MK4 or MK7 for Heart: Which Is Best for Your Cardiac Wellness?

Vitamin K2 is essential for cardiovascular health, particularly in regulating calcium metabolism and arterial function. Among its forms, menaquinone-4 (MK4) and menaquinone-7 (MK7) are the most studied for heart health, yet they differ in absorption, distribution, and biological activity. Understanding these differences helps determine which form is more effective for cardiac wellness.

While both MK4 and MK7 support vascular health, their distinct properties influence how they function in the body.

Molecular Characteristics of MK4 and MK7

Menaquinone-4 (MK4) and menaquinone-7 (MK7) are subtypes of vitamin K2 with structural differences that affect their role in cardiovascular health. MK4 has four isoprenoid units, making it structurally similar to phylloquinone (vitamin K1) and allowing for rapid uptake by tissues such as the liver, pancreas, and arterial walls. MK7, with seven isoprenoid units, has greater stability and a longer half-life in circulation, influencing its interaction with vitamin K-dependent proteins involved in vascular function.

MK4 is quickly cleared from the bloodstream within a few hours, requiring frequent dosing for sustained effects. In contrast, MK7 remains in circulation for up to 72 hours, providing prolonged activation of proteins like matrix Gla-protein (MGP) and osteocalcin, which regulate calcium homeostasis and arterial integrity.

The structural differences also impact tissue distribution. MK4 is absorbed by extrahepatic tissues, including arterial walls, where it may have localized effects on vascular smooth muscle cells. MK7’s longer half-life allows for broader systemic distribution, potentially offering more sustained cardiovascular benefits.

Bioavailability in Circulation

The bioavailability of MK4 and MK7 is shaped by differences in absorption, transport, and metabolism, affecting their effectiveness in vascular health. MK4 is rapidly absorbed in the intestines but cleared from the bloodstream within hours due to its uptake by tissues, particularly the liver and arterial walls. Studies show that MK4 reaches peak plasma concentrations within one to two hours but declines quickly, necessitating frequent dosing.

MK7, with a longer side chain, has significantly greater bioavailability. It remains in circulation for 48 to 72 hours, leading to sustained plasma levels. Research published in The British Journal of Nutrition found that a single MK7 dose resulted in detectable blood concentrations for days, whereas MK4 levels dropped below measurable thresholds within hours.

MK4 is transported primarily by triglyceride-rich lipoproteins, which the liver rapidly clears. MK7 associates with low-density lipoproteins (LDL) and high-density lipoproteins (HDL), allowing for slower clearance and broader systemic distribution. Clinical trials show that MK7 supplementation leads to sustained increases in plasma vitamin K2 levels, enhancing its role in calcium metabolism and arterial flexibility.

Role in Arterial Calcification

Arterial calcification, the buildup of calcium in arterial walls, contributes to cardiovascular disease by reducing vascular flexibility. Vitamin K2, particularly MK4 and MK7, helps regulate this process by activating matrix Gla-protein (MGP), which inhibits vascular calcification. Without sufficient activation by vitamin K2, MGP cannot bind calcium and prevent its deposition in arteries.

MK7’s prolonged circulation allows for continuous MGP activation, which may help prevent arterial calcium buildup. Longitudinal studies indicate that populations with higher MK7 intake have lower arterial calcification and reduced cardiovascular mortality. A study in Thrombosis and Haemostasis found that MK7 supplementation significantly increased active MGP levels and reduced arterial stiffness in postmenopausal women.

MK4 can also activate MGP but is rapidly cleared from the bloodstream. Some research suggests MK4 accumulates in arterial tissues, where it may influence vascular smooth muscle cells involved in arterial tone and calcification. However, due to its short half-life, MK4 may require higher or more frequent doses to achieve benefits similar to MK7.

Relevance to Lipid Metabolism

Menaquinones influence lipid metabolism, which impacts cardiovascular health. MK7 has been linked to improved lipid profiles, with research suggesting it may help reduce LDL cholesterol and triglycerides. A randomized controlled trial in Atherosclerosis found that MK7 supplementation over 12 weeks led to a modest but significant decrease in LDL cholesterol in postmenopausal women.

MK4 appears to affect lipid metabolism at the cellular level, potentially influencing gene expression related to lipid synthesis and breakdown in the liver. Animal studies indicate that MK4 supplementation may reduce hepatic lipid accumulation, which could help prevent fatty liver disease. However, human studies on MK4’s effects on cholesterol and triglycerides remain limited.

Dietary and Supplemental Forms

The availability of MK4 and MK7 in food and supplements varies, influencing how individuals obtain these menaquinones for cardiovascular support. MK4 is found in animal-based foods such as organ meats, egg yolks, and dairy, though in relatively low concentrations. Unlike MK7, which is synthesized by bacteria during fermentation, MK4 is derived from the conversion of phylloquinone (K1) in animal tissues.

Because MK4 is rapidly cleared from circulation, maintaining sufficient levels through diet alone is challenging. Supplements often provide 5 to 45 mg per serving to compensate for its short half-life. Some research suggests multiple daily doses may be necessary for consistent activation of vitamin K-dependent proteins.

MK7 is abundant in fermented foods such as natto, aged cheeses, and fermented vegetables. Natto is the richest source, providing several hundred micrograms per serving. MK7 supplements typically offer 90 to 200 mcg per serving, reflecting its longer half-life. This allows for once-daily dosing, making it a convenient option for long-term cardiovascular support. The extended bioavailability of MK7 ensures continuous activation of MGP and other calcium-regulating proteins, contributing to arterial flexibility and reduced calcification risk.

Interactions With Other Nutrients

The effectiveness of MK4 and MK7 in arterial health is influenced by interactions with nutrients involved in calcium metabolism and vascular function. Vitamin D is particularly important, as it regulates calcium absorption while vitamin K2 directs calcium away from arteries and into bones. High vitamin D intake without sufficient vitamin K2 may contribute to arterial stiffness, highlighting the need for balance. MK7’s longer half-life makes it more effective for sustained calcium regulation.

Magnesium also plays a role, serving as a cofactor for enzymes in vitamin K metabolism. It supports MGP activation, enhancing vitamin K2’s ability to regulate calcium deposition. Inadequate magnesium levels may reduce the effectiveness of MK4 and MK7 in preventing vascular calcification.

Because menaquinones are fat-soluble, consuming MK4- or MK7-rich foods with dietary fats, such as olive oil or avocados, improves absorption and enhances cardiovascular benefits.