Book Gibson RS, Principles of Nutritional
Assessment: Development of
Nutrient Reference Values


3rd Edition
April, 2021

Abstract

This chapter describes the evolving process of setting nutrient reference values (NRVs) from a single value to a multi-level approach designed to address multiple users and needs. This multi-level approach with some modifications has been adopted by several authoritative groups. However, discrepancies in the terminology and methodologies has led to an initiative to develop a  four-step framework for harmonizing the process for deriving two core NRVs. The feasibility of the proposed framework has been tested with three exemplar micronutrients (zinc, iron, folate) on two high-risk pop­ula­tion sub­groups — young children and women of reproductive age. The framework can be applied across countries and a variety of pop­ula­tion sub­groups, while taking into account culturally and context-specific food choices and dietary patterns. Derivation of the two core NRVs depicted in the framework — the Average Requirement (AR) and Upper Level of Safe Intake (UL) — is presented here. Details of additional NRVs used are also described. They include the Recom­mended Intake (RI) (analogous to the RDA or RNI) used to guide intakes of individuals, the Lower Reference Intake (equivalent to the AR −2SD), and a Safe or Ade­quate Intake value used when insufficient information is available to set an AR. Details of the different methods used to establish recommendations for energy and macronutrients are also described. A review of the NRVs currently in use by the United Kingdom, USA and Canada, European Union, and WHO/FAO is also presented, together with the potential sources of discrepancy. In a final section under “Future directions”, reasons for harmonizing the process to derive NRVs globally are emphasized together with the six core values considered essential for the success of this initiative.

CITE AS: Gibson RS. Principles of Nutritional Assessment. Nutrient Reference Values. https://nutritionalassessment.org/nrv/
Email: Rosalind.Gibson@Otago.AC.NZ
Licensed under CC-BY-SA-4.0

8a.1 Development of Nutrient Reference Values

The first set of nutrient reference values (NRVs) was produced by the Technical Commission on Nutrition, League of Nations, (1938). The recommendations of this Commission formed the basis for the first Canadian Dietary Standard compiled by the Canadian Council on Nutrition (1940). In 1943, the United States Food and Nutrition Board (1943) prepared the first U.S. Recom­mended Dietary Allowances (RDAs) for protein, energy, and eight vitamins and minerals. This was followed by periodic revisions of the U.S RDAs and a number of joint publications by the World Health Organization/Food and Agriculture Organization on recommendations for different groups of nutrients (FAO/WHO, 1974; FAO/WHO, 1988). By 1989, the U.S RDAs included 25 vitamins and minerals in addition to protein and energy.

Until this time, these reports provided a single estimate of requirements (i.e., the RDA or equivalent) that was sufficient to meet the needs of almost all individuals in a specific life-stage group. Nevertheless, despite being set for individuals, the RDAs were being applied to pop­ula­tion data and used for many different purposes. This misuse of the RDA led to the development of new approaches to address multiple users and needs. The first country to adopt a framework that embraced three nutrient reference levels was the United Kingdom (COMA,1991) (Section 8a.4). This was followed by the release by the U.S. Food and Nutrition Board (FNB) of a new paradigm of Dietary Reference Intakes (DRIs) (National Academic Press, 2000). Their approach, developed jointly by the U.S. and Canada, also provided multiple reference levels for each nutrient and included for the first time an upper intake value (UL) as well as the concept of reducing the risk of chronic diseases

This new multi-level approach was soon adopted with some modifications by other authoritative bodies worldwide, including in China; Korea and Southeast Asia; Germany, Austria, Switzerland; Australia and New Zealand; and Mexico. Most established an Estimated Average Requirement (EAR) and a RDA (or equivalent) at two standard deviations above the EAR, although the exact terms used differed. Some authorities also included a UL for certain nutrients, and in many cases, a safe or ade­quate intake value (or range) when insufficient information was available to set an EAR (King et al., 2007).

One of the latest developments includes the introduction of a systematic review process to identify data relevant to the derivation of NRVs. This initiative was introduced in 2007 by the EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence (NoE) (Dhonukshe-Rutten et al., 2013), and used for the first time for the revision of the NRVs for vitamin D and calcium in the U.S. and Canada (IOM, 2011). More recently, efforts have been made to overcome some of the challenges encountered when setting nutrient reference values for chronic disease prevention; these efforts are on-going (Yetley et al., 2017).

There is now considerable interest in providing a framework for harmonizing the process to derive NRVs that can be applied across countries and a variety of pop­ula­tion sub­groups, while taking into account culturally and context-specific food choices and dietary patterns. This international harmonizing initiative first began in 2005 with the development and publication of several background review papers and a consensus report on “Harmonization of nutrient intake values” (King and Garza, 2007)

The first harmonization initiative was followed a decade later with an international workshop convened in 2017 by the National Academies of Sciences, Engineering, and Medicine (NASEM) in partnership with WHO and FAO to explore the evidence for achieving global harmonization of methodological approaches to derive NIVs across countries; see NASEM, 2018a for the report of the workshop proceedings. At this workshop, the term Nutrient Reference Values (NRVs) was adopted to describe collectively the nutrient intake recommendations and is analogous to terms currently in use such as Dietary Reference Intakes (DRIs) in the United States and Canada and Dietary Reference Values (DRVs) in the United Kingdom and the European Union (Table 8a.1).

Table 8a.1: Comparison of the suggested “recommended” terminology with terms in use at present by USA/Canada, UK, European Union/EFSA and WHO/FAO.
AI, adequate intake; AMDR, adequate macronutrient distribution range; AR, average requirement; DRI, dietary reference intake; DRV, dietary reference value; EAR, estimated average requirement; LRNI, lower reference nutrient intake; LTI, lowest threshold intake; NIV, nutrient intake value; PRI, population reference intake; RDA, recommended dietary allowance; RI, reference intake range for macro-nutrients; RNI, reference nutrient intake (UK), recommended nutrient intake (WHO/FAO); SIV, Safee intake value; SUL, Safe upper level; UL, tolerable upper intake level; UNL, upper nutrient level
Adapted from King and Garza (2007).
Recom-
mendation
Recom
mended
terms
USA/
Canada
UKEuropean
Union/
EFSA
WHO/
FAO
Umbrella term for
the set of recom-
mendations
NRV DRIDRVDRV
Average
requirement
AREAREARAR
Recommended
intake level
RIRDARNIPRIRNI
Lower reference
intake
LRNILTI
Adeqiate
intake
AIAISIVAI
Safe upper level
of intake
ULULSULULUL
Appropriate
macronutrient
distribution
range
AMDRAMDRRIPopulation
mean intake
goals

Recom­mendations from the workshop for the terms for the four core reference values and the relationship between them is shown in Figure 8a.1.

Figure 8a.1
Figure 8a.1: United States and Canadian Dietary Reference Intakes definitions showing the relationship of the observed level of intake to the risk of inadequacy/toxicity. The Estimated Average Requirement (EAR) is the intake at which the risk of inadequacy is 0.5 (50%) to an individual. The Recommended Dietary Allowance (RDA) is the intake at which the risk of inadequacy is very small — only 0.02 to 0.03 (2% to 3%). At intakes above the Tolerable Upper Intake Level (UL), the risk of adverse effects increases. Modified from NASEM (2018).
The four reference values are: the Average Requirement (AR), Recom­mended Intake (RI), Ade­quate Intake (AI), and Safe Upper intake level (UL). Of these, both the AR and UL are used to plan, assess, and evaluate nutrient intakes at the pop­ula­tion level, whereas the RI is the appropriate reference to use for the assessment and planning of intakes for an individual. However, when there is insufficient evidence to set an AR, then an AI is derived based on observed or experimentally determined estimates for an apparently healthy pop­ula­tion. For more details of the derivation of these core reference values, see Sections 8a.2.4 for AR and Section 8a.3 for RI and the AI.

8a.2 Harmonization of methodological approaches to derive Nutrient Reference Values

An initial organizing framework for deriving NRVs, developed in the 2005 workshop (King and Garza, 2007), is depicted in Figure 8a.2.
> Figure 8a2
Figure 8a.2: An initial organizing framework for deriving NRVs. Adapted from King and Garza (2007).
This initial organizing framework emphasizes on the left the concepts that serve as the basis for setting the two recom­mended NRVs. Their uses at both the individual and pop­ula­tion level are shown on the right, along with other critical health applications of the NRVs. The two core reference values — the AR and the UL — are prioritized, from which other reference values are derived. The individual recom­mended intake level (RI) is used to guide intakes at the individual level, and is conventionally set to cover the needs of 98% of individuals.

Of the two core reference values, the AR is defined as the intake needed by 50% of a pop­ula­tion sub­group (based on age, gender, and physiological status) to meet a  specific criterion of nutrient ade­quacy. NASEM, 2018 emphasize that the AR should:

* Some nutrient-nutrient interactions are now known to alter requirements (e.g., calcium-protein-sodium, protein-energy; vitamin E and polyunsaturated fatty acids).

** The term “apparently healthy” has come into question because of the implication of rising global prevalence of overweight and obesity and the corresponding increase in chronic disease risk. The NASEM (2017) report on developing dietary reference intakes based on chronic disease recommends that for future NRVs, the health status of the pop­ula­tion should be characterized in terms of who is included and excluded for each NRV.

The second core reference value — the UL — is defined as the highest level of usual daily nutrient intake that poses no risk of adverse health effects in most individuals in the pop­ula­tion and is based on a toxicological risk assessment model (IOM, 1998). For details of the derivation of the AR and UL, see Sections 8a.2.4 and 8a.2.5.

Based on the deliberations of a second workshop held in 2017 that reviewed the strengths and weaknesses of the methods currently in use, a new framework for harmonizing the process for deriving the two core nutrient reference values (i.e., AR and UL) was developed. This is presented in Figure 8a.3
Figure 8a.3
Figure 8a.3: Framework for harmonizing the process to derive NRVs. Modified from Russell et al. (2018b).
that shows the four major steps required to estimate the key NRVs, with the components needed to complete the steps itemized. The four steps are:
  1. Choosing the appropriate tools and resources;
  2. Collecting relevant data from the tools and other resources;
  3. Identifying the best approach for the nutrient under consideration; and
  4. Deriving the two core nutrient reference values, the average requirement (AR) and the tolerable Upper Limit (UL).

The feasibility of this proposed harmonization framework was tested using three exemplar nutrients —z inc, iron, and folate, nutrients of concern for young children and women of reproductive age; for more details, see NASEM (2018b).

8a.2.1 Choosing the appropriate tools and resources

The primary tools and resources needed to develop the NRVs are: systematic reviews, comprehensive databases, and information about relevant local and regional factors that can influence the NRVs, as shown in Figure 8a.3. The EURECCA network applied the systematic review process to identify data relevant to the derivation of NRVs, using six micronutrients as examples; see Hooper et al., 2009; Van 't Veer et al., 2013; and Dhonukshe-Rutten et al., 2013 for more details. sub­sequently, systematic reviews of bio­markers of status for vitamin B12, zinc, iodine, copper, riboflavin, magnesium, vitamin D, poly­phenols, n-3 long-chain poly­unsaturated fatty acids, and selenium were published (Allen et al., 2009; Pérez-Jiménez et al., 2010; Witkowski et al., 2011). These existing systematic reviews can be updated, or new systematic reviews initiated, where necessary.

Efforts have been made to harmonize the protocols for systematic reviews (Moher and Tricco,2008.) The first step is to use the PICO/PECO model to define the search terms and concepts for the systematic review; this model is described in Box 8a.1.

Box 8a.1: The PICO/PECO Model

The elements in the model are:

Modified from NASEM, 2018b

In addition to using the PICO/PECO model, construction of a predefined analytic framework (e.g., a causal pathway) is also recom­mended to help identify systematic review questions. An example for a generic analytic framework for NRVs is depicted in Figure 8a.4.

Figure 8a.4
Figure 8a.4: Generic analytic framework for a systematic review of studies on the association between a nutrient and health outcomes. Modified from Russell et al. (2009) and NASEM (2018b).
The representation includes putative associations between an exposure (e.g. a nutrient) and dietary biomarkers of intake (e.g., status biomarkers such as serum or tissue nutrient concentrations, (non-validated) intermediate biomarkers (possible predictors of health or clinical outcomes), (valid) surrogate biomarkers (predictors of health or clinical outcomes), and health or clinical outcomes. The solid arrows represent established associations among factors. Line thickness represents the relative directness of an association and the strength of the relation with the health or clinical outcome. Dotted lines represent associations to surrogate biomarkers for which there is no good evidence of an association. Surrogate biomarkers are often used when the study duration is too short to show an effect on health or clinical outcome.

The analytic framework describes the relationships between “exposure” (i.e., nutrient intake) and outcomes of interest, and helps to emphasize what aspects are known and unknown. Note that the analytic framework should be modified to reflect the underlying biological factors associated with a specific nutrient, the life-stage group, and the reference value of interest (i.e., AR or UL). For example, if the AR is the reference value of interest, then the outcome could be a clinical or health condition or a surrogate biomarker (preferably a functional biomarker of nutrient status) associated with deficiency of the nutrient, whereas for the UL, the clinical or health condition or surrogate biomarker associated with nutrient excess would be selected; see Hooper et al., 2009; and Calder et al., 2017 for details on the selection of reliable surrogate biomarkers. In most cases, a single outcome that serves as a measure of exposure is selected for the AR or UL for a specific nutrient, sex, and life-stage group.

The review of the literature for the systematic review should be guided by the completed PICO elements, associated inclusion criteria, and the analytic framework for the nutrient, life-stage group, and NRV of interest. Quality assessment instruments (QAIs) must be used to evaluate the evidence at the individual study level, the choice depending on the study design. Numerous QAIs are available. SIGN 50 is an example of a QAI that can be used for both randomized controlled trials and observational studies. In addition, a risk-of-bias tool such as the Cochrane Risk of Bias Tool for evaluating randomized controlled trials (Higgins and Green, 2011), or the RoB 2 tool (Sterne et al., 2019) for randomized studies, can also be used.

The strength of the body of evidence generated from a systematic review must also be evaluated using QAIs. Examples include PRISMA , AMSTAR2 (Shea et al., 2017), and GRADE (Balshem et al., 2011). The latter has been used by both Australia/New Zealand and WHO in their revisions of Nutrient Reference Values. These tools have quality descriptors for criteria such as study selection and data exclusion, risk of bias, sources of funding, inclusion of nonrandomized studies, and issues around heterogeneity, etc. Application of QAIs at both the individual study level and systematic review level serves to enhance the scientific rigor and transparency of the decision- making process for deriving the NRVs. Note: nutrition-specific QAIs are under development and will be available in the future.

Readers interested in conducting a systematic review are advised to consult the Systematic Review Data Repository (SRDR). This is an open access, Web-based repository of systematic review data compiled by the U.S. Agency for Healthcare Research and Quality and is available free to users worldwide.

8a.2.2 Collecting data from the tools

The next step is to collect the data generated from the tools that are essential for selecting the biomarkers of status, surrogate outcomes, and health/clinical outcomes. Data on the dietary factors with the potential to influence nutrient bioavailability and the health factors (e.g., infection) that can affect nutrient requirements must also be included.

8a.2.3 Identifying the best approach for deriving the NRVs for the nutrient of interest

Once the relevant data have been collated, the evidence appraised and integrated using the appropriate resources, and any sources of uncertainty identified, the next step is to identify the best approach for deriving the NRVs for the nutrient under study. Three approaches are available: factorial approach, balance studies, and an intake (dose)-response assessment. Limitations of each of these approaches are discussed in Claessens et al., 2013. The decision on which approach to use depends on the availability of data, and the types and quality of studies reviewed (Section 8a.2.1). Table 8a.2
Table 8a.2: Approaches and study types used to derive micronutrient requirements
* The factorial approach relies on measurements of a variety of factors including requirements for growth, pregnancy and lactation, and fecal and urinary losses that determine requirements to maintain plasma levels or body stores resulting in normal tissue and body function and prevention of adverse health effects (reference values derived by this approach also rely on the application of a bioavailability factor to convert the physiological requirement into a dietary intake value)
** The dose–response approach is based on the prediction of a physiologically relevant outcome that could be the measurement of an accepted micronutrient status biomarker in response to dietary intake, or the assessment of clinical disease endpoints in relation to intake or status.
RCT: Randomized controlled trials. Adapted from Matthys et al., 2011.
Study type Principle of method Study design Applicable
groups
Factorial Approach*: Physical or metabolic outcome
Metabolic balance
studies at various
intake levels
Long-term intake = Long-term losses
Requirement: intake level at which
balance (stable body pool, rate of
absorption and excretion) cannot be
maintained.
Cross-sectional
and prospective
All age
groups
Growth studies,
biochemical
studies
Rate of accumulation of nutrients in
the body (fetus, placenta, etc.), breast
milk composition and volume
Cross-sectional
and prospective
Fetus, infants,
pregnant, &
lactating
women
Dose-response**: Health Outcome
Depletion/
repletion
studies
Symptoms occur in response to
dietary insufficiency and alleviate
with sufficiency
RCT Young adults
Biochemical/
biological
studies)
Identification of subclinical defic-
iencies or reduction/lack of function
in relation to specific micronutrient
RCT and
cross-sectional
All age
groups
Epidemiological
studies
Identification of (chronic) diseases
(functional outcomes)
Observational,
interventional
Adults,
elderly
provides examples of the types of studies required to derive ARs based on the factorial approach and dose response modeling.

The factorial approach is currrently used to determine NRVs for iron and zinc, as in these cases the relationship between exposure (nutrient intake) and surrogate biomarkers or a clinical/health outcome is weak or non-existent and cannot be derived mathematically. Factorial estimates are derived from the sum of obligatory losses (i.e, through fecal, urine, skin, menses etc ) plus any additional needs for growth and development (fetus, pregnancy, lactation etc), adjusted by a bioavailability factor to convert the physiological requirement into the dietary requirement (Fairweather-Tait and Collings, 2010). The Average Requirement (AR)is derived from a resultant pooled estimate of needs, taking into account the bioavailability (Dhonukshe-Rutten et al., 2013). State-of-the-art isotope techniques are now used to measure nutrient fluxes and “true” absorption and retention rates. The potential influence of diet- and host-related factors on nutrient bioavailability is reviewed in Gibson, 2007.

Balance studies are used when no reliable biomarker representative of actual nutrient status exists. They measure input and excretion — when they are equal it is assumed that the body is saturated. Additional assumptions are that the size of the body pool of the nutrient is appropriate, and that increasing the levels of nutrient intake do not provide additional benefit. Balance studies are used to determine protein, and in some cases, mineral requirements (e.g., calcium, copper and molybdenum).

Intake (dose)-response modeling, usually based on randomized controlled trials (RCTs) and epidemiological studies, describes how a known physiological outcome changes according to the exposure (i.e., intake) of a nutrient. It is used when there is a clear relationship between the exposure (i.e., intake) of a nutrient and the physiological relevant outcome. The latter may be a biomarker of function, disease, or other health outcome (see Figure 8a.4). These may differ for a specific nutrient from one life-stage group to another because the critical function or the risk of disease may be different. EURECCA conducted a series of systematic reviews (Hooper et al., 2009; Van 't Veer et al., 2013; and Dhonukshe-Rutten et al., 2013) examining the intake-response relationship for several micronutrients in relation to health/clinical outcomes or surrogate outcomes associated with deficiency in order to establish a causal relationship between nutrient intake and a deficiency disease. Such relationships can be complex and influenced by many confounders and effect modifiers (e.g., ethnicity, life-stage group, body mass index, acute illness, and genotype etc). As noted earlier, surrogate outcomes are often used in RCTs when the study duration is too short to show an effect on health or clinical outcomes.

In addition to the focus on the prevention of nutrient deficiency, intake-response modeling can also be used to determine a safe upper intake level (i.e., ULs) (Section 8a.2.5) and chronic disease endpoints (Section 8a.3).

The final stage is to establish the two core NRVs for the nutrient(s) of interest and for the defined sex and life-stage group using the approach selected based on the available evidence. The two core NRVs are the Average Requirement (AR) together with the associated distribution of the requirement, and the Upper Level of Intake (UL). Strenuous efforts should be made to establish the AR for each nutrient because it is the basis for the multiple reference values; details are given below.

8a.2.4 Deriving the Average Requirement (AR) for a nutrient

The requirements for a specific nutrient vary from individual to individual and thus form a distribution of requirements. For most nutrients except iron, this variation in requirements is assumed to follow a normal symmetrical distribution as shown in Figure 8a.5,
Figure 8a.5
Figure 8a.5: Frequency distribution of the individual requirements (mg) of nutrient X in women 30–50y, reflecting variability in requirements among individuals. Adapted from King et al., 2007.
valid for a defined level of nutrient ade­quacy and a specific sex and life-stage group. Consequently, a coefficient of variation (CV) (i.e., the standard deviation divided by the mean × 100%) can be used to estimate the variation. In cases where requirements are not normally distributed (e.g., iron requirements for menstruating adolescent girls and women of child bearing age), data are transformed to achieve normality. For many nutrients, the distribution of requirements is unknown, and instead is assumed to have a CV of about 10% (i.e., the standard deviation is about 10% of the mean requirement), assuming a normal distribution (King et al., 2007).

Inter-individual variability in requirements is affected by numerous diet- and host-related factors (Gibson, 2012). However, many of these factors are difficult to measure, or their impact is unknown. EURRECA explored the biological variation in requirements associated with single nucleotide polymorphisms (SNPs) on the metabolism of five micronutrients (Claessens et al., 2013) but to date no information related to SNPs has been used in the derivation of NRVs due to a lack of relevant data. The EURRECA database, for example, in the future may allow some of these host-related factors to be considered when compiling ARs, to take into account inter-individual variations in requirements.

The median of the requirement distribution represents the Average Requirement (AR) for that particular group of individuals (Figure 8a.6)
Figure 8a.6
Figure 8a.6: Average requirement (AR) for a nutrient. The nutrient requirements are defined in relation to a frequency distribution of individual requirements. RI or the equivalent is defined as two standard deviations above the AR.
and is used to assess the prevalence of ade­quacy within that group (see Chapter 8b for more details). Therefore, by definition the AR is:
“the amount of nutrient that is estimated to meet the nutrient requirement of half the healthy individuals in a specific life-stage and sex group”.

For certain groups (e.g., the elderly, infants, children, pregnant and lactating women), the requirements are often extrapolated from measurements made on young adults, because of the paucity of relevant research data available for these "understudied” life-stage groups. Various methods of scaling (both interpolation and extrapolation) can be used to define values for these sub­groups based on known data for other pop­ula­tions (e.g., adults). Extrapolation can be based on body size, lean body mass, energy intakes, and activity levels, although the methods and factors used are not always transparent and consistent across expert groups; see Atkinson and Koletzko (2007) for more details.

8a.2.5 Deriving the Upper Intake Level (UL)

Upper levels of intake (ULs) represent daily intakes, that if consumed chronically over time, will have a very low risk of causing adverse effects. Intakes from all sources are considered: food, water, nutrient supplements, and pharmacological agents. The UL is defined as:
“The highest level of habitual nutrient intake that is likely to pose no risk of adverse health effects in almost all individuals in the general pop­ula­tion (King and Garza, 2007).”
The ULs are based on a toxicological risk assessment model involving a four-step process:

Box 8a.2: Four-step toxicological risk assessment model

The dose-response assessment is built upon three toxicological terms: no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL), and uncertainty factor (UF). These terms are defined in Box 8a.3.

Box 8a.3: Dose-response assessment

From (IOM, 1998).

At present, ULs are only set for those nutrients for which there is strong, high quality evidence. Like ARs, ULs vary by age and sex and tend to be lower for young children and pregnant women. The goal is to have less than 5% of a pop­ula­tion sub­group with an intake greater than the UL, including intakes from supplements and fortified foods (IOM, 1998). This goal can sometimes be challenging for pop­ula­tion sub­groups consuming fortified cereals (Arsenault and Brown, 2003). For more details on the derivation of ULs, refer to WHO/FAO (2005).

8a.3 A review of Nutrient Reference Values set by the UK, U.S./Canada, European Union, and WHO/FAO

Before reviewing the NRVs established by each of the four individual authorities, it is stressed again that the process of setting nutrient reference values has evolved from setting a single value, equivalent to the RI, to specifying multiple reference values: In addition to establishing the two core NRVs — the Average Requirement (AR) and Upper Intake Levels (UL) — for a specific nutrient and described in Sections 8a.2.4 and 8a.2.5, other NRVs are often specified and used for multiple purposes, some with a focus on optimizing health and preventing chronic diseases rather than the prevention of nutritional deficiencies. The more important of these other NRVs( the RI, LRI, and AI) are listed in Table 8a.1 and summarized below. The reader is advised to consult Table 8a.1 for a comparison of the recommended terminology with the terms currently used by these four authorities (Lupton et al., 2016).

In addition, the problems of setting NRVs for energy and some macronutrients, as well as NRVs for Chronic Disease Prevention, have also been faced by all four authorities. Comments on these difficulties are also considered below.

Nevertheless, many of the principles used previously to define NRVs remain the same (Box 8a.4); see Section 8a.2 for more details.

Box 8a.4: Underlying principles in defining NRVs

Recommended Intake (RI) (or equivalent) has been established by all authoritative groups. The RI is derived from the AR and its distribution (Figure 8a.6) and is used to assess intakes and plan diets for individuals. Currently, the convention has been to add 2SD to the observed AR to cover the needs of most (i.e., 98%) of individuals of the pop­ula­tion. This means that an individual whose intake is equal to RI98 (i.e., AR + 2SD of the AR) has a 98% probability that their intake meets their needs (Figure 8a.6).

In the initial harmonization initiative in 2005 (King and Garza, 2007) it was suggested that in the future countries might wish to choose a lower percentile level deemed to represent an acceptable risk for nutrient inade­quacy for an individual in their country instead of the conventional 98% (i.e., RI98). To date, this suggestion has not been adopted.

Lower Reference Intake (LRI) (or equivalent) is also derived from the AR and its distribution and is set at 2 SD below the AR for each nutrient. This reference level represents the lowest intake that will meet the needs of some individuals. It has been established only by the UK and EFSA (Table 8a.1).

Ade­quate Intake (AI) (or equivalent) is applied when there is not enough information to establish an AR for a specific nutrient. The AI is defined as the observed or experimentally derived usual intake by a pop­ula­tion group that appears to sustain health (King and Garza, 2007).. The methods used to estimate the AIs vary. For example, for infants < 6mo, AIs are generally based on mean nutrient intakes (except vitamin D) supplied by human milk, whereas for children and adults the AIs can be derived from observed median intakes from national survey data, based on limited experimental data, or in some cases, epidemiological studies (Trumbo et  al., 2013).

In general, mean usual nutrient intakes at the pop­ula­tion level at or above the AI indicate a low probability of inade­quacy. No assumptions can be made, however, about the prevalence of inade­quate intakes when the mean intake of a group falls below the AI. Likewise, if an individual's usual intake equals or exceeds the AI, the diet is almost certainly ade­quate but again when the usual intake of an individual falls below the AI, no estimate can be made of the probability of nutrient inade­quacy (IOM, 2000). As noted previously, the Harmonization Committee urged that strenuous efforts should be made to establish an AR for each nutrient so that the inappropriate use of an AI can be avoided.

Energy Requirements are based on the average requirements (AR) for energy of individuals in a specified sex and life-stage group. The recommendations are are not appropriate for the definition of requirements at the individual level. Adding an increment equivalent to 2SD to the average energy requirement would result in a recommendation that exceeds requirements and lead to overweight and obesity over the long term. Energy requirements are derived with the assumption that the requirements for all other nutrients are met (King et al., 2007).

The energy requirement is defined by FAO/WHO/UNU (2004) as:

“The amount of food energy needed to balance energy expenditure in order to maintain body size, body composition, and a level of physical activity consistent with long-term good health. This includes the energy needed for optimal growth and development of children, for the deposition of tissues during pregnancy, and for the secretion of milk during lactation consistent with the good health of mother and child.”
The criterion chosen on which to base the AR for energy is the total energy expenditure (TEE). When body weight and composition is stable in normal-weight individuals, the energy requirement is equal to TEE . In the past TEE for some life-stage groups was estimated indirectly by estimating the amount of energy consumed from self-reported food intakes and equating it with the amount of energy expended. This procedure was used by FAO/WHO/UNU (1985) and the United Kingdom (COMA,1991) to set the energy requirement for young children, but has now been abandoned in view of the concerns about the underestimation of energy intakes due to under-reporting; see Chapter 7 for more details.

The doubly labeled water method (DLW) method is the most accurate method for measuring TEE in free-living individuals and is now used by several authoritative groups including FAO/WHO/UNU (2004), the U.S. IOM (2005 and the UK SACN (2012); see Chapter 7 for details of the DLW method. TEE measured with DLW method includes the energy used to synthesize growing tissues but does not include the additional energy content of the tissue constituents (basically fat and protein) laid down during normal growth and pregnancy, or the milk produced during lactation.

Appropriate Macronutrient Distribution Range (or equivalent) serves as a guide to the distribution of percentage energy consumed as protein, fat, and carbohydrate said to be consistent with both the maintenance of health and a reduced risk of diet-related chronic disease, while providing ade­quate levels of essential nutrients. Increasingly, recommendations are being made for the contribution of free sugars as percentage of energy from total carbohydrate, as well as daily intakes of salt (WHO, 2012; WHO, 2015), dietary fiber, fruits and vegetables. Although in general the range of intakes set are comparable, their meaning and application differ, with those of the United Kingdom (Section 8a.4.6), EFSA (Section 8a.6.6) and WHO (Section 8a.7.6) being pop­ula­tion mean intake goals, whereas those established by the United States and Canada (Section 8a.5.6) are intended for individuals.

NRVs for Chronic Disease Prevention are being developed by several authoritative groups. However, several challenges have been encountered; these are itemized in Box 8a.5:

Box 8a.5: Challenges in defining NRVs for chronic disease prevention Adapted from Yaktine and Ross, 2019.
A Chronic Disease Risk Reduction (CDRR) has been established for sodium in relation to the benfits of a reduced intake of sodium on cardiovascular disease risk, hypertension risk, systolic blood pressure and diastolic blood pressure. The CDRR for sodium was defined as:
“The intake above which intake reduction is expected to reduce chronic disease risk within an apparently healthy pop­ula­tion.” (NASEM, 2019)
For further discussion of these challenges and proposed solutions, see Yetley et al. (2017).

