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DRI Dietary Reference Intakes Calcium Vitamin D 5 Dietary Reference Intakes for Adequacy: Calcium and Vitamin D OVERVIEW Bone health has been selected as the indicator to serve as the basis of the Dietary Reference Intakes (DRIs) for calcium and vitamin D. The review that underpins this conclusion has been described in Chapter 4, the component of this report addressing the hazard identification step of risk assessment and specifying the selected indicator. The next step in the risk assessment approach for DRI development—the hazard characterization component of risk assessment—is contained in this chapter. The dose–response relationship between the nutrient intake and bone health is examined and dietary reference values for adequacy are specified. In the case of DRIs for calcium and vitamin D, such values take the form of Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) or, alternatively, Adequate Intakes (AIs). The discussions related to the Tolerable Upper Intake Level (UL), which is also a DRI value, are contained in Chapter 6. Currently available data on bone health outcomes—when considered as an integrated body of evidence—can be used to derive EARs and RDAs for calcium and vitamin D for all life stages except infants. Bone health measures associated with bone accretion, bone maintenance, and bone loss are relevant to different DRI life stages, and thus the indicator of bone health has been reflected by different bone health measures depending upon the life stage. With respect to infants 0 to 12 months of age, for whom data were very sparse, an AI can be specified for each nutrient based on the available evidence concerning levels of intake observed to be adequate.
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DRI Dietary Reference Intakes Calcium Vitamin D The DRIs for calcium and vitamin D established in 1997 (IOM, 1997) also relied on bone health as the indicator in setting reference values for adequacy. However, the 1997 report established an AI for all life stage groups; no EARs or RDAs were specified. Newer data plus an integration of data have allowed the estimation of EARs and RDAs for all life stages except infants. Quantitative comparisons between AIs and EARs and RDAs are not appropriate. In 1997, AIs were established for calcium in lieu of EARs and RDAs as a result of uncertainties associated with balance studies, lack of concordance between observational and experimental data, and lack of longitudinal data to verify the relationship between calcium intake, calcium retention and bone loss (IOM, 1997). In the past 10 years, newer evidence on skeletal health has emerged from a combination of large-scale randomized trials and calcium balance studies as described in Chapter 4. Further, there are now data relative to a number of life stage groups, and these help to avoid reliance on extrapolating or scaling data from one life stage to another unstudied life stage. In the case of vitamin D, the 1997 report concluded that there were inadequate data available for EARs and RDAs as a result of uncertainties about sun exposure, the vitamin D content of the diet, and vitamin D stores (IOM, 1997). In the intervening years data have emerged that allow a requirement distribution to be simulated for vitamin D, which, in turn, has been found to be concordant with other available data. This analysis unexpectedly indicated that the dose–response relationship regarding median requirements is not significantly affected by age. Further, several newer studies can be used to elucidate the contributions made by sun exposure and to help separate total intake contributions from contributions stemming from cutaneous synthesis. Strides have been made in estimating the vitamin D content of foods as well as the amounts of vitamin D consumed by the U.S. and Canadian populations. Despite new data since the earlier Institute of Medicine (IOM) report (IOM, 1997), there remain a number of uncertainties that have caused challenges in estimating DRI values for calcium and vitamin D. Notable among these is the absence of intervention trials that study dose–response relationships for the nutrients. Rather, most of the evidence is derived from a single dose that is often relatively high. Further, some studies fail to specify information about the background diet and hence the total level of intake is lacking. When this is the case, the mean population requirement may be below the dose used in the study, but cannot be further specified. In addition, there is the common practice of designing studies to examine calcium and vitamin D in combination, thereby precluding the ability to discern the effects of each nutrient alone, which is of interest when establishing a reference value for a nutrient.
