Vitamin K1/K2
Vitamin K1/K2 (Phylloquinone/MK-7)
1. Introduction
Vitamin K is a group of fat-soluble vitamins that are essential cofactors for the activation of various proteins involved in critical physiological processes, including blood coagulation, bone metabolism, and cardiovascular health [1]. The term Vitamin K encompasses two main natural forms: Vitamin K1 (Phylloquinone) and Vitamin K2 (Menaquinones).
Phylloquinone (Vitamin K1) is primarily found in green leafy vegetables and is the main dietary source of Vitamin K. It is rapidly absorbed and primarily utilized by the liver for the synthesis of blood clotting factors [1].
Menaquinones (Vitamin K2) are a series of compounds designated as MK-4 through MK-13, based on the length of their side chain. They are predominantly found in fermented foods and animal products, and are also produced by gut bacteria. Menaquinone-7 (MK-7) is a long-chain menaquinone that is particularly significant due to its longer half-life and superior bioavailability, allowing it to reach extrahepatic tissues like bone and blood vessel walls more effectively than K1 [2, 3].
Mechanism of Action
Vitamin K functions as a coenzyme for the enzyme Vitamin K-dependent carboxylase (VKDC). This enzyme catalyzes the carboxylation of specific glutamic acid residues in Vitamin K-dependent proteins (VKDPs), converting inactive precursor proteins into their biologically active forms. This activation is crucial for their function in:
- Hemostasis: Activating blood clotting factors (e.g., Prothrombin/Factor II).
- Bone Health: Activating Osteocalcin (OC), which helps bind calcium to the bone matrix, promoting bone mineralization.
- Cardiovascular Health: Activating Matrix Gla-protein (MGP), the most potent inhibitor of soft tissue calcification, which prevents calcium from depositing in arterial walls and cartilage [1, 2].
2. Chemical Composition/Key Bioactive Roles
Vitamin K is characterized by a common 2-methyl-1,4-naphthoquinone ring. The different forms are distinguished by the side chain at the 3-position.
| Compound | Common Name | Source | Primary Role |
|---|---|---|---|
| Phylloquinone | Vitamin K1 | Green leafy vegetables (spinach, kale, broccoli) | Primarily liver-based, essential for blood clotting factors (hemostasis) [1]. |
| Menaquinone-7 (MK-7) | Vitamin K2 | Fermented foods (Natto), some animal products | Extrahepatic activity, crucial for bone mineralization (Osteocalcin) and preventing vascular calcification (MGP) [2]. |
Key Bioactive Roles of Activated Proteins:
| Protein | Tissue Location | Function |
|---|---|---|
| Prothrombin (Factor II) | Liver | Essential for blood coagulation (clotting) [1]. |
| Osteocalcin (OC) | Bone | Binds calcium to the bone matrix, promoting bone strength and mineralization [2]. |
| Matrix Gla-protein (MGP) | Vascular smooth muscle, Cartilage | Inhibits the deposition of calcium in soft tissues, protecting against arterial calcification [2]. |
3. Health Benefits
The health benefits of Vitamin K, particularly the highly bioavailable MK-7 form of K2, are primarily centered on optimizing calcium utilization in the body, leading to improved bone and cardiovascular health.
Cardiovascular Health (Prevention of Arterial Calcification)
Vitamin K2 is essential for the activation of MGP, which acts as a powerful inhibitor of arterial calcification.
“Vitamin K2-dependent proteins activate a protective mechanism preventing the development of vascular calcification. Furthermore, vitamin K2, in the form of MK-7, has been proven in numerous trials… to have a long-term protective effect on the development of calcification” [2].
- Reduced Risk of Coronary Heart Disease (CHD): Studies, such as the Rotterdam Study, have shown that a high intake of natural Vitamin K2 (MK-7, MK-8, MK-9) is associated with protection against cardiovascular events. For every 10 mcg of dietary K2 consumed, the risk of CHD was reduced by 9% [3].
- Improved Vascular Elasticity: Adequate intake of K2 is linked to increased elasticity of the vessel wall and a significant reduction in the risk of blood-vessel calcification [3].
Bone Health (Osteoporosis Prevention)
Vitamin K2 ensures that calcium is directed to the bone matrix where it is needed, rather than accumulating in soft tissues.
“Vitamin K2 is known to improve bone quality, which in turn reduces fracture risk as demonstrated by numerous studies with population groups above the age of 50” [2].
- Increased Bone Mineral Density (BMD): By activating Osteocalcin, MK-7 promotes the incorporation of calcium into bone, which is crucial for maintaining and improving BMD, especially in postmenopausal women with osteopenia [2, 4].
