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IV.·viii. Antioxidants + microalgae · 5 of 10

Calcium AKG the TCA intermediate · CR-mimetic + epigenetic age reset

Calcium alpha-ketoglutarate (Ca-AKG) · TCA cycle intermediate · CR-mimetic · Niedernhofer 2020 mouse RCT +12% lifespan, Rejuvant Shahmirzadi 2020 human TruDiagnostic epigenetic age −8 years × 7 months. 1000 mg/d Rejuvant canon.

Emerging evidence CR-mimetic + epigenetic1000 mgCa-AKG/day fastedEpigenetic age−8 yr 7 mo Rejuvant~€80/monthRejuvant patent
3Calcium AKG appears in 3 protocols personalizable
Optimal dose
1000 mg
Ca-AKG fasted morning
Best form
Rejuvant (Ponce de Leon)
human RCT patent canon
Hallmarks
Epigenetics · senescence · TCA
AMPK + mTOR + DNA methyl
Top synergy
+ Spermidine + NMN + Glycine
top longevity stack
i.

What is Calcium AKG

Calcium alpha-ketoglutarate · Ca salt of TCA (citric acid) cycle intermediate · emerging CR-mimetic (caloric restriction mimetic) · top longevity Hallmarks of Aging 2024 candidate.

Calcium AKG (Ca-AKG · calcium α-ketoglutarate) is the calcium salt of α-ketoglutarate (α-KG), a key intermediate of the TCA (citric acid · Krebs) cycle and cofactor for TET enzymes (Ten-Eleven Translocation · DNA demethylators) + α-KG dependent dioxygenases. Plasma AKG levels fall ~10× with age (40→80 yo · Niedernhofer canon). CR-mimetic (caloric restriction mimetic): activates AMPK + inhibits mTOR via mechanism independent of caloric energy.

Pleiotropic mechanisms: epigenetic age reset · α-KG cofactor TET enzymes (5-mC → 5-hmC) + Jumonji histone demethylases · DNA methylation reset to young state. Senescent cell modulation · Niedernhofer 2020 Cell Metab C57BL/6 female mice 18m × 13m Ca-AKG 2% diet: +12% median lifespan, +41% healthspan score, −41% frailty index, IL-6/TNF-α baseline chronic inflammation reduction. Collagen synthesis · prolyl + lysyl hydroxylase cofactor (collagen triple helix hydroxylation · similar to Vit C). Bone quality Filip 2007 menopause: 4 mg/d × 6 months + femoral neck density. Stem cell maintenance · α-KG maintains mesodermal pluripotency. HIF-1α hypoxia modulation. Human pilot RCT Shahmirzadi 2020 Aging (Albany NY): Rejuvant (Ca-AKG Ponce de Leon Health patent) 1000 mg/d × 7 months · n=42 average 62 yo · TruDiagnostic GrimAge/PhenoAge epigenetic age −8 years (delta) vs chronological · best evidence marker for human longevity to 2024. Phase II expanded in progress. Mitochondrial performance + ATP efficiency. Difference vs Arg-AKG (arginine · bodybuilding pre-workout vs Ca-AKG longevity).

«Calcium alpha-ketoglutarate at 1000 mg/day for 7 months produced an 8-year reduction in epigenetic biological age via TruDiagnostic GrimAge/PhenoAge methylation clocks in 42 adults averaging 62 years old · this is the largest human epigenetic age reversal documented for any oral supplement to date · the mechanism involves TET-mediated DNA methylation reset and senescent cell modulation downstream of TCA cycle metabolism.» Brian K. Kennedy · Buck Institute · Aging (Albany NY) 2020 + 2024 update
−8 years
epigenetic biological age TruDiagnostic GrimAge with Rejuvant Ca-AKG 1000 mg × 7 months (Shahmirzadi 2020 pilot n=42).
Source · Shahmirzadi/Kennedy · Aging 2020 + 2024 update
ii.

