Vitamin K2 – The Lesser Known Vitamin

In the world of vitamins, we have vitamins A, B, C, D, E and K.  Vitamin K is the most recently discovered vitamin, first detected and named in 1929.  But why was it not called vitamin F?  Partly this was because the letters F, G, and H had been used up by other chemicals that were thought at first to be vitamins but turned out not to be.  The Danish discoverer of vitamin K, Henrik Dam, decided to call his new nutrient the “koagulation vitamin” or vitamin K because he found it while studying bleeding in chickens on a fat-free diet. (1)

 

Vitamin K is a fat-soluble vitamin which means it doesn’t dissolve in water.   Only very small amounts of Vitamin K circulate within our bloodstream at any given time.  Some Vitamin K can be stored in the liver and fat but much of the vitamin that we take in through food or supplements is removed from the body as waste.  (2).

 

 

Vitamin K comes in two forms; 

Vitamin K1 (Phylloquinone)

About 75% of the vitamin K obtained from the diet is vitamin K1 (3).  Good dietary sources are cauliflower, broccoli, Brussels sprouts and leafy greens such as spinach, kale and cabbage.  It appears that only about 10% of the vitamin K1 consumed is absorbed.  However, most people can still acquire enough vitamin K1 from their diet and are not lacking in it.  In addition, vitamin K1 can be recycled by the body and reused many times (1,2).

 

Vitamin K2 (Menaquinone)

There are a variety of menoquinones.  They are designated as MK-4 through MK-15 based on the length of the side chain in their chemical structure.  MK-4, MK-7 and MK-9 are the most well studied. Almost all of the menaquinones are synthesized by bacteria; MK-4 is the only one that is not.  MK-4 is derived through conversion from vitamin K1. (4) The longer side chains in the chemical structure of vitamin K2 allow it to circulate in the blood longer than vitamin K1, making it more accessible to tissues throughout the body and potentially more easily absorbed than vitamin K1. (3)

 

 

Vitamin K Health Benefits

Both vitamin K1 and K2 play the following roles in our bodies;

Blood coagulation:  Vitamin K manages the proteins involved in the clotting of blood. (5)

Bone health:  Vitamin K regulates calcium balance by promoting calcification of bones thus increasing bone strength. Inadequate vitamin K intake is linked to an increase in osteoporosis (soft, porous bones) and higher risk of bone fracture (6,7).  Vitamin K2 is more efficient in moving calcium around the body than vitamin K1 (8).

Cardiovascular health:  Vitamin K prevents calcification of blood vessels and the kidneys. Calcium build-up in the arteries around the heart is a huge risk factor for heart disease. Vitamin K2 appears to be better than K1 at reducing these calcium deposits and lowering the risk of heart disease (6,9,10,11)

 

 

Vitamin K2 Specific Health Benefits

When vitamin K was first identified, it was assumed that its numerous forms were simply structural variations and that they all performed the same biological actions in the synthesis of blood coagulation factors.  However, as research continued, the distinct nature of vitamin K2 began to emerge.

 

Multiple clinical trials have reported that daily supplementation with vitamin K2 can improve bone mineral density, reduce bone loss and boost measures of bone strength (12,13).  A 2001 investigation noted that high doses of vitamin K2 have been used very successfully to prevent bone mineral loss and reduce fracture risk in people with osteoporosis (14).  In a 2006 systematic review, vitamin K2 administration was associated with reducing spinal fractures by 60%, hip fractures by 77% and all non-spinal fractures by 81% (13).  Research from 2021 looked at blood levels of vitamin K2 in postmenopausal patients with osteoporosis and showed that the patients had significantly lower vitamin K2 levels than the healthy controls. The study concluded that vitamin K2 deficiency should be considered a factor in postmenopausal osteoporosis (15).

 

Vitamin K2 can help to prevent the build-up of calcium in arteries that is associated with atherosclerosis and increased risk of heart disease.  The Rotterdam Study included 4807 healthy men and women older than 55 years of age and examined the relationship between dietary intake of vitamin K2 and the presence of heart disease, calcification of the aorta, and death from all causes in the participants.  Results showed that high dietary intake of vitamin K2 (at least 32 mcg per day) was associated with a 50% reduction in death from cardiovascular events related to calcification of arteries.  A 25% reduction in death from all causes was also identified.  In addition, no undesirable side effects of vitamin K2 were observed (11).  A prospective cohort study from 2009 following over 16,000 women concluded that for every 10 mcg of vitamin K2 intake there was an associated reduction in the risk of coronary heart disease of 9%.  Vitamin K1 intake on the other hand was not associated with any change in heart disease risk (16).

