Proceedings of a Workshop

Global Harmonization of Methodological Approaches to Nutrient Intake Recommendations

Proceedings of a Workshop—in Brief

The Food and Nutrition Board (FNB) of the National Academies of Sciences, Engineering, and Medicine, in partnership with the Department of Nutrition for Health and Development of the World Health Organization (WHO) and the Nutrition Division of the Food and Agriculture Organization (FAO) of the United Nations (UN), convened a workshop to explore the evidence for achieving global harmonization of methodological approaches to establishing nutrient intake recommendations.¹ The workshop was held at FAO headquarters in Rome, Italy, September 21–22, 2017. In his welcoming remarks, Kostas Stamoulis, FAO assistant director-general, Economic and Social Development Department, noted that, with one in three people worldwide suffering from some form of malnutrition, the UN declared 2016 through 2025 the “decade of nutrition.” The challenge, he said, is to translate this political commitment into action at the country level. Currently, there is little consistency in setting country-level nutrient intake recommendations and few processes in place for updating these recommendations.

For Stephanie Atkinson, McMaster University professor of pediatrics and chair of the workshop planning committee, this workshop was an outcome of a nearly 25-year journey, one that began with the harmonization of U.S. and Canadian Dietary Reference Intakes (DRIs), which itself was a 10-year process. The next big step, Atkinson recalled, was the 2005 international initiative, led by Janet King, Children’s Hospital Oakland Research Institute Senior Scientist, and Cutberto Garza, Cornell University Professor Emeritus, and jointly sponsored by the UN, FAO, and WHO, to review the harmonization of concepts and approaches for developing nutrient-based dietary standards. Atkinson viewed this workshop as a continuation of these efforts.

This Proceedings of a Workshop—in Brief highlights key points made by individual speakers during the workshop presentations and discussions.² The information presented here reflects the knowledge and opinions of individual workshop participants and should not be construed as consensus on the part of the workshop planning committee, the FNB, or the National Academies.

DEFINING THE PROBLEM: PARTNER PANEL

Like Atkinson, Chizuru Nishida, WHO coordinator of the Nutrition Policy and Scientific Advice Unit in the Department of Nutrition for Health and Development, viewed this workshop as an opportunity to build on the 2005 discussion. She mentioned additional relevant efforts that have occurred since then, including a 2010 WHO meeting in Geneva where attendees agreed that harmonization of national nutrition-related guideline development would be important, but

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expressed uncertainty in how to move forward. Nishida hoped that an outcome of this workshop would be a mapping of possible next steps toward the global harmonization of approaches to establishing nutrient intake values,³ including the identification of priority areas, or nutrients, for testing harmonization. Following Nishida, Anna Lartey, FAO director of nutrition, discussed the relevancy of harmonization to FAO’s ongoing work in nutrition and its emphasis over the past 5 years on food system reform. She echoed other calls to put harmonization “into action.” Such action will be particularly important, she said, for countries without the resources and technical capacity to develop their own national recommended nutrient intakes.

BACKGROUND FOR THE WORKSHOP

Janet King provided an overview of concepts put together by the 2005 international harmonization initiative, which encompassed a meeting of experts in Florence, Italy, in 2005, followed by the publication of 10 commissioned background review papers in Food and Nutrition Bulletin in 2007. At the 2005 meeting, attendees developed a new term, Nutrient Intake Value (NIV), but emphasized that NIV is analogous to other terms used around the world (e.g., DRI, dietary reference value). They agreed to focus on only two NIVs: Average Nutrient Requirement (ANR, which King said some people call EAR, or Estimated Average Requirement) and Upper Nutrient Level (UNL, formally known as UL, or tolerable upper intake level). They then developed separate frameworks (i.e., factors and criteria to consider) for estimating ANRs and UNLs. King described several other issues also addressed by 2005 meeting attendees, such as criteria for indicators to use when developing NIVs (e.g., that there should be a demonstrated change in response as intake changes and that this change in response should be resistant to rapid changes in intake).

