Ca-AKG: Calcium Alpha-Ketoglutarate
Aging's silent metabolite: what the science says
Ca-AKG declines by up to tenfold from your thirties onward, cannot be obtained from a normal diet, and sits at the enzymatic heart of collagen synthesis. Here we cover the academic studies, the clinical evidence, and Celluragen, Turkey's first biotechnological collagen complex with Ca-AKG.
The molecule your body makes, then loses
Calcium alpha-ketoglutarate (Ca-AKG) is a critical metabolite that declines dramatically with age and cannot be replenished except through supplementation.
Alpha-ketoglutarate (AKG) is the central intermediate of the Krebs cycle, the body's cellular energy production system. It sits at the crossroads of carbohydrate, fat, and amino acid metabolism, contributing to intracellular energy production, amino acid synthesis, collagen biosynthesis, and epigenetic regulation.
Research shows that AKG falls by up to tenfold in blood plasma between the ages of 40 and 80. AKG cannot be obtained in sufficient amounts from ordinary foods, and supplementation is the only practical way to support its levels.
Ca-AKG is the calcium salt form of AKG. It is released more gradually in the gastrointestinal system, a property that helps maintain more stable levels in the blood over time and supports bioavailability.
"AKG cannot be obtained from a normal diet; supplementation is therefore the only practical way to replenish declining levels."
Shahmirzadi et al., Cell Metabolism, 2020 [1]Why collagen supplements may not be enough on their own
Collagen synthesis is not a single-step process, and its critical enzymatic step depends on AKG.
Fibroblasts produce procollagen, the precursor of collagen. For this molecule to become a mature collagen chain, the enzymes prolyl 4-hydroxylase and lysyl hydroxylase must be active. The scientific literature shows that, alongside molecular oxygen and ascorbate (vitamin C), alpha-ketoglutarate is also required for the activity of these enzymes.
From fruit fly to human: a 20-year scientific journey
Ca-AKG has produced consistent findings at every link of a research chain that began with nematodes, culminating in human clinical data in 2021.
Su and colleagues gave Drosophila melanogaster a 5 μM AKG supplement to examine two core aging pathways that also operate in humans. AKG inhibited the mTOR pathway and activated AMPK. These are evolutionarily conserved aging pathways. Autophagy activation and increased resistance to heat stress were also observed.
Researchers at the Buck Institute for Research on Aging ran a double-blind, longitudinal study giving Ca-AKG to middle-aged mice. In the Ca-AKG group, chronic systemic inflammatory cytokine levels decreased and production of anti-inflammatory IL-10 increased. Preservation of muscle mass and improvements in gait quality and grip strength were reported.
42 healthy individuals (28 men, 14 women; average age ~63) used a formulation containing 2 g of Ca-AKG per day for 4 to 10 months. Biological age was measured with the TruAge DNA methylation test. Across the full cohort of 42, an average reduction of 7.96 years in biological age was observed, with a positive change reported in 40 of the 42 participants. For comparison, the biological age reduction reported from exercise and fasting alone generally stays at around 1 to 2 years.
The ABLE study compared 1 g of sustained-release Ca-AKG against placebo over 6 months in 120 participants (aged 40 to 60). Early observational data were reported as supporting a significant biological age reduction after 6 months of use (p = 0.04).
Son and colleagues (2007) observed that AKG supplementation contributed to procollagen synthesis in cultured human dermal fibroblasts. Yang and colleagues (2021) reported, with clinical measurements, that an AKG-containing formulation supported skin hydration and the appearance of wrinkles.
Celluragen: where the Ca-AKG difference begins
Supported by TÜBİTAK R&DThe vast majority of collagen supplements on the market contain only collagen peptides. Celluragen was developed by bringing together, in a holistic approach, components that support collagen metabolism. Ca-AKG sits at the center of the formulation as a metabolite shown in the literature to help meet the substrate needs of the prolyl and lysyl hydroxylase enzymes.
From among 41 potential cofactors, antioxidants, and bioactive compounds aimed at supporting collagen metabolism, the most suitable components, doses, and combinations were determined through in vitro studies with a holistic effect in mind. Each component was added to the formulation through a scientific selection process.
- Shahmirzadi A.A. et al. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metabolism, 32(3):447-456, 2020. PubMed · PMC
- Su Y. et al. Alpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPK. Aging (Albany NY), 11:4183-4197, 2019. PMC
- 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 (Albany NY), 13(22):24485-24499, 2021. PMC
- Sandalova E. et al. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE). GeroScience, 45(5):2897-2907, 2023. PubMed · PMC
- Son E. et al. Alpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts. Arch. Dermatol. Res., 2007. PubMed
- Yang F. et al. Skin hydration and anti-wrinkles function improvement with alpha-ketoglutarate. J. Cosmetic Dermatology, 2021. Wiley
- Çevik et al. SIRT1, resveratrol and aging. Frontiers in Genetics, 2024. PMC
- Myllyharju J. Collagen prolyl 4-hydroxylases and their clinical importance. Trends Biochem Sci, 33(11):535-549, 2008. PubMed
- Wu N. et al. Alpha-Ketoglutarate: Physiological Functions and Applications. Biomolecules & Therapeutics, 24(1):1-8, 2016. PMC
- Xie et al. Advances in alpha-Lipoic Acid for Disease Prevention. PMC, 2025. PMC
- Ishaque S. et al. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Med, 2012. PMC
- Jean-Gilles D. et al. Inhibitory effects of polyphenol punicalagin on type-II collagen degradation in vitro. Chem Biol Interact, 2013. PubMed
- Du X. et al. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia, 2008. PubMed
This content is for informational purposes only. Celluragen is a food supplement; it cannot be used to diagnose, treat, or prevent any disease. Supplements cannot replace a balanced and varied diet. Results reported in academic studies of the individual components do not constitute a guarantee of the product's individual effectiveness.