Longevity & Aging · Metabolic & Cardiometabolic
metabolic vulnerability index (MVX) predicts 5-year all-cause mortality (out-predicting chronological age)
In plain terms: Can a blood-metabolite 'vulnerability' score predict death better than your age?
Part of: • Aging
In its derivation cohort the NMR-based MVX score predicted near-term mortality strongly and added prediction beyond chronological age, with several independent cohorts now replicating it.
📅 Last reviewed: 2026-07-14 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Population patterns (Observational)
How the studies fall
What the evidence shows
In UK Biobank the NMR-based metabolic vulnerability index showed a graded association with all-cause mortality and added prediction beyond chronological age. Support comes largely from its own derivation cohort and related metabolomic scores, several of which add only marginally once standard risk factors are included, so this is a promising predictor, not a validated tool.
The evidence (14)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Li J, Man Q, Wang Y, Cui M, Li J, Xu K, Liu Z, Jin L, Chen X, Suo C, Jiang Y 2025 · Redox Biol | observational | mixed | high | In 274,092 UK Biobank participants the metabolic vulnerability index (MVX) showed a graded association with all-cause mortality (top-quartile HR 1.21). |
| Mateus P, Garst S, Yu J, Cats D, Harms AGJ, Birhanu M, Beekman M, Slagboom PE, Reinders M, van der Grond J, Dekker A, Jansen JFA, Beran M, Schram MT, Visser PJ, Moonen J, Ghanbari M, Roshchupkin G, Vojinovic D, Bermejo I, Mei H, Bron EE 2025 · J Healthc Inform Res | observational | mixed | moderate | Federated analysis of three cohorts found MetaboAge and MRI-based BrainAge acted synergistically to predict time to all-cause mortality. |
| Gu J, Gao L, Li J, Wu S, Chen Y 2026 · Nutr Metab Cardiovasc Dis | observational | supports | moderate | An externally validated plasma metabolomic signature predicted 3-year all-cause mortality in older CAD patients with incremental value over clinical risk factors. |
| Wang X, Gao Y, Lip GYH, Guo J, Zhang J 2026 · NPJ Cardiovasc Health | observational | mixed | high | In 239,135 UK Biobank participants, higher MVX (six NMR biomarkers) was associated with higher MACE risk (HR=1.08 per unit, 95% CI 1.07-1.10) over median 13.6 years; low CVH plus high MVX had HR=2.84 for MACE. |
| van Holstein Y, Mooijaart SP, van Oevelen M, van Deudekom FJ, Vojinovic D, Bizzarri D, van den Akker EB, Noordam R, Deelen J, van Heemst D, de Glas NA, Holterhues C, Labots G, van den Bos F, Beekman M, Slagboom PE, van Munster BC, Portielje JEA, Trompet S 2024 · Geroscience | observational | mixed | moderate | In 192 older cancer patients MetaboHealth was associated with 1-year mortality (HR 2.32/SD) but added only marginally (AUC 0.76 to 0.80) beyond clinical predictors. |
| Lau CE, Manou M, Markozannes G, Ala-Korpela M, Ben-Shlomo Y, Chaturvedi N, Engmann J, Gentry-Maharaj A, Herzig KH, Hingorani A, Järvelin MR, Kähönen M, Kivimäki M, Lehtimäki T, Marttila S, Menon U, Munroe PB, Palaniswamy S, Providencia R, Raitakari O, Schmidt AF, Sebert S, Wong A, Vineis P, Tzoulaki I, Robinson O 2024 · Aging Cell | observational | mixed | high | Independent UK/Finnish multicohort (~133k): NMR metabolomic age/mortality models only moderately track chronological age but DO add mortality prediction beyond age — supports added value, tempers 'out-predicts age' framing. |
| Zheutlin AR, Ning H, Allen NB, Carnethon MR, Murthy VL, Goonewardena SN, Vaughan DE, Otvos JD, Wilkins JT 2026 · Circ Popul Health Outcomes | observational | supports | high | In MESA (5887 adults, CVD-free at baseline), NMR-derived MVX (GlycA, small HDL particles, valine, leucine, isoleucine, citrate) quartile 4 had HR=1.73 (95% CI 1.49-2.01) for total mortality over 17.9 years median follow-up, with minimal att |
| Kunutsor SK, Rikhtehgaran R, Xu Y, Connelly MA, Shalaurova I, Chaker L, Bakker SJL, Dullaart RPF 2026 · Endocrinol Diabetes Metab | observational | supports | high | In PREVEND (5446 participants), per-SD increases in MVX, IVX, and MMX (all NMR-derived) were associated with all-cause mortality HRs of 1.28, 1.23, and 1.16 respectively, with graded dose-response relationships; associations were unaffected |
| Otvos JD, Shalaurova I, May HT, Muhlestein JB, Wilkins JT, McGarrah RW, Kraus WE 2023 · Lancet Healthy Longev | observational | supports | moderate | MVX origin paper (Otvos/Shalaurova/McGarrah/Kraus; NO Norwitz/Feldman/Soto-Mota=independent of LMHR net): NMR metabolic+inflammation markers predict mortality strongly. NMR-platform-dev COI noted. |
| Horne BD, May HT, Muhlestein JB, Ronnow BS, Lappé DL, Renlund DG, Kfoury AG, Carlquist JF, Fisher PW, Pearson RR, Bair TL, Anderson JL 2009 · Am J Med | observational | supports | moderate | A risk score from routine complete-blood-count and metabolic-panel components strongly predicted all-cause mortality, showing multi-analyte scores add prognostic information. |
| Conners KM, Shearer JJ, Joo J, Park H, Manemann SM, Remaley AT, Otvos JD, Connelly MA, Sampson M, Bielinski SJ, Wolska A, Turecamo S, Roger VL 2024 · JACC Heart Fail | observational | supports | moderate | Independent group: MVX predicted mortality in heart-failure patients, adding prognostic value beyond conventional markers — external replication of MVX mortality signal. |
| Fischer K, Kettunen J, Würtz P, Haller T, Havulinna AS, Kangas AJ, Soininen P, Esko T, Tammesoo ML, Mägi R, Smit S, Palotie A, Ripatti S, Salomaa V, Ala-Korpela M, Perola M, Metspalu A 2014 · PLoS Med | observational | supports | high | NMR biomarker profiling in 17,345 persons identified a 4-biomarker score predicting short-term all-cause mortality, adding to conventional risk factors. |
| Kuiper LM, Polinder-Bos HA, Bizzarri D, Vojinovic D, Vallerga CL, Beekman M, Dollé ET, Ghanbari M, Voortman T, Reinders MJT, Verschuren WMM, Slagboom PE, van den Akker EB, van Meurs JBJ 2023 · J Gerontol A Biol Sci Med Sci | observational | supports | high | MetaboHealth (mortality-trained metabolomic score) predicted mortality and frailty independent of epigenetic clocks, outperforming age-trained markers. |
| Wang T, Beyene HB, Yi C, Cinel M, Mellett NA, Olshansky G, Meikle TG, Wu J, Dakic A, Watts GF, Hung J, Hui J, Beilby J, Blangero J, Kaddurah-Daouk R, Salim A, Moses EK, Shaw JE, Magliano DJ, Huynh K, Giles C, Meikle PJ 2024 · EBioMedicine | observational | supports | moderate | A lipidomic metabolic age score captured cardiometabolic risk and associated with all-cause mortality independent of chronological age across validation cohorts. |
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