Dietary Reference Intakes for Calcium and Vitamin D (2011) / Chapter Skim
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5 Dietary Reference Intakes for Adequacy: Calcium and Vitamin D
5 Dietary Reference Intakes for Adequacy: Calcium and Vitamin D
Pages 345-402
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From page 345... ...
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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From page 346... ...
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)
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From page 347... ...
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.
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From page 348... ...
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.
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From page 349... ...
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.
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From page 350... ...
. 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)
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From page 351... ...
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.
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From page 352... ...
352 TABLE 5-2 Calcium Intake Estimated to Achieve Average Bone Calcium Accretion for Children and Adolescents Using the Factorial Method Average Estimated Calcium Urinary Endogenous Total Total Intake Age/ Accretion Losses Fecal Calcium Sweat Losses Needed Absorption (Adjusted for Study Author, Year Gender (mg/day)
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From page 353... ...
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.
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From page 354... ...
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.
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From page 355... ...
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.
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From page 356... ...
However, women -- who have been undergoing the loss longer -- are more at risk for adverse consequences. It is important to underscore that the goal of calcium intake during these life stages is to lessen the degree of bone loss; calcium intake at any level is not known to prevent bone loss.
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From page 357... ...
On balance, there is somewhat more evidence for a benefit of higher calcium intake among women over the age of 60 years, a group that is likely about half of the DRI life stage of women 51 through 70 years of age. Specifically, the meta-analysis conducted by Tang et al.
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From page 358... ...
, and therefore fracture risk is not a particularly relevant factor, although to the extent that a subgroup analysis can be relied upon, women greater than 60 years of age appear to experience some benefit from calcium intake relevant to fracture risk reduction. It would appear that the life stage consisting of women 51 through
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From page 359... ...
It also identifies menopausal women between the ages of 51 and 70 years as the basis for the reference value, rather than nonmenopausal women, on the assumption that during this life stage many and eventually all will become menopausal. The value cannot be more certain until such time as there is information on calcium balance specifically for women experiencing the early stages of menopause, as well as wellcontrolled trials that more clearly elucidate dose–response measures for menopausal younger women relative to calcium intake and bone health.
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From page 360... ...
(2006) , who studied calcium intake alone, were unable to demonstrate benefits for bone health among persons over 70 years of age with supplemental calcium intakes (750 to 1,200 mg/day)
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From page 361... ...
of calcium supplementation during pregnancy that reveal no evidence that additional calcium intake beyond normal non-pregnant requirements has any benefit to mother or fetus (Koo et al., 1999; Jarjou et al., 2010)
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From page 362... ...
Likewise, the RDA values for non-lactating women and adolescents are applicable, providing RDAs of 1,000 and 1,300 mg/ day, respectively. VITAMIN D: DIETARY REFERENCE INTAKES FOR ADEQUACY The EARs, RDAs, and AIs for vitamin D are shown in Table 5-3 by life stage group.
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From page 363... ...
In short, a dose–response relationship between vitamin D intake and bone health is lacking. Rather, measures of serum 25OHD levels as a biomarker of exposure (i.e., intake)
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From page 364... ...
Next, the available data -- notably those obtained under conditions of limited sun exposure -- were integrated in order to estimate a total intake that would result in the desired serum 25OHD relative to measures of bone health. This step-wise process for simulating a dose–response relationship for vitamin D considered, first, the relevance to this study of the confounding introduced by 25OHD assay methodologies and related measurement problems, including "assay drift." Next, the data from three bodies of evidence described in Chapter 3 -- the relationship between calcium absorption and serum 25OHD levels; serum 25OHD levels and bone health in children; and serum 25OHD levels and bone health in older adults -- were summarized and used to specify a dose–response curve for serum 25OHD.
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From page 365... ...
Simulation of a Dose–Response Relationship for Vitamin D Intake and Bone Health "Assay Drift" and Implications for Interpretation of Serum 25OHD Data in the Literature In considering serum 25OHD levels as reported by various studies, the committee was aware of the so-called "assay drift" associated with longitudinal comparison of assay results collected in the National Health and Nutrition Examination Survey (NHANES) , as well as the large interlaboratory variation worldwide (Carter et al., 2010)
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From page 366... ...
