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human health include arsenic, boron, nickel, silicon, and vanadium. Arsenic has been shown to have a role in methionine metabolism in rats, and a deprivation of arsenic has been associated with impaired growth in various animals. Embryonic defects have been demonstrated in boron-depleted trout. Abnormal metabolism of vitamin D and estrogen has been proposed as a related function for boron in humans. Nickel has been demonstrated to be essential for animals, and its deprivation in rats can result in retarded growth. Silicon is involved with the formation of bone and collagen in animals. Vanadium has been shown to mimic insulin and stimulate cell proliferation and differentiation in animals.

METHODOLOGICAL CONSIDERATIONS

Types of Data Used

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 therapeutic or 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.

Animal Models

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.

Human Feeding Studies

Controlled feeding studies, usually in a confined setting such as a metabolic ward, can yield valuable information on the relationship between nutrient consumption and health-related biomarkers.



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