Vitamin K exists in two primary forms: K1 (phylloquinone) and K2 (menaquinones). Vitamin K1 is found in green leafy plants and is essential for blood clotting. Vitamin K2 includes several subtypes called menaquinones, labeled MK-4 through MK-13, based on the length of their side chains. MK-4 is unique, found in animal tissues, synthesized from K1, and is critical for bone and cardiovascular health. MK-5 to MK-13 are bacterial-origin forms, often produced in the gut or derived from fermented foods, like natto. Vitamin K molecules also exist in cis- and trans-isomers, with the trans form being the biologically active configuration in humans.
Vitamin K1, or phylloquinone, plays a crucial role in blood clotting (coagulation). It is essential for synthesizing various clotting factors (such as factors II, VII, IX, and X) and proteins (like protein C and protein S) in the liver. Vitamin K1 acts as a cofactor for the enzyme gamma-glutamyl carboxylase, which activates these clotting proteins by enabling them to bind calcium ions, a key step in the coagulation cascade. Without sufficient vitamin K1, blood clotting is impaired, leading to a higher risk of bleeding. Additionally, vitamin K1 supports bone health and cellular functions, although K2 is more active in these areas.
Vitamin K2 plays a vital role in bone health and vascular health by activating proteins that regulate calcium metabolism. One key protein it activates is matrix Gla protein (MGP), which prevents calcium deposition in blood vessels, thus reducing arterial calcification and promoting cardiovascular health. This anti-calcification effect of K2 helps counteract excessive calcium buildup, which can occur with high vitamin D intake, reducing the risk of vitamin D toxicity and calcium overload in soft tissues.
In bones, K2 activates osteocalcin, a protein responsible for binding calcium within the bone matrix, thus supporting bone formation and strength. Together, K2 helps direct calcium into bones and away from blood vessels, balancing skeletal health with cardiovascular protection.
Vitamin K levels in human plasma vary depending on dietary intake and form. Vitamin K1 (phylloquinone) levels are generally between 0.2 to 2.0 ng/mL in plasma, reflecting recent consumption of green vegetables. Vitamin K2 (menaquinones), especially MK-4, is found at lower concentrations, typically below 1 ng/mL, as it is quickly taken up by tissues like the liver, bones, and arteries. Other menaquinones, like MK-7 (found in fermented foods), also appear in low levels but can remain in circulation longer than K1 due to slower metabolism. Individual levels are influenced by diet, gut microbiota, and liver function.
Quantifying vitamin K, particularly its different forms (K1 and various K2 menaquinones), is challenging due to their low concentrations in biological samples and structural complexity. Vitamin K levels in plasma can vary significantly, requiring high sensitivity to detect even trace amounts, especially of long-chain menaquinones (like MK-7 or MK-13). Additionally, the varying fat solubility and stability of vitamin K compounds complicate sample preparation and analysis. Advances in analytical methods, particularly high-end LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry), provide the sensitivity and selectivity needed to accurately measure vitamin K forms, offering precision in both clinical research and nutritional studies.