$1000 of AKG Could Have 8 Years of Antiaging Benefits

Rejuvant AKG had an average 7 month study on people and it reversed 8 years of biological age according to methylization biomarker clocks. This work needs to be validated with more studies.

The time released combination of Calcium and Alpha-Ketoglutarate in Rejuvant’s LifeAKG™ seems to reset methylation patterns in your DNA. However, there needs to be placebo controlled trials and methylization clocks have not b een validated.

By rebalancing your methylation patterns, Rejuvant® can potentially turn back the aging clock, reducing age-related ailments and extending healthspan in four important ways.

Methylization biomarker clocks have not been correlated with increased physical function.

AKG works in the Krebs cellular cycle which where the popular supplement NAD+ also works. AKG levels decline as we age.

Rejuvant is charging about $110-150 per month of supply of AKG. It would seem a 7 month supply is enough to deliver the observed methylization changes.

Alpha-ketoglutarate (AKG) was discovered in 1937 by Hans Adolf Krebs and William Arthur Johnson at the University of Sheffield. Krebs won the Nobel Prize for Physiology or Medicine in 1953. The discovery of AKG was part of the overall identification of the citric acid cycle, which is commonly known as the Krebs cycle.

The Krebs cycle is a series of chemical reactions that is used to generate energy via the oxidation of acetate, which is derived from carbohydrates, fats, and proteins, into carbon dioxide.

A 2014 study showed that AKG extends the lifespan of adult C. elegans by roughly 50% by inhibiting ATP synthase and the target of rapamycin (TOR).

Brian Kennedy performed a mouse study. He and his team administered a calcium salt of AKG, CaAKG, to 18-month-old male and female Black 6 mice, which represents the equivalent of human middle age, and continued dosing them with it for the rest of their lives in order to test its effects on lifespan and healthspan.

The gains in lifespan were relatively modest. Female Black 6 mice, which normally live shorter lives than male mice of this strain, received a 10% benefit in lifespan, while male mice received a 5% improvement. They observed a benefit of delaying frailty in older mice. This could mean it increases healthspan aka the number of years we have healthy life. The AKG-fed mice scored an average of more than 40% better on tests of “frailty,” as measured by 31 physiological attributes including hair color, hearing, walking gait, and grip strength. And female mice lived a median of 8% to 20% longer after AKG treatment began than control mice, the group reports today in Cell Metabolism. The AKG-eating mice did not perform better on tests of heart function or treadmill endurance.

AKG is part of the metabolic cycle that our cells use to make energy from food. In addition to its use by bodybuilders, doctors sometimes treat osteoporosis and kidney disease with the supplement.

No significant side effects caused by alpha-ketoglutarate have been reported in humans but as with any supplement, if you do experience any adverse effects you should cease taking it immediately and consult your doctor.

How Do Body Builders Use AKG?

Creatine AKG products with contains 2-5 grams creatine in each serving. Take a serving before and after your workouts, and for additional benefits, add a serving at night and first thing in the morning. Creatine provides quick energy for completing more reps, and AKG helps restore energy levels between sets, the combination of the two is an extremely effective way to keep your energy and strength levels high during your workout. Creatine AKG is absorbed more efficiently into the muscle tissue. Therefore, you don’t need to take quite as much as you would with creatine monohydrate. Creatine AKG readily crosses into muscle tissue without creatine transporters. Therefore, you no longer need to take in 100 g of carbohydrates with your creatine.

The old method of getting creatine was creatine monohydrate. It was a chalky substance but it worked for bodybuilding. The main drawaback of creatine monohydrate was that it could cause intestinal distress and diarrhea. It sat in the intestines, pulling in water.

21 thoughts on “$1000 of AKG Could Have 8 Years of Antiaging Benefits”

  1. Well. I’ve got the test in front of me. I’ll spit on it and send it in and try to post back here when I get the results back, and then again for the retest in 4 months.

  2. Having been possibly burned by cancer-enhancing NAD+ supplements – I had a Basil Carcinoma removed from my face recently – I am swearing off those and speculative products like this for the foreseeable future.
    Dr. Brad Stanfield explains that NMN which leads to NAD+ enhancements can both prevent cancer and accelerate it if you get it, here: https://www.youtube.com/watch?v=YBWQNsWi9lc
    and here:
    It’s easy to make mice live longer; they are programmed to live fast and die young anyway. Humans are much more complicated and environmental factors probably have more effect than anything currently available on the market. Exercise increases NAD+ levels more than any marketed substance anyway, and without those nasty side effects.