8a.4 U.K. Dietary Reference Values

The United Kingdom was the first country to adopt a frame-work for developing Nutrient Reference Values and these are termed “Dietary Reference Values” (DRVs) in COMA,1991; the frame-work used is depicted in Figure 8a.1. The generic term “Dietary Reference Values” was used to embrace three reference levels: the “Estimated Average Requirement” (EAR = AR), the “Reference Nutrient Intake” (RNI = RI), and the “Lower Reference Nutrient Intake” (LRNI, set at 2SDs below the AR). The term “reference values” was adopted in an effort to prevent users interpreting the figures as recom­mended or desirable intakes. Instead, the expert panel hoped that users would select the figure most appropriate for its intended use (Beaton, 1998).

UK Nutrient Reference Values for certain nutrients are not available for children < 5y of age. NRVs for thiamin and niacin equivalents were recalculated in 2011, based on the revised energy requirements established using a new approach (Section 8a.4.5) (SACN, 2012).

The NRVs for vitamin D for males and females aged 1–18y were also revised in 2016 (SACN) and now include a recommendation for selected life-stage groups to take a daily vitamin D supplement, especially from October to March.

A recent review of nutritional requirements of adults aged > 65y in the UK (Dorrington et al., 2020) has concluded there is evidence to support age-specific UK recommendations for those aged > 65y, for the RNIs for protein (1.2g per kg/d), calcium (1,000mg/d), folate (400µg/d), vitamin B12 (2.4µg/d) although to date, none of these suggested changes have been made by SACN (2016). In contrast, the recommendations for the general pop­ula­tion for sugars, dietary fiber and fatty acids, sodium and alcohol are probably appropriate for older adults.

8a.4.1 U.K. Estimated Average Requirement (EAR = AR) for nutrients

The term “Estimated Average Requirement” (EAR) in COMA,1991 represents the level of the nutrients estimated to meet the nutrient requirement of 50% of the healthy individuals in a particular sex and life- stage group. The EAR is especially useful for evaluating the possible ade­quacy of nutrient intakes of pop­ula­tion groups.

8a.4.2 U.K. Reference Nutrient Intake (RNI)

Reference Nutrient Intakes (RNIs) were defined as 2SDs above the average requirement for each nutrient and represent the target for an individual's nutrient intake COMA (1991) and are shown in (Appendix 8a.1 and 8a.2 ). When data about variability in requirements were insufficient to calculate a SD, a coefficient of variation for the EAR of 10% was assumed. Habitual intakes above the RNI98 will be ade­quate for all but 2–3% of individuals in a specific sex and life-stage group. The RNI should not be used in relation to groups (COMA,1991).

8a.4.3 U.K. Safe Upper Intakes for Nutrients

Safe upper intake levels were set by the U.K Expert Group on Vitamins and Minerals (EVM, 2003). They represents an intake that can be consumed daily over a lifetime without significant risk to health. Intakes from all sources were taken into account. The EVM group defined ULs for vitamin B6, β-carotene, vitamin E, zinc, copper, selenium, boron and silicon, and also provided guidance for those nutrients for which the database was inade­quate to establish a UL. Nutrients in this category included biotin, folic acid, niacin, riboflavin, pantothenic acid, thiamin, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin K, chromium, cobalt, iodine, manganese, molybdenum, nickel, tin, calcium, phosphorus, magnesium, iron, iodine, chromium, tin, and potassium. Suggested levels for these nutrients would not be expected to be associated with any adverse effects. Nevertheless, the EVM acknowledged that for those nutrients for which the database was inade­quate to establish a UL, the suggested levels may not be applicable to all life stages or for lifelong intake, and should not be used as a UL.

8a.4.4 U.K. Additional Levels

Lower Reference Nutrient Intakes (LRNIs) were set by COMA,1991 at two standard deviations below the AR for each nutrient. The LRNIs represent the lowest intakes that will meet the needs of some individuals in the group. The LRNIs are used as a monitoring tool for the UK National Diet and Nutrition Surveys. Habitual intakes below the LNRI are almost certainly inade­quate for most individuals. For confirmation, however, biological parameters should be measured, especially when the nutrient intake of the individual lies between the LRNI and the EAR.

Safe Intake values were also set for some nutrients with important functions in humans, but for which the expert committee considered there were insufficient data to set DRVs (e.g., biotin, pantothenic acid, vitamin E, vitamin K, manganese, molybdenum, and chromium). Safe Intake was judged to be a level or range of intake at which there is no risk of deficiency and below a level where there is a risk of undesirable effects (COMA,1991).

8a.4.5. U.K. Average Requirement for Energy

In view of the increasing risk of overweight and obesity in the U.K., the SACN (2012) adopted a prescriptive approach and identified energy requirement values in relation to the best estimates of healthy body weights. Using this prescriptive approach, an overweight group consuming the amount of energy recom­mended for a healthy weight group are likely to lose weight whereas those underweight should gain weight SACN (2011).

The U.K average requirements for energy for adults of specified age, sex, and height assuming a median physical activity level (PAL) of 1.63 and expressed as MJ/d or kcal/d are available as tables in SACN (2011). Values given in the tables are derived from mean heights in 2009 for England (Health Survey for England 2009). These revised values apply to all adults unless energy expenditure is impaired, when a lower PAL value of 1.49 should be used. For children aged 1-18y, age and sex specific energy requirements, with PAL values ranging from 1.40 to 1.75, are presented, expressed as MJ/d or kcal/d. Separate tables for infants by age and sex who are breast-fed, fed breast-milk sub­stitutes, mixed-feeding or unknown by age and sex are given, expressed as both MJ/kg or kcal/kg per day and MJ/d or kcal/day. The energy requirements for infants were adopted from FAO/­WHO/­/UNU (2004).

The U.K has developed a new factorial approach to establish energy requirements (SACN, 2011). This approach was developed in recognition of the large unpredictable variation between individuals (inter-individual variation) in discretionary activity, This prevents the prediction of total energy expenditure (TEE) as a function of physical activity levels (PALs) predicted from lifestyle information, from being used. This large inter-individual variation in discretionary activities is attributed in part to spontaneous physical activity (SPA). SPA includes body movements associated with activities of daily living, changes in posture, fidgeting, and a propensity for locomotion. An additional issue recognized by SACN (2011), is that PAL values, previously assumed to be independent of body weight, appear to have a complex relationship with body weight (Millward, 2012).

Conventionally, TEE is expressed as a multiple of Basal Metabolic Rate (BMR) and (PAL). Therefore: \[\small \mbox{TEE = PAL × BMR}\] Hence \[\small \mbox{PAL = TEE / BMR}\] In this new approach, the PAL values were derived directly from DLW measurements of TEE in a reference pop­ula­tion instead of applying PAL values predicted from lifestyle information, as used earlier by COMA in 1991 and 1994. Hence, to extract PAL values, TEE values measured by DLW in a suitable adult reference pop­ula­tion were divided by BMR measured or calculated from prediction equations from that same reference pop­ula­tion (Tooze et al., 2007; Moshfegh et al., 2008). From the data on the distribution of PAL values in the adult reference pop­ula­tion, PAL values for the 25th, median, and 75th percentiles corresponding to sedentary, low, and moderate activity were identified: i.e., 1.49; 1.63, and 1.78, respectively.

A separate 2006 data set for children was compiled of all DLW studies of children aged over one year. From these data, PAL values for children aged 1–3y, 3 to less than 10y, and 10–18y were identified. To account for the cost of energy deposition during growth of the children (not included in TEE measured by DLW), the PAL values were adjusted by a simple +1% adjustment of PAL (PAL × 1.01). This results in acceptably low levels of error for children aged 1–18y. Adjusted median PAL values for the three age groups were 1.40, 1.58, and 1.75. The reader is advised to consult SACN (2012) for more details.

8a.4.6 U.K. Ade­quate Macronutrient Distribution Range (AMDR)

The United Kingdom also proposed recommendations for carbohydrate, sugars, fats, and fatty acids. These are not defined in the same way as those for the micronutrients. They represent average intakes for pop­ula­tions and not for individuals, which are consistent with good health, and are expressed as a percentage of daily total energy intake and as a percentage of food energy (i.e., excluding the contribution from alcohol). Table 8a.3
Table 8a.3 UK dietary reference values (DRVs) and the WHO ranges of population nutrient intake goals (2003) for the energy supplying macronutrients for the prevention of diet-related chronic diseases.
Figures are for percentage of total energy, unless otherwise stated. The U.S. and Canadian Acceptable Macronutrient Distribution Ranges (AMDRs) intended for individual adults are shown for comparison.
1 Recommendations apply to adults and children > 5y, unless otherwise stated.
2 Represent the population average intake that is judged to be consistent with the maintenance of health in a population.
a Total fat includes all saturated and unsaturated fat (mono-and polyunsaturated)
b Saturated fat – several studies have shown a high saturated fat intake to be linked with high blood cholesterol. Elevated blood cholesterol is a risk factor for coronary heart disease Studies have shown that replacing saturated fat with unsaturated fat in the diet reduces blood cholesterol and lowers the risk of heart disease and stroke
c This is calculated as total fat−(saturated fatty acids + unsaturated fatty acids + trans fatty acids)
d Total carbohydrate includes all starch, sugars and dietary fiber
e Free sugars are sugars added to foods and drinks by the manufacturer, cook, or consumer, plus sugars naturally present in honey, syrups and fruit juice
f Total fiber is the combination of Dietary Fiber, the edible, nondigestible carbohydrate and lignin components as they exist naturally in plant foods and Functional Fiber, which refers to isolated, or synthetic fiber that has proven health benefits.
g Women should not regularly drink more than 2-3 units of alcohol/day; Men – should not regularly drink more than 3-4 units of alcohol/day
h Target salt intakes set for adults (and children) do not represent ideal or optimum consumption levels, but achievable population goals
* Based on SACN 2015 recommendations for the population ≥ 2y
** Based on COMA 1991 recommendations for the population ≥ 5y
+ Based on WHO Guideline, 2015: Sugars intake for adults and children. Geneva, World Health Organization
++ Based on WHO.Guideline, 2012: Sodium Intake for Adults and Children; World Health Organization: Geneva, Switzerland.
## From USDA U.S. Department of Health and Human Services Dietary Guidelines for Americans (2010) www.dietaryguidelines.gov
### Based on Sodium Intake in Populations: Assessment of Evidence (2013) IOM of the National Academies Press
Dietary
component
UK1, 2WHO2 US/Canadian
AMDRs
Total Fat* Reduce to less than
35% of food energya
(excluding alcohol)
15–30% 20–35%
Saturated Fat Reduce to less than
11% of food energyb
(excluding alcohol)
<10% As low as possible
with a nutritionally
adequate diet
PUFAs 6.5% 6–10%
n-6 PUFAs
(linoleic acid)
5–8%5–10%
n-3 PUFAs
α-linolenic acid
1–2%0.6–1.2%
Trans fatty
acids
< 2% ≤ 1% As low as possible
with a nutritionally
adequate diet
MUFAs By differencec UL not set
Totald
carbo-
hydrate**
50% of food energyd
with free sugars
less than 5%e
55–75% with
free sugars <10%
preferably <5%
(25g/d)
45–65% with added
sugar < 5–15%
total energy##
Protein 15% 10–15% 10–35%
Cholesterol No specific
recom
mendations
< 300mg/d As low as possible
with a nutritionally
adequate diet
Dietary fiber Adults 30g/d Adults 25g/d fTotal fiber AI:
19–50y: 25g/d
> 51y: 21g/d
Fruit and
Vegetables
Increase to ≥ 5
portions (400g) of a
variety of fruit and
vegetables per day
≥ 400g/d 9–10 servings/d
for Canadian adults
5–9 servings/d
for U.S. adults
Alcohol Should not provide
more than 5% of
energy in dietg
Salt (Adults) Not > 6g/d
(2.4g Na)
Not > 5g/d
(2g Na)
< 2.3g/d;
if ≥51y then
< 1.5mg/dh###
summarizes the current U.K. recommendations for the macronutrients (COMA,1991; 1994; SACN, 2016) and compares them with the WHO (2003) pop­ula­tion nutrient intake goals for the prevention of diet-related chronic diseases (Section 8a.7.6). The U.S. and Canadian Acceptable Macronutrient Distribution Ranges (AMDRs) for adults (IOM, 2002) (Section 8a.5.6) are also given for comparison. Note that these U.S. and Canadian recommendations, unlike those set by the United Kingdom, EFSA, and WHO, are intended for use by individuals, as noted earlier.

