Study linking calcium to increased CVD risk contains many confounding factors

ZURICH, Switzerland — While headlines in the past two weeks warned consumers that calcium supplementation could increase the risk of cardiovascular disease, authors of the study that prompted those headlines — published last month in the peer-reviewed journal Heart — identified four significant confounding factors in the design of the study.



For example, the dietary data contained measurement errors and could not adequately account for long-term variation in calcium intake due to changes in diet.



In addition, most of the clinical trials included in the above-mentioned meta-analyses measured daily intake of equal to or more than 1,000 mg of calcium in its elemental form. The recommended dietary allowance of calcium established by the National Institutes of Health's Office of Dietary Supplements ranges between 1,000 mg and 1,300 mg in adults.



McNeil Nutritional's Viactiv, a brand well-known as a calcium supplement, supplies 1,000 mg of calcium daily in its Viactiv Calcium Plus D formulation and 200 mg of calcium daily in its Viactiv Multi-Vitamin formulation.



According to the ODS, about 43% of the U.S. population — including almost 70% of older women — use dietary supplements containing calcium, increasing calcium intakes by about 330 mg/day among supplement users. According to NHANES 2003-2006 data, mean total calcium intakes from foods and supplements range from 918 mg to 1,296 mg per day.



Not all calcium consumed actually is absorbed in the gut, the ODS noted. "Humans absorb about 30% of the calcium in foods, but this varies depending upon the type of food consumed." Other factors that also affect calcium absorption include the amount of calcium consumed — calcium absorption decreases as intake increases; age — net calcium absorption is as high as 60% in infants and young children who are building bones, but that decreases to absorption rates of between 15% and 20% in adulthood; vitamin D intake, which improves calcium absorption — that's a factor that would be difficult to account for in a clinical study let alone a meta-analysis of a group of studies because the body generates vitamin D when exposed to sunlight; and foods with high levels of oxalic acid, which inhibits calcium absorption. Those foods include spinach, collard greens, sweet potatoes, rhubarb and beans.



Another limitation identified by the authors: the study only excluded patients who had had a heart attack, stroke or mini stroke and did not exclude individuals with other pre-existing cardiovascular conditions. However, authors suggested this "incomplete exclusion" would only have minor implications as heart attacks and strokes account for the "vast majority of cardiovascular disease."



"Lastly, it needs to be noted that 44.5% of vitamin/mineral users in this study did not report the names of their supplements and we therefore only identified a limited number of calcium supplement users, who accounted for 3.6% of all cohort participants," the authors added. "This prevalence is lower than that observed in a small German elderly population (about 8% in men and 27% in women). It is also lower than the prevalence (11%) reported by a U.S. national survey. It is possible that the unreported calcium supplementation would affect the accuracy of our results if identified calcium supplement users had a different cardiovascular risk profile than unidentified calcium supplement users."



The Council for Responsible Nutrition, in a statement issued the day the study was published, identified another confounding factor. "The original study wasn’t designed to measure cardiovascular events; consequently confounding factors for cardiovascular disease were not equally distributed across the study groups," noted Taylor Wallace, senior director scientific and regulatory affairs for CRN. "So, for example, the calcium supplement group had a population with a greater incidence of high cholesterol at baseline, and also included more smokers who were more likely to smoke for a longer duration. The association between smoking and heart disease is well-established," Wallace noted. "[And] in terms of considering the relative risk, of the 851 individuals taking supplements containing calcium, only seven events occurred in users of supplements containing only calcium."



The study was named an "editor's pick" by Heart and made available for viewing without charge. The study can be viewed in its entirety here.

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