A new joint clinical guideline from the National Osteoporosis Foundation (NOF) and the American Society for Preventive Cardiology (ASPC) states that dietary and supplemental calcium are safe for cardiovascular health when consumed in recommended amounts. The recommendation applies to calcium consumed either alone or with vitamin D that does not exceed the National Academy of Medicine's tolerable upper intake limit of 2000 to 2500 mg/day.
"Discontinuation of supplemental calcium for safety reasons is not necessary and may be harmful to bone health when intake from food is suboptimal," Stephen L. Kopecky, MD, from the Mayo Clinic, Rochester, Minnesota, and colleagues write in the guideline, published online October 24 in the Annals of Internal Medicine.
The NOF and ASPC convened an expert panel to evaluate and grade the strength of evidence regarding the effects of calcium on cardiovascular disease. That panel wrote the guideline after considering the findings of an externally conducted systematic review and meta-analysis. Researchers Mei Chung, PhD, from the Department of Public Health and Community Medicine at Tufts University, Boston, Massachusetts, and colleagues report the new findings in the same issue of Annals of Internal Medicine.
A 2010 meta-analysis concluded that calcium increased the risk for myocardial infarction and stroke, but a 2011 meta-analysis concluded that calcium had no statistically significant effects on coronary heart disease events or mortality.
Dr Chung and colleagues reviewed English-language papers that described, in total, four randomized controlled trials, one nested case-control study, and 26 cohort studies.
Among the trials, cardiovascular disease outcomes were secondary endpoints, and none reported levels of calcium intake from both foods and supplements. Two of the studies found no statistically significant differences in cardiovascular disease or mortality between groups receiving placebo and groups receiving both calcium and vitamin D. Three studies examined the effects of calcium supplements alone and also concluded that there was no statistically significant effect on cardiovascular outcomes.
"We synthesized trials and cohort studies separately but based our conclusions on the total body of evidence. We did not perform a meta-analysis of trial data, because trials reported outcomes with heterogeneous definitions," Dr Chung and colleagues write.
The case-control and cohort studies included investigations from the Nurses' Health Study, Health Professionals Follow-Up Study, and Swedish Mammography Cohort, among others. The studies reported varying results, and were judged to have a moderate risk for bias. Most found no statistically significant link between calcium and cardiovascular outcomes. One study even found lower cardiovascular and mortality risk in women who took more than 1000 mg supplementary calcium per day compared with those who did not take supplements.
"Although a few trials and cohort studies reported increased risks with higher calcium intake, risk estimates in most of those studies were small (±10% relative risk) and not considered clinically important, even if they were statistically significant," the review authors conclude.
The researchers note that data are lacking for very high calcium intakes, and that most studies did not carefully measure dietary calcium. The studies also adjusted for confounders differently, meaning their results may not be directly comparable.
The issue is important because many people consume supplemental calcium, Karen Margolis, MD, from Health Partners Institute in Minneapolis, Minnesota, and Joann Manson, MD, DrPH, from Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, write in an accompanying editorial.
"[O]utcome data from self-reports, hospital codes, and death certificates cannot be given the same weight as data from trials with rigorous ascertainment and adjudication methods, and 'publication bias' may occur in this setting," the editorialists write.
The review authors looked for dose–response relationships to overcome the limitation of the different intake levels used in the studies, they note.
An important point for clinicians is that dietary calcium should be recommended over supplements. Calcium supplements can increase kidney stone formation, where dietary calcium does not, Dr Margolis and Dr Manson explain. No evidence has been found suggesting that calcium intakes over the recommended dietary allowance are any better than intakes that just meet the allowance, they add.
"[B]ased on the totality of evidence for both calcium and vitamin D, more is not better," Dr Margolis and Dr Manson conclude.
The work was funded by the National Osteoporosis Foundation through Pfizer Consumer Healthcare. One guideline author reports personal fees from Amarin, Amgen, AstraZeneca, Gemphire, Kowa, Merck, and Regeneron Pharmaceuticals/Sanofi outside the submitted work. One author reports personal fees from Amgen, Aegerion, Merck, Regeneron Pharmaceuticals/Sanofi, Kastle Therapeutics, True Health Diagnostics, Akcea Therapeutics, Alexion Pharmaceuticals, Pfizer, Recombine, and Invitae outside the submitted work. The other guideline authors have disclosed no relevant financial relationships. The authors of the review and meta-analysis and the editorialists have disclosed no relevant financial relationships.
Ann Intern Med. Published online October 24, 2016.
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Cite this: New Guideline Says Calcium Safe From CVD Standpoint - Medscape - Oct 24, 2016.
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