In the UK, SACN, 2016 included a recommendation for free sugars, stating that the average pop­ula­tion intake of free sugars should not exceed 5% of total dietary energy for persons from 2y of age. They defined free sugars as those sugars added to food or those naturally present in honey, syrups and unsweetened fruit juices, but excluded lactose in milk and milk products. This report also stated that consumption of sugar-sweetened beverages should be minimized in children and adults in view of the evidence that consumption of sugar-sweetened beverages as compared with non-calorically sweetened beverages leads to greater weight gain and increases in BMI. SACN, 2016 also adopted a broader definition of dietary fiber than that adopted earlier, and provided for the first time average pop­ula­tion dietary recommendations for fiber intake for children and adolescents ranging from 15g/d (2–5y) to 30g/d (16–18y); see Pyne and Macdonald (2016) for more details.

8a.5 United States and Canada: Dietary Reference Intakes (DRIs)

The United States and Canada have also adopted a paradigm for nutrient reference values that incorporates data to optimize health, prevent risk of chronic disease and avoid deficiency. Their approach also provides multiple reference values for each nutrient to meet an expanding list of uses. Specifically, the U.S. Food and Nutrition Board has expanded their definition of requirements to:

The nutrient reference values were established by a joint committee of both Canadian and U.S. scientists set up by the U.S. Food and Nutrition Board. The Committee adopted the generic term “Dietary Reference Intakes” (DRIs) for a set of reference values for each life-stage and sex group.

The criterion chosen by the U.S. Food and Nutrition Board to define nutrient ade­quacy differs for each nutrient and, sometimes, within the life-stage groups for the same nutrient; details are given in the separate reports published by the Food and Nutrition Board (1997, 1998, 2000, 2001, 2002) for 35 vitamins and minerals. Updated DRIs for calcium and vitamin D are given in IOM, 2011.

8a.5.1 U.S. and Canadian Estimated Average Requirement (EAR = AR) for nutrients

This is defined as the median requirement for a specified criterion of ade­quacy for individuals of a certain life-stage and gender group. The specific criterion selected is defined by a specific function or biochemical measurement for each nutrient. Values for the EARs for nutrients are available in separate reports of the IOM (1997, 1998, 2000, 2001, 2002). When the mean usual intake of the group is equal to the EAR, 50% of the healthy individuals in that particular life-stage and sex group, meet their requirement and the other half of the group do not. Hence, usual intake at this level is associated with a 50% risk of inade­quacy (Barr et al.,2003).

As noted earlier (Section 8a.2.4), each EAR refers to the average daily nutrient intake of apparently healthy persons over time, and this quantity does not have to be consumed every day. The EAR is especially useful for evaluating the possible ade­quacy of nutrient intakes of pop­ula­tion groups.

8a.5.2 U.S. and Canadian Recommended Daily Allowance (RDA = RI)

This refers to the intake level that meets the daily nutrient requirements of almost all (≈ 98%) of the individuals in a specific life-stage and sex group. Values are given in the separate reports of the IOM (1997, 1998, 2000, 2001, 2002) (Barr et al., 2003). If the variation in requirement is well defined and symmetrically distributed, then the RDA is set at two standard deviations above the EAR: intakes at this level have a probability of ade­quacy ≈ 98% \[\small \mbox{RDA} _{98} \mbox{ = EAR + (2 SD)}\] If a coefficient of variation (CV) for the EAR of 10% is assumed the CV is equal to the SD/EAR, then: \[\small \mbox{RDA} _{98} \mbox{ = 1.2 × EAR }\] Alternatively, if the CV is 15%, then: \[\small \mbox{RDA} _{98} \mbox{ = 1.3 × EAR }\] When the DRIs were first derived, a CV of 12.5% for protein, 15% for copper, molybdenum, and niacin, and 20% for vitamin A, and iodine was applied (King et al., 2007).

No RDA was proposed when there was not enough data to establish an EAR for that nutrient. Because the usual intake at the level of the RDA98 is, by definition, associated with a very low (2–3%) risk of inade­quacy to an individual, the RDA98 is used as a recom­mended intake when assessing intakes and planning diets for individuals. For example, the appropriate target for phosphorus intake for a woman aged 31–50y is the RDA of 700mg. The RDA hould not be used to assess the intakes of groups. RDA values are given in (Appendix 8a.3 and 8a.4 ).

8a.5.3 U.S. and Canada: Upper Tolerable Intake Level (UL) for nutrients

The Upper Tolerable Intake level (UL)for nutrients is the highest usual daily nutrient intake level likely to pose no risk of adverse health effects for almost all individuals in a life-stage and sex group. ULs have not been set for some nutrients with limited scientific data. Details of the adverse health effects used to set the ULs are given in the IOM reports (2000, 2001, IOM, 2011).

For some nutrients such as vitamin C, vitamin A, vitamin D, calcium, phosphorus, magnesium, copper, zinc, iron, selenium, iodine, and manganese, the UL refers to the total intake from all sources, including food, fortified food, water, supplements, and medications, where relevant. For others such as niacin and folate, the UL applies to forms from supplements, fortificants, and medications. The UL for magnesium represents intake from pharmacological agents only and does not include intake from food and water. In some cases, the form of the nutrient for the UL differs from that used for the RDA; examples include vitamin E, niacin, and folate.

The UL should be used by health professionals to ensure that nutrient intakes are not too high. As intake increases above the UL, the risk of adverse health effects increases. The UL is based on risk-assessment methodologies similar to those used in toxicological studies (1998). Figure 8a.1 shows the relationship of the observed level of intake to the risk of inade­quacy and toxicity for the EAR, RDA, and the UL reference values.

8a.5.4. U.S. and Canada Additional Levels

Ade­quate Intake (AI) was also defined by the IOM and refers to a recom­mended average daily nutrient intake level based on observed or experimentally derived approximations or estimates of the nutrient intake by a group (or groups) of apparently healthy people. As noted earlier, for infants aged 0–6mo, the AI represents the nutrient intake values (except vitamin D) supplied by human milk (Allen et. al., 2018). The observed or derived intakes are assumed to be ade­quate. The AI is used when there are not enough scientific data to establish an AR (e.g., for fluoride, chromium, manganese, total fiber, and vitamins pantothenate, choline, and biotin), and is used as an intake goal for individuals. Recently, AIs have also been set for sodium and potassium (NASEM,2019).

8a.5.5 U.S. and Canada: Estimated Energy Requirements

Estimated energy requirements (EER) were compiled by the IOM, and are detailed in IOM, 2005. The EER is defined as the average energy intake required to maintain current body weight and physical activity level (PAL) (and to allow for growth or milk production, where relevant) in healthy, normal-weight individuals of a specified age, gender, height, weight, and PAL. Tables provide values as well as equations based on height, weight, sex, age, and level of activity to predict TEE.

The EER values were based on DLW measurements of energy expenditure, and where relevant, the energy content of the tissue constituents (basically fat and protein) laid down in growing infants and children. When body weight and composition is stable in normal-weight individuals, the energy requirement is equal to total energy expenditure.

