Alpha-ketoglutarate (AKG) is a molecule your cells make every day as part of the Krebs cycle, the chemical loop that turns food into energy. It became a longevity topic after a 2020 study found a calcium form of AKG extended lifespan in female mice and reduced frailty in both sexes. In people, the evidence so far is one uncontrolled study and one survey, and the first placebo-controlled trial hasn't published its results.
That gap between the mouse data and the human data is the whole story with AKG right now. This guide explains what AKG is, what the animal studies found, what the human studies can and can't tell you, and what to look for on a label if you're comparing products.
Last reviewed: November 9, 2026
Key Takeaways
- AKG (alpha-ketoglutarate, also called 2-oxoglutarate) is an intermediate in the Krebs cycle. The body makes it; it isn't an essential nutrient.
- In worms, AKG extended lifespan in a 2014 Nature study. In mice, a 2% calcium AKG diet started at 18 months of age extended median lifespan in females by 10.5% to 16.6% and reduced frailty in both sexes.
- The best-known human report followed 42 people taking a commercial calcium AKG product and found lower epigenetic age scores, but it had no placebo group.
- ABLE, a placebo-controlled trial of 1 g a day of sustained-release calcium AKG in 120 adults aged 40 to 60, finished its main data collection in August 2025. Its primary results weren't published as of November 5, 2026.
- Several authors of the mouse and human AKG studies have financial ties to a company that sells an AKG product, which the papers disclose.
What is alpha-ketoglutarate?
Alpha-ketoglutarate is one of the molecules in the tricarboxylic acid (TCA) cycle, better known as the Krebs cycle. That cycle runs inside your mitochondria and is a central step in getting energy out of food (Asadi Shahmirzadi et al., 2020). Our guide to mitochondrial health explains where the Krebs cycle fits.
AKG also sits at a crossroads with amino acids. Cells use it to build and break down amino acids such as glutamate, and it's involved in collagen production and in the enzymes that adjust how genes are switched on and off (Asadi Shahmirzadi et al., 2020). For more on that side of metabolism, see the role of amino acids in metabolism.
In supplements, AKG usually appears as a salt: calcium alpha-ketoglutarate (Ca-AKG), which is the form used in the main longevity studies, or arginine alpha-ketoglutarate (AAKG), which is common in sports formulas.
Why do researchers link AKG to aging?
Researchers link AKG to aging because its levels shift with fasting, exercise and age, and because adding it extended lifespan in worms and mice. The 2020 mouse study notes that AKG levels in the blood fall with age in mice and that earlier work showed oral AKG could restore them (Asadi Shahmirzadi et al., 2020). Whether the same decline matters in people hasn't been shown.
The first big result came from worms. A 2014 Nature study found AKG extended the lifespan of adult C. elegans by partly slowing ATP synthase, part of the cell's energy machinery, with effects running through the TOR growth pathway. AKG didn't extend lifespan further in worms already on dietary restriction, which suggested it works through some of the same routes as eating less (Chin et al., 2014). For the difference between living longer and staying healthy longer, see healthspan vs lifespan.
What did the AKG mouse study find?
In the 2020 Cell Metabolism study, mice ate a diet with 2% calcium AKG by weight starting at 18 months of age, roughly middle age for a mouse. The researchers ran two separate groups to check whether the results repeated (Asadi Shahmirzadi et al., 2020).
| Measure | Female mice | Male mice |
|---|---|---|
| Median lifespan from the start of feeding | Up 16.6% (cohort 1) and 10.5% (cohort 2), both significant | Up 9.6% and 12.8%, but the survival difference wasn't statistically significant |
| Frailty (31-item index) | Lower | Lower |
| Immune signaling (cytokines) in the blood | Lower levels of several cytokines, plus more IL-10 from immune cells | The IL-10 effect wasn't seen |
The authors' main conclusion was about healthspan: the drop in frailty was larger than the gain in lifespan, so the mice spent less of their life frail. They also listed limits. The control diet had no added calcium, the IL-10 explanation only held in females, and they didn't measure AKG levels in the mice (Asadi Shahmirzadi et al., 2020).