 

Vitamin K2 may also protect the aging brain and in several ways. Vitamin K2 appears to be able to reduce the cell death induced by the amyloid plaques present in Alzheimer’s Disease as well as to limit inflammation and oxidative stress in neurons (cells of the brain and nervous system).  Vitamin K2 shows potential in slowing and even preventing the progression of Alzheimer’s Disease. Also, sphingolipids are complex fats found in the brain that are essential in the development, and survival of neurons.  Alterations in their metabolism is implicated in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntingdon’s disease. Both vitamin K1 and K2 are involved in the synthesis and regulation of sphingolipids.  Additionally, vitamin K2, in the form of MK-4, is important in the maintenance of the protective layer of insulation (myelin) that wraps around cells of the brain and nervous system. In Parkinson’s disease, vitamin K2 shows promise in boosting the ability of neurons to remove old and failing mitochondria (the powerhouses of cells) and produce new ones thus slowing the development and progression of the disease.  The anti-inflammatory effects of vitamin K2 may also reduce the consequences of multiple sclerosis. (17,18,19,20,21)

 

Vitamin K2 appears to reduce the recurrence of liver cancer and increase survival. A study from 2008 showed that men with a high intake of vitamin K2 had a 63% lower risk for advanced prostate cancer. (22,23)

A growing body of evidence is uncovering even more potential health benefits of vitamin K2 in areas such as eye health, migraine relief, prevention of dental cavities and relieving depression (24,25).

 

 

What do we know about how vitamin K2 exerts its health benefits?

Our bones are living substances with our entire skeletons being replaced every 7 to 10 years.  Bones are remodeled by releasing some of their calcium into the bloodstream and then changing in size and shape as calcium is replaced into growing or repairing bones.  Such remodeling is regulated by cells in the bones called osteoblasts, which build up the skeleton, and osteoclasts, which break down the skeleton (26).

 

Living organisms perform many biological reactions and most of these occur because of the action of specific proteins.  There are special proteins in our bodies that are responsible for moving calcium around the body. One of these proteins is osteocalcin (bone gla protein or BGP) which is produced by the osteoblasts in the bone.  Osteocalcin promotes the movement of calcium from the blood into the bones and teeth where it is needed.  Another calcium-moving protein is matrix gla protein (MGP), produced by cells in the smooth muscle of blood vessels.  MGP removes calcium from soft tissues such as arteries and veins where it is a factor in the development of potentially fatal atherosclerosis.  But here’s the catch.  Both of these proteins are dependent on vitamin K to activate them by altering their structure so that they can bind to calcium.  Without activation, neither of these proteins can do their jobs of drawing calcium into the bones where the osteoblasts can incorporate it into the bone matrix or removing calcium from soft tissues like arteries (26). Though vitamin K1 can perform this activation, it requires very large amounts, 250 to 1000 mcg of vitamin K1 per day.  Vitamin K2, in the form of MK-7 at doses of around 90 to 180 mcg per day, has been found to execute the same job much more efficiently (8).  In addition, vitamin K2, when combined with vitamin D3, helps to inhibit osteoclasts, the cells in the bone that are responsible for breakdown and reabsorption of bone (27).

 

Recent studies are bringing to light the intricacies of these processes.  Having healthy bones is not simply a matter of getting lots of calcium.  Though calcium supplements can promote increased bone mineral density and prevent osteoporosis, high consumption of calcium in supplemental form is associated with accelerated deposition of calcium in blood vessel walls and other soft tissues and increased risk of heart disease.  A study from 2013 tracked the health of over 200,000 men and 169,000 women for twelve years.  It discovered that men taking more than 1000 mg of calcium per day from supplements actually had a 20% higher risk of death from cardiovascular causes than the participants taking no calcium supplements (28).   The Women’s Health Initiative revealed that women taking 1000 mg of calcium daily in supplements, with or without the addition of 400 IU per day of vitamin D, increased their risk of cardiovascular events by 15 to 22%.  This effect was seen particularly in women who were not taking calcium supplements at the beginning of the study (29).  And the 23,980 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC – Heidelberg) found an 86% increased risk for heart attack in those taking a calcium supplement when compared to those not taking a supplement (30).  Lack of vitamin K2 and low activation of the proteins, osteocalcin and MGP, may be at the root of the problems being encountered with calcium supplementation.