Suzanne Murphy, University of Hawaii (emerita), continued where King left off, that is, how an NIV, once established using a globally harmonized methodology, can be used or applied at a country or a region level. She briefly covered the uses of NIVs to assess and plan intakes for individuals (e.g., to offer dietary advice) and populations (e.g., to design food fortification programs). She reviewed in more detail the many critical health applications that depend on accurate nutrient intake recommendations, one of which, the setting of global nutrient standards, was, she said, “the reason we are here today.” She added that while many of the other applications are country specific (e.g., designing food assistance programs), an often overlooked advantage of harmonization is an increased understanding of these other applications.

HARMONIZATION FRAMEWORKS

Session 1 speakers and panelists offered a sketch of harmonization work completed since the 2005 initiative. First, Peter Clifton, professor of nutrition at the University of South Australia, described consulting work he was involved with in Australia regarding which existing (2005–2006) Nutrient Reference Values (NRVs) to review (e.g., all or some) and how the review process should occur. The existing NRV process had followed the Institute of Medicine (IOM) recommendations almost completely,⁴ Clifton recalled, but the process had generated considerable confusion because of its lack of transparency. Among other recommendations for future NRV revisions, the consultative group called for greater transparency in the decision-making process, including clear justification for the inclusion of experts on committees and clear documentation of the process of determining nutrient values. He cited folate as an example of what he described as a “real problem” of harmonization in approach even within individual countries, with recommended intakes fluctuating over time. This lack of harmonization stems not from the use of different criteria among different working groups, Clifton said, but rather differences in the way data are interpreted.

Next, Amanda MacFarlane, research scientist at Health Canada, discussed the challenges of developing DRIs based on chronic disease endpoints, as opposed to traditional nutrient deficiency (or excess) endpoints. She explained how risk assessment is at the heart of the DRI framework, but that several key assumptions of this approach, such as causality, do not always fit for chronic disease endpoints. Causality relies heavily on randomized controlled trials (RCTs), she said, yet most data comparing nutrient intake and chronic disease endpoints come from observational studies. This difference in the nature of the evidence that is available in the scientific literature is “not good or bad,” MacFarlane said, “it just is what it is.” Another key assumption is that there is no overlap between beneficial intake and harmful intake. However, as MacFarlane explained (see Figure 1), because a nutrient can be related to multiple chronic diseases, the relationship between nutrient intake level and chronic disease risk is more complex than that between nutrient intake level and risk of toxicity. In the hypothetical scenario in Figure 1, while the risks of diseases A and C decrease with increased

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intake (represented by the green and blue curves), the risk of disease B increases (represented by the black curve). This makes it difficult to set DRI values for chronic disease endpoints.

Continuing the focus on chronic disease endpoints, King highlighted key findings from a recently published National Academies report, Guiding Principles for Developing Dietary Reference Intakes Based on Chronic Disease.⁵ A key difference between traditional versus chronic disease DRIs, she pointed out, is that the latter are not warranted unless sufficient evidence exists, in contrast to traditional DRIs, which affect everyone. The National Academies committee issued two sets of recommendations: first, how to determine whether specific levels of nutrients or food substances can ameliorate chronic disease risk, and, second, how to develop DRIs based on chronic disease outcomes. Its recommendations covered how to select and judge chronic disease evidence (e.g., how to extrapolate intake-response data from one population to another); how chronic disease DRIs should be structured (e.g., as ranges, rather than single numbers); and the DRI process itself (e.g., continue to use the current DRI process, but, as a first step, conduct a thorough evidence-based systematic review of the nutrient and associated chronic disease risk). King noted that as a first test of these guiding principles, a National Academies review of whether there should be chronic disease DRIs for sodium and potassium was already under way.

