Calcium Supplementation and Incident Kidney Stone Risk: A Systematic Review

AbstractBackground: A report of a small increase in kidney stone risk in the calcium treatment arm of the Women's Health Initiative (WHI) led to a reduction in U.S. calcium supplement sales.Objective: To reassess kidney stone risk in postmenopausal women using data accumulated in calcium supplement trials, bone active agent registration trials, and in unpublished WHI data available online; and to compare these estimates with formal published epidemiological studies of stone risk.Methods: Literature review of published studies relating calcium intake to stone risk; adverse event report data from pharmaceutical industrial trials designed to evaluate bone active agents.Results: Stone risk in postmenopausal women has increased substantially in the past 40 years, but absolute population incidence estimates vary widely from a low of about 70 incidents/100,000/yr for Olmsted County, MN, today, to a concurrent high of approximately 190/100,000/yr for the Nurses' Health Study II. Reported WHI incidence rates are higher still, with values around 300/100,000/yr for various WHI subgroupings. The reasons for these discordances are unclear. Despite this uncertainty about background rate, most of the studies show no increase in stone risk with high calcium intake (from either diet or supplements). Contrariwise there is a substantial body of evidence, both from controlled trials and from observational studies, indicating that there is an inverse relationship between calcium intake and stone risk.Keywordskidney stonescalcium intakecalcium supplements The author thanks D. Valent (P&G-Aventis), M. Draper and L. Schuh (Eli Lilly), A. Bendich and G. Dasic (GlaxoSmithKline), and J. Rossouw (NIH; WHI) for their assistance in making available the previously unpublished stone data from the adverse event reports of the pharmaceutical and WHI trials. This project was supported entirely from Creighton University research funds.NotesThe author performs occasional contracts for the National Dairy Council and from time to time has performed bioavailability studies for various supplement manufacturers.