Use of laboratory studies for the design, explanation, and validation of human micronutrient intervention studies

Many micronutrient supplementation trials have led to important new findings relevant to public health, but some outcomes have been unclear or concerning. Can and should laboratory studies and animal models be used more extensively to pretest the proposed designs of human studies? This paper illustrates, as examples, the contributions that animal models have made to several major advances in understanding the biology of the micronutrients vitamin A and carotenoids, and it proposes that animal studies can play a more integrated role in public health nutrition by serving as a first line of interrogation for study designs and thereby as a means of refining the designs of human studies so that large, expensive, and logistically difficult human trials will yield the best possible information.