CURRENT MODELS FOR ESTABLISHING INTAKE RECOMMENDATIONS

Four panelists from different regions of the world described their experiences with harmonizing approaches to developing intake recommendations. First, Hasan Hutchinson, Health Canada director general of the Office of Nutrition Policy and Promotion, provided an overview of the joint effort by Canada and the United States to develop harmonized DRIs, an effort that began in 1994 and continues to this day. By 2005, he said, a fairly complete set of DRIs had been established, but with no formal process to keep the DRIs up to date. Thus, a joint steering committee developed a structured process for deciding which nutrients to update based on changes in evidence, new methodologies, and other criteria. As King noted previously, the sodium and potassium DRI reviews will be updated first, using the new guiding principles for chronic disease endpoints.

Clifton summarized recommendations issued in 2012 for South Australia and New Zealand, actions taken since then, and challenges faced. The 2012 recommendations included an immediate review of the chronic disease and macro-nutrient section, less comprehensive reviews of some micronutrients (e.g., UL for fluoride), and greater transparency in the decision-making process. Actions taken since then include the establishment of a steering committee to decide on priority nutrients and the establishment of several working groups, including one for fluoride. Work completed by the fluoride working group, all of which Clifton said is clearly documented and available online, was approved in 2016 by the Australian National Health and Medical Research Council. The fluoride work was an 18-month to 2-year process, illustrating for Clifton the time-consuming nature of a review of a relatively targeted area, but one done comprehensively.

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Next, Hee Young Paik, Seoul National University (emerita), described how Recommended Dietary Allowances (RDAs) in South Korea have changed over the past several decades, beginning in 1962 when the first RDAs were published. Most recently, in 2015, a committee composed of 78 members, with subcommittees for different nutrients, reviewed the DRIs for 36 nutrients.⁶ Paik emphasized the 2015 committee’s use of Korean data from the literature. For international harmonization, she suggested that core processes and methods be standardized (e.g., by having an international expert group review the international literature), but such processes should be adaptable to specific countries (e.g., by having an expert group in each country review local literature using a standardized methodology).

Finally, Ann Prentice, director of the Medical Research Council (UK) Elsie Widdowson Laboratory, described past and current nutrition risk assessment work by the UK Scientific Advisory Committee on Nutrition. She emphasized that the committee’s remit is in risk assessment, not risk management. Its dietary recommendations are derived using the same basic EAR framework that other speakers described, according to Prentice, and have been since 1981, when the United Kingdom’s first Reference Nutrition Intakes (RNIs) were published. When evaluating data, the committee often uses systematic reviews from the United States and Canada as a starting point and then determines whether more recent data are available and also examines the assumptions of those reviews. The committee’s recent vitamin D recommendation, however, went beyond the traditional EAR/RNI framework, because of the risk of bone health problems below a particular intake value and the desire for everyone in the population to reach that value year-round (i.e., not just when sun exposure is greatest). Instead, they set a “population protective value.” In her experience, Prentice has found that some of the biggest problems are the acceptance, interpretation, and understanding of new terminology.

APPROACHES USED IN EVALUATING EVIDENCE

“Not all evidence is created equal,” said George Wells, University of Ottawa professor of epidemiology, public health, and preventive medicine, as he began his overview of tools for assessing the quality of evidence from individual studies and systematic reviews. There are several types of individual study designs (i.e., experimental, quasi-experimental, observational), each having different qualities and “things that can go wrong,” he said. Based on an evaluation of many of the hundreds of available quality assessment instruments (QAIs), Wells and colleagues selected one known as SIGN 50 to use for assessing both RCTs and observational studies (both case-control and cohort studies), but they believed that a nutrition-specific QAI would be even more sensitive to identifying bias in nutrition studies in particular. He explained how, using SIGN 50 as a starting point, they developed their own nutrition-specific QAI guidance for use by Health Canada. Of the many available instruments for quality assessment of nutrition studies at the systematic level of review, Wells remarked that probably the most widely used for RCTs is AMSTAR, published in 2007. An updated AMSTAR2 for use with nonrandomized studies in addition to RCTs, and thus of relevance to the types of reviews being discussed at this workshop, he noted, will be the latest QAI tool in the marketplace. Wells described several other nutrition-specific QAIs, as well as risk-of-bias tools, that have recently been developed or are currently in development or planning.

