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 Bone Health

Verdict: Weak evidence; not proven for bone health

Calcium alpha-ketoglutarate (Ca-AKG) is not established for bone health. One small trial lowered a bone-resorption marker, but it did not significantly improve bone density, and no fracture data exist.

C 🟠 C Weak Evidence Published

🔬Why this grade7-layer evidence engine

The grade rests on thin human data. The only clinical trial (Filip 2007, PMID 17896582) randomized 76 postmenopausal women with osteopenia to AKG-calcium (6 g AKG plus 1.68 g calcium daily) versus calcium alone. The bone-resorption marker CTX fell about 37% at 24 weeks (p=0.006), but the between-group lumbar-spine bone-density difference (+0.9%) was not statistically significant, and no fracture outcomes were measured.

Supporting evidence is preclinical. In mice, AKG increased bone mass and slowed age-related loss via histone-methylation changes (Wang 2020, PMID 33154378), and a cell study showed AKG curbs osteoclast formation through NF-kB/PHD1 signaling (Tian 2023, PMID 36771407). These give a plausible mechanism but do not prove benefit in people.

Regulators and clinics do not endorse it. The US FDA treats Ca-AKG only as a DSHEA supplement ingredient that must follow GMP and avoid unverified therapeutic claims; the EU EFSA has not authorized it as a novel food; the UK NHS and WHO do not address it. With one small, unreplicated trial, a non-significant density endpoint, and a study dose (6 g/day) far above typical retail doses, the evidence stays Weak (Tier C). Calcium plus vitamin D and weight-bearing exercise remain the guideline-backed options.

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable
Raw score 0.52
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
C · Published
Confidence
60%
Broadly consistent
Evidence level
E7
Single small RCT

How strongly each layer supports this effect

lower = less supportive
L11 AI re-checkIndependent read
0.30
L1 ExamineGlobal benchmark
0.50
L3 MechanismPlausibility
0.50
L5 Clinical bodiesAuthoritative stance
0.55
L2 PubMedPrimary literature
0.60
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 = 0.523
  2. tier_from_score — 依分數區間映射至 tier letter
  3. apply_hec_rules — 無高階證據可裁決
  4. tier_strict_requirement_check — Tier 條件達標,未降階
  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 decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study
PMID: 17896582 2007 RCT (randomized, parallel-group, double-blind) n = 76
Finding: AKG-Ca group: maximum mean CTX decrease 37.0% at 24 weeks (p=0.006); between-group CTX difference significant at 12 and 24 weeks. Lumbar spine BMD increased 1.6% from baseline in AKG-Ca group, but between-group BMD difference (0.9%) was NOT statistically significant. Authors conclude AKG-Ca induced beneficial changes in serum CTX consistent with preserving lumbar bone mass; long-term effect needs further study.
Effect size: CTX -37.0% at 24 wk (p=0.006); BMD between-group +0.9% (NS)
View on PubMed
Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
PMID: 33154378 2020 Animal study (mouse / rodent osteoporosis models)
Finding: AKG increased bone mass of aged mice, attenuated age-related bone loss, accelerated bone regeneration, and prevented bone loss in ovariectomized models. Mechanism: AKG decreased H3K9me3/H3K27me3 accumulation in bone-marrow MSCs, upregulating BMP signaling and Nanog, ameliorating senescence-associated phenotypes. ANIMAL evidence only.
Academic Effect size: Increased bone mass / attenuated loss (preclinical)
View on PubMed
Elevation of Intracellular Alpha-Ketoglutarate Levels Inhibits Osteoclastogenesis by Suppressing the NF-κB Signaling Pathway in a PHD1-Dependent Manner
PMID: 36771407 2023 In vitro / mechanistic study (cell culture)
Finding: Raising intracellular AKG (via DM-AKG) inhibited RANKL-induced osteoclast differentiation and suppressed NF-κB signaling and oxidative phosphorylation; effect reversed by PHD1 blockade (PHD1/EglN2-dependent). Provides mechanistic basis for AKG reducing bone resorption. IN VITRO evidence only.
Academic Effect size: Inhibited osteoclastogenesis (in vitro)
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-bone-health-INT-calcium-alpha-ketoglutarate-001 繁體中文版 →