Tier 2 — strong

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Calcium Alpha-Ketoglutarate Supplementation on Biological Aging, Physical Performance, and Metabolic Health in Middle-Aged and Older Adults

Jiaomei Li, Chenxiang Shi

ClinicalTrials.gov (trial registry) 2025 NCT07114536

Bibliography

DOI: To be updated
PubMed: PMID To be updated
Funding: Sponsor: Shenzhen Hygieia Biotech Co., Ltd (industry — commercial manufacturer of calcium alpha-ketoglutarate supplements). Academic collaborator: School of Public Health, Zhejiang University of Traditional Chinese Medicine. Ethics approval: Medical Ethics Committee of Zhejiang University of Traditional Chinese Medicine (Application 20250613-2, approved 13 June 2025). Reviewed under Ethics Review Methods for Human Life Sciences and Medical Research (2023), SFDA GCP (2020), WMA Declaration of Helsinki, and CIOMS International Ethical Guidelines.
Competing interests: Direct commercial conflict of interest. The trial sponsor, Shenzhen Hygieia Biotech Co., Ltd, manufactures the intervention product being evaluated in this trial. No independent funding source is disclosed. The academic collaborator (Zhejiang University of Traditional Chinese Medicine) is contracted via a "horizontal topics" project arrangement with the industry sponsor.

Study snapshot

Design	Randomised, double-blind, placebo-controlled parallel-group trial with block randomisation (Stata 13.0) stratified by age and gender. Quadruple masking (participant, care provider, investigator, outcomes assessor). Intention-to-treat analysis.
Model	Middle-aged and older human adults aged 40–75 years, both sexes, recruited from urban Hangzhou community service centres, Zhejiang Province, China.
Sample	30 total (15 CaAKG arm, 15 starch placebo arm)
Intervention	Oral calcium alpha-ketoglutarate tablets vs starch placebo, 12 weeks. Dose discrepancy in source documents — requires sponsor confirmation before citation. ClinicalTrials.gov registry states 0.5 g × 2 tablets × twice daily = 2 g/day; the uploaded protocol PDF states two 0.5 g tablets once daily at lunch = 1 g/day.
Duration	12 weeks (day 0 baseline to day 90 endpoint)
Endpoints	Primary: 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 is a Chinese clinical trial that started in August 2025 and is scheduled to finish reporting its main results in early 2026. Thirty healthy adults aged 40 to 75 from Hangzhou were split into two groups of fifteen. One group takes calcium alpha-ketoglutarate tablets every day for three months; the other takes identical-looking starch placebo tablets. Neither the participants nor the researchers measuring the results know who is in which group.

The main question the trial is trying to answer is whether calcium alpha-ketoglutarate lowers biological age. Biological age here is measured by PhenoAge — a formula that combines nine standard blood test results with chronological age to estimate how old someone's body appears to be, biologically. The trial also measures dozens of other things: bone density, muscle strength, gene activity linked to ageing, immune cell counts, blood sugar control, cholesterol, inflammation markers, and gut bacteria composition.

Results have not been published yet. When they are, this page will be updated with the actual findings and their limitations. Until then, this entry documents what was planned and pre-registered — which is important, because pre-registered trials are harder for sponsors to selectively report from than trials that are analysed only after the data comes in.

Key findings

No results are published yet. This entry documents the trial's pre-registered design so that when results become available they can be compared against what was planned. The following are the pre-specified endpoints, not findings:

Primary endpoint: change in PhenoAge from baseline to Week 12. PhenoAge is the Levine 2018 composite of nine clinical chemistry markers plus chronological age.
Bone: dual-energy X-ray absorptiometry (DXA) at baseline and Week 12.
Cellular senescence: β-galactosidase activity and mRNA expression of a 17-gene senescence panel including SIRT1–7, TERT/TERC, p21 (CDKN1A), and p16INK4a (CDKN2A).
Immune: T-cell subset counts (CD3+, CD4+, CD8+) and CD4/CD8 ratio.
Metabolic: HbA1c, fasting glucose, fasting insulin, HOMA-IR, full lipid panel including apolipoproteins.
Inflammation: hs-CRP plus a 13-cytokine panel (TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-α, IFN-γ).
Function: grip strength, finger-tap rate, physical activity questionnaire.
Body composition: weight, BMI, fat mass, muscle mass, body water.
Exploratory: 16S rRNA gut microbiota sequencing.
Safety: full liver panel, kidney panel, blood count, vital signs including arterial stiffness.

Trial status as of the last registry update (18 November 2025): active, not recruiting. Primary completion date: 30 January 2026.

What this study can and cannot tell us

This entry describes a protocol, not results. Whatever the trial reports, several structural limitations already apply.

Sample size is small. Thirty participants (fifteen per arm) is underpowered for the extensive secondary and exploratory endpoint panel this trial plans to analyse. The primary endpoint (PhenoAge) may be detectable at this sample size if the effect is large; most secondary endpoints will not be.

Twelve weeks is short. The Demidenko 2021 Rejuvant study required four to ten months of supplementation to detect meaningful methylation-clock shifts. Whether a shorter 12-week window is sufficient for a PhenoAge shift is unknown.

PhenoAge is not a DNA methylation clock. It is a composite of clinical chemistry markers plus chronological age. Results here will not be directly comparable to prior Rejuvant DNAm studies (Demidenko 2021, Pabis 2026).

Industry-sponsored, with a direct commercial conflict. The sponsor manufactures the intervention product. No independent funder is disclosed.

Population is narrow. All participants are recruited from a single geographic area (urban Hangzhou) and a single ethnicity, limiting generalisability to other populations.

Dose discrepancy in source documents. The ClinicalTrials.gov registry lists 2 g/day; the uploaded protocol PDF lists 1 g/day. The true administered dose must be confirmed with the sponsor before this trial can be cited in any Biohack Blueprint article.

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 3

Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease

Navakkode S et al. · Aging Cell · 2025