Over the last two decades, with marked advances in science and technology, the most recent research on vascular or coronary pathology are revealing that the lipid theory might not be as definitive as once thought as being the major cause of Cardiovascular Disease and Peripheral Vascular Disease.
Many cardiologists across the globe are now supporting what they believe to be a more likely cause of vascular diseases is the accumulation of excess calcium mixed with plaque in coronary arteries due to low vitamin K and magnesium levels. Low levels in either of the two are associated with calcifications in the blood vessels, tissues and organs as well. Vitamin K keeps calcium in its proper place, the bones and out of the tissues. Magnesium helps activates an enzyme required for new bone to form and prevents the toxic effects of calcium such as solidifying crystals or kidney stones.
Also, studies shows that the ratio of calcium to magnesium in the Paleolithic diet was 1:1, compared to 10:1 ratio in our present-day diets. With an average of ten times more calcium than magnesium in our current diet, there is no doubt this will cause an imbalance with other vitamins or minerals in the body.
High Calcium Scores
Taking too much vitamin D (Over 2000 UI) for longer periods can cause absorption of too much calcium in the body and also reduce other vitamins or minerals such as magnesium, vitamin K and A. Without vitamin K, the body cannot direct calcium where it’s needed and instead, resides in soft tissue. High artery calcium scores are associated with increased cardiovascular events, and research shows that a high calcium score and a high Osteocalcin serum can reflect a low vitamin K status.
There is the renowned doctor, Arthur Agatston, a Florida cardiologist, that became well known for his studies on the excess calcification found in many of his patients with atherosclerosis and coronary artery disease. He developed the scoring sheet for calcification of the arteries, now known as the agatston score. Also, UCLA cardiologist, Dr. Matt Budoff, a long-time champion of the coronary calcium scan, even stated that the total amount of coronary calcium or agatston score predicts coronary disease events beyond standard risk factors.
Vitamin D Absorption
There are some people who do not consume much of vitamin D or calcium in their diet, or live in Northern latitudes who may benefit from taking 1000-2000 units daily. However, usually more is needed in the winter season and less in the summer season. Those who have hardly any sun exposure, or have certain chronic medical conditions, may need 5000-8,000 units a day for about 12-16 weeks and then down to 800-1500 units daily for maintenance.
We should also take vitamin D3 with your largest meal of the day or with some fat such as a slice of cheese or avocado because it is a fat soluble vitamin and needs some fat to be absorbed properly. We should never take vitamin D3 supplements with ‘Vegetable Oils’ such as canola oil, safflower, soy or other any shelf stable oils. They should not be in your vitamin D capsules because the oil will go rancid. If you prefer a gel, choose a vitamin D3 that has a carrier of extra virgin olive oil, and added vitamin E to prevent the oil from going rancid. Also, keep in your refrigerator. Don’t forget to eat plenty of vitamin K foods while supplementing vitamin D.
To be safe I prefer a dry formula of vitamin D3 and take it with at lunch or dinner. Plus, it is low maintenance when traveling and does not go rancid. Some may need a higher dosage in the dry formula, depending on their absorption. There are some formulas that include liquid drops of vitamin D3 with K2, but it is best to take them separate so we can control how much we are getting and not overdo it. To keep your vitamin D levels at 50-60 you should test every two months until they are completely stable, then three times a year afterwards. The tests would include 25-hydroxyvitamin D for deficiency and 1,25-dihydroxyvitamin D for inflammatory problems. A high level of 1,25-dihydroxyvitamin D can be seen in chronic pain and is one of the earliest changes to occur in persons with early kidney failure. Also, a high level of 1,25-dihydroxyvitamin D may occur when there is excess parathyroid hormone or diseases, such as sarcoidosis or some lymphomas, which can make 1,25-dihydroxyvitamin D outside of the kidneys.
The Effects of Vitamin K
People with malabsorption issues that have intestinal diseases or the elderly are quite often deficient in vitamin K among other fat solubles. However, this deficiency can affect us all eventually because our diet provides more foods with plenty of K1 (plant base) such as broccoli, kale, spinach, turnips, beans, nuts, cabbage, asparagus, celery, oregano, lettuce, okra, seaweed, rhubarb, grapes, cucumber, peas, cauliflower, and little in vitamin K2 such as soft cheese, eggs, chicken, pork.
The ability of vitamin K2 and these proteins to prevent against Atherosclerosis and Cardiovascular Disease is published in several compelling studies. For instance, in one study, people with higher intake of vitamin K2 from natto (Mk-7), developed from fermented soybean, had a 55% reduction in risk of dying from cardiovascular disease. This is why the Japanese live longer and have reduced heart disease because they eat fermented soy (natto). Those with blocked arteries and damaged heart valves show low vitamin K status. Also, another study showed 26 women taking vitamin K2 (MK-4) have reductions in fractures as high as 80%.
