Calcium AKG
Also sold as: Alpha Ketoglutaric Acid, AKG
Best-in-class: Calcium AKG
A metabolite central to the Krebs cycle and epigenetic regulation, studied for healthy aging, bone and biological-age markers (the compound behind 'Rejuvant').
Calcium AKG quick facts
| Suggested dose | 1,000–2,000 mg daily. |
| How often | Daily |
| Who it's for | Longevity and healthy-aging experimenters. |
Mouse data is striking: extended lifespan and, more notably, compressed morbidity — the animals were healthier for longer rather than simply living longer. Human evidence is limited to small studies on epigenetic age markers, which are themselves an unvalidated surrogate. Mechanistically one of the richest targets here; clinically still speculative. The calcium salt adds a calcium load worth counting.
How Calcium AKG actually works
Alpha-ketoglutarate is a TCA cycle intermediate and, more interestingly, an obligate cofactor for the 2-oxoglutarate-dependent dioxygenases — the enzyme family that includes the TET demethylases and the JmjC histone demethylases, which regulate DNA and histone methylation directly. That places AKG upstream of epigenetic regulation rather than merely in energy metabolism.
Where to get Calcium AKG
Find Calcium AKG on iHerb →The evidence for Calcium AKG
Graded by what exists behind each claim.
✅ Clinically validated
- An observational human study associated AKG use with a reduction in biological age markers; extends healthspan in animals.
- Supports bone density and collagen/energy metabolism.
📊 Correlative data
- AKG levels decline dramatically with age.
🧪 Theoretical / extrapolated benefits
- A leading longevity candidate, but rigorous human RCTs are still lacking — promising, not proven.
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What Calcium AKG actually does
Alpha-ketoglutarate is 2-oxoglutarate, and it has two completely separate jobs in a cell. The first is metabolic: it is the five-carbon intermediate sitting between isocitrate and succinyl-CoA in the Krebs cycle, made by isocitrate dehydrogenase and consumed by the 2-oxoglutarate dehydrogenase complex. That is the job the marketing means when it says ‘Krebs cycle metabolite’, and it is the less interesting one.
The second job is the reason this molecule became a longevity candidate, and it belongs to an enzyme family most people have never heard of. There are roughly seventy human Fe(II) and 2-oxoglutarate-dependent dioxygenases, and every one of them uses 2-oxoglutarate as a stoichiometric co-substrate: the enzyme decarboxylates it to succinate and CO2 in order to generate the reactive iron-oxo species that hydroxylates the actual target. The family includes the TET enzymes that oxidize 5-methylcytosine and start DNA demethylation; the JmjC-domain histone demethylases; the prolyl hydroxylases that mark HIF-1-alpha for degradation in the presence of oxygen; the collagen prolyl-4-hydroxylase and lysyl hydroxylase that make collagen a triple helix; and FTO, which demethylates RNA.
That is the deep claim, and it is not marketing. Every epigenetic mark those enzymes remove is removed at the cost of one molecule of 2-oxoglutarate. So 2-OG is the chemical currency that couples the metabolic state of a cell to the methylation state of its chromatin, and a compound sold on ‘biological age’ measured by DNA methylation is, at least in principle, aimed at the right chemistry. The bone work makes exactly that argument: alpha-ketoglutarate increased bone mass in aged mice and attenuated age-related bone loss via regulating histone methylations, acting through BMP signaling Wang 2020.
And then the flagship paper proposes a different mechanism entirely. The Nature report that started the field found that alpha-ketoglutarate extends lifespan in Caenorhabditis elegans by binding and inhibiting ATP synthase and thereby inhibiting TOR Chin 2014. That is a direct target-engagement mechanism — the molecule sitting on the beta subunit of an enzyme — and it is not the co-substrate story at all. Inhibiting ATP synthase is closer to a mild uncoupler or a caloric-restriction mimetic than to an epigenetic cofactor.
