vitamin K 2 spurs d3

 

 

Int J Endocrinol. 2017; 2017: 7454376.
Published online 2017 Sep 12. doi:  10.1155/2017/7454376
PMCID: PMC5613455
PMID: 29138634

The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review

Abstract

Vitamins D and K are both fat-soluble vitamins and play a central role in calcium metabolism. Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly. The purpose of this review is to summarize available evidence of the synergistic interplay between vitamins D and K on bone and cardiovascular health. Animal and human studies suggest that optimal concentrations of both vitamin D and vitamin K are beneficial for bone and cardiovascular health as supported by genetic, molecular, cellular, and human studies. Most clinical trials studied vitamin D and K supplementation with bone health in postmenopausal women. Few intervention trials studied vitamin D and K supplementation with cardiovascular-related outcomes. These limited studies indicate that joint supplementation might be beneficial for cardiovascular health. Current evidence supports the notion that joint supplementation of vitamins D and K might be more effective than the consumption of either alone for bone and cardiovascular health. As more is discovered about the powerful combination of vitamins D and K, it gives a renewed reason to eat a healthy diet including a variety of foods such as vegetables and fermented dairy for bone and cardiovascular health.

Millions of people take calcium supplements to maintain healthy bone. Yet few patients or physicians realize that optimizing bone integrity involves more than taking a single mineral supplement. A critical additional component for bone and cardiovascular health is vitamin K2.

Recent research has revealed that, without vitamin K2, calcium regulation is disrupted. In fact, low levels of vitamin K2 are associated with an increased risk of heart disease and atherosclerosis.1 Astute doctors have long known that people with a lack of calcium in their bones are more likely to possess an excess of calcium in their arteries, and vice versa. The resulting lack of calcium in bone leads to osteoporosis, while the deposition of calcium in the arterial wall leads to coronary heart disease and other manifestations of cardiovascular, renal, and neurodegenerative disease.

Although vitamin K has been around for decades, dietary recommendations have been overshadowed by the nominal amount required for healthy blood clotting—and have ignored the optimal amounts of vitamin K needed to maintain healthy bones and arteries. In this article, we’ll explore how vitamin K2 regulates calcium as well as the recent evidence supporting this unique vitamin in preventing heart disease and osteoporosis as well as certain types of cancer.

Vitamin K2—Essential for Healthy Arteries and Bones

Osteoporosis and heart disease—they seem as unconnected as two conditions can possibly be. On the surface, they do share a few common features. Both conditions develop with age. It’s rare for someone to have either condition at age 30, but both are common in the sixth or seventh decade of life. Both conditions don’t develop overnight, but require many years to emerge. Just as osteoporosis requires decades to develop, coronary atherosclerosis also accumulates bit by bit over decades, starting in a person’s 20s (or earlier) and building gradually until a heart attack or other catastrophe occurs.

SVitamin K2—Essential for Healthy Arteries and Bones

But the resemblance appears to stop there—that is, until we dig beneath the surface. As long ago as the 19th century, scientists knew that an unknown material lining diseased arteries resembled a bone-like structure. For the next 100 years, however, this finding was dismissed as a curiosity, an inevitable accompaniment of aging, and evidence of “wear and tear,” just like arthritis.

Dr. Linda Demer and her team at the University of California, Los Angeles, were among the first to unravel this curious connection by successfully identifying a protein in human atherosclerotic tissue, which was previously believed to reside only in bone tissue. This protein, called bone morphogenetic protein-2, plays an important role in bone formation.2 Since then, several other key regulators of bone formation have been identified in atherosclerotic plaque tissue, such as matrix GLA-protein and osteopontin, suggesting that common factors might influence both arterial and bone health.3

Osteoporosis and Vitamin K2 Intervention—the Evidence

Another curious observation increased the momentum to find a link between bone and arterial diseases. People who had osteoporosis, or a lack of calcium in their bones, were more likely to possess an excess of calcium (bone) in arteries and vice versa. In fact, what had often been simply assumed to be calcium deposits or calcified plaque was actually fully formed bone tissue. Vascular calcification should therefore be more properly designated as vascular ossification—bone formation within blood vessels. Likewise, many “risk factors” for coronary atherosclerosis were also prevalent in osteoporosis: aging, diabetes, sedentary lifestyle, smoking, and high cholesterol.3Scientists questioned why there was such a tight link between excess calcium in one organ (bones) and deficient calcium in another (arteries). And why, in some apparently healthy people, are the two present simultaneously to such extremes?

Initially, some proposed that there may be an abnormal transfer of calcium from bones to arteries. This did not hold up to scrutiny, however, since each system proved to be under its own regulation.

Although certain prescription drugs, such as raloxifene (Evista®) and alendronate (Fosamax®), addressed the problem of osteoporosis, no solution emerged to address both bone and arterial health, that is, until now. Current research is highlighting the importance of nutritional solutions to control the link between arterial and bone diseases by addressing calcium metabolism in the body—in particular, the role played by vitamin K2.

VITAMIN K BASICS
In nature, vitamin K is found in two forms: vitamin K1 (phylloquinone) in leafy, green vegetables, and vitamin K2 (menaquinone) in organ meats, egg yolks, and dairy products.

Vitamin K is required by the human liver to manufacture blood-clotting proteins (factors II, VII, IX, X; and proteins S and C). This is the basis for administering the vitamin K-blocking drug, warfarin (Coumadin®) to people who have blood clots or are at risk for blood clot formation, since clot formation is effectively suppressed by the drug.

Determination of the human need for vitamin K was therefore based on the amount necessary to maintain a normal balance between blood clotting and thinning. Blood shouldn’t be excessively “thinned” and prone to abnormal bleeding, nor excessively “thick” and prone to clotting in the wrong place.

Beyond its role in blood clotting, recent research has revealed that vitamin K also plays a vital role in maintaining healthy bones and arteries by keeping calcium in the bones and out of the arteries.

Unfortunately, the recommended dietary intake of vitamin K required for blood clot regulation is much lower than that required for optimal bone and arterial health.

Osteoporosis and Vitamin K2 Intervention—the Evidence

Since it was first discovered in 1929, vitamin K has been best been known for its crucial role in the blood-clotting process. Since that time, scientists have uncovered compelling evidence that vitamin K plays an equally important role in bone health.

The majority of vitamin K research to date has focused on vitamin K1, the dominant dietary form of vitamin K that occurs in green, leafy vegetables. Yet it appears that vitamin K2, which occurs in organ meats, egg yolks, and dairy products, is a more important inducer of bone mineralization in human osteoblasts (bone-building cells) than vitamin K1.4

Vitamin K2 Protects Against Coronary Heart Disease

The Japanese long ago recognized the power of vitamin K2 to maintain or restore bone health. In certain regions of Japan, a staple dish called natto or fermented soybean, frequently eaten several times a week, is uniquely rich in vitamin K2. Recent scientific examination has pinpointed vitamin K2, and in particular vitamin K2 as menaquinone-7 (MK-7), as the active ingredient in this popular eastern Japanese dish, as having a supportive effect on bone quality during osteoporosis treatment.5

People living in the Japanese regions where this dish is eaten have several-fold greater blood levels of vitamin K2 (MK-7), accompanied by less osteoporosis and bone fractures.6

These findings are supported by clinical trials, in which vitamin K2 has been shown to successfully reduce the incidence of bone fractures. A two-year Japanese study found that vitamin K2 (MK-4) reduced the incidence of vertebral (spine) fractures by 52% in 120 patients with osteoporosis, compared with patients who did not receive this nutrient.7 The high dose used in this trial—as with most studies examining vitamin K2’s effect on bone density—was 45 mg/day, a prescription dose used in Japan to treat osteoporosis that is unavailable in the US. As you will read later, lower doses of K2 found in dietary supplements appear to also provide significant benefits.

CASE HISTORY: HEART DISEASE LINKED WITH OSTEOPOROSIS
Fit and trim at age 67, Walter had no reason to believe that he had any hidden health conditions.

He’d had annual physicals for the past seven years, passing them all. According to his doctor, his cholesterol numbers had been fine for years. But Walter’s brother-in-law, a physician whose own brush with heart disease prompted him to warn everyone else in the family about the possibility, suggested that he undergo a computed tomography heart scan. Walter’s heart scan score was 3,367, a high score that signaled a dangerous content of calcified atherosclerotic plaque in his coronary arteries linked to a high risk for heart attack. In fact, Walter’s score put him in the 99th percentile, meaning that his calcium score was in the worst 1% of all men in his age group (and carried an annual risk for heart attack of 25% without preventive efforts).

