underestimate the true potential for risk because: (1) for ethical reasons, adverse outcomes are secondary outcomes, (2) studies are of relatively short duration, (3) adverse outcomes are not always adequately monitored or completely reported, and (4) adverse outcomes generally lack adequate statistical power for detection (Brannon et al., 2008). Further, inclusion and exclusion criteria prevent persons at greatest risk from being study participants (Yetley et al., 2009).
Over the years, excess intake of vitamin D has been considered in the context of “intoxication” or “hypervitaminosis D”; as such, the condition is perhaps best regarded as a relatively acute response. Symptoms can appear in less than 4 weeks of continual excess ingestion. The hallmark of vitamin D intoxication is hypercalcemia, which is associated with a rise in serum 25OHD levels. The conditions of hypercalcemia and hypercalciuria were described previously in the section on calcium. Vitamin D intoxication generally presents with non-specific symptoms that may vary and often include anorexia, weight loss, polyuria, and heart arrhythmias (Jones, 2008). The condition eventually leads to vascular and tissue calcification with subsequent renal and cardiovascular damage.
Although data about vitamin D intoxication are informative, avoiding this relatively acute toxicity is not the intended purpose of a UL. Rather, the UL reflects a long-term level of intake that will not cause harm to the normal, free-living population. The 2007 AHRQ analysis (Cranney et al., 2007; hereafter referred to as AHRQ-Ottawa) concluded that few adverse outcomes could be identified for intakes “above current recommended levels,” but it raised concerns about potential previously unrecognized adverse effects, including an increased risk of pancreatic cancer. The later AHRQ-Tufts analysis further identified all-cause mortality as an emerging concern, but the authors also pointed to the dearth of data.
Unfortunately, as pointed out in the earlier IOM report on DRIs for vitamin D, there continues to be a large uncertainty about the progressive health effects for regular ingestion of even moderately high amounts of vitamin D over several decades (IOM, 1997). Most available evidence is based on short-term exposures (less than 6 months). Generalization to long-term exposures—as would occur during a lifetime—is challenging. Also, most evidence is derived from adult populations with few data specific to children or vulnerable groups. For the purposes of an overview of the literature concerning adverse effects of excess vitamin D, the effects related to vitamin D intoxication (hypervitaminosis D) are discussed first and are based on a paper prepared for the committee by Hector DeLuca (DeLuca, 2009). They can provide a starting point for UL considerations. The emerging concerns about the adverse effects at higher intakes that are less than those associated with the toxicity are discussed next and are