Now don’t go running out to purchase vitamin K2 supplements before checking your levels first because it could be quite harmful for some people. Anyone on coumadin, estrogen replacement or have any clotting disorders, needs to be careful supplementing with vitamin K. It could cause your blood to clot more creating thrombosis, so please consult with your physician first.
Mechanism of Vitamin K2 and Osteoblastogenesis
A group of key proteins in bone metabolism has emerged as new players in cardiovascular diseases: the receptor activator of nuclear factor kB, receptor activator of nuclear factor kB ligand and osteoprotegerin. Nuclear factor kB (NF-KB) stands for nuclear factor kappa-light-chain-enhancer of activated B cells. It is a protein complex that controls the transcription of DNA. This NF-KB complex is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. Incorrect regulation of this nuclear factor kappa-chain enhancer of activated B cells has been also linked to cancer, inflammatory and autoimmune diseases, cardiovascular disease, viral infection, and improper immune development.
In the bone, osteoprotegerin are expressed in osteoblasts, and the receptor activator of nuclear factor KB are expressed in osteoclast cells. Osteoblasts involves the formation of bone, whereas, osteoclasts involves the breakdown of bone tissue. Osteoprotegerin is an inhibitor of osteoclastic bone resorption or breakdown, and has a variety of functions including anti-inflammatory effects and a protective role in cardiovascular.
The major role of these NF-KB receptors in bone is the stimulation of osteoblast activity to promote bone growth, but inhibition of osteoclast apoptosis. Studies have shown that vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis. In osteoprotegrin-deficiency, mice develop severe osteoporosis resulting from marked increase in bone turner and two-thirds of the animals have profound vascular calcification. Similar to K deficient mouse, postmenopausal women also have high incidence of osteoporosis and vascular calcification, which suggests that these two NF-kB receptor systems may work not only in osteoporosis, but also in arterial calcification. In vitro, vitamin K treatment increased osteoprotegerin production in bone marrow cells. Another study of patients being treated with glucocorticoid medication for kidney disease, vitamin K treatment prevented a glucocorticoid-induced reduction in serum osteoprotegerin, which in turn lowers vitamin K. This is sometimes seen on MRI as decrease bone marrow.
Research indicates that vascular calcification is a complex and actively regulated process involving tissue proteins that depend on the presence of vitamin K. This means that it may be possible to modify or reverse the disease process by taking vitamin K2 supplements a couple times a week. There is a growing line of research highlighting the profound benefits of vitamin K2 for cardiac health, including protection to other vascular disease, decreasing calcification, inhibiting calcification from occurring, and reducing the risk by at least 75-80%.
Calcifications of the pineal gland, choroid plexus, basal ganglia and dura mater are commonly seen with aging and are usually not associated with pathological clinical phenomena. However, calcium deposits can be associated with several intracranial pathologies including tumors, cerebrovascular diseases, congenital conditions, trauma and metabolic disorders. The location and characteristics of the calcification in these lesions are very important indicators in diagnosis and differential diagnosis. Although MRI has been thought to be the best imaging modality in the central nervous system, there are occasions when a CT scan needs to be obtained to confirm the presence of calcification suspected on MRI when it becomes a critical sign in diagnosis.
Other vitamin K-dependent proteins involved in vascular calcium metabolism are Matrix Gla-proteins. Matrix Gla proteins are dependent on vitamin K and contains five gamma-carboxyglutamic acid (Gla) residues that are believed to be important in binding Ca (2+) calcium crystals and bone protein. It needs an adequate amount of vitamin K available in order to function effectively, inhibit excess calcium and prevent reduction in vascular or arterial calcification. Even though calcium and vitamin D are needed, they should be temporarily limited if the levels of vitamin K is suspected to be low. One needs to increase their low vitamin K levels to the proper ideal range before adding calcium or vitamin D. People with malabsorption issues may not absorb enough vitamin K from foods so therefore, a supplement may be needed to get the daily recommended allowance.
The most abundant non-collagen protein in bone matrix is a bone-specific, calcium binding protein. Serum osteocalcin levels are related to the rate of bone turnover in various disorders of bone metabolism, osteoporosis, primary and secondary hyperparathyroidism, and Paget’s disease. Several studies show that increase serum ostecalcin and vitamin K after supplementing with Mk-4.
