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Simplifying the K Confusion
By Dr. John Neustadt, ND

Vitamin K has been getting a lot of attention lately, with some people calling it the "next vitamin D." And as we know, those are big shoes to fill! Vitamin K deficiency is common, so most people would benefit from understanding the nutrient and increasing their intake of it. But with several different forms available, how do we know which one to take?

There are two types of natural vitamin K called vitamin K1 and vitamin K2. They are naturally-occurring, fat-soluble vitamins. MK4 is a specific form of vitamin K2. Plants synthesize vitamin K1 and humans 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 benefit humans. While there are different forms of vitamin K2, only MK4 is produced by our bodies, and only MK4 has been shown in clinical trials to reduce fractures and impede some cancers.

MK4 compiles in tissues throughout the body, where it has beneficial effects. It accumulates in the spleen, liver, kidneys, brain, testes, breast, pancreas, lungs, and other tissues. 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.

In Japan, MK4 has been approved as a medicinal treatment for osteoporosis and the associated pain since 1995. In the United States, MK4 is not considered a medicine and is available only as a dietary supplement.

MK4 Reduces Fractures in Clinical Trials

Multiple clinical trials using 45 mg per day of MK4 show that taking this amount daily may decrease fractures up to 87%, independent of the number of falls sustained. MK4 also has been cited as a potential strategy for drug-induced bone loss. In clinical trials, MK4 (45 mg daily) prevented bone loss and/or fractures caused by:

  • corticosteroids (eg, prednisone, dexamethasone, prednisolone)
  • anorexia nervosa
  • cirrhosis of the liver
  • postmenopausal osteoporosis
  • disuse from stroke
  • Alzheimer's disease
  • Parkinson's disease
  • primary biliary cirrhosis
  • leuprolide treatment (for prostate cancer)

    Fractures are a serious problem resulting from skeletal unloading in handicapped children. A case report was published of an institutionalized, bedridden, eight year-old girl with Arnold-Chiari deformity with low bone mineral density (BMD) whose BMD increased with MK4 treatment. MK4 also inhibited druginduced bone loss in rats; prevented and increased bone formation in neurectomized rats (an animal model to increase risk of osteoporosis); prevented and increased bone formation in orchidectomized rats(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.

    MK4 for Cardiovascular Health
    MK4 affects proteins involved in the process of arterial calcifications, 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." And in another study, MK4 (but not vitamin K1) was shown to prevent calcium buildup in arteries.

    MK4 for Brain and Peripheral Nervous System Health
    In the brain, MK4 is involved in maintaining and promoting healthy nerves as part of the pathway for the production of sphingolipids. Sphingolipids are 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, meaning that MK4 may have powerful beneficial effects on brain and nerve function.

    MK4 Reduces Inflammatory Markers
    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.

    MK4 Dose and Safety
    The dose approved in Japan for osteoporosis is 45 mg daily of MK4. All the clinical trials on osteoporosis have used 45 mg daily, except one, which used a lower dose and did not show a benefit. So be sure to take the 45 mg daily for bone health. More than 6,000 patients have been given MK4 in published studies for up to eight years, even some with kidney failure and liver cirrhosis without any dangerous side effects.

    Maturitas 31(2): 161-164, 1999
    Archives of Internal Medicine 166(12): 1256-1261, 2006 L
    eukemia 14(6): 1156-1157, 2000
    Annals of Hematology 81(1): 16-19, 2002
    Thrombosis Research 122(3): 411-417, 2008

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