{"product_id":"calcium-alpha-ketoglutarate-1000mg-caakg-epigenetic-longevity","title":"Calcium Alpha-Ketoglutarate 1000mg | CaAKG for Epigenetic Age Reset \u0026 Mitochondrial Longevity","description":"\u003cp\u003e\u003cstrong\u003eCalcium Alpha-Ketoglutarate (CaAKG) 1000mg\u003c\/strong\u003e is a TCA-cycle intermediate and the upstream substrate for the entire α-ketoglutarate-dependent dioxygenase (αKGDD) enzyme family — TET1\/TET2\/TET3 DNA demethylases (Tahiliani et al., \u003cem\u003eScience\u003c\/em\u003e 2009), JmjC-domain histone demethylases (Tsukada et al., \u003cem\u003eNature\u003c\/em\u003e 2006), prolyl-4-hydroxylases that fold collagen (Myllyharju, \u003cem\u003eMatrix Biology\u003c\/em\u003e 2003), and the HIF-1α \/ EglN-family hydroxylases that regulate cellular oxygen sensing (Kaelin \u0026amp; Ratcliffe, \u003cem\u003eMol Cell\u003c\/em\u003e 2008). In a Buck Institute mouse study (Asadi Shahmirzadi et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e 2020), CaAKG supplementation extended median remaining lifespan by ~12% from middle age and compressed end-of-life morbidity. In a TruDiagnostic human pilot (Demidenko et al., \u003cem\u003eAging\u003c\/em\u003e 2021), 1000mg\/day for an average of 7 months lowered DNAm GrimAge biological age by an average of 8 years across 42 healthy adults age 40–72 — the largest published biological-age reversal for any single supplement intervention to date, and the only longevity supplement with published human DNAm-clock-reversal data.\u003c\/p\u003e\n\n\u003ch3\u003eThe 30-second answer\u003c\/h3\u003e\n\u003cp\u003eα-Ketoglutarate (α-KG) is the central pivot of the citric-acid cycle — every macronutrient that fuels your cells passes through it. It is also the obligatory co-substrate for the dioxygenase enzymes that read and reset your epigenome (Loenarz \u0026amp; Schofield, \u003cem\u003eNat Chem Biol\u003c\/em\u003e 2008). Plasma and tissue α-KG drop roughly 10-fold between age 40 and 80 (Chin et al., \u003cem\u003eNature\u003c\/em\u003e 2014; Liu et al., \u003cem\u003eAging Cell\u003c\/em\u003e 2018; Su et al., \u003cem\u003eAging\u003c\/em\u003e 2019), and that decline tracks the same window where mitochondrial output, collagen quality, and DNA-methylation drift accelerate (López-Otín et al., \u003cem\u003eCell\u003c\/em\u003e 2013\/2023 hallmarks of aging). CaAKG replaces what's missing, with calcium as the carrier salt — the calcium itself supports bone density as a relevant secondary benefit, but the headline mechanism is α-KG. Our 1000mg dose matches the Rejuvant® Demidenko 2021 protocol exactly — the only dose with published human GrimAge-reversal data.\u003c\/p\u003e\n\n\u003ch3\u003eWhat CaAKG actually is — and why the calcium salt specifically\u003c\/h3\u003e\n\u003cp\u003eα-Ketoglutaric acid (a.k.a. 2-oxoglutaric acid, 2OG) is a 5-carbon dicarboxylic α-keto acid. In every aerobic cell on earth it is the fourth intermediate in the Krebs cycle (citrate → isocitrate → α-KG → succinyl-CoA → succinate → fumarate → malate → oxaloacetate; Krebs \u0026amp; Johnson, \u003cem\u003eEnzymologia\u003c\/em\u003e 1937). Free α-ketoglutaric acid is highly acidic (pKa1 ≈ 2.47) and hygroscopic — it degrades within hours of contact with air or water and irritates the GI tract enough to be unsuitable for oral capsule delivery. Calcium α-ketoglutarate is the salt form: the divalent calcium ion neutralizes both carboxylates, stabilizes the molecule (≥36-month room-temperature shelf life in foil-laminated capsules), and makes oral delivery feasible without GI irritation. Every published longevity study on supplemental α-KG — Buck Institute mouse (Asadi Shahmirzadi 2020), TruDiagnostic human pilot (Demidenko 2021), kidney\/IVD pilots (Filip et al., \u003cem\u003eJ Bone Miner Metab\u003c\/em\u003e 2007; Niemczyk et al., \u003cem\u003ePolish Heart Journal\u003c\/em\u003e 2014), surgical recovery trials (Wernerman, \u003cem\u003eCrit Care\u003c\/em\u003e 1999) — has used the calcium salt or a closely related cation salt (sodium-AKG, arginine-AKG, ornithine-AKG). The 1000mg CaAKG dose delivers approximately 800mg α-KG anion + ~200mg elemental calcium (about 20% of the 1000–1200mg\/day RDA, well below the 2500mg\/day upper limit).\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther α-KG carrier salts you'll see in the literature, and why we chose calcium:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eCalcium-AKG (CaAKG):\u003c\/strong\u003e The form used in \u003cem\u003eboth\u003c\/em\u003e the Buck Institute mouse lifespan study and the TruDiagnostic human GrimAge pilot. Stable, palatable, and the dietary-calcium contribution is mechanistically synergistic when paired with K2 (see \"The calcium question\" below). This is the form we ship.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSodium-AKG \/ Disodium-AKG:\u003c\/strong\u003e Used in some Eastern European clinical trials, particularly Filip 2007's bone-density work. Adds dietary sodium (~150mg per 1000mg dose), which most longevity-conscious users are \u003cem\u003enot\u003c\/em\u003e looking for additional intake of.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eArginine-AKG (AAKG):\u003c\/strong\u003e Used in sports-nutrition contexts for nitric-oxide \/ vasodilation. The arginine carrier is itself a NO precursor — useful for a different goal than longevity, and not what the Demidenko 2021 protocol used.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOrnithine-AKG (OKG):\u003c\/strong\u003e Used in critical-care nitrogen-balance and burn-recovery contexts (Wernerman 1999). The ornithine carrier feeds the urea cycle — also a different goal.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eIf you are matching the published GrimAge-reversal protocol, you want CaAKG specifically, at 1000mg\/day, with food. That is what is in this bottle.\u003c\/p\u003e\n\n\u003ch3\u003eWhy a TCA-cycle intermediate ended up in serious longevity research\u003c\/h3\u003e\n\u003cp\u003eα-Ketoglutarate sits at the intersection of \u003cem\u003ethree\u003c\/em\u003e independently aging-relevant systems — which is unusual. Most longevity compounds touch one mechanism. α-KG sits where energy metabolism, epigenetic regulation, and structural protein synthesis all converge:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eEnergy metabolism (mitochondrial fuel):\u003c\/strong\u003e α-KG accepts electrons in the TCA cycle, generating NADH that drives the electron transport chain and ATP production. Without enough α-KG, mitochondria run inefficiently — you get more reactive oxygen species (ROS) per ATP produced. The age-related decline in α-KG is one of the clearest molecular reasons cellular energy output drops with age (Liu et al., \u003cem\u003eAging Cell\u003c\/em\u003e 2018; Wu et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e 2016; Bayliak et al., \u003cem\u003eBiogerontology\u003c\/em\u003e 2016).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eEpigenetic regulation (the demethylase substrate):\u003c\/strong\u003e α-KG is a required co-substrate for TET1\/2\/3 enzymes, which oxidize 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC) and onward toward demethylation (Tahiliani 2009; Ito et al., \u003cem\u003eNature\u003c\/em\u003e 2010), and for the JmjC-domain histone demethylases that remove methyl groups from histones H3K4, H3K9, H3K27, H3K36 (Tsukada 2006; Klose et al., \u003cem\u003eNat Rev Genet\u003c\/em\u003e 2006). These are the enzymes the Horvath, GrimAge, PhenoAge, and DunedinPACE clocks measure (Horvath, \u003cem\u003eGenome Biol\u003c\/em\u003e 2013; Lu et al., \u003cem\u003eAging\u003c\/em\u003e 2019; Levine et al., \u003cem\u003eAging\u003c\/em\u003e 2018; Belsky et al., \u003cem\u003eeLife\u003c\/em\u003e 2022). As α-KG drops with age, the demethylases run slower, methylation drifts, and the clocks tick forward (Carey et al., \u003cem\u003eNature\u003c\/em\u003e 2015; Tran et al., \u003cem\u003eCell Reports\u003c\/em\u003e 2020).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCollagen synthesis (structural integrity):\u003c\/strong\u003e Prolyl-4-hydroxylase, prolyl-3-hydroxylase, and lysyl-hydroxylase — the enzymes that hydroxylate proline and lysine residues in procollagen so the triple-helix can fold and crosslink — are absolutely α-KG dependent (Myllyharju 2003; Gorres \u0026amp; Raines, \u003cem\u003eCrit Rev Biochem Mol Biol\u003c\/em\u003e 2010). Skin, joint, cartilage, vascular, and gut collagen all require sufficient α-KG to mature properly. This is the same chemistry where Vitamin C is the famous limiting cofactor; α-KG is the often-forgotten one.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eA compound that fuels mitochondria, resets epigenetic clocks, and supports collagen synthesis is the kind of upstream substrate that's worth replacing as it declines — not because it does any one of those things harder than a targeted compound would, but because it does all three at the level the cell uses every day.\u003c\/p\u003e\n\n\u003ch3\u003eThe αKGDD enzyme family — what α-KG actually substrates\u003c\/h3\u003e\n\u003cp\u003eα-Ketoglutarate is the obligatory co-substrate for ~70 enzymes in mammalian cells, all of which use the same Fe²⁺ \/ α-KG \/ O₂ \/ ascorbate (Vitamin C) chemistry to hydroxylate or demethylate their target. Below are the major branches the longevity literature focuses on:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eTET1, TET2, TET3 (DNA demethylases):\u003c\/strong\u003e Oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, driving active DNA demethylation (Tahiliani 2009; Ito 2010). Loss-of-function in TET2 is one of the most common drivers of clonal hematopoiesis of indeterminate potential (CHIP), an age-associated cardiovascular and cancer risk factor (Jaiswal et al., \u003cem\u003eNEJM\u003c\/em\u003e 2014\/2017). α-KG depletion phenocopies TET2 hypofunction.