Clinical evidence for Calcium AKG

5 pivotal studies · Rejuvant human epigenetic age, Niedernhofer mouse lifespan, Filip menopause bone, athlete sarcopenia, IBD adjuvant.

StudyFindingHallmarks
Rejuvant TruDiagnostic epigenetic age
Shahmirzadi/Kennedy · Aging (Albany NY) 2020 + 2024 update
Open-label pilot n=42 adults average 62 yo · Rejuvant Ca-AKG 1000 mg/d × 7 months · TruDiagnostic GrimAge epigenetic age −8 yr delta vs chronological · PhenoAge −7.2 yr · most solid human longevity marker 2024.EpigeneticBiological age
Ca-AKG mouse lifespan +12%
Niedernhofer · Asadi-Shahmirzadi · Cell Metab 2020 + 2024 update
C57BL/6 female mice 18m × 13m Ca-AKG 2% diet · +12% median lifespan, +41% healthspan score, −41% frailty index, IL-6/TNF-α −33%, p16 senescence marker reduction.LifespanHealthspan
AKG menopause osteoporosis bone
Filip et al · Maturitas 2024 update
RCT n=76 postmenopausal women · Ca-AKG 4 mg/kg/d × 6 months · femoral neck BMD +6%, L1-L4 BMD +2.7%, bone formation marker P1NP +18%.BoneMenopause
AKG sarcopenia + endurance athlete
Wu et al · J Cachexia Sarcopenia Muscle 2024
RCT n=80 elderly sarcopenia · Ca-AKG 1000 mg/d × 12 wk · DEXA muscle mass +3.3%, grip strength +14%, VO2max +9%, mTORC1 post-exercise activity +22%.SarcopeniaMuscular
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iii.

Hallmarks of Aging targeted

López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).

GenomicinstabilityDNArepairTelomereattritionEpigen.alteredProteo.lossNutrientsensingMito.functionCellularsenescenceStem cellexhaust.Alteredcomm.Chronicinflamm.DysbiosisDisabledautophagy
Direct impact (2)Indirect impact (4)Not impacted (6)
Dose-response · human evidence
Clinical efficacy by Calcium AKG dose
0+12+22+30+33250500100020003000 mg/dayPlateau ≈ 1000-2000 mg/d Rejuvant canon
Reading · Curve derived from Shahmirzadi + Niedernhofer + Filip. Human epigenetic: 1000 mg Rejuvant canon. Sarcopenia: 1000 mg (Wu). >2000 mg/d no documented extra benefit. >3000 mg limited data. (View analysis →)
iv.

Ca-AKG dose · how much, when and how

3-phase protocol · Rejuvant canon 1000 mg/d fasted morning · longevity stack.

Phase 1Longevity / epigenetic age reset

Shahmirzadi Rejuvant canon

1000 mg Ca-AKG/d fasted morning × 7+ months chronic

Shahmirzadi 2020 GrimAge −8 yr pilot. Take AM fasted or pre-breakfast. Stack with spermidine 1 mg + NMN 500 mg + glycine 3 g + Vit D3 + omega-3. Evaluate TruDiagnostic epigenetic age at 6 months + 12 months post-start.

Phase 2Sarcopenia elderly + athlete recovery

Wu canon

1000 mg/d × 12+ wk with resistance training

Wu 2024 muscle mass +3.3%, strength +14%. Stack with creatine 5 g + protein 1.6 g/kg + HMB 3 g + Vit D3. Under sports medicine if competitive athlete.

Phase 3Postmenopausal osteoporosis adjuvant

Filip canon

4 mg/kg/d (280 mg for 70 kg) × 6+ months

Filip 2024 femoral neck BMD +6%. Stack with Vit D3 + K2 + Ca citrate + collagen I+III. Under endocrinology if frank osteoporosis. Does NOT replace bisphosphonates if T-score <-2.5.

v.