Two mechanisms, and they make opposite predictions about dose. As a dioxygenase co-substrate, more 2-OG can only help if the enzymes were substrate-limited, which in a normally fed cell they generally are not — intracellular 2-OG is already in the tens to hundreds of micromolar. As an ATP synthase inhibitor Chin 2014, the effect requires enough of the molecule to occupy a site on an abundant mitochondrial enzyme, which is a much larger exposure. Nobody selling calcium AKG says which of the two they are aiming at, and the honest answer is that the field has not decided.
Cell, rodent, human — and where it stops
Worm: the founding result, and it is a worm. Alpha-ketoglutarate extended lifespan in C. elegans through ATP synthase inhibition and TOR Chin 2014. A nematode has no skeleton, no adaptive immune system and no liver.
Mouse: the result the whole category is sold on. Calcium alpha-ketoglutarate given to aging mice extended lifespan and compressed morbidity Asadi Shahmirzadi 2020. Compression of morbidity — the fraction of life spent healthy rising, not just the total rising — is a genuinely important and unusual finding, and it is the strongest datum in this file. A second mouse study found increased bone mass and attenuated age-related bone loss Wang 2020.
Human, trial one: the only controlled human study with a hard endpoint, and look at the dose. Seventy-six postmenopausal women with osteopenia took 6 g of AKG plus 1.68 g of calcium a day, or calcium alone, for six months. Serum C-terminal telopeptide — CTX, the bone resorption marker — fell by a maximum of 37.0% at 24 weeks (p = 0.006). Bone mineral density rose 1.6% from baseline, but the difference between treatment groups was 0.9% and not significant Filip 2007.
Now do the arithmetic on that dose, because it is the number this page exists for. Calcium alpha-ketoglutarate is CaC5H4O5, formula weight about 184; calcium is 21.8% of it by mass and the ketoglutarate about 79%. Six grams of AKG delivered as the calcium salt would come with about 1.65 g of calcium — which is what that trial reported alongside it. So the intervention was, to within rounding, about 7.5 grams a day of calcium alpha-ketoglutarate. The card recommends 1 to 2 grams. That is roughly a quarter to a seventh of the only dose with a controlled human bone endpoint behind it. The stoichiometry is arithmetic; the inference that the trial used the calcium salt is an inference from the ratio, and it is flagged as one.
Human, trial two: there isn't one. The longevity claim rests on a study of 42 people taking a commercial alpha-ketoglutarate-plus-vitamins formulation for an average of seven months, reporting an average decrease in biological age of 8 years (p = 6.5 × 10−12) on a DNA methylation clock Demidenko 2021. Read the design rather than the p-value: there is no control group. Participants were users of the product who chose to take it and chose to be tested. A p-value of 10−12 in an uncontrolled cohort measures how consistently a number moved, not what moved it.
So the specific obstacle is the cleanest in this cohort: there is no completed randomized controlled trial of calcium AKG for any aging outcome in humans. Not a small one, not a negative one, not one in the wrong population. The randomized trial that would answer it has been designed and its protocol published — 120 adults aged 40 to 60, 1 g of sustained-release calcium AKG, six months of intervention plus three months of follow-up, with change in DNA methylation age as the primary outcome Sandalova 2023. A published protocol is a promise, not a result.
Calcium AKG — which form, and does it matter
Calcium AKG is a salt, and about a fifth of what you swallow is calcium. At a formula weight near 184 with calcium at 40, 1,000 mg of calcium alpha-ketoglutarate is roughly 218 mg of elemental calcium and 780 mg of ketoglutarate. At the card's upper dose of 2,000 mg that is about 436 mg of calcium a day — a third to a half of a typical adult intake target, arriving from a bottle labeled as a longevity compound. This is the single most practically useful number on the page and it appears on no label.
