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To supplement or not to supplement? Where the science now stands on calcium and cardiovascular risk.
Calcium is an essential mineral that is a major structural component of bones and teeth. The vast majority of calcium (around 99%) in the body is found in these two tissues. In addition to this important structural role, calcium plays a significant part in blood vessel function, nerve impulse transmission, muscle contraction, and the secretion of hormones.
Dietary intake of calcium is often less than optimal among certain groups in the population. According to the National Institutes of Health (NIH) Office of Dietary Supplements, the groups at greatest risk of calcium inadequacy are males between the ages of 9–13, females between the ages of 9–18, women aged 51–70, and both men and women older than 70.1 Some estimates suggest that 54% of Americans fail to meet estimated average requirements (EAR) for calcium with diet alone, while 38% fail to meet EARs even when calcium supplement use is taken into consideration.2
Still, many take the logical step of using supplements to make up the difference. Current estimates suggest that approximately 43% of the U.S. population use supplements containing calcium to complement the intake of calcium from food.1 However, recent scientific investigations have raised concerns regarding the safety of calcium supplements, particularly focusing on the impact of calcium from supplements on the risk of heart and vascular disease.
Calcium Supplements and Heart Disease
The evidence that calcium is linked to poor heart and vascular health outcomes includes a randomized controlled trial conducted by Mark Bolland and colleagues from the University of Auckland in New Zealand.3 The study included 1,471 healthy postmenopausal women with a mean age of 74 who were not taking calcium supplements or other treatments for osteoporosis at the time of enrollment. The women were randomized into two groups: the treatment group (732 women) consumed 1,000 mg of elemental calcium (as calcium citrate) daily in two divided doses, while the second group (739 women) was given an identical placebo. The women were followed up every six months for five years, at which time adverse events were noted. The authors report that the incidence of myocardial infarction was significantly more common in those supplementing with calcium versus those in the placebo group (45 events in 31 women versus 19 events in 14 women, respectively), while a composite endpoint measuring the incidence of myocardial infarction, stroke, or sudden death was also elevated in those supplementing with calcium.
Bolland’s group published a paper in 2011 in which they reanalyzed data from the Women’s Health Initiative Calcium and Vitamin D study (WHI CaD).4 The original trial was a seven-year randomized clinical study of calcium (1 g/day) and vitamin D (400 IU/day) in 36,282 postmenopausal women. The authors of WHI CaD originally reported no adverse effect of calcium and vitamin D supplements on cardiovascular events.5 However, according to Bolland and colleagues, the fact that a majority of study participants of WHI CaD were consuming personal calcium supplements influenced the conclusions of the study. The purpose of their reanalysis was to analyze data from just those WHI CaD participants who were not taking calcium supplements at baseline. The researchers incorporated this subset of data into a meta-analysis that included eight other trials of calcium supplementation. After analyzing data for 28,072 participants (from the eight trials in addition to the subset from WHI CaD not consuming calcium supplements at baseline), Bolland and colleagues concluded that supplementation of calcium, with or without vitamin D, modestly increases the risk of cardiovascular events, especially myocardial infarction.4
Additionally, Qian Xiao and colleagues from the NIH investigated the relationship of dietary and supplemental intake of calcium to mortality from cardiovascular disease by analyzing a subset of data from the NIH-AARP Diet and Health Study.6 Study participants were AARP members (men and women) between the ages of 50–71. The cohort that was used for the analysis performed in this study consisted of 219,059 men and 169,170 women who were followed for an average of 12 years. Dietary and supplemental calcium intakes were estimated at baseline using a food frequency questionnaire. The authors’ analysis of the data found that men consuming greater than 1,000 mg of calcium per day from supplements had a significantly elevated risk of cardiovascular disease and heart disease mortality compared to men who were non-users of calcium supplements. However, no such associations were noted for women. Furthermore, dietary intake of calcium was not associated with an increase in cardiovascular disease mortality.
However, not all studies on calcium supplementation point to an increased risk of heart and vascular conditions. Joshua Lewis and colleagues from the University of Western Australia conducted an analysis of data from a five-year randomized clinical trial and a 4.5-year follow-up study (the Calcium Intake Fracture Outcome Study) examining the efficacy of calcium in preventing fractures. The analysis looked at 1,460 women over the age of 70 with no current use of medications for osteoporosis and no present illness likely to limit involvement in the five-year study. They were asked to consume 600 mg of calcium carbonate tablets twice per day (1,200 mg total) or an identical placebo.7 The results of the analysis, which was designed specifically to investigate the association of calcium supplementation and the risk of atherosclerosis and vascular disease, found that women receiving calcium supplements over the five-year study period or during the 4.5-year follow-up did not have a higher risk of death or first-time hospitalization from atherosclerotic vascular disease (including myocardial infarction); in fact, further analysis by the authors showed a protective effect of calcium supplements in those with preexisting atherosclerotic cardiovascular disease.
Moreover, in response to the findings by Mark Bolland’s group, Ross Prentice and others who were investigators on the original WHI CaD trial conducted a further analysis of the data from that trial and a subsequent observational study.8 When this group looked at the women in the trial not taking personal calcium or vitamin D supplements at baseline, they found no apparent effects associated with calcium or vitamin D supplementation on the risk of myocardial infarction, coronary heart disease, total heart disease prevalence, stroke, or total mortality. In addition to the 36,282 women initially included in the WHI CaD trial, the companion WHI prospective observational study included almost 94,000 postmenopausal women aged 50–79. Data from these combined studies thus was used to generate a broad view of trends associated with calcium and vitamin D supplementation. After analyzing the data, the authors concluded that there was no significant elevation of risk of myocardial infarction in either study. In addition, when 754 women enrolled in the WHI CaD study underwent cardiac CT scans for coronary artery calcium scores at the end of the study, no correlation between calcium scores and supplementation was observed, further supporting the lack of adverse heart or vascular effects.
