An important component of Vitamin D in Immunodrops™
Written by Rebecka Sadler; Edited by N. Karrow and L.Wagter-Lesperance
Vitamin K is a fat-soluble compound that was first discovered in chickens for its role in preventing excessive bleeding (1). While vitamin K is primarily known for enabling proper blood clotting, it also plays critical roles in improving bone health, reducing inflammation, lowering cancer incidence, enhancing brain function, preventing heart diseases, aiding immune system function, and much more (2).
The core ring structure of vitamin K is identical among all three different forms (2). Vitamin K1, also known as phylloquinone, is made by green plants, cyanobacteria and algae (2). Dietary sources of vitamin K1 include broccoli, dandelion leaves, kale, spinach, cabbage and brussels sprouts (2). Vitamin K2, also known as menaquinone (MK), includes a range of subtypes, spanning from MK-4 to MK-13 (3). Almost all subtypes of K2 are synthesized by aerobic and anaerobic bacteria (4). Dietary sources of vitamin K2 include cheese, sauerkraut, natto and certain meats (2). Finally, vitamin K3, also known as menadione, is both synthetically derived and found as an intermediate in the body (8, 10), and it is not typically the focus of vitamin K research.
Vitamin K2 in ImmunoDrops is derived from geraniol, a flower extract of the geranium plant. This MK-7 has the highest bioactivity and bioavailability out of all the vitamin K2 subtypes (3). Many studies have shown that MK-7 is the most effective at activating various vitamin K-dependent proteins, which include osteocalcin and matrix Gla protein (MGP) (6). Without the proper activation of osteocalcin, the risk of poor bone density and fracture increases (9). Additionally, insufficient levels of activated MGP can lead to the accumulation of calcium in blood vessel walls leading to atherosclerosis and cardiovascular damage (9). Overall, MK-7 has received much attention for use as a supplement due to its superior ability to be absorbed and utilized in the body to optimize health.
In a typical Western diet, an insufficient amount of vitamin K is consumed, partly due to standard food manufacturing processes (9). Therefore, vitamin K must be intentionally consumed to meet daily requirements. The table below includes the daily vitamin K intake values recommended by Health Canada, which does not differentiate between vitamin K1 and K2 subtypes (5). Taking any vitamin K supplements while on vitamin K-dependent anti-coagulant treatments such as acencoumarol, indandione, phenprocoumon or warfarin is not recommended due to vitamin K interfering with the drug’s mechanism of action (7). If you are on a vitamin K-dependent anti-coagulant treatment, consult your healthcare provider before supplementing with vitamin K.
How does MK-7 compare with other types of Vitamin K supplements?
There are many types of Vitamin K supplements for sale at the pharmacy. They will be found in the forms of MK-4, MK-7, K1, or a combination of these. An MK-4 supplement is usually organically synthesized (4). The most common vitamin K supplement, K1, is typically synthetically derived (4). On the other hand, MK-7 is extracted from natto, a Japanese food made from fermented soybeans (4). While it is possible to purchase any desired vitamin K supplement, not all have the same bioactivity or bioavailability.
Current scientific evidence points to MK-7 as the best vitamin K form. As evidence for this, MK-7 has a much longer elimination half-life than K1 does (1). Their half-lives have been recorded as 1-2 hours and around three days, respectively (1). Additionally, K1 and MK-4 are completely removed from the circulatory system approximately 24 hours after consumption (2). This does not leave much time for them to elicit their biological function of carboxylating extra-hepatic proteins.
In another study, prolonged supplementation of MK-4 did not increase its concentration in the blood, leading researchers to conclude that its dietary bioavailability is very poor (3). Likewise, low absorptive rates and bio-activities are noted for the long-chain menaquinones: MK-10-13 (5). However, supplementation with MK-7 yields a prolonged, noticeable increase in serum concentrations (4). The potency of MK-7 is also three to four times higher than K1 on a molar basis (6). These factors make it very effective at carboxylating essential extra-hepatic proteins (4). For these reasons, many researchers conclude that MK-7 is the most beneficial vitamin K supplement to enhance whole-body health.
The protective effects of Vitamins K and D against cardiovascular disease
Heart disease is Canada’s second highest cause of death, contributing to the mortality of 52,541 people in 2019 (1). Consequently, finding ways to promote cardiovascular health is imperative to reduce negative health outcomes and improve people’s quality of life.
Vitamin K plays an important role in maintaining blood calcium homeostasis (2). Without sufficient vitamin K-dependent matrix gla protein (MGP) carboxylation, calcified plaques will build up in blood vessels, increasing the thickness of vascular walls (2). As a result, vascular stiffness and blood pressure rise (2). This occurs because dephosphorylated, uncarboxylated matrix gla protein (dp-ucMGP) is not active to prevent this unwanted calcium deposition (2). The proposed mechanism of action through which MGP prevents calcification is via its ability to bind minerals and ions (6). In fact, mice with a nonfunctional Mgp gene die within the first two months of life due to arterial calcification (6). Therefore, when a person is vitamin K deficient, the risk for atherosclerosis and cardiovascular injury increases drastically (2).
