Vitamin K2 MK-4
Vitamin ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Short-acting form of K2 that reaches bone and brain tissue rapidly.
Exploratory record, not a reviewed medical publication.
See the editorial and medical-review policies for the publication gate.
This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.
What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
Vitamin K2 MK-4 is a vitamin most often used for bone health, brain health, dental health. NutriStack rates the overall evidence as moderate. A typical adult dose is 5-45 mg daily (much higher doses than MK-7), commonly taken as menaquinone-4 (mk-4). This profile indexes 16 sources.
The bottom line
Evidence rating moderate. Most-documented uses: bone health, brain health, dental health. 16 sources indexed (2000–2023), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Rapidly absorbed, short half-life (~6 hours vs MK-7's ~72 hours). Preferentially activates osteocalcin in bone. May have unique effects on gene expression via SXR/PXR nuclear receptor.7
Dosing & protocol.
What it actually costs.
Real-world pricing across three quality tiers. Assumes Vitamin K2 MK-4.
Assumes a practical daily MK-4 dose. MK-4 products are usually costlier than MK-7 because doses are larger and repeat dosing is common. Updated 2026-04-02.
The same dose, as food.
How much you'd eat to match a supplemental dose.
MK-4 supplement doses are usually much higher than what food alone provides.
Full safety detail.
Side effects
- Very well tolerated even at high doses
Contraindications
- Blood thinners (warfarin)
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
2- 1Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trialsPMIDMa ML et al. · Front Public Health · 2022
Meta-analysis of 16 RCTs (6,425 subjects) showed VK2 significantly improves lumbar spine BMD, reduces fracture incidence, and decreases uncarboxylated osteocalcin in postmenopausal women.
- 2Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trialsPMIDCockayne S et al. · Arch Intern Med · 2006
Meta-analysis of Japanese MK-4 trials showed significant fracture reduction: OR 0.40 for vertebral, 0.23 for hip, and 0.19 for all nonvertebral fractures.
Randomized controlled trials
6- 3Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese womenPMIDKoitaya N et al. · J Bone Miner Metab · 2014
Low-dose MK-4 (1.5 mg/day) for 12 months improved bone turnover markers and prevented forearm bone mineral density loss in postmenopausal women aged 50-65.
- 4Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose-response studyPMIDNakamura E, Aoki M, Watanabe F et al. · Nutrition journal · 2014
Nakamura E, Aoki M, Watanabe F et al.. Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose-response study. Nutrition journal. 2014
- 5The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trialPMIDSato Y, Honda Y, Umeno K et al. · The Kurume medical journal · 2011
Sato Y, Honda Y, Umeno K et al.. The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial. The Kurume medical journal. 2011
- 6Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsulesPMIDInoue T, Fujita T, Kishimoto H et al. · Journal of bone and mineral metabolism · 2009
Inoue T, Fujita T, Kishimoto H et al.. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. Journal of bone and mineral metabolism. 2009
- 7Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective studyPMIDShiraki M, Itabashi A · Journal of bone and mineral metabolism · 2009
Shiraki M, Itabashi A. Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. Journal of bone and mineral metabolism. 2009
- 8Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosisPMIDShiraki M et al. · J Bone Miner Res · 2000
In 241 osteoporotic patients over 24 months, 45 mg/day vitamin K2 significantly reduced clinical fracture incidence and maintained lumbar BMD compared to untreated controls.
Reviews & position papers
5- 9The biological responses of vitamin K2: A comprehensive reviewPMIDHalder M et al. · Clin Nutr · 2023
Comprehensive review confirming MK-4's unique functions as SXR/PXR ligand, mitochondrial electron carrier, and transcriptional regulator, with roles beyond carboxylation in bone and brain.
- 10Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplementsPMIDMeinitzer A, Enko D, Zelzer S et al. · Clinical chemistry and laboratory medicine · 2022
Meinitzer A, Enko D, Zelzer S et al.. Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements. Clinical chemistry and laboratory medicine. 2022
- 11Vitamin K2 therapy for postmenopausal osteoporosisSource linkedPMIDIwamoto J, Takeda T, Sato Y · Nutrients · 2014
- 12Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese womenPMIDKoitaya N, Ezaki J, Nishimuta M et al. · Journal of nutritional science and vitaminology · 2009
Koitaya N, Ezaki J, Nishimuta M et al.. Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Journal of nutritional science and vitaminology. 2009
- 13The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot studyPMIDMizuta T, Ozaki I, Eguchi Y et al. · Cancer · 2006
Mizuta T, Ozaki I, Eguchi Y et al.. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study. Cancer. 2006
Mechanistic & preclinical
1- 14Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in ratPMIDFarhadi Moghadam B, Fereidoni M · PloS one · 2020
MK-4 increased SOD activity and GLT-1 mRNA levels in brain, inhibiting oxidative stress and neurotoxicity, demonstrating neuroprotective effects against cerebral ischemia/reperfusion injury.
Reference material
2- 15Tan J, Zhu R, Li Y et al.. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA internal medicine. 2024Source linkedPMID
- 16Diederichsen ACP, Lindholt JS, Möller S et al.. Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation. 2022Source linkedPMID
Common questions.
Quick answers about Vitamin K2 MK-4, drawn from the data on this page.
What is Vitamin K2 MK-4?
Short-acting form of K2 that reaches bone and brain tissue rapidly.
What is Vitamin K2 MK-4 used for?
Commonly cited benefits of Vitamin K2 MK-4 include: Bone health; Brain health; Dental health. NutriStack rates the overall evidence as moderate.
What is a typical dose of Vitamin K2 MK-4?
A typical adult dose of Vitamin K2 MK-4 is 5-45 mg daily (much higher doses than MK-7). The commonly recommended form is Menaquinone-4 (MK-4). These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Vitamin K2 MK-4?
Reported side effects include very well tolerated even at high doses. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Vitamin K2 MK-4?
NutriStack rates this as Moderate, meaning several aligned RCTs or one large RCT plus supporting reviews. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Vitamin K2 MK-4 in NutriStack.
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