A comprehensive review of trials reporting on the link between calcium supplementation and cardiovascular disease risk was undertaken by a group of academics and researchers led by Robert Heaney of the Osteoporosis Research Center at Creighton University.2 Among the contributors to this review were Douglas MacKay of the Council for Responsible Nutrition association (CRN; Washington, DC) and Taylor Wallace, also at CRN at the time. The authors reviewed 16 studies involving more than 358,000 individuals and concluded that there was no indication of a connection between calcium intake and atherosclerotic heart disease or stroke. While a few of the studies included showed a weak positive association with heart disease endpoints, a similar number of trials showed associations in the opposite direction. Taking the overall data into account, the authors suggested that the evidence for adverse cardiovascular effects from calcium supplementation is lacking and does not warrant a change in current Institute of Medicine (IOM) recommendations for calcium. The IOM currently designates a 2500 mg/day tolerable upper intake level of calcium for adults 19–50 years of age and 2000 mg/day for adults aged 50 and older.
Given the state of current data, the link between calcium supplementation and increased risk of heart and vascular conditions seems speculative at best. As the majority of currently available data show, calcium supplementation is likely safe. However, the findings showing positive associations for adverse heart health effects cannot be totally discounted without additional studies. While the associations are weak, some practical steps may be advisable to ensure that the calcium needs of individuals are being met in a way that mitigates any potential risk of heart health concerns.
Meeting Daily Calcium Needs
As calcium is a critical nutrient for bones and plays significant roles in other areas, ensuring adequate intake is paramount. A finding that doesn’t currently seem to be in conflict is that the intake of calcium from foods is a healthy practice and doesn’t carry any increased risk of adverse heart and vascular conditions. Efforts should be made to increase the intake of calcium-rich foods as a part of the diet.
If calcium requirements aren’t being met through the diet, supplementation is advisable. Calcium supplements should be taken with food and perhaps in smaller divided doses throughout the day. While trying to explain the adverse findings in certain studies of supplemental calcium, Ian Reid and Mark Bolland speculate that bolus doses of calcium are unnatural and acutely raise blood levels of calcium to levels that are potentially harmful.9 When calcium is taken in food form, the amount of calcium present may be less than amounts commonly present in supplements, while other nutrients and compounds that antagonize calcium absorption are concurrently present in those foods, mitigating the elevation in blood calcium levels. It’s likely that taking calcium in divided doses and ensuring that supplements are taken with food may alleviate this concern.
Nutrients required by the body are often co-dependent on other nutrients to support physiological function. Ensuring that overall nutritional intake is adequate goes a long way towards facilitating optimal health. Indeed, the body’s ability to efficiently use calcium is dependent on the supply of several critical cofactors. Three important helpers of calcium that are often inadequate in large percentages of the population are vitamin D, vitamin K2, and magnesium.
The prevalence of vitamin D deficiency in elderly individuals in the U.S., Canadian, and European populations has been estimated by various sources at between 20%–100%. Vitamin D interacts with calcium to facilitate its absorption from the intestinal tract. The active form of vitamin D also supports calcium balance in bone tissue, while it facilitates calcium reabsorption from the kidneys.10
While vitamin K intake is often adequate in humans, 90% of vitamin K in the western diet is in the form of vitamin K1. This form plays a functional role in the liver in supporting healthy clotting; however, the menaquinone form of vitamin K (vitamin K2) plays significant roles in the blood stream by activating two important calcium transport proteins-namely matrix Gla protein and osteocalcin-which enhance the efficient utilization of calcium and facilitate the transport of excess calcium to bone tissue. Inactive (or unphosphorylated) forms of these transport proteins have been associated with arterial calcification.11 A striking indication that suggests the widespread nature of a lack of vitamin K2 in the western diet comes from research showing that up to 50% of osteocalcin in the serum of normal individuals is present in its inactive form.12
Magnesium intake has long been thought to be inadequate in the U.S. population. Estimates show that nearly half of individuals consume less than the daily requirement of magnesium from foods. Magnesium deficiency has been associated with heart and vascular diseases, diabetes, and osteoporosis.13 Like calcium, magnesium is an essential structural component of bone tissue. Magnesium also balances calcium levels in the blood and is important for the metabolism and utilization of vitamin D.14
Ensuring the adequate intake of these three important cofactors along with calcium can go a long way towards mitigating the possibility of any adverse effects associated with imbalanced nutrient intake. The presence of an optimal supply of these helpers facilitates efficient utilization of calcium from supplements and dietary sources, while also potentially reducing overall calcium requirements.
Further research is needed to continue to explore the benefits and potential adverse effects of calcium supplements. The state of research today seems to favor the safety of supplementation with calcium, though concerns will remain given the divergent opinions of scientists. As studies continue to tease out the risks versus benefits, prudent measures include increasing the intake of calcium-rich foods, using calcium supplements smartly to support dietary intake levels, and addressing deficiencies in other nutrients that improve optimal calcium utilization. This can ensure calcium needs are met in the safest way possible.