A review of the quality of evidence of nutrient reference values

Abstract

Nutrient reference values (NRVs) serve as key benchmarks for assessing nutrient adequacy and informing dietary guidelines. However, their accuracy depends on the quality of the underlying evidence. In this Review, we evaluate the evidence base used by the US Institute of Medicine (IOM) and the European Food Safety Authority (EFSA) to establish NRVs for 21 micronutrients across all life stages. We assessed methodological approaches, sample sizes, publication timelines, and study durations and developed a classification of the quality of evidence based on these factors. Our findings highlight key limitations, including reliance on small and outdated studies, scarce experimental data, and the use of indirect methods such as balance studies and factorial modelling. Although EFSA incorporates more recent evidence than the IOM, gaps in the quality of evidence persist. Strengthening the evidence base through the use of direct, adequacy-related methods, large and long-term studies, and meta-analyses is essential for improving the accuracy of NRVs. Until more robust NRVs are established, our findings suggest that current NRVs are best used cautiously in nutritional assessments, that conclusions should be based on a subset of NRVs with at least a moderate quality of evidence, and that the existing uncertainties should be clearly communicated.