Cardiovascular diseases are the leading cause of death and, as it turns out, alarming problems with vitamin K2 deficiency are a contributing factor, according to a new review article that is published in Open Heart. Vitamin K2 regulates the body’s calcium distribution and lack of the vitamin increases the risk of atherosclerosis, arterial stiffness, insulin resistance, and heart failure. Supplementation with vitamin K2 has been seen to improve circulatory health in a number of different ways, and it also has a positive effect on inflammation and type 2 diabetes. Unfortunately, modern diets are not all that rich in vitamin K2 and the problem is made worse by the fact that different types of medicine disrupt the body’s ability to utilize the nutrient.
Vitamin K2 is a lipid-soluble vitamin that is found naturally in two forms with entirely different functions. Vitamin K1 (phylloquinone) helps the blood coagulate and is mainly found in cabbage and dark greens. A well-functioning gut flora is even able to convert vitamin K1 into vitamin K2 but the amounts are often limited.
Vitamin K2 (menaquinone K4 - K10) is found in liver and fermented foods such as natto, sauerkraut, kefir, and cheese where the vitamin is produced by bacteria as part of the fermentation. Vitamin K2 activates matrix GLA protein (MGP) that is found inside the blood vessels. Activated MGB binds calcium and works by removing excess calcium from the arteries. Vitamin K2 also activates a protein called osteocalcin that embeds calcium in bone tissue. That way, vitamin K2 counteracts atherosclerosis and osteoporosis by regulating the distribution of calcium in the different tissues.
The authors behind the new review article describe a list of studies of the link between vitamin K2, atherosclerosis, and different cardiovascular diseases, peripheral arteries, and capillaries in the eyes and kidneys. They also look at whether or not supplements of vitamin K2 can improve blood flow and prevent early death.
Using a marker to measure vitamin K2 levels
The body only stores limited quantities of vitamin K which makes it difficult to measure levels of the nutrient in the blood. In order to assess vitamin K2’s role in the circulatory system, one must use a biomarker of the body’s vitamin K status. This is done by measuring levels of MGP protein that is activated with help from vitamin K2. MGP’s ability to bind calcium requires a process that involves carbolyxation of MGP. By measuring uncarbolyxated MGP (inactive MGP), it is possible to see if there is too little vitamin K2 in the body.
Atherosclerosis and arterial stiffness
Atherosclerosis is a thickening of the arterial wall that is often seen in the coronary arteries, the brain, and the legs. Atherosclerosis also causes stiff arteries and may eventually result in symptoms linked to impaired blood supply and, in worst case, heart infarction and stroke, which are the leading causes of death in the western world.
Atherosclerosis consists of deposits of calcium, fat, and oxidized LDL cholesterol. However, there is too little focus on the calcium deposits that are a result of improper calcium distribution in the body. The review article mentions several studies and meta-analyses that show how vitamin K2-dependent proteins reduce atherosclerosis and arterial stiffness by clearing excess calcium from the bloodstream.
Aortic stenosis is a narrowing of the heart’s aortic valve that prevents blood from flowing to all the different parts of the body. Eventually, it puts that much strain on the body that you have breathing difficulty, chest pain, and dizziness. It is a degenerative disease characterized by a progressive calcification of the aortic valve.
In their review, the authors write that blood-thinners like warfarin that are used to prevent blood clots can trigger the development of aortic stenosis. This is because warfarin is a vitamin K antagonist and counteracts both vitamin K1 and vitamin K2. Because of this mechanism, blood-thinners deplete levels of vitamin K2 and increase the risk of aortic stenosis. As the authors write, it may be a good idea to measure patients’ levels of inactive MGB as a way to gauge vitamin K2 deficiency.
