CAAKG
Calcium Alpha-Ketoglutarate
Calcium Alpha-Ketoglutarate (Ca-AKG) is a calcium salt of alpha-ketoglutarate, a key intermediate in the Krebs cycle, increasingly studied for its longevity and healthspan-extending properties. It is primarily used to support cellular energy metabolism, reduce age-related inflammation, and has demonstrated the ability to compress morbidity and extend healthspan in preclinical models. Growing interest surrounds its role in epigenetic regulation and as a substrate for collagen synthesis and amino acid metabolism.
Mechanism of Action
Alpha-ketoglutarate serves as a critical Krebs cycle intermediate and acts as a cofactor for over 60 dioxygenase enzymes, including TET enzymes and histone demethylases (KDMs), which regulate DNA and histone methylation patterns central to aging and gene expression. It competitively inhibits ATP synthase and modulates mTOR signaling, potentially mimicking caloric restriction at the cellular level. AKG also functions as a nitrogen scavenger, facilitating amino acid transamination and serving as a glutamate and proline precursor, supporting collagen biosynthesis and gut mucosal integrity.
Evidence by Health Goal(18 goals)
Dosing Protocols
On empty stomach or 30 minutes before a meal, typically in the morning
Most human studies and longevity-focused protocols use 1000mg daily; some researchers use up to 3000mg. The calcium component contributes approximately 20% elemental calcium, so total daily calcium intake should be considered. Start at lower dose to assess gastrointestinal tolerance.
Safety & Side Effects
Ca-AKG has a generally favorable safety profile in healthy adults at recommended doses, with most adverse effects being mild and gastrointestinal in nature. Individuals with kidney disease, hypercalcemia, or those taking calcium-sensitive medications should use caution and consult a physician, as long-term human safety data remains limited and large-scale clinical trials are still ongoing.
Possible Side Effects
- !Gastrointestinal discomfort including bloating and loose stools, particularly at doses above 2000mg
- !Nausea when taken on a fully empty stomach
- !Hypercalcemia risk at very high doses due to calcium content
- !Mild constipation in some individuals, attributed to calcium fraction
- !Transient headache reported in a minority of users during initial use
- !Potential interference with iron absorption due to calcium content when taken with meals
Interactions
- -May reduce absorption of iron, zinc, and fluoride when taken simultaneously due to calcium content - separate by 2 hours
- -Can potentiate hypercalcemia when combined with other calcium supplements, vitamin D3 at high doses, or thiazide diuretics
- -May interact with bisphosphonate medications (e.g., alendronate) by impairing absorption - take at least 2 hours apart
- -Theoretical additive effect with other mTOR-modulating compounds such as rapamycin or berberine - monitor for excessive mTOR suppression
- -May modestly enhance effects of metformin through overlapping AMPK and metabolic pathway activation
Cost & Where to Buy
Price varies significantly by brand, purity certification, and dose per serving. Budget brands offering 1000mg daily run approximately $25-35/month, while premium or clinically validated brands (e.g., Rejuvant) with higher doses can reach $60-75/month. Bulk powder sourcing can reduce costs substantially.
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