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Vitamin K for Bone, Brain, Immune and Liver Health

Article at-a-glance:

  • MK4 is the most studied form of vitamin K2.
  • MK4 maintains strong bones; supports brain, liver, and immune health; and promotes healthy bone marrow and blood cell production.
  • No other form of vitamin K2 has been shown to do all these things.
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By Dr. John Neustadt

People often talk of vitamin K as though it was a single vitamin; however, vitamin K is a category that contains different subtypes. While they’re all fat-soluble and structurally similar, they’re not identical. This leads to different effects.

The two broad categories of naturally occurring vitamin K are Vitamins K1 and K2. Vitamin K1 is found in green leafy plants like swiss chard and lettuce and is also called phylloquinone. There’s only one type of vitamin K1. 

Vitamin K2, however, has many subtypes. Of all the forms of vitamin K2, your body only produces MK4. It does this by converting vitamin K1 to MK4. Other mammals also do this, which is why MK4 is found in dairy products like cheese and yogurt. Unlike other forms of vitamin K, MK4 is the major form of vitamin K that accumulates throughout the body—in the testes, pancreas, kidneys, brain, and arteries.1,2  In fact, tissues that accumulate high amounts of MK4 have a remarkable capacity to convert up to 90% of the available K1 into MK4. 3,4

This hints at MK4’s wide-ranging health benefits. While MK4 is best known for bone health, it’s an important nutrient used throughout your body. Among all the forms of vitamin K2, only MK4 has been shown to maintain strong bones; support brain, liver, and immune health; and promote healthy bone marrow and blood cell production. 

Strong bones

The health benefits of MK4 have been researched for more than thirty years and it’s the most-studied form of vitamin K2 for bone health. More than 25 clinical trials with over 7000 volunteers conclude that MK4 (45 mg/day) maintains strong bones.5,6 After more than thirty years of research, we have a better understanding of how MK4 uniquely promotes bone health and other systems in the body. 


Two primary cells maintain bone health—osteoblasts and osteoclasts. Osteoblasts build new bone while osteoclasts break down and recycle old bone. Vitamin K as MK4 activates genes that promote the creation of osteoblasts. It does this by binding to the steroid and xenobiotic receptor (SXR)/pregnane X receptor (PXR).7-9 


Nuclear factor kappa beta (NF-kB) helps regulate inflammation. Elevated levels of NF-kB are associated with increased inflammation, which in turn stimulates the production of osteoclasts. It also helps osteoclasts stay alive longer, giving them more time to destroy the bone. Since too much osteoclast activity can lead to osteoporosis, having a healthy inflammation balance is important for maintaining strong bones. MK4 has been shown to inhibit NF-kB.10,11


RANKL is a cellular receptor that’s involved in bone health. Increased RANKL activity damages bone. MK4 has been shown to reduce RANKL activity, which has been associated with improved bone health.12

Bone collagen genes 

MK4 activates genes involved in bone collagen accumulation. These include growth differentiation factor 15 (GDF15), Stanniocalcin, Tenascin-c, bone morphogenic protein-2 (BMP-2). Only MK4 activates all these genes.11,12,13

Vitamin D

MK4 enhances the ability of vitamin D to add minerals to the bone.15

Healthy bone marrow

In addition to bones allowing you to stand up and walk around, they also produce blood cells. Bone marrow creates red blood cells, white blood cells and platelets. Red blood cells carry oxygen throughout your body. White blood cells power your immune system and platelets are required for healthy blood clotting. All of these cells are produced by stem cells in your bone marrow, and MK4 promotes healthy stem cell production.16

Brain health

MK4 helps maintain brain health by supporting sphingolipid production. Sphingolipids are a group of molecules that, among other things, insulate nerves so they can efficiently transmit their electrical impulses. Sphingolipids are necessary for healthy cognition, mood and movement. MK4 is used for one step in the creation of sphingolipids, and more MK4 in the brain is associated with higher amounts of sphingolipids. 

MK4 accumulates in different brain regions, such as the:

  • midbrain (movement of your eyes and processing sounds and vision)
  • pons (generates respiratory rhythm and breathing)
  • cerebellum (helps maintain balance)
  • olfactory bulb (your sense of smell)
  • thalamus (regulates consciousness and alertness)
  • hippocampus (plays a major role in memory and learning)
  • striatum (important for movement)

Since MK4 accumulates in these areas, it suggests this form of the nutrient is the active form in the brain and may have powerful benefits for healthy brain and nerve function.17,18 

Liver Health

MK4 supports liver health by maintaining healthy cells. MK4 inhibits NF-kB and matrix metalloproteinase (MMP) in liver cells.19,20 MMP plays a key role in regulating the immune system, and lowering MMP activity is associated with improved immune health and healthy cell structure.21 

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1 Shearer MJ, Newman P. 2008;100(4):530-547.

2 Shearer MJ, Newman P. 2014;55(3):345-362.

3 Ronden JE, Drittij-Reijnders M-J, Vermeer C, Thijssen HHW. 1998;1379(1):69-75.

4 Davidson RT, Foley AL, Engelke JA, Suttie JW. 1998;128(2):220-223.

5 Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. 2015;26(3):1175-1186.

6 Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ.2006;166(12):1256-1261.

7 Igarashi M, Yogiashi Y, Mihara M, et. al.  2007;27(22):7947-7954.

8 Tabb MM, Sun A, Zhou C, et al.2003;278(45):43919-43927.

9 Ichikawa T, Horie-Inoue K, Ikeda K, et. al. 2006;281(25):16927-16934.

10 Yamaguchi M, Weitzmann MN. 2011;27(1):3-14.

11 Ichikawa T, Horie-Inoue K, Ikeda K, et. al. 2006;281(25):16927-16934.

12 Wu WJ, Kim MS, Ahn BY. 2015;6(10):3351-3358.

13 Ichikawa T, Horie-Inoue K, Ikeda K, et. al. 2007;39(4):239-247.

14 Akbari S, Rasouli-Ghahroudi AA. 2018;2018:4629383.

15 Miyake N, Hoshi K, Sano Y, Kikuchi K, et. al. 2001;12(8):680-687.

16 Fujishiro A, Iwasa M, Fujii S, et al. 2020;112(3):316-330.

17 Carrié I, Portoukalian J, Vicaretti R, et. al. 2004;134(1):167-172.

18 >Ferland G. 2013;39(8):849-855.

19 Ide Y, Zhang H, Hamajima H, et al. 2009;22(3):599-604.

20 Ozaki I, Zhang H, Mizuta T, et al. 2007;13(7):2236-2245.

21 Naim A, Pan Q, Baig MS. 2017;7(4):367-372.

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