Vitamin K

Association of Vitamin K with Cardiovascular Events and All-Cause Mortality: A Systematic Review and Meta-Analysis 

Study: This meta-analysis, published in 2019, reviewed prospective studies assessing the association between vitamin K (dietary intake or circulating levels) and cardiovascular disease (CVD) events, including coronary heart disease (CHD), stroke, and all-cause mortality. It included data from multiple studies, analyzing biomarkers like desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) and osteocalcin. 

Findings: Higher dietary vitamin K intake was associated with a moderately lower risk of CHD but not with stroke or all-cause mortality. Elevated dp-ucMGP (a marker of vitamin K deficiency) was linked to a 1.84-fold increased risk of all-cause mortality and a 1.96-fold increased risk of CVD mortality. No significant association was found between circulating osteocalcin and CVD or mortality. The study noted that causal relationships cannot be confirmed due to limited studies, calling for larger RCTs. 

Link: https://link.springer.com/article/10.1007/s00394-019-01998-3   

A Systematic Review and Meta-Analysis of the Association Between Vitamin K Antagonist Use and Fracture 

Study: Published in 2018, this meta-analysis examined 23 studies (22 observational, 1 RCT) with 1,121,582 participants to investigate whether vitamin K antagonists (VKAs, e.g., warfarin) increase fracture risk compared to controls or non-vitamin K antagonist oral anticoagulants (NOACs). It assessed fracture odds in adults using VKAs. 

Findings: No increased fracture risk was found in VKA users compared to controls (pooled OR 1.01, 95% CI 0.89–1.14) or NOAC users (pooled OR 0.95, 95% CI 0.78–1.15). Long-term VKA use (≥1 year) also showed no increased risk. However, a slight increase in fracture odds was noted in women (OR 1.11) and older VKA users (≥65, OR 1.07), though clinical significance was questionable. The study suggests fracture risk should not heavily influence anticoagulant choice. 

Link: https://link.springer.com/article/10.1007/s11606-018-4758-3    

Effect of Vitamin K Supplementation on Serum Calcification Propensity and Arterial Stiffness in Vitamin K-Deficient Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial 

Study: This 2021 RCT involved 40 vitamin K-deficient kidney transplant recipients (KTRs) with high dp-ucMGP levels (≥500 pmol/L). Participants received vitamin K2 (menaquinone-7, MK-7) or placebo for an unspecified duration to assess effects on serum calcification propensity (T50) and arterial stiffness (pulse wave velocity, PWV). 

Findings: Vitamin K supplementation significantly improved vitamin K status (reduced dp-ucMGP by 385 pmol/L vs. placebo’s increase of 39 pmol/L). It prevented progression of arterial stiffness (PWV change: -0.06 m/s vs. +0.27 m/s in placebo, p=0.010) but had no effect on calcification propensity (T50 change: +2.3 vs. +0.8 minutes, p=0.88). Most patients remained vitamin K-deficient, suggesting longer-term studies are needed to explore vascular benefits. 

Link: https://www.sciencedirect.com/science/article/pii/S0272638621000800   

Vitamin K2 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women: A Double-Blind Randomized Clinical Trial 

Study: This 2015 RCT (Knapen et al.) involved 244 healthy postmenopausal women randomized to receive 180 µg/day of MK-7 or placebo for 3 years. The study measured arterial stiffness (via carotid-femoral PWV) and vascular health markers like dp-ucMGP. 

Findings: MK-7 supplementation significantly reduced arterial stiffness (PWV decreased compared to placebo) and lowered dp-ucMGP levels, indicating improved vitamin K status. The effect was most pronounced in women with higher baseline stiffness. No adverse events were reported, supporting MK-7’s safety. The study suggests vitamin K2 may benefit vascular health in postmenopausal women, though larger trials are needed for clinical recommendations. 

Link: https://www.thieme-connect.com/products/ejournals/abstract/10.1160/TH14-08-0675

Inhibiting the Progression of Arterial Calcification with Vitamin K in Hemodialysis Patients (iPACK-HD) Trial: Rationale and Study Design for a Randomized Trial of Vitamin K in Patients with End-Stage Kidney Disease 

Study: This 2015 trial (protocol described by Holden et al.) is an RCT designed to assess whether vitamin K1 supplementation (10 mg/day) slows arterial calcification in hemodialysis patients with end-stage kidney disease. The study measures coronary artery calcification scores and other vascular markers over 12 months. 

Findings: As a protocol paper, no results are provided, but the rationale highlights vitamin K’s role in activating matrix Gla protein (MGP) to inhibit calcification. Preliminary data suggested high dp-ucMGP in hemodialysis patients, indicating vitamin K deficiency. The trial aims to provide evidence for vitamin K’s potential to reduce vascular calcification, but results are not yet published in the provided sources. 

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443636/   

Protocol for a Randomised Controlled Trial to Investigate the Effects of Vitamin K2 on Recovery from Muscle-Damaging Resistance Exercise in Young and Older Adults 

Study: This ongoing RCT (registered 2020, ClinicialTrials.gov NCT04676958) involves 80 adults (40 young ≤40 years, 40 older ≥65 years) receiving vitamin K2 or placebo for 12 weeks. It assesses muscle strength (primary outcome), pain-free range of motion, inflammation, and oxidative stress markers post-resistance exercise. 

Findings: No results are available yet, as the trial is ongoing. The study hypothesizes that vitamin K2 may enhance recovery by modulating inflammation and redox balance, given its role in vitamin K-dependent proteins (VKDPs). Findings will be disseminated via conferences and journals, potentially informing exercise recovery strategies. 

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662620/

Vitamin K Supplementation and Vascular Calcification: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 

Study: This 2023 meta-analysis reviewed 14 RCTs to evaluate vitamin K supplementation’s effect on vascular calcification (VC), measured by coronary artery calcification (CAC) scores, vascular stiffness, and dp-ucMGP levels. It included diverse populations, including those with chronic kidney disease. 

Findings: Vitamin K supplementation significantly reduced dp-ucMGP and slowed VC progression in some trials but showed inconsistent effects on CAC scores. Anti-inflammatory effects via NF-κB pathway inhibition were noted, suggesting a mechanism for VC reduction. Heterogeneity in vitamin K forms, doses, and study populations limited conclusions, and no significant adverse events were reported. Larger, high-quality RCTs are needed. 

Link: https://www.frontiersin.org/articles/10.3389/fnut.2023.1115069/full