BlogCalciumMagnesiumVitamin DVitamin K2

Calcium Perfected

Sharing is caring:

Calcium: a double edge sword?

Inadequate calcium intake can lead to decreased bone mineral density, which can increase the risk of bone fractures. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis, particularly among the elderly and postmenopausal women (1, 2). It is believed that calcium supplements are safe and well tolerated, and incur only mild side effects. Good idea, right?

Scientific evidence suggests that elevated calcium consumption accelerates calcium deposits in blood vessel walls and soft tissues (Fig. 1), raising the risk for heart disease (3-9).
 

Calcium Artery stiffening

Fig. 1 - Stiffening of arteries (i.e., atherosclerosis) is triggered, among other factors, by calcium deposits in blood vessels, making them progressively stiff and narrow.

Several studies have cast doubt on the notion that “more is better” when it comes to calcium intake and cardiovascular disease prevention.

 
So, how can we reap the benefits of calcium without suffering its ‘side’ effects?
 

OSTEOCALCIN & MATRIX Gla PROTEIN (The dynamic duo in bone & cardiovascular health)

BONE HEALTH − Bone relies on calcium for its structure, function and health. Its structure is secured by two types of cells – osteoblasts, which build bones and osteoclasts, which remodel bones (Fig. 2). Osteoblasts produce a K-dependent protein called osteocalcin (OC), which is responsible for properly organizing the deposition of calcium and phosphorus salts in bones and teeth (10).
 

Bone structure

Fig. 2 - Bone is a living material comprised of a hard outer shell and spongy inner tissue structured to withstand the physical stress of bearing body mass. The entire skeleton is replaced approximately every seven years due to the remodeling action of osteoclasts. Vitamin K2 is needed for activation of osteocalcin (OC). A diet low in vitamin K2 reduces bone strength and density.

 
 
HEART HEALTH − Cardiovascular disease (CVD) is the leading cause of death globally. Usually, by the time the symptoms are detected, the underlying cause is quite advanced and difficult to treat. Often it is atherosclerosis, a process that develops over decades and is characterized by plaque formations that might clog arteries (11).

Calcium ions are the main mineral component of arterial plaques,(11) leading to arterial calcification, which was once believed to be an irreversible result of aging, contributing significantly to CV risk. However, it is now known that calcium accumulation is an actively regulated process, involving vitamin K2-dependent matrix Gla protein (MGP).

MGP is synthesized by vascular smooth muscle cells and is the most important inhibitor of arterial mineralization currently known (12-16). The highest levels of MGP are found in heart, lungs, kidney and cartilage.
 

VITAMINS K2, D & A (The 3 musketeers)

THE WINNING TRIO − When it comes to the preservation of bone and heart health, few vitamins are better paired than Vitamins K2, D and A in regulating OC and MGP. How does this synergy work? While K2 is required to activate these proteins, D3 and A are needed for the creation of these proteins (17-19). Basically, vitamin K2 is the molecule that makes OC and MGP come to life, giving them the physical ability to do their job.

Here’s another way to think about this. If you wanted to build a wall around your house, you have basically two ways to go about doing it:

  • WRONG WAY − The wrong way is to purchase a bunch of bricks from your local Home Depot, have them delivered to the back yard of your home, and start piling them at random on top of one another. Sure! You will get a wall, but it is highly doubtful that you will build something that is lasting.
  • RIGHT WAY − With the right way, you still need to purchase the bricks and have them delivered, but the difference is that you will need to hire AND pay a contractor to ensure proper deposition of the bricks around your home’s perimeter to build a wall. This is definitely the more expensive and lengthy route to take, but it will guarantee a more durable and strong (not to mention, architecturally pleasing) wall.
In our example, think of OC or MGP as the contractors, vitamins D and A as the ones who are in charge of finding and calling the contractors, while vitamin K2 is the payment required to ‘entice’ (or activate) the contractors to do their job right.
 

Vitamins K2, D and A are an essential trio in both production and activation of OC and MGP, the two proteins essential for organizing the deposition of calcium and phosphorus salts in bones and teeth (OC) and protecting arteries from calcification (MGP).