Several regression equations were developed for estimating the energy requirements of different life-stage and gender groups. Separate equations for individuals with a normal body weight (ie BMI 18.5–24.9kg/m2) and those overweight or obese (BMI > 25kg/m2) were developed. An example for the equation for normal-weight men aged 19y and above is given below: \[\small\mbox{EER = 661.8 −  (9.53 ×  Age [years]) + PA × (15.91 × Weight [kg] + 539.6 × Height [m])}\] Where PA = physical activity coefficient corresponding to a given physical activity level (PAL). Table 8a.4.
Table 8a.4: Estimated energy requirements (EER) for men of 30y of age1.
1 For each year below 30, add 10kcal/d. For each year above 30 subtract 10kcal/d
2 PAL = Physical activity level
3 Derived from this regression equation based on doubly labeled water data: EER = 661.8−9.53×Age(y) ×PA×(15.91×Wt(kg)+539.6×Ht(m))
Where:
      PA refers to coefficient for Physical Activity Levels (PAL).
      PAL = total energy expenditure  + basal energy expenditure
      PA = 1.0 if PAL ≥ 1.0 < 1.4 (sedentary)
      PA = 1.12 if PAL ≥ 1.4 < 1.6 (low active)
      PA = 1.27 if PAL ≥ 1.6 < 1.9 (active)
      PA = 1.45 if PAL ≥ 1.9 < 2.5 (very active)
Modified from Trumbo et al. (2002).
Height
(m)
Weight (kg)
for BMI of
18.5 kg/m2
Weight (kg)
for BMI of
24.99 kg/m2
PAL2 EER3 (kcal/d)
BMI of
18.5 kg/m2
EER3 (kcal/d)
BMI of
24.99 kg/m2
1.5041.656.2 Sedentary
Low active
Active
Very active
1,848
2,009
2,215
2,554
2,080
2,267
2,506
2.898
1.6550.4 1.50 Sedentary
Low active
Active
Very active
2,068
2,254
2,490
2,880
2,349
2,566
2,842
3,296
1.8059.9 81.0 Sedentary
Low active
Active
Very active
2,301
2,513
2,782
3,225
2,635
2,884
3,200
3,370
shows some sample calculations of EER for men with two different BMI values at three different heights and four different physical activity levels (PALs). Sample values for women are also available (Trumbo et al., 2002). More details of the four different physical activity categories are given in Table 8a.5.
Table 8a.5: Description of physical activity level (PAL) categories. *Walking distance is estimated for the midpoint of the range (i.e., PAL = 1.5 for low active, 1.75 for active, and 2.2 for very active) and for midweight individuals weighing 70kg. Values in parentheses reflect walking distances at the same PAL for relatively heavy weight (120kg) and relatively light weight (44kg) individuals, respectively. Modified from Barr et al., Nutrition Reviews 61: 352–360, 2003.
Physical
activity
category
PAL (multiples of
basal energy
expenditure)
Description Physical Activity
Coefficient (PA)
M ≥ 19y F ≥ 19y
Sedentary 1.0 to < 1.4 Activities of daily
living (ADL) only
1.00    1.00
Low active ≥ 1.4 to < 1.6 ADL plus walking
about 2 miles/d
(1.5/2.9)* or equivalent
1.11    1.12
Active ≥ 1.6 to < 1.9 ADL plus walking
about 7 miles/d
(5.3/9.9)* or equivalent
1.25    1.27
Very active ≥ 1.9 to < 2.5 ADL plus walking
about 17 miles/d
(12.3/22.5)* or equivalent
1.48    1.45
The physical activity coefficients (PAs) for these PAL categories vary slightly among the different regression equations, although the PAL for sedentary individuals is always 1.0 (Barr et al., 2003).

Note for individuals with a BMI ≥ 25, the estimated energy intake required to maintain current weight and activity level is termed the Total Energy Expenditure (TEE) and not the EER. This practice has been adopted because overweight is not consistent with long-term good health (Barr et al., 2003).

8a.5.6. U.S. and Canada Acceptable Macronutrient Distribution Range

This is defined as a range of intakes for a particular energy source associated with reduced risk of chronic disease, while providing ade­quate levels of essential nutrients (IOM, 2002). They are intended for use by individuals, and have been established for carbohydrate, protein, total fat, n-6 poly-unsaturated fatty acids, and α-linolenic acid, as shown in Table 8a.3. Individuals should have intakes that fall within the limits of the AMDRs. If the usual intake of an individual is below or above the AMDR, there is a potential for increased risk of both inade­quate intakes of essential nutrients and chronic diseases (IOM, 2002). Note that IOM have also defined an EAR and RDA for protein.

8a.6 European Dietary Reference Values

In 1993, the Scientific Committee for Food of the European Community (SCEC, 1993) proposed three reference values for each nutrient (Box 8a.6).
Box 8a.6 SCEC Dietary Reference Values
sub­sequently, over a seven-year period, the European Food Safety Authority (EFSA) has generated separate publications on the NRVs for water, fats, carbohydrates, dietary fiber, protein, energy and 14 vitamins and 13 minerals, as well as a summary report (2017).

8a.6.1 European Average Requirements (ARs) for nutrients

The Average Requirement defined by EFSA is the mean requirement of a specific gender and life-stage group. The group was assumed to have a normal, symmetrical distribution, with the exception of the iron needs of menstruating women (2017).

8a.6.2 European Pop­ula­tion Reference Intake (PRI = RI)

EFSA (2017) defined “Pop­ula­tion Reference Intakes” as the intake level ade­quate for virtually all people in a pop­ula­tion group. It corresponds conceptually with the RI98, and hence represents the AR + 2SD.

8a.6.3 European Tolerable Upper Intake Level (UL) for nutrients

This was defined by EFSA as the maximum level of total chronic daily intake of a nutrient (from all sources — food, supplements, fortificants, water) judged to be unlikely to pose a risk of adverse health effects in humans (2017). ULs for six vitamins and eight minerals were established by SCEC in 2006 which are available in a summary report (EFSA, 2018). This report also provides updated information for the UL for vitamin D for infants aged 0–6mo and 6–12mo.

8a.6.4. European Additional Levels

Table 8a.6 European Food Safety Authority Dietary Reference Values for adults. From EFSA (2017). Data for women, where different from that for men, are given in parentheses. MJ: megajoules; DFE: dietary folate equivalents. For combined intake of food folate and folic acid, DFEs can be computed as follows: µg DFE = µg food folate + (1.7 × µg folic acid); NE: niacin equivalent (1mg niacin = 1 niacin equivalent = 60mg dietary tryptophan); RE: retinol equivalent, 1µg RE = 1µg of retinol, 6µg of β-carotene and 12µg of other provitamin A carotenoids. *18–24y; ** > 25y; *** AI (no AR has been set); ^ premenopausal; ^^ postmenopausal; Zn AR and PRI associated with 300, 600, 900, 1200mg phytate/d
Nutrient Average
Requirement
(AR)
Population
Reference
Intake (PRI)
Protein (g) 0.66 g/kg/BW/d 0.83 g/k/BW/d
Vitamins
Vitamin A (µg/d) 570 (490) 750 (650)
Thiamin (mg/MJ) 0.072 0.1
Riboflavin (mg/d) 1.3 1.6
Niacin (mg NE/MJ) 1.3 1.6
Vitamin B6 (mg/d) 1.5 (1.3) 1.7 (1.6)
Cobalamin(µg/d) 4.0*** 4.0
Vitamin C (mg/d) 90 (80) 110 (95)
Folate (µg DFE/d) 250 330
Minerals
Calcium (mg/d) 860*, 750** 1000*, 950**
Phosphorus (mg/d) 550***
Potassium (mg/d) 3500***
Trace elements
Iron (mg/d) 6 (7^, 6^^) 11 (16^; 11^^)
Zinc (mg/d) 7.5;9.3;11.0;12.7
(6.2;7.6;8.9;10.2)
9.4;11.7;14.0;16.3
(7.5;9.3;11.0;12.7)
Copper (mg/d) 1.6*** (1.5***)
Selenium (ug/d) 70***
Iodine (ug/d) 150***
Lower Threshold Intake (LTI) is one of two additional levels defined by the EFSA (2017) panel. The LTI is the intake below which almost all individuals in the pop­ula­tion will be unable to maintain metabolic integrity according to the criterion chosen for each nutrient. The LTI represents the mean − 2SD.

Ade­quate Intake (AI) represents a value estimated when a Pop­ula­tion Reference Intake cannot be established because an average requirement cannot be determined. An AI is the average observed daily level of intake by a pop­ula­tion group (or groups) of apparently healthy people that is assumed to be ade­quate.

The (EFSA, 2017) report presents AI values for infants 0–6mo based on the nutrient supply from human milk. An AI is also given for those nutrients for which the data were deemed inade­quate to set an AR (i.e., fluoride, iodine, manganese, molybdenum, phosphorus, potassium, selenium, copper, magnesium, biotin, choline, cobalamin, pantothenic acid, vitamin D, vitamin K). For a detailed discussion of these reference values, refer to (EFSA, 2017).

The revised European DRVs for micronutrients for adults (> 18y) are shown in Table 8a.6. For some life-stage groups where no data were available, interpolation or extrapolation was used by EFSA to set ARs and PRIs. The reference heights and body weights used by EFSA for children aged 0–2y are from the WHO Child Growth Standard (WHO, 2006), whereas for older children 2–18y they use data from European children (van Buuren et al., 2012). Details of the reference body weights for children and adults used for scaling are given in (EFSA, 2017). Details of the criteria used to set the DRVs for infants (7–11mos, children (1–17y), adults, and pregnant and lactating women together with the type of studies used are also presented.

8a.6.5. European Average Requirement for Energy

The average requirements (ARs) for energy expressed as MJ/d for pop­ula­tion groups within Europe are presented for specified age groups, and by gender for selected physical activity levels (PALs), depending on age; they are of limited use for individuals. ESFA applied the following equation to estimate total energy expenditure (TEE): \[\small\mbox{TEE = PAL × REE}\] where PAL is a given physical activity level, and REE is resting energy expenditure predicted from anthro­pometric measure­ments, as shown in Table 8a.7.
Table 8a.7: ARs for energy (MJ/d) for adults. Note: The ARs for energy (1MJ = 238.83kcal) are calculated by multiplying estimates of resting energy expenditure (REE) predicted from anthropometric measures (Henry, 2005) with PAL values.
PAL values of 1.4. 1.6, 1.8, and 2.0 reflect low-active (sedentary), moderately active, active, and very active lifestyles, respectively.
Data from EFSA : ARs for infants and children and adjustments for pregnancy and lactation are also presented in EFSA (2017).
Age PAL=1.4
M     F
PAL=1.6
M     F
PAL=1.8
M     F
PAL=2
M     F
18–29y9.8  7.911.2  9.012.6  10.114.0  11.2
30–39y9.5  7.610.8  8.712.2  9.813.5  10.8
40–49y9.3  7.510.7  8.612.0  9.713.4  10.7
50–59y9.2  7.510.5  8.511.9  9.613.2  10.7
60–69y8.4  6.89.6  7.810.9  8.812.1  9.7
70–79y8.3 6.89.5 7.710.7 8.711.9 9.6

ESFA (2017) selected REE as a proxy for the slightly lower basal metabolic rate (BMR) because in most studies REE has been measured. For adults individual data of measured body heights derived from 13 representative national European surveys were applied. Corresponding data for body masses calculated for a BMI of 22kg/m2 (i.e., the mid-point of the range of healthy BMI as defined by WHO), were used.

