Predicting which nutrients will emerge as life-saving superstars can be challenging. For example, a vitamin introduced just a decade ago is demonstrating profound anti-aging effects that extend far beyond its original indications. Based on an abundance of positive findings, scientists have developed a more cost-effective form of this nutrient that enables it to stay in the body much longer than before. The incredible news is that maintaining constant levels of this nutrient not only protects against atherosclerosis, but may reverse arterial calcification as well! A wealth of studies published in 2008 reveals this same nutrient possesses anticancer properties while suppressing factors involved in common age-related diseases.1-15 A hallmark of normal aging involves calcification in soft tissues throughout the body such as heart valves, glands, and blood vessels.16-18 One might erroneously think that dietary calcium is a culprit behind pathological calcification processes. The opposite is true. When rabbits are fed calcium-deficient diets, calcification rates rise by 2.7-fold. Calcium-supplemented diets, on the other hand, reduce calcification by 62%.19 The reason for this contradiction is that in response to a deficit of calcium in the blood, the body excessively robs our bones20 and saturates soft tissues with calcium. As we age, we lose our ability to regulate calcium balance and then suffer the lethal consequences of systemic calcification. It is encouraging to know that a low-cost nutrient (vitamin K) can quickly restore calcium homeostasis. Warfarin (Coumadin®) is an anticoagulant drug that inhibits normal vitamin K function in the body. The alarming result of vitamin K impairment is rapid development of osteoporosis and arterial calcification.21,22 Vitamin K is absolutely essential for regulating calcium balance in the body. A deficiency of vitamin K status causes brittle bones and a vascular system that hardens to a state of poor functionality.23-26 People who take Coumadin® suffer more osteoporotic fractures21 and show substantially more abnormal calcium deposition in other areas, such as heart valves—twice as much as non-Coumadin® takers.22 The fact that these pathological changes are allowed to occur in humans prescribed warfarin is unconscionable given the knowledge about the value of low-dose vitamin K supplementation, even in patients at high risk for abnormal arterial blood clots. Atherosclerosis is the leading cause of disability and death in civilized societies. Many factors are involved in its initiation and progression.27,28 Homocysteine or oxidized low-density lipoprotein (LDL) can initially damage the inner arterial lining (the endothelium).29 To repair this damage, the endothelium produces collagen that forms a cap over the injury site. These endothelial collagen caps attract calcium that accumulates (calcifies) and forms a hard material resembling bone. This is why atherosclerosis is sometimes referred to as “hardening of the arteries.” A substantial volume of studies shows that insufficient vitamin K2 accelerates arterial calcification.31 A new study shows that restoring vitamin K2 reverses arterial calcification.49 Vitamin K functions to keep calcium in the bone and prevent its buildup in the arteries.23-26,28,31 If that is all vitamin K did, it would be one of the most important nutrients for aging humans to take. Newly published research, however, indicates vitamin K2 possesses a host of additional benefits. Bone is living tissue that is in a constant state of renewal. The maintenance of bone first requires old bone to be dissolved by cells called “osteoclasts.” When the activity of osteoclasts is too high, large holes develop that weaken the bone and lead to osteoporosis. Vitamin K2 is a key to turning off excess osteoclast activity and bone degradation. The holes left by osteoclasts are prepared for remodeling by osteoblast cells. The osteoblasts secrete a protein called osteocalcin, which when activated (or carboxylated) enables new calcium to be laid down into the bone. The calcium-binding properties of osteocalcin require vitamin K, whereas the synthesis of osteocalcin itself requires vitamin D3. Vitamin K thus provides two critical benefits to the bone. It first protects against excess bone degradation (resorption) by turning off excess osteoclast activity. It then supports the critical role of new bone formation by enabling osteocalcin to pull calcium from the blood and layer it on to the bone. From this brief description, it is clear that maintenance of healthy bone density requires adequate levels of calcium, vitamin D, and vitamin K. Without vitamin D, there will be no osteocalcin for vitamin K to work on. Without vitamin K, the osteocalcin that is produced will be inactive. And of course without calcium (and other minerals), there will be no minerals for the activated osteocalcin to attract to the bone for structural density. The Nurses’ Health Study followed more than 72,000 women for 10 years and