Moreover, when calcium intakes are inadequate, vitamin D supplementation to the point of serum 25OHD concentrations up to and beyond 75 nmol/L has no effect. • Serum 25OHD level and fracture risk: Randomized clinical trials using adults Because available trials often administered relatively high doses of vitamin D, serum 25OHD concentrations varied considerably.
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From page 367... ...
The data, however, do not allow specification of serum 25OHD levels above which half of the population is protected from osteomalacia and half is at risk; rather the evidence indicated that even relatively low serum 25OHD levels were not associated with the specified measures of osteomalacia, mostly likely owing to the impact of calcium intake. This is consistent with a number of studies, both from trials and from observational work, indicating that vitamin D alone appears to have little effect on bone health outcomes; it is most effective when coupled with calcium.
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From page 368... ...
in children and adolescents; increased risk of osteomalacia and impaired fetal skeletal outcomes; impaired fractional calcium absorption and an increased risk of osteomalacia in young and middle-aged adults; and impaired fractional calcium absorption and fracture risk in older adults. Similarly, for all age groups, there appears to be little causal evidence of additional benefit to any of these indicators of bone health at serum 25OHD levels above 50 nmol/L, suggesting that this level is consistent with an RDAtype reference value in that this value appears to cover the needs of 97.5 percent of the population.
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From page 369... ...
Calcium appears to be the more critical nutrient in the case of bone health, and therefore has an impact the dose– response relationship. Therefore, calcium or lack thereof may "drive" the need for vitamin D
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From page 370... ...
. Instead, the best remaining approach is to describe the relationship between total intake and serum 25OHD levels under conditions of minimal sun exposure.
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From page 371... ...
The committee examined information from controlled trials in younger and older adults and in children that could be used in the simulation to describe the relationship between vitamin D intake and changes in serum 25OHD concentrations. Of interest was the condition of minimal sun exposure, which occurs in northern latitudes and in Antarctica during their respective winters.
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From page 372... ...
Description Intake (IU/day) (nmol/L)
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From page 373... ...
obese and nonobese n = 41 Young and middle-aged adults Latitudes ≥ 50°N and Antarctica Cashman Cork, October/ mean 29.9 ± 6.2 y 135 65.7 0 135 37.4 (31.4–47.9) et al., 2009 Ireland November– range 20–40 y (80–200)
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From page 374... ...
TABLE 5-4 Continued 374 Vitamin Total Reference; Baseline Baseline D Dose Vitamin Type of Location Season Population Vitamin D 25OHD Level (IU/ D Intake Achieved 25OHD Study (Latitude) (Duration)
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From page 375... ...
Holick et al., Boston, MA February– mean 35.5–40.5 y 316c 46.5 ± 22.2 0 316 47.0 ± 19.8 2008 (42°N) May men and women (n = 55)
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From page 376... ...
= 23) Van Der Klis Groningen, April–May 61 y 64e 61.2 ± 2.4 0 64 NS from baseline et al., 1996 Netherlands (5 wk)
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From page 377... ...
(n = 14) NOTE: BMD = bone mineral density; FFQ = food frequency questionnaire; IU = International Units; mo = month(s)
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From page 378... ...
. These observations suggest that the assumption of minimal sun exposure was met.
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From page 379... ...
At this time, it is not possible to clarify which of these possibilities occur. Non-linear response to vitamin D dosing The available data suggest a non-linear response of serum 25OHD above baseline levels to doses of vitamin D for all age groups.
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From page 380... ...
This finding suggests that across ages under conditions of minimal sun exposure, similar intakes of vitamin D result in similar serum 25OHD concentrations, as shown in Figure 5-4. Because there was no age effect in the response of serum 25OHD level to total intake of vitamin D, a single, combined regression analysis with study as a random effect was carried out.
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From page 381... ...
Thus, the committee used the simulated dose–response at the higher latitudes to ensure minimal sun exposure to ensure as little contribution from endogenous production as the evidence allows. Given the lack of an age effect in the response of the achieved serum 25OHD levels to any total intake of vitamin D, the intake to achieve the EAR-type value of 40 nmol/L was the same across all groups.
