WHAT ARE DIETARY REFERENCE INTAKES?

Dietary Reference Intakes (DRIs) are reference values that are quantitative estimates of nutrient intakes to be used for planning and assessing diets for apparently healthy people. They include not only Recommended Dietary Allowances (RDAs) but also three other types of reference values (see Box S-1). Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the question. Thus, scientific judgment was required for evaluating the evidence and in setting the reference values, and that process is delineated for each nutrient in Chapters 4 through 13.

Box S-1

Dietary Reference Intakes. Recommended Dietary Allowance (RDA): the average daily dietary nutrient intake level sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group. (more...)

Recommended Dietary Allowances

The process for setting the RDA depends on being able to set an Estimated Average Requirement (EAR). Before the EAR is set, a specific criterion of adequacy is selected on the basis of a careful review of the literature. In the selection of the criterion, reduction of disease risk is considered along with many other health parameters.

If the standard deviation (SD) of the EAR is available and the requirement for the nutrient is symmetrically distributed, the RDA is set at two SDs above the EAR:

RDA = EAR + 2 SD_EAR.

If data about variability in requirements are insufficient to calculate an SD, a coefficient of variation (CV) for the EAR of 10 percent is assumed, unless available data indicate a greater variation in requirements.

If 10 percent is assumed to be the CV, then twice that amount when added to the EAR is defined as equal to the RDA. The resulting equation for the RDA is then

RDA = 1.2 × EAR.

This level of intake statistically represents 97.5 percent of the requirements of the population. If the distribution of the nutrient requirement is known to be skewed for a population, as with iron, other approaches are used to find the ninety-seventh to ninety-eighth percentile to set the RDA.

The RDA for a nutrient is a value to be used as a goal for dietary intake for the healthy individual. As discussed in Chapter 14, the RDA is not intended to be used to assess the diets of either individuals or groups or to plan diets for groups. Only if intakes have been observed for a large number of days (i.e., usual intake) and are at or above the RDA, or if observed intakes for fewer days are well above the RDA, should one have a high level of confidence that the intake is adequate (see Box S-2). The EAR is also used as the basis to address diets of groups.

Box S-2

Uses of Dietary Reference Intakes for Healthy Individuals and Groups.

Comparison of Recommended Dietary Allowances and Adequate Intakes

Although both the RDA and AI are to be used as a goal for intake by individuals, the RDA differs from the AI. Intake of the RDA for a nutrient is expected to meet the needs of 97 to 98 percent of the apparently healthy individuals in a life stage and gender group (see Figure S-1). However, because no distribution of requirements is known for nutrients with an AI, it is not possible to know what percentage of individuals are covered by the AI. The AI for a nutrient is expected to exceed the RDA for that nutrient, and thus it should cover the needs of more than 97 to 98 percent of the individuals. The degree to which an AI exceeds the RDA is likely to differ among nutrients and population groups.

FIGURE S-1

Dietary reference intakes. This figure shows that the Estimated Average Requirement (EAR) is the intake at which the risk of inadequacy is 0.5 (50 percent) to an individual. The Recommended Dietary Allowance (RDA) is the intake at which the risk of inadequacy (more...)

For people who have diseases that increase specific nutrient requirements or who have other special health needs, the RDA and AI each may serve as the basis for adjusting individual recommendations. Qualified health professionals should adapt the recommended intake to cover higher or lower needs.

Tables S-1 through S-9 provide the recommended intake levels, whether RDAs or AIs, for vitamin A, vitamin K, chromium, copper, iodine, iron, manganese, molybdenum, and zinc by life stage and gender group. For most of these micronutrients, AIs rather than RDAs are proposed for infants to age 1 year. EARs and RDAs, however, are proposed for iron and zinc for infants 7 to 12 months of age because the level of iron and zinc in human milk does not meet the needs of the older infants and because factorial data are available to estimate the average requirement. Neither AIs nor RDAs were proposed for arsenic, boron, nickel, silicon, or vanadium.

TABLE S-1

Criteria and Dietary Reference Intake Values for Vitamin A by Life Stage Group.

TABLE S-9

Criteria and Dietary Reference Intake Values for Zinc by Life Stage Group.

APPROACH FOR SETTING DIETARY REFERENCE INTAKES

The scientific data used to develop Dietary Reference Intakes (DRIs) have come from observational and experimental studies. Studies published in peer-reviewed journals were the principal source of data. Life stage and gender were considered to the extent possible, but the data did not provide a basis for proposing different requirements for men and for nonpregnant and nonlactating women in different age groups for many of the micronutrients. Two of the categories of reference values—the Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA)—are defined by specific criteria of nutrient adequacy; the third, the Tolerable Upper Intake Level (UL), is defined by a specific endpoint of adverse effect, when one is available. In all cases, data were examined closely to determine whether a functional endpoint could be used as a criterion of adequacy. The quality of studies was examined by considering study design; methods used for measuring intake and indicators of adequacy; and biases, interactions, and confounding factors.

Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the various questions that confronted the panel. Therefore, many of the questions raised about the requirements for and recommended intakes of these micronutrients cannot be answered fully because of inadequacies in the present database. Apart from studies of overt deficiency diseases, there is a dearth of studies that address specific effects of inadequate intakes on specific indicators of health status, and a research agenda is proposed (see Chapter 15). The reasoning used to establish the values is described for each nutrient in Chapters 4 through 13. While the various recommendations are provided as single rounded numbers for practical considerations, it is acknowledged these values imply a precision not fully justified by the underlying data in the case of currently available human studies.

The scientific evidence related to the prevention of chronic degenerative disease was judged to be too nonspecific to be used as the basis for setting any of the recommended levels of intake for all these nutrients. For all of the micronutrients, the EAR is higher than the amount needed to prevent overt deficiency diseases in essentially all individuals in the life stage group and is based on limited data indicating laboratory evidence of sufficiency. The indicators used in deriving the EARs, and thus the RDAs, are described below.

NUTRIENT FUNCTIONS AND THE INDICATORS USED TO ESTIMATE REQUIREMENTS

Vitamin A functions to maintain normal reproduction, vision, and immune function. A deficiency of vitamin A, although uncommon in North America, can result initially in abnormal dark adaptation (night blindness) followed by xerophthalmia. The method used to set an Estimated Average Requirement (EAR) for vitamin A is based on a computational analysis to assure adequate body stores of vitamin A. The Recommended Dietary Allowance (RDA) for adults for vitamin A is set at 900 μg RAE/day for men and 700 μg RAE/day for women. One μg retinol activity equivalent (μg RAE) is equal to 1 μg all-trans-retinol, 12 μg β-carotene, and 24 μg α-carotene or β-cryptoxanthin.

Vitamin K functions as a coenzyme in the synthesis of the biologically active form of a number of proteins involved in blood coagulation and bone metabolism. Because of the lack of data to set an EAR, an Adequate Intake (AI) is set based on representative dietary intake data from healthy individuals from the Third Nutrition and Health Examination Survey (NHANES III). The AI for adults is 120 and 90 μg/day, for men and women, respectively.

Chromium potentiates the action of insulin in vivo and in vitro. There was not sufficient evidence to set an EAR for chromium. Therefore, an AI was set based on estimated intakes of chromium derived from the average amount of chromium/1,000 kcal of balanced diets and average energy intake from NHANES III. The AI is 35 μg/day for young men and 25 μg/day for young women.

Copper functions to catalyze the activity of many copper metalloenzymes that act as oxidases to achieve the reduction of molecular oxygen. Frank copper deficiency in humans is rare; the deficiency symptoms include normocytic and hypochromic anemia, leukopenia, and neutropenia. The method used to set an EAR for copper is based on the changes in a combination of biochemical indicators resulting from varied levels of copper intake. The RDA for copper is 900 μg/day for men and women. There were insufficient data to set a different EAR and RDA for each gender.

Iodine is an important component of the thyroid hormones that are involved with the regulation of metabolism. Severe iodine deficiency can result in impaired cognitive development in children and goiter in adults. The method used to set an EAR for iodine is iodine accumulation and turnover. The adult RDA for iodine is 150 μg/day. There were insufficient data to set a different EAR and RDA for each gender.

Iron functions as a component of hemoglobin, myoglobin, cytochromes, and enzymes. Iron deficiency anemia is the most common nutritional deficiency in the world, resulting in fatigue and impaired cognitive development and productivity. The required amount of absorbed iron is estimated based on factorial modeling. The EAR is determined by dividing the required amount of absorbed iron by the fractional absorption of dietary iron, estimated to be 18 percent for adults for the typical North American diet. The RDA for men and premenopausal women is 8 and 18 mg/day, respectively. The RDA for pregnant women is 27 mg/day.

Manganese is involved in the formation of bone and in amino acid, lipid, and carbohydrate metabolism. There were insufficient data to set an EAR for manganese. An AI was set based on median intakes reported from the U.S. Food and Drug Administration Total Diet Study. The AI for adult men and women is 2.3 and 1.8 mg/day, respectively.

Molybdenum functions as a cofactor for several enzymes in a form called molybdopterin. An inborn error of metabolism that leads to a deficiency of sulfite oxidase is due to the lack of molybdopterin, which results in neurological dysfunction and mental retardation. Molybdenum balance data were used to set an EAR. The RDA for adults for molybdenum is 45 μg/day for men and women. There were insufficient data to set a different EAR and RDA for each gender.

Zinc functions through the catalysis of various enzymes, the maintenance of the structural integrity of proteins, and the regulation of gene expression. Overt human zinc deficiency is rare, and the symptoms of a mild deficiency are diverse due to zinc's ubiquitous involvement in metabolic processes. Factorial analysis of zinc losses and requirements for growth, as well as fractional absorption, were used to set an EAR. The RDA for zinc is set at 11 mg/day for men and 8 mg/day for women.

CRITERIA AND PROPOSED VALUES FOR TOLERABLE UPPER INTAKE LEVELS

A risk assessment model is used to derive Tolerable Upper Intake Levels (ULs). The model consists of a systematic series of scientific considerations and judgments. The hallmark of the risk assessment model is the requirement to be explicit in all of the evaluations and judgments made.

The adult ULs for vitamin A (3,000 μg/day), boron (20 mg/day), copper (10,000 μg/day), iodine (1,100 μg/day), iron (45 mg/day), manganese (11 mg/day), molybdenum (2,000 μg/day), nickel (1.0 mg/day), vanadium (1.8 mg/day), and zinc (40 mg/day), as shown in Table S-10, were set to protect the most sensitive individuals in the general population (such as those who might be below the reference adult weight).

Members of the general, apparently healthy population should be advised not to routinely exceed the UL. However, intake above the UL may be appropriate for investigation within well-controlled clinical trials to ascertain if such intakes are of benefit to health for specific reasons. Clinical trials of doses above the UL should not be discouraged, as it is expected that participation in these trials will require informed consent that will include discussion of the possibility of adverse effects and will employ appropriate safety monitoring of trial subjects.

The ULs for vitamin A, boron, copper, iodine, iron, manganese, molybdenum, nickel, and zinc are based on adverse effects of intake from diet, fortified foods, and/or supplements. ULs could not be established for vitamin K, arsenic, chromium, and silicon because of lack of suitable data, a lack that indicates the need for additional research. The absence of data does not necessarily signify that people can tolerate chronic intakes of these substances at high levels, particularly elements such as arsenic which are known to cause serious adverse effects at very high levels of intake. Like all chemical agents, nutrients and other food components can produce adverse effects if intakes are excessive. Therefore, when data are extremely limited, extra caution may be warranted.

USING DIETARY REFERENCE INTAKES TO ASSESS NUTRIENT INTAKES OF GROUPS

Suggested uses of Dietary Reference Intakes (DRIs) appear in Box S-2. The transition from using previously published Recommended Dietary Allowances (RDAs) and Reference Nutrient Intakes (RNIs) to using each of the DRIs appropriately will require time and effort by health professionals and others.

