ReviewCalcium supplementation: Balancing the cardiovascular risks☆
Introduction
Calcium supplements have been regarded as a cornerstone of the prevention and treatment of osteoporosis, over the last 50 years. Calcium supplements have been promoted on the grounds that calcium is a major constituent of the skeleton, so more calcium should lead to a stronger skeleton. This paradigm treats the skeleton as being akin to a stalagmite in a limestone cave, expected to grow more rapidly if we drip more calcium-rich fluid onto it. This ignores the reality that bone is a collagen-based connective tissue and that bone mass is determined by the balance between the activity of the bone forming cells (osteoblasts) and that of bone resorbing osteoclasts. While substrate deficiency would be expected to have a negative impact on bone mass, oversupply of calcium should not, ipso facto, be expected to increase the bone mass.
In the last 20 years a solid evidence base has been built describing the skeletal effects of calcium, both through bone density measurements and through assessments of fracture risk. While beneficial effects have been found, they have been relatively modest, and low compliance has been a consistent feature of the large scale studies of calcium supplementation. Many physicians have continued to encourage calcium use on the grounds that it should be beneficial and there is no reason to think it does any harm. The latter assumption is now called into doubt by accumulating evidence that calcium supplement use increases the risk of cardiovascular disease. This suggestion requires that we carefully consider the balance of risk and benefit with calcium supplement use, as we would with any pharmaceutical intervention.
Section snippets
How important is calcium for bone health?
Very low calcium intakes have been associated with impaired mineralisation of the skeleton because the critical calcium-phosphate product is not reached adjacent to the mineralising osteoid [1]. However, most studies have shown remarkably little correlation between dietary calcium intake and either bone density [2], [3], [4] or fracture rates [5], [6] (Fig. 1). Indeed, some of the lowest fracture rates internationally are observed in Africa and Asia, where dietary calcium intakes of 300 mg/day
Calcium monotherapy
During the period that trials have been undertaken to determine the skeletal effects of calcium supplements, there has also been interest in the possibility that calcium supplements might have an impact on vascular disease. The outcome most frequently studied is blood pressure, where a consistent body of evidence has developed showing small reductions in both systolic and diastolic pressures from the introduction of calcium supplements [16], [17], [18]. There have also been reports that calcium
Conclusion
The consistent message from the meta-analyses of clinical trials is that calcium supplements probably carry a small but significant adverse effect on cardiovascular risk. Their beneficial effect on fractures is also small, so it is likely that there is no net benefit from their use. This suggests that we need to look elsewhere for strategies for preventing postmenopausal bone loss. Lifestyle interventions should include smoking cessation, weight maintenance, and moderation of alcohol intake.
Contributors
The article was drafted by IRR, then critically revised by the other authors.
Conflict of interests
IRR has received research support from and acted as a consultant for Fonterra and had study medications for clinical trials of calcium supplementation supplied by Mission Pharmacal. The other authors have no conflicts.
Provenance and peer review
Commissioned and externally peer reviewed.
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Cited by (26)
Calcium and vitamin D supplementation on bone health: Current evidence and recommendations
2014, International Journal of GerontologyCitation Excerpt :The Institute of Medicine Committee, an American non-governmental organization established in 1970, examined the totality of the available evidence and concluded that calcium absorption reaches near maximum at serum 25OHD levels of 8–20 ng/mL9. Beyond the role of calcium and vitamin D supplements in maintaining bone health, emerging evidence suggests that calcium with or without vitamin D supplementation might have potential adverse effects in the general population, such as cardiovascular events10–15, sudden death, cancer, or urinary tract stone16–18. Although several studies showed a reduction in cancer incidence for those taking vitamin D or vitamin D plus calcium12,18–22, the evidence is insufficient to make a conclusion about the benefits or harms of vitamin D or vitamin D plus calcium supplementation for cancer prevention18,23.
Osteoporosis
2014, Seminars in Nuclear MedicineCitation Excerpt :The average dairy-free diet contains 250 mg of calcium per day and calcium-rich foods should be encouraged for motivated patients. Some, but not all, recent studies have suggested an association between prescribed calcium intake and cardiovascular disease; however, these relationships have been difficult to confirm for patients taking both calcium plus vitamin D.46,49-58 There is no evidence that calcium supplements change carotid intimal thickness, a surrogate of vascular disease.54 Analysis of one cohort did not find a relationship between osteoporosis and atherosclerosis.59
The high heart health value of drinking-water magnesium
2013, Medical HypothesesCitation Excerpt :Calcium intakes from food have risen substantially in the USA over the past 30 years [78], just as recommendations for calcium supplementation to prevent osteoporosis became widespread. Both of these high calcium trends have occurred in the face of low magnesium intakes, and there is rising evidence that this trend poses dangers to heart health [9,79–84]. It would be wise and forward-thinking for public health officials to consider how high-magnesium drinking water might be made available to communities, i.e., water with magnesium levels of at least 10 ppm and ideally 25–100 ppm.
EMAS position statement: Diet and health in midlife and beyond
2013, MaturitasCitation Excerpt :Thus the Women's Health Initiative (WHI) study found an increased risk of kidney stones [51]. Also calcium supplement use is associated with an increased risk of myocardial infarction and, possibly, stroke [52]. This risk is not mitigated by co-administration of vitamin D.
EMAS position statement: Vitamin D and postmenopausal health
2012, MaturitasCitation Excerpt :Calcium, PTH and calcitriol were not associated with measures of carotid health [47]. The use of calcium supplements, with and without vitamin D, has been associated to cardiovascular events in a reanalysis of the Women's Health Initiative cohort and a meta-analysis [48,49]. In this study calcium supplements, with or without vitamin D (400 IU/day), increased the risk of cardiovascular events, especially myocardial infarction, suggesting that the excess of calcium supplementation may have negative consequences on cardiovascular health.
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Supported by the Health Research Council of New Zealand.