“We have arrived at a stage in which the use and usefulness of systematic reviews to inform nutrition decisions are no longer debated,” Joseph Lau, Brown University (emeritus), claimed. This was not true 10 to 15 years ago, he said. In a 2005 study on different authoritative bodies’ rationales for UL recommendations for vitamin A, Lau and colleague Alice Lichtenstein found that different workgroups used different sets of studies, the criteria for inclusion/exclusion were unclear, and rationales for using the selected studies to support recommendations were unclear.

Lau and Lichtenstein hypothesized that one reason for these differences was lack of a predefined analytic framework to help clarify systematic review questions. Lau explained the value of such a framework, using his work with vitamin D as an example. Additionally, he described several available resources to facilitate global harmonization of systematic review methods, including standards for conducting systematic reviews (e.g., Cochrane Handbook for Systematic Review of Interventions) and Web-based collaborative systematic review tools (e.g., the open-access Systematic Review Data Repository [SRDR]). In closing, among other key points, Lau emphasized the likelihood that different countries may need to convene their own expert panels to develop nutrient intake recommendations, but with the different panels using the same systematic reviews. As he put it, “Evidence is global, decision is local.”

In the final presentation of this session, Hans Verhagen, European Food Safety Authority (EFSA) head of risk assessment and scientific assistance, used his past work with folic acid at the Dutch National Institute for Public Health and the Environment to illustrate how risk–benefit assessment can be used to estimate the public health burden associated with the risk of inadequacy (at low intake levels) and/or the risk of an adverse effect (at high intake levels). Verhagen and colleagues modeled the public health burden of folic acid fortification of flour at different doses and found that fortification would have both benefits and risks, including a decreased incidence of neural tube defects and an increased incidence

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of masked vitamin B12 deficiency. The potential public health burden associated with the risk of colorectal cancer was less clear, according to Verhagen. Overall, their results suggested that a moderate level of fortification would decrease the public health burden associated with folic acid intake. Verhagen emphasized, however, that the work of scientists is to describe risk–benefit relationships, in contrast to the work of policy makers, which is to make decisions with that information. In fact, he noted, the government decided not to fortify, but to supplement instead. Additionally, Verhagen called attention to what he considered one of the most important EFSA publications in the past 15 years: its uncertainty guidance, Promoting Methods for Evidence Use in Scientific Assessments (PROMETHEUS), which he said was designed in such a way that once a risk–benefit assessment is completed, a new team of scientists should be able to conduct another assessment and achieve similar results.

CONTEXTUAL FACTORS: HOST, DIET/ENVIRONMENT, AND HEALTH STATUS

In session 3, six speakers representing a wide geographic range discussed contextual factors related to host genetics and physiology, diet and environment, and health status. To start the session, Patrick Stover, Cornell University professor and director of the Division of Nutritional Sciences, stated that a number of physiological processes can be modified in ways that change what a nutrient requirement may or may not be. Genetics is one of these modifiers. He showed examples illustrating that although the strongest evidence for a diet-related gene remains for the lactase gene and its evolution to allow lactose tolerance, proof-of-concept evidence exists for several other diet-related genes. But the “real” question, he said, is whether genetic variation in diet-related genes matters in terms of nutrient requirements. According to Stover, most genes that have an elevated effect on nutrient requirements are also high-risk factors for miscarriage, with most conceptions not proceeding to birth and, thus, naturally being selected out. He explained how variation in a common folate-related variant is a rare example of a diet-related gene that does have an effect. Individuals with the T allele (20 percent), as opposed to the C allele (80 percent), have a lower folate status, so a higher folate requirement, and are at risk of spina bifida and miscarriage, but if they survive gestation they also have one of the lowest rates of colon cancer known. In 2015, WHO used these data to develop new guidelines for red blood cell folate concentrations for women of reproductive age.