For statistical reasons that are addressed in the report Dietary Reference Intakes: Applications in Dietary Assessment (IOM, 2000) and briefly in Chapter 14, the Estimated Average Requirement (EAR) is the appropriate reference intake to use in assessing the nutrient intake of groups, whereas the RDA is not appropriate. When assessing nutrient intakes of groups, it is important to consider the variation in intake in the same individuals from day to day, as well as underreporting. With these considerations, the prevalence of inadequacy for a given nutrient may be estimated by using national survey data and determining the percent of the population below the EAR. Assuming a normal distribution of requirements, the percent of surveyed individuals whose intake is less than the EAR equals the percent of individuals whose diets are considered inadequate based on the criteria of inadequacy chosen to determine the requirement. For example, intake data from the Continuing Survey of Food Intakes by Individuals and the Third National Health and Nutrition Examination Survey, which collected 24-hour diet recalls for 1 or 2 days, indicate that:

• Between 10 and 25 percent of children 1 to 3 years of age consume dietary vitamin A or its precursors at a level less than the EAR. The percent of adults consuming intakes of vitamin A below the EAR is higher than for children. The EAR is based on a criterion of adequate vitamin A stores in the liver (> 20 μg vitamin A/g liver); thus, these data suggest that a considerable number of people have liver vitamin A stores that are less than desirable. It should be recognized that this does not represent a clinical deficiency state, such as dark adaptation, which is not commonly seen in North Americans.
• Between 5 and 10 percent of adolescent girls consume dietary iron at a level less than the EAR. The criterion chosen for the EAR for this age group was based on iron loss and accretion, using an upper limit of absorption that provides minimal iron stores.
• The prevalence of iron intakes less than the EAR ranges from 15 to 20 percent for premenopausal women which corresponds with a 13 to 16 percent prevalence of low iron status (based on serum ferritin concentration).

• A high percentage of pregnant women consume dietary iron at a level less than the EAR; this corresponds with a high prevalence of low hemoglobin concentration (anemia).

CONSIDERATION OF THE RISK OF CHRONIC DEGENERATIVE DISEASE

Close attention was given to the evidence relating intake of all the micronutrients to reduction of the risk of chronic disease. Data linking intake of vitamin K and chromium with the risk of chronic disease in North America were available but insufficient to set Estimated Average Requirements (EARs).

Diabetes Mellitus

A number of studies have demonstrated a beneficial effect of chromium on circulating glucose and insulin concentrations; however, not all reports of supplementation are positive. Progress in this field has been limited by lack of a simple, widely acceptable method for identification of subjects who are chromium depleted and therefore would be expected to respond to chromium supplementation. Recent studies suggest that a low molecular weight chromium binding substance may amplify insulin receptor tyrosine kinase activity in response to insulin. Additional dose response data linking chromium and prevention of diabetes will be needed before this can be used as an indicator to estimate the EAR.

TABLE S-10

Tolerable Upper Intake Levels (UL), by Life Stage Group.

RESEARCH RECOMMENDATIONS

Five major types of information gaps were noted: a lack of data demonstrating a specific role of some of these micronutrients in human health; a dearth of studies designed specifically to estimate average requirements in presumably healthy humans; a lack of data on the micronutrient needs of infants, children, adolescents, the elderly, and pregnant women; a lack of studies to determine the role of these micronutrients in reducing the risk of certain chronic diseases; and a lack of studies designed to detect adverse effects of chronic high intakes of these many of these micronutrients.

Highest priority is thus given to studies that address the following research topics:

• studies to identify and further understand the functional (e.g., cognitive function, regulation of insulin, bone health, and immune function) and biochemical endpoints that reflect sufficient and insufficient body stores of vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc;
• studies to further identify and quantify the effects of interactions between micronutrients and interactions between micronutrients and other food components, the food matrix, food processing, and life stage on micronutrient (vitamin A, vitamin K, chromium, copper, iron, and zinc) bioavailability and therefore dietary requirement;
• studies to further investigate the role of arsenic, boron, nickel, silicon, and vanadium in human health; and
• studies to investigate the influence of non-nutritional factors (e.g., body mass index, glucose intolerance, infection) on the biochemical indicators for micronutrients currently measured by U.S. and Canadian nutritional surveys, such as for iron and vitamin A.