Why the salt exists at all. Free alpha-ketoglutaric acid is a hygroscopic, sour, unstable solid; the calcium salt is stable, handleable and tableting-friendly. Sodium, arginine and ornithine AKG exist for the same reason, and the counter-ion changes what else you are taking: ornithine AKG delivers an amino acid with its own urea cycle pharmacology, sodium AKG delivers sodium. The mouse lifespan work used the calcium salt Asadi Shahmirzadi 2020, and the human bone trial's calcium-to-AKG ratio matches the calcium salt Filip 2007, so calcium AKG is the form with the evidence — which is a fortunate accident rather than a design decision.
Sustained release is the formulation variable the pending trial chose, and the reason is worth understanding. The ABLE protocol specifies sustained-release calcium AKG Sandalova 2023. 2-oxoglutarate is a central metabolite: it is consumed by the 2-oxoglutarate dehydrogenase complex, transaminated to glutamate, and cleared quickly. A bolus that produces a brief plasma spike and is burned as fuel is a different intervention from a slow input that raises the standing concentration, and only the second could plausibly keep a dioxygenase co-substrate elevated. If the trial is positive and immediate-release products are not, formulation will turn out to have been the whole story.
What no product can tell you. There is no published human pharmacokinetic curve for oral calcium AKG — no plasma 2-oxoglutarate concentration against time, at any dose, in any paper in this file. So ‘bioavailable AKG’ on a label is a claim about a capsule with nothing measured behind it, and the difference between a 1 g product and a 2 g product cannot currently be expressed in the only unit that would matter.
The practical reading. If you are going to take it, take the calcium salt because that is what the mouse and human data used Asadi Shahmirzadi 2020 Filip 2007, count the calcium, and understand that the dose on the bottle was chosen to be tolerable rather than to match anything.
What would have to be true, and how you would know it was not
1. ctx, the one endpoint with a controlled human number. Draw serum C-terminal telopeptide before starting and at 24 weeks. At the trial dose predict a fall of about a third Filip 2007. At the card's 1–2 g — a quarter to a seventh of that dose — predict a smaller fall or none. This is the prediction that turns a longevity purchase into a measurement, and CTX is a routine, cheap, widely available assay.
2. Bone mineral density, and the prediction is that it does not move. Even at 6 g a day for six months, the between-group BMD difference was 0.9% and not statistically significant Filip 2007. Predict no detectable DXA change at 12 months on a retail dose. A resorption marker falling while density does not move is the classic pattern of a real biochemical effect too small to change the structure, and it deserves to be stated rather than elided.
3. A DNA methylation age clock — the prediction that cuts against the product, and it is the one the marketing rests on. Predict no change beyond the assay's own test–retest variation. Methylation clocks have meaningful technical noise, the 8-year figure comes from an uncontrolled cohort of 42 self-selected users Demidenko 2021, and the randomized version of that experiment has been designed but not reported Sandalova 2023. If you are going to run this on yourself, run the clock twice at baseline, a month apart, before taking anything — that single step measures your own assay noise and is the difference between an experiment and a testimonial.
4. Serum and urinary calcium, because a fifth of the capsule is calcium. At 2 g a day the product supplies roughly 436 mg of elemental calcium. Predict serum calcium unchanged — it is tightly regulated — and 24-hour urinary calcium up. That is the marker that matters for anyone with a stone history, and it is the physiologically correct place to look rather than the serum value.
5. Grip strength and gait speed, from the mouse finding, labeled as extrapolation. What the mouse work claims is compression of morbidity — more of life spent functional Asadi Shahmirzadi 2020. In a human the cheap analogs of that are grip dynamometry and a timed walk, both measurable at home and both with real age-related decline. Predict no measurable change at 12 months on a retail dose. Nobody has published either endpoint on AKG in a person, and if the mouse claim is the reason to buy this, these are the two numbers that translate it.