 

THE K FAMILY (Vitamin K1 & K2)

VITAMIN K − Vitamin K was first discovered in 1935 by Henrik Dam, when it was found to be an essential nutrient to prevent abnormal bleeding in chickens (20). For decades thereafter, vitamin K was identified as the “coagulation vitamin” (in fact, the initial “K” comes from the German spelling, “Koagulation”). During that time, it was established that vitamin K worked by activating certain proteins made in the liver that are required for normal blood clotting. Without sufficient vitamin K, blood would not clot, leading to severe bleeding (21, 22).

Although the name suggests differently, Vitamin K is not a single compound. It consists of a group of fat-soluble vitamins that are essential for the body to utilize calcium for healthy bones, healthy arteries and soft tissues. The vitamin K family is divided into two groups (Fig. 3):

  • Vitamin K1 − K1 is composed of one molecule, called phylloquinone. It is synthesized solely by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis. K1 is poorly absorbed from fresh vegetables and only about 10–20% of K1 obtained from such food reaches the circulatory system, from where it is rapidly excreted and thus unavailable to supply peripheral tissues, such as vasculature or bone
  • Vitamin K2 − This is a group of molecules called menaquinones. It is the main storage form in animals, has several sub-types, each characterized by the number of side chain residues. Menaquinones are abbreviated as MK-n, where n represents the number of side chain residues. The main dietary sources for menaquinone (Table 1) in Western populations are meats (MK-4) and fermented foods, especially cheese and curds (mainly in the form of MK-8 and MK-9) (23, 24). Natto contains the highest concentration of vitamin K2 of any food measured; nearly all of it is present as MK-7, which research has shown to be one of the most effective forms (25).

 

Vitamin K Structure

Fig. 3 - Different types of vitamin K vary in length and saturation (double versus single bonds) of the isoprenoid side chain. Vitamin K2 (Menaquinones) are abbreviated as MK-n, where “n” symbolizes the number of isoprene repeats.

 
Table (Vitamin K2)

Table 1 - Best food sources of vitamin K2.

 
WHAT IS THE DIFFERENCE BETWEEN K1 and K2? The K vitamins have been underrated and misunderstood up until very recently in both the scientific community and the general public. It has been commonly believed that the benefits of vitamin K are limited to its role in blood clotting. Another popular misconception is that vitamins K1 and K2 are simply different forms of the same vitamin – with the same physiological functions. Research has confirmed that vitamin K2’s role in the body extends far beyond blood clotting to include protecting us from heart disease (26, 27), reducing the risk of diabetes (28), ensuring healthy skin (29), forming strong bones (30), promoting brain function (31), and helping to prevent cancer (32, 33) – to name a few. In fact, vitamin K2 has so many functions not associated with vitamin K1 that many researchers insist that K1 and K2 are best seen as two different vitamins entirely.
 

People at risk for dangerous blood clots include those with various heart rhythm abnormalities (e.g., atrial fibrillation) (34), as well as those with artificial heart valves (35) stents, etc, and those at risk for certain kinds of strokes. For them, blood-thinning drugs (aka, anticoagulants) offer significant protection (36).

But many traditional blood thinners, such as Coumadin® (warfarin), act specifically by inhibiting the action of vitamin K to produce clotting proteins. Science is revealing a disturbing fact: While inhibiting vitamin K action on blood clotting proteins, these drugs also inhibit other vitamin K-dependent proteins, including the matrix Gla protein that naturally prevents arterial calcification (36).

Studies in both animals and humans now show that the use of drugs such as Coumadin®, while effective at clot prevention, do indeed accelerate arterial calcification, placing patients at increased risk for cardiovascular disasters (37, 38). The good news is that by supplementing with low-dose vitamin K, you may help rescue arteries from calcification induced by Coumadin® (39).

However, if you are taking a blood-thinning drug, DO NOT stop using it and DO NOT begin any vitamin K supplementation on your own. Instead, speak with your doctor about starting a vitamin K supplement at a proper dose. With careful monitoring, you are much more likely to find a balance between the benefits and the risks of anticoagulant use (40, 41).