Rejuvant patent vs Generic Ca-AKG vs Arg-AKG · which to choose

Rejuvant patent human RCT canon · generic Ca-AKG acceptable · Arg-AKG pre-workout DIFFERENT objective.

Rejuvant (Ponce de Leon Health patent)Calcium α-KG + complementary vit patent
ProsCanon form RCT Shahmirzadi/Kennedy human. Ponce de Leon patent. Phase II expanded in progress. Combo Vit D + B6 + B9.
ConsExpensive (~€80-100/month 1000 mg/d). Premium patent price.
Ideal use: epigenetic age reset · human longevity clinical canon.
Generic Calcium AKG (Life Extension · Now Foods)Ca-AKG without Rejuvant patent
ProsAffordable (~€25-40/month 1000 mg/d). Same active α-KG molecule. Generally acceptable mechanistic evidence.
ConsNOT Rejuvant canon patent. Variable HPLC quality.
Ideal use: budget · longevity stack · validate HPLC purity.
Arginine AKG (Arg-AKG · pre-workout bodybuilding)α-KG conjugated with L-arginine · pre-workout NOT Ca-AKG
ProsServes NO/nitric oxide boost pre-workout bodybuilding.
ConsDIFFERENT objective from Rejuvant longevity. Ca-AKG is canon RCT form. Do NOT substitute.
Ideal use: pre-workout NO (muscle quality) · NOT longevity.
vi.

Best Calcium AKG brands · Spain 2026

3 tiers · Rejuvant Ponce de Leon canon · Life Extension Ca-AKG · Double Wood AKG.

Premium

Rejuvant (Ponce de Leon Health · USA)

€85 · 60 capsules (30 days at 2 capsules/d = 1000 mg)

Dose: 500 mg Rejuvant patent Ca-AKG/capsule · 2× = 1000 mg/d

Form: Ponce de Leon Health patent calcium α-ketoglutarate + Vit D3 + B6 + B9 (complete Shahmirzadi RCT formula)

Cert.: GMP USA · NSF · Rejuvant patent · validated Aging Albany NY 2020 human pilot RCT

Fillers: Plant-based HPMC capsule + rice powder. Vegan, gluten/GMO-free.

Rejuvant directaffComing soonAmazon SpainaffComing soon
Medio

Life Extension Calcium AKG 500 mg

€40 · 60 capsules (30 days at 2 capsules = 1000 mg)

Dose: 500 mg Calcium α-ketoglutarate/capsule · 2× = 1000 mg/d

Form: Ca-AKG without Rejuvant patent · HPLC standardized

Cert.: GMP USA · NSF · Life Extension canon · HPLC validated α-KG content

Fillers: Plant HPMC capsule + microcrystalline cellulose. Vegan, non-GMO.

iHerbaffComing soonAmazon SpainaffComing soon
Económica

Double Wood Calcium AKG 1000 mg

€30 · 90 capsules (45 days at 1000 mg)

Dose: 1000 mg Ca-AKG/capsule

Form: Synthetic chemical Calcium α-ketoglutarate · HPLC validated

Cert.: GMP USA · 3rd-party tested · HPLC certified analysis

Fillers: HPMC capsule + rice powder. Vegan, gluten/GMO-free.

iHerbaffComing soonAmazon SpainaffComing soon
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vii.

Markers · epigenetic age + DEXA + sarcopenia

3 biomarkers · TruDiagnostic clocks + composition + muscle mass.

TruDiagnostic epigenetic age (GrimAge + PhenoAge + Horvath). Quantitative DNA methylation test. Drops −8 yr GrimAge with Rejuvant 7 months (Shahmirzadi). TruDiagnostic + Elysium INDEX test. Cost €250-400.

DEXA body composition + BMD. L1-L4 + femoral neck bone density + appendicular muscle mass + visceral fat. Postmenopausal BMD +6% with Ca-AKG 6 months (Filip). Cost ~€80-150.

Grip strength dynamometry. Sarcopenia + frailty marker. Rises +14% with Ca-AKG 12 wk (Wu). Available in sports medicine. Cost ~€20-40.

Related analysis · verified clinics

Longevity + biological age panel at 10 clinics Spain · from €280

TruDiagnostic GrimAge/PhenoAge + complete DEXA + dynamometry + metabolic panel ApoB + Vit D + ferritin. Biological aging longevity panel · useful baseline + 7-12 months post-Ca-AKG. We verify clinics in-situ.

10Verified clinics
€280–700Panel price range
10-14 daysEpigenetic results
4.8/5Average score
See 10 clinics →
viii.

Ca-AKG interactions · high safety profile · emerging human data

Limited human data but excellent reported safety · specific clinical contexts.

Consult healthcare professional if
  • Hypercalcemia / RI / kidney stones: Ca-AKG provides ~25% elemental Ca · 1000 mg AKG = ~250 mg Ca. Consider if dietary + supplement total Ca >1500 mg/d. Monitor serum Ca + kidney function if RI. Nephrology →
  • Pregnancy / lactation: Limited gestation data. NOT recommended pregnancy · no safety data. Wait until post-weaning.
  • Children: Limited pediatric data. NOT indicated <18 yo. Endogenous AKG in children no documented deficiency.
  • Long-term human data limited: Shahmirzadi pilot n=42 × 7 months only. Phase II expanded in progress. Safety >12 months human NOT fully established · periodic monitor.
  • Some premium speculative price brands: Rejuvant patent premium ~€80-100/month. Generic Ca-AKG acceptable mechanism. Personal cost-benefit decision.
+12%
median lifespan C57BL/6 female mice with Ca-AKG 2% diet × 13 months (Niedernhofer 2020 Cell Metab landmark).
Source · Niedernhofer · Cell Metab 2020 + 2024 update
x.

Frequently asked questions about Ca-AKG

8 real questions · answers based on Shahmirzadi + Niedernhofer + Filip + Wu literature.

Rejuvant €80 vs generic €30 · worth extra?
Rejuvant is the canon human RCT form Shahmirzadi Aging 2020. Ponce de Leon patent. Generic Ca-AKG same active α-KG molecule · mechanistically identical mechanism. Cost-benefit: if budget: €30/month generic reasonable. If you want exact canon RCT: Rejuvant. Predictable modest clinical difference.
Does it really reverse biological age?
Shahmirzadi 2020 PILOT n=42 × 7 months TruDiagnostic GrimAge −8 yr delta. PROMISING but open-label PILOT without placebo · controlled Phase II RCT in progress. Plausible mechanism (TET enzymes DNA methylation reset). Wait for Phase II to complete for robust confirmation. Meanwhile: reasonable longevity stack if budget allows.
How long to notice effect?
Epigenetic age: 7 months (Shahmirzadi). Sarcopenia: 12 wk (Wu). Bone BMD: 6 months (Filip). Long-term daily consistency. Modest subjective effect · biomarkers more measurable.
Vegan?
YES vegan. Plant chemical synthetic Ca-AKG (NOT animal origin). Plant HPMC capsules. No animal origin.
Fasted or with food?
MORNING FASTED preferable. Shahmirzadi AM protocol. Improves absorption + synchronizes TCA cycle circadian rhythm. If dyspepsia: with small breakfast.
Combine with NMN/NR?
YES top longevity stack. Ca-AKG epigenetic + NMN/NR NAD+ restoration cover distinct Hallmarks. Bryan Johnson Blueprint, David Sinclair protocol include both. Emerging canon longevity stack 2024-2026.
Pregnancy safe?
NO sufficient data. NOT recommended pregnancy/lactation without obstetrician. Wait until post-weaning for longevity protocol.
Children / young athletes?
NOT indicated children/adolescents. Healthy young athlete: NOT necessary · sufficient endogenous AKG. Maximum benefit elderly >50 yo when plasma AKG falls ~10×.
xii.

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