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, epidemiological cohort studies, 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 nutritional deficiencies, chronic diseases, and toxic effects in humans, but selected animal studies are considered in the absence of human data. The strategies used for identifying potentially relevant studies are summarized in Appendix D.

As a principle, only studies published in peer-reviewed journals have been used. However, studies published in other scientific journals or readily available reports were considered if they appeared to provide important information not documented elsewhere. To the extent possible, original scientific studies and quantitative metaanalyses have been used to derive the DRIs. A thorough review of the scientific literature resulted in the identification of clinical and functional indicators of nutritional adequacy for each nutrient for each life stage and gender group. Anything that might affect dietary requirements, such as an interaction with other nutrients and the bioavailability of the nutrient, was considered when relevant. For example, the effect of energy intake was considered for thiamin, riboflavin, and niacin; the effect of protein intake was considered for vitamin B₆.

Because of the growing evidence that some B vitamins may prevent the occurrence of developmental abnormalities and chronic degenerative and neoplastic diseases, special consideration was given to the possible use of such indicators as criteria of adequacy. It was beyond the scope of the report to consider the use of nutrients in the treatment of disease or other disorders.

The quality of studies was considered in weighing the evidence. The characteristics examined included the study design and the representativeness of the study population; the validity, reliability, and precision of the methods used for measuring intake and indicators of adequacy; the control of biases and of confounders; and the power of the study to demonstrate a given difference or correlation. When applicable, greatest weight was given to randomized con-