At about the same time, Walter enrolled for a screening service that came to his church offering ultrasound screening for abdominal aneurysm, carotid disease, and osteoporosis. While Walter proved to have no aneurysm or carotid issues, he did show the bone density of someone 20 years older, revealing an advanced state of osteoporosis.

While seemingly unrelated, Walter’s arterial calcification and osteoporosis were likely connected through the common mechanism of inadequate levels of vitamin K.

Vitamin K2 has also proven to be as effective as prescription drugs in reducing the incidence of bone fractures. In one Japanese study in post-menopausal women that 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 drug therapy. Furthermore, women taking both MK-4 and the drug experienced a 3.8% fracture rate—a dramatic combined effect. In comparison, in a placebo group who received neither K2 nor drug therapy, nearly 21% of women experienced bone fractures.8

Experimental animal models of osteoporosis have also revealed that MK-4 improves bone architecture, increases bone mass and mechanical strength, stimulates mineralization (deposition of calcium), and enhances collagen architecture—a cross-linking of fibrous tissue that yields tough but supple bone that is more resistant to fracture.9

On the other hand, osteoporosis—the excessive loss of bone mineral density—results in fractures and leads to devastating events common in those over 65 years, even with minor injuries like a fall. Unfortunately, the drug industry focuses on prescribing drugs late in life when the risk for fracture is high. Strategies that involve nutritional supplements are different. Firstly, they lack the high cost and side effects of prescription drugs. Secondly, they can potentially be started at an earlier age and taken over 20, 30, or more years in order to yield possibly greater benefit than drug therapy started at the age of 60 to bail out a process that has developed over decades. Although there are no clinical trials for such an extended period, this is an area worthy of future investigation.

WHAT YOU NEED TO KNOW: VITAMIN K2
  • While calcium is essential for good health, aberrant calcium metabolism can lead to disorders such as osteoporosis and cardiovascular disease. Vitamin K2 is emerging as a key factor in regulating calcium in the body.
  • Insufficient vitamin K2 leads to decreased bone mineral density, a key factor in osteoporosis, and an excess of calcium in the arterial wall, which increases the risk of heart disease.
  • In Japan, vitamin K2 has been shown to substantially improve osteoporosis when given either as a high-dose prescription agent or in the staple Japanese dish called natto, which is particularly rich in K2.
  • Studies have also shown that even modest amounts of vitamin K2 fight heart disease by controlling calcium-regulating proteins in vascular tissue, which keeps calcium out of the arteries and prevents the formation of dangerous calcified plaques.
  • Vitamin K2 occurs in much smaller quantities in the diet than vitamin K1. Most of us, therefore, get little of these K2-rich foods.
  • Current dietary guidelines for vitamin K focus on how much is needed to regulate blood clotting and have largely ignored the much higher amount needed to maintain healthy bones and arteries.

Vitamin K2 Protects Against Coronary Heart Disease

Cumulative Incidence of Hepatocellular
Carcinoma Diagnosed in Women Treated with Vitamin K2
Vitamin K2 Protects Against Coronary Heart Disease
This chart shows the dramatic risk reductions in the incidence of primary liver cancer (hepatocellular carcinoma) in high-risk women treated with vitamin K2 compared with a control group.

Normal deposition of calcium occurs in two organs: bone and teeth. Abnormal deposition of calcium in the body occurs in three places: the inner lining of the arteries (the intima) where atherosclerotic plaque accrues; the muscle layer of arteries (“medial calcification”); and heart valves. Vitamin K2 appears to be the form of vitamin K that contributes to controlling all of these phenomena.

However, calcium has historically been viewed as a passive marker, certainly not an active participant in heart disease. Some maintained that calcium was nothing more than a remnant of prior “rupture,” a scar from dangerous inflammatory activity of soft plaque. They even argued that calcium was, in fact, a reflection of increased plaque stability, as the “hard” material was not itself prone to rupture. Thus, they believed that calcium played no active role in contributing to atherosclerotic plaque.

Does Vitamin K2 Prevent Cancer?

Those arguments have now been dashed by new observations. A definitive connection between vitamin K2 levels and heart disease, in terms of a large-scale, well-controlled clinical trial, was first described in 2004 in the Rotterdam Heart Study—a Dutch trial that tracked 4,800 participants for seven years.1 The study revealed that participants who ingested the greatest quantities of vitamin K2 in their diet experienced a 57% reduction in death from heart disease than people who ingested the least. The same relationship did not hold for vitamin K1. Unfortunately, in this study MK-4 and MK-7 intake and levels were not separately analyzed but were grouped together, along with other MK categories such as MK-8 and MK-9.

Higher intakes of vitamin K2 also corresponded to less calcium deposition in the aorta (an indirect measure of atherosclerosis), whereas participants who ingested less K2 were more likely to show moderate or severe calcification. The lowest risk of heart attack and aortic calcification was seen in participants who included more than 32.7 mcg a day of vitamin K2 in their diet.1

The size and quality of the Rotterdam Heart Study gave credibility to the powerful association between vitamin K2 dietary intake and heart disease and suggests that vitamin K2 may confer cardiovascular benefits by inhibiting arterial calcification.

Physicians and scientists are now intensely interested in monitoring and halting the accumulation of coronary calcium, since they know that it comprises a significant portion of atherosclerotic plaque volume.

It appears therefore that the accumulation of calcium signals actively growing atherosclerotic plaque and that vitamin K deficiency may set the stage for this pathogenic process.

VITAMIN K2 ENCOMPASSES A GROUP OF IMPORTANT SUBSTANCES KNOWN AS MENAQUINONES
The menaquinones make up about 10% of vitamin K consumption and can also be synthesized in the gut by healthy microflora. There are several different forms of menaquinone. Menaquinones are short-listed using the notation MK-n, where the ‘n’ specifies the number of prenyl side chains. MK-4 is available in high doses by prescription. MK-8 and MK-9 are found in fermented food products like cheese. Soy natto is a rich source of the highly bioavailable form of K2 known as MK-7.

MK-4, also known as menatetrenone, is distinct from other menaquinones because it is not a major constituent of MK-n produced by gut microflora.

Does Vitamin K2 Prevent Cancer?

Exciting preliminary evidence is emerging that vitamin K2 may suppress cancer.

In a serendipitous study, initially conducted to explore whether vitamin K2 provided protection against bone loss, investigators noticed that this nutrient dramatically reduced the risk of liver cancer.

In this small Japanese study of 40 women who had liver cirrhosis from viral infections, there was a marked difference in the incidence of liver cancer, with only 2 of 21 developing cancer in the MK-4 group compared with 9 of 19 in a control group.15 The chart on this page shows the significant protective effect against primary liver cancer conferred by vitamin K2 in this study.

Similarly, a pilot study in 61 people recovering from surgical removal of hepatocellular carcinoma (liver cancer) showed that 45 mg/day of MK-4 (the dose used in Japan to treat osteoporosis) enhanced cancer-free survival by a wide margin.16

In the laboratory, vitamin K2 demonstrates inhibitory effects against myeloma and lymphoma, suggesting possible applications for individuals fighting these hematologic cancers.17

Perhaps this is just the tip of the iceberg with vitamin K2’s fascinating effects on cancer. As most of the observations are just getting underway and some have arisen by chance observations, this is an area worth watching. Perhaps even more exciting for our purposes is discovering whether vitamin K2 prevents cancer if taken over a long period.

Obtaining Optimal Amounts of Vitamin K2

Vitamin K1 occurs naturally in green leafy vegetables, whereas vitamin K2 is found in relatively few foods. Organ meats, egg yolks, and the Japanese condiment natto, are sources of vitamin K2, of which natto is by far the richest source. Unfortunately, natto is an acquired taste and a dish that the average American may be unwilling to try. Vitamin K2 is also found in modest quantities in traditionally fermented

cheeses, in particular, Swiss Emmental and Norwegian Jarlsberg.18 Of total vitamin K dietary intake, only about 10% is the K2 form.

Vitamin K deficiency can also result from impaired absorption, in addition to not getting enough in the diet. It can also be caused by prolonged use of anti-biotics, since bacteria that normally reside in the colon (and are obliterated by antibiotic use) are responsible for producing approximately half of the vitamin K needed every day.

Unfortunately, the present recommended dietary intake of vitamin K, 90 mcg/day for women and 120 mcg/day for men, may be inadequate to maintain optimal heart and bone health.4,9,19

Although vitamin K1 is rapidly cleared from the blood, K2 lingers in the blood for an extended period when taken orally and can rise to much greater levels than seen with K1. Vitamin K2 appears to be safe, with no side effects identified even at high doses. In Japan, K2 substantially improves bone density and prevents osteoporotic fractures, given either as a high-dose prescription agent (45 mg/day) or in the Japanese dish natto.7,20 Together, these findings suggest that vitamin K2 may be the preferred form of vitamin K for supplemental use.

What dose of vitamin K2 is best? Scientists are still debating this question. Supplements generally contain between 50 mcg and 1,000 mcg of vitamin K2. Even the low end of the supplement dose of 50 mcg a day may help to support healthy bone density and protect the arterial wall from calcification. Life Extension has long recommended about 1,000 mcg a day of vitamin K2, along with 9,000 mcg vitamin K1 for most people.

CALCIUM-REGULATING PROTEINS
The possible role of vitamin K2 in preventing coronary plaque development has emerged from observations of its effects on several bone proteins, whose main function is to keep calcium where it belongs in the body.

Osteocalcin is a calcium-regulating protein that is controlled by vitamin K2. When vitamin K is present, osteocalcin normally undergoes a process called carboxylation, which binds osteocalcin to the mineral portion of bone. However, in vitamin K2 deficiency, osteocalcin cannot perform this function, resulting in unrestrained calcium resorption (removal) from bone tissue that leads to osteoporosis.

The opposite situation seems to occur in the arteries. Calcium is deposited because another protein called matrix GLA-protein, which is a calcification inhibitor and is also K2-controlled, cannot undergo the process of carboxylation in a vitamin K-deficient state. Because only carboxylated matrix GLA-protein inhibits calcification, undercarboxylated matrix GLA-protein has been found to occur in unusually high concentration at the edge of calcified and atherosclerotic plaques, suggesting it plays an active role in depositing calcium in plaque.4 Impairment of the function of osteocalcin and matrix GLA-protein due to incomplete carboxylation results in an increased risk for developing osteoporosis and vascular calcification, respectively.

Further evidence for the connection between vitamin K2 and arterial calcium comes from other research:

People with more advanced atherosclerotic plaque have reduced levels of carboxylated matrix GLA-protein, a vitamin K-dependent protein.10

  • In animal studies, mice genetically bred to lack a protein that uses vitamin K2 develop unrestrained calcium deposition in the arteries (aorta and coronary) so powerful that they die within a few weeks of birth.11
  • A similar mutation in the human gene that controls vitamin K production doubles the likelihood of atherosclerotic diseases like coronary disease, stroke, and aortic disease.12
  • Furthermore, pregnant women taking the potent blood-thinning agent and vitamin K blocker, warfarin (Coumadin®), give birth to babies with severe abnormalities of bone structure.13
  • Likewise, people who take Coumadin® suffer more osteoporotic fractures.14 They also show substantially more abnormal calcium deposition in other areas, such as heart valves—twice as much as non-Coumadin® takers.13

Safety Caution

If you take Coumadin® (warfarin), use of vitamin K should be discussed with your doctor before you begin supplementation, as changes in blood thinning (prothrombin time or INR [international normalized ratio]—measures of how quickly blood clots) will occur. Note, however, there are data to suggest that modest supplementation of vitamin K1 and perhaps K2 adds to long-term stability of blood coagulation.21 Further discussion can be found in the report, Vitamin K and Warfarin: Stabilizing Anticoagulant Therapy—While Protecting Cardiovascular and Bone Health, in the June 2007 edition of Life Extension Magazine.

Conclusion

The vitamin K2 experience requires further exploration to establish the scope of this exciting and underappreciated nutrient. Given the compelling science behind vitamin K2, enormously powerful benefits of supplementation may soon be realized for both good bone and arterial health.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-800-226-2370.

Dr. William Davis is an author and cardiologist practicing in Milwaukee, Wisconsin. He is author of the book, Track Your Plaque: The only heart disease prevention program that shows you how to use the new heart scans to detect, track, and control coronary plaque.

He can be contacted through www.trackyourplaque.com.

References
1. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.

2. Bostrom K, Watson KE, Horn S, et al. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993 Apr;91(4):1800-9.

3. Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1161-70.

4. Schurgers LJ, Dissel PE, Spronk HM, et al. Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90 Suppl 3:57-63.

5. Iwamoto J, Takeda T, Sato Y. Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis. Nutr Rev. 2006 Dec;64(12):509-17.

6. Kaneki M, Hodges SJ, Hosoi T, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition. 2001 Apr;17(4):315-21.

7. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000 Mar;15(3):515-21.

8. Iwamoto J, Takeda T, Ichimura S. Combined treatment with vitamin K2 and bisphosphonate in postmenopausal women with osteoporosis. Yonsei Med J. 2003 Oct 30;44(5):751-6.

9. Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Curr Pharm Des. 2004;10(21):2557-76.

10. Schurgers LJ, Teunissen KJ, Knapen MH, et al. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1629-33.

11. Luo G, Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997 Mar 6;386(6620):78-81.

12. Wang Y, Zhang W, Zhang Y, et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Circulation. 2006 Mar 28;113(12):1615-21.

13. Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF. Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Arch Intern Med. 2006 Jan 23;166(2):241-6.

14. Schurgers LJ, Aebert H, Vermeer C, Bultmann B, Janzen J. Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood. 2004 Nov 15;104(10):3231-2.

15. Habu D, Shiomi S, Tamori A, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004 Jul 21;292(3):358-61.

16. Mizuta T, Ozaki I, Eguchi Y, et al. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study. Cancer. 2006 Feb 15;106(4):867-72.

17. Tsujioka T, Miura Y, Otsuki T, et al. The mechanisms of vitamin K2-induced apoptosis of myeloma cells. Haematologica. 2006 May;91(5):613-9.

18. Hojo K, Watanabe R, Mori T, Taketomo N. Quantitative measurement of tetrahydromenaquinone-9 in cheese fermented by propionibacteria. J Dairy Sci. 2007 Sep;90(9):4078-83.

19. Shoji S. Vitamin K and vascular calcification. Clin Calcium. 2002 Aug;12(8):1123-8.

20. Katsuyama H, Ideguchi S, Fukunaga M, et al. Promotion of bone formation by fermented soybean (natto) intake in premenopausal women. J Nutr Sci Vitaminol (Tokyo). 2004 Apr;50(2):114-20.

21. Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007 Mar 15;109(6):2419-23.

Vitamins D3 and K2 – The Dynamic Duo

by Ron Hunninghake, MD

Every fall, leading into winter, the sun sets further and further into the south. The days get shorter and the sun’s rays diminish in duration and intensity. This is when D3—”the sunshine vitamin”—blood levels drop in sun-exposed mammals.

That imperceptible signal results in profound behavioral changes that are easily observed in foxes, bears, and many other land roaming creatures: their activity slows while their foraging increases. They are fattening up their calorie stores for the long winter’s hibernation.

With the advent of spring, the bright summer sun’s UVB rays once again bathe their skin and fur. This is where abundant D3 is synthesized from the photo-transformation of cholesterol. This hormone-like vitamin slowly absorbs into the blood stream where it is delivered to the liver, then to the kidneys, where it is finally converted into the activated form of vitamin D.

Rising levels of activated D signals renewed growth, heightened metabolic activity, better immunity, sharpened reproductive instincts, and accelerated tissue repair/regeneration. For millions of years, rising vitamin D levels were synonymous with health, healing and vitality in our mammalian relatives.

Recalibrating Vitamin D Standards

In contrast, my medical school training taught me only that vitamin D prevents rickets. Very small doses were all that was required to keep young kids from having weak, rubbery bones. “Feed ’em vitamin D2 fortified milk and the kids will be fine.” These small doses did stop the spread of endemic rickets.

Because vitamin D is a fat soluble vitamin, the medical standard, until recently, was limited to only 400 IU (International Units) per day. The fear was that an excessive intake of vitamin D would build up in the fatty tissues of the body, possibly leading to excessive calcium absorption and toxicity. “Hypercalcinosis” might then result in the formation of kidney stones, calcified arteries, and other manifestations of excessive calcium in the urine, blood, and body tissues.

Is vitamin D more a drug than a nutrient? This question evokes the famous Paracelsus quote: “The dose makes the poison.” Rodenticides are pesticides that kill rodents, such as rats, mice, and yard destructive moles. Most readers are aware that Coumadin is a carefully dosed medical blood thinner that, when used at the higher pesticide dosages, kills rodents.

Lead - D3-webresizeIt will probably come as a very big shock for our Health Hunters readers to learn that vitamin D3—cholecalciferol—is also used as a rodenticide! That’s right, vitamin D3, if given in a high enough dose over a short enough period of time, effectively kills rodents through massive hypercalcinosis of their organs.

That fact sheds a whole new light on why many “old school” vitamin D researchers are very wary of patients “getting carried away” with their ultra high doses of vitamin D3 as a modern cure all. Is vitamin D3 really the superhero nutrient ready to “save the day”…or could it be the malevolent evil-doer secretly disguised as a “good guy”?!