Side note: Newer blood-thinning drugs such as Pradaxa® (dabigatran) and Eliquis® (apixaban) are not affected by vitamin K intake, meaning you can take a full-dose vitamin K and not compromise the desired anticoagulant effects.

 

MAGNESIUM (The wünder mineral that ties it all together)

Functional practitioners have long known that if you supplement with calcium, you should also take adequate amounts of magnesium. The reason is that magnesium is a natural calcium channel blocker.
 
Magnesium-01
 
Magnesium is the fourth most abundant mineral inside the body. Inside cells, magnesium concentration is ~10,000 fold higher than calcium. About 60% of the magnesium in the body is found in bone, 26% in muscle, and the rest in the organs and blood (42). Magnesium is critical to ~350+ enzymatic functions in the body, from energy production, protein formation, cell replication, to muscle relaxation.

Like I mentioned above, we now know that the active form of vitamin D is a necessary component in activating proteins such as OC and MGP, which help structure bone and keep calcium out of our arteries, respectively. However, what most people may not realize is that magnesium is necessary to convert vitamin D into its active form so that it can do its job.

It turns out that ALL the enzymes involved in metabolizing vitamin D require magnesium as a necessary co-factor. When you take high doses of Vitamin D and if your body’s deficient in magnesium, the increased amount of metabolic work drains magnesium from its muscle storage sites. And that’s probably why muscles are the first to suffer magnesium deficiency symptoms − twitching, leg cramps, and restless legs. Arrhythmia and even heart attacks affecting the heart muscle are all magnesium deficiency symptoms.
 

We could say that part of the vitamin D deficiency epidemic is an underlying magnesium deficiency. So, instead of extraordinarily high doses of vitamin D, we need a combination of vitamin D (moderate levels) along with magnesium to make the vitamin D work.

 
Here’s what happens if you have low magnesium:

  1. No magnesium means that the body cannot convert vitamin D3 (cholecalciferol) into its active form, calcitriol.
  2. In the absence of calcitriol, cells cannot make OC and MGP.
  3. Lack of OC and MGP means that there’s nothing for Vitamin K2 to activate.
  4. Lack of active OC and MGP compromises deposition of calcium in bones and clearance of calcium from arteries.

In addition, magnesium plays a regulatory role. It stimulates the hormone calcitonin, helping to preserve bone structure by drawing calcium out of the blood and soft tissues back into the bones. This helps lower the likelihood of osteoporosis, some forms of arthritis, heart attack and kidney stones. So, if you’re taking lots of calcium and not much magnesium, you are susceptible to these conditions.
 

Almost half the population of the U.S. (almost 70% of adult women) uses dietary supplements containing calcium. In general, we absorb less than half of the calcium we ingest.

 

Best food sources of magnesium

You could keep your magnesium levels in normal range without having to resort to supplements. How? Simply by eating a diet rich in dark-green leafy vegetables. One way to really boost your magnesium (as well as many other important plant-based nutrients), is by juicing your greens*. This is the regimen we take on at home.

*Note of caution: You have to be careful with how this affects your detox as many juicing protocols may be too aggressive for people with a compromised phase I and/or II liver detox systems. I will cover this topic in more detail in a later post (and seminar).
 
That said, it’s important to remember that the magnesium content of your foods depends on the richness of magnesium in the soil in which the plant was grown. Most soils today are so severely depleted of nutrients that I believe that virtually everyone needs to take supplemental magnesium. Organic foods may have more magnesium if grown in nutrient-rich soils, but it is hard to make that determination.

Based on data collected by The World’s Healthiest Foods, the following are among the richest food sources of magnesium:
 

Table (Magnesium source)

Table 2 - Best food sources of magnesium.