  3. The above diagram is also pointing out NAD+, so it would be nice if Brian did a roundup of the current status of NAD+ related stuff

  4. You’re right to point out the G.I. risk with unbuffered AKG. It’s highly acidic and will alter gut flora. The magnesium/calcium salts work even better than plain Ca-AKG.

    Aluminum poisoning is a factor in Alzheimer’s development in part via its interruption of AKG metabolism. Aluminum also damages the production of digestive enzymes the same way, affecting the energy metabolism of cells in the gut.

    AKG is also a treatment for motorneurons under stress and is mentioned in the literature as preventing incipient cases of ALS. (Again, heavy metals poisoning can induce ALS/FTD cases via Nrf2/SOD1/TDP-43 misfolding.)

    One caution: AKG appears to feed fibrosis in heart failure and kidney failure – and probably male-pattern baldness but probably not lung fibrosis. AKG stokes the energy metabolism of specific cells mediating fibrosis. (Male-pattern baldness involves three pathways: a DHT/TGF-beta/DKK pathway, RXR and PGC-1alpha – the later affected adversely by AKG).

    You should be cautious using AKG for this reason given the prominent role of fibrosis in aging. I’m unaware of whether or not any specific delivery method or form for AKG could mitigate this risk – and I have to take it for heavy metals poisoning. If every AKG formulation does stoke fibrosis, I wouldn’t be surprised to see clinical trials show positive benefits for a few years in test subjects but higher complication rates and mortality long term. (Growth hormone supplementation by itself paints the same problematic picture in short term vs. long term studies.)

    It’s possible you might need to balance this out with H2S signaling, which serves to brake fibrotic TGF-beta cascades – but H2S is its own problem.

    • I was wondering about that. This is time release, vitamin A, Calcium, and AKG.

      The amount of vitamin A is less than I get in my senior multivitamin. Check.
      The amount of calcium is less than you get in a glass of milk. I drink milk. Check.
      And 1000mg of the Calcium salt of AKG. A month’s supply of that in capsule form is about $25, as a bulk supplement a 3 month supply is $50.

      So, really, you’re buying the time release element of it, at a hefty premium. Is it worth it?

      Doing some quick research, the half life of AKG in the blood is about 5 minutes; It basically goes straight from your gut to your bladder. So, yeah, it’s quite possible the only way you’ll sustain any kind of blood AKG level during the day is with a time release formula. But I can’t say that definitively because I saw no data on how fast it transfers from the gut.

      Could go either way, really. But I suspect it’s a bad buy if you don’t mind popping a capsule every couple of hours during the day, or just dissolving it and taking a swig occasionally.

      OTOH, you do get 2 epigenetic aging tests as part of the package, and that’s worth a couple hundred bucks right there, so maybe it’s reasonable.

  5. Eh, I turn 40 in December and I enjoy being an age reversal guinea pig. I’ll give it a shot. Pricey but it’d be worth it, I’d only for curiosity that might pan out. It’s at least accessible.

  6. Definitely interesting for self experimentation. There are companies online that offer epigenetic age testing and AKG is readily available at low cost on Amazon. Matching the vitamin A or D supplements in the study is easy. Everything is generally accepted as safe, few if any side effects.

    • That was what interested me: They’re a bit pricey compared to buying the ingredients separately, but the purchase includes 2 epigentic age tests, one with the first bottle, one after four months, which makes it a better deal.

      I’ve been putting off that sort of test, because after going through some fairly rigorous chemo, I suspect I’ll get bad news. But I guess it’s time to bite the bullet.

  7. One thing bothers me about this. The only difference between the men’s and the women’s formula is the amount of vitamin A; 900mcg per serving for men, 25mcg per serving for women. The amount of calcium and AKG is identical. Now, I’m willing to accept the notion that the difference in vitamin A content is justified; Maybe women process it differently.

    I’m about 220 pounds. My wife is 80. We’re supposed to get the same dose???

