A CaAKG-supplemented diet extends lifespan of middle-aged female mice
AKG supplementation extends healthspan of both female and male mice
AKG compresses morbidity. Reduction in frailty is more dramatic than lifespan extension
AKG reduces chronic inflammation and induces IL-10 in T cells of female mice
http://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30417-4
The link between AKG and DNA methlation was mentioned in this thread
I have been doing a lot of reading around Krebs metabolites (Citrate/AKG) and how they get out of the mitochondria.
AKG is interesting because it sort of exists in a pool including Glutamine and Glutamate in the cytosol.
It comes out of the mitochondria as part of the Malate-Aspartate shuttle so appears in the cytosol together with ATP. Arguably as Citrate links to the Mitochondrial Membrane Potential you can say high AKG indicates a high energy state whereas high citrate indicates a high power state.
Not all Krebs metabolites are positive. Malate is generally swapped back into the mitochondria when citrate or AKG come out.
AIUI DNA methylation indicates a lower probability of transcription of genes. Hence if you have more AKG you have less methylation and a greater range of mRNA. However, even if you use citrate to acetylate the histone and AKG to demethylate the DNA you still need ATP to make the proteins (and make the mRNA).
Hence it is quite logical that AKG and Citrate will help to compress morbidity. You will need more efficient mitochondria to extend lifespan and also to minimise senescence.
Excellent. I already supplement Ca-AKG, Citrate (Magnesium) and Malate (Citrulline Malate).
Now, the question is whether I’ll live to 150 or not. 
I have wondered about malate. Obviously higher levels of malate enable higher levels of citrate and AKG to leave the mitochondria. Hence arguably it should improve gene transcription.
Supplementing AKG (which I think is disassociated possibly into Glutamine and then absorbed into the cells) and Citrate has the potential to increase cytosolic levels. Citrate I know does this. The arguments on AKG are that it cannot get through the cell boundary, but there were reports that labelled carbon gets into cells.
The serum half life of AKG is really short (about 5 mins), but that’s not the issue. The issue is getting increased cytosolic levels of AKG.
Because these are metabolites, however, material amounts are needed to move the dial.
This is one of the papers I used. If people wish to read up on this this one may be useful:
@John_Hemming Yes, dosing is the question, and maybe the problem. I have stopped chasing every new “extends life in X” because it always seems like the equivalent dose is impossible or impossibly expensive for the gamble in effectiveness vs side effects. Maybe I’ve just gotten bored of chemicals, and am missing out.
What are the best bets now …in which a modest dose is very likely to move the needle?
The point about the metabolites is that moving the needle is not easy with a modest dose as you start with a certain endogenous concentration and to change that requires a lot of inputs.
At the moment I am messing around with dosing to get an idea of impact. However, there are side effects from too high dosing (scores of grams) because of the cations.
Hence I keep going with my weekly blood tests and checking things out. It would be nice if there were other people willing to do frequent blood tests as it would be easier to work things out.
New mouse study from Brian Kennedy’s group at NUS:
Overall, our findings suggest that CaAKG has neuroprotective effects in APP/PS1 mice. We propose CaAKG as a promising therapeutic target not only for aging but also for AD and potentially other age-associated neurodegenerative diseases, highlighting geroprotective strategies as viable alternatives for the prevention and treatment of AD.
All I can buy is Arginine alpha-keto glutarate.
All I see used in the literature is Ca-AKG.
Can anyone suggest if Arg-AKG provides the same benefits as Ca-AKG?
I have spent a lot of time recently studying the influences on citrate efflux from the mitochondria. As a byproduct of this I had a small look at AKG and it appears that it increases when there is spare ATP available as that blocks up the citrate cycle.
CaAKG (calcium-alphaketoglutarate) is available produced by Moleqular GmbH in Berlin Germany.
www.moleqlar.de caps. 1000 mg that contain 770 mg alphaketoglutarate that can be opened with some effort. Or as a 150 g parcel from amazon.de.
Thank you Karel.
Published in Aging Cell, a new study led by Professor Brian K Kennedy, Department of Biochemistry, Chair of the Healthy Longevity Translational Research Programme (TRP), NUS Medicine, has discovered that calcium alpha-ketoglutarate (CaAKG), a safe, naturally occurring metabolite commonly studied for healthy ageing, can restore key memory-related brain functions that have been disrupted in Alzheimer’s disease. The main aim of the study was to evaluate whether CaAKG could also enhance synaptic plasticity in the Alzheimer’s brain, restore memory-related signalling, protect neurons from early degenerative changes, and contribute to healthier cognitive ageing. For healthcare and medicine, this shift opens the door to geroprotective strategies—treatments that target ageing biology itself rather than individual disease symptoms.
It’s a mouse study, not a human study. If it has any effect on Alzheimer’s in humans it will probably take 5 years before you find out.
Abstract
Severe burns unleash a hyper-catabolic and immunosuppressive state that erodes lean tissue and delays repair. Alpha-ketoglutarate (α-KG), usually delivered enterally as the dipeptide ornithine α-ketoglutarate (OKG), feeds the tricarboxylic-acid cycle, donates nitrogen for amino-acid synthesis, and modulates collagen formation and immunity. We systematically appraised the biological mechanisms, delivery strategies, and clinical outcomes associated with α-KG/OKG in burn care to clarify its therapeutic value and translational readiness. A PRISMA-2020-compliant search of PubMed, EMBASE, Web of Science, Cochrane, and Google Scholar up to May 2025 identified clinical, in vivo, and relevant in vitro studies linking α-KG or OKG with thermal injury. Study quality was assessed using the Newcastle-Ottawa Scale, SYRCLE Risk-of-Bias tool, and Oxford Levels of Evidence. Fifteen studies published between 1984 and 2024 met inclusion criteria, including clinical, animal, and mechanistic work, most conducted in France. Across studies, OKG supplementation replenished glutamine and arginine pools, improved nitrogen balance, preserved muscle mass, and promoted wound healing through enhanced collagen synthesis and immune modulation. Clinical data confirmed improved nitrogen retention, reduced muscle breakdown, and faster wound closure. Preclinical studies further showed that α-KG preconditioning enhances stem cell-driven regeneration and vascularization. Additional effects, such as improved glucose tolerance and hepatic enzyme preservation, suggest some benefits occur independently of glutamine pathways. This review highlights α-KG and OKG as promising adjuncts to enhance metabolic recovery, wound repair, and immune competence after burns. Evidence supports improved nitrogen balance and healing, but findings remain limited by heterogeneity and small cohorts, warranting renewed and well-powered studies.