Not only is variation the norm for human physiology, Anura Kurpad, St. John’s Medical College professor of physiology and nutrition, continued, but it is also heritable. In his opinion, the EAR and UL are not the only two nutrient intake reference values that need to be measured. Variability is another. “You can’t just ‘grab’ study participants ‘off the road’ and enroll them in RCTs for nutrient requirements,” he said. Because baseline measurements of habitual intake, nutrient status, and body composition are so critically important, subjects need to be “normalized” before measuring these values. For example, in past work for WHO, Kurpad and colleagues demonstrated that a 7-day adaptation was sufficient for measuring protein requirement. According to Kurpad, the consequences of not adapting subjects before studying them in an RCT can have economic consequences (e.g., if subjects are eating higher amounts of a nutrient when enrolled, their intake requirements will appear to be higher than they would be otherwise). Another problem that worries Kurpad is scaling (i.e., scaling nutrient intake requirements to body weight). In closing, among other reflections, Kurpad wondered if the EAR should be philosophically reconsidered with respect to what is “necessary” versus “sufficient.” He pointed out that, currently, the EAR for protein, for example, is the minimum, not optimal, intake that assures balancing intake against daily losses.

The next two speakers focused on health status and its effect on nutrient intake requirements. In his overview on the role of infections, Seth Adu-Afarwuah, senior lecturer in the Department of Nutrition and Food Science at the University of Ghana, emphasized that despite massive reductions over the past 15 years in infectious diseases in children under 5 years of age, such diseases still account for a high percentage of child mortality worldwide. He listed four ways that infections can impair nutrient metabolism and, consequently, nutrient requirements: (1) decreased food intake, (2) impaired nutrient absorption, or reabsorption, (3) loss of body nutrients (i.e., wastage), and (4) uptake, diversione, or sequestration of body nutrients. He used examples from the literature to illustrate each. For example, for the first mechanism, data from Kenya (measles), Peru (diarrhea), Bangladesh (cholera), and Zambia (malaria) all show similar findings on the effects of reduced energy consumption associated with various infections on nutrient intake requirements. “One of the hallmarks of infection is the breakdown or loss of muscle protein,” Adu-Afarwuah said, in reference to the third mechanism. Again, data from multiple studies have all shown associations between infection and loss of nitrogen or protein. In conclusion, Adu-Afarwuah suggested considering two sets of recommendations: one for developed countries and the other for developing countries with allowance for infections.

Caryl Nowson, professor of nutrition and aging at Deakin University, continued the discussion on health status, but in the context of aging. Among other physiological changes with age, by 70 years people have lost, on average, 40 percent of muscle mass and strength, which has a major effect on quality of life. Likewise with bone loss. She

emphasized that not only does the older population have diverse health needs, but also several lifestyle factors, such as exercise, including type of exercise (e.g., resistance training), that influence nutrient requirements. Nowson emphasized the importance of not just physiological and metabolic responses to nutrient intakes, but also functional (e.g., risk of falls, ability to maintain activities of daily living) and chronic disease outcomes. For example, while both calcium and vitamin D have biochemical indices related to nutrient deficiency, both also have functional outcomes (e.g., fracture risk). In closing, among other challenges in setting NRVs for older people, Nowson questioned the extent to which functional outcomes overlap with chronic disease outcomes in this population and how NRVs for highly interrelated nutrients, like vitamin D and calcium, should be developed and communicated.

Next, Rosalind Gibson, University of Otago (emerita), provided an overview of bioavailability.⁷ She emphasized that if host conditions, diet, or environment do not affect bioavailability, then the physiological and dietary requirements will be the same. Dietary factors known to influence bioavailability (or bioefficiency) include chemical form, nature of the dietary matrix, effects of other food components (e.g., certain organic components inhibit, while others enhance), and pretreatment of food (e.g., blending, fermentation). Among the several types of methods used in the past to estimate nutrient bioavailability, the most accurate, Gibson said, are isotopic methods based on whole diets, not single meals. As an example, she discussed how WHO and FAO have used isotopic data, along with other data on food consumption patterns, to develop algorithms for classifying diets into high, low, or medium bioavailability for iron and zinc. Next, she discussed two types of potential tools to estimate bioavailability in a harmonized manner that allows for cross-country comparisons: (1) tools based on food supply data (i.e., from either FAO food balance sheets or the FAO/WHO Global Environment Monitoring System (GEMS) cluster diet database); and (2) tools based on food consumption data, namely the FAO/WHO Global Individual Food consumption data Tool (GIFT) platform. She called for more exploration of the use of the GIFT platform in particular.

Continuing the focus on bioavailability, Umi Fahmida, University of Indonesia deputy director at the Southeast Asian Ministers of Education Organization Regional Center for Food and Nutrition, discussed estimates of bioavailability in Southeast Asian countries derived using the same tools described by Gibson. She commented on the variation in iron bioavailability data obtained from isotope studies for different types of diets across India, Myanmar, and Thailand (ranging from 2 to 20 percent) and how this variation reflects the complexity of diet in Asian countries. Balance sheet data on energy from animal source foods show the same variation. For example, animal source foods provide 6.6 percent of energy in the Indonesia diet, compared to 21.5 percent in Brunei Darussalam. Similarly, food consumption data reveal variation in dietary intake not just among countries, but even within countries and also among people in different stages of life. Fahmida shared conclusions from a 2005 report (on harmonizing RDAs across Southeast Asia) regarding when and how to estimate bioavailability for what she described as “typical problem nutrients” in Southeast Asia, that is, calcium, iron, and zinc. Today, Fahmida said, despite these efforts, each country still has its own way of estimating bioavailabilities. She emphasized that it is not the values themselves that need to be harmonized, rather the approaches for estimating these values.

BREAKOUT DISCUSSIONS: APPLICATIONS, FACILITATING QUALITY, AND COST-EFFECTIVENESS

The breakout discussions in session 4 were designed to encourage all workshop participants to provide input into how to harmonize methods for setting nutrient reference values. Each breakout discussion addressed one of three questions: (1) What are the advantages of global harmonization of methodologies for developing nutrient intake recommendations from your standpoint? (2) What additional resources and expertise would facilitate the adoption of a harmonized approach in your region or country? (3) What are the likely barriers and challenges to achieving global harmonization from your standpoint? Afterward, representatives from each discussion reported back to the workshop at large the key points made by individual discussants. Their reports are summarized here.

As reported by MacFarlane and Kurpad, individuals in the breakout discussion assigned to the first question recognized many of the same advantages previously described by workshop presenters, a prime one being better use of limited resources. This, in turn, could facilitate easier extrapolation and adaptation across regions, increased country-specific applications, and greater scientific capacity (e.g., expertise around particular nutrients) both within countries and across regions. Additional advantages raised by individual breakout discussants included increased transparency, increased trust and confidence in nutrition science and recommendations stemming from this science, empowerment of countries and regions to set their own nutrient reference values and to implement these values, facilitation of the global trade of staples

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and processed foods (i.e., because of the use of similar standards), easier identification of gaps in knowledge once a common scientific paradigm is in place (e.g., gaps in knowledge around folate requirements), and the opportunity for a systematic review repository.

Regarding additional resources that would facilitate adoption of a harmonized approach (i.e., the second question), Fahmida and Lau reported that several individuals envisioned an evidence repository containing a wide range of information, not just systematic reviews, but also food composition tables, food consumption data, bioavailability data, and other related data. For the sake of transparency, this information repository, or database, could also include detailed documentation of the process, some participants suggested. Others suggested something that occupies a single location online where anyone can access it. Additionally, many discussants also envisioned a technical brief, or guide, to facilitate a harmonized approach, with the brief detailing methods not only for developing nutrient recommendations but also how adjustments can be made to these methods to account for differences in genetics, physiology, infection, aging, and bioavailability. A statistical software package to support the technical brief would be needed, as well as an online or face-to-face collaborative training on the use of the manual.

