Legacy AI grade · Sources dated 2026-06-02. Not expert reviewed. Coverage is limited to the listed sources. About the new summary workflow

Calcium Alpha-Ketoglutarate for Frailty

Verdict: Insufficient Evidence

Across 3 PubMed studies, the evidence for Calcium Alpha-Ketoglutarate in Frailty grades Tier U — unverified / insufficient. Research is still too limited to draw a firm conclusion.

U ⚫ U Unverified Insufficient Evidence

🔬Why this grade7-layer evidence engine

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable
Raw score 0.45
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
U · Insufficient Evidence
Confidence
57%
Conflicting evidence
Evidence level
E10
Mechanism / case reports / no human evidence

How strongly each layer supports this effect

lower = less supportive
L11 AI re-checkIndependent read
0.20
L2 PubMedPrimary literature
0.40
L1 ExamineGlobal benchmark
0.50
L3 MechanismPlausibility
0.50
L5 Clinical bodiesAuthoritative stance
0.55
Against Mixed Supports
▸View the full decision path (audit trail)
  1. compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.453
  2. tier_from_score — 依分數區間映射至 tier letter
  3. apply_hec_rules — 僅有 E10 級證據 (cohort/animal/mechanism),不足以下結論
  4. tier_strict_requirement_check — C 級條件未達 (需 E1-E8;實際 E10 僅機轉)
  5. detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
  6. decide_status — 依 tier + dispute 結果決定 status

📄PubMed studies (3)L2 · primary research & systematic reviews

Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice
PMID: 32877690 2020 Animal study (mouse healthspan/frailty)
Finding: Ca-AKG reduced frailty (lower frailty index) and compressed morbidity in aging mice of both sexes, alongside extended female lifespan (+16.6% median). Proposed mechanism: dietary AKG induces IL-10, suppressing chronic inflammation ('inflammaging'). This is the central preclinical frailty/healthspan signal for Ca-AKG. ANIMAL evidence only.
Mixed funding Effect size: Reduced murine frailty index; compression of morbidity (both sexes)
View on PubMed
α-Ketoglutarate Ameliorates Sarcopenia in D-Galactose-Induced Aging Mice by Modulating Protein Homeostasis and Optimizing Mitochondrial Function
PMID: 41228408 2025 Animal study (mouse sarcopenia model)
Finding: AKG significantly improved muscle mass, exercise endurance, grip strength, and cold tolerance in D-gal-induced aging mice; enhanced myofiber protein composition/size; activated SIRT1/PGC-1α/Nrf2, boosting antioxidant (SOD) activity and mitochondrial function. Directly relevant to sarcopenia/frailty mechanisms. ANIMAL evidence only.
Academic Effect size: Improved muscle mass / grip strength / endurance (preclinical)
View on PubMed
α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway
PMID: 28939592 2018 Animal / cell mechanistic study (muscle atrophy)
Finding: AKG attenuated corticosterone-induced protein degradation and rescued muscle atrophy/dysfunction via a PHD3/ADRB2-mediated mechanism (AKG inhibits PHD3, stabilizing β2-adrenergic receptor ADRB2). Mechanistic basis for AKG preserving muscle mass relevant to sarcopenia/frailty. ANIMAL/CELL evidence only.
Academic Effect size: Rescued muscle atrophy (preclinical mechanism)
View on PubMed

🏛️Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …

L4a US FDA
Cautious
calcium alpha-ketoglutarate is legal in the U.S. as a supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA), provided manufacturers follow GMP standards and avoid unverified therapeutic claims source↗
L4b EU EFSA
Neutral
EFSA has not granted specific authorization for novel food use of calcium alpha-ketoglutarate source↗
L4d TW TFDA / 衛福部
Cautious
可供食品使用原料彙整一覽表 source↗
✓PMID 100% verifiedevery citation checked via NCBI Entrez
🔬3 PubMed studiesindependently re-checked by multiple sub-agents
engine_version: v1.0 claim_id: CLM-COND-frailty-INT-calcium-alpha-ketoglutarate-001 繁體中文版 →