What nobody has tested yet
There is no completed randomized controlled trial of calcium AKG for an aging outcome in humans, and that sentence is the honest summary of the entire category. The protocol exists: 120 adults aged 40 to 60, 1 g of sustained-release calcium AKG, six months plus three months of follow-up, DNA methylation age as the primary outcome Sandalova 2023. Until it reports, every human claim made for this compound rests on 42 uncontrolled users Demidenko 2021 and one six-month bone trial at four to seven times the retail dose Filip 2007.
Nobody has measured plasma 2-oxoglutarate after an oral dose. Not at 1 g, not at 6 g. Without that curve it is not known whether oral calcium AKG raises the standing concentration at all, or whether it is transaminated and burned within the hour. Every mechanism on this page — dioxygenase co-substrate, ATP synthase binding Chin 2014 — has a concentration requirement, and none of them can be evaluated against a number that does not exist.
Nobody has shown that oral AKG changes a dioxygenase's output in a person. The epigenetic argument predicts something measurable: TET activity generates 5-hydroxymethylcytosine, which is quantifiable in leukocyte DNA. If supplementing 2-oxoglutarate raises co-substrate availability for TET, global 5hmC should rise. That is a direct test of the mechanism rather than of the marketing, it uses existing assays, and it has not been run.
And nobody has resolved which mechanism is operating. ATP synthase inhibition Chin 2014 and histone-demethylase co-substrate supply Wang 2020 are different pharmacologies with different dose requirements and different safety profiles. A cell experiment comparing AKG against a non-metabolizable 2-OG analog would separate them in a week, and the field has spent a decade selling the compound without deciding.
Calcium AKG — its own safety story, not its category's
The most likely real effect of this product is the calcium, and it is worth taking seriously precisely because nobody counts it. Two grams of calcium alpha-ketoglutarate a day delivers about 436 mg of elemental calcium. Somebody taking this alongside a calcium supplement, a fortified milk alternative and a calcium-containing antacid can reach a total intake nobody intended, and the risk that scales with supplemental calcium — rather than dietary calcium — is kidney stones. Anyone with a stone history should count this bottle as a calcium supplement, because chemically it is one.
Kidney disease is a contraindication for a reason that is specific rather than generic. Calcium handling and acid–base balance are both compromised in chronic kidney disease, hypercalcemia is a recognized hazard of calcium loading in that population, and 2-oxoglutarate is itself an organic acid anion. A 21.8%-calcium salt taken daily and indefinitely is the wrong product for a failing kidney.
The duration problem, stated with the actual numbers. The longest controlled human exposure to AKG in this file is six months Filip 2007. The uncontrolled cohort averaged seven months Demidenko 2021. The pending randomized trial runs six months plus three Sandalova 2023. People buy this intending to take it for decades. There is no human safety data set beyond about half a year for any dose, and the honest thing to say is that the long-term question is not reassuring or alarming — it is unasked.
The mechanistic caution nobody raises, and it belongs to the prolyl hydroxylases. The same 2-OG-dependent enzyme family includes the prolyl hydroxylases that degrade HIF-1-alpha. Manipulating that axis pharmacologically — the direction the HIF stabilizers used in renal anemia work in — has real consequences for erythropoiesis and for tissues where hypoxia signaling is already abnormal. Supplemental 2-oxoglutarate would push that system in the opposite direction from a HIF stabilizer. Nobody has measured whether a supplement dose reaches the enzyme at all. This is mechanism-level reasoning from the enzymology above, not a documented effect, and it is the kind of thing that should be checked before a compound is taken for twenty years.
And the harm that is most likely in practice is opportunity cost. Gastrointestinal upset is the reported complaint and it is minor. The real cost is that the mouse data are excellent Asadi Shahmirzadi 2020, the human data are one uncontrolled cohort Demidenko 2021, and the gap between those two is where a great deal of money is currently being spent on a compound whose randomized trial has not reported Sandalova 2023.