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DRI Dietary Reference Intakes Calcium Vitamin D As discussed in Chapter 4, there are very limited data to suggest that there may be some biological differences in the way in which different ethnic/racial groups respond to calcium and vitamin D, most notably among those of African American ancestry. The extent to which such observations may affect requirements for the nutrients is unknown at this time. Although it is important to take into account biological differences where they may exist among, for example, African Americans, Hispanics, and those of Asian descent, the available data are too limited to permit the committee to assess whether separate, quantitative reference values for such groups are required. The DRIs established in this report are based on the current understanding of the biological needs for calcium and vitamin D across the North American population. Other factors may come into play in terms of ensuring adequate intakes of these nutrients—for example, lactose intolerance or food choices—but as far as is known these factors do not affect the basic biological need for these nutrients. Rather, they are discussed in Chapter 8 as issues relevant to the application of the DRIs by dietary practitioners. Described in this chapter is the committee’s decision-making regarding the dose–response relationships for calcium and bone health, and for vitamin D and bone health. From these conclusions, DRI values for adequacy are specified. A significant underlying assumption made by the committee is that the DRIs for calcium are predicated on intakes that meet requirements for vitamin D and that the DRIs for vitamin D rest on the assumption of intakes that meet requirements for calcium. In other words, the requirement for one nutrient assumes that the need for the other nutrient is being met. This is an essential assumption, for three reasons: Given that reference values are intended to act in concert for the purposes of planning diets, health policy makers would be working to meet all nutritional needs; therefore it would be inappropriate to establish requirements for such purposes on the basis that one or more related nutrients would be consumed by the population in inadequate amounts. An inadequacy in one of the nutrients could cause changes in the efficient handling of or physiological response to the other nutrient that might not otherwise be present. For example, in vitamin D–deficient states with minimal calcium intake, absorption of calcium from the gut cannot be enhanced. The compensatory metabolic response to this scenario is the accelerated conversion of 25-hydroxyvitamin D (25OHD) to its active form (calcitriol) through an increase in parathyroid hormone (PTH) levels. Such perturbations confound the estimation of the true requirement under neutral circumstances.
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DRI Dietary Reference Intakes Calcium Vitamin D No amount of vitamin D is able to compensate for inadequate total calcium intake; thus, setting a realistic DRI value for vitamin D requires that calcium is available in the diet in adequate amounts. However, the committee has also commented on the consequences for one nutrient when the other is inadequate, in order to be transparent regarding the science underpinning the determination of reference values for these two nutrients. CALCIUM: DIETARY REFERENCE INTAKES FOR ADEQUACY The EARs, RDAs, and AIs for calcium are shown in Table 5-1 by life stage group. The studies used to estimate these values have been included in the review of potential indicators contained in Chapter 4. Therefore, in the discussions below, the relevant data are highlighted but not specifically critiqued again. Infants 0 to 12 Months of Age Infants 0 to 6 Months of Age AI 200 mg/day Calcium Infants 6 to 12 Months of Age AI 260 mg/day Calcium Data are not sufficient to establish an EAR for infants 0 to 6 and 7 to 12 months of age, and therefore AIs have been developed based on the available evidence. An AI value is not intended to signify an average requirement, but instead reflects an intake level based on approximations or estimates of nutrient intakes that are assumed to be adequate. Whether and how much the AI values for infants could be lowered and still meet the physiological needs for human milk-fed infants are unknown because mechanisms for adaptation to lower intakes of calcium are not well described for the infant population, and experimental data with overall relevance to estimating average requirements are extremely limited. Calcium requirements for infants are presumed to be met by human milk (IOM, 1997). There are no functional criteria for calcium status that reflect response to calcium intake in infants (IOM, 1997). Rather, human milk is recognized as the optimal source of nourishment for infants (IOM, 1991; Gartner et al., 2005). There are no reports of any full-term, vitamin D–replete infants developing calcium deficiency when exclusively fed human milk (Mimouni et al., 1993; Abrams, 2006). Therefore, AIs for calcium