    Well, I suppose if she tries it out she can take just one capsule, instead of two. But it always bothers me when things that are supposed to be biologically active don’t have their doses adjusted for body weight. It’s one of the reasons my wife routinely gets bad side effects from prescriptions!

    Note, I just looked it up, and apparently, in the US anyway, the average weight of men and women is not so far apart. Wow. But the point remains: Biologically active substances should have their doses adjusted for body mass.

    • To do that, clinical trials would need to include body mass as a covariate for response level. And because many biological relationships are not linear, a little bit of weight variation around the median wouldn’t be enough to capture the relationship, so they would need to recruit a larger sample population with various weights.

      • Any clinical trial not destined for the circular file measures participant weights. And all else being equal, dosage *normally* scales with surface area within a given species and sex. (Obviously omitting topical products…)

        Sure, there are situations where you depart from that rule, like extremely obese people, but I’ve never heard of a drug where the appropriate dose for an 80 pound person was actually the same as for a 220 pound person.

        Rather often, though, the medical community just doesn’t bother adjusting dosage, with negative consequences for anybody not of an average body size and composition.

        • That’s one reason why the medical community has an enormous preference for drugs with a wide therapeutic window.
          ie. The minimal effective dose and the maximum safe dose should be as far apart as possible.

          (There are other reasons to want a wide window.)

          • Yeah, they don’t necessarily work better, or even as well, but they’re enormously more convenient… For the doctors.

            So I and my wife both get a bacterial respiratory infection. We both get prescribed the same Z pack. She gets cured promptly, but suffers such severe intestinal upset that she’s reluctant to get these sorts of things treated, would rather suffer through them. Me? Often the full course isn’t sufficient to finish off the bug, and I end up having to go back for a second course of treatment with a different antibiotic. (Which is why I’ve got tinnitus!)

            But it was really convenient for the doctor.

            • Not just the doctor.
              As we’re swapping medical stories:

              I needed to go on powerful blood thinners about 15 years ago. The weapon of choice was warfarin. (Literally rat poison. Google it.)
              Which has a narrow therapeutic window.
              Take too little, you don’t treat your problem. Take too much you can die like a poisoned rat.
              And the exact spot you are in the window depends on not just your mass. Diet, exercise, bodyfat content, a host of things.
              So the result was I needed a blood test every week to monitor my exact state of biochemistry and the dosage tweaked up and down if I was drifting off-target.
              I was given a list of foods I could and couldn’t eat, because they’d affect the results.
              I was careful not to drastically alter things like sleep patterns, exercise, alcohol etc.

              Now I’m getting treated again. But since then there has been a much better drug developed. A great big wide window to aim for.
              Result: No limits on my behaviour (at least, not limited by the drugs). Doctor just prescribes 5mg twice a day. No need to check blood, no need to have tests weekly. No dietary restrictions.

              As a patient, it’s a huge improvement.

  8. That’s interesting. It’s not much more than I’m currently spending on SAMe to slow the progress of my arthritis. Does it have enough prompt effects to know it’s doing something? With my high dose Quercetin regimen, I saw effects almost immediately, skin lesions becoming irritated, and then healing back healthier.

    “the combination of the two is an extremely effective way to keep your energy and strength levels high during your workout.”

    Heh. At 63, I have plenty of energy to work out until I’ve injured myself, “energy” is not the limiting factor here, it’s recovery time: If I overdo it in the gym, (Which I can easily do without realizing it until the next day.) I’m set back for weeks.

    So I have to be fairly conservative in the gym, I’ve got all the energy I need to put myself back into months of physical therapy. Again.

  9. Pricing of Rejuvant AKG is absurd ($150 for 30 day supply), if you compare it with other very similar AKG products available on the market. So it is a rip off and I am surprised Brian supports it.
    Is this article sponsored by Rejuvant ? You should clearly state it.

    • I did not say I support it, I provide info. I am not sponsored by Rejuvant. They did a published study which shows biological clock improvement. I said the biological clock is unproven and they have not done placebo trials. I also mentioned AKG is widely used by body builders. You can decide what to do. I am not taking AKG yet. I might. Waiting a year or two to get more study results. The Singapore group is testing it and many other products.

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