Sex Hormones That Modulate Vitamin K
Vascular calcification is one of the major complications of cardiovascular disease and an independent risk factor for myocardial infarction and cardiac death among other outcomes. Arterial calcification is also associated with women and men over 55 that have Estrogen or Testosterone deficiency. Several studies have also shown that Estrogen and Testosterone regulates bone metabolism by osteoblastogenesis, which consist of osteoblast expression in osteoprotegrin which inhibits vascular calcification progression. Oral estrogen or testosterone increases hepatic synthesis of vitamin K dependent clotting factors, but the transdermal method by passes the liver so it may be ok. This is one reason why hormones help with bone density.
In the controlled Women’s Health Initiative Study, postmenopausal women aged 50 to 60 years treated with long-term estrogen therapy had lower levels of coronary artery calcification than those who received placebo. However, the androgen hormones such as Dhea or Testosterone during different phases of skeleton development are still far from clear. There is fairly convincing evidence that aromatization from Testosterone to estrogen is an important mechanism for mediating the action of androgens on bone physiology. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Also, both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor. These hormones increase hepatic synthesis of vitamin K.
Different Forms of Vitamin K and Testing
There are several different forms of vitamin K such as K1 which is from plants, K2 from fermented soy foods, and K3 which is synthetic and should not be used as a supplement. The best forms of vitamin K to supplement are MK-4, MK-7, MK-8, MK-9. The form of vitamin K that has the most relevance for health benefits is MK7 a newer and longer acting form with more practical applications. MK7 is extracted from the Japanese fermented soy product called natto. You could actually get plenty of MK7 from consuming natto, as it is relatively inexpensive and available in most Asian food markets. This is the one that reduces calcifications in the tissues or organs and helps with a little bone strength. The recommendation is 50-90mcg of vitamin MK-7 two times a week, to prevent calcifications while taking vitamin D and calcium. However, MK-4 at 5-10mg will improve bone health, teeth, skin and hair, but because it is short lived, it may be supplemented more often, especially if taken in pill form. There is a great liquid formulation of MK-4 by Thorne which is top quality and only one or two drops is needed a day or every other day. It is best to alternate between the two to get the benefit of both worlds, but not together, as they may cancel each other out. It is worth the effort.
However, as a cautionary note: Do not take vitamin K if you are on Coumadin (warfarin) or any blood thinning medicines. This will interfere with vitamin K synthesis. There are a few tests by quest diagnostic labs to get an idea of how much vitamin K is being absorbed. These are prothrombin time and plasma osteocalcin, N-MID.
Unfortunately there really isn’t a great commercial assay for vitamin K2 yet. Sure there is a blood test that may give you an idea because it measures the clotting time to see how fast you clot. Normally, if you do not clot by a certain time, it may indicate that you are low in some version of vitamin K analogs. And if you have other symptoms like mild to moderate bleeding in gums, gastrointestinal tract, blood in urine, bruising easily and petechia on lower legs. The only thing with this type of testing is that it provides almost no value for determining vitamin K deficiency in your bones or arteries. In fact in some cases, blood levels of vitamin K may appear normal while a real deficiency exists in your bones. So, more research needs to be done in this area of testing.
If you are considering vitamin D, K or calcium supplements, please consult with a registered dietitian or physician to check your levels first. It’s better to be safe than sorry!
Gundberg CM, Nieman SD, Abrams S, Rosen H. Vitamin K status and bone health; An analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metabolism,1998.
Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood; 1999
Tsaioun KI. Vitamin K-dependent proteins in the developing and aging nervous system; 1999
Campbell GR, Campbell J. Vascular smooth muscle and arterial calcification. Z Kardiol; 2000
Shearer MJ. Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care.; 2000.
Gailani d, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Shattil SJ. Hoffman Hematology: Basic Principles;Churchill Livingstone Elsevier;2008
A. Falahati-Nini, B. L. Riggs, E. J. Atkinson, W. M. O’Fallon, R. Eastell, and S. Khosla, “Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men,” Journal of Clinical Investigation; 2000.
Fusaro M, Noale M, Viola V, Galli F, Tripepi G, Vajente N, Plebani M, Zaninotto M, Guglielmi G, Miotto D, Dalle Carbonare L, D’Angelo A. Institute of Neuroscience, Padua, Italy.”Vitamin K, vertebral fractures, vascular calcifications, and mortality” Italian dialysis study; J Bone Miner Res. 2012
S. Kaptoge, N. Dalzell, E. Folkerd, D. Doody, K.-T. Khaw, T. J. Beck, N. Loveridge, E. B. Mawer, J. L. Berry, M. J. Shearer, M. Dowsett, and J. Reeve
“Sex Hormone Status May Modulate Rate of Expansion of Proximal Femur Diameter in Older Women alongside Other Skeletal Regulators”; 2006