Part 1: Background on Nutrient Reference Values
Methodologies used to derive nutrient reference values (NRVs) were developed initially in the United Kingdom, beginning in the 1990s and subsequently in the United States and Canada through early 2000s. Similar approaches were then developed by other high-income countries.
The increasing globalization of information and the identification of factors that influence the nutritional needs of specific population groups, however, changed the dynamic of deriving NRVs. Increasingly, international scientific bodies and national governments recognized that a need existed to develop methods for deriving NRVs that could be applied across multiple countries and regions, and especially for low- and middle-income countries. They noted that an important consideration in this process was ensuring that NRVs would be pertinent to the needs of selected population subgroups, particularly young children and women of reproductive age. A glossary of relevant NRV terms is included in Appendix 2.
A means to harmonize the process of deriving NRVs on a global scale was first proposed at a meeting in Florence, Italy, in 2005 (King and Garza, 2007). Meeting participants articulated four strategic reasons for harmonizing the NRV process:
- Improve the objectivity and transparency of values developed by different groups.
- Provide a common basis for deriving nutrient intake values.
- Allow developing countries, which often have limited access to resources, to convene expert groups to identify how to modify the standards relative to their specific resource constraints (e.g. food supplies) or national policies.
- Provide a common basis across countries and regions for establishing public and clinical health objectives, developing food and nutrition policies, and addressing trade and regulatory issues.
Recognizing the need for guidance and recommendations to further this process, the Bill & Melinda Gates Foundation asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to undertake a two-part process to explore questions and frameworks currently used for developing NRVs and to assess the feasibility of harmonizing a methodology globally. The Food and Nutrition Board of the National Academies, in partnership with Department of Nutrition for Health and Development of the World Health Organization (WHO) and the Nutrition Division of the Food and Agriculture Organization of the United Nations (FAO), convened a public workshop, which was held at the FAO Headquarters in Rome, Italy, in 2017 (NASEM, 2018a). The workshop provided a venue for dialogue and discussion of current approaches to deriving NRVs.
The second part of the process was the convening of a committee to develop a
methodologic approach that could be implemented globally to guide countries in their approach to setting NRVs. The Gates Foundation specifically asked the committee to apply its findings to children up to age 5 and women of reproductive age. The consensus study report, Harmonization of Approaches to Nutrient Reference Values: Applications to Young Children and Women of Reproductive Age, recommended a framework for deriving NRVs and presented case scenarios to demonstrate how the framework could be applied to the two populations of interest (NASEM, 2018b).
Key Findings, Recommendations, and Conclusions
The committee’s review led to two key findings and six key recommendations.
Key Findings
- The purpose of developing NRVs is to assure that, if met, the majority of a generally healthy population will have sufficient intake levels to prevent nutrient deficiency disease and to avoid adverse effects of excessive intake. When applicable, reference values may also be determined to reduce risk of chronic disease.
The traditional risk assessment model for deriving NRVs led to the development of a set of values. These include the average requirement (AR), which is the amount of a nutrient estimated to meet the nutrient requirement of 50 percent of the healthy individuals of a population subgroup, to meet a specific criterion of adequacy; the recommended nutrient intake (RNI), which is derived from the AR; and the safe upper intake level (UL), which is the highest level of nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals. The AR and the UL are core reference values. A glossary of NRV terms is included in Appendix 2. To reach global agreement on the most appropriate methods and procedures for deriving standards used to establish NRVs, and their application, the focus must be on these two values. Detailed descriptions of the NRVs are provided in Part 3 below.
Recommendations and Conclusions
Recommendation 1
Nutrient reference expert panels should make two values their priority: specifically, the population average requirement (AR) and safe upper levels of intake (ULs). Their reports should estimate the inter-individual variability of requirements and use it to derive the AR. The expert panel should also acknowledge the basis and uncertainty in estimation of both values.
The need for nutritional benchmarks is critical all over the world. This shared need, combined with the substantial effort and expense of deriving NRVs, is a strong justification for international cooperation. Indeed, convening a global expert panel would be ideal for promoting a harmonized process and making efficient use of the funding to support these efforts. WHO and FAO are both international organizations responsible for facilitating cooperation in global health, nutrition, and agriculture.
Given the interface between their missions, WHO and FAO have a history of collaboration, they share funding for the Codex Alimentarius, and have over time established a trust fund to support the capacity of participants in low- and middle-income countries to participate in the nutrient reference setting process. Alternatively, it is possible that a technical organization, such as the International Union of Nutritional Sciences (IUNS), might have equally good convening authority among scientific experts needed for an international harmonization effort. Another possibility is that international collaboration could be carried out at the regional level.
Recommendation 2
To set a nutrient reference value, ideally, a global body such as the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), or the International Union of Nutritional Sciences (IUNS), or secondarily, a regional consortium should convene an expert panel to identify relevant outcome measures and request a systematic review for the nutrient of interest, and appoint a panel to advise on how to adapt the values to different population subgroups and settings.
Regardless of the convening organization, there are certain key steps in the process of deriving NRVs that should be consistent across countries. Inherent in the decision-making process is the determination of whether an existing NRV can be accepted, updated, or a new value should be derived. Either way, selecting a methodological approach for a nutrient review depends on the role of the nutrient in meeting physiological needs, intake patterns, bioavailability of the nutrient, and the presence of infection and other local factors that influence the requirement for the population under consideration. The option to accept, update, or adapt existing NRVs means that it is not necessary to go into a full review; rather, adjust existing reference values and document how it was done. For new values, a full review is required.
Recommendation 3
Expert groups should assess relevant evidence and, as needed, analyze existing or new data to assess the characteristics of various diets that can affect the bioavailability of specific nutrients.
Recommendation 4
When deriving nutrient reference values, countries or regions should look at existing values derived by expert panels and determine whether to accept, update, or adapt them to their context, if possible. If values are not relevant locally, an expert panel should adapt values to the local context or modify existing values from other experts.
A thorough understanding of the uncertainties that affect the review process is essential to maintaining the credibility of the nutrient review process, as well as the accuracy and relevance of NRVs; enabling decision makers to use NRVs in nutrition policy; and developing quantitative evidence assessment models.
Recommendation 5
After having adapted or created new nutrient reference values (NRVs), to achieve transparency the nutrient review expert panel should clearly report the reference population, adjustment factors, and the methodology used. Expert panels should also document the uncertainty in the evidence and in the methods used to develop the NRVs quantitatively. If this is not possible, then they should provide a qualitative evaluation of the confidence in the body of evidence and in the methods used.
A Sixth Recommendation
Based on its review of the current process for deriving NRVs and the application of new tools for this process and its examination of three nutrient case studies, the committee also concluded that it is possible to develop a harmonized global process for NRVs. This conclusion supported one additional recommendation.
Recommendation 6
Researchers and funding organizations should advance the knowledge of nutrient requirement research by supporting research that uses modern technology, techniques, or methods for assessing requirements.