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Cohort Study
Daily calcium intake in excess of 1400 mg is associated with increased all-cause and cardiovascular disease mortality in women
  1. Howard D Sesso,
  2. Lu Wang
  1. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. Correspondence to : Dr Howard D Sesso
    Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, 3rd Floor, Boston, MA 02215, USA; hsesso{at}hsph.harvard.edu

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Implications for practice and research

  • Greater calcium intake is encouraged for bone health, but has unclear cardiovascular consequences.

  • In a large cohort of Swedish women, total calcium intake of <600 or ≥1400 mg/day was associated with an increased risk of total mortality (TM) and cardiovascular disease mortality (CVDM).

  • It is important to emphasise adequate dietary calcium intake in patients, with calcium supplementation only when necessary.

Context

Sufficient calcium intake is required for bone health. Recommended daily calcium increases with age, reaching 1500 mg/day by the age of 65 years. Intake of calcium-rich foods tends to be inadequate, with a large proportion of predominantly older women taking high-dose calcium supplements1 to increase the total calcium intake. The effect of dietary and supplemental calcium on cardiovascular disease (CVD) has been increasingly debated. Prospective cohort studies have been conflicting, and secondary analyses of randomised clinical trials of non-CVD endpoints testing long-term calcium supplementation, with or without vitamin D, have not found significant differences in CVD between calcium and placebo groups.2

Methods

The association between calcium intake and mortality was assessed in the Swedish Mammography Cohort, a prospective cohort established in 1987–1990 among 61 433 women with baseline dietary data and complete linkage through the Swedish death registry for TM, CVDM, ischaemic heart disease (IHD) and stroke mortality till the year 2008. Dietary calcium intake was estimated from a 96-item food frequency questionnaire (FFQ). A total of 38 984 women completed a second FFQ in 1997 with additional information on the lifetime use of calcium (500 mg calcium) and multivitamin (150 mg calcium) supplements. Prespecified categories of dietary and total (<600, 600–999, 1000–1399 and ≥1400 mg/day) calcium intake were examined using Cox proportional hazards. Spline models evaluated non-linear trends and cumulative averages were generated for calcium intake and other baseline covariates.

Findings

The authors compared women in the prespecified categories using multivariable-adjusted scores expressed as HRs. Those consuming <600 mg/day had a TM score of 1.38 (95% CI 1.27 to 1.51) and a CVDM score of 1.63 (95% CI 1.42 to 1.87). Those consuming 1000–1399 mg/day had a TM score of 1.00 (95% CI 0.96 to 1.04) and a CVDM score of 1.01 (95% CI 0.94 to 1.09). Those consuming ≥1400 mg/day calcium had a TM score of 1.40 (95% CI 1.17 to 1.67) and a CVDM score of 1.49 (95% CI 1.09 to 2.02). A larger, significant increased risk of IHD mortality was noted for dietary and total calcium intake of ≥1400 mg/day, whereas an increase in stroke mortality was confined to low-dietary and total calcium intake of <600 mg/day. The greater risk of TM at high total calcium intake may be driven by calcium and other dietary supplements that contain calcium.

Commentary

Michaëlsson and colleagues presented important new data on calcium and mortality. Daily calcium intake generally remains below current recommendations, particularly among elderly adults and women. The prevalence of calcium supplementation continues to rise, but with no clear understanding of its long-term effects beyond bone health, including CVD. There are several strengths to this study, including comprehensiveness of covariate data, complete mortality follow-up with ample power, calibrated calcium intake levels and an array of sensitivity analyses. However, data on calcium supplementation were limited to women updating FFQs, a decade into follow-up, and only two dietary assessments defined their cumulative calcium intake. These findings in Swedish women do not resolve the inconsistencies across previously published cohort studies. In the recently published National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study of 388 229 people aged between 50 and 71 years, followed for a mean of 12 years, dietary calcium was not associated with CVD mortality, whereas supplemental calcium was associated with an excess risk of CVD death in men, but not women.3 The lack of randomised controlled trials testing the cardiovascular effects a priori of a calcium-enriched diet or calcium supplementation has yet to delineate the potential mechanisms and short-term and long-term risks and benefits of calcium on CVD. Meanwhile, dietary recommendations continue to emphasise increased calcium intake through diet and/or supplements without clear effects beyond bone health. These data on Swedish women suggest that adequate dietary calcium intake of 600–1400 mg/day, without calcium supplementation, may help avoid adverse effects on TM and CVDM.

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Footnotes

  • Competing interests None.

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