extreme pathological condition, and the ability to consider other adverse events associated with sustained, high levels of intake has emerged. Specifically, kidney stone formation is an adverse outcome, notably among post-menopausal women. Although there is also evidence related to calcium-alkali syndrome among adults, most of the data relate to those with compromised kidney function. Vascular calcification in postmenopausal women has emerged as an interesting hypothesis, but available data are conflicting, and threshold levels for intake are unknown. Evidence related to prostate cancer, although concerning, was too confounded to allow this disease risk to serve as an indicator for establishing ULs for calcium intake. Further, neither constipation nor nutrient interactions were associated with data to suggest that these outcomes would serve as indicators for UL development.
Given the size and quality of the WHI trial, its outcome relative to the incidence of kidney stones (Jackson et al., 2006) results in the selection of kidney stones as the indicator for adults for DRI purposes. The levels of calcium intake that may cause kidney stones within a normal population cannot be specified with certainty and are known to be variable depending upon a number of factors, including baseline renal function, pre-existing disease conditions, and interactions with drugs. Based on the findings of Jackson et al. (2006), and with the understanding that the data are derived from women between the ages of 50 and 79 years, there is a concern for kidney stone risk at total calcium intakes of approximately 2,000 mg/day. Underpinning the concern is the recognition that intakes of calcium from food do not readily result in excess intakes and are not associated with adverse effects; rather, the adverse effects appear to be a function of calcium supplementation added to baseline intake. The level of 2,000 mg of calcium per day is established as the LOAEL for adults, including men, more than 50 years of age. The very limited data available for adults 19 to 50 years of age do not allow the specification of a LOAEL or NOAEL for this younger group and the UL for this group is derived from considerations used for the UL for persons above 50 years of age. For this reason the ULs for older adults are discussed first below, followed by adults 19 to 50 years of age.
The committee considered the option of applying an uncertainty factor to lower the LOAEL, given the limited data. However, the unknowns surrounding the precision of the LOAEL coupled with the observation that the LOAEL is very close to intakes that are considered adequate and recommended, caused the committee to conclude that, until there are