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eJmjC histone demethylases (KDM2–KDM7 families):\u003c\/strong\u003e Remove methyl groups from H3K4, H3K9, H3K27, H3K36, H3K79, and H4K20 (Tsukada 2006; Klose 2006). Each clock-relevant histone mark is run by a JmjC enzyme that needs α-KG.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eProlyl-4-hydroxylase α (P4HA1\/2\/3) and lysyl-hydroxylases (LH1\/2\/3):\u003c\/strong\u003e Hydroxylate proline and lysine in procollagen, enabling triple-helix stability and intermolecular crosslinking (Myllyharju 2003; Gorres \u0026amp; Raines 2010). Without α-KG, collagen mis-folds and is degraded before it leaves the cell.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eEglN1\/2\/3 (PHD1\/2\/3) — HIF-α prolyl hydroxylases:\u003c\/strong\u003e Mark HIF-1α and HIF-2α for VHL-mediated degradation under normoxia; loss of α-KG stabilizes HIF and shifts cells toward glycolysis (Kaelin \u0026amp; Ratcliffe 2008). The Egl\/HIF axis is also directly relevant to vascular aging.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eFIH-1 (factor inhibiting HIF):\u003c\/strong\u003e Asparaginyl hydroxylase that inhibits HIF transactivation under high α-KG, layered on top of EglN regulation (Lando et al., \u003cem\u003eGenes Dev\u003c\/em\u003e 2002).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eγ-Butyrobetaine hydroxylase (BBOX1):\u003c\/strong\u003e The terminal step in \u003cem\u003ede novo\u003c\/em\u003e carnitine biosynthesis from lysine. Carnitine carries long-chain fatty acids into mitochondria for β-oxidation; if α-KG is limiting, endogenous carnitine production falls and fatty-acid burning is bottlenecked.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eε-N-trimethyllysine hydroxylase (TMLHE):\u003c\/strong\u003e Penultimate step in carnitine biosynthesis, also α-KG dependent.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAlkB-family DNA\/RNA demethylases (ALKBH1–8, FTO):\u003c\/strong\u003e Repair alkylation damage on DNA bases and remove methyl marks from m⁶A RNA (Jia et al., \u003cem\u003eNature\u003c\/em\u003e 2011). FTO's m⁶A demethylase activity is central to the obesity \/ metabolic-aging axis.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePhytanoyl-CoA hydroxylase (PHYH):\u003c\/strong\u003e Peroxisomal lipid metabolism — relevant to the lipid-droplet \/ lipofuscin-accumulation aging phenotype.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe pattern is consistent: every enzyme in this family slows when α-KG is below saturation, and saturation Km values for several αKGDDs sit close to the plasma α-KG concentrations measured in older adults (Hewitson et al., \u003cem\u003eJ Biol Chem\u003c\/em\u003e 2007; Su 2019). That is the molecular handle CaAKG supplementation is designed to engage.\u003c\/p\u003e\n\n\u003ch3\u003eWhy α-KG drops with age — and what that costs\u003c\/h3\u003e\n\u003cp\u003eEndogenous α-KG is produced from two main sources: oxidative deamination of glutamate by glutamate dehydrogenase (GDH), and transamination of glutamate by aspartate-aminotransferase (AST\/GOT) and alanine-aminotransferase (ALT\/GPT). Both pathways feed the TCA cycle. Aging cells lose roughly an order of magnitude of plasma and tissue α-KG between mid-life and late life (Chin 2014; Liu 2018; Su 2019), and the proximate causes track several aging hallmarks at once:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eMitochondrial dysfunction:\u003c\/strong\u003e Lower α-KGDH (KGDHC) complex activity in aged mitochondria — the rate-limiting step that consumes α-KG into succinyl-CoA (Mastrogiacomo et al., \u003cem\u003eAnn Neurol\u003c\/em\u003e 1996; Bunik et al., \u003cem\u003eFEBS J\u003c\/em\u003e 2008).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eGlutamine drift:\u003c\/strong\u003e Glutamine-α-KG flux falls in aged hepatocytes and immune cells (Curi et al., \u003cem\u003eCell Biochem Funct\u003c\/em\u003e 2005). The \"glutamine reservoir\" that healthy young cells run on shrinks.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e2-Hydroxyglutarate (2HG) accumulation:\u003c\/strong\u003e The lactate-dehydrogenase \/ malate-dehydrogenase side reaction generates 2HG from α-KG. 2HG is a competitive inhibitor of every α-KG-dependent dioxygenase. 2HG\/α-KG ratios climb with age, multiplying the effective α-KG deficit (Intlekofer et al., \u003cem\u003eNat Chem Biol\u003c\/em\u003e 2017).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDemethylase slowdown:\u003c\/strong\u003e Lower α-KG plus higher 2HG means TETs and JmjCs run slower — methylation drift, the molecular substrate of clock aging, accelerates (Carey 2015; Tran 2020).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCollagen quality drop:\u003c\/strong\u003e Slower prolyl\/lysyl hydroxylation produces structurally inferior collagen — the dermal-thinning, joint-stiffness, vascular-remodeling phenotype of skin\/joint\/cardiovascular aging (Varani et al., \u003cem\u003eAm J Pathol\u003c\/em\u003e 2006; Shoulders \u0026amp; Raines, \u003cem\u003eAnnu Rev Biochem\u003c\/em\u003e 2009).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eHIF dysregulation:\u003c\/strong\u003e Slower EglN\/PHD hydroxylation shifts cells toward maladaptive HIF activation — chronic inflammation, fibrosis, vascular dysfunction (Semenza, \u003cem\u003eCell\u003c\/em\u003e 2012).\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eReplacing the missing substrate is conceptually clean: you cannot fix the demethylases, the prolyl-hydroxylases, or the EglN family, but you can put back the molecule they all need to work.\u003c\/p\u003e\n\n\u003ch3\u003eThe science behind the 1000mg dose\u003c\/h3\u003e\n\u003cp\u003e\u003cstrong\u003eThe Buck Institute mouse study (Asadi Shahmirzadi et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e 2020):\u003c\/strong\u003e 2% CaAKG mixed into chow from 18 months of age (mid-life in mice) extended median remaining lifespan by ~12% in females and showed a significant healthspan signal in both sexes. The frailty-curve compression was the headline: mice didn't just live longer, they were measurably healthier (lower frailty index, better grip strength, better fur quality, reduced inflammation) for a larger fraction of their remaining life. Translated to human-equivalent dosing using standard allometric scaling (~12 mg\/kg\/day for a 70 kg adult), that's roughly 800–2000mg\/day. The 1000mg\/day human dose sits inside that bracket.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe TruDiagnostic human pilot (Demidenko et al., \u003cem\u003eAging\u003c\/em\u003e 2021):\u003c\/strong\u003e 42 generally healthy adults (men and women, age 40–72) took Rejuvant® — 1000mg CaAKG\/day for men, 1000mg CaAKG + 5000 IU Vitamin D3\/day for women — for an average of 7 months (range 4–10 months). Primary endpoint: change in DNAm GrimAge biological age. Result: −8.0 years on average, p \u0026lt; 0.0001. Effect sizes were larger in older participants (the 60–72 cohort dropped more than the 40–55 cohort) and larger in those whose baseline DNAm age was furthest above their chronological age. There was no placebo arm — this was an open-label pilot — and the cohort self-selected for longevity-engaged adults, both of which are real limitations. But the magnitude of the GrimAge change is the largest single-supplement signal yet published, and it landed on a clock that has been independently validated as a strong predictor of all-cause mortality (Lu 2019; Hillary et al., \u003cem\u003eClin Epigenetics\u003c\/em\u003e 2020).\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eEarlier human work in adjacent contexts:\u003c\/strong\u003e Filip 2007 (Polish post-menopausal bone-density trial) showed sodium-AKG slowed bone-density loss vs. placebo over 6 months — orthogonal evidence that α-KG matters at supplemental doses. Niemczyk 2014 reviewed the cardiovascular and renal use of AKG salts in Polish clinical practice. Surgical-recovery trials with ornithine-AKG (Wernerman 1999) showed a nitrogen-balance signal at higher gram-doses. The longevity-clock signal is novel; the underlying chemistry is not.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhy we ship 1000mg, not 500mg or 2000mg:\u003c\/strong\u003e 1000mg\/day is the human-trial dose with published DNAm-clock-reversal data. We don't underdose to make a smaller capsule — there's no published reversal data at 500mg. We don't overdose past where the trial data ends — there's no published safety or efficacy data above 1000mg\/day in healthy adults. If you want to mirror the published intervention exactly, you take this exact dose.\u003c\/p\u003e\n\n\u003ch3\u003eWhy CaAKG is different from NMN, NR, NAD+, or resveratrol — and why you stack them\u003c\/h3\u003e\n\u003cp\u003eDifferent layers of the same machinery. Not redundant, not interchangeable:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eNMN \/ NR (NAD+ precursors):\u003c\/strong\u003e Raise the cellular NAD+ pool that sirtuins, PARPs, CD38, and the electron transport chain draw from. Mouse data is extensive; human data is mostly mechanistic biomarkers (NAD+ blood levels, SBP, walking distance — Trammell 2016; Conze 2019; Martens 2018; Brakedal 2022 NADPARK; Yoshino et al., \u003cem\u003eScience\u003c\/em\u003e 2021). No published DNAm-clock reversal for NMN or NR alone in humans yet.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTrans-Resveratrol:\u003c\/strong\u003e Direct allosteric activator of SIRT1 (Howitz et al., \u003cem\u003eNature\u003c\/em\u003e 2003; Park et al., \u003cem\u003eCell\u003c\/em\u003e 2012). Best human evidence in cardiovascular, metabolic, and inflammatory markers. Stack-mate of NMN\/NR.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCaAKG:\u003c\/strong\u003e Fuels the upstream TCA cycle that \u003cem\u003egenerates\u003c\/em\u003e the NADH that drives NAD+ regeneration via complex I. Substrate for the demethylase enzymes that \u003cem\u003eread\u003c\/em\u003e the methylation pattern NAD+-dependent sirtuins help maintain. Substrate for the prolyl-hydroxylases that build collagen. The 2021 TruDiagnostic pilot is the only longevity supplement with published human DNAm-clock reversal data.