 
Cheers,
Robert
 

RECOMMENDATIONS
WHAT YOU SHOULD KNOW AND DO

  • The optimal amounts and kind of vitamin K2 are still under investigation, but it seems likely that 150 to 200 micrograms of vitamin K2 might be enough to activate K2-dependent proteins (e.g., OC and MGP) to shuttle calcium to the proper areas.
  • If you take oral vitamin D, you also need to take vitamin K2. Vitamin K2 deficiency is actually what produces the symptoms of vitamin D toxicity, which includes inappropriate calcification that can lead to hardening of your arteries.
  • If you take a calcium supplement, maintain the proper balance between calcium, vitamin K2, vitamin D, and magnesium. Lack of this balance is why calcium supplements have become associated with increased risk of CVD and stroke.
  • Recommended supplement: FLOZ NUTRIK2 is a scientifically formulated fat-soluble liquid supplement with the ideal balance between Vitamin K2 (in the form of MenaQ7), Vitamin D3 and Vitamin A.
  • Vitamin A can activate expression of OC. But, it also downshifts the expression of MGP. This allows for proper calcium balance between bone, arterial and soft tissues.
  • Consume plenty of organic green leafy vegetables, nuts and seeds. Foods with exceptionally high magnesium content include seaweed, coriander, pumpkin seeds, unsweetened cocoa powder, and almond butter.
  • If you take a magnesium supplement, you also need to pay attention to your ratios of calcium, vitamin K2, vitamin D, and vitamin A as these nutrients work together synergistically.
  • Maintain an appropriate calcium-to-magnesium ratio of 1:1 (as per our Paleolithic DNA makeup). Americans in general tend to have a higher ratio, from 5:1 to as much as 15:1.