One study investigated the relationship between vitamin K status and calciphylaxis, which is pathogenic vascular calcification (5). The researchers found that patients with a lower vitamin K status, as seen in those with a higher relative ucMGP concentration, were also more likely to have calciphylaxis than the control group (5). The exact percentage of vitamin K-deficient patients who contracted calciphylaxis was 90%, while those in the control group had a 50% case rate (5).
However, vitamin D also plays a relevant role alongside vitamin K in maintaining homeostasis in the cardiovascular system. MGP, synthesized mainly in arterial vessel walls and cartilage, requires vitamin D to enhance its expression (3). One study showed that supplementing K1 and vitamin D together improved vascular elasticity (3). However, vitamin D alone did not elicit any long-term effects on the measured parameters, showing the necessity for both vitamins (3).
A study in the Netherlands assessed how vitamin D and the level of uncarboxylated MGP, an indicator of vitamin K status, influenced blood pressure (4). Those who had low vitamin D (25(OH)D ≤50nmol/L) and vitamin K (dp-ucMGP ≥ 323 pmol/L) statuses had the highest systolic and diastolic blood pressures (4). Moreover, in comparison to those with the highest vitamin K and vitamin D levels, those in the low-status group had a risk of acquiring hypertension that was 69% greater (4). Overall, much scientific evidence supports the synergistic protective benefits of both vitamins K and D supplementation on cardiovascular health.
The necessity of Vitamins K and D in promoting bone and joint health
Another essential role that vitamins K and D play is found in their promotion of bone and joint health (1). To prevent pathological mineralization in other tissues like vasculature and chondrocytes, vitamin K helps to carboxylate matrix Gla protein (MGP) (4). However, vitamin D is also needed to enhance the expression of this protein (2). When active MGP is deficient, the mineralization of osteoarthritic cartilage and arthritic inflammation is increased (3). Additionally, the undesired and disorganized cartilage calcification was observed in mice with a nonfunctional Mgp gene (5). This led to the improper formation of the growth plate chondrocyte columns, which are needed for adequate bone matrix deposition and normal growth (5). Consequently, the mutant mice were shorter and did not grow as quickly as their wild-type counterparts (5). They also incurred osteopenia and fractures, showing the necessity of MGP for maintaining optimal bone density too (5).
Another relevant vitamin K-dependent protein that prevents undesired calcification is Gla-rich protein (GRP) (3). One positive effect of this protein is its hindrance of osteoarthritis’ pathogenesis (3). Vitamin K2 is even used to treat osteoarthritis in Japan (6). Additionally, cGRP and uncarboxylated GRP can elicit anti-inflammatory effects on chondrocytes and synoviocytes in vitro (3). GRP reduces inflammation by lowering the accumulation of Prostaglandin E2 and reducing the expression of COX2 and MMP13 (3). Other studies have also shown the necessity of GRP, found in the cartilage of zebrafish, for proper skeletal growth and development (7). Without the gene coding for GRP, the length of the fish is shortened, and the notochord development is disrupted (7). Since the gene structure coding for GRP is very similar between zebrafish and other mammals, this suggests that GRP may also contribute significantly to human skeletal formation (7).
Finally, osteocalcin is another relevant γ-carboxyglutamic acid protein. The inner matrix of the bone requires osteocalcin, synthesized by osteoblasts, to sequester calcium within the hydroxyapatite (1). However, osteocalcin is only activated by the vitamin K-dependent carboxylation of its three glutamic acid residues (4). Therefore, vitamin K is essential to ensure proper bone mineralization and the prevention of fractures (1).
Nonetheless, vitamin K is not the only vitamin required to activate the function of osteocalcin. Studies have shown that a signal from vitamin D is also necessary to initiate osteocalcin’s transcription before vitamin K can activate it through carboxylation (8). Specifically, a 1,25(OH)D-responsive element found in osteocalcin’s promoter must be bound by vitamin D before transcription can occur (9). Since vitamin K and vitamin D are needed for osteocalcin’s function, both vitamins are necessary to increase the levels of active osteocalcin, as much research has shown (9). Moreover, several studies have found that the risk for bone fractures increases when vitamin K and D levels are low, again showing their essentiality in maintaining strong skeletal structure (9). Additionally, while many postmenopausal women must adapt to the challenge of osteoporosis, research shows that vitamin K and D supplementation can increase bone mineral density to lower the risk of such conditions (9). Overall, it is clear that both vitamins K and D play an important role in helping maintain strong bone structures.