Mechanism of Action
Vitamin K2 acts as a cofactor for an enzyme, gamma-glutamyl carboxylase. This enzyme activates so-called vitamin K-dependent proteins by adding carboxyl groups to some of their amino acids.
Two of these proteins matter for calcium metabolism. Osteocalcin, produced by osteoblasts (the cells that build bone), binds calcium to the bone matrix only in its carboxylated form. MGP (Matrix Gla Protein), secreted by the smooth muscle cells of the vessel wall, likewise exerts its regulatory function on mineralisation only once carboxylated.
Supplementation shifts this carboxylation step, and that is the most reproducible effect of MK-7: in adults, the carboxylated share of osteocalcin rises within a few weeks, in proportion to the dose taken.
The MK-7 form stands out for its long plasma half-life of about 72 hours. It remains available in the bloodstream for close to three days, where vitamin K1 stays one to two hours.
Key Benefits
- Strong
Better-preserved bones with age: vitamin K contributes to the maintenance of normal bones. In the laboratory, it is the cofactor of the enzyme that carboxylates osteocalcin, the bone protein that binds calcium.
- 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.
- Moderate
Less bone loss over time: a three-year controlled trial measured, in 244 postmenopausal women taking 180 mcg of MK-7 daily, a slowdown in bone mineral density loss at the lumbar vertebrae and the femoral neck.
- Emerging
Fewer nocturnal leg cramps: an eight-week randomised trial followed 199 adults aged 65 and over prone to nocturnal leg cramps. On 180 mcg of MK-7 daily, the weekly frequency, intensity and duration of episodes fell compared with placebo.
Dosage & Forms
Vitamin K2 exists in several forms, differing in the length of their side chain. MK-4 (menaquinone-4) has a plasma half-life of one to two hours: the Japanese bone trials that studied it administer 45 mg per day, in several intakes. MK-7 (menaquinone-7) stays in the circulation for about 72 hours, which allows a single daily intake and a stable serum level.
Two production routes coexist on the market: bacterial fermentation, historically from natto, and chemical synthesis. They yield the same molecule, and the European novel food list covers them under a single entry, with a specification for each. No direct human pharmacokinetic comparison separates them.
MK-7 bone trials have administered between 90 and 375 mcg per day, over one to three years. Activation of circulating osteocalcin is measurable at lower doses: a dose-finding trial in postmenopausal women places the effective threshold at 100 mcg per day over four weeks. No tolerable upper intake level has been set for vitamin K; national caps vary, Switzerland setting 225 mcg per day for total vitamin K.
In the Singular Formula
Inclusion rationale
Vitamin K contributes to the maintenance of normal bones. Vitamin K contributes to normal blood clotting. The selected menaquinone-7 (MK-7) form is produced by synthesis and has an all-trans configuration, the only one human enzymes recognise. It stands apart from other forms of vitamin K by its long plasma half-life, about 72 hours against one to two hours for K1, which gives it a prolonged presence in the circulation on a single daily intake. In the laboratory, vitamin K2 is the cofactor of the enzyme that carboxylates osteocalcin, the bone protein that binds calcium to the matrix. That step is the one supplementation shifts most reproducibly. K2-MK7 complements vitamin D3, also present in the formula, with which it shares the calcium metabolism axis. This same bone axis includes magnesium, which contributes to the maintenance of normal bones.
Selected form
Pharmaquinone® is a synthetic vitamin K2 as all-trans MK-7, containing more than 1% vitamin K2 and carried on microcrystalline cellulose using MCT oil. This configuration is the biologically active form of MK-7. Its extended half-life, approximately 72 hours compared with a few hours for MK-4, supports stable blood levels with a single daily intake. Vitamin K contributes to the maintenance of normal bones. Vitamin K contributes to normal blood clotting.
Formula dosage
0 to 180 µg.
Dose expressed as active substance, excluding excipients and carriers of the raw material.
Synergies in the formula
Linked Biomarkers
Safety & Precautions
Vitamin K2-MK7 has a favourable safety profile at common nutritional doses. No tolerable upper intake level has been established for vitamin K. Authorities attribute this absence to insufficient data to evaluate one, which is a reason to stay within documented doses.
The main precaution concerns people taking vitamin K antagonist anticoagulants such as warfarin or acenocoumarol. These medicines work by blocking vitamin K recycling, and additional intake can alter their effect. Vitamin K2 is therefore not recommended in this situation, and Singular removes it from the formula as soon as such treatment is declared. Direct oral anticoagulants are not affected by this interaction.
In people not taking anticoagulants, MK-7 at doses of 90 to 200 mcg per day does not alter coagulation parameters in a clinically significant way. Published trials have reported no adverse effect attributable to MK-7.
Pregnancy and breastfeeding carry no restriction specific to nutritional vitamin K intake.
Scientific Studies
| Authors | Year | Type | Journal | |
|---|---|---|---|---|
| Mott A et al. | 2019 | Meta-analysis | Osteoporosis International | View on PubMed |
Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials Systematic review of 36 randomised trials on vitamin K, bone mineral density and fractures in adults. In postmenopausal or osteoporotic patients, the authors conclude there is no evidence of an effect on bone mineral density or vertebral fractures, and that a possible effect on clinical fractures remains too weakly supported to be confirmed. Other populations have too few trials to draw conclusions. | ||||
| 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 Three-year controlled trial in 244 postmenopausal women: 180 mcg per day of MK-7 slows bone mineral density loss at the lumbar vertebrae and femoral neck, with no measured effect at the total hip. Two other European trials, run at 360 and 375 mcg per day, did not reproduce this effect on density. | ||||
| Zhang Y et al. | 2020 | Randomised Controlled Trial | Calcified Tissue International | View on PubMed |
Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study One-year controlled trial in 311 men and postmenopausal women aged 50 to 75, allocated to placebo, 50 mcg, 90 mcg, or 90 mcg combined with calcium and vitamin D3. Femoral neck bone loss was significantly lower on 90 mcg in postmenopausal women, with no effect in men and no additional benefit from the combination. | ||||
| Rønn SH et al. | 2021 | Randomised Controlled Trial | Osteoporosis International | View on PubMed |
The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial Three-year controlled trial in 142 postmenopausal women with osteopenia receiving 375 mcg per day of MK-7 on top of calcium and vitamin D. Osteocalcin carboxylation improves markedly from the first year, with no difference in bone mineral density or bone microarchitecture at three years. | ||||
| Tan J et al. | 2024 | Randomised Controlled Trial | JAMA Internal Medicine | View on PubMed |
Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial Multicentre double-blind randomised trial in 199 adults aged 65 and over prone to nocturnal leg cramps: 180 mcg per day of MK-7 for eight weeks reduces the frequency, intensity and duration of episodes. The article was republished in 2025 after its analysis was corrected, with a smaller between-group difference than in the original version. | ||||
| Fusaro M et al. | 2020 | Review | Nutrients | View on PubMed |
Vitamin K and Osteoporosis Review of the role of vitamin K in the carboxylation of osteocalcin and MGP, and of what this biochemistry implies for bone tissue. | ||||