Vitamin K is a fat-soluble nutrient well-known for its involvement in blood coagulation, but its functions extend far beyond clotting factors. The vitamin exists in two primary natural families: K1 (phylloquinone), found mainly in green leafy vegetables, and K2 (menaquinones), which are a series of compounds designated as MK-n. Vitamin K2 is particularly noted for its roles in calcium metabolism beyond the liver, supporting bone and cardiovascular health. Within the K2 family, MK-4 and MK-7 are the most studied and commercially available forms, yet they differ significantly in their characteristics and behavior in the body.
Structural and Origin Differences
The fundamental difference between MK-4 and MK-7 lies in their molecular structure, specifically the length of their isoprenoid side chain, indicated by the number in their name. MK-4 has a short side chain composed of four isoprenoid units. Conversely, MK-7 features a longer side chain containing seven isoprenoid units. This structural variation influences how the body absorbs, transports, and utilizes each compound.
The origins of these two forms also diverge. MK-4 is the only form synthesized by mammals, including humans, in various tissues from other vitamin K forms. While MK-4 is found in animal products, the form used in most supplements is synthetic. In contrast, MK-7 is generated through bacterial fermentation, primarily found in natto, a traditional Japanese fermented soybean dish.
Bioavailability and Metabolism
The length of the isoprenoid side chain dictates the pharmacokinetic properties of MK-4 and MK-7, leading to a difference in how long each remains active in circulation. MK-4 is rapidly absorbed but quickly cleared from the bloodstream, exhibiting a short half-life, typically measured in just a few hours (two to eight hours). This rapid turnover means MK-4 must be consumed frequently or in large doses to maintain consistently elevated serum levels. MK-4 is packaged into triglycerides after absorption, contributing to its short residence time in the blood.
MK-7, due to its longer side chain, is metabolized much more slowly and has a significantly longer half-life, which can be up to 72 hours or more. This extended duration of activity allows it to remain active in the body for days. MK-7 is incorporated into low-density lipoprotein (LDL) cholesterol, which circulates systemically for a prolonged period. The stable presence of MK-7 in the blood allows it to accumulate over time with consistent daily intake, ensuring continuous access to the nutrient throughout the body.
The distribution pattern also differs, reflecting their metabolic pathways. MK-4 is highly localized and rapidly taken up by specific extra-hepatic tissues, including the brain, pancreas, salivary glands, and arterial walls. This localized distribution suggests MK-4 may have specialized roles within these organs, distinct from its general function in the liver. Conversely, MK-7 achieves higher and more stable levels of systemic circulation, making it more readily available to extra-hepatic tissues like bone and blood vessels.
Targeted Physiological Roles
The difference in half-life and distribution translates into distinct physiological roles. MK-7 is effective for systemic calcium regulation due to its sustained presence in the bloodstream. Its prolonged circulation ensures continuous activation of two proteins: osteocalcin, which incorporates calcium into the bone matrix, and Matrix Gla Protein (MGP), which prevents calcium from depositing in soft tissues like artery walls. This dual action supports long-term bone mineralization and cardiovascular health by reducing arterial calcification.
MK-4, while capable of activating these proteins, appears to exert unique functions related to its localized concentration in specific organs. High levels of MK-4 found in the brain and nervous system suggest specialized, non-hepatic roles, potentially supporting neurological function. Furthermore, high-dose MK-4 (e.g., 45 milligrams daily) has a history of use in clinical settings, particularly in Japan, for improving bone density and reducing fracture rates. These high-dose protocols are thought to overcome the challenge of its short half-life and rapid clearance, suggesting a potent, localized function when delivered at significantly higher concentrations.
Practical Application: Dietary Sources and Supplementation
The natural dietary sources for MK-4 are primarily animal-based, including liver, meat, and egg yolks, though the amounts found are relatively small. For MK-7, the primary source is the fermented soybean product natto, which contains exceptionally high concentrations, along with certain aged cheeses. Individuals who do not regularly consume natto may find it challenging to meet K2 needs from food alone.
The choice of supplementation hinges on the unique pharmacokinetic profiles of the two forms. Due to its long half-life and systemic delivery, MK-7 is generally considered the more practical form for daily, long-term supplementation. MK-7 doses are typically in the microgram range (e.g., 100 to 180 mcg) and require only once-daily dosing to maintain stable blood levels. Conversely, MK-4 supplements require much higher doses, often in the milligram range, and must be taken several times throughout the day to sustain therapeutic concentrations. While MK-4 is used for specific therapeutic applications requiring high dosing, MK-7 is the preferred choice for general maintenance of bone and vascular health.