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

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#biomarkers #dietary-supplements #humans #vascular-calcification #vascular-diseases

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

Lees et al., 2019 | Heart | Meta Analysis

Citation

Lees Jennifer Susan, Chapman Fiona A, ... Mark Patrick B. Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis. Heart. 2019-Jun;105(12):938-945. doi:10.1136/heartjnl-2018-313955

Abstract

OBJECTIVES: Vascular stiffness (VS) and vascular calcification (VC) are surrogate markers of vascular health associated with cardiovascular events. Vitamin K-dependent proteins (VKDP) are associated with VS and VC and require vitamin K for activity. We conducted a systematic review and meta-analysis of: (1) the effect of vitamin K supplementation on VS and VC and (2) association of inactive VKDP levels with incident cardiovascular disease and mortality. METHODS: Two authors searched MEDLINE and Embase databases and Cochrane and ISRCTN registries for studies of vitamin K clinical trials that measured effects on VC, VS or VKDP and longitudinal studies assessing effect of VKDP on incident CVD or mortality. Random effects meta-analyses were performed. RESULTS: Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with median follow-up of 7.8 (IQR 4.9-11.3) years, VKDP levels were associated with a combined endpoint of CVD or mortality (HR 0.45 (95% CI 0.07 to 0.83), p=0.02). CONCLUSIONS: Supplementation with vitamin K significantly reduced VC, but not VS, compared with control. The conclusions drawn are limited by small numbers of studies with substantial heterogeneity. VKDP was associated with combined endpoint of CVD or mortality. Larger clinical trials of effect of vitamin K supplementation to improve VC, VS and long-term cardiovascular health are warranted. TRIAL REGISTRATION NUMBER: CRD42017060344.

Key Findings

Thirteen controlled clinical trials (n=2162) and 14 longitudinal studies (n=10 726) met prespecified inclusion criteria. Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS. In longitudinal studies with m

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 2162
Age Range See abstract
Condition See abstract

MeSH Terms

  • Biomarkers
  • Dietary Supplements
  • Humans
  • Vascular Calcification
  • Vascular Diseases
  • Vitamin K
  • Vitamins

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review
  • Vertical: vitamin-k-cardiovascular

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09