Long-latency deficiency disease: insights from calcium and vitamin D.

Nutrient intake recommendations and national nutritional policies have focused primarily on prevention of short-latency deficiency diseases. Most nutrient intake recommendations today are based on prevention of the index disease only. However, inadequate intakes of many nutrients are now recognized as contributing to several of the major chronic diseases that affect the populations of the industrialized nations. Often taking many years to manifest themselves, these disease outcomes should be thought of as long-latency deficiency diseases. Sometimes they come about by the same pathophysiologic mechanism that produces the index disease, but sometimes the mechanisms are completely different. Well-documented examples of both short- and long-latency deficiency states involving calcium and vitamin D are described briefly. Then, the insights derived from these nutrients are tentatively applied to folic acid. Discerning the full role of nutrition in long-latency, multifactorial disorders is probably the principal challenge facing nutritional science today. The first component of this challenge is to recognize that inadequate intakes of specific nutrients may produce more than one disease, may produce diseases by more than one mechanism, and may require several years for the consequent morbidity to be sufficiently evident to be clinically recognizable as "disease." Because the intakes required to prevent many of the long-latency disorders are higher than those required to prevent the respective index diseases, recommendations based solely on preventing the index diseases are no longer biologically defensible.