 
Cheers,
Robert

 
PhD_Stat_supplements1


References
  1. Cumming, R.G., Cummings, S.R., Nevitt, M.C., et al. (1997). Calcium intake and fracture risk: results from the study of osteoporotic fractures. Am. J. Epidemiol. 145: 926-934.
  2. Hodgson, S.F., Watts, N.B., Bilezikian, J.P., et al. (2003). American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr. Pract. 9: 544-564.
  3. Bolland, M.J., Barber, P.A., Doughty, R.N., Mason, B., et al. (2008). Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 336(7638): 262-266.
  4. Bolland, M.J., Avenell, A., Baron, J.A., et al. (2010). Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341: c3691.
  5. Bolland, M.J., Grey, A., Avenell, A., et al. (2011). Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 342: d2040.
  6. Li, K., Kaaks, R., Linseisen, J.,et al. (2012). Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart 98: 920-925.
  7. Michaëlsson, K., Melhus, H., Warensjo Lemming, E., et al. (2013). Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ 346: f228.
  8. BPentti, K., Tuppurainen, M.T., Honkanen, R., et al. (2009). Use of calcium supplements and the risk of coronary heart disease in 52-62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study. Maturitas. 63: 73-78.
  9. Xiao, Q., Murphy, R.A., Houston, D.K., et al. (2013). Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study. JAMA Intern. Med. 173: 639-646.
  10. Shearer, M.J., and Newman, P., (2008). Metabolism and cell biology of vitamin K. Thromb. Haemost. 100: 530-547.
  11. Iribarren, C., Sidney, S., et al. (2000). Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA. 283(21): 2810-2815.
  12. Spronk, H.M., Soute, B.A., et al. (2001). Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall. Biochem. Biophys. Res. Commun. 289(2): 485-490.
  13. Proudfoot, D., Skepper, J.N., et al. (1998). Calcification of human vascular cells in vitro is correlated with high levels of matrix Gla protein and low levels of osteopontin expression. Arterioscler. Thromb. Vasc. Biol. 18(3): 379-388.
  14. Luo, G., Ducy, P., McKee, M.D., et al. (1997). Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386(6620): 78-81.
  15. Schurgers, Leon J., et al. (2008). Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb. Haemost. 100(4): 593-603.
  16. Schurgers, L.J., et al. (2005). Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler. Thromb. Vasc. Biol. 25(8): 1629-1633.
  17. Kidd, P.M. (2010). Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern. Med. Rev. 15(3): 199-222.
  18. Oliva, A., Ragione, F.D., et al. (1993). Effect of retinoic acid on osteocalcin gene expression in human osteoblasts. Biochem. Biophys. Res. Commun. 191(3): 908-914.
  19. Kirfel, J., Kelter, M., et al. (1997). Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene. Proc. Natl. Acad. Sci. USA. 94(6): 2227-2232.
  20. Carpenter, K.J. (2003). A short history of nutritional science: part 3 (1912–1944). Proc. Natl. Acad. Sci. USA. 133(10): 3023-3032.
  21. Mammen, E.F. (1992). Coagulation abnormalities in liver disease. Hematol. Oncol. Clin. North Am. 6(6): 1247-1257.
  22. Mammen, E.F. (1994). Coagulation defects in liver disease. Med. Clin. North Am. 78(3): 545-554.
  23. Shearer, M.J., Bach, A., & Kohlmeier, M. (1996). Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J. Nutr. 126(4): 1181S-1186S.
  24. Schurgers, L.J., & Vermeer, C. (2000). Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30: 298-307.
  25. Schurgers, L.J., et al. (2007). Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109(8): 3279-3283.
  26. Braam, L.A., Hoeks, A.P. et al. (2004). Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb. Haemost. 91(2): 373-380.
  27. Jie, K.S., Bots, M.L., et al. (2010). Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis 116(1): 117-123.
  28. Beulens, J.W., van der AD, et al. (2010). Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care 33(8): 1699-1705.
  29. Cranenburg, E.C.M., Schurgers, L.J. et al. (2007). Vitamin K: the coagulation vitamin that became omnipotent. Thromb. Haemost. 98(1): 120-125.
  30. Knapen, M.H.J., et al. (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos. Intl. 24(9): 2499-2507.
  31. Ferland, G. (2012). Vitamin K and the nervous system: an overview of its actions. Adv. Nutr.: An Intl. Review J. 3(2): 204-212.
  32. Ogawa, M., Nakai, S., et al. (2007). Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells. Int. J. Oncol. 31(2): 323-331.
  33. Kawakita, H., Tsuchida, A., et al. (2009). Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis. Int. J. Mol. Med. 23(6): 709-716.
  34. Choi, H.W., Navia, J.A., et al. (2013). Stroke propensity is increased under atrial fibrillation hemodynamics: a simulation study. PLoS One. 8(9): e73485.
  35. Dasi, L.P., Simon, H.A., et al. (2009). Fluid mechanics of artificial heart valves. Clin. Exp. Pharmacol. Physiol. 36(2): 225-237.
  36. Chatrou, M.L., Winckers, K., et al. (2012). Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 26(4): 155-166.
  37. Price, P.A., Faus, S.A., et al. (1998). Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler. Thromb. Vasc. Biol. 18(9): 1400-1407.
  38. McCabe, K.M., Booth, S.L., et al. (2013). Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease. Kidney Int. 83(5): 835-844.
  39. Schurgers, L.J., Spronk, H.M., et al. (2007). Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 109(7): 2823-2831.
  40. Ford, S.K., Misita, C.P., et al. (2007). Prospective study of supplemental vitamin K therapy in patients on oral anticoagulants with unstable international normalized ratios. J. Thromb. Thrombolysis. 24(1): 23-27.
  41. Sconce, E., Avery, P., et al. (2007). Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 109(6): 2419-2423.
  42. Swaminathan, R. (2003). Magnesium metabolism and its disorders. Clin. Biochem. Rev. 24(2): 47.
Sharing is caring:

2 thoughts on “Calcium Perfected

    1. Hi Anita,
      There are tons of Ca supplements on the market. If you need Ca, make sure you get one that has organic or amino acid linked Calcium such as Citrate, Glycinate, Succinate, Malate, etc format. Avoid products that have Calcium Carbonate…it has very low bioavailability.

      What most people need is not Calcium per se, but vitamins and minerals that support calcium homeostasis in the body. These are: (1) Vitamin K2 (90%+ of our western population is deficient in this vitamin), (2) Vitamin D3 (as much as 50% of the population is D3 insufficient), (3) Magnesium (60%+ of us are deficient in this mineral).

      We make a supplement called NutriK2. It contains vitamin K2 (in the form of MenaQ7), Vitamin D3, and Vitamin A. The link to NutriK2 is: http://flozinc.com/product/nutrik2-vitamink2/

      Let me know if any questions,
      Robert

Leave a Reply

Your email address will not be published. Required fields are marked *