The MK4 Power™

NBI is a global leader in MK4 research and product development. NBI and MK4 have a rich history and heritage, and NBI created the only MK4 products (Osteo-K and Osteo-K Minis) in the world with the amount of MK4 (45 mg daily) and supporting micronutrients shown in human clinical trials to grow stronger bones, reduce fractures up to 87%, help people with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), liver cancer and promyelocytic leukemia. Studies also conclude that MK4 reduces inflammatory markers, decalcifies arteries, promotes collagen growth and is essential for healthy blood clotting.

Although initially thought to only have a role in promoting healthy blood clotting (coagulation), MK4 have many other important activities, including healthy effects on bone metabolism, vascular (blood vessel) integrity, and cellular process involved in killing cancer cells. MK4 is a powerfully versatile nutrient.

What is MK4?

MK4 is a specific form of vitamin K2. It is a naturally occurring, fat-soluble vitamin. There are two types of natural vitamin K called vitamin K1 and vitamin K2. Plants synthesize vitamin K1 and animals can create the MK4 form of vitamin K2 by converting K1 to MK4. In foods MK4 is found in dairy and meats but at levels much smaller than those studied and shown to be helpful in humans. While there are different forms of vitamin K2, only MK4 has been shown in clinical trials to reduce fractures and reverse some cancers.

MK4 has been approved as a treatment for osteoporosis and the pain of osteoporosis in Japan since 1995.1 In the United States MK4 is not considered a medicine and is available only as a dietary supplement.

MK4 accumulates in tissues throughout the body, where it has its beneficial effects. It accumulates in the spleen, liver, kidneys, brain, testes, breasts, pancreas, lung and other tissues.2,3,4 Like other nutrients, MK4 is involved in many biochemical pathways. It helps promote healthy platelet and blood production, decreases markers of inflammation, and promotes connective tissue (collagen) production, making it helpful in tissues throughout the entire body.

MK4 Safety

From a large number of clinical trials using dosages in excess of 40 mg/day, there were no reports of side effects associated with any type of hypercoagulable (increased blood clotting) state. Both animal and clinical studies support the conclusion that MK4 has no dangerous effects on blood clotting.

More than 6,000 people (view table summarizing these studies) with AML, MDS, osteoporosis, Parkinson disease, Alzheimer disease, hepatocellular carcinoma, liver failure, liver cirrhosis, myelofibrosis and kidney failure on hemodialysis have taken 45 mg daily (and higher doses) of MK4 for up to eight years without any serious side effects.However, it should be noted that the anticoagulant effect of warfarin, functioning by its interference with the clotting effect of vitamin K, can be offset with as little as 1 mg of vitamin K. If you are on anticoagulant therapy (e.g., taking warfarin), you should not take Osteo-K. For everyone else, Osteo-K is safe.

Tissue

Potential MK4 Health Benefits. See research citation.

Bone

Promotes healthy platelet, white and red blood cell production in people with leukemias.
Grows stronger bones and shown in clinical trials to reduce fractures up to 87%.
Stopped and reversed bone loss from medications (eg, prednisone) in multiple clinical trials.

Brain

May improve brain health by promoting healthy nerve production.

Breast

MK4 appears in the breast milk of lactating women.
Role still unknown.

Kidney

Role still unknown.

Liver

Reduced by 80% development of liver cancer in people with Hepatitis C.
Decreased recurrence of liver cancer.
Caused regression of liver cancer in published studies.
Caused normalization of liver cancer blood markers.

Lung

Role still unknown.
Administered to lung transplant patients in one clinical trial and prevented bone loss.

Pancreas

Role still unknown.

Spleen

Role still unknown.

Testes

Role still unknown.

Blood

Promotes healthy platelets, white and red blood cells.
Used for healthy blood clotting.

MK4 and the Fundamental Role of Collagen

MK4 promotes healthy collagen production, and collagen is the most abundant protein in the body. It is the caffolding that gives shape and strength to cell sand organs. Collagen is a category that includes 29 different types that differ in size, structure, and function. Collagen is required for every cell in our bodies to grow, divide and carry out their important functions. It is so abundant that it accounts for 30% of all proteins. Collagen is found in bones, tendons, ligaments, skin and nerves. Collagen is vital for skin elasticity and helps create and maintain firmness and suppleness. Without it our skin would literally sag like a heavy sack.

Collagen creates the shape of the lungs, and exists throughout our cardiovascular system in blood vessels and the heart, as well as in the kidneys, nerves, pancreas, liver, testes, breasts, brain and eyes. In cancer, it is breakdown of the collagen by cancer cells that allow the cancer to spread throughout the body. This process is called metastasis. Liver cancer studies show that MK4 reduces chemicals called matrix metalloproteinase (MPP) that cause connective tissue breakdown and are invovled in the spread of cancer cells. But when you reduce the degradation of connective tissue you help promote health throughout the body.

