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Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis

Systematic review and meta-analysis (13 controlled trials, n=2,162) reporting vitamin K supplementation was associated with lower vascular calcification and large reductions in inactive vitamin K–dependent protein biomarkers versus control; pooled vascular stiffness change was not statistically significant, with substantial heterogeneity across trials.

Design

Two authors searched MEDLINE, Embase, trial registries (Cochrane, ISRCTN) for vitamin K clinical trials reporting vascular calcification (VC), vascular stiffness (VS), or VKDP markers, plus longitudinal studies linking inactive VKDP levels to incident CVD or mortality.

Pooled supplementation results (random-effects meta-analyses)

  • Vascular calcification: −9.1% (95% CI −17.7% to −0.5%; p = 0.04) with vitamin K supplementation vs control (13 trials, n = 2,162).
  • dp-ucMGP (inactive matrix Gla protein): −44.7% (95% CI −65.1% to −24.3%; p < 0.0001).
  • Uncarboxylated osteocalcin: −12.0% (95% CI −16.7% to −7.2%; p < 0.0001).
  • Vascular stiffness: no significant pooled improvement in the abstract’s summary of the supplementation meta-analysis.

Longitudinal VKDP arm (association tier)

Across 14 longitudinal studies (n = 10,726; median follow-up 7.8 years), authors report inactive VKDP burden associated with a combined CVD or mortality endpoint (HR 0.45, 95% CI 0.07–0.83; p = 0.02) in abstract framing—read full text for endpoint definitions and heterogeneity.

Evidence hygiene

  • Formulation mix: included trials used vitamin K1 and/or menaquinone (K2) products at varying doses—do not treat pooled VC movement as MK-7–only or HRV evidence.
  • Wearables: this review does not report RMSSD / HF-HRV outcomes; pair with vitamin-k2-supplementation N=1 rows only as separate evidence tier.
  • Causality: authors stress small trial counts, heterogeneity, and need for larger trials tying biomarker shifts to hard cardiovascular endpoints.

Outcomes

  • other
    -9.1
  • other
    Inactive VKDP biomarkers: dp-ucMGP −44.7% (95% CI −65.1% to −24.3%; p < 0.0001); uncarboxylated osteocalcin −12.0% (95% CI −16.7% to −7.2%; p < 0.0001) vs control
  • other
    Vascular stiffness: no statistically significant pooled improvement in the supplementation meta-analysis (per abstract); longitudinal VKDP–outcome associations reported separately with heterogeneity caveats
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