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

NCT07114536 | Active Not Recruiting DMC

• 1 other identifier: Evaluation of AKG-Ca on Aging
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of calcium alpha-ketoglutarate (CaAKG) supplementation on biological aging and age-related health indicators in middle-aged and older adults. Alpha-ketoglutarate (AKG), a key intermediate in the Krebs cycle, has been investigated for its potential role in modulating aging-related metabolic and cellular pathways. Due to the poor oral bioavailability of free AKG, its stabilized form-calcium alpha-ketoglutarate (CaAKG)-is used to enhance absorption and additionally provides calcium supplementation benefits. At the population level, there is currently a lack of systematic assessment studies on the effects of CaAKG on human ageing-related indicators. The study will recruit generally healthy adults aged 45 to 75 years. Participants will be randomly assigned to receive either CaAKG or a placebo daily for 12 weeks. The primary objective is to assess changes in biological aging, as measured by PhenoAge. Secondary outcomes include changes in physical performance, inflammatory markers, glucose and lipid metabolism, ageing-related gene expression, and self-reported quality of life. This trial is designed to provide evidence on the efficacy and safety of CaAKG as a potential dietary intervention to support healthy aging. All participants will undergo pre- and post-intervention assessments. The study has been reviewed and approved by Medical Ethics Committee of Zhejiang Chinese Medical University, and informed consent will be obtained from all participants prior to enrollment.

Conditions

Aging

Keywords

a-ketoglutaric acid; Phenoage*age; Healthy aging

Outcome Measures

Primary Outcomes (1)

• Change in PhenoAge from Baseline to Week 12

  Phenotypic Age (PhenoAge) is a composite biomarker-based estimate of biological age. The primary outcome is the change in PhenoAge from baseline to the end of the 12-week intervention period. PhenoAge will be calculated using the algorithm developed by Levine et al. (2018), based on a validated mortality risk model.

  Baseline and Week 12

Secondary Outcomes (23)

• Change in Calcium Content of Bone

  Baseline and Week 12

• Change in β-Galactosidase Activity

  Baseline and Week 12

• Change in Age-related Gene Expression

  Baseline and Week 12

• Change in Grip strength

  Baseline,12-week study

• Change in body Weight

  Baseline and Week 12

Other Outcomes (16)

• Change in Gut Microbiota

  Baseline, 12-week study

• Change in Urea (UREA)

  Baseline and 12-week study

• Change in Blood routine test

  Baseline, 12-week study

Study Arms (2)

Intervention group: calcium-a-ketoglutarate

EXPERIMENTAL

The experimental group subjects took four Ca-AKG tablets (0.5 g/tablet) daily.

Dietary Supplement: Calcium-a-ketoglutarate

Control group: starch

PLACEBO COMPARATOR

Placebo-controlled group subjects took four starch placebo tablets (0.5g/tablet) daily.

Other: Placebo(starch)

Interventions

Calcium-a-ketoglutarate DIETARY_SUPPLEMENT

Description: Participants in the intervention group will receive oral calcium alpha-ketoglutarate (CaAKG) in granular tablet form. Each tablet contains 0.5 grams of CaAKG.Participants will take two tablets twice daily (morning and evening). The total daily dose is 2 grams. The intervention period will last for 12 weeks. CaAKG is a stabilized form of alpha-ketoglutarate that enhances bioavailability and provides supplemental calcium. The tablets are identical in appearance and texture to those in the placebo group to maintain blinding.

Intervention group: calcium-a-ketoglutarate

Placebo(starch) OTHER

Participants in the placebo group will receive oral tablets identical inappearance and texture to the CaAKG tablets, but containing starch with no active calciumalpha-ketoglutarate. Each tablet weighs 0.5 grams. Participants will take two tablets twicedaily (morning and evening), for a total daily intake of 2 grams. The placebo tablets arepackaged and administered in the same manner as the CaAKG tablets to ensure blindingthroughout the 12-weekintervention period.

Control group: starch

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 40-75 years old, no gender restrictions.
• Has not taken any other anti-ageing research products in the past two months.
• Able to use a smartphone.
• Informed consent, voluntarily signed informed consent form, and agreed to participate in all visits and treatments in accordance with the trial protocol.

You may not qualify if:

• Patients with cardiovascular disease, severe/uncontrolled hypertension, rheumatic heart disease, congenital heart disease, deep vein thrombosis, or pulmonary embolism .
• Patients with Type I/Type II diabetes (treated with oral metformin or insulin) or diabetes complications .
• Patients with cancer or who have undergone surgery, systemic drug therapy, or radiation therapy within the past 3 years.
• Chronic obstructive pulmonary disease (COPD), severe asthma (requiring daily medication).
• Multiple sclerosis, autoimmune/immunodeficiency disorders.
• Recent history of sepsis or infection (hospitalisation within the past 3 months).
• Any mental illness or neurodegenerative disease.
• Any metallic implants in the body.
• Hepatitis/cirrhosis.
• Severe kidney disease (GFR \<30 mL/min/1.73 m²).
• Suffering from other conditions deemed unsuitable for participation in this trial (as determined by the investigator).

Sponsors & Collaborators

• Shenzhen Hygieia Biotech Co., Ltd: lead
• Zhejiang Chinese Medical University: collaborator

Study Sites (1)

Zhejiang Chinese Medicine University

Hangzhou, Zhejiang, 310051, China

Location

Related Publications (4)

• Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK, Budovskaya YV. Rejuvant(R), 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. Aging (Albany NY). 2021 Nov 30;13(22):24485-24499. doi: 10.18632/aging.203736. Epub 2021 Nov 30.

  PMID: 34847066 RESULT

• Sandalova E, Goh J, Lim ZX, Lim ZM, Barardo D, Dorajoo R, Kennedy BK, Maier AB. Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)-intervention study protocol. Geroscience. 2023 Oct;45(5):2897-2907. doi: 10.1007/s11357-023-00813-6. Epub 2023 May 23.

  PMID: 37217632 RESULT

• Liu Z, Kuo PL, Horvath S, Crimmins E, Ferrucci L, Levine M. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study. PLoS Med. 2018 Dec 31;15(12):e1002718. doi: 10.1371/journal.pmed.1002718. eCollection 2018 Dec.

  PMID: 30596641 RESULT

• Liu C, Hua L, Xin Z. Synergistic impact of 25-hydroxyvitamin D concentrations and physical activity on delaying aging. Redox Biol. 2024 Jul;73:103188. doi: 10.1016/j.redox.2024.103188. Epub 2024 May 10.

  PMID: 38740004 RESULT

Study Officials

• Li Jiaomei

  Zhejiang Chinese Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 11, 2025
• Study Start: August 20, 2025
• Primary Completion: January 30, 2026
• Study Completion: January 30, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)