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From page 382... ...
Given these limitations and the uncertainties, the committee selected the estimated intakes needed in a fashion that would err on the side of the specified intake "overshooting" the targeted serum value to ensure that the specified levels of intake achieved the desired serum 25OHD levels of 40 and 50 nmol/L. This approach is used despite possible contributions to serum 25OHD from sun exposure that could not be taken into account.
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From page 383... ...
has been back-transformed to total vitamin D for presentation in this figure. Specification of Vitamin D Dietary Reference Intakes for Adequacy The DRIs for adequacy for vitamin D have been introduced previously in Table 5-3.
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From page 384... ...
were analyzed by regression using mixed effect model following log transformation controlling for study effect by a random effects model because there was no effect of age on the response of serum 25OHD level to total intake of vitamin D The relationship for achieved vitamin D is y achieved 25OHD in nmol/L = 9.9 ln (total vitamin D intake)
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From page 385... ...
/day Vitamin D RDA 600 IU (15 µg) /day Vitamin D For these life stage groups, ensuring normal, healthy bone accretion is central to the DRI values.
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From page 386... ...
Although the prevention of rickets can be a factor in establishing reference values, it is important to seek measures that are consistent with favorable bone health outcomes. Maximizing calcium absorption, especially for this life stage group, is therefore a reasonable parameter to take into account.
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From page 387... ...
Taken as a body of evidence and in the absence of measures that directly relate total intake to health outcomes, the information concerning serum 25OHD concentrations associated with rickets prevention, calcium absorption, and positive effects on BMC measures are consistent with discussions above concerning a requirement distribution based on serum 25OHD concentrations. They support the conclusion that an average requirement for vitamin D for these life stage groups is associated with the achievement of concentrations of 25OHD in serum of 40 nmol/L.
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From page 388... ...
The results are inconsistent, in part because the confounding inherent in observational studies. Serum 25OHD concentrations relative to calcium absorption, therefore, provide an important basis for DRI development for vitamin D for these life stage groups.
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From page 389... ...
/day Vitamin D For persons in these life stage groups of 51 through 70 years and >70 years, the ability to maintain bone mass and reduce the level of bone loss is the primary focus for DRI development. Evidence related to fracture risk becomes central.
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From page 390... ...
There are no dose–response data that would allow comparisons for adults more than 70 years of age regarding the effects of intakes of 600 IU of vitamin D per day with that of a higher level of intake such as 800 or 1,000 IU/day. Moreover, the evidence for fracture risk in relation to vitamin D intake for this older life stage is confounded by study protocols that do not allow separation of the effect of calcium from vitamin D; as discussed previously there is reasonably compelling evidence that calcium alone in this age group can modestly reduce the risk of fracture.
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From page 391... ...
The reason not to dismiss the effect of 800 IU of vitamin D per day as an aberration because of a lack of dose–response data, even in the face of data generally not supportive of an effect of vitamin D alone regarding reduced fracture risk for the oldest adults, is that persons more than 70 years are a very diverse group. This group is undergoing a number of physiological changes with aging that could have an impact on and increase the variability around an average requirement, particularly in light of the known and high variability of these physiological changes among aging individuals.
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From page 392... ...
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.
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From page 393... ...
, 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.
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From page 394... ...
2006. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?
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From page 395... ...
Proceedings of a conference held September 2007 in Bethesda, Maryland, USA. American Journal of Clinical Nutrition 88(2)
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From page 396... ...
2007. Effectiveness and safety of vitamin D in relation to bone health.
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From page 397... ...
1995. Effect of calcium supplements and stage of lactation on the calcium absorption efficiency of lactating women accustomed to low calcium intakes.
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From page 398... ...
2010. Effect of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake.
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From page 399... ...
1998. Bone changes after 3 mo of lactation: influence of calcium intake, breast-milk output, and vitamin D-receptor genotype.
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From page 400... ...
1997. Vitamin D status does not influence the breast-milk calcium concentration of lactating mothers accustomed to a low calcium intