priate to conduct clinical research with doses exceeding the UL, as long as there is monitoring and the protocol is carefully considered.

Beyond the challenge of limited data and the resulting uncertainties, the study faced two additional challenges. The first is that vitamin D, an essential nutrient, is also synthesized in the skin following exposure to sunlight. Thus, the examination of data is complicated by the confounding factors this introduces. Further, vitamin D requirements could not address the level of sun exposure because public health concerns about skin cancer preclude this possibility. There have not been studies to determine whether ultraviolet B (UVB)–induced vitamin D synthesis can occur without increased risk of skin cancer. The best approach was to estimate vitamin D requirements under conditions of minimal sun exposure.

Second, vitamin D when activated functions as a hormone and is regulated by metabolic feedback loops. The intertwining of the effects of vitamin D and calcium represents an extreme case of nutrient–nutrient inter-relationships. Indeed, many studies administered these nutrients together rather than separately. For this reason, distinguishing the health outcomes for one nutrient versus the other was challenging.