuvant is more expensive in small part because of the additional cost of formulating an extended-release tablet, but also because the formula includes the additional ingredients (which are researched and patented based on mouse lifespan and frailty studies), the branding, the scientific affiliations, and the fact that it's being used in clinical trials.

    Like 1
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