Boning Up on What is New with Calcium

Abstract & Commentary

By Ralph R. Hall, MD, FACP, FACSM, Professor of Medicine Emeritus, University of Missouri, Kansas City School of Medicine. Dr. Hall reports no financial relationship relevant to this field of study.

Synopsis: This study does not support the hypothesis that high calcium intake increases coronary artery calcification

Source: Samelson EJ, et al. Calcium intake is not associated with increased coronary artery calcification: The Framingham study. Am J Clin Nutr 2012;96:1274-1280.

Adequate calcium intake is known to protect the skeleton. However, studies have reported adverse effects of calcium supplementation on vascular events that have raised widespread concern.

The authors assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors.

The study was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 years; range, 36-83 years) who attended clinic visits and completed food frequency questionnaires in 1998-2001 and underwent computed tomography scans in 2002-2005.

The mean age-adjusted coronary artery-calcification Agatston score decreased with increasing calcium intake, and the trend was not significant after adjusting for age, body mass index, smoking, alcohol consumption, vitamin D supplement use, energy intake, and, for women, menopause status and estrogen use. Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P trend = 0.74), respectively, with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use.

The study does not support the hypothesis that calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk.

Commentary

Bolland et al published several articles using subgroup post hoc analysis in major medical journals from a randomized, placebo-controlled trial designed to evaluate fracture outcomes. In these post hoc analysis groups, it was noted that there was a marked increase in myocardial infarctions in women who took supplements of 1000 mg of calcium citrate relative to placebo.1 Further studies suggested supplemental calcium was associated with increased vascular calcium scores.2,3 Following this study. there was widespread news commentary regarding the potential dangers of calcium supplementation.

Other researchers advised caution in interpreting the post hoc subgroup analysis and noted that they should be hypothesis generating rather than being considered conclusive. In the Letters to the Editor section of the American Journal of Clinical Nutrition, Bolland et al stated, “Because these analysis were exploratory post hoc subgroup analysis, the results should be treated cautiously and as “hypothesis generating.’”4

Still, there remained doubt about continuing to recommend calcium supplements. The Samelson et al study, however, is reassuring. The mean total calcium intake in women was 1185 mg/d, with 425 mg from supplements. The mean calcium intake in men was 797 mg/d, with 94 mg from supplements.

Samelson et al note that osteoporosis and atherosclerosis are leading causes of mortality in the Western world. There is growing evidence suggesting an association between vascular calcification and skeletal fragility that is independent of age and other risk factors. Postmenopausal women with bone loss have the greatest progression of vascular calcification,5,6 and the incidence of cardiovascular events is greater in women with lower bone mass and men with higher levels of bone resorption.

It is preferable to obtain calcium and vitamin D intake from the diet alone. However, it may be difficult for older individuals to limit their calcium and vitamin intake because of their decreased need for calories.

Vitamin D intake from diet has just been made easier with the FDA’s approval to allow vitamin D in bread. Their new guidelines will allow 400 IU in three slices of bread.7

References

1. Bolland MJ, et al. Vascular events in healthy older women receiving calcium supplementation. BMJ 2008; 336:262-266.

2. Bolland MJ, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: Meta-analysis. BMJ 2010;341:c3691.

3. Bolland MJ, et al. 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;342:d2040.

4. Bolland MJ, et al. Reply to RT Chlebowski et al. Am J Clin Nutr 2012;95:259.

5. Hak AE, et al. Progression of aortic calcification is associated with metacarpal bone loss during menopause: A population-based longitudinal study. Arterioscler Thromb Vasc Biol 2000;20:1926-1931.

6. Kiel DP, et al. Bone loss and the progression of abdominal aortic calcification over a 25 year period: The Framingham Heart Study. Calcif Tissue Int 2001;68:271-276.

7. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; Vitamin D2. Federal Register, August 29, 2012.