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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
30
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.
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.
Zhejiang Chinese Medicine University
Hangzhou, Zhejiang, China
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.
Time frame: Baseline and Week 12
Change in Calcium Content of Bone
The calcium content of bone will be measured at baseline and at Week 12 to evaluate changes resulting from CaAKG supplementation. Bone calcium will be assessed using dual-energy X-ray absorptiometry (DXA) with mineral content analysis at specific skeletal sites. The primary metric is the change in bone calcium content (mg/cm2 or mg) over the 12-week intervention period.
Time frame: Baseline and Week 12
Change in β-Galactosidase Activity
β-Galactosidase activity will be measured in serum collected at baseline and at Week 12.
Time frame: Baseline and Week 12
Change in Age-related Gene Expression
e.g., SIRT1\~7、TERT/TERC、p21(CDKN1A)、p16INK4a(CDKN2A)、PDGFRB、PLOD1、MAP4K4、NFKBIA、GFAP、F2RL3、HERPUD1、PPPIR15A、PCBP1、TFAM、MMP7
Time frame: Baseline and Week 12
Change in Grip strength
The change in Grip strength (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline,12-week study
Change in body Weight
The change in body weight (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in body mass index(BMl)
The change in Body Mass Index (BMl) kg/m2 of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in body fat mass
The change in body fat mass(kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in alkaline phosphatase (ALP)
The change in alkaline phosphatase (ALP) in U/L of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in body fat percentage
The change in body fat percentage (%) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in fat-free mass
The change in fat-free mass(kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in muscle mass
The change in muscle mass (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in body water
The change in body water (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in blood creatinine (CREA)
The change in blood creatinine (CREA) in mol/L of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and 12-week study.
Change in protein
The change in protein (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in inorganic salts
The change in inorganic salts (kg) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in TotalT lymphocytes (CD3+)
The change in TotalT lymphocytes (CD3+) (cells/μl) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in helper T cells(cD4+)
The change in helper T cells (CD4+) (cells/μl) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in cytotoxicT cells(CD8+)
The change in cytotoxic T cells (CD8+)(cells/μL) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in Glycated haemoglobin (HbAlc)
The change in Glycated haemoglobin (HbA1c) (%) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in Fasting blood glucose
The change in Fasting blood glucose (mmol/L) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in Fasting insulin
The change in Fasting insulin (pmol/L) of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
Change in Physical activity questionnaire Scores
International Physical Activity Questionnaire - Long Form (IPAQ-LF). At baseline and 12 weeks, measure changes in participants' Physical activity questionnaire scores. There is no fixed upper or lower limit to the total score, but scores at different activity intensities (walking, moderate intensity, high intensity) can be accumulated based on metabolic equivalents (MET-min/week). Higher score: Reflects the greater the total amount of physical activity an individual has engaged in in the past week.
Time frame: Baseline and Week 12
Change in number of finger taps in one minute
The change in number of finger taps in one minute of 30 volunteers before and after the intervention was measured.
Time frame: Baseline and Week 12
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