Tier 4 — mechanistic

Evaluation of the Efficacy of Calcium a-Ketoglutarate(AKG-Ca) in Improving Human Aging

Jiaomei Li, Chenxiang Shi
ClinicalTrials.gov (trial registry) 2025 NCT07114536

Bibliography

Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Lead sponsor: Shenzhen Hygieia Biotech Co., Ltd. Zhejiang Chinese Medical University is listed as a collaborator in the trial registry.
Competing interests
ClinicalTrials.gov does not provide a formal competing-interests declaration. The lead sponsor is Shenzhen Hygieia Biotech Co., Ltd, an industry sponsor involved with the calcium alpha-ketoglutarate intervention.

Study snapshot

DesignRandomized, double-blind, placebo-controlled, parallel-group interventional trial.
ModelGenerally healthy adults aged 40–75 years.
Sample34 participants (actual enrollment)
InterventionClinicalTrials.gov registry: calcium alpha-ketoglutarate (CaAKG) 2 g/day (four 0.5 g tablets daily) versus four 0.5 g starch placebo tablets daily for 12 weeks. The uploaded protocol PDF appears to describe 1 g/day, so the source documents are internally inconsistent; the registry dose is used for the structured trial record pending sponsor clarification.
Duration12 weeks
EndpointsPrimary: Change in PhenoAge (Levine 2018 composite biomarker) baseline to Week 12; Bone density (DXA/DEXA) baseline to Week 12; Senescence-associated gene expression (SIRT1–7, TERT, TERC, p21/CDKN1A, p16INK4a/CDKN2A, PDGFRB, PLOD1, MAP4K4, NFKBIA, GFAP, F2RL3, HERPUD1, PPP1R15A, PCBP1, TFAM, MMP7); β-galactosidase activity and SOD2/CAT; Body composition (weight, BMI, fat mass, fat percentage, fat-free mass, muscle mass, body water, protein, inorganic salts); T-cell subsets (CD3+, CD4+, CD8+, CD4/CD8 ratio); Grip strength and finger-tap kinematic tests; Glucose metabolism (HbA1c, fasting glucose, fasting insulin, HOMA-IR); Lipid metabolism (TG, total cholesterol, LDL-C, HDL-C, ApoA-I, ApoB); Inflammation panel (hs-CRP, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-α, IFN-γ); Gut microbiota (16S rRNA sequencing); Safety: liver function, kidney function, blood routine, vital signs

What the study showed, in plain terms

This completed randomized, double-blind, placebo-controlled trial tested calcium alpha-ketoglutarate (CaAKG) for 12 weeks in generally healthy adults aged 40 to 75 years. ClinicalTrials.gov lists an actual enrollment of 34 participants. The registered intervention is CaAKG 2 g/day (four 0.5 g tablets) versus a matching starch placebo, although an uploaded protocol document appears to describe 1 g/day, so the source documents contain a dose discrepancy that should be resolved before quoting the dose without qualification.

The prespecified primary endpoint was change in PhenoAge, a composite biological-age measure based on clinical chemistry markers and chronological age. Secondary and exploratory endpoints included bone density, body composition, grip strength, glucose and lipid metabolism, inflammatory markers, immune-cell subsets, senescence-related gene expression, beta-galactosidase activity, antioxidant enzymes and gut microbiota.

The trial completed on November 30, 2025. As of the September 2026 registry update, no results had been posted to ClinicalTrials.gov. The record therefore documents the completed trial design and prespecified outcomes, not evidence that CaAKG lowered biological age or improved any clinical outcome.

Key findings

No efficacy results have been posted. The following are verified registry facts and prespecified endpoints, not treatment findings.

  • Trial status: completed November 30, 2025; no results posted as of the September 2026 ClinicalTrials.gov update.
  • Actual enrollment: 34 participants aged 40–75 years.
  • Design: randomized, double-blind, placebo-controlled, parallel-group human trial.
  • Primary endpoint: change in PhenoAge from baseline to Week 12.
  • Registered intervention: CaAKG 2 g/day versus starch placebo for 12 weeks; an uploaded protocol document appears to list 1 g/day, creating a source-document dose discrepancy.
  • Secondary/exploratory measures include DXA bone density, body composition, grip strength, metabolic markers, inflammatory cytokines, T-cell subsets, senescence-related genes and gut microbiota.

What this study can and cannot tell us

No results are available in the registry. A completed trial record without posted results cannot establish efficacy, safety beyond the registered monitoring plan, or a treatment effect on biological age.

The sample is small. Actual enrollment was 34 participants. That is a modest sample for a trial with a large panel of secondary and exploratory outcomes, increasing uncertainty for endpoint-specific conclusions even when results are eventually reported.

The intervention lasted 12 weeks. This is insufficient to determine long-term clinical outcomes, disability, chronic disease incidence or lifespan effects.

PhenoAge is a biomarker composite, not a clinical outcome. A change in PhenoAge would not by itself prove slower aging, disease prevention or longer life.

The trial is industry-sponsored. Shenzhen Hygieia Biotech Co., Ltd is the lead sponsor, with Zhejiang Chinese Medical University listed as a collaborator.

The source documents contain a dose discrepancy. ClinicalTrials.gov lists CaAKG 2 g/day, while an uploaded protocol document appears to describe 1 g/day. The actual administered dose should be confirmed from a results publication or sponsor clarification before it is presented as settled fact.

Related papers in the corpus

Tier 2
Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test
Oleksandr Demidenko et al. · Aging (Albany NY) · 2021
Tier 4
Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease
Navakkode S et al. · Aging Cell · 2025

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology