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). The United States Food and Nutrition Board (in 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 Tolerable Upper Intake Level (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 in the U.S. and Canada for the first time for the revision of the NRVs for vitamin D and calcium (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).

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, lower threshold intake; NIV, nutrient intake value; PRI, population reference intake; RDA, recommended dietary allowance; RI, reference intake range for macronutrients; RNI, reference nutrient intake (UK), recommended nutrient intake (WHO/FAO); SIV, Safe intake value; SUL, Safe upper level; UL, tolerable upper intake level (USA/Canada & EFSA), upper tolerable nutrient intake level (WHO/FAO).
Adapted from King and Garza (2007).

Recom- mendation	Recom mended terms	USA/ Canada	UK	European Union/ EFSA	WHO/ FAO
Umbrella term for the set of recom- mendations	NRV	DRI	DRV	DRV
Average requirement	AR	EAR	EAR	AR
Recommended intake level	RI	RDA	RNI	PRI	RNI
Lower reference intake			LRNI	LTI
Adequate intake	AI	AI	SIV	AI
Safe upper level of intake	UL	UL	SUL	UL	UL
Appropriate macronutrient distribution range		AMDR	AMDR	RI	Population mean intake goals

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. (Table 8a.1). 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.

Recom­mendations from the workshop for the terms for three reference values and the relationship between them is shown in Figure 8a.1. The three reference values are: the Average Requirement (AR), Recom­mended Intake (RI), 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 Adequate Intake (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.

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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:

• Be based on the mean nutrient intake of a specific pop­ula­tion;
• Be established for all essential nutrients and food components that have public health relevance;
• Include acceptable macro­nutrient distribution ranges for carbohydrates, protein, and fat that reduce chronic disease risks associated with the intake of these macro­nutrients;
• Consider nutrient-nutrient interactions* and quantify them, if possible; and
• Consider sub­pop­ula­tions with special needs, keeping in mind, however, that reference values are intended for appar­ently healthy** indi­viduals.

* 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

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:

• Choosing the appropriate tools and resources;
• Collecting relevant data from the tools and other resources;
• Identifying the best approach for the nutrient under consideration; and
• 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 — zinc, 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.

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.

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. Alternatively RoB 2, a revised Cochrane risk-of-bias tool for randomized trials, can be used (Sterne et al., 2019).

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 second 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 third step is to identify the best approach for deriving the NRVs for the nutrient under study. 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). Three approaches are frequently used: factorial approach, balance studies, and an intake (dose)-response assessment. Limitations of each of these approaches were noted by Claessens et al. (2013). Table 8a.2

Table 8a.2: Types of studies and examples of their application in the development of the U.S / Canadian Dietary Reference Intakes. Modified from Yates. (2007).

Type of study	Measurement	Examples
Nutrition intervention studies (rand- omized, placebo-controlled studies)	Functional out­come	Calcium fracture rate with increased calcium intake via supplements or placebo
	Biochemical measurements	Red blood cell folate response to varying levels of folate
Depletion/repletion studies	Biochemical measurements	Leukocyte ascorbate concen- trations for vitamin C Urinary excretion of 4-pyridoxic acid for vitamin B6
Balance studies	Controlled intake and excretion	Protein require­ments
Factorial estimation	Measure losses + bio­avail­ability	Iron & zinc require­ments
Epidemiologic observational studies	Estimate intake and measure losses	Iodine intake and excretion
	Functional out­come	Vitamin A and night-blindness
Observed intakes in healthy populations	Dietary intake data	Vitamin K

provides examples of the types of studies used in the development of the U.S / Canadian Dietary Reference Intakes.

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 was reviewed by 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. Limitations of balance studies have been reviewed by Mertz (2007). Balance studies are used to determine protein and, in some cases, mineral require­ments (e.g., calcium 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 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,

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.

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. Hence, 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). 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 median of the require­ment distribution represents the Average Requirement (AR) for that particular group of indi­viduals (Figure 8a.6)

and is used to assess the prevalence of nutrient 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, or 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 Safe Upper Levels of Intake

The Safe 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:

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.

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 Safe Upper Level of Intake (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.

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 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, dietary fiber, fruits and vegetables. (WHO, 2012; WHO, 2015), 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:

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, Dorrington et al. (2020) suggest that the current 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. The U.K. RNIs for minerals and vitamins are shown in Appendix 8a.1 and Appendix 8a.2 respectively. 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 Levels for Nutrients

Safe upper 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 new U.K. factorial approach to establish energy require­ments is based on the assumption that total energy expenditure (TEE) (or EAR) is equal to BMR × PAL (SACN, 2011). This approach was developed in recognition of the large unpredictable variation between indi­viduals (inter-indi­vidual variation) in discretionary activity. 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 calculated from prediction equations of Henry (2005) and applying healthy body weights equivalent to a BMI of 22.5kg/m² and at the appropriate height of the adult population. 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 from all DLW measurements of TEE of children aged over one year. The BMR for children was estimated using the equations of Henry (2005), applying healthy body weight based on the 50^th percentile of the UK‑WHO Growth Standards (aged 1–4y) and the 50^th percentile of the UK 1990 reference for children and adolescents aged > 4y. 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, 2	WHO2	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 (WHO/FAO, 2002) 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

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 intakes 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:

• Consider reduction in the risk of chronic degenerative disease, where possible
• Establish an upper level of intake designed to avoid risk of adverse health effects, where data exist
• Include components of food not conven­tionally considered to be essential nutrients (eg choline, carotenoids, lycopenes, boron, vanadium) but which may have a possible benefit to health.

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. U.S. and Canadian EARs for elements and vitamins are included in Appendix 8a.3 and Appendix 8a.4 respectively.

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, and as CV=SD/EAR, then . \[\small \mbox{RDA} _{98} \mbox{ = EAR + (0.1 × EAR) + (0.1 × EAR)}\]     Or: \[\small \mbox{RDA} _{98} \mbox{ = 1.2 × EAR }\] 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 both 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 should not be used to assess the intakes of groups. RDA values for elements and vitamins are shown in Appendix 8a.3 and Appendix 8a.4 respectively.

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

The Tolerable Upper 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. If the an indi­vidual's usual intake equals or exceeds the AI, their intake is almost certainly adequate, but if it falls below the AI, no estimate of the prob­ability of nutrient adequacy can be made (IOM, 2000). 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
1.50	41.6	56.2	Sedentary Low active Active Very active	1,848 2,009 2,215 2,554	2,080 2,267 2,506 2.898
1.65	50.4	1.50	Sedentary Low active Active Very active	2,068 2,254 2,490 2,880	2,349 2,566 2,842 3,296
1.80	59.9	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

The Acceptable Macronutrient Distribution Range (AMDR) of intakes 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). 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). The EFSA ARs for vitamins, minerals, and trace elements for adults only shown in Table 8a.6. For the ARs for all life-stage groups for minerals and vitamins, see Appendix 8a.5 and Appendix 8a.6 respectively.

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. The EFSA PRIs for vitamins, minerals, and trace elements for adults only are given in Table 8a.6 For the PRIs for all life-stage groups for minerals and vitamins, see Appendix 8a.7 and Appendix 8a.8 respectively.

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.6.3 European Tolerable Upper Intake Level for nutrients

The Tolerable Upper Intake Level (UL) 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).

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 (Table 8a.7); they are of limited use for indi­viduals. ESFA also chose total energy expenditure (TEE) as the criterion on which to base the AR for energy for both adults and children. However, they determined TEE factorially from estimates of resting energy expenditure (REE), plus the energy needed for various levels of physical activity (PAL) associated with sustainable lifestyles in healthy indi­viduals. The equation is shown below: \[\small\mbox{TEE = PAL × REE}\] where PAL is a given physical activity level, and REE is resting energy expenditure. 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 (2013).

Age	PAL=1.4 M     F	PAL=1.6 M     F	PAL=1.8 M     F	PAL=2 M     F
18–29y	9.8  7.9	11.2  9.0	12.6  10.1	14.0  11.2
30–39y	9.5  7.6	10.8  8.7	12.2  9.8	13.5  10.8
40–49y	9.3  7.5	10.7  8.6	12.0  9.7	13.4  10.7
50–59y	9.2  7.5	10.5  8.5	11.9  9.6	13.2  10.7
60–69y	8.4  6.8	9.6  7.8	10.9  8.8	12.1  9.7
70–79y	8.3 6.8	9.5 7.7	10.7 8.7	11.9 9.6

ESFA (2017) selected REE as a proxy for the slightly lower basal metabolic rate (BMR) because most studies estimated or measured REE. REE was estimated using the predictive equations of Henry (2005) which are derived from large datasets covering wide age groups. For adults 18–79y, the calculated REE was based on indi­vidual body heights measured in representative national surveys in 13 EU Member States, and body masses calculated from the measured heights assuming a BMI of 22kg/m².

PAL values were estimated from time-allocated lists of daily activities expressed as physical activity ratios available from the Compendium of Physical Activities compiled by Ainsworth et al. (2011) Examples of lifestyles associated with certain PALs estimated over 24h are tabulated in ESFA (2013).

To derive TEE as REE × PAL, PAL values of equal steps within the observed range of physical activity levels associated with a sustainable lifestyle were chosen for calculating AR for energy. In this way, PAL values could be allocated to lifestyles where values of 1.4, 1.6, 1.8 and 2.0, 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 (i.e., ARs) 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 estimated by regression equations using DLW data, adding energy deposited in tissues for growth from the literature. Body masses for this age group were based on the WHO Child Growth Standards (WHO, 2006).

For children 1–18y, ARs for energy were based on predicted REE using the equations of Henry (2005) and 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. Energy expenditure for growth was accounted for 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 (2013) 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 and are intended as population averages. 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)	20–35	20–35	20–35
SFA	ALAP	ALAP	ALAP
LA (E%)(b)	4	4	4
ALA (E%)(b)	0.5	0.5	0.5
EPA+DHA (mg/d)(b)	250	250	250
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). 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:

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. In the interim, Allen et al. (2006) have calculated the ARs from the RNIs for a limited range of vitamins and minerals for infants, children and adults. The conversion factors used were based on SDs derived by the U.S. Food and Nutrition Board of the Institute of Medicine (FNB/IOM) for calculating the U.S and Canadian RDAs. They are tabulated in Annex C of Allen et al. (2006). These calculated ARs are shown in Appendix 8a.9 .

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

The Recommended Nutrient intake 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 trimester	—	4.2	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.10 and Appendix 8a.11 summarize the mineral and vitamin Requirement Intakes (RNIs) of WHO/FAO (2004).

8a.7.3 WHO/FAO Upper Tolerable 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).

In October, 2017, the WHO held a technical consultation entitled: “Risk of excessive intake of vitamins and minerals delivered through public health interventions — current practices and case studies”. The proceedings of this technical consultation are available in a special issue. The reader is advised to consult the following for further details: (Pike and Zlotkin, 2019).

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 (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 Basal Metabolic Rate (BMR). The recom­men­dations for dietary energy intake are also accompanied by guidelines for desirable physical activity levels: see FAO/WHO (2004) for more details.

Note that, like the U.K and EFSA, the FAO/WHO 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 (2004). energy require­ments are based on estimates of TEE in free-living persons measured by DLW 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 (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: FA0/WHO (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 (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 (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/MJ	14.0B
Vitamin B6 (mg/d)	1.4	1.5	1.2B
Vitamin B12 (µg/d)	2	4A	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:

• Disparities in philosophy about the most appropriate method­ological approach to use
• Interpretation of data on which ARs are based
• Differences in selection of the criteria used to define nutrient ade­quacy
• Uncertainty in extent of metabolic adaption during pregnancy and lactation due to limited data
• Differences in number of life-stage groupings among countries
• Limited data on require­ments for certain nutrients and life-stage groups
• Differences in scaling (both interpolation and extrapolation) for sub­groups based on known data for other pop­ula­tions (e.g., adults)
• Varying bio­avail­ability factors depending on the composition of habitual national diets
• Unknown factors influencing nutrient require­ments.

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).

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.

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:

• NRVs are regularly updated
• The process is clear and transparent
• The methods are rigorous and relevant
• Factors influencing the NRVs are documented
• The strength of the evidence is determined
• The review is complete and efficient.

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.