found that women whose vitamin K intakes were in the lowest quintile (1/5) had a 30% higher risk of hip fracture than women with vitamin K intakes in the highest four quintiles.67 A seven-year study in over 888 elderly men and women (Framingham Heart Study) found that men and women with dietary vitamin K intakes in the highest quartile (1/4) had a 65% lower risk of hip fracture than those with dietary vitamin K intakes in the lowest quartile (approximately 254 micrograms/day vs. 56 micrograms/day of vitamin K).68 Vitamin K2 has proven to be as effective as prescription drugs in reducing the incidence of bone fractures. A Japanese study in postmenopausal women compared the effect of K2 (MK-4) with the drug etidronate (Didronel®) on the incidence of vertebral (spine) fracture. Women taking K2 at a dose of 45 mg per day experienced a fracture rate of 8.0% compared with 8.7% for those taking the etidronate drug therapy. Furthermore, women taking both MK-4 and the drug experienced only a 3.8% fracture rate. In a placebo group that received neither K2 nor drug therapy, nearly 21% of women experienced bone fractures.69 Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation in the joints and other organs in the body. Those afflicted with rheumatoid arthritis have startlingly high rates of cardiovascular diseases.33 In a study published in June 2008, Japanese scientists found that vitamin K2 inhibited the proliferation of synovial cells and prevented the development of collagen-induced rheumatoid arthritis in the rat model. The scientists concluded that vitamin K2 may represent a new agent for the treatment of rheumatoid arthritis in combination with other anti-inflammatory drugs.34 A recent human study showed that the use of vitamin K2 alone or in combination with bisphosphonate drugs (like Fosamax®) for treatment of osteoporosis in patients with rheumatoid arthritis may inhibit osteoclast induction via decreases in levels of inflammatory mediators.35 Excess osteoclast activity depletes bone mineral density. Americans afflicted with osteoporosis or low bone mineral density scores are sometimes prescribed drugs like Fosamax® or Actonel®. Side effects from these drugs sometimes preclude their long-term use. Japanese patients are often prescribed high doses of vitamin K2 instead of drugs. Published studies demonstrate the ability of vitamin K2 by itself to halt the loss of bone mineral density.23,36,37 A study published in May 2008 used both Fosamax® and vitamin K2 in postmenopausal women in Japan for one year. The results showed that addition of vitamin K2 led to a greater increase of femoral neck bone density, compared with Fosamax® alone. The doctors confirmed the specific bone-protecting mechanism unique to vitamin K2, a finding that had been established in previous studies.38 Doctors in Germany conducted a study examining the relationships between dietary intake of vitamin K1 and K2 on the development of prostate cancer in 11,319 men over an 8.6-year follow-up.4 Compared with the lowest intake of vitamin K2, men with the highest vitamin K2 dietary consumption showed a 63% reduced incidence of advanced prostate cancer. Intake of vitamin K1 was not related to prostate cancer incidence in this 2008 study.4 Skeletal fractures cause significant disability and there is growing interest in identifying methods to accelerate the healing time of broken bones. The synergistic effect of vitamin D3 and vitamin K2 in preventing osteoporosis has been documented in clinical practice.39 Up until now, however, there were no reports investigating if these nutrients could enhance fracture healing. An in vitro study published in January 2008 showed that combining vitamins D3 and K1 favorably modulated the proliferation and differentiation of cells required to heal bone. This led the doctors to conclude that these nutrients taken together offer clinicians a promising low-cost strategy for laying down new bone material.39 Vitamin K2 induces differentiation and apoptosis in a wide array of human cancer cell lines. A search of PubMed reveals studies published in 2008 that discuss the role of different forms of vitamin K in the treatment of cancer.1-15 A goal of cancer researchers is to identify compounds that cause cancer cells to self-destruct. Vitamin K2 has been shown to induce apoptosis (cell destruction) in leukemia cells in vitro. A study published in July 2008 identified yet another pathway by which vitamin K2 causes the degradation (via autophagy) of leukemia cells’ own components. The scientists noted that apoptosis and autophagy in leukemia cells could be simultaneously induced by vitamin K2.8 In the laboratory, vitamin K2 demonstrates inhibitory effects against myeloma and lymphoma, suggesting possible applications for individuals fighting these all too common cancers.40 Infection with the hepatitis B or C virus is a major risk factor in developing primary liver cancer, known medically as hepatocellular carcinoma. It can also occur in those who do not have hepatitis. A study published in the Journal of the American Medical Association showed that in those with viral-induced liver cirrhosis, less than 10% of patients given vitamin K2 developed liver cancer. In similar patients not given vitamin K2, a startling 47% developed primary liver cancer.41 Vitamin K2 decreased the risk of hepatocellular carcinoma to about 20% compared with the control group. In a study published in early 2008, 61 primary liver cancer patients who were in remission after treatment were separated into two groups. One group was given supplemental vitamin K2. After one year, only 13% of the group that received K2 experienced recurrence of liver cancer, compared with 55% of the group who did not receive K2. Three-year survival in the vitamin K2-supplemented group was 87% compared with 64% in the group not receiving the vitamin K2.42 In 2007, scientists identified specific anticancer mechanisms for vitamin K2, including inhibition of proinflammatory nuclear factor-kappa B (NFkB) that is often over-expressed in cancer cells.43 Tumor cells use proinflammatory factors to develop survival mechanisms that thwart conventional attempts to eradicate them. Drugs like Coumadin® that antagonize vitamin K do more than cause bone loss and arterial calcification. In a model of melanoma in mice, the oral administration of anticoagulant drugs that antagonize vitamin K “drastically promoted metastasis.” The promotion of metastasis was almost completely suppressed by the pre-administration of vitamin K3, suggesting that these anticoagulant drugs promote metastasis by specifically antagonizing vitamin K.44 While vitamins K1 and K2 are safe and effective, vitamin K3 is potentially toxic and its use has been limited to treating aggressive cancers. A study published in early 2008 identified several specific mechanisms by which vitamin K3 damages pancreatic cancer cells, leading the researchers to state that, “the action of vitamin K3 may lead to a favorable outcome against pancreatic cancer.”7 What You Need to Know: Protection Against Arterial Calcification, Bone Loss, Cancer, and Aging! One of the pathological processes that occur with aging is calcification of tissues throughout the body. Arterial calcification increases heart attack risk. Vitamin K helps regulate calcium balance, keeping calcium in the bones and out of the arteries. Insufficient vitamin K accelerates arterial calcification, while restoring vitamin K2 can help reverse arterial calcification. Vitamin K shows promise in the prevention and treatment of numerous cancers, including prostate cancer. Vitamin K2 is often utilized in Japan to halt bone loss and prevent fractures, and it may complement prescription osteoporosis therapies such as Fosamax®. Vitamin K2 shows numerous advantages over vitamin K1, including better absorption and increased protection against heart disease The MK-4 and MK-7 forms of vitamin K2 have demonstrated important health benefits in numerous studies. While the MK-4 form has been shown to support cardiovascular and bone health, the MK-7 form is exceptionally long acting and reaches higher levels in the blood. Individuals who use Coumadin® have long been advised to avoid vitamin K, and as a result, they may suffer increased atherosclerosis and osteoporosis. Under a doctor’s supervision, vitamin K can help stabilize blood indicators of coagulation in Coumadin® users while conferring other health benefits. Apatone® is a drug consisting of vitamin C and vitamin K3. It has been granted orphan drug status by the FDA to treat advanced bladder cancer. Apatone® selectively targets tumors by entering cancer cells as readily as glucose. It then suppresses inflammatory responses (such as those induced by nuclear factor-kappa B) that cancer cells use to escape destruction by chemotherapy agents. Vitamin K3 is being clinically tested as an agent to administer prior to chemotherapy to decrease the resistance tumor cells develop to chemo drugs. In March 2008, the results of a study were published on prostate cancer patients who had failed standard therapy and were given the drug Apatone® at a dose that equaled 5,000 mg of vitamin C and 50 mg of vitamin K3. The results showed that PSA velocity decreased and the time it took PSA to double increased in 13 of 17 patients. Of the 15 patients who continued on Apatone®, only one death occurred after 14 months of treatment. The doctors concluded, “Apatone® showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.”5 Based on the plethora of studies published in 2008, vitamins K2 and K3 have emerged as intriguing agents in both cancer prevention and treatment. Normal deposition of calcium occurs in only two places: bone and teeth. the inner lining of the arteries (the intima) where atherosclerotic plaque accrues; the heart valves, especially the aortic valve causing aortic stenosis Vitamin K2 appears to be the most important factor in steering calcium into the bone and away from heart valves and the arterial system.