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DRI Dietary Reference Intakes Calcium Vitamin D TABLE 5-1 Calcium Dietary Reference Intakes (DRIs) for Adequacy (amount/day) Life Stage Group AI EAR RDA Infants 0 to 6 mo 200 mg — — 6 to 12 mo 260 mg — — Children 1–3 y — 500 mg 700 mg 4–8 y — 800 mg 1,000 mg Males 9–13 y — 1,100 mg 1,300 mg 14–18 y — 1,100 mg 1,300 mg 19–30 y — 800 mg 1,000 mg 31–50 y — 800 mg 1,000 mg 51–70 y — 800 mg 1,000 mg > 70 y — 1,000 mg 1,200 mg Females 9–13 y — 1,100 mg 1,300 mg 14–18 y — 1,100 mg 1,300 mg 19–30 y — 800 mg 1,000 mg 31–50 y — 800 mg 1,000 mg 51–70 y — 1,000 mg 1,200 mg > 70 y — 1,000 mg 1,200 mg Pregnancy 14–18 y — 1,100 mg 1,300 mg 19–30 y — 800 mg 1,000 mg 31–50 y — 800 mg 1,000 mg Lactation 14–18 y — 1,100 mg 1,300 mg 19–30 y — 800 mg 1,000 mg 31–50 y — 800 mg 1,000 mg NOTE: AI = Adequate Intake; EAR = Estimated Average Requirement; RDA = Recommended Dietary Allowance. for infants are based on mean intake data from infants fed human milk as the principal fluid during the first year of life and on the studies that have determined the mean calcium content of breast milk. Additionally, information on calcium absorption and calcium accretion is taken into account. With respect to estimating AIs for calcium for infants, studies reviewed previously in this report have provided the following information: Based on infant weighing studies, a reasonable average amount of breast milk consumed is 780 mL/day. The average level of calcium within a liter of breast milk is 259 mg (± 59 mg). It is therefore estimated that the intake of calcium for infants fed exclusively human milk is 202 mg/day. This number is rounded to 200 mg/day.
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DRI Dietary Reference Intakes Calcium Vitamin D Calcium absorption for this age group ranges somewhat above and below 60 percent depending upon the total amount of calcium consumed. For development of the AI, a 60 percent calcium absorption rate was assumed. The usual accretion rate for calcium in infants can be estimated using the approximation of 100 mg/day overall during the first year of life, with the recognition that the available literature contains reports of varying rates above and below that level. Infants 0 to 6 Months of Age Using the estimates described above for the calcium content of breast milk and the amount of milk consumed per day, the AI for calcium for infants 0 to 6 months of age is 200 mg/day, a value reflective of the calcium provided to exclusively breast-fed infants. The expected net retention of calcium from human milk assuming 60 percent absorption would be 120 mg/day, which is in excess of the values predicted from calcium accretion based on cadaver and metacarpal analysis. An AI of 200 mg/day is expected, therefore, to result in retention of sufficient amounts of calcium to meet growth needs. Further, for infants in the first 4 months of life, balance studies suggest that 40 to 70 percent of the daily calcium intake is retained by the human milk-fed infant (Widdowson, 1965; Fomon and Nelson, 1993). In balance studies using human milk–fed infants, the mean calcium intake was 327 mg/day, and calcium retention was 172 mg/day on average (Fomon and Nelson, 1993). If infants consume calcium at the AI daily, they would achieve similar or greater calcium retention even if the efficiency of absorption was at the lower observed value of 30 percent. Thus, the AI should meet most infants’ needs. The AI established here of 200 mg/day is similar to the AI of 210 mg/day derived by the 1997 report (IOM, 1997). The difference is extremely small—only 10 mg/day—and likely within measurement error; however, the new AI reflects the current best estimate for calcium levels obtained exclusively from human milk Infants 6 to 12 Months of Age Estimation of the AI for infants 6 to 12 months of age takes into account the additional intake of calcium from food. From 6 to 12 months of age, the intake of solid foods becomes more significant, and calcium intakes may increase substantially from these sources. Only extremely limited data are available for typical calcium intakes from foods by older milk-fed infants, and mean calcium intake from solid foods has been approxi-
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DRI Dietary Reference Intakes Calcium Vitamin D mated as 140 mg/day for formula-fed infants (personal communication, Dr. Steven Abrams, February 22, 2010). For the purpose of developing an AI for this age group, it is assumed that infants who are fed human milk have intakes of solid food similar to those of formula-fed infants of the same age (Specker et al., 1997). Based on data from Dewey et al. (1984), mean human milk intake during the second 6 months of life would be 600 mL/day. Thus, calcium intake from human milk with a calcium concentration of about 200 mg/L during this age span (Atkinson et al., 1995) would be approximately 120 mg/day. Adding the estimated intake from food (140 mg/day) to the estimated intake from human milk (120 mg/day) gives a total intake of 260 mg/day. Again, this AI is slightly and probably insignificantly less than the 1997 AI (IOM, 1997) but is the current best estimate. Children and Adolescents 1 Through 18 Years of