 

 

How much Vitamin K is Needed for Health?

Until recently, recommended vitamin K intake levels focused only on vitamin K1.  Most people can easily obtain enough vitamin K1 for health if they’re eating enough calories.  Health Canada and the National Institute of Health (NIH) in the US agree that an Adequate Intake (AI) for Vitamin K is 120 mcg daily for adult men and 90 mcg daily for adult women. These amounts are not hard to achieve. (4,31)

 

However, it appears that human requirements for vitamin K2 are not being met. Indeed, vitamin K2 deficiency is widespread (32).  Part of the problem lies in the fact that the consumption of vitamin K in general has been decreasing since the 1950s.  Modern production practices, in which animals are allowed only limited or no access to the outside world and green plants, have gradually taken their toll, reducing the vitamin K content of the food supply.  Consequently, relying on the diet as a source of vitamin K2 no longer satisfies the needs of our bodies (26,33).

 

Prospective studies have found health benefits with doses of 10 to 45 mcg per day of MK-7; clinical trials have studied doses as high as 360 mcg of MK-7 daily and observed no toxicity (34).  A large meta-analysis including 19 randomized controlled trials revealed significant improvement in bone mineral density of the vertebrae from vitamin K2 supplements of both 45 to 90 mg/day of MK-4 or 100 to 180 mcg/day of MK-7 (35).

 

Scientists are now recognizing that both menaquinones and phylloquinone should be considered when making recommendations for vitamin K intake and that there should be a separate recommendation for each of these vitamin K forms (3).  Vitamin K2 clearly passes the nine criteria set out for establishing an official Recommended Daily Intake (RDI).  Moreover, the contribution of vitamin K2 from meat animals has declined due to their lack of access to green plants from which they obtained vitamin K1, making the amount they convert to vitamin K2 much lower than it has been in the past (40). Clinical trial evidence clearly shows significant health benefits from high vitamin K2 consumption.  There are no toxic consequences of vitamin K2 overconsumption.  It is only a matter of time before countries around the world formulate an RDI specific to vitamin K2 (34).  In the meantime, there is nothing stopping each of us from ensuring that we have a daily source of this beneficial vitamin.

 

 

Where Can I Acquire Vitamin K2?

The many subtypes of vitamin K2 are found in different food sources.  MK-4 is the only form not produced by bacteria.  It can be obtained through conversion from vitamin K1, however, human conversion of vitamin K1 to MK-4 in the gut appears to be inefficient and inadequate to meet health needs (4).  Some animal species are better converters and animal-sourced foods such as meat, fish and egg yolk can be sources of MK-4 (10,19) but, as discussed above, their contributions to dietary vitamin K2 are waning (40).

 

Vitamin K2 forms MK-5 through MK-15 have longer side chains.  They are all produced by bacteria and can be found in fermented foods such as natto, sauerkraut, pickled vegetables and some types of cheese.  However, Vitamin K2 concentrations in fermented foods can vary drastically, especially those readily available in the Western diet. Natto, a Japanese fermented soybean dish, is particularly high in MK-7 (10,19).

 

For those not eating any animal-sourced foods, natto is the best dietary source for vitamin K2, providing about 850 mcg of vitamin K2 in 3 ounces of natto (36).  This is so because Bacillus subtilis, the strain of bacteria used in its fermenting process, produces MK-7.   Studies from Japan have linked frequent consumption of natto to more activated osteocalcin, increased bone formation, higher bone mineral density and lower risk of hip fracture (37).  One analysis illustrated that the regular consumption of natto in eastern Japan is associated with significantly lower risks of hip fractures when compared with Japanese women living in western Japan where natto is not eaten regularly (32). These results are corroborated by another study encompassing 944 women aged between 20 and 79 years who took MK-7-rich natto for over three years and showed considerable increases in bone mineral density (38).

 

Unfortunately, natto is an acquired taste.  It has a strong smell and a slimy, sticky texture which can be off-putting.  Those who grow up eating natto are not bothered by these characteristics but introducing natto into the diet of someone not accustomed to it may be an uphill battle.  Fortunately, vitamin K2 supplements providing MK-7 sourced from natto are readily available and well absorbed.  As well, the MK-4 form of vitamin K2 in supplements is produced synthetically from an extract of the Nicotiana plant and is also available as a supplement.  (39,40)

 

Given the low amounts of vitamin K2 present in modern foods, and the difficulty in tolerating natto, the most reliable way to secure adequate intake of vitamin K2 is from a supplement.  This is obvious for vegetarians and vegans but even people who eat meat, fish and eggs are likely not getting enough vitamin K2. (26)

 

 

Practical Guidelines for Vitamin K2 Supplementation

MK-4 is the natural form of vitamin K2 that is present in animal-sourced foods.  MK-4 supplements contain synthetic MK-4 but they appear to offer all the benefits of the natural form.  Unfortunately, MK-4 remains in the bloodstream for only a few hours meaning that an MK-4 supplement must be taken three times a day.  Furthermore, the recommended daily dose of MK-4 is 45 milligrams but Health Canada limits the content of a single dose of all types of vitamin K to 120 micrograms (1 milligram is equivalent to 1000 microgram).  Consequently, in Canada at least, it would be impractical to try to achieve a therapeutic dose of MK-4 through this supplement.  (40)

 

MK-7 supplements are sourced from natto, the fermented soy product. They are just as effective as MK-4 supplements but, since they remain in the bloodstream for longer periods of time, they need be taken only once a day.  Moreover, an effective dose for MK-7 seems to be about 120 micrograms daily although doses of 90 to 360 micrograms have been used successfully in studies (40,41,42).   A 2013 trial using a dosage of 180 micrograms of MK-7 per day derived from natto demonstrated reductions in bone loss and maintenance of high bone strength in healthy postmenopausal women (43).

 

Be sure that whatever supplement you buy specifies the form of vitamin K contained in the product.  Look for products that contain MK-4 in a strength of around 45 milligrams per dose or MK-7 in a strength of at least 120 micrograms per dose.  (Note:  milligrams for MK-4 and micrograms for MK-7.)  You’re not looking for vitamin K1; it is easily obtained from the diet.  (40)

 

Current knowledge suggests that, since menaquinone is a fat-soluble nutrient, look for a supplement that comes in a soft gelatin capsule or an oil-based liquid suspension to enhance bioavailabilty.  In addition, taking vitamin K2 supplements with food should also increase absorption (40).

 

If you are taking blood thinning medications such as warfarin, note that vitamin K2 can interfere with the action of these medications.  If you decide you want to take vitamin K2, you MUST enlist your medical practitioner’s help when starting the K2.  Your dose of blood-thinning medication will need to be altered as your dose of K2 increases and, once you reach a therapeutic dose of K2, your doctor can stabilize your medication dose to the level of K2 that you are taking.  Thereafter, you must take your increased dose of blood thinner and your vitamin K2 daily supplement consistently every day in order to keep your risk of bleeding at a low and steady level (44,45,46).

 

 

Final Thoughts on Vitamin K2

Vitamin K2 is now recognized as a nutrient that is deficient in most people.  Recent and ongoing research is illustrating the many important actions of vitamin K2 on human health, especially as we age.  The beneficial effects of vitamin K2 for bone and cardiovascular health are clear and its possible involvement in brain health and in other assorted health conditions are becoming increasingly apparent.    It is easy enough and safe to take a daily vitamin K2 supplement.  Or, if you are feeling adventurous, try incorporating natto into your diet.  Whichever path you choose, you will be providing your body with an important nutrient required to maintain crucial body processes such as the cardiovascular system and structures such as the skeleton.  In addition, other health benefits of this less understood vitamin are being uncovered in research that is underway right now.

 

 

 

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38 Ikeda, Y., Iki, M., Morita, A., et al. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J Nutr. 2006; 136(5):1323–1328.

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My name is Debra Harley (BScPhm) and I welcome you to my retirement project, this website. Over the course of a life many lessons are learned, altering deeply-rooted ideas and creating new passions.

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