Atherosclerosis in the tiny blood vessels
From the arteries, our blood continues through smaller blood vessels and eventually reaches the tiny blood vessels (capillaries) that are no thicker than a human hair strand. Apparently, MGP is found in abundance in the capillaries of the eyes, retina, kidneys, and heart and it is therefore assumed that MGP plays a major role in maintaining the structural integrity of these capillaries through its role in counteracting atherosclerosis and stiffness. A population study lasting 11 years has demonstrated higher levels of inactive MGP are associated with narrowing of the retinal capillaries and is used for cardiovascular risk assessment.
Cardiovascular disease and mortality
More and more evidence suggests a link between low levels of vitamin K2 (inactive MGP) and the development of cardiovascular disease and premature death. Numerous studies have linked vitamin K2 deficiency to atherosclerosis, chronic heart failure, and stroke. A study of 894 patients suffering from ischemic heart disease (coronary occlusion) has shown that low vitamin K2 doubles or even triples the risk of dying of heart failure or stroke within a five-year period.
Inflammation, diabetes, and chronic kidney disease
Chronic inflammation is the common thread of many chronic diseases. Vitamin K2’s anti-inflammatory properties are mainly tied to its role in regulating the body’s calcium distribution. If cells in blood vessels or other types of soft tissue are flooded by calcium ions, they may become stressed and respond with inflammation that is tied to oxidative stress and oxidation of cholesterol. Cholesterol, which is otherwise an essential compound, becomes harmful when it oxidizes and is embedded in the vessel walls.
Markers of vitamin K2 deficiency (inactive MGP) are associated with inflammation and, subsequently, linked to kidney function, diabetes, and obesity. More than 60 percent of those with chronic kidney disease have low levels of vitamin K2 which increases their risk of early death. This is also the case with kidney-transplanted patients. The authors mention how vital the body’s calcium distribution is for our kidney function and for preventing kidney stones.
Osteocalcin that is activated by vitamin K2 is even important for our insulin sensitivity. Lack of vitamin K2 is therefore linked to insulin resistance, an early stage of type 2 diabetes. What makes diabetes potentially harmful is the risk of serious circulatory disturbances and hypertension.
Vitamin K2 supplements for prevention and therapy
According to the review article, supplements of vitamin K2 in combination with a healthy diet and lifestyle can help prevent atherosclerosis, arterial stiffness, metabolic syndrome, diabetes, and heart failure. Vitamin K2 supplements are also relevant as part of the treatment for heart disease. Although many promising studies have been made, several of the studies are limited in terms of their design, their duration, and their dosage and vitamin K formulas. Still, it looks as if vitamin k2 supplements may be useful for people with atherosclerosis, arterial stiffness, and aortic stenosis. What is more, it is a safe and convenient therapy form.
How much vitamin K do we need?
The daily reference intake (RI) level for vitamin K1 for adults is 75 micrograms, while no RI level has been set for vitamin K2. Even though the jury is still out with regard to vitamin K2, several studies point to daily intake levels in the range of 75-180 micrograms as being advantageous. No side effects have been observed with such intake levels. Several studies have even tested daily doses of 180-360 micrograms for improved cardiovascular health.
Vitamin K2 occurs naturally in different forms. Vitamin K2 in the form of MK-7 remains in the body for much longer time and has a better effect on calcium distribution. That is why it is recommended to supplement with this form of vitamin K2.
Things that cause vitamin K2 deficiency
Essa Hariri et al. Vitamin K2 – a neglected player in cardiovascular health: a narrative review. Open Heart. 2021
Jaime W. Bellinge et al. Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study. Journal of the American Heart Association. 7 Aug. 2021
Stephen Daniells. New Study show importance of vitamin K for vascular function. Nutraingredients.com 2020
S. Thamratnopkoon et al. Correlation of Plasma Desphosporylated Uncarboxylated matrix Gla Protein with Vascular Calcification and Stiffness in Chronic Kidney Disease. Nephron. 2017 Published online.
M. Sardana el al. Inactive Matrix GLA-Protein and Arterial stiffness in Type 2 diabetes Mellitus. American Journal of Hypertension 2016
8 Foods High in Vitamin K2 and Why You Need It (webmd.com)
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