Putting Safe D3 Dosing in Perspective

Up until recently, the highest dose of vitamin D3 we typically recommended at the Riordan Clinic was 50,000 IU as a convenient once a week dose. Our maximum daily dose was 5,000 IU. This is a very safe dose as is documented on the website of the Vitamin D Council.  Children can safely take about 1000 IU for every 25 lbs. of body weight.

That information may not seem reassuring now that the reader knows that vitamin D3 is used to kill rats. But here’s the data on the LD50 of vitamin D3—the Lethal Dose to kill half of the animals tested: Rats—42 mg/kg, Dogs—88 mg/kg.

Because an accurate LD50 for cholecalciferol in humans has never been determined (thank God!) most researchers use the LD50 for dogs as an estimate for humans. Using a hypothetical human subject weighing 110 pounds: in order to reach the LD50 dose, that subject would need to consume over 3,500 of the 50,000 IU D3 caps in a 24 hour period (146 capsules an hour) in order to have a 50% chance of dying.

I think we’re all safe! (It is actually 10 times easier to kill yourself by over consuming water than it would be by overdosing on vitamin D3 capsules.) Author’s note: I actually had a patient who took too many capsules of various and sundry supplements…and developed a gelatin bezoar that obstructed his small intestine! Don’t overdo capsules!

Of course there are other toxicity and sensitivity issues that can arise in the human consumption of vitamin D3. Generally these can be avoided by having your 25(OH)D level measured once a year and keeping it around 60 ng/dl for optimal health.

Keep in mind that we evolved from primitive, naked humans who lived near the equator, and who, like swimming pool life guards, got around 10,000 IU of D3 from the sun on a regular basis. Canadian researcher Dr. Reinhold Vieth has studied the question of D3 toxicity extensively and states categorically that there is no published evidence for this causing toxicity in adults taking 10,000 IU of a daily D3 supplement.

Why Bother Taking Supplemental D3?

The following chart is taken from the Vitamin D Council’s website where the reader will find extensive documentation for how vitamin D3 can be of benefit for those who have or are at risk of having the following health conditions:

d3 benefits these

Would Even Higher Doses of D3 Make Sense?

Given the over 56,000 published studies on the benefits of vitamin D3 when dosed optimally in humans, it only makes orthomolecular sense to wonder if higher doses might be of greater benefit in chronically ill patients.

The real question here is “What is an optimal dose?” Orthomolecular medicine is defined as “using the correct dose, of the right molecule, for the right condition, in the appropriately chosen patient.”

At the Riordan Clinic, we are using this orthomolecular approach in our application of vitamin D3 in the care of patients suffering from sustained illnesses as delineated on the previous page. However, we don’t just dole out vitamin D3 in a reckless manner. We use several principles of care and safety that were highlighted during Dr. Riordan’s life and tenure at the clinic:

  1. Patients as co-learners. Our patients are encouraged to read and be responsible and self-educated about their illness and the orthomolecular treatments they are using. We provide extensive info on vitamin D3.
  2. Identify and treat actual causes. Rather than temporarily mitigating symptoms, this approach actively searches for and corrects underlying and sustained causes, such as vitamin D deficiency.
  3. Characterize biochemical individuality. Measuring baseline vitamin D levels accomplishes two goals: diagnosis, plus the ability to verify correction of a deficiency later on when progress is being assessed.
  4. Care for the whole person. Taking even the best vitamins at the optimal doses is never enough to maintain the “whole person perspective” in true health care.
  5. Let food be thy medicine. Modern medicine may not even know about small amounts of phytonutrients that only whole foods can provide.
  6. Cultivate healthy reserves. During challenging times of stress and illness, key nutrient reserves may get depleted. Plus, nutrients always work as a team.
  7. The healing power of nature. The doctor treats, but nature heals.

D3:K2—The Birth of a Superhero Combo

Speaking of team work, vitamin D3’s natural partner is vitamin K2. The genius of this combo begins with proper respect for D3’s function of powerfully enhancing calcium absorption. Recent research has shown that excessive calcium intake alone can be harmful to the body. The additional calcium must be correctly utilized or it can show up in the wrong places and cause disease.

This is how very high doses of cholecalciferol kills rodents: excessive calcium uptake, deposition, and interference with normal cardiac and renal function. By conscientiously using vitamin K2 in conjunction with D3, this issue of “metastatic calcium” is thoroughly avoided.

