Anyone else attending the conference? Brian Kennedy is one of the speakers.
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More company reps than researchers.
There is one politician. That is a breed whose lives I do not want extended.
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That’s true, it’s not got many of the top researchers. I am going there in large part because of Brian Kennedy.
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I am taking Rejuvant, a patented extended release version of Alapa Keto-Glutarate that Brian Kennedy co-authored a trial on that indicated an average 8 years lowered biological age according to mehylation markers 10.18632/aging.203736 Whether that version is worth the extra cost compared to other AKG I don´t know.
At least a couple of years should be subtracted because there was no placebo arm. And, whilst the methylation markers are relatively robustely association with a number of aging/health markers, causation is of course by no means proven.
Anyway, I thought it would be interesting to hear Brian Kennedy and maybe get to ask him some questions.
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I conversed with Bryan through email about this long ago. I was not convinced about the superiority of the patented calcium AKG over simple arginine AKG. I don’t think the calcium form is proven to be any better and haven’t seen evidence that convinces me that it is better. That said, I can’t say for sure that it isn’t superior. We need more studies either way. My guess is that the arginine form is just as good but we need more studies on this. We need studies testing both forms head to head to see their effects on epigenetic age. Once epigenetic age tests become cheaper, perhaps some people can take an epigenetic test and try one form for a few months, then take an epigenetic age test and then test the other form and take a test again at the end to compare them.
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Do you remember what the rationale was for initially using the calcium form of AKG over the others?
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Yes, it was something about the calcium form being more slow release and that being important for the benefits of AKG. They weren’t sure why it’s supposed to be more beneficial but they thought it was more active in the gut and that that is important. I’m not convinced of that being true because it doesn’t sound so plausible and I haven’t seen good evidence of it. I’m also skeptical of AKG being able to reduce epigenetic age, regardless of whether it’s the calcium form or some other form. I’ve been hoping for more studies on this.
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Brian Kennedy is clear on his view that the extended release version of AKG that the Rejuvant formulation incorporates is superior since otherwise AKG will rapidly be lost from the blood and not absorbed by the gut.
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Indeed, it would be valuable to have more studies on AKG, including a placebo-controlled trial.
That said, to my understanding the trial on AKG showing an average of eight years lower biological age according to methylation markers is about the strongest there is, since it is done on humans. AFAIK, the studies on other longevity supps showing lowered biological age are based on animals or human cells in labs. Please let me know what I may have missed!
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how long have you been taking it? what dose? it is better than the regular ones that are quite cheap?
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This issue is that the company behind the trials both designed the trial and chose the end points (the epigenetic age test), so it could be just a simple case of end-point/data shopping. Choosing the approach that provides the desired outcome. This is not an independent third party doing the testing.
And - Brian Kennedy has also said that what they see is that if people are already healthy, they don’t see an impact on from the AKG, so its mostly seen in the unhealthy cohort (I think this was seen both in animals and humans).
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While the study that reported on calcium AKG reducing epigenetic age by 8 years is very intriguing and impressive, if the results are true, I am skeptical of the results for several reasons. It’s only one small study that had no control group and was done by people with vested interest in calcium AKG. In addition there are a lot of uncertainties about epigenetic age clocks and they are pretty inaccurate. I have a hard time believing some intervention that is supposed to work mainly on the digestive tract (or whatever else is the reason for the delayed release supposedly working better) is actually reducing epigenetic age systematically. If the superiority of the calcium form was supported by a life span study on mice or something that shows that it works better than the arginine form then I would find it more plausible that it reduces epigenetic age. In the meantime I am not convinced that calcium AKG reduces epigenetic age or even if it does, that the calcium form is better than the arginine form. If epigenetic age tests weren’t so inaccurate, it would actually be easy to test whether AKG reduces epigenetic age and whether calcium AKG works better. As of now, we don’t have solid answers.
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Jonas:
I have been taking Rejuvant for three weeks. Same dose as in the trial, two capsules daily with a total of 1000 mg calcium alpha keto glutarate. It is claimed that that this extended release version of AKG, almowing a lengthy gradual release, is superior to the cheaper versions which peak rapidly and then dissolve. I don’t know if this is correct but I do not want to take the risk that it isn’t.