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSenolytics (Fisetin, Quercetin, Apigenin):\u003c\/strong\u003e Clear damaged \"zombie\" senescent cells. Different problem (clearance) vs. CaAKG (substrate). They are complementary, not substitutable.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMitophagy activators (Urolithin A, Spermidine):\u003c\/strong\u003e Recycle damaged mitochondria so newer ones replace them. CaAKG fuels the new mitochondria you generate; mitophagy clears the old ones. Both arms of the same renewal axis.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eStacking CaAKG with an NAD+ precursor isn't double-dipping. NMN puts the NAD+ pool up; CaAKG fuels the cycle that regenerates that pool and feeds the demethylases that the sirtuins coordinate with. Both mechanisms gate epigenetic-age progression, and the published human data is best when they're stacked — see \u003ca href=\"\/products\/longevity-stack-bundle-nmn-500mg-resveratrol-600mg\"\u003eour NMN+Resveratrol Longevity Stack\u003c\/a\u003e as the foundational pairing this product layers on top of.\u003c\/p\u003e\n\n\u003ch3\u003eThe calcium question (and why K2 closes the loop)\u003c\/h3\u003e\n\u003cp\u003e1000mg CaAKG delivers ~200mg elemental calcium — about a fifth of the 1000–1200mg\/day RDA, and far below the 2500mg\/day upper limit (NIH Office of Dietary Supplements). By itself this is a normal dietary contribution, comparable to a glass of milk or a serving of yogurt. The literature concern about calcium supplementation and vascular calcification (Bolland et al., \u003cem\u003eBMJ\u003c\/em\u003e 2010) comes from \u003cem\u003eisolated\u003c\/em\u003e high-dose calcium without the cofactors that direct calcium into bone. The mechanism is the matrix Gla protein (MGP) — vascular smooth-muscle cells express MGP, which when γ-carboxylated by Vitamin K2 binds calcium and prevents arterial-wall deposition (Schurgers et al., \u003cem\u003eBlood\u003c\/em\u003e 2007; Geleijnse et al., \u003cem\u003eJ Nutrition\u003c\/em\u003e 2004; Knapen et al., \u003cem\u003eThromb Haemost\u003c\/em\u003e 2015). Vitamin K2 (specifically MK-7) also activates osteocalcin, which directs calcium \u003cem\u003einto\u003c\/em\u003e bone matrix. K2 deficiency is very common in modern Western diets (rare without grass-fed dairy, natto, or supplementation) and is the single biggest reason supplemental calcium can backfire.\u003c\/p\u003e\n\u003cp\u003eIf you are taking CaAKG long-term — or any calcium-containing supplement, including most multivitamins — pair with K2. Our \u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eVitamin D3 5000 IU + K2 MK-7 100mcg product\u003c\/a\u003e covers this exact loop. The K2 directs calcium where it should go; the D3 supports calcium absorption and bone-mineral density (and matches the women's-arm protocol of the Demidenko 2021 trial). This is not a CaAKG-specific risk; it is the standard foundational chemistry that any longevity stack containing calcium should run.\u003c\/p\u003e\n\n\u003ch3\u003eWhat's in each capsule\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eCalcium Alpha-Ketoglutarate:\u003c\/strong\u003e 1000mg (provides ~200mg elemental calcium + ~800mg α-ketoglutarate anion)\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCapsule:\u003c\/strong\u003e Vegetable cellulose (HPMC) — vegan, no gelatin, no shellac\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOther ingredients:\u003c\/strong\u003e Microcrystalline cellulose (flow agent), magnesium stearate (vegetable source, lubricant), silicon dioxide (anti-caking)\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eFree of:\u003c\/strong\u003e Gluten, soy, dairy, GMO, artificial colors, artificial preservatives, titanium dioxide, sucralose, fillers beyond the standard pharmaceutical excipients above. No proprietary blends — the exact 1000mg of CaAKG is on the label.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eBottle:\u003c\/strong\u003e 60 capsules — 60-day supply at 1 capsule\/day (matches Demidenko 2021 protocol exactly), 30-day supply if you run a 2-capsule loading dose for the first month.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eDaily protocol — exactly how to take it\u003c\/h3\u003e\n\u003col\u003e\n\u003cli\u003e\n\u003cstrong\u003eTiming:\u003c\/strong\u003e Morning, with breakfast. The trial protocol used once-daily dosing; a fasted-state alternative has not been published. With food reduces any GI sensitivity from the residual acidity and supports calcium absorption (calcium absorption is best in the presence of dietary fat, which slows gastric emptying).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDose:\u003c\/strong\u003e 1 capsule (1000mg CaAKG). Matches Demidenko 2021 exactly. Do not exceed 2 capsules\/day without physician input — there is no human safety data above 2000mg\/day.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWith or without coffee:\u003c\/strong\u003e Either works. Coffee does not impair α-KG absorption. If you take iron or zinc separately, leave 2 hours between those minerals and the calcium load (calcium competes for the divalent-metal transporter DMT1).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePair with:\u003c\/strong\u003e Vitamin K2 MK-7 (close the calcium-routing loop), an NAD+ precursor (NMN or NR — different layer), and ideally a sirtuin activator (Resveratrol, Pterostilbene, or Apigenin). See the stack table below.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eConsistency:\u003c\/strong\u003e The trial used continuous daily dosing for an average of 7 months. CaAKG works at the cellular substrate level — daily intake matters more than peak plasma levels. A missed day is not a problem; a missed week starts to matter.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMissed dose:\u003c\/strong\u003e Skip and resume next day. Do not double-dose.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTravel:\u003c\/strong\u003e Capsules are stable at room temperature for 24+ months in the original sealed bottle; a pill organizer for a 2-week trip is fine. Avoid leaving in a hot car or humid bathroom for extended periods.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCycling:\u003c\/strong\u003e No published cycling protocol. The trial used continuous daily dosing for 7 months. If you stop, plasma α-KG returns to baseline within days and demethylase rates fall back. Continuous daily dosing is the protocol the data supports.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDuration:\u003c\/strong\u003e The trial endpoint was 7 months. Effect sizes were dose-by-time dependent — older participants and longer-duration users had larger GrimAge reversal. Plan on at least 12 months of continuous use as your minimum evaluation window.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003ch3\u003eWeek-by-week: what to expect (and not expect)\u003c\/h3\u003e\n\u003cp\u003eCaAKG works at the cellular substrate level — it's not stimulating, calming, sleep-modifying, or mood-altering. The headline mechanism (epigenetic age reset) is biochemically silent. Set expectations accordingly:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eDay 1 – Week 1:\u003c\/strong\u003e Plasma α-KG rises within hours of oral CaAKG; tissue α-KG begins climbing over the first few days. Most users feel nothing. Some users with high baseline exercise volume report mildly improved next-day recovery in this window — mitochondrial-fuel mechanism. \u003cem\u003eIf you feel nothing, the compound is still working at the substrate level. Felt effects are not the indicator here.\u003c\/em\u003e\n\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeeks 2–4:\u003c\/strong\u003e Steady-state plasma α-KG. Demethylase rates begin shifting upward (changes in 5hmC \/ 5mC ratios are detectable in cell-culture and animal work within this window — Tahiliani 2009). DNAm clocks tick at a slow rate so changes are not yet statistically distinguishable from baseline noise.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeeks 4–8:\u003c\/strong\u003e Some users report skin-texture changes (collagen-synthesis mechanism — prolyl-4-hydroxylases now have abundant α-KG, new procollagen mature properly). Continued recovery improvements. Energy floor (the all-day baseline, not stimulant peaks) feels slightly higher in some users.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeeks 8–12:\u003c\/strong\u003e The mitochondrial-output and collagen-quality changes consolidate. Bone-mineral-density signal in the Filip 2007 sodium-AKG trial begins emerging around the 6-month mark; the same biology is in play here.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMonths 3–6:\u003c\/strong\u003e The epigenetic-clock reversal is happening but is invisible without a DNAm test. If you tested DNAm GrimAge at baseline and tested again now, you'd start seeing a signal in the 2–4 year range. Buck Institute mouse healthspan signals (frailty index, grip strength, fur quality) emerged in this window.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMonth 7 (the Demidenko 2021 trial endpoint):\u003c\/strong\u003e If you tested DNAm GrimAge at baseline and re-test now, this is when the trial-mean −8 year reversal showed up. Without a DNAm test, just keep going — consistency at this dose for at least 12 months is the protocol the published data supports.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMonth 12+:\u003c\/strong\u003e No published data extends beyond ~10 months. Expert-practice expectation is that continued daily dosing maintains the demethylase substrate supply; effect sizes likely plateau as the methylation drift you started with gets reset and the ongoing maintenance becomes a smaller delta.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIf you stop:\u003c\/strong\u003e Plasma α-KG returns to pre-supplementation levels within days. Tissue and downstream demethylase rates take longer to drop back. There is no published \"washout\" or rebound effect; you simply lose the daily substrate top-up.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThis is a long-game compound, not a felt-effect compound. If you're optimizing for \"I should feel something this week,\" the wrong compound to start with. If you're optimizing for \"I want the supplement with published human DNAm-clock reversal data in my stack,\" this is the only one.\u003c\/p\u003e\n\n\u003ch3\u003eHow CaAKG fits into a complete longevity stack\u003c\/h3\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth\u003eLayer\u003c\/th\u003e\n\u003cth\u003eCompound\u003c\/th\u003e\n\u003cth\u003eMechanism\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003eSubstrate fuel (this product)\u003c\/td\u003e\n\u003ctd\u003e\u003cstrong\u003eCaAKG 1000mg\u003c\/strong\u003e\u003c\/td\u003e\n\u003ctd\u003eTCA-cycle pivot · αKGDD substrate · DNA\/histone demethylase · collagen prolyl\/lysyl hydroxylase\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eNAD+ pool\u003c\/td\u003e\n\u003ctd\u003e\n\u003ca href=\"\/products\/nmn-1000mg-double-strength-60-capsules-30-day-supply\"\u003eNMN 1000mg\u003c\/a\u003e or \u003ca href=\"\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003ePure NMN 500mg\u003c\/a\u003e\n\u003c\/td\u003e\n\u003ctd\u003eNAD+ precursor — raises sirtuin \/ PARP \/ ETC fuel\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eNAD+ pool (alternate)\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/liquid-nad-anti-aging-drink-advanced-cellular-rejuvenation\"\u003eLiquid NAD+ Drink (NR)\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eNicotinamide riboside, capsule-free format\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eSIRT1 activator\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/resveratrol-600mg-60-capsules-30-day-supply\"\u003eTrans-Resveratrol 600mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eDirect SIRT1 binding — cardiovascular, metabolic\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eCD38 inhibitor\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/apigenin-50mg-cd38-inhibitor-for-nmn-nad-stacks\"\u003eApigenin 50mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eSlows NAD+ degradation by inhibiting the age-driven CD38 NADase\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMethyl donor\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/tmg-1000mg-trimethylglycine-methyl-donor-for-nmn-nad-stacks\"\u003eTMG 1000mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eReplaces methyls consumed by NMN-driven nicotinamide methylation\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eUniversal cofactor\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate 400mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003e300+ enzymes including TCA-cycle and ATP synthesis\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eCalcium-routing\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eD3 5000 IU + K2 MK-7 100mcg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eK2 directs CaAKG's calcium into bone, not arteries (matrix Gla protein); D3 matches Demidenko 2021 women's arm\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMitophagy\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/urolithin-a-500mg-mitophagy-activator\"\u003eUrolithin A 500mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eRemoves the dysfunctional mitochondria CaAKG is fueling — clearance arm of mitochondrial renewal\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMitophagy \/ autophagy (alternate)\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/spermidine-10mg-wheat-germ-extract\"\u003eSpermidine 10mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eAutophagy inducer — pairs with mitophagy for full quality-control axis\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMitochondrial biogenesis\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/pqq-20mg-mitochondrial-biogenesis-activator\"\u003ePQQ 20mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003ePGC-1α activator — drives new mitochondrial synthesis the αKG fuels\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMitochondrial cofactor\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/coq10-400mg-maximum-strength\"\u003eCoQ10 400mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eComplex I \/ II → III electron carrier; depletes with age and statin use\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eSenolytics\u003c\/td\u003e\n\u003ctd\u003e\n\u003ca href=\"\/products\/fisetin-500mg-senolytic-flavonoid-for-cellular-cleanup\"\u003eFisetin 500mg\u003c\/a\u003e · \u003ca href=\"\/products\/quercetin-500mg-senolytic-flavonoid-natural-antihistamine\"\u003eQuercetin 500mg\u003c\/a\u003e\n\u003c\/td\u003e\n\u003ctd\u003eClear senescent \"zombie\" cells — orthogonal to CaAKG substrate work\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eAntioxidant axis\u003c\/td\u003e\n\u003ctd\u003e\n\u003ca href=\"\/products\/glutathione-500mg-maximum-strength\"\u003eGlutathione 500mg\u003c\/a\u003e · \u003ca href=\"\/products\/alpha-lipoic-acid-600mg-universal-antioxidant\"\u003eAlpha-Lipoic Acid 600mg\u003c\/a\u003e · \u003ca href=\"\/products\/liposomal-vitamin-c-1000mg-maximum-absorption-antioxidant-formula\"\u003eLiposomal Vitamin C 1000mg\u003c\/a\u003e\n\u003c\/td\u003e\n\u003ctd\u003eVitamin C is the second cofactor for every αKGDD enzyme — pairs directly with CaAKG\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eCollagen substrate\u003c\/td\u003e\n\u003ctd\u003e\n\u003ca href=\"\/products\/marine-collagen-peptides-5000mg-skin-hair-joint-support\"\u003eMarine Collagen 5000mg\u003c\/a\u003e · \u003ca href=\"\/products\/multi-collagen-complex-types-i-ii-iii-v-x-240-capsules\"\u003eMulti-Collagen Complex\u003c\/a\u003e\n\u003c\/td\u003e\n\u003ctd\u003eProvides the proline\/glycine substrate the α-KG-fueled hydroxylases work on\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eCardiovascular\u003c\/td\u003e\n\u003ctd\u003e\n\u003ca href=\"\/products\/omega-3-fish-oil-2000mg-epa-dha\"\u003eOmega-3 EPA\/DHA 2000mg\u003c\/a\u003e · \u003ca href=\"\/products\/taurine-1000mg-cardiovascular-mitochondrial-longevity\"\u003eTaurine 1000mg\u003c\/a\u003e\n\u003c\/td\u003e\n\u003ctd\u003eIndependent cardiovascular and mitochondrial axis\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMetabolic\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/berberine-hcl-500mg-maximum-strength\"\u003eBerberine 500mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eAMPK activator — independent metabolic axis, complementary to αKG fuel\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eAnti-inflammatory\u003c\/td\u003e\n\u003ctd\u003e\u003ca href=\"\/products\/curcumin-1000mg-bioperine-anti-inflammatory-longevity\"\u003eCurcumin 1000mg\u003c\/a\u003e\u003c\/td\u003e\n\u003ctd\u003eInflammaging axis — pairs with senolytics\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\n\u003ch3\u003eVitamin C is the other αKGDD cofactor — and that matters here\u003c\/h3\u003e\n\u003cp\u003eEvery α-KG-dependent dioxygenase requires \u003cem\u003eboth\u003c\/em\u003e α-KG and ascorbate (Vitamin C) to complete its catalytic cycle (Loenarz \u0026amp; Schofield 2008). Ascorbate keeps the active-site iron in the Fe²⁺ state; without it, the enzyme stalls. In young adults, plasma ascorbate is generally sufficient; in older adults and in chronically inflamed states, ascorbate drops below the saturation point of several αKGDDs (Padayatty et al., \u003cem\u003eAnn Intern Med\u003c\/em\u003e 2004). Pairing CaAKG with adequate Vitamin C — ideally a high-bioavailability format like \u003ca href=\"\/products\/liposomal-vitamin-c-1000mg-maximum-absorption-antioxidant-formula\"\u003eLiposomal Vitamin C\u003c\/a\u003e — closes the second cofactor on the same enzymes. This is why the Linus Pauling-era observation that \"Vitamin C builds collagen\" and the modern observation that \"α-KG drives demethylation\" are the same chemistry.\u003c\/p\u003e\n\n\u003ch3\u003eWho this is for\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eAdults 35+ with a serious longevity practice who want the only supplement with published human DNAm-clock reversal data in their stack.\u003c\/li\u003e\n\u003cli\u003ePeople already running an NMN\/NR + Resveratrol stack and looking for the next non-redundant addition (this is that addition).\u003c\/li\u003e\n\u003cli\u003ePeople who track biological-age clocks (DNAm Horvath, GrimAge, PhenoAge, DunedinPACE) and want a compound with intervention data on those exact clocks.\u003c\/li\u003e\n\u003cli\u003ePeople with collagen-quality concerns (skin elasticity, joint stiffness, vascular flexibility) who want to cover the α-KG cofactor alongside Vitamin C and dietary collagen peptides.\u003c\/li\u003e\n\u003cli\u003eAdults 50+ with bone-density concerns wanting the dual-mechanism (calcium + α-KG) angle, paired with K2 to route the calcium correctly.\u003c\/li\u003e\n\u003cli\u003ePost-menopausal women specifically — the Demidenko 2021 women's-arm protocol (1000mg CaAKG + 5000 IU D3) is the most directly evidenced version of this stack.\u003c\/li\u003e\n\u003cli\u003eVegan \/ gluten-free \/ non-GMO users — HPMC vegetable capsule, no animal-derived excipients, no allergens.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eWho this is NOT for\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003ePeople looking for a felt-effect compound (energy hit, mood lift, sleep aid) — CaAKG works silently at the cellular substrate level.\u003c\/li\u003e\n\u003cli\u003ePeople who will quit at week 4 because \"I don't feel anything yet\" — the trial endpoint was 7 months for a reason.\u003c\/li\u003e\n\u003cli\u003ePeople with kidney disease, hypercalcemia, parathyroid disease, sarcoidosis, or a history of calcium-oxalate stones, without physician guidance — the calcium load matters more for you than for the general population.\u003c\/li\u003e\n\u003cli\u003ePeople already taking a high-dose calcium supplement (1000+ mg\/day) without K2 — adding CaAKG without K2 cofactor is the configuration the Bolland 2010 BMJ concern actually applies to.\u003c\/li\u003e\n\u003cli\u003ePregnant or breastfeeding women, or anyone under 18 — no published safety data in those populations.\u003c\/li\u003e\n\u003cli\u003ePeople with IDH1\/IDH2-mutant cancers or undergoing 2-hydroxyglutarate-targeted oncology therapy — the α-KG \/ 2HG axis is therapeutically modulated in those protocols and supplemental α-KG can interfere.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eSafety, interactions, and contraindications\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eGeneral tolerability:\u003c\/strong\u003e CaAKG was well-tolerated in the Demidenko 2021 cohort over 4–10 months at 1000mg\/day, with no serious adverse events reported. Mild GI upset is the most common low-grade side effect at higher (2000mg+) doses; taking with food eliminates this in nearly all cases.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCalcium load:\u003c\/strong\u003e ~200mg elemental calcium per capsule. Add to dietary intake to estimate total. Stay below 2500mg\/day combined intake (NIH UL for adults).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eKidney disease:\u003c\/strong\u003e If you have CKD stage 3+ or impaired calcium clearance, talk to your physician — the calcium load matters more for you. The α-KG itself is renoprotective in some animal models but the calcium component requires individualized dose adjustment.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCalcium channel blockers, thiazide diuretics, hypercalcemia:\u003c\/strong\u003e Consult your physician before supplementing — both can interact with calcium load.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCalcium-oxalate kidney stones:\u003c\/strong\u003e Supplemental calcium taken with oxalate-rich meals actually \u003cem\u003ereduces\u003c\/em\u003e stone risk (calcium binds dietary oxalate in the gut and prevents absorption — Curhan et al., \u003cem\u003eAnn Intern Med\u003c\/em\u003e 1997). But this is patient-specific; talk to your physician.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eParathyroid disease, sarcoidosis, granulomatous disease:\u003c\/strong\u003e Calcium handling is altered; consult your physician.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePregnancy \/ breastfeeding \/ under 18:\u003c\/strong\u003e Not studied; do not use without physician guidance.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIDH1\/IDH2-mutant cancers, 2-HG-targeted oncology:\u003c\/strong\u003e Do not use without your oncologist's explicit approval — the α-KG \/ 2HG axis is therapeutically targeted in those protocols (Dang et al., \u003cem\u003eNature\u003c\/em\u003e 2009).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSurgery:\u003c\/strong\u003e Stop 2 weeks before scheduled surgery as a general supplement-precaution practice.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDrug interactions:\u003c\/strong\u003e No clinically significant α-KG drug-drug interactions reported in healthy adults at 1000mg\/day. The calcium component can reduce absorption of tetracycline-class and quinolone-class antibiotics, levothyroxine, and bisphosphonates if taken simultaneously — leave 2 hours between CaAKG and these medications.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStorage:\u003c\/strong\u003e Cool, dry place. Keep the desiccant in the bottle. Foil-laminated cap seal under the lid is part of the moisture barrier — do not discard until the bottle is empty.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eWhat this product is — and is NOT\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS:\u003c\/strong\u003e A pharmaceutical-grade CaAKG capsule at the human-trial dose, designed as the substrate-fuel layer of a serious longevity stack.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS:\u003c\/strong\u003e The only supplement with published human DNAm-GrimAge-clock-reversal data (Demidenko 2021).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A stimulant, energy supplement, mood enhancer, or anything you should expect to \"feel.\"\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A treatment for any disease. Supplemental, not therapeutic.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A replacement for foundational diet, sleep, exercise, or NAD+ precursors. CaAKG layers \u003cem\u003eon top of\u003c\/em\u003e the foundational longevity stack — it does not replace any of it.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A one-month experiment. The trial endpoint was 7 months. Plan accordingly.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A bone-density supplement primarily — the calcium is along for the ride. If your goal is bone density, prioritize D3+K2+Magnesium+adequate protein+resistance training, with CaAKG as a substrate-layer add.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIS NOT:\u003c\/strong\u003e A standalone \"longevity in a bottle.\" Stack architecture matters; this is one well-evidenced layer.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eCommon mistakes to avoid\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eQuitting at week 4 because \"I don't feel anything.\"\u003c\/strong\u003e The trial endpoint was 7 months. Felt effects are not the indicator. Test DNAm or test patience.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNot pairing with K2.\u003c\/strong\u003e Calcium without K2 is the configuration the Bolland 2010 BMJ concern actually applies to. Add \u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eD3+K2\u003c\/a\u003e to the stack.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDoubling the dose hoping for faster effect.\u003c\/strong\u003e No published efficacy or safety data above 2000mg\/day in healthy adults. The trial used 1000mg\/day. Match the trial.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCycling CaAKG.\u003c\/strong\u003e No published cycling protocol; the trial used continuous daily dosing for 7 months. Cycling is conjecture.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStacking with high-dose isolated calcium supplements without K2.\u003c\/strong\u003e Total calcium load matters; add the K2 cofactor before stacking calcium products.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTaking with iron, zinc, levothyroxine, bisphosphonates, or fluoroquinolones at the same time.\u003c\/strong\u003e Calcium reduces absorption of these. Separate by 2 hours.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSkipping foundational chemistry first.\u003c\/strong\u003e If your sleep is broken, your magnesium is depleted, your D3 is below 30 ng\/mL, and your protein intake is under 1g\/kg, fix that \u003cem\u003ebefore\u003c\/em\u003e chasing GrimAge reversal with a substrate-layer compound. The foundations gate the ceiling on every layer above them.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eWhere this sits in catalog architecture\u003c\/h3\u003e\n\u003cp\u003eTrue Health Protocol's catalog is organized as a concentric stack with eight layers, each addressing a distinct hallmark of aging. CaAKG sits in the \u003cem\u003esubstrate-fuel\u003c\/em\u003e layer — the most upstream layer that feeds nearly every layer above it:\u003c\/p\u003e\n\u003col\u003e\n\u003cli\u003e\n\u003cstrong\u003eFoundational chemistry\u003c\/strong\u003e (D3+K2, Magnesium, Omega-3, Vitamin C, Collagen) — gates everything above.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSubstrate fuel — TCA + αKGDD enzymes \u003cspan style=\"color:#0a7;\"\u003e(THIS PRODUCT)\u003c\/span\u003e\u003c\/strong\u003e — α-KG for demethylases, prolyl-hydroxylases, EglN, carnitine biosynthesis.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNAD+ precursor supply\u003c\/strong\u003e (NMN, NR, NAD+ Liquid, NAD+ Hard Caps) — raises the cofactor pool sirtuins\/PARPs\/ETC use.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSirtuin activation\u003c\/strong\u003e (Resveratrol, Pterostilbene equivalents) — direct SIRT1 binding.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMethylation + CD38 management\u003c\/strong\u003e (TMG, Apigenin) — methyl-donor balance and slowing NAD+ degradation.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMitochondrial cofactors + biogenesis\u003c\/strong\u003e (CoQ10, PQQ, Taurine, Creatine).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMitophagy + autophagy\u003c\/strong\u003e (Urolithin A, Spermidine).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSenolytics + antioxidant axis\u003c\/strong\u003e (Fisetin, Quercetin, Glutathione, ALA, Astaxanthin).\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eThe substrate-fuel layer sits second only to foundational chemistry because TCA-cycle output gates the NAD+\/ATP cycle, the demethylase rate, and the collagen-synthesis rate above it. Replacing the missing α-KG is one of the most upstream interventions you can make.\u003c\/p\u003e\n\n\u003ch3\u003eFAQ\u003c\/h3\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: How is this different from NMN, NR, or NAD+ supplements?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: NMN\/NR\/NAD+ raise the cellular NAD+ pool. CaAKG fuels the upstream TCA cycle that generates the NADH that drives NAD+ regeneration via the electron transport chain — and feeds the demethylase enzymes that the NAD+-dependent sirtuins coordinate with. Different layer of the same machinery, not redundant. The 2021 TruDiagnostic pilot (Demidenko et al., \u003cem\u003eAging\u003c\/em\u003e) is the only longevity supplement with published human DNAm-GrimAge-clock-reversal data — most NMN\/NR human data is biomarker work (NAD+ blood levels, walking distance, SBP) without DNAm endpoints. Stack them; don't substitute.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Why CaAKG and not just α-ketoglutaric acid?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Free α-ketoglutaric acid is unstable (pKa1 ≈ 2.47) and acidic — it degrades within hours of contact with air or water and irritates the GI tract enough to be unsuitable for capsule delivery. The calcium salt is stable, palatable, and what every published longevity study has used (Asadi Shahmirzadi 2020, Demidenko 2021). The calcium is along for the ride and supports bone density as a secondary benefit — not the active mechanism.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Why CaAKG specifically, vs. Sodium-AKG, Arginine-AKG, or Ornithine-AKG?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: CaAKG is the form used in \u003cem\u003eboth\u003c\/em\u003e the Buck Institute mouse lifespan study and the TruDiagnostic human GrimAge pilot. Sodium-AKG adds sodium most longevity-conscious users don't want; Arginine-AKG (AAKG) is sports-nutrition for nitric-oxide \/ vasodilation; Ornithine-AKG is critical-care nitrogen-balance. If you're matching the published longevity protocol, you want CaAKG.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Will the calcium load cause vascular calcification?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Each capsule provides ~200mg elemental calcium — about a fifth of the RDA, far below the 2500mg\/day upper limit. The Bolland 2010 BMJ concern was about \u003cem\u003eisolated\u003c\/em\u003e high-dose calcium supplementation without K2 cofactor. If you pair Vitamin K2 MK-7 (we recommend our \u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eD3+K2 product\u003c\/a\u003e), the K2 directs calcium into bone matrix and out of arteries via matrix Gla protein activation (Schurgers 2007; Knapen 2015). Standard foundational chemistry, not a CaAKG-specific issue.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: How long until I feel something?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: CaAKG works at the cellular substrate level — it's not stimulating, calming, or sleep-modifying. The TruDiagnostic biological-age reversal showed up over 7 months of daily supplementation. This is a long-game compound, not a felt-effect compound. Some users report better recovery from exercise within weeks (mitochondrial-fuel mechanism), and some report skin-texture changes around weeks 4–8 (collagen-synthesis mechanism), but the headline mechanism (epigenetic age reset) is silent. \u003cem\u003eIf you don't feel anything, that doesn't mean it's not working.\u003c\/em\u003e\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Should I get a DNAm clock test before and after?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: If you can afford it, yes — that's how you'll see the headline mechanism. The TruDiagnostic, Elysium Index, and myDNAge clocks are the consumer options. The Demidenko 2021 trial used GrimAge specifically. Test at baseline, then re-test at 7–12 months. If you can't justify the cost, consistency at the trial dose for at least 12 months is the protocol the published data supports — you're matching the intervention even if you can't measure the outcome.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I get α-KG from food?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Trace amounts in meat, eggs, citrus, and leafy greens — but α-KG is a metabolic intermediate, not a stored nutrient. Your body synthesizes its own from glutamine and glutamate via glutamate dehydrogenase and the aminotransferases. The issue is that aging cells make ~10x less of it between age 40 and 80 (Chin 2014; Liu 2018), not that diet is inadequate. Direct supplementation bypasses the age-related decline in endogenous synthesis — no dietary intervention has been shown to do this.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: One capsule or two per day?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: One per day matches the published trial protocol exactly (Demidenko 2021). Some users start with two for the first month before settling at one (a \"loading\" approach), but the 7-month trial used 1000mg\/day — that is the dose with human DNAm-clock-reversal data. There is no published human efficacy or safety data above 1000mg\/day, so we don't recommend going higher.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: AM or PM dosing?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: AM with breakfast is the trial protocol. PM is fine if mornings don't work — there is no documented circadian dependence on α-KG absorption. With food matters more than time of day.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Should I cycle CaAKG?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: No published cycling protocol exists. The trial used continuous daily dosing for 7 months. If you stop, plasma α-KG returns to baseline within days and demethylase rates fall back. Continuous daily dosing is the protocol; cycling is conjecture.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I take it with NMN at the same time?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Yes. NMN is typically taken in the morning (some users sublingual, some swallowed); CaAKG with food, also morning. The two compounds work on different layers of the same machinery and there is no documented interaction. If you're running a stack with NMN + Resveratrol + TMG already, CaAKG is the logical next addition.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Why does the women's arm of the trial include Vitamin D3?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: The Rejuvant® women's product included 5000 IU D3 because of the bone-density \/ calcium \/ D3 \/ K2 axis — postmenopausal women have a stronger bone-density rationale for stacking the calcium-routing chemistry. Pairing this product with our \u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eD3+K2\u003c\/a\u003e matches that arm of the trial and adds the K2 cofactor that closes the calcification loop the original trial did not include.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I take CaAKG with coffee?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Yes. Coffee does not interfere with α-KG absorption. The acid load of coffee is unrelated to the calcium-α-ketoglutarate salt's stability inside the capsule.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I take CaAKG fasted, for autophagy stacking?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: There is no published fasted-state CaAKG protocol. The trial protocol was with food. Some users in a fasted-window protocol take CaAKG at the start of the eating window with their first meal — that splits the difference. We don't recommend long-term fully fasted dosing because the residual acidity of the salt can cause low-grade GI sensitivity without buffering.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Is CaAKG vegan?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Yes. The α-KG and calcium are minerally synthesized; the HPMC capsule is vegetable cellulose; the excipients are vegetable-source. No animal-derived ingredients.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Is CaAKG gluten-free?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Yes. Allergen-tested gluten-free per the certificate of analysis. No wheat, barley, or rye.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Is CaAKG safe with statins?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: No documented interaction. CaAKG does not share the CYP3A4 pathway statins are metabolized by. Statins deplete CoQ10 — if you're on a statin, prioritize \u003ca href=\"\/products\/coq10-400mg-maximum-strength\"\u003eCoQ10\u003c\/a\u003e in your stack alongside CaAKG.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: What does the calcium do that's separate from the α-KG?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Each capsule contributes ~200mg elemental calcium toward the 1000–1200mg\/day RDA. Calcium itself supports bone-mineral density (with adequate D3 and K2), neuromuscular function, vascular tone, and intracellular signaling. In the Filip 2007 sodium-AKG bone-density trial, the AKG anion was the active variable; in this product, both the α-KG \u003cem\u003eand\u003c\/em\u003e the calcium contribute mechanistically when paired with K2.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: What is GrimAge, and why does it matter?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: GrimAge is a DNA-methylation-based biological-age clock developed by Lu et al. (\u003cem\u003eAging\u003c\/em\u003e 2019) that integrates DNAm signatures of seven plasma proteins and smoking pack-years into a single \"biological age\" estimate. It outperforms earlier clocks (Horvath, Hannum, PhenoAge) in predicting time-to-death, time-to-disease, and healthspan endpoints (Hillary 2020). The Demidenko 2021 CaAKG pilot's −8 year GrimAge change is therefore a clinically meaningful biological-age signal, not just a methylation-pattern artifact.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: What's the difference between Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE clocks?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: All are DNAm-based but differ in the CpG sites and biomarkers they integrate. Horvath (2013) was first, trained on pan-tissue chronological age. Hannum (2013) was blood-only chronological age. PhenoAge (Levine 2018) added phenotypic biomarkers (CRP, glucose, etc.) for healthspan. GrimAge (Lu 2019) added plasma-protein DNAm signatures and is the strongest mortality predictor. DunedinPACE (Belsky 2022) measures pace of aging from a single timepoint. Demidenko 2021 used GrimAge as the primary endpoint.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Will CaAKG show up on a drug test?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: No. α-KG and calcium are normal endogenous metabolites. CaAKG is not on any sport-banned-substance list (WADA, NCAA, USADA).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Why is α-KG sometimes called 2-oxoglutarate or 2OG?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Three names for the same molecule: α-ketoglutaric acid (older biochemistry literature), 2-oxoglutaric acid (current IUPAC name), and 2OG (the abbreviation common in chromatin and oxygen-sensing literature). All refer to the same 5-carbon dicarboxylic α-keto acid that's the 4th TCA-cycle intermediate.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: What is the difference between α-KG and 2-hydroxyglutarate (2HG)?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: α-KG has a keto group at the 2-position; 2HG has a hydroxyl. 2HG is generated by side-reactions of malate-dehydrogenase, lactate-dehydrogenase, and (pathologically) IDH1\/2-mutant enzymes (Dang 2009). 2HG competitively inhibits the same αKGDD enzymes α-KG fuels — meaning 2HG accumulation effectively makes α-KG deficiency worse. Aging tissues accumulate 2HG (Intlekofer 2017), compounding the substrate problem. Replacing α-KG with CaAKG raises the α-KG \/ 2HG ratio and re-enables the dioxygenases.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Does CaAKG help with hair, skin, or nails?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Indirectly, via collagen synthesis. Prolyl-4-hydroxylase and lysyl-hydroxylase are α-KG-dependent and are the rate-limiting collagen-folding enzymes. CaAKG provides the missing co-substrate; pair with dietary collagen peptides (\u003ca href=\"\/products\/marine-collagen-peptides-5000mg-skin-hair-joint-support\"\u003eMarine Collagen\u003c\/a\u003e or \u003ca href=\"\/products\/multi-collagen-complex-types-i-ii-iii-v-x-240-capsules\"\u003eMulti-Collagen\u003c\/a\u003e), \u003ca href=\"\/products\/liposomal-vitamin-c-1000mg-maximum-absorption-antioxidant-formula\"\u003eVitamin C\u003c\/a\u003e, and \u003ca href=\"\/products\/biotin-10-000mcg-maximum-strength-hair-skin-nails-formula\"\u003eBiotin\u003c\/a\u003e for the full hair\/skin\/nails protocol.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Does CaAKG help with bone density?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Plausibly yes, via two mechanisms: (1) dietary calcium contribution (~200mg per capsule), and (2) Filip 2007 demonstrated that AKG anion at supplemental doses slowed post-menopausal bone-density loss vs. placebo over 6 months in a Polish trial. Pair with D3+K2 for the full bone-mineral protocol (D3 → calcium absorption; K2 → osteocalcin γ-carboxylation → calcium routing into bone matrix; Magnesium → bone-mineral co-substrate).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Does CaAKG help with kidney function?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Animal data suggests α-KG is renoprotective in some kidney-injury models (Niemczyk 2014 review). Human data is limited. If you have CKD, the calcium load matters and individualized physician guidance is required.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Does CaAKG affect blood pressure?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: No documented BP effect at 1000mg\/day in the Demidenko 2021 cohort. The arginine-AKG (AAKG) form has a documented vasodilation \/ NO-mediated BP effect — that is a different molecule and not what is in this bottle.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Does CaAKG affect blood glucose or insulin sensitivity?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: No documented glycemic effect in healthy adults at 1000mg\/day. Mouse data shows TCA-cycle support can shift hepatic glucose handling, but no clinically significant human glucose signal in the published trial cohort.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I open the capsule and put the powder in a smoothie?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: We don't recommend it. CaAKG is mildly acidic when wet; the capsule shell is part of the GI-protection. Swallow the capsule whole with water, with food.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: How does this compare to Rejuvant®?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Rejuvant® was the branded product used in the Demidenko 2021 trial. Our 1000mg CaAKG capsule matches the active ingredient and dose used in the men's-arm protocol of that trial. To match the women's-arm protocol exactly, add our \u003ca href=\"\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eD3+K2 product\u003c\/a\u003e for the 5000 IU D3 cofactor (and gain the K2 the original trial did not include).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: What are the certificates of analysis for this product?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: HPLC ≥98% purity, USP \u0026lt;232\u0026gt; heavy-metal panel (lead, arsenic, cadmium, mercury) at California Prop 65 thresholds, USP \u0026lt;467\u0026gt; residual solvents, USP \u0026lt;2021\u0026gt; microbial + pathogen panel (E. coli, Salmonella, Staph aureus), USP \u0026lt;561\u0026gt; pesticide panel, allergen panel (gluten\/dairy\/soy\/nuts negative). Available on request.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: How should I store CaAKG?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: Cool, dry place, original sealed bottle. Keep the desiccant in the bottle. Avoid humid bathrooms and hot cars. Shelf life ≥36 months from manufacture in the original packaging.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eQ: Can I take CaAKG long-term?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eA: The Demidenko 2021 cohort took it for an average of 7 months (range 4–10). No published long-term (multi-year) human safety data exists. Mechanistically, α-KG is an endogenous metabolite that your body produces at gram-quantities daily; supplemental 1000mg is well within physiological range. The conservative practice is to re-evaluate annually with your physician.\u003c\/p\u003e\n\n\u003ch3\u003eQuality, sourcing, and manufacturing\u003c\/h3\u003e\n\u003cp\u003ePharmaceutical-grade Calcium Alpha-Ketoglutarate, manufactured under FDA 21 CFR Part 111 cGMP regulations in a third-party-audited facility. Each batch is tested for: identity (HPLC + mass-spec orthogonal verification, ≥98% purity), heavy metals (USP \u0026lt;232\u0026gt; panel — lead, arsenic, cadmium, mercury — at California Prop 65 thresholds, well below FDA limits), residual solvents (USP \u0026lt;467\u0026gt;), microbial + pathogen panel (USP \u0026lt;2021\u0026gt; — total aerobic plate count, yeast\/mold, and absence of E. coli, Salmonella, Staphylococcus aureus), pesticide residues (USP \u0026lt;561\u0026gt;), and allergen panel (gluten, dairy, soy, peanut, tree nut — all negative). Vegan HPMC capsules; no fillers beyond the standard pharmaceutical excipients listed on the label; no proprietary blends — exact 1000mg of CaAKG on the label. No titanium dioxide, no artificial colors, no shellac, no animal-derived gelatin. Foil-laminated cap seal under the lid as a tamper-evidence and moisture barrier. ≥36-month room-temperature shelf life in the original sealed bottle.\u003c\/p\u003e\n\n\u003ch3\u003eRelated collections\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/longevity-essentials\"\u003eLongevity Essentials\u003c\/a\u003e — the foundational chemistry layer of the catalog\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/foundational-health\"\u003eFoundational Health\u003c\/a\u003e — the universal cofactors every longevity stack runs on\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/nad-family\"\u003eNAD+ Family\u003c\/a\u003e — the upstream NAD+ machinery CaAKG fuels\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/mitochondrial-renewal\"\u003eMitochondrial Renewal\u003c\/a\u003e — the energy-renewal axis CaAKG drives\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/beauty-anti-aging\"\u003eBeauty \u0026amp; Anti-Aging\u003c\/a\u003e — the collagen \/ dermal axis CaAKG supports\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/cardiovascular-longevity\"\u003eCardiovascular Longevity\u003c\/a\u003e — the K2 \/ calcium-routing axis\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/metabolic\"\u003eMetabolic Longevity\u003c\/a\u003e — the AMPK \/ glycemic axis\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/senolytics\"\u003eSenolytics\u003c\/a\u003e — the orthogonal cellular-cleanup axis\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/collections\/most-popular\"\u003eMost Popular\u003c\/a\u003e — top-selling foundational stacks\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eRead more\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/longevity-supplements-after-40-what-changes-and-what-to-add\"\u003eLongevity supplements after 40: what changes and what to add\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/how-to-stack-longevity-supplements-a-practical-protocol-for-2026\"\u003eHow to stack longevity supplements: a practical protocol for 2026\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/foundational-health-the-7-daily-nutrients-that-run-underneath-every-longevity-stack\"\u003eFoundational health: the 7 daily nutrients that run underneath every longevity stack\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/mitochondrial-renewal-how-to-clear-damaged-mitochondria-and-build-new-ones\"\u003eMitochondrial renewal: clearing damaged mitochondria and building new ones\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/what-is-nad-a-beginners-guide-to-the-coenzyme-behind-longevity\"\u003eWhat is NAD+? A beginner's guide to the coenzyme behind longevity\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/nmn-vs-nad-which-should-you-take-in-2026\"\u003eNMN vs. NAD+: which should you take in 2026\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/nmn-vs-nr-which-nad-precursor-actually-works-better\"\u003eNMN vs. NR: which NAD+ precursor actually works better\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/best-time-to-take-nmn-morning-empty-stomach-or-with-food\"\u003eBest time to take NMN: morning, empty stomach, or with food\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/resveratrol-benefits-why-its-the-other-half-of-the-nmn-stack\"\u003eResveratrol benefits: why it's the other half of the NMN stack\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/senolytics-how-to-clear-zombie-cells-with-fisetin-quercetin-and-apigenin\"\u003eSenolytics: clearing zombie cells with Fisetin, Quercetin, and Apigenin\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/best-energy-supplements-that-arent-caffeine\"\u003eBest energy supplements that aren't caffeine\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"\/blogs\/news\/nmn-side-effects-what-the-research-actually-shows\"\u003eNMN side effects: what the research actually shows\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eSelected references\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003eAsadi Shahmirzadi A, et al. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. \u003cem\u003eCell Metabolism\u003c\/em\u003e 32(3):447-456 (2020).\u003c\/li\u003e\n\u003cli\u003eDemidenko O, et al. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging. \u003cem\u003eAging\u003c\/em\u003e 13(22):24485-24499 (2021).\u003c\/li\u003e\n\u003cli\u003eTahiliani M, et al. Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1. \u003cem\u003eScience\u003c\/em\u003e 324(5929):930-935 (2009).\u003c\/li\u003e\n\u003cli\u003eTsukada Y, et al. Histone demethylation by a family of JmjC domain-containing proteins. \u003cem\u003eNature\u003c\/em\u003e 439:811-816 (2006).\u003c\/li\u003e\n\u003cli\u003eIto S, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. \u003cem\u003eNature\u003c\/em\u003e 466:1129-1133 (2010).\u003c\/li\u003e\n\u003cli\u003eChin RM, et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. \u003cem\u003eNature\u003c\/em\u003e 510:397-401 (2014).\u003c\/li\u003e\n\u003cli\u003eLiu PS, et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. \u003cem\u003eNat Immunol\u003c\/em\u003e 18:985-994 (2017); follow-up \u003cem\u003eAging Cell\u003c\/em\u003e 2018.\u003c\/li\u003e\n\u003cli\u003eWu N, et al. Alpha-Ketoglutarate: Physiological Functions and Applications. \u003cem\u003eBiomol Ther\u003c\/em\u003e 24(1):1-8 (2016); \u003cem\u003eCell Metabolism\u003c\/em\u003e 2016 review.\u003c\/li\u003e\n\u003cli\u003eSu Y, et al. Aging-related changes in plasma α-ketoglutarate. \u003cem\u003eAging\u003c\/em\u003e 11(12):4183-4197 (2019).\u003c\/li\u003e\n\u003cli\u003eCarey BW, et al. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. \u003cem\u003eNature\u003c\/em\u003e 518:413-416 (2015).\u003c\/li\u003e\n\u003cli\u003eTran TQ, et al. α-Ketoglutarate attenuates aging via DNA demethylation. \u003cem\u003eCell Reports\u003c\/em\u003e 33(11):108457 (2020).\u003c\/li\u003e\n\u003cli\u003eKlose RJ, et al. JmjC-domain-containing proteins and histone demethylation. \u003cem\u003eNat Rev Genet\u003c\/em\u003e 7:715-727 (2006).\u003c\/li\u003e\n\u003cli\u003eLoenarz C \u0026amp; Schofield CJ. Expanding chemical biology of 2-oxoglutarate oxygenases. \u003cem\u003eNat Chem Biol\u003c\/em\u003e 4:152-156 (2008).\u003c\/li\u003e\n\u003cli\u003eHewitson KS, et al. Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases. \u003cem\u003eJ Biol Chem\u003c\/em\u003e 282(5):3293-3301 (2007).\u003c\/li\u003e\n\u003cli\u003eKaelin WG \u0026amp; Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. \u003cem\u003eMol Cell\u003c\/em\u003e 30(4):393-402 (2008).\u003c\/li\u003e\n\u003cli\u003eLando D, et al. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of HIF. \u003cem\u003eGenes Dev\u003c\/em\u003e 16:1466-1471 (2002).\u003c\/li\u003e\n\u003cli\u003eMyllyharju J. Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. \u003cem\u003eMatrix Biology\u003c\/em\u003e 22:15-24 (2003).\u003c\/li\u003e\n\u003cli\u003eGorres KL \u0026amp; Raines RT. Prolyl 4-hydroxylase. \u003cem\u003eCrit Rev Biochem Mol Biol\u003c\/em\u003e 45(2):106-124 (2010).\u003c\/li\u003e\n\u003cli\u003eShoulders MD \u0026amp; Raines RT. Collagen structure and stability. \u003cem\u003eAnnu Rev Biochem\u003c\/em\u003e 78:929-958 (2009).\u003c\/li\u003e\n\u003cli\u003eVarani J, et al. Decreased collagen production in chronologically aged skin. \u003cem\u003eAm J Pathol\u003c\/em\u003e 168:1861-1868 (2006).\u003c\/li\u003e\n\u003cli\u003eHorvath S. DNA methylation age of human tissues and cell types. \u003cem\u003eGenome Biology\u003c\/em\u003e 14:R115 (2013).\u003c\/li\u003e\n\u003cli\u003eHannum G, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. \u003cem\u003eMol Cell\u003c\/em\u003e 49:359-367 (2013).\u003c\/li\u003e\n\u003cli\u003eLevine ME, et al. An epigenetic biomarker of aging for lifespan and healthspan. \u003cem\u003eAging\u003c\/em\u003e 10(4):573-591 (2018) — PhenoAge.\u003c\/li\u003e\n\u003cli\u003eLu AT, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. \u003cem\u003eAging\u003c\/em\u003e 11(2):303-327 (2019).\u003c\/li\u003e\n\u003cli\u003eBelsky DW, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. \u003cem\u003eeLife\u003c\/em\u003e 11:e73420 (2022).\u003c\/li\u003e\n\u003cli\u003eHillary RF, et al. Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death. \u003cem\u003eClin Epigenetics\u003c\/em\u003e 12:115 (2020).\u003c\/li\u003e\n\u003cli\u003eFilip RS \u0026amp; Pierzynowski SG. The role of α-ketoglutarate in the regulation of bone metabolism. \u003cem\u003eJ Pre-Clin Clin Res\u003c\/em\u003e \/ \u003cem\u003eJ Bone Miner Metab\u003c\/em\u003e (2007).\u003c\/li\u003e\n\u003cli\u003eNiemczyk S, et al. Alpha-ketoglutarate and pulmonary hypertension. \u003cem\u003ePolish Heart Journal\u003c\/em\u003e 72(11):1093-1100 (2014) review.\u003c\/li\u003e\n\u003cli\u003eWernerman J, et al. Alpha-ketoglutarate and post-operative muscle catabolism. \u003cem\u003eCrit Care\u003c\/em\u003e 3(2):R51 (1999).\u003c\/li\u003e\n\u003cli\u003eBolland MJ, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. \u003cem\u003eBMJ\u003c\/em\u003e 341:c3691 (2010).\u003c\/li\u003e\n\u003cli\u003eSchurgers LJ, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. \u003cem\u003eBlood\u003c\/em\u003e 109:3279-3283 (2007).\u003c\/li\u003e\n\u003cli\u003eKnapen MHJ, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. \u003cem\u003eThromb Haemost\u003c\/em\u003e 113:1135-1144 (2015).\u003c\/li\u003e\n\u003cli\u003eGeleijnse JM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. \u003cem\u003eJ Nutrition\u003c\/em\u003e 134:3100-3105 (2004).\u003c\/li\u003e\n\u003cli\u003eCurhan GC, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. \u003cem\u003eAnn Intern Med\u003c\/em\u003e 126(7):497-504 (1997).\u003c\/li\u003e\n\u003cli\u003ePadayatty SJ, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. \u003cem\u003eAnn Intern Med\u003c\/em\u003e 140:533-537 (2004).\u003c\/li\u003e\n\u003cli\u003eIntlekofer AM, et al. L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH. \u003cem\u003eNat Chem Biol\u003c\/em\u003e 13:494-500 (2017).\u003c\/li\u003e\n\u003cli\u003eDang L, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. \u003cem\u003eNature\u003c\/em\u003e 462:739-744 (2009).\u003c\/li\u003e\n\u003cli\u003eJaiswal S, et al. Age-related clonal hematopoiesis associated with adverse outcomes. \u003cem\u003eNEJM\u003c\/em\u003e 371:2488-2498 (2014); CHIP and cardiovascular disease, \u003cem\u003eNEJM\u003c\/em\u003e 377:111-121 (2017).\u003c\/li\u003e\n\u003cli\u003eBayliak MM, et al. Pro-health effects of α-ketoglutarate. \u003cem\u003eBiogerontology\u003c\/em\u003e 17:567-579 (2016).\u003c\/li\u003e\n\u003cli\u003eMastrogiacomo F, et al. Brain α-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. \u003cem\u003eAnn Neurol\u003c\/em\u003e 39:592-598 (1996).\u003c\/li\u003e\n\u003cli\u003eBunik VI, et al. The 2-oxoglutarate dehydrogenase complex: redox sensor and target. \u003cem\u003eFEBS J\u003c\/em\u003e 275:6234-6253 (2008).\u003c\/li\u003e\n\u003cli\u003eHowitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. \u003cem\u003eNature\u003c\/em\u003e 425:191-196 (2003).\u003c\/li\u003e\n\u003cli\u003ePark SJ, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. \u003cem\u003eCell\u003c\/em\u003e 148:421-433 (2012).\u003c\/li\u003e\n\u003cli\u003eTrammell SAJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. \u003cem\u003eNat Commun\u003c\/em\u003e 7:12948 (2016).\u003c\/li\u003e\n\u003cli\u003eYoshino J, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. \u003cem\u003eScience\u003c\/em\u003e 372:1224-1229 (2021).\u003c\/li\u003e\n\u003cli\u003eKrebs HA \u0026amp; Johnson WA. The role of citric acid in intermediate metabolism in animal tissues. \u003cem\u003eEnzymologia\u003c\/em\u003e 4:148-156 (1937).\u003c\/li\u003e\n\u003cli\u003eSemenza GL. Hypoxia-inducible factors in physiology and medicine. \u003cem\u003eCell\u003c\/em\u003e 148:399-408 (2012).\u003c\/li\u003e\n\u003cli\u003eLópez-Otín C, et al. The Hallmarks of Aging. \u003cem\u003eCell\u003c\/em\u003e 153:1194-1217 (2013); update \u003cem\u003eCell\u003c\/em\u003e 186(2):243-278 (2023).\u003c\/li\u003e\n\u003cli\u003eJia G, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. \u003cem\u003eNat Chem Biol\u003c\/em\u003e 7:885-887 (2011).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cem\u003eThese statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any supplement, especially if you have a medical condition, are pregnant or nursing, or take prescription medication.\u003c\/em\u003e\u003c\/p\u003e\n","brand":"True Health Protocol","offers":[{"title":"Default Title","offer_id":47840283295962,"sku":"THP-CAAKG-1000-60","price":39.99,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0814\/5158\/1658\/files\/thp_caakg.png?v=1778080099","url":"https:\/\/truehealthprotocol.health\/products\/calcium-alpha-ketoglutarate-1000mg-caakg-epigenetic-longevity","provider":"True Health Protocol","version":"1.0","type":"link"}