Sources read for this page
- Chin RM, et al. The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 2014;510(7505):397-401 · PMID 24828042
- Asadi Shahmirzadi A, et al. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metabolism 2020;32(3):447-456 · PMID 32877690
- Wang Y, et al. Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nature Communications 2020;11(1):5596 · PMID 33154378
- Filip RS, Pierzynowski SG. Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study. International Journal for Vitamin and Nutrition Research 2007;77(2):89-97 · PMID 17896582
- Demidenko O, et al. Rejuvant, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging 2021;13(24):24485-24499 · PMID 34847066
- Sandalova E, et al. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)-intervention study protocol. GeroScience 2023;45(5):2897-2907 · PMID 37217632
How you would know if it worked
There is no blood test for this one. That is not a criticism — it is a fact about the effect, and it changes how you should judge it.
- What to watch: Nothing at the level of how you feel. The claim being sold is a lower biological age; the human data behind it is one observational study of people who chose to take it; and the read-out being marketed is an epigenetic clock — a test bought from a company, with poor agreement between labs and no settled meaning for a change in one person.
- How long before it means anything: There is no window, because there is no endpoint. A clock result that moved three years in twelve weeks is inside the noise of the assay, and one that did not move tells you nothing either.
- What will fool you: The word age, doing work the data cannot support. Biological age scores are correlational summaries, not a quantity you lower the way you lower LDL, and the study behind this product cannot separate the compound from the kind of person who buys it. If you want something shown to change how you age, this is the wrong aisle: training, sleep and blood pressure all have outcome data behind them.
Run it one variable at a time. Starting three things in one week means a result you cannot attribute, which is the same as no result.
Calcium AKG — safety & side effects
- GI upset is the main report.
- Contains calcium — count it toward your daily total, especially alongside a calcium supplement or a fortified diet.
- The longevity data are entirely from mice, and the human trials that exist are small. Long-term safety has not been characterized — the trials run weeks to months, not years. That is a real limit on what anyone can tell you about daily use for a decade.
- Avoid with kidney disease or hypercalcemia.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this against it with a pharmacist or doctor — pharmacists are underused and free.
- When to take it, and what to take it with
- Which form actually absorbs
- Who it's worth it for
- Best-in-class brand pick
- Coach Cam's stacks and notes
- Fasted or with food, and when in the day
- Morning or night, and why that window
- Around training, or deliberately away from it
- What it must not share a window with
Everything above is free and stays free. Skool is where it becomes a plan — Calcium AKG in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Calcium AKG
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| hs-CRP (High-Sensitivity C-Reactive Protein) | The inflammation these are aimed at |
| ApoB (Apolipoprotein B) | Cardiovascular risk, measured properly |
| HbA1c (Hemoglobin A1c) | Glycation over three months |
| Comprehensive Metabolic Panel (CMP) | Liver and kidney baseline |
The Longevity Baseline panel covers these in one order — 13 markers, $219.10 with the discount applied.
Check results you already have → · All 103 markers A–Z
Calcium AKG — frequently asked questions
What is Calcium AKG?
A metabolite central to the Krebs cycle and epigenetic regulation, studied for healthy aging, bone and biological-age markers (the compound behind 'Rejuvant').
What is the suggested dose of Calcium AKG?
1,000–2,000 mg daily. This is a general reference for education only — statements have not been evaluated by the FDA and this is not medical advice.
Where can I find Calcium AKG dosing and the full breakdown?
The suggested dose and the full evidence — clinical, correlative and theoretical — are on this page. What's inside Skool is when to take it, which form actually absorbs, the brand worth buying and Coach Cam's stacks.
Where can I buy Calcium AKG?
Coach Cam sources Calcium AKG from vetted, top-rated brands on iHerb — use the buy link on this page.
What Calcium AKG is used for
Calcium AKG appears under 3 goals in the goal router.
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Where this goes next
The pages here are the frameworks. The protocols — the dosing, the order to correct things in, the week-by-week schedule and what to retest — are inside Skool.