For practical reasons, ESFA assigned only one AR for energy for adults of a defined age and sex group with a healthy BMI of 22. PAL values of 1.4, 1.6, 1.8 and 2.0, selected to correspond to the four lifestyles to approximately reflect: low active (sedentary), moderately active, active, and very active lifestyles, were used, as shown in Table 8a.7. No ARs for energy were calculated for adults > 80y in view of the paucity of European anthropometric data for this age group.

For infants from 0–6mos, energy requirements were considered to be equal to the energy supply from human milk, and no AR was given. For infants aged 7–11mos, ARs were derived from TEE based on DLW method, adding energy deposited in tissues for growth from the literature. BMIs for this age group were based on the WHO Child Growth Standards (WHO, 2006).

For children 1–18y, ARs were based on predicted REE using body masses and height from the WHO Growth Standards for children up to 2y, or from harmonized European growth curves for children 3–17y (van Buuren et al., 2012). PAL values of 1.4, 1.6, 1.8, and 2.0 were also applied for children, but adjusted for energy expenditure for growth by a 1% increase in PAL values for each of the three age groups (1–3y, > 3 – < 10y, and 10–18y).

For pregnant women, additional energy requirements were based on a mean gestational increase in body mass of 12kg, whereas for women exclusively breastfeeding during the first 6mos, the additional energy requirement during lactation was estimated factorially: see EFSA (2017). for more details.

8a.6.6 EFSA Reference Intake Ranges for Macronutrients

Reference Intake Ranges for Macronutrients have also been set by EFSA and are available in the 2017 summary report . The Reference Intake Ranges are defined as the intake range for macronutrients, expressed as a percentage of the energy intake. They apply to ranges of intakes that are ade­quate for maintaining health and associated with a low risk of selected chronic diseases.

Table 8a.8
Table 8a.8: Reference Intake Ranges for total fat and carbohydrates and AIs for fatty acids and dietary fiber for adults ≥ 18y, and during pregnancy and lactation. From EFSA, 2017.
Adults ≥18 Pregnancy Lactation
Total Carbohy-
drates (E%)(a)
45–60
Dietary fiber
(g/d)(b)
25
Total Fat
(E%)(a)
20–3520–3520–35
SFA ALAP ALAP ALAP
LA
(E%)(b)
4 44
ALA
(E%)(b)
0.5 0.50.5
EPA+DHA
(mg/d)(b)
250 250250
DHA
(mg/d)(b)
+100–200(c)+100–200(c)
TFA ALAP ALAP ALAP
presents the macronutrients with a defined reference intake range expressed as the percentage of the energy intake for adults (> 18y) for total carbohydrate, total fat, linoleic acid (LA), and α-linolenic acid (ALA) and compares them with those set by the UK and WHO, also intended as pop­ula­tion averages. A comparison with those set by the UK and WHO, also intended as pop­ula­tion averages is presented in Table 8a.3. In contrast, the U.S and Canadian recommendations, also shown in Table 8a.3, are intended for use by individuals. Note for saturated fatty acids (SFAs) and trans-fatty acids (TFAs), an intake as low as possible is advised, whereas for dietary fiber and eicosa­pentanoic acid (EPA) plus docosa­hexanoic acid (DHA) , an AI is given. No reference intake ranges are given for protein, n-6 poly­un­saturated fatty acids (PUFAs) or n-3 PUFAs, unlike WHO (see Section 8a.7.6). Likewise, no recommendation to restrict daily intake of cholesterol (mg/d) is stated, although an AI has been set for dietary fiber (g/d) which varies by age group. Note the data shown in Table 8a.8 can be used to assess the proportion of individuals in the pop­ula­tion in a specified life-stage group with usual intakes outside the reference lower and upper limits of the range.

8a.7 WHO/FAO Nutrient Reference Values

When vitamin and mineral requirements for a specific country are not available, the most recent NRVs in the WHO/FAO (2004) report are often used. In this report WHO/FAO defined three levels shown in Box 8a.7:
Box 8a.7 WHO/FAO Nutrient Reference Values

8a.7.1 WHO/FAO Requirement (R = AR) for Nutrients

The requirement is defined by WHO/FAO as an average daily nutrient intake level that meets the needs of 50% of the “healthy” individuals of a particular age and gender. It is based on a given criteria of ade­quacy which varies depending on the specified nutrient. Where necessary, an allowance for variations in nutrient bioavailability has been included. However, a requirement has been set by WHO/FAO for only a few nutrients.

8a.7.2 WHO/FAO Recommended Nutrient Intake (RNI)

This requirement is defined as a daily nutrient intake set at the requirement (AR) plus 2SD. This meets the nutrient requirements of almost all apparently healthy individuals in an age and sex-specific pop­ula­tion group. Thus, it is equivalent to, and derived in the same way as individual requirements set by COMA (1991) for the U.K., by IOM (2001) for the U.S. and Canada, and by EFSA (2017) in Europe. When the standard deviation for the nutrient requirement is unknown, WHO/FAO (2004) has generally assumed a CV of 10%–12.5%, although there are exceptions for some nutrients (e.g., zinc, see below).

RNI values for dietary iron and zinc are based on estimates that meet the normative storage requirements, and are adapted from earlier reports (FAO/WHO, 1988; 1996). In these reports the normative requirement was defined as the mean requirement to maintain a level of tissue storage that is judged to be desirable. In Table 8a.9,
Table 8a.9: Recommended nutrient intakes for dietary zinc (mg/d) to meet the normative storage requirements from diets differing in zinc bioavailability. Unless otherwise specified, the within-subject variation of zinc requirements is assumed to be 25%.
a For infants receiving maternal milk only, assumed CV = 12.5%. The bioavailability of zinc from human milk is assumed to be 80%.
b Formula-fed infants; moderate bioavailability for whey-adjusted milk formula and for partly breastfed infants or given low-phytate feeds supplemented with other milks; assumed CV = 12.5%.
c Formula-fed infants; low bioavailability applicable to phytate-rich vegetable-protein based formula with or without whole-grain cereal; assumed CV = 12.5%.
d Not applicable to infants consuming human milk only. From WHO/FAO (2004).
Age group Assumed
  weight (kg)  
Bioavailability
High   Mod.   Low
Infants & children
0–6mo 6 1.1a 2.8b 6.6c
7–12mo 9 0.8a
7–12mo 9 2.5d 4.1 8.4
1–3y 12 2.4 4.1 8.3
4–6y 17 2.9 4.8 9.6
7–9y 25 3.3 5.6 11.2
Adolescents
F. 10–18y 47 4.3 7.2 14.4
M. 10–18y 49 5.1 8.6 17.1
Adults
F. 19–65y 55 3.0 4.9 9.8
M. 19–65y 65 4.2 7.0 14.0
F. > 65y 55 3.0 4.9 9.8
M. >65y 65 4.2 7.0 14.0
Pregnant women
1st trimester 3.4 5.5 11.0
2nd trimester4.2 7.0 14.0
3rd trimester 6.0 10.0 20.0
Lactating women
0–3 mo 5.8 9.5 19.0
3–6 mo 5.3 8.8 17.5
6–12 mo 4.3 7.2 14.4
the RNIs for zinc (mg/d) are given for diets with three levels of zinc bio­avail­ability. For these derivations, a CV for the dietary zinc requirement of 25% is assumed. Appendix 8a.7 and 8a.8 summarize the Recom­mended Nutrient Intakes (RNIs) by WHO/FAO, 2004 Vitamin and Mineral Requirements in Human Nutrition.

8a.7.3 WHO/FAO Tolerable Upper Intake Level (UL) of Nutrients

The WHO/FAO Upper Tolerable Nutrient Intake Levels are defined for a limited range of nutrients as the maximum intake from food (including fortified products), water and supplements of that nutrient that is unlikely to pose risk of adverse health effects from excess in almost all (97.5%) apparently healthy individuals in an age and sex-specific pop­ula­tion group. The ULs were developed using the model outlined in (WHO/FAO, 2006).

8a.7.4 WHO/FAO Additional Levels

WHO/FAO (2004) adopted additional terms for certain nutrients. For vitamin A, for example, they adopted the term “Recom­mended Safe Intake,” as was used in their earlier report (FAO/ WHO, 1988), because of the lack of data for deriving a true mean requirement and variance for any group. The recom­mended Safe Intake level is set to prevent clinical signs of deficiency and allow normal growth, but it does not allow for prolonged periods of infection or other stresses. As such, it represents the normative storage requirement plus 2SDs.

8a.7.5 WHO/FAO Human Energy Requirements

Energy requirements set by FAO/WHO/UNU/ in 2004 are presented by gender and selected age groups and are expressed as energy (as kJ or kcal) per day and energy per kilogram of body weight. Requirements are also expressed as multiples of BMR. The recommendations for dietary energy intake are also accompanied by guidelines for desirable physical activity levels: see FAO/WHO/UNU (2004) for more details.

Note that, like the U.K and EFSA, the FAO/WHO/UNU energy requirements are specifically “prescriptive” in relation to body weights, defining suitable reference ranges consistent with long-term good health, amd should be applied to pop­ula­tion groups and not to individuals.

The FAO/WHO/UNU (2004) energy requirements are based on estimates of TEE in free-living persons measured by doubly-labeled water or other methods (e.g., individually calibrated heart rate monitoring) that give comparable results. They also modified their earlier factorial estimates of energy requirements which used occupational-related mean values of physical activity levels (PALs). Instead FAO/WHO/UNU (2004) used a range of life-style PAL values for each of the three lifestyles — sedentary, active, vigorously active, and shown in Table 8a.10.
Table 8a.10: FAU/WHO/UNICEF (2004) Class­ification of lifestyles in relation to the intensity of habitual physical activity, or PAL.
* PAL values > 2.40 are difficult to maintain over long periods
Category PAL value
Sedentary or light-activity lifestyle 1.40–1.69
Active or moderately active lifestyle 1.70 –1.99
Vigorous or vigorously active lifestyle  2.00–2.40*
The PAL values were calculated from the measurement of TEE and measurements or estimates of BMR (i.e., PAL = TEE/BMR). Both men and women are assigned to a PAL category using th same PAL values. The estimates of BMR were derived from the age and sex-specific predictive equations of Schofield (1985) using body weight alone.

The additional energy needs for pregnancy and lactation were also calculated using factorial estimates for the growth of maternal and fetal tissues, the metabolic changes associated with pregnancy, and the synthesis and secretion of milk during lactation.

