Ca-AKG

Q: What is alpha-ketoglutarate and why supplement it?

Alpha-ketoglutarate (AKG) is a metabolite your body naturally produces. It occupies a central position in the Krebs cycle, the primary pathway for cellular energy production. Plasma AKG concentrations decrease over the decades, which has motivated the exploration of oral supplementation. The Ca-AKG form combines AKG with calcium for improved stability and a dual nutritional benefit.

Q: What is the difference between Ca-AKG and other forms of AKG?

Ca-AKG is the calcium salt of alpha-ketoglutarate. It differs from free acid (unstable, poorly tolerated) and ornithine salt (OKG, used in hospital settings). The calcium form stabilises the molecule, improves digestive tolerance and provides elemental calcium. It is the most widely used form in recent clinical nutrition trials.

Q: Can Ca-AKG replace a standard calcium supplement?

Ca-AKG contains approximately 19.5% elemental calcium. It contributes to daily calcium intake without being the sole source. Its value lies in combining calcium with alpha-ketoglutarate, a metabolite with multiple cellular functions. For individuals with high calcium needs, a dedicated supplement may still be necessary depending on the individual profile.

Q: Is Ca-AKG suitable for people following a vegan diet?

Ca-AKG is a synthetic mineral salt that contains no animal-derived ingredients. It is suitable for vegan diets. For vegans, it holds particular interest as it simultaneously contributes to calcium intake (often limited in the absence of dairy products) and alpha-ketoglutarate.

Q: How long does it take to notice the effects of Ca-AKG?

Ca-AKG acts at the level of cellular metabolism, a process that does not produce immediately perceptible effects. The only published human clinical trial measured changes in biological markers after seven months of supplementation. Calcium-related effects (bone support, muscle function) also develop over time. Regular intake over several months is recommended.

Alpha-cétoglutarate de calcium · Calcium Alpha-Ketoglutarate · CaAKG · Calcium 2-oxoglutarate

MetabolitesMitochondrial energy

Ca-AKG embodies an emerging nutritional approach: supplementation with an intermediary metabolite. Where conventional nutrition targets vitamins and minerals, alpha-ketoglutarate operates upstream, at the heart of fundamental cellular metabolic pathways. Its roles extend beyond energy production alone. It participates in collagen synthesis and cellular regulation processes that are drawing growing scientific interest. Several human clinical trials are currently exploring its potential.

Last updated: March 24, 2026

Mechanism of Action

Alpha-ketoglutarate holds a strategic position within the Krebs cycle (the central energy production loop inside mitochondria). It serves as a substrate to generate reducing equivalents, the molecules that feed the respiratory chain and ATP synthesis (the cell's energy currency).

Its role extends further. AKG is an essential cofactor for 2-oxoglutarate-dependent dioxygenases, a family of enzymes involved in collagen maturation. These enzymes hydroxylate proline and lysine, two amino acids critical to collagen fibre structure. AKG also participates in amino acid metabolism by serving as a carbon skeleton in transamination reactions (the transfer of nitrogen groups between molecules).

As a calcium salt, Ca-AKG releases alpha-ketoglutarate and elemental calcium after dissociation in the digestive tract. The released calcium contributes to the maintenance of normal bones and muscle function.

Key Benefits

Strong
Calcium contributes to the maintenance of normal bones. Several meta-analyses confirm a significant increase in bone mineral density in supplemented adults, particularly when calcium is combined with vitamin D.
Strong
Calcium contributes to normal muscle function. Its role in excitation-contraction coupling of muscle fibres is documented by decades of physiological research.
Strong
Calcium contributes to normal energy-yielding metabolism. Ca-AKG offers a coherent dual supply: the metabolic substrate (AKG) and the mineral (calcium) jointly support this process.
Strong
Calcium contributes to normal neurotransmission. This role in nerve signalling is fundamental for daily intercellular communication.
Moderate
Alpha-ketoglutarate is a required cofactor for collagen hydroxylation. This biochemical process conditions the stability of collagen fibres throughout connective tissue.
Emerging
A preliminary open-label trial in adults supplemented with Ca-AKG observed changes in epigenetic markers associated with cellular aging. These results remain to be confirmed by larger controlled trials.

Dosage & Forms

Several forms of alpha-ketoglutarate are available: free acid, sodium salt, ornithine salt (OKG) and calcium salt (CaAKG). Free acid is unstable and may irritate the digestive tract. OKG, studied primarily in hospital settings, serves a distinct clinical purpose. Sodium salt adds excess sodium unsuitable for daily supplementation.

Calcium salt offers the best fit for regular oral use: molecular stability, good tolerance and a concomitant supply of elemental calcium. Documented human dosages in the literature range from 500 mg to 2,000 mg of CaAKG per day. Singular calibrates the dose according to each member's profile, in non-GMO powder form with no excipient.

In the Singular Formula

Inclusion rationale

Calcium salt of alpha-ketoglutarate, a central intermediate of the Krebs cycle (the primary energy production pathway in every cell). In this calcium-bound form, it offers oral bioavailability suited to supplementation and a dual nutritional benefit: supporting intermediary energy metabolism while contributing to calcium needs, essential for the maintenance of normal bones and teeth. Alpha-ketoglutarate is an endogenous metabolite whose plasma concentrations naturally decline with age, a decline that coincides with the progressive weakening of cellular energy metabolism. This decline has sparked growing interest in aging research. A study published in 2020 observed in CaAKG-supplemented mice a compression of morbidity and a reduction in biological age assessed by epigenetic clock. These preliminary animal results have paved the way for ongoing human clinical trials. Beyond its metabolic role, the calcium provided by this form integrates into the formula's bone axis alongside vitamin D3, vitamin K2 MK-7, magnesium and boron (all present in the formula). Calcium contributes to the maintenance of normal bones, and its combination with vitamin D and vitamin K2 optimizes its utilization by bone tissue.

Selected form

Calcium salt of alpha-ketoglutaric acid (AKG), a key intermediate in the Krebs cycle, the primary pathway for cellular energy production. The calcium form simultaneously provides elemental calcium (approximately 19.5%) and AKG in a single compound, with no added excipient. Unlike free forms of AKG, calcium chelation stabilises the molecule and improves digestive tolerance. AKG naturally participates in amino acid metabolism and energy production within the mitochondria. Quality: non-GMO, no excipient.

Formula dosage

0 to 1 g.

Synergies in the formula

Ca-AKG integrates into several axes of the Singular formula. On the bone front, the calcium it releases benefits from four cofactors. Vitamin D3 promotes intestinal calcium absorption. Vitamin K2-MK7 directs it toward bone tissue rather than soft tissues. Magnesium participates in bone mineralisation. Boron supports calcium and magnesium metabolism. On the energy metabolism front, AKG feeds the Krebs cycle upstream. Nicotinamide riboside (NR), a NAD+ precursor, supports the same chain downstream by providing the necessary coenzymes. PQQ, which promotes mitochondrial biogenesis (the production of new mitochondria), completes this trio by acting on the number of available mitochondria. AKG is involved in collagen maturation through proline hydroxylation. Vitamin C, a cofactor for the same enzymatic reaction, reinforces this pathway. Glycine, a constituent amino acid of collagen, provides the complementary structural substrate.

Linked Biomarkers

Combined eGFR

Safety & Precautions

Ca-AKG has a favourable safety profile at the doses studied (500 to 2,000 mg/day). Alpha-ketoglutarate is an endogenous metabolite naturally present in the body, which affords it good general tolerance.

Minor digestive effects (gastric discomfort, bloating) have been occasionally reported at higher doses. These effects are generally transient. The calcium intake associated with this form should be factored into total daily calcium intake calculations. A total calcium intake exceeding 2,500 mg/day (from all sources) is not recommended.

Ca-AKG supplementation is not recommended for pregnant or breastfeeding women due to insufficient data. Individuals monitored for a renal health condition or calcium excess should consult a healthcare professional before use. No data are available in children.

Scientific Studies

Authors	Year	Type	Journal
Weaver CM et al.	2016	Meta-analysis	Osteoporosis International	View on PubMed
Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation National Osteoporosis Foundation meta-analysis of controlled trials on calcium and vitamin D supplementation. Confirms a significant reduction in total fracture risk in supplemented adults.
Tai V et al.	2015	Meta-analysis	BMJ	View on PubMed
Calcium intake and bone mineral density: systematic review and meta-analysis Systematic review and meta-analysis evaluating the effect of calcium intake on bone mineral density. Shows a modest but significant increase in bone density with supplementation.
Asadi Shahmirzadi A et al.	2020	Preclinical Study	Cell Metabolism	View on PubMed
Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice Preclinical study in mice showing that CaAKG supplementation extends healthy lifespan and compresses late-life morbidity. These animal results paved the way for human trials.
Demidenko O et al.	2021	Pilot Study	Aging	View on PubMed
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 Open-label trial in 42 adults supplemented with Ca-AKG combined with vitamins for an average of 7 months. Observed reduction in epigenetic markers associated with biological age. Preliminary results requiring confirmation through a controlled trial.
Chin RM et al.	2014	Preclinical Study	Nature	View on PubMed
The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR Foundational study demonstrating for the first time that alpha-ketoglutarate extends lifespan in an animal model (C. elegans). This preclinical data established the biological rationale for subsequent research.

Frequently Asked Questions

What is alpha-ketoglutarate and why supplement it?#[ + ]

What is the difference between Ca-AKG and other forms of AKG?#[ + ]

Can Ca-AKG replace a standard calcium supplement?#[ + ]

Is Ca-AKG suitable for people following a vegan diet?#[ + ]

How long does it take to notice the effects of Ca-AKG?#[ + ]

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