Age Children 1 Through 3 Years of Age EAR 500 mg/day Calcium RDA 700 mg/day Calcium Children 4 Through 8 Years of Age EAR 800 mg/day Calcium RDA 1,000 mg/day Calcium Children 9 Through 13 Years of Age Adolescents 14 Through 18 Years of Age EAR 1,100 mg/day Calcium RDA 1,300 mg/day Calcium For these life stage groups, the focus is the level of calcium intake consistent with bone accretion and positive calcium balance. Studies conducted primarily between 1999 and 2009 (see Table 5-2) provide a basis for estimating EARs and calculating RDAs. In contrast to earlier reference value deliberations for which there were virtually no available studies focused on children and adolescents, this committee benefited from several recent studies that used children as subjects. The approach used for children was to determine average calcium accretion through bone measures such as DXA and average calcium retention as estimated by calcium balance studies (i.e., positive balance). Next, the factorial method (IOM, 1997) was used with these two data sets to estimate the intake needed to achieve the bone accretion. Average bone calcium accretion is used rather than peak calcium accretion because the committee judged this value to be more consistent with meeting the needs
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DRI Dietary Reference Intakes Calcium Vitamin D TABLE 5-2 Calcium Intake Estimated to Achieve Average Bone Calcium Accretion for Children and Adolescents Using the Factorial Method Study Author, Year Age/Gender Average Calcium Accretion (mg/day) Urinary Losses (mg/day) Endogenous Fecal Calcium Losses (mg/day) Sweat Losses (mg/day) Total Needed (mg/day) Absorption (percent) Estimated Total Intake (Adjusted for Absorption) Lynch et al., 2007 1–3 Male/Female 142 34 40 — 216 45.6 474 Abrams et al., 1999; Ames et al., 1999 4–8 Male/Female 140–160 40 50 — 240 30.0 800 Vatanparast et al., 2010 9–13 Female 151 106 112 55 424 38.0 1,116 9–13 Male 141 127 108 55 465 38.0 1,224 14–18 Female 92 106 112 55 365 38.0 961 14–18 Male 210 127 105 55 500 38.0 1,316 9–18 Female 121 106 112 55 394 38.0 1,037 9–18 Male 175 127 108 55 465 38.0 1,224
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DRI Dietary Reference Intakes Calcium Vitamin D of 50 percent of this population, and hence an EAR (rather than an AI). Moreover, as discussed in Chapter 2, peak calcium accretion with higher total calcium intakes is likely transitory and, thus, not consistent with DRI development. The application of the factorial method using average bone calcium accretion allows an estimate of the calcium intake required to support bone accretion and net calcium retention, as shown in Table 5-2. The approach is described below, specifically for each life stage for children and adolescents. Children 1 Through 3 Years of Age The data are very limited for children 1 through 3 years of age given the challenges in studying young children. However, a report by Lynch et al. (2007) provides relevant data. Linear and non-linear modeling in this study suggested a target average calcium retention level of 142 mg/day, consistent with the growth needs of this life stage group. Through the factorial method, a calcium intake of 474 mg/day is estimated to meet this need (see Table 5-2). Given that these data are derived from mean estimates and are assumed to be normally distributed, the mean value is very likely the median value. An estimated EAR is, therefore, established as 500 mg of calcium per day, rounded from 474 mg/day. An assumption specified by Lynch et al. (2007) is that an additional 30 percent calcium retention would meet the needs of 97.5 percent of this age group. This was calculated as 180 mg/day and is based on calcium absorptive efficiency for young children, and it is judged reasonable. This results in an estimated RDA for calcium of 700 mg/day calcium, with rounding. Clearly, there are uncertainties when reliance is placed on a single study. The ability to study calcium requirements in a controlled study, however, does offer the ability to estimate an average requirement rather than an AI. The study is of high quality, and the reference values specified are in line with those specified for younger and older children. Children 4 Through 8 Years of Age The work of Abrams et al. (1999) and Ames et al. (1999) has indicated that, like that for younger children, an average calcium retention level of approximately 140 mg/day is consistent with the needs of bone accretion. However, there is evidence of a small increase during pre-puberty, yielding a calcium retention range of approximately 140 to 160 mg/day to allow for bone accretion across this age group of which a portion will be pre-pubertal. Using the factorial method (see Table 5-2) and from the non-linear dose–response relationship identified by the work of Ames
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DRI Dietary Reference Intakes Calcium Vitamin D et al.(1999) and Abrams et al. (1999), a calcium intake of 800 mg/day could be expected to achieve the levels of calcium needed for bone accretion. Again, the assumption that another approximately 30 percent is needed to cover about 97.5 percent of the population—through derivation as mean estimates and the assumption of normal distribution—results in a calculated and rounded RDA value for calcium of 1,000 mg/day. Again, as with younger children, there are relatively few studies available and most have small sample sizes. While the studies included some ethnic/racial diversity, they focused on girls. These limitations cannot be remedied at this time. However, the data are sufficiently robust to support an estimation of an average requirement of 800 mg/day calcium. Children 9 Through 13 Years of Age and Adolescents 14 Through 18 Years of Age As reviewed in Chapter 4, data from a recent study (Vatanparast et al., 2010) have provided bone calcium accretion levels for children and adolescents ranging from 92 to 210 mg/day. Average bone calcium accretion was included in the factorial method, and the intake levels can be estimated as shown in Table 5-2. While the committee was aware of data suggesting that calcium retention may vary by gender among children, these differences between girls and boys and between the 9- to 13- and 14- to 18-year age groups are relatively small quantitatively, and the limited nature of the data do not allow further specification of these differences to the extent they are real. Given the application of DRI values in real world settings such as school meal planning, recommending that boys receive a small amount more calcium than girls is not practicable, but it is also not warranted given the limited nature of the data suggesting this possibility. Additionally, there is wide variability in the onset of puberty and the pubertal growth spurt, and it is reasonable to conclude that increases in calcium intake may be needed early in puberty at times when children may be only 9 or 10 years old. Thus, for reference values for both boys and girls in the 9- to 13- and 14- to 18-year life stages, the differences in calcium intake to achieve mean bone calcium accretion as elucidated by Vatanparast et al. (2010) have been interpolated between 9- to 18-year old girls (1,037) and boys (1,224). This interpolation yields an estimated mean need for calcium for boys and girls of 1,100 mg/day with rounding, a value approximately at the midpoint between the two groups. Again, assuming a normal distribution, this estimate to achieve a mean calcium accretion represents the median and, thus, an EAR. The EAR is therefore set at 1,100 mg for both boys and girls for both life stages encompassed by the 9 through 18 year age range. In order to cover 97.5 percent of the population, an estimated RDA value for calcium of 1,300 mg/day is established.
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DRI Dietary Reference Intakes Calcium Vitamin D The uncertainties surrounding the reference value stem from reliance on primarily a single study. Although carefully carried out, the study included only white children. These newer data, however, provide the opportunity to identify an average requirement. Adults 19 Through 50 Years of Age Adults 19 Through 30 Years of Age Adults 31 Through 50 Years of Age EAR 800 mg/day Calcium RDA 1,000 mg/day Calcium While there is evidence of minor bone accretion into early adulthood, the levels required to achieve this accretion—which appears to be site dependent—are very low. The goal, therefore, is intakes of calcium that promote bone maintenance and neutral calcium balance. The report from Hunt and Johnson (2007) provides virtually the only evidence for these life stage groups. Based on a series of controlled calcium balance studies, they have established a calcium intake level of 741 mg/day to maintain neutral calcium balance. They further provide the 95 percent prediction interval around the level required for neutral calcium balance. Other available measures that relate to bone maintenance include bone mineral density (BMD), but studies that measured bone mass concomitant to calcium intake are highly confounded by failures to control for other variables that impact bone mass and to specify a dose–response relationship. There is no evidence that intakes of calcium higher than those specified by Hunt and Johnson (2007) offer benefit for bone health in the context of bone maintenance for adults 19 to 50 years of age. Osteoporotic fracture is not a relevant measure for this life stage, therefore extrapolating from the more prevalent data focused on older adults is not appropriate, nor is extrapolating from the data for younger persons for whom the concern is bone accretion. Therefore, the Hunt and Johnson (2007) data, which reflect the outcomes of a series of metabolic studies, provide a reasonable basis for an EAR for calcium of 800 mg/day calcium. That is, the observed value of 741 mg/day is rounded, but rounded up to 800 mg/day given the uncertainty. The upper limit of the 95 percent prediction interval around this estimate (1,035 mg/day) is appropriate as the basis for an RDA for calcium and rounded to 1,000 mg/day. As is the case with younger life stage groups, there is now the 2007 Hunt and Johnson study on the topic of calcium and bone health, which has allowed the estimation of an average requirement.
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DRI Dietary Reference Intakes Calcium Vitamin D RDA for persons more than 70 years of age would be higher due to this variability. In addition, there is insufficient evidence to provide assurances that 600 IU/day vitamin D is as effective as 800 IU/day. By comparing the projected RDA based on the simulation analysis (600 IU/day) with the available evidence indicating benefit at 800 IU of vitamin D per day, taking into account the uncertainties would result in an estimation of an RDA of approximately one-third higher than the simulation analysis suggests. Overall, this is a small increase that is not known to increase the possibility of adverse events while providing a certain level of caution for this particularly vulnerable and potentially frail segment of the population. This approach is predicated on caution in the face of uncertainties, and it is anticipated that newer data in the future will help to clarify the uncertainties surrounding the level of intake of vitamin D that could be expected to cover 97.5 percent of persons over the age of 70 years. The EAR of 400 IU/day and RDA of 800 IU/day for this life stage group, consistent with the DRIs for other life stage groups, assume minimal sun exposure. Adults 51 Through 70 Years of Age A question in establishing an EAR and RDA for this life stage group is the relevance of vitamin D in affecting bone loss due to the onset of menopause. Men in this life stage group have not yet reached the levels of bone loss and fracture rates associated with aging as manifested in persons more than 70 years of age and, unlike their female counterparts, they are not experiencing significant bone loss due to menopause. However, a portion—in fact perhaps the majority—of women in this life stage group are likely to be experiencing some degree of bone loss due to menopause. As discussed above for adults more than 70 years of age, the available data do not suggest that median requirements increase with aging, resulting in support for an EAR of 400 IU/day, the same as for younger adults. Likewise, the EAR for both women and men in the 51 through 70 year life stage group is set at 400 IU of vitamin D per day. With respect to women 51 through 70 years of age, fracture risk is lower than it is later in life; and as such, it is not entirely congruent with the situation for adults more than 70 years of age. Further, findings for this age group are at best mixed, but are generally not supportive of an effect of vitamin D alone on bone health. Although the AHRQ analyses of studies using vitamin D alone found the results to be inconsistent for a relationship with reduction in fracture risk, more recent studies have trended toward no significant effects (Bunout et al., 2006; Burleigh et al., 2007; Lyons et al., 2007; Avenell et al., 2009b). For those studies showing benefit for BMD with a vitamin D and calcium combination, interpretation
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DRI Dietary Reference Intakes Calcium Vitamin D is confounded by the effects of calcium especially since calcium alone appears to have at least a modest effect on BMD. The report from the WHI (Jackson et al., 2006), a very large cohort study, has limited applicability to the question of the effect of vitamin D on bone health among women because of relatively high levels of calcium intake (baseline mean calcium intake of approximately 1,150 mg/day at randomization plus 1,000 mg/day supplement) and the confounding due to hormone replacement therapy. Given these data plus the inability to extrapolate the variability seen in the requirements surrounding persons 70 or more years of age to this life stage group, the RDA for women 51 through 70 years of age is set at 600 IU of vitamin D per day, the same level as that for younger adults. With respect to men 51 through 70 years of age, there is also no basis to deviate from the RDA set for younger adults. The available evidence for men is extremely limited, and there are not data to suggest that bone health is enhanced by vitamin D intake among men in this life stage group. An RDA of 600 IU/day is established for