The preeminent role that collagen plays in bone health, fracture healing, and fracture prevention has been well documented. Bone matrix is a dynamic, two-phase system in which the mineral phase provides the stiffness and the collagen-fibers phase provides the ductility and ability to absorb energy (ie, the toughness). Therefore, alterations of collagen properties can affect the mechanical properties of bone and increase fracture susceptibility.7 In studies of people with osteoporosis, a loss of bone collagen has been associated with increase fracture risk.

The important role of collagen is demonstrated in rare diseases where collagen production is damaged. There are more than 200 disorders that affect connective tissue. Some of these are inherited at birth (genetic) and some are acquired during someone's lifetime. Examples of genetic connective tissue disorders include Ehlers-Danlos syndrome, Marfan syndrome and osteogenesis imperfecta. Those that can be acquired include osteoarthritis, systemic lupus erythematous (SLE) and emphysema.

The importance of maintaing and promoting collagen health cannot be overemphasized. MK4, which accumulates throughout the body, promotes healthy collagen.

Systemic Benefits of MK4

MK4 promotes collagen health, but it does much more. It grows stronger bones, kills cancer cells, promotes healthy nerves, decreases inflammatory markers and has been shown to remove calcium from arterial walls.

Bone Health

MK4 has been shown to decrease fractures, and has even been approved by the Ministry of Health in Japan since 1995 for the treatment of osteoporosis and osteoporosis pain. Multiple clinical trials using 45 mg per day of MK4 show that this amount, and only this amount, of MK4 taken daily may decrease fractures up to 87% independent of the number of falls sustained.5,6,7,8 MK4 also has been cited as a potential strategy for drug-induced bone loss.9In clinical trials MK4 (45 mg daily) prevented bone loss and/or fractures caused by:

  • corticosteroids (eg, prednisone, dexamethasone, prednisolone),10, 11, 12, 13, 14
  • anorexia nervosa,15
  • cirrhosis of the liver,16
  • postmenopausal osteoporosis, 17, 18, 19, 20, 21, 22
  • disuse from stroke,23
  • Alzheimer’s disease,24
  • Parkinson’s disease, 25
  • primary biliary cirrhosis,26
  • leuprolide treatment (for prostate cancer).27

Fractures are a serious problem resulting from skeletal unloading in handicapped children. A case report was published of an institutionalized, bedridden 8-year-old girl with Arnold-Chiari deformity with low BMD whose BMD increased with MK4 treatment.28 MK4 also inhibited phenytoin-induced bone loss in rats;29 prevented and increased bone formation in neurectomized rats,30, 31 an animal model for immobilization osteoporosis; prevented and increased bone formation in orchidectomized rats,32 an animal model for secondary osteoporosis caused by testosterone deficiency; and improved healing time and bone quality in experimentally induced osteotomy in rats alone and in the presence of glucocorticoids.33

Cancer

Many clinical trials, case reports and basic research studies show that MK4 promotes cellular health in many types of cancer. These studies are summarized on the MK4 Research Summaries page.

Brain and Peripheral Nervous System

In the brain MK4 is involved in maintaining and promoting healthy nerves as part of the pathway for the production of sphingolipids. Sphingolipids for the lining around nerve cells that allow for healthy nerve impulses.  The brain and spinal cord form the central nervous system. Nerves going to and from the spinal cord to muscles, bone, skin and internal organs make up the peripheral nervous system. Nerves provide a common pathway for electrochemical communication to and from tissues throughout the body. Each nerve is covered externally by a dense sheath of connective tissue (collagen), the epineurium. Surrounding nerves are “myelin sheaths.” MK4 promotes collagen production and in the brain MK4 accumulates in the mid-brain, pons medulla, cerebellum, olfactory bulb, thalamus, hippocampus and striatum,5 meaning that MK4 may have powerful beneficial effects on brain and nerve function.

Brain region
What it does
Midbrain The midbrain or mesencephalon is associated with vision, hearing, motor control, sleep/wake, arousal (alertness), and temperature regulation.
Pons medulla The pons medulla is the lower half of the brainstem. It is frequently referred to as simply the medulla. It contains the cardiac, respiratory, vomiting and vasomotor centers and deals with involuntary functions such as breathing, heart rate and blood pressure.
Cerebellum The cerebellum plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established. The cerebellum does not initiate movement, but it contributes to coordination, precision, and accurate timing.
Olfactory bulb The olfactory bulb is involved in the perception of smell.
Thalamus

The thalamus relays sensory and motor signals to the cerebral cortex along with the regulation of consciousness, sleep, and alertness.

Hippocampus The hippocampus plays important roles in short- and long-term memory and spatial navigation.

Inflammatory Marker

Inflammation plays a role in the initiation and progression of many diseases, including cardiovascular disease, cancer, diabetes, obesity and depression. MK4 reduces the expression of nuclear factor kappa beta (NF-κB), a major marker of inflammation.34,35

Cardiovascular Health

MK4 affects proteins involved in the process of arterial calficications, also called hardening of the arteries, which can cause heart attacks. In one study of the effect of MK4 on this process, the researchers concluded, "These findings suggest that MK4 acts as an anti-calcification component in the vessel wall."36 And in another study MK4 (but not vitamin K1) was shown to prevent calcium buildup in arteries.37