Vitamin K, a fat-soluble nutrient, is most widely known for its foundational role in blood coagulation. Beyond this function, a specific form of the vitamin, K2 (menaquinone), has gained substantial attention for its profound impact on cardiovascular health. As consumers seek ways to support their heart and vascular system, they often encounter two primary supplemental types, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), leading to confusion about which is superior. Understanding the distinct differences in how these two molecules are structured and metabolized is the first step in determining the best choice for systemic vascular protection.
Defining the Differences Between MK-4 and MK-7
MK-4 and MK-7 differ fundamentally in their chemical structure, specifically the length of their side chain. MK-4 is a short-chain menaquinone, produced endogenously in human tissues from Vitamin K1. It is naturally found in animal products like liver and egg yolks, though supplemental MK-4 is often synthetic.
MK-7 is a long-chain menaquinone, typically derived from bacterial fermentation, such as in the Japanese food natto. This longer side chain dictates a different metabolic profile. MK-4 is rapidly cleared from the bloodstream, exhibiting a short half-life of only a few hours.
The long-chain structure of MK-7 allows it to persist in the blood for a much longer duration, with a half-life extending to approximately 72 hours. This sustained presence enables MK-7 to be distributed more effectively to extrahepatic tissues, including the arterial walls. This superior systemic bioavailability is why MK-7 shows differing effects in clinical studies focusing on cardiovascular outcomes.
How Vitamin K2 Protects the Cardiovascular System
Vitamin K2 supports heart health by actively regulating where calcium is deposited within the body. Calcium buildup in the arteries, known as vascular calcification, is a major contributor to arterial stiffening and cardiovascular disease risk. K2’s protective action centers on its ability to activate a specific protein called Matrix Gla Protein (MGP).
MGP is the body’s most potent inhibitor of soft tissue calcification. For MGP to function and prevent calcium from crystallizing in blood vessel walls, it must undergo carboxylation, for which Vitamin K2 acts as a cofactor. If K2 levels are insufficient, MGP remains inactive, allowing calcium to deposit freely in the arteries.
Measuring inactive, uncarboxylated MGP (dp-ucMGP) in the blood serves as a marker for functional Vitamin K status. Higher levels of inactive MGP correlate directly with increased arterial stiffness. Adequate K2 availability ensures MGP is fully activated, effectively binding to excess calcium and preventing it from hardening the walls of the arteries.
Clinical Evidence: Comparing MK-4 and MK-7 for Heart Health
Clinical evidence generally favors MK-7 due to its sustained bioavailability. The long half-life allows for continuous activation of MGP throughout the day, providing consistent protection against arterial calcification. The Rotterdam Study observed that a high intake of dietary menaquinones, particularly the longer-chain forms, correlated with a 50% reduction in arterial calcification and a lower risk of heart disease mortality.
Intervention trials have demonstrated MK-7’s efficacy in improving arterial health. A study involving healthy postmenopausal women showed that daily supplementation with 180 micrograms of MK-7 improved arterial elasticity and reduced arterial stiffness over three years. This effect is directly linked to MK-7’s superior ability to reduce circulating levels of inactive MGP.
Clinical studies examining supplemental MK-4 on vascular calcification are less conclusive. One trial using a very high dose of 45 milligrams of MK-4 per day failed to show a reduction in coronary artery calcification scores over one year. While MK-4 is an active form, its rapid clearance means it may not be available long enough to effectively target extrahepatic tissues like the arteries.
Therefore, for systemic cardiovascular protection and reducing arterial stiffness, research supports MK-7 as the more effective supplemental choice. The superior results are attributed to its extended systemic action, which ensures a prolonged biological effect at the site of vascular action.
Safe Use and Practical Dosage Guidelines
Dosages required for MK-4 and MK-7 differ substantially, reflecting their metabolic characteristics and bioavailability. For general cardiovascular and bone support, MK-7 is often dosed in micrograms, typically ranging from 100 to 300 micrograms per day. This microgram dosing is effective because its long half-life allows it to accumulate and provide sustained benefits.
MK-4 requires milligram-level doses for any potential systemic effect, with some clinical trials using as much as 45 milligrams daily. This makes it impractical for standard supplementation. When choosing a supplement, select an MK-7 form to achieve consistent systemic levels with a single, lower daily dose.
Individuals taking anticoagulant medications, such as warfarin, must exercise caution with any form of Vitamin K supplementation. Since Vitamin K directly influences the clotting cascade, taking MK-7 can interfere with the drug’s effectiveness, potentially reducing the International Normalized Ratio (INR). Patients on blood thinners should consult their physician before introducing a Vitamin K2 supplement.