Mechanism of Action
Vitamin K2 acts as a cofactor for an enzyme called gamma-glutamyl carboxylase. This enzyme activates vitamin K-dependent proteins by adding carboxyl groups to their glutamic acid residues.
Two of these proteins play a decisive role in calcium management. Osteocalcin, produced by osteoblasts (bone-building cells), can only bind calcium to the bone matrix in its carboxylated form. MGP (Matrix Gla Protein), secreted by vascular smooth muscle cells, prevents calcium deposits in arterial walls once activated.
Without sufficient vitamin K2, both proteins remain in their inactive form. Calcium absorbed thanks to vitamin D then circulates without being properly directed. The MK-7 form stands out for its long plasma half-life, which keeps it available in the bloodstream for approximately three days and allows it to efficiently reach peripheral tissues.
Key Benefits
- Strong
Better-preserved bones with age: vitamin K contributes to the maintenance of normal bones. Controlled trials confirm this, with improved bone mineral density and reduced fracture risk in postmenopausal women supplemented with MK-7 for three years.
- Strong
Blood that clots normally: vitamin K contributes to normal blood clotting. It activates clotting factors II, VII, IX and X through carboxylation, a role established since the 1930s.
- Strong
More bone density in the lower back: a meta-analysis of 16 controlled trials (2022, 6,425 subjects) measures improved mineral density at the lumbar vertebrae in postmenopausal women supplemented with vitamin K2.
- Strong
Less bone loss over time: a three-year controlled trial (Knapen et al., 2013) shows that 180 mcg/day of MK-7 limits density loss at the femoral neck and lumbar vertebrae in postmenopausal women.
- Moderate
Less calcified arteries: a large cohort (Rotterdam Study, 4,807 subjects followed for 7 years) associates high menaquinone intake with a significant reduction in aortic calcification.
- Moderate
More supple arteries: a three-year controlled trial (Knapen et al., 2015) measures improved arterial stiffness (pulse wave velocity) in healthy postmenopausal women supplemented with MK-7.
Dosage & Forms
Vitamin K2 exists in several forms. MK-4 (menaquinone-4) has a very short half-life (1 to 2 hours) and requires multiple daily doses at high levels (often 15 mg in Japan for osteoporosis). MK-7, produced by bacterial fermentation, has a half-life of approximately 72 hours. This extended pharmacokinetics allows a single daily dose and stable serum levels.
The literature places the effective MK-7 dosage between 90 and 200 mcg per day for complete carboxylation of circulating osteocalcin. The trials by Knapen et al. (2013, 2015) used 180 mcg/day for three years.
Singular selects the all-trans MK-7 form from the Pharmaquinone brand, produced by fermentation. The all-trans isomer is the only biologically active form; cis isomers, found in some lower-quality raw materials, are inactive.
In the Singular Formula
Inclusion rationale
Vitamin K contributes to the maintenance of normal bones and to normal blood coagulation. Menaquinone-7 (MK-7) form, naturally produced by bacterial fermentation, the same process that gives Japanese natto its characteristic texture. MK-7 stands out from other forms of vitamin K by its long plasma half-life (approximately 72 hours versus 1 to 2 hours for K1), ensuring prolonged presence in the circulation and efficient distribution to extra-hepatic tissues, notably bones and blood vessels. Vitamin K2 activates two key proteins. In bones, osteocalcin binds calcium to the bone matrix. In blood vessels, MGP (Matrix Gla Protein) inhibits arterial calcification. This dual action directs calcium toward bones and away from arteries. K2-MK7 is an essential complement to vitamin D3 (also present in the formula), with which it shares the calcium metabolism axis. This same bone axis includes magnesium, boron and calcium alpha-ketoglutarate, forming a coherent network of cofactors working in concert to maintain bone health.
Selected form
Vitamin K2 as menaquinone-7 (MK-7), Pharmaquinone brand, all-trans isomer produced by fermentation. The all-trans isomer is the only biologically active form of MK-7. Unlike MK-4 forms (short half-life of a few hours), MK-7 has an extended half-life (approximately 72 hours), allowing stable blood levels with a single daily intake. Vitamin K contributes to the maintenance of normal bones and to normal blood clotting. Microcrystalline cellulose (MCC) carrier.
Formula dosage
0 to 180 µg.
Synergies in the formula
Linked Biomarkers
Safety & Precautions
Vitamin K2-MK7 has a favorable safety profile at common nutritional doses. No tolerable upper intake level has been established for vitamin K, given the absence of reported toxicity even at high doses.
The main precaution concerns individuals taking vitamin K antagonist anticoagulants (warfarin, acenocoumarol). Vitamin K2 can alter the effectiveness of these medications by restoring carboxylation of clotting factors. In this situation, it is inadvisable to start vitamin K2 supplementation without informing your physician.
For individuals not taking anticoagulants, MK-7 at doses of 90 to 200 mcg per day does not alter coagulation parameters in a clinically significant manner. Pregnancy and breastfeeding carry no specific restrictions, as vitamin K is administered to newborns at birth to support coagulation.
Scientific Studies
| Authors | Year | Type | Journal | |
|---|---|---|---|---|
| Ma ML et al. | 2022 | Meta-analysis | Frontiers in Public Health | View on PubMed |
Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials Meta-analysis of 16 controlled trials (6,425 subjects) evaluating the effect of vitamin K2 on bone density in postmenopausal women. Ten studies show significant improvement in lumbar spine density. | ||||
| Knapen MHJ et al. | 2013 | Randomised Controlled Trial | Osteoporosis International | View on PubMed |
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women Controlled trial in 244 postmenopausal women: 180 mcg/day of MK-7 for 3 years reduces bone density loss at lumbar vertebrae and femoral neck. | ||||
| Knapen MHJ et al. | 2015 | Randomised Controlled Trial | Thrombosis and Haemostasis | View on PubMed |
Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial Double-blind randomized trial: 180 mcg/day of MK-7 for 3 years improves arterial stiffness in healthy postmenopausal women. | ||||
| Geleijnse JM et al. | 2004 | Cohort Study | The Journal of Nutrition | View on PubMed |
Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study Prospective cohort study on 4,807 subjects followed for 7 years: high menaquinone intake is associated with reduced severe aortic calcification. | ||||
| van Summeren MJH et al. | 2009 | Randomised Controlled Trial | British Journal of Nutrition | View on PubMed |
The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children Controlled trial in 55 prepubertal children: 45 mcg/day of MK-7 for 8 weeks improves osteocalcin carboxylation, a bone activation marker. | ||||
| Fusaro M et al. | 2020 | Systematic Review | Nutrients | View on PubMed |
Vitamin K and Osteoporosis Review on the role of vitamin K in osteocalcin and MGP carboxylation, and the implications for bone health. | ||||