The paper's conflict-of-interest statement says several authors were shareholders in Ponce de Leon Health, a company that sells a calcium AKG product, and named inventors on a related patent application. That doesn't make the results wrong, but it's worth knowing when the same names show up in the human studies.
Does AKG work in humans?
We don't know yet. No placebo-controlled trial of AKG for aging had published results as of November 5, 2026. Here's what exists:
| Study | Design | Who | What it found |
|---|---|---|---|
| Demidenko et al., 2021 | Look-back analysis, no placebo | 42 customers taking Rejuvant, a timed-release calcium AKG product with vitamin A (men) or vitamin D (women), for 4 to 10 months | Average drop of about 8 years on a saliva DNA methylation (epigenetic age) test |
| Pabis et al., 2026 | Cross-sectional survey | 4,260 people who bought a saliva epigenetic test | People using the delayed-release AKG plus vitamin product scored 1.8 years younger on average; people using regular AKG showed a smaller difference that wasn't statistically significant |
| ABLE trial (protocol, 2023) | Randomized, double-blind, placebo-controlled | 120 adults aged 40 to 60 in Singapore whose epigenetic age was older than their actual age | Tests 1 g a day of sustained-release calcium AKG for 6 months, plus 3 months of follow-up. Main results not yet published |
The 2021 study's authors wrote that it wasn't placebo controlled and that a placebo-controlled study is needed. Everyone in it had chosen to buy and take the product, and the testing company had a service agreement with the product's maker (Demidenko et al., 2021). The 2026 survey authors flag healthy-user and recruitment bias: people who buy epigenetic tests and supplements may differ in many ways from people who don't (Pabis et al., 2026).
Epigenetic age tests are also an indirect measure. A lower score isn't the same as living longer or staying healthier, which is why our guide to biological age tests and epigenetic clocks is worth reading before you put weight on any clock result.
When will the ABLE trial results be out?
There's no published date. ClinicalTrials.gov lists ABLE (NCT05706389) as active but no longer recruiting, with primary data collection completed on August 15, 2025 and overall completion estimated for January 2027 (ClinicalTrials.gov). So far the team has published papers on recruitment and on wearable activity trackers: 120 people enrolled, more than 90% stuck with the supplement, and 17% dropped out (Lim et al., 2025; Lu et al., 2026). Those papers don't report whether AKG changed epigenetic age.
How much AKG did the studies use?
The ABLE trial uses 1 g of sustained-release calcium AKG a day (Sandalova et al., 2023). The mouse study mixed 2% calcium AKG into the food, which doesn't translate neatly into a human dose. If you're comparing products, check three things on the Supplement Facts panel:
- Which salt: calcium AKG is the form in the longevity studies. Arginine AKG (AAKG) is a different compound used mostly in sports formulas.
- How much per serving: compare the milligrams with the 1 g used in ABLE.
- Release type: the human studies used timed- or sustained-release versions.
Our guide on how to read a Supplement Facts label walks through serving sizes and blends.
Is AKG safe, and what are the side effects?
There isn't much long-term safety data in people yet. The mouse study didn't find significant adverse changes with calcium AKG (Asadi Shahmirzadi et al., 2020), and the ABLE results, including side effects, haven't been published. Calcium AKG also adds calcium to your daily total, which matters if you already take a calcium supplement. Talk to your doctor or pharmacist before starting AKG, especially if you take prescription medication, are pregnant or breastfeeding, or are under medical care.
What is AAKG, and is it the same as AKG?
AAKG (L-arginine alpha-ketoglutarate) pairs the amino acid arginine with AKG. It's been studied mainly for exercise, not aging. In an 8-week trial, 35 resistance-trained men aged 30 to 50 took 12 g a day of AAKG or a placebo; the AAKG group improved more on 1-rep-max bench press and peak power, with no difference in body composition or aerobic capacity, and the supplement was well tolerated (Campbell et al., 2006). None of the longevity studies above used AAKG.