Individual breakout discussants identified many barriers and challenges to achieving global harmonization (i.e., the third question). As reported back to the workshop at large by James Ntambi, professor of nutritional science at the University of Wisconsin, and Laura Martino, EFSA, these challenges include reluctance to accept global harmonization; confusing terminology, with different terms being used to define the same concept and different concepts being associated with the same term (e.g., even the term recommendation has multiple interpretations); lack of resources, not just funding, but also scientific interest and political acceptability (e.g., because of trade implications); lack of data in some countries or populations (e.g., HIV/AIDS population); lack of openness, or sharing, of data, technology, and results because of legal or political constraints; lack of clarification around uncertainties of recommended numbers; difficult decisions about inclusion versus exclusion of evidence when setting recommendations; different endpoints among countries and regions; differences in the updating of recommendations; the difficulty of bringing existing methodologies together (i.e., from different regions or countries); and lack of access to information on harmonization (e.g., at meetings like this).

BENEFITS, BARRIERS, AND CHALLENGES ASSOCIATED WITH GLOBAL HARMONIZATION OF METHODOLOGIES FOR NUTRIENT INTAKE RECOMMENDATIONS

In the final session, panelists shared experiences from countries that have collaborated with other countries or entities to develop nutrient intake recommendations. First, Christophe Matthys, assistant professor in human nutrition at the University of Leuven, provided an overview of how the European Micronutrient Recommendations Aligned (EURRECA) network has addressed a range of scientific questions and policy development issues, beginning with how to define endpoints in the determination of nutrient requirements. EURECCA’s approach, he described, is based on three criteria: (1) new scientific evidence, (2) public health relevance, and (3) heterogeneity in existing recommendations (e.g., different vitamin D recommendations in neighboring countries). EURRECA’s other work revolves around translating physiological requirements into recommendations, particularly in the case of uncertainty; questions on the added value of a scientific advisory body and issues around stakeholder involvement; the use of nutrient recommendations in policy making; and involvement of consumers in dietary guideline development, with a main challenge being how to explain uncertainty.

Unlike EURRECA, which EFSA’s Hildegard Przyrembel, Federal Institute for Risk Assessment, Berlin (emerita), described as a project, EFSA, she emphasized, is an institution. Specifically, EFSA is an independent organization that assesses and communicates risks associated with the food chain, but is not allowed to make recommendations. She discussed EFSA’s recent growth in response to a 2005 request from the European Commission to revise and add missing values to the 1993 dietary reference values. In Przyrembel’s opinion, the approach for setting reference values is similar in different regions of the world. The difference, she said, lies in the amount of money, personnel, knowledge, data collection, and time available. Thus, one of the challenges to harmonization, and one that EFSA has faced, is finding experts with enough time and knowledge and the readiness to travel. Another challenge, she observed, is finding consensus in a heterogeneous group of experts. But there are advantages too, she continued, such as EFSA’s comprehensive databases on food consumption and composition. She encouraged between-country technical conferences and better between-institution communication when setting nutrient reference values.

Ntambi offered insights into several challenges to harmonization across Africa: limited capacity to handle food and nutrition issues, including NIVs; diversity in foods, dietary patterns and habits, seasonal food supplies, and agricultural practices (e.g., the nutrients in plantains in one region may be very different than those in plantains in another region); the reality that the challenge is not only to develop a unified approach to determining NIVs, but also to build the capacity needed to develop this approach both in individual countries and across Africa as a whole; the scattering of information

among academic institutions and interested agencies; and questions around how to coordinate existing national and regional bodies across Africa that handle food and nutrition issues. He noted that many of these organizations have begun the process of generating NIVs but have run out of resources.

