quired for normal cellular function. Severe potassium deficiency is characterized by hypokalemia, and its adverse consequences include cardiac arrhythmias, muscle weakness, and insulin resistance. More subtle deficiency signs of potassium are increased blood pressure, increased sensitivity of blood pressure to sodium intake (“salt sensitivity”), increased risk of kidney stones, and increased bone turnover. Sodium chloride is required to maintain fluid and electrolyte balance, extracellular volume, and serum osmolality.

The scientific data for developing the Dietary Reference Intakes (DRIs) have essentially come from observational and experimental studies in humans. Observational studies include single-case and case-series reports and cross-sectional, cohort, and case-control studies. Experimental studies include randomized and nonrandomized prevention trials and controlled dose-response, balance, turnover, and depletion-repletion physiological studies. Results from animal experiments are generally not applicable to the establishment of DRIs, but selected animal studies are considered in the absence of human data.

Basic research using experimental animals affords considerable advantage in terms of control of nutrient exposures, environmental factors, and even genetics. In contrast, the relevance to free-living humans may be unclear. In addition, dose levels and routes of administration that are practical in animal experiments may differ greatly from those relevant to humans. Nevertheless, animal feeding experiments were sometimes included in the evidence reviewed to determine the ability to specify DRIs.

Controlled feeding studies, usually in a confined setting such as a metabolic unit, can yield valuable information on the relationship between nutrient consumption and health-related biomarkers. Much of the understanding of human nutrient requirements to prevent deficiencies is based on studies of this type. Studies in which the subjects are confined allow for close control of both in-