- Reduced Fracture Risk: Clinical trials have demonstrated that K2 supplementation can reduce the incidence of vertebral and non-vertebral fractures [4].
Other Potential Benefits
Emerging research suggests roles for Vitamin K2 in other areas:
- Diabetes Mellitus: Long-term K2 supplementation has been shown to reduce the risk of diabetes development, potentially by activating Osteocalcin which promotes the proliferation of pancreatic beta cells and increases insulin production [2].
- Neurological Health: K2 has demonstrated a protective effect on neurons and may play a role in mitigating symptoms related to Parkinson’s disease [2].
4. Dosage and Usage
Recommended Dosages
While the U.S. Adequate Intake (AI) for total Vitamin K is 120 mcg for adult males and 90 mcg for adult females [1], this recommendation is based on the amount needed for blood clotting (K1) and may not be sufficient to fully carboxylate all extrahepatic VKDPs (K2).
Clinical studies demonstrating benefits for bone and cardiovascular health often use the following dosages for Vitamin K2 (MK-7):
| Compound | Condition | Typical Dosage | Source |
|---|---|---|---|
| Vitamin K2 (MK-7) | Bone & Cardiovascular Health | 45 mcg to 180 mcg per day | Clinical Trials [3, 4] |
| Vitamin K2 (MK-7) | Minimum effective dose | 32 mcg per day | Population-based studies [3] |
Food Sources
| Food Source | Primary Vitamin K Form | Typical Amount (per 100g) |
|---|---|---|
| Natto (fermented soybeans) | K2 (MK-7) | ~1,000 mcg |
| Kale (cooked) | K1 (Phylloquinone) | 817 mcg |
| Spinach (cooked) | K1 (Phylloquinone) | 888 mcg |
| Hard Cheeses (e.g., Gouda) | K2 (MK-4 to MK-9) | ~75 mcg |
| Egg Yolk | K2 (MK-4) | ~34 mcg |
5. Safety and Precautions
Vitamin K, in both K1 and K2 forms, is generally considered safe, and no Tolerable Upper Intake Level (UL) has been established due to its low potential for toxicity [1, 5].
Side Effects
- Reported side effects of Vitamin K supplementation are rare and generally limited to local reactions [5].
- A comprehensive safety evaluation concluded that menaquinone-7, when ingested as a dietary supplement, “is not associated with any serious risk to health” [5].
Contraindications and Drug Interactions
Serious Warning: Warfarin and other Anticoagulants
Vitamin K can have a serious and potentially dangerous interaction with anticoagulants such as warfarin (Coumadin). Warfarin works by antagonizing the activity of Vitamin K.
- Individuals taking warfarin must maintain a consistent intake of Vitamin K (both from diet and supplements) to ensure their International Normalized Ratio (INR) remains stable.
- Any change in Vitamin K intake (starting or stopping a supplement, or a major dietary change) must be discussed with a healthcare provider immediately as it can alter the drug’s effectiveness and lead to dangerous clotting or bleeding [1].
- Low-dose MK-7 supplementation (as low as 10 mcg) has been shown to significantly influence anticoagulation sensitivity, underscoring the need for careful medical supervision [1].
Warnings
- Allergy: Individuals with known allergies to Vitamin K or its components should avoid supplementation.
- Renal Impairment: Caution is advised in patients with renal impairment [1].
6. References
[1] Office of Dietary Supplements (ODS). (2021, March 29). Vitamin K – Health Professional Fact Sheet. National Institutes of Health (NIH). https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/ [2] Halder, M., Petsophonsakul, P., Akbulut, A. C., Pavlic, A., Bohan, F., Anderson, E., … & Schurgers, L. (2019). Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. International Journal of Molecular Sciences, 20(4), 896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413124/ [3] Maresz, K. (2015). Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integrative Medicine: A Clinician’s Journal, 14(1), 34–39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566462/ [4] Rønn, S. H., Harsløf, T., Oei, L., & Pedersen, S. B. (2021). The effect of vitamin MK-7 on bone mineral density and bone markers in postmenopausal women with osteopenia: a 3-year randomized, placebo-controlled, double-blinded clinical trial. European Journal of Nutrition, 60(8), 4381–4392. https://pubmed.ncbi.nlm.nih.gov/33030563/ [5] Marles, R. J., Roe, A. L., & Oketch-Rabah, H. A. (2017). US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K. Nutrition Reviews, 75(7), 553–578. https://pubmed.ncbi.nlm.nih.gov/28838081/Category: Vitamin