OPA Nutrition L-Arginine with L-Citrulline
OPA Nutrition doesn't sell a calcium AKG supplement. Our L-Arginine with L-Citrulline capsules include 400 mg of L-Arginine AKG (2:1) per two-capsule serving, alongside L-arginine, L-citrulline, beta-alanine and niacin. It's an active-lifestyle amino acid formula, not a longevity product, and it isn't the calcium AKG tested in the studies above.
Where does AKG fit in a healthy aging routine?
AKG is one of the more interesting longevity compounds in animal research, and the ABLE results should give the first fair test in people. Until then, the habits with the strongest human evidence haven't changed: regular movement, enough protein, good sleep and not smoking. Our guides to exercise and longevity and nutrition for healthy aging cover those, and our no-hype longevity supplements guide compares other popular compounds.
Frequently Asked Questions
Does AKG reverse aging?
No study has shown that. AKG extended lifespan in worms and female mice. In people, one uncontrolled study and one survey linked a calcium AKG product to lower epigenetic age scores, which isn't the same as reversing aging.
How much AKG should I take?
There's no established dose. The ABLE trial uses 1 g a day of sustained-release calcium AKG. Follow the product label and ask a clinician if you're unsure.
Who should not take AKG?
Anyone pregnant or breastfeeding, taking prescription medication or under medical care should talk to a doctor first. If you already take calcium, count the calcium in Ca-AKG too.
What is another name for alpha-ketoglutaric acid?
It's also called 2-oxoglutarate or 2-ketoglutaric acid. "Alpha-ketoglutarate" and "AKG" are the names most labels use.
Is calcium AKG the same as AKG?
Calcium AKG is AKG bound to calcium, a stable form for supplements. It's the form used in the mouse lifespan study and in the ABLE trial.
Can you get AKG from food?
Your body makes AKG itself during normal energy metabolism, so you don't need it from food. We couldn't find reliable measurements of AKG in foods, so we haven't listed any.
Sources
- Asadi Shahmirzadi A, Edgar D, Liao CY, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 2020;32(3):447-456. PubMed 32877690
- Chin RM, Fu X, Pai MY, et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature. 2014;510(7505):397-401. PubMed 24828042
- Demidenko O, Barardo D, Budovskii V, 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 (Albany NY). 2021;13(22):24485-24499. PubMed 34847066
- Pabis K, Wang W, Selvarajoo K, et al. Supplements and drugs are associated with biological age in a cohort of exceptionally healthy individuals. Aging Cell. 2026;25(6):e70517. PubMed 42166733
- Sandalova E, Goh J, Lim ZX, et al. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE): intervention study protocol. GeroScience. 2023;45(5):2897-2907. PubMed 37217632
- Lim ZM, Chew YE, Guan L, et al. Recruitment evaluation of a gerotherapeutic randomized controlled trial testing alpha-ketoglutarate in biologically older, middle-aged adults (ABLE). Exp Gerontol. 2025;209:112867. PubMed 40819772
- Lu JK, Wang W, Chew YE, et al. Optimizing accelerometer implementation in a gerotherapeutic trial: feasibility, adherence, and operational insights of ABLE. PLOS Digit Health. 2026;5(9):e0001691. PubMed 42789532
- ClinicalTrials.gov. NCT05706389: Alpha-ketoglutarate supplementation and biological age in middle-aged adults (ABLE). Record last updated May 2026. clinicaltrials.gov
- Campbell B, Roberts M, Kerksick C, et al. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men. Nutrition. 2006;22(9):872-881. PubMed 16928472
- Images: Kindel Media (featured image), Ivan S and ready made, via Pexels (free Pexels license).
Disclosure: OPA Nutrition sells supplements, including products mentioned in this article. This content is for education only and is not medical advice. Statements about dietary supplements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. Talk to your healthcare provider before using any supplement, especially if you take medication or have a medical condition.
