tuneTypical Dose
90-360 mcg/day
Vitamin
Vitamin K2
Menaquinone (MK-4, MK-7)
Evidence TierAWADA NOT PROHIBITED
watchEffect Window
Biomarker shifts over weeks to months; structural outcomes over longer horizons.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Vitamin K2 (menaquinones such as MK-7) activates proteins that regulate calcium placement in bone and soft tissue. It is used for bone density support and vascular calcification-related biomarker goals.
Recent evidence still supports vitamin K2 mainly through biomarker and bone-turnover pathways rather than through hard fracture or cardiovascular outcomes. A newer meta-analysis in postmenopausal osteoporosis found better osteocalcin carboxylation and lower ucOC and TRAP, which strengthens the bone-metabolism story. Vascular outcome evidence remains mixed and population specific, so K2 is best framed as a bone-focused adjunct with possible but unproven vascular benefit.
Vitamin K2 activates vitamin K-dependent proteins such as osteocalcin and MGP to improve calcium handling in bone and vasculature.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Supports bone mineralization and vitamin K-dependent carboxylation pathways.
Secondary Outcomes
- May improve vascular stiffness/calcification risk markers over long durations.
Safety
Contraindications and Interactions
Contraindications
- Active warfarin or vitamin K antagonist therapy without clinician management
Side effects
- Usually mild gastrointestinal discomfort
Interactions
- Warfarin and related vitamin K antagonist medications
Avoid if
- Unstable anticoagulation management
Evidence
Study-level References
vitamin-k2-SRC-001Randomized controlled trial
Sourceopen_in_newKnapen MHJ, et al. "Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women." Thromb Haemost. 2015.
Population: Healthy postmenopausal women
Key findings: MK-7 improved vitamin K status and vascular stiffness-related measures over multi-year follow-up.
Paper content
MK-7 improved vitamin K status and vascular stiffness-related measures over multi-year follow-up.
vitamin-k2-SRC-002Review
Sourceopen_in_newBeulens JWJ, et al. "The role of menaquinones (vitamin K2) in human health." Br J Nutr. 2013.
Population: Adults across observational and intervention studies
Key findings: Supports mechanistic and cohort-level links for bone and vascular outcomes, with endpoint heterogeneity across studies.
Paper content
Supports mechanistic and cohort-level links for bone and vascular outcomes, with endpoint heterogeneity across studies.
vitamin-k2-SRC-003Multicenter randomized controlled trial
Sourceopen_in_newNaiyarakseree N, Phannajit J, Naiyarakseree W, Mahatanan N, Asavapujanamanee P, Lekhyananda S, Vanichakarn S, Avihingsanon Y, Praditpornsilpa K, Eiam-Ong S, Susantitaphong P. Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial. Nutrients. 2023;15(11):2422. doi:10.3390/nu15112422. PMID:37299386.
Population: Chronic hemodialysis patients with elevated arterial stiffness.
Dose protocol: MK-7 375 mcg once daily for 24 weeks in chronic hemodialysis patients.
Key findings: No overall primary-endpoint improvement in arterial stiffness, but slower progression and better cfPWV change appeared in the diabetes subgroup.
Notes: Useful as a corrective modern vascular RCT showing that benefit is not universal.
Paper content
This randomized trial did not improve the primary arterial-stiffness endpoint overall, but it suggested slower stiffness progression in the diabetes subgroup and reported no serious adverse events.
vitamin-k2-SRC-004Systematic review and meta-analysis
Sourceopen_in_newZhang Z, Li Y, Li J, et al. The effect of vitamin K2 supplementation on bone turnover biochemical markers in postmenopausal osteoporosis patients: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2025;16:1703116. doi:10.3389/fendo.2025.1703116. PMID:41268154.
Population: Postmenopausal women with osteoporosis enrolled in randomized vitamin K2 trials.
Dose protocol: Vitamin K2 across 9 randomized trials in postmenopausal osteoporosis
Key findings: Meta-analysis found higher osteocalcin and bone-specific alkaline phosphatase, lower undercarboxylated osteocalcin and TRAP, and no clear NTX change.
Notes: Best modern source for keeping the K2 benefit centered on bone-turnover biology rather than overstated fracture or vascular promises.
Paper content
Vitamin K2 improved several bone-turnover biomarkers in postmenopausal osteoporosis, particularly osteocalcin carboxylation-related measures, while leaving NTX unchanged. This is an important modernization source because it strengthens the biomarker case for K2 without overstating hard fracture or vascular outcomes.