For infants 1–12mos, the energy requirements were estimated from equations for TEE, adding the energy needs for growth. Separate energy requirements (as kJ/kg/d) are available for breastfed and formula fed infants with the same body weight up to 12mos of age because TEE is lower among breastfed than formula-fed infants during the first year of life.

For children and adolescents, measurements of TEE were derived using both DLW and heart rate monitoring, from which predictive quadratic polynomial regression equations for boys and girls were derived; equations are available in FAO/WHO/UNU (2004). The sum of TEE and the additional energy deposited in growing tissue and laid down during normal growth, represents the mean daily energy requirement (kcal or MJ/day). For more details, see FAO/WHO/UNU, (2004).

8a.7.6 WHO/FAO Pop­ula­tion Average Intake Goals for Macronutrients

The WHO ranges of pop­ula­tion nutrient intake goals for preventing diet-related chronic diseases are shown in Table 8a.3. The recommendations are expressed as a proportion of the daily total energy intake rather than the absolute amount, with the exception of cholesterol and sodium, which are given in mg/d and g/d, respectively. This approach was adopted because the desirable up or down change will depend on the existing intakes in a given pop­ula­tion (Nishida et al., 2004). The recommendations represent the pop­ula­tion average intake that is judged to be consistent with the maintenance of health (i.e., low prevalence of diet-related diseases) in a pop­ula­tion (IOM, 2002). Hence these focus on the maintenance of low pop­ula­tion risk rather than low individual risk. In general, most of the ranges set are comparable to those of the U.K and the U.S. and Canada, although the meaning and application of the ranges differ. Exceptions are the recommendations by WHO/FAO for total fat intake which take into account countries with usual fat intake (as % energy) > 30% and < 15%. Total fat (as % energy) of at least 20% is consistent with good health.

The recommendation to restrict the intake of free sugars to less than 10% energy was made in view of the recognition that higher intakes of free sugars provide significant energy without supplying specific nutrients, and hence can have a negative impact on diet quality. In addition, increasing or decreasing intake of free sugars is associated with parallel changes in body weight, a relationship that exists irrespective of the level of the intake of free sugars. The excess body weight associated with intake of free sugars arises from excess energy intake. Free sugars include monosaccharides and disaccharides added to foods and beverages by the manufacturer, cook, or consumer, and sugars naturally present in honey, syrups, fruit juices and fruit juice concentrations.

WHO emphasize that whole grain cereals, fruits and vegetables are the preferred sources of non-starch polysaccharides (NSP). (See Table 8a.3). They state that whole grain foods should together provide > 20g per day of NSP and > 25g/d of total dietary fiber. Note that fruits and vegetables do not include tubers (i.e., potatoes, cassava).

In addition to the pop­ula­tion nutrient intake goals presented in Table 8a.3, WHO also emphasize the importance of maintaining at the pop­ula­tion level an adult median BMI of 21–23kg/m2, and for individuals a BMI in the range 18.5–24.9kg/m2, with the avoidance of a weight gain greater than 5kg during adult life. Physical activity is also highlighted with a recommendation for a total of one hour per day on most days of the week of moderate- intensity activity , such as walking.

8a.8 Sources of discrepancies in Nutrient Reference Values

In light of the preceding discussion, it is not surprising that estimates for AR for nutrients and the RI98 derived from them vary among countries. (Table 8a.11)
Table 8a.11 A comparison of the ARs for male adults for selected micronutrients set by the US IOM in 1997–2011 (Otten et al, 2006; IOM, 2011), the European Food Safety Authority (EFSA, 2017), and the UK (COMA, 1991; SACN 2016).
*1 8–24y; ** > 25y
A AI as no AR set. B Based on an EAR of 2550kcal.
NE niacin equivalents, DFE dietary folate equivalents.
For zinc, the EFSA sets three alternative ARs for levels of phytate intake above 300mg/d, of 600, 900, and 1200mg/d
Nutrient IOM AR EFSA AR UK EAR
Vitamins
Vitamin A (µg/d) 625 570 500
Vitamin D (µg/d) 10 15A -
Vitamin C (mg/d) 75 90 25
Thiamin (mg/d) 1.0 0.072/MJ 0.80B
Riboflavin (mg/d) 1.1 1.3 1.0
Niacin (mg NE/d) 12 1.3/MJ14.0B
Vitamin B6 (mg/d) 1.4 1.5 1.2B
Vitamin B12 (µg/d)24A 1.25
Folate (µg DFE/d) 320 250 150
Minerals
Calcium (mg/d) 800 860*; 750** 525
Phosphorus (mg/d) 580 550A 400
Magnesium (mg/d) 350 350A 250
Trace elements
Iodine (µg/d) 95 150A -
Iron (mg/d) 6 6 6.7
Selenium (µg/d) 45 70A -
Zinc (mg/d) 9.4 7.5
9.3;11.0;12.7
7.3
compares the ARs for selected micronutrients set by the IOM in the U.S., by EFSA in Europe, and by COMA in the UK. Some of the discrepancies seen in Table 8a.11 arise because of differences in judgment by the expert groups setting the requirement estimates even when the same evidence-base has been consulted. Other potential sources of discrepancies in the AR and thus RI98 include:

Such discrepancies may be especially large for those nutrients and specific age groups for which the available data on requirements are very limited (e.g., children, adolescents, and the elderly). In such cases, requirements are often interpolated or extrapolated from data for other age groups, or they are not compiled at all. In addition, during pregnancy and lactation, maternal metabolic adaptation for certain nutrients may occur, but because the adaptation has not been firmly characterized, the additional nutrient needs are still equivocal.

A further source of discrepancy arises from the adjustments required that take into account the bioavailability of nutrients in the habitual national diet. The adjustments required depend on the nature of the diet ingested, the chemical form of the nutrient in the diet, and a variety of systemic factors known to affect the absorption and utilization of the nutrient. For many nutrients, factors affecting their bioavailability have yet to be established, so appropriate adjustments to yield dietary requirement estimates cannot be made. For others, fixed bioavailability factors are applied, even though the efficiency of absorption may vary with the dietary level of the nutrient or the life-stage group. For example, in U.K. diets, iron is assumed to have a fixed bioavailability of 15%, irrespective of the age and life-stage group (COMA,1991), whereas in the U.S. a factor of 18% is used except for women during the second and third trimester of pregnancy when a bioavailability factor of 25% is assumed (IOM, 2001). Other expert groups such as WHO/FAO (2004) employ differing factors to adjust for bioavailability, depending on the composition of the diet.

Several other factors besides sex, life-stage, and the habitual diet, are known to influence the requirements for many nutrients. Examples include body size, lean body mass, and activity level. For this reason, the requirement estimates are often set using a “standard” height and weight, and/or energy intake for a particular age and life-stage group; standards that may vary across countries. Therefore, those nutrients with requirements expressed per kg body weight or per MJ, may also differ. For example, reference heights and body weights used by EFSA (2017) are from the WHO Child Growth Standard (WHO, 2006) for children aged 0–2y, although for children 2–17y, data from European children are used (van Buuren et al., 2012). In the U.S., reference weights and heights for children and adults were based on anthropometric data collected from 1988–1994 as part of the Third National Health and Nutrition Examination Survey (NHANES III). However, the report on macro-nutrients (IOM, 2003) used data on median BMI and height-for-age from the CDC/NCHS growth charts (Kuczmarski et al., 2002).

In the future, factors such as race or ethnicity, lifestyle (e.g., vegetarians, smokers, oral contraceptive users), the existence of chronic disease (eg asthma, diabetes), environment, family history, and genetic predisposition to disease may also be taken into account when setting requirement estimates (Gibson, 2012). Examples of potential factors affecting requirements are summarized in (Figure 8a.7).

Figure 8a.7
Figure 8a.7 Sources of biological variability of individual nutrient requirements. Modified from Ashwell et al., 2008.

In the United States and Canada, vegetarianism and some other lifestyle factors are already considered. As an example, the EAR for iron for vegetarians is higher than that for persons consuming a mixed Western diet to take into account the lower bioavailability of iron from a vegetarian diet (i.e., 10% vs 18%) (IOM, 2001), whereas the EAR for vitamin C for smokers is higher than for non-smokers (IOM, 2000).

The life-stage groupings are not defined in the same way among countries. North America has 22 such groups. Fewer groupings are defined in the U.K and Europe: Germany and the Netherlands have 14 each, but the number is presently not standardized, even within the European Economic Community (Trichopoulou and Vassilakou, 1990).

Finally, knowledge of the SD associated with the AR is required to set the RI98. In many cases, however, the SD is calculated from the AR and an assumed CV, because the SD is unknown. Although a CV of 10% or 15% is often assumed, this is not always the case. WHO/FAO (2004), for example, has assumed a CV of 25% for the dietary zinc requirement estimate, resulting in a further source of discrepancy for the RI98 for zinc.

8a.9 Future directions in harmonizing the process for deriving Nutrient Reference Values

Nutrient Reference Values are used to assess the ade­quacy of nutrient intakes and for planning diets at both the individual and the pop­ula­ tion level. They also have several important applications in food and nutrition policy, food regulation and trade. However, as highlighted above, the terminology and methodological approaches that are used for setting NRVs differ markedly among countries resulting in discrepancies in NRVs worldwide. Such disparate recommendations lead to international discrepancies in health, food policies and trade, highlighting important reasons for harmonizing the process for deriving NRVs globally; these reasons are summarized in Box 8a.8.
Box 8a.8 Reasons for harmonizing the process of deriving NRVs globally From King and Garza (2007) and NASEM (2018b).

Recently, the feasibility of the new harmonized approach for deriving Nutrient Reference Values on a global scale has been confirmed following testing with three exemplar nutrients (zinc, iron, and folate) on two high-risk pop­ula­tion sub­groups — young children and women of reproductive age, as noted in Section 8.2. The success of the new framework depicted in Figure 8a.3, however, depends on six core values:

Several barriers have been identified that must be overcome before the proposed new organizing framework can be implemented globally. In addition, as highlighted earlier, many gaps in the scientific information required to compile NRVs still remain. This results in sources of uncertainty that must be considered, acknowledged and managed appropriately when deriving the NRVs,

Acknowledgements

RSG would like to thank past collaborators, particularly my former graduate students, and is grateful to Michael Jory for the HTML design and his tireless work in directing the trans­lation to this HTML version.