Even though Norway is considered “one of the richest and best countries in the world,” Helle Margrete Meltzer, research director at the Norwegian Institute of Public Health, said it cannot afford to develop guidelines on its own. It has been collaborating with the other four Nordic countries for decades, most recently on the fifth edition of nutrition recommendations (issued in 2012). The fifth edition, according to Meltzer, focuses on nutrients of particular relevance to the Nordic countries, namely vitamin D, iodine, iron, fatty acids, and fats. Of note, it was also the first revision that involved working with systematic reviews. Because working on systematic reviews was new to most of the approximately 100 nutrition experts involved with the revision, combined with the fact most of the reviewers were unpaid and working during their free time, it was, she said, a “huge undertaking.” It was a slow process, one with many pitfalls (e.g., conducting systematic reviews requires knowledge about biases) and with large volumes of publications to examine. One of the “learning points” from this work, Meltzer concluded, is that global harmonization will require a nutrition specialty in systematic reviews.

The final speaker of this session, Emorn Udomkesmalee, senior advisor at the Mahidol University Institute of Nutrition, called attention to the wide range of recommended protein intakes across Southeast Asia. For example, among 4- to 6-year-olds, the recommended protein intake is 35 grams per day (g/day) in Indonesia, 21–22 g/day in the Philippines (females/males), 25 g/day in Vietnam, and 16 g/day in Malaysia. Such differences across very connected countries is “why we are here,” she said. In her opinion, it is not the approach to setting recommendations that is the problem, as all of these countries use similar approaches. Rather, the problem, she said, is judgment. These countries are challenged by limited expertise on local committees and major gaps in relevant data, even when setting recommendations for healthy populations. Udomkesmalee called for harmonized guiding principles that countries can follow when decisions need to be made and evidence is missing. More specifically, she called for harmonized guiding principles that address the diversity in context among countries.

THOUGHTS ON MOVING THE CONVERSATION FORWARD

In her closing summary, Atkinson identified three key messages.⁸ First, she said, “We would value a standardized methodological approach with rigorous scientific review of the literature.” Preferably, she added, this would be a centralized collaborative. She referred to King’s concept of a global consultative group on nutrient recommendations (i.e., King had proposed that such a group could serve as a resource for countries to build on the experiences of others) and suggested that perhaps FAO or WHO consider organizing such a group. Second, she called for recognition of the special needs of particular geographic regions, or countries, related to food composition, dietary surveys, bioavailability, and health status. Third, she stated that there is a desperate need to fill knowledge gaps and improve the science on which to derive nutritional requirements that include phenotypic differences across the world.

Atkinson suggested, as a first next step, a scoping of already completed work, perhaps through the aforementioned global consultative group. “I do feel this isn’t the end,” she said. “It’s only the beginning.”

The workshop’s parting words were provided by Francesco Branca, director of the WHO Department of Nutrition for Health and Development, who commented on the many divergences in nutrient intake recommendations not grounded in real biological differences, but in differences in interpretation, methodology, and terminology. We are “humbly here,” he said, and will build on “what you have started to construct today.”♦♦♦

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DISCLAIMER: This Proceedings of a Workshop—in Brief was prepared by Leslie Pray as a factual summary of what occurred at the workshop. The statements made are those of the rapporteur or individual workshop participants and do not necessarily represent the views of all workshop participants; the planning committee; or the National Academies of Sciences, Engineering, and Medicine.

REVIEWERS: To ensure that it meets institutional standards for quality and objectivity, this Proceedings of a Workshop—in Brief was reviewed by Hildegard Przyrembel, Federal Institute for Risk Assessment; and Inga Thorsdottir, University of Iceland. Lauren Shern, National Academies of Sciences, Engineering, and Medicine, served as the review coordinator.

SPONSORS: This workshop was partially supported by the Bill & Melinda Gates Foundation, the Food and Agriculture Organization of the United Nations, and World Health Organization.

For additional information regarding the workshop, visit https://nationalacademies.org/hmd/activities/global/approachestonutrientintakerecommendations.

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Global harmonization of methodological approaches to nutrient intake recommendations: Proceedings of a workshop—in brief. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24989.

Health and Medicine Division

Copyright 2018 by the National Academy of Sciences. All rights reserved.