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RapAdmin:
If the epigenetic test chosen, TruAge, was because it made the results more impressive for AKG/Rejuvant, it is indeed very foul play.
Is it naive to believe this is unlikely, given the renown of co-author Brian Kennedy? Do vested interests corrupt even at that level? It’s a question, not a statement.
40 out of 42 persons had a lowered biological age after the intervention. Those who gained significantly more than the average person were, as you write, the unhealthy (higher biological than chronological age) but also the chronologically old.
A statistical analysis of the results gave an equation, that I entered my own data into. My low biological compared to chronological age makes me gain 3.5 years less than the average. My high chronological age makes me gain, coincidentally, precisely the same 3.5 extra above the average.
This gives me the same net gain of eight years lower biological age, as the average for the 42 participants. IF the average plays out for me. And IF the methylation test really measures biological age. Two big IF:s! But how can I avoid supplementing and take the risk of not gaining eight years?
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Olafurpall:
Alas, Brian Kennedy told me there won’t be additional studies coming soon that will shed more light on AKG.
One disconcerting admission at the bottom of page 14 in the report on the lowering of biological age by eight years: “However, the AKG supplementation leads to both demethylation and hyper methylation of some CpG sites in saliva cells, suggesting that Rejuvant may have a larger effect on methylation-based aging clocks than other indicators of biological age”.
Still, the lowering of biological age by several years can’t be ruled out. We don’t know, but it could happen. As is the case with various other substances.
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Olafurpall: I managed to find one study on absorption of AKG - not on humans but on pigs! - showing that absorption is highest from the upper intestine, as opposed to more distal (distant) regions. Do you think this may strengthen the claim that the extended release form is superior?
Yes I think it does. It does give some credibility to the idea that the calcium form (if it acts as a time release form as Brian Kennedy claims) has different effects than non-calcium forms of AKG. On the other hand, if the calcium AKG is indeed acting mostly in the distal intestinal tract, I am even more skeptical of it having longevity benefits in healthy humans since in that case it’s likely having some effects on the intestinal flora and I don’t see that as a mechanism that is likely to result in actual strong reversal of epigenetic age. Note that the main claims of benefits of calcium AKG is that it reversed epigenetic age in humans.
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Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use
If the absorption is highest from the upper intestine, to wherever it is absorbed, I would have thought that effects on the intestinal flora as such would not be the prime driver of possible lowering of biological age. But I am on uncertain ground here!
In any case, I agree there are strong uncertainties on the claims for many years of lowered biological aging. But I will still continue with the calcium/Rejuvant based on
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The possible health benefits from supplementation of AKG on a range of parameters as shown e.g. in the article just posted by Joseph. Even if AKG doesn’t lower biological aging, I may gain health benefits. .The benefits indicated are for AKG in general and not the calcium / Rejuvant form; I will pay the extra cost of the latter in case the effect will be stronger.
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My own level of alpha ketoglutarate is low, 6.64 mg/g crea. The reference range given by the testing company is 0 - 30; another range given is 4 - 54. My low value fits in well with the drastic drop indicated for high chronological age in humans. I can only see potential upside to restoring this to a youthful level and little downside.
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The possibility that the trial of the calcium form, for all its uncertainties, holds true on is claim for lowered biological age…
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Joseph: This is a fascinating compilation of possible benefits of AKG supplementation, ranging from immunomodulation to anti-tumor action and epigenetic regulation.
The strongest evidence of all is for bone-strengthening, since the trial was on humans (menopausal women). Some of the other evidence is from mammals closer to us than mice: pigs and sheep.
Could all the studies referred to, if transferable to humans, improve the odds that there could be a longevity benefit from AKG, be it the calciumform or not?
Tantalizingly, the article ends with (but on species far from humans):
“Recent studies suggest that AKG can also regulate the ageing process of the organism and have an influence on prolonging the lifespan (Chin et al. 2014; Salminen et al. 2014). Research performed in the next few years will probably give us an answer to the question whether to expand the characteristics of AKG with another feature, which is maintaining the longevity”
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