Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort studyBMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f228 (Published 13 February 2013) Cite this as: BMJ 2013;346:f228
- Karl Michaëlsson, professor1,
- Håkan Melhus, professor2,
- Eva Warensjö Lemming, researcher1,
- Alicja Wolk, professor3,
- Liisa Byberg, associate professor1
- 1Department of Surgical Sciences, Section of Orthopedics, Uppsala University, SE-751 85 Uppsala, Sweden
- 2Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University, Uppsala, Sweden
- 3Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Correspondence to: K Michaëlsson
- Accepted 28 December 2012
Objective To investigate the association between long term intake of dietary and supplemental calcium and death from all causes and cardiovascular disease.
Design Prospective longitudinal cohort study.
Setting Swedish mammography cohort, a population based cohort established in 1987-90.
Participants 61 433 women (born between 1914 and 1948) followed-up for a median of 19 years.
Main outcome measures Primary outcome measures, identified from registry data, were time to death from all causes (n=11 944) and cause specific cardiovascular disease (n=3862), ischaemic heart disease (n=1932), and stroke (n=1100). Diet was assessed by food frequency questionnaires at baseline and in 1997 for 38 984 women, and intakes of calcium were estimated. Total calcium intake was the sum of dietary and supplemental calcium.
Results The risk patterns with dietary calcium intake were non-linear, with higher rates concentrated around the highest intakes (≥1400 mg/day). Compared with intakes between 600 and 1000 mg/day, intakes above 1400 mg/day were associated with higher death rates from all causes (hazard ratio 1.40, 95% confidence interval 1.17 to 1.67), cardiovascular disease (1 49, 1.09 to 2.02), and ischaemic heart disease (2.14, 1.48 to 3.09) but not from stroke (0.73, 0.33 to 1.65). After sensitivity analysis including marginal structural models, the higher death rate with low dietary calcium intake (<600 mg/day) or with low and high total calcium intake was no longer apparent. Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55).
Conclusion High intakes of calcium in women are associated with higher death rates from all causes and cardiovascular disease but not from stroke.
Contributors: KM designed the study, interpreted the data, and drafted the manuscript. LB analysed the data. LB, HM, EWL, and AW contributed to the interpretation of the data and revision of the manuscript. KM and AW financed the study. All authors had full access to all data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. KM is the guarantor.
Funding: Supported by the Swedish Research Council, grant numbers 2008-2202 and 2009-6281. The funding source was not involved in the design, conduct or interpretation of the study, or in the writing of the submitted work.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by the regional ethics committee at Karolinska Institutet, Stockholm, Sweden, and all participants gave their informed consent.
Data sharing: No additional data available.
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