these men. The DRIs for these two life stage groups assume minimal sun exposure. Pregnancy and Lactation Pregnant 14 Through 18 Years of Age Pregnant 19 Through 30 Years of Age Pregnant 31 Through 50 Years of Age EAR 400 IU (10 μg)/day Vitamin D RDA 600 IU (15 μg)/day Vitamin D Lactating 14 Through 18 Years of Age Lactating 19 Through 30 Years of Age Lactating 31 Through 50 Years of Age EAR 400 IU (10 μg)/day Vitamin D RDA 600 IU (15 μg)/day Vitamin D Pregnancy The EAR for non-pregnant women and adolescents is appropriate for pregnant women and adolescents based on: (1) AHRQ-Ottawa’s finding of insufficient evidence on the association of serum 25OHD level with maternal BMD during pregnancy and (2) the 1 available RCT (Delvin et al., 1986) and 14 observational studies reviewed in Chapter 4 regarding vitamin D deficiency and genetic absence of the vitamin D receptor (VDR) or 1α-hydroxyalase, which all demonstrate no effect of maternal 25OHD level on fetal calcium homeostasis or skeletal outcomes. Of the limited number (i.e., four) of observational studies that suggest an influence of maternal serum 25OHD levels on the offspring’s skeletal outcomes later in life (so-called developmental programming), one study reports associa-
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DRI Dietary Reference Intakes Calcium Vitamin D tions consistent with an EAR-type value of approximately 40 nmol/L below which negative fetal skeletal outcomes were reported (Viljakainen et al., 2010), and another reports an RDA-type value of 50 nmol/L late in gestation above which reduced skeletal BMC was not seen in offspring at 9 years of age (Javaid et al., 2006). In addition, development of the fetal skeleton without dependence on maternal vitamin D is also biologically plausible as indicated by the studies in animal models in rats, mice, pigs, and sheep (see review in Chapter 3). Finally, there is no evidence that the vitamin D requirements of pregnant adolescents differ from those of non-pregnant adolescents. The EAR is thus 400 IU of vitamin D per day for pregnant women and adolescents. Likewise, the RDA values for non-pregnant women and adolescents are applicable, providing an RDA of 600 IU/day for each group. Lactation The EAR for non-lactating women and adolescents is appropriate for lactating women and adolescents based on evidence from RCTs (Rothberg et al., 1982; Ala-Houhala, 1985; Ala-Houhala et al., 1988; Kalkwarf et al., 1996; Hollis and Wagner, 2004; Basile et al., 2006; Wagner et al., 2006; Saadi et al., 2007), which are consistent with observational data (Cancela et al., 1986; Okonofua et al., 1987; Takeuchi et al., 1989; Kent et al., 1990; Alfaham et al., 1995; Sowers et al., 1998) that increased maternal vitamin D intakes increase maternal serum 25OHD levels, with no effect on the neonatal serum 25OHD levels of breast-fed infants unless the maternal intake of vitamin D is extremely high (i.e., 4,000 to 6,400 IU/day) (Wagner et al., 2006). Observational studies report no relationship between maternal serum 25OHD levels and BMD (Ghannam et al., 1999) or breast milk calcium content (Prentice et al., 1997). Also, there is no evidence that lactating adolescents require any more vitamin D or higher serum 25OHD levels than non-lactating adolescents. The EAR is thus 400 IU of vitamin D per day for lactating women and adolescents. Likewise, the RDA values for non-lactating women and adolescents are applicable, providing an RDA of 600 IU/day for each group. REFERENCES Abrams, S. A., K. C. Copeland, S. K. Gunn, J. E. Stuff, L. L. Clarke and K. J. Ellis. 1999. Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American and Caucasian girls despite hormonal differences. Journal of Nutrition 129(3): 666-71. Abrams, S. A. 2006. Building bones in babies: can and should we exceed the human milk-fed infant’s rate of bone calcium accretion? Nutrition Reviews 64(11): 487-94. Abrams, S. A., P. D. Hicks and K. M. Hawthorne. 2009. Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently associated with increased calcium absorption. Journal of Clinical Endocrinology and Metabolism 94(7): 2421-7.
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