Calcium and CVD, Is There a Connection?

Is there a difference between, “I have blue paint in my bedroom,” and “My bedroom walls are painted blue?”  A gallon of paint in the closet or on the floor in your bedroom verifies the first quote. An empty can and blue walls verify the second. Maybe this isn’t the best analogy, but you can apply it to the calcium in your body, which is either part of your bones or used as an electrolyte, or not. It’s either where it belongs, or not. The body has a remarkable system for keeping the concentrations of calcium in the blood and tissues just right, for ensuring that calcium is where it belongs. If the balance gets upset, certain organs will suffer. You see, besides bones and teeth, calcium helps muscles by keeping nerve impulses firing properly; otherwise the muscles can twitch and cramp. This is the last thing we want to happen to the heart muscle. If necessary, calcium is drawn from bone, where ninety-nine percent is stored, to maintain body pH in times of calcium deficiency. The protein-bound calcium of the blood is a secondary reservoir of calcium, usually becoming available locally to meet needs, as in clotting after getting cut. In the electrophysiology of the heart, calcium works with sodium to enable a heartbeat.

Research on calcium in the last ten years, particularly on supplements, has raised eyebrows about calcium intake and the form in which it is taken. Whether inadvertently or by design, co-factors that enhance calcium bioavailability and absorption from supplements were overlooked by some researchers and the supplements were accused of causing heart attacks. One study, published in the British Medical Journal in 2008, decided that adverse cardiac events were attributable to calcium supplements. The study included almost fifteen hundred women over seventy years old, and reported that those who used calcium supplements experienced more heart problems than those who did not (Bolland, 2008). Neither health conditions, smoking habits, environmental and lifestyle status, prior illnesses, family history, dietary regimens, type of supplement used (carbonate, malate, citrate, etc.), nor other influences were scrutinized. Later study by the same group added vitamin D to the equation and arrived at the same conclusion, that calcium supplements with or without vitamin D modestly increased the risk of cardiovascular episodes, but only in women who did not take calcium supplements regularly and scrupulously prior to the study. It seems, then, that the sudden onrush of calcium nutrition was too much for the body of a geriatric subject, who might even have suffered a different pathology, to handle at one time, and that instead of moving to bone, the mineral clogged up the works (Bolland, 2011). These papers recommended that the role of calcium supplementation in the management of osteoporosis be reassessed. But it doesn’t stop here.

Critics of these studies question the accuracy of the conclusions by closely examining coronary artery calcification, wondering how the calcium got there in the first place, when it’s supposed to make bone, not arterial plaques. When comparing / contrasting dietary calcium and supplemental calcium, the results were similar:  there is no support for the hypothesis that high calcium intake increases risk for coronary artery calcification, held to be a definitive measure of atherosclerosis burden (Samelson, 2012) (Prince, 2011).

We know that vitamin D is necessary for the absorption of calcium and that its insufficiency is common in the northern latitudes. Oddly, insufficiency also occurs in the sub-tropical areas of the planet, partly because of sun avoidance and partly because of sunscreen use, though other factors weigh in, such as cloud cover, altitude and air pollution. Vitamin D is supposed to regulate serum calcium and phosphorus concentrations. In the absence of vitamin D, only about 10% of calcium is absorbed. Maybe the rest goes to places where it doesn’t belong, like your arteries. But you have to get enough vitamin D to make a difference.  The 400 IU used in the study (Bolland, 2011) is barely enough to prevent outright deficiency.

An inflammatory model of CVD has challenged the cholesterol model, and vitamin D plays a role in sequestering the cascade of activities that lead to cardiac episodes. When monocytes rush to the site of inflammation they become macrophages that swallow oxidized LDL and then provide the basis for plaque formation, part of which is trapped calcium. Because vitamin D can suppress macrophage cholesterol uptake, it can interrupt the foam cell cycle and subsequent plaques (Oh, 2009), thereby disrupting the cardiac incident. That’s cool. Hold on, there’s more…vitamin K. Most of us consider blood clotting and vitamin K in the same thought. While that’s true, this compound, associated with green leafy vegetables, does a few more things. There is evidence that low vitamin K levels are associated with reduced bone mineral density and increased arterial calcification (Jie, 1996). Concurrent work shows that vitamin K is able to escort calcium to the place where it belongs—bone. Although deficiency of this vitamin is infrequent, insufficiency is common, and that almost certainly would account for the presence of calcium where it isn’t supposed to be (Vermeer, 2000). Proteins that rely on vitamin K for their activity have shown the ability to inhibit vascular calcification. Even accounting for smoking, diabetes, age, dietary habits and other factors, it was found that subjects with the highest vitamin K levels in the menaquinone form (vitamin K2) experienced fewer incidents of all-cause mortality (Geleijnse, 2004), especially coronary heart disease (Beulens, 2009).

Humans can absorb only about 500 mg of supplemental calcium at a time, with the citrate form having better assimilation than the carbonate. Taking it with food, which encourages stomach acid formation to aid mineral metabolism, practically evens the field (Heaney, 2001, 1999). Considering that calcium is essential to human health, that dairy is not a significant player in most adult diets, that some vegetables high in calcium are also high in oxalates that bind the calcium,  that produce with available calcium contains only small amounts, and that too many of us shun beans for social reasons, supplementation remains the option. Get a dietitian to look at your diet and determine your calcium sources and values. Then take a supplement to bring daily intake up to about a thousand milligrams.  By monitoring vitamins D and K, too, vascular calcification becomes a relative non-issue. An important matter, though, remains for those taking warfarin. It might thin your blood and prevent a clot, but it also interferes with the activity of the proteins supported by menaquinone, and replaces the clot with a plaque.

Bo Abrahamsen, Opinder Sahota Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ 2011; 342; (19 April 2011): d2080

Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93. Epub 2008 Jul 19.

Mark J Bolland, P Alan Barber, Robert N Doughty, Barbara Mason, Anne Horne, Ruth Ames, Gregory D Gamble, Andrew Grey, Ian R Reid Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial BMJ. 31 Jan 2008; 336:262

Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010 Jul 29;341:c3691. doi: 10.1136/bmj.c3691.

Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. 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. 2011 Apr 19;342:d2040. doi: 10.1136/bmj.d2040.

Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. 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.

Heaney RP, Dowell MS, Barger-Lux MJ. Absorption of calcium as the carbonate and citrate salts, with some observations on method. Osteoporos Int. 1999;9(1):19-23.

Heaney RP, Dowell MS, Bierman J, Hale CA, Bendich A. Absorbability and cost effectiveness in calcium supplementation. J Am Coll Nutr. 2001 Jun;20(3):239-46.

Heller HJ, Greer LG, Haynes SD, Poindexter JR, Pak CY. Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. J Clin Pharmacol. 2000 Nov;40(11):1237-44.

Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int. 1996 Nov;59(5):352-6.

Khurana C, Rosenbaum CG, Howard BV, Adams-Campbell LL, Detrano RC, Klouj A, Hsia J. Coronary artery calcification in black women and white women. Am Heart J. 2003 Apr;145(4):724-9.

Li K, Kaaks R, Linseisen J, Rohrmann S. 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. 2012 Jun;98(12):920-5.

Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation. 2009 Aug 25;120(8):687-98. Epub 2009 Aug 10.

Richard L Prince, Kun Zhu, Joshua R Lewis Calcium, vitamin D, and risk: Evidence of harm is unconvincing BMJ. 7 Jun 2011; 342: d3541

Elizabeth J Samelson, Sarah L Booth, Caroline S Fox, Katherine L Tucker, Thomas J Wang, Udo Hoffmann, L Adrienne Cupples, Christopher J O'Donnell, and Douglas P Kiel Calcium intake is not associated with increased coronary artery calcification: the Framingham Study Am J Clin Nutr December 2012 vol. 96 no. 6 1274-1280

Vermeer C, Schurgers LJ. A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin North Am. 2000 Apr;14(2):339-53.

Weber P. Vitamin K and bone health. Nutrition. 2001 Oct;17(10):880-7.

*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.