Blood ClottingVitamin K2 activates several important proteins in the body. Henrick Dam, a Danish researcher, discovered vitamin K in 1939 (and won the Nobel Prize for his discovery in 1943). Because the Danish word for blood clotting was koagulation, Dam named the molecule vitamin K. Vitamin K is essential for the functioning of eight proteins involved in blood clotting.

A major medical misunderstanding surrounds vitamin K. Most doctors believe that vitamin K “causes” coagulation. It is true that babies born deficient in K need injections of it to restore coagulation. It is also well known that Coumadin, another rodenticide, poisons vitamin K coagulation function which does cause thinning of the blood. At really high doses this can kill a rat. At properly controlled doses, it can dissolve a threatening blood clot in a human patient.

Lead - K2-webresizeThe correct understanding is that vitamin K, through a chemical step called carboxylation, REGULATES and balances the coagulation system as a whole. Keep in mind that the coagulation system stands ready to CLOT if you are hemorrhaging to death, but it must also PREVENT THE CLOT if there are no lacerations or bleeding points. The eight proteins counter-regulate one another in this balancing act. Vitamin K is needed for this amazing feat.

Carboxylation of osteocalcin is another regulation feat of vitamin K which keeps bones properly mineralized with a strong protein matrix. Activated osteocalcin also stimulates adiponectin, a potent fat metabolism stimulator which helps people maintain normal weight. It is believed that all the antibiotics used in animal feed lots these days are finding their way into consumer’s guts where the beneficial bacteria that convert vitamin K into its active form are being badly disrupted. (Hence, low vitamin K in the body may be a contributing factor in the modern obesity epidemic!)

Activation of the vascular GMP protein is crucial in preventing calcification of coronary and carotid arteries. This explains the 50+% reduction in heart disease in regular vitamin K users. This same protein may also prevent bone spurs. Vitamin K is thus helping us age better with “hard bones and soft arteries”…not the other way around.

Finally, like vitamin D3, strong evidence demonstrates vitamin K’s amazing ability to reduce cancer risk. For example, men taking vitamin K2 mk7 (a naturally occurring long acting form of K2) at 45 mcg a day can statistically reduce their risk of prostate cancer by 60%! That is just one of many cancer risks that are reduced significantly by regular K2 ingestion.

As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.

VITAMIN D TOXICITY & BONE SPURS at Livestrong

Nov 8, 2011 | By Sirah Dubois

Clips from the page

BONE SPURS

Bone spurs are abnormal calcifications that occur in places beyond the boundaries of normal bone. Bone spurs commonly form on the heel and around joints such as your knee, shoulder, spine and fingers. Bone spurs cause problems because they interfere with the motion of joints and often physically irritate surrounding connective tissue such as ligaments and tendons. Reduced range of motion, inflammation and pain are common symptoms of bone spurs. Conventional treatment for bone spurs involves surgical removal, but natural remedies attempt to reverse the biochemical or hormonal conditions that caused the spur in hopes your body will naturally dissolve it.

CAUSES

Bone is made of minerals, primarily calcium, magnesium and boron. For abnormal, noncancerous bone growth to occur, high levels of minerals need to be circulating within your bloodstream, which then collect near tendon and ligament attachments to bone. Over time, the minerals calcify and attach to the bone, forming thin projections that can be sharp. According to the book “Human Biochemistry” by Charles Dreiling, a common underlying condition that leads to bone spurs is systemic over-acidity, which forces your body to mobilize alkaline minerals from your bones and deposit them in tissues that are too acidic. Hormonal imbalance also leads to loss of minerals from bone, which is where vitamin D comes into play.

VITAMIN D

Vitamin D is essential for the maintenance of blood calcium levels within a narrow range, as well as for bone growth and maintenance of bone density. Vitamin D acts much like a hormone and is involved in calcium absorption from your intestines and its efficient use throughout your body. Vitamin D deficiency leads to too little calcium in your body, which eventually manifests as bone diseases such as osteoporosis and osteomalacia. Suggested daily amounts of vitamin D consumption range from 600 to 800 international units, depending on your age, although your skin can produce many times that per hour when exposed to midday, summer sunshine.

That site also has articles on bone spurs and Magnesium, Vitamin K2, and excess Calcium

Be very careful to not have too much Calcium with > 2,000 IU of vitamin D
See IoM again fails to look at interactions – Nov 2010 which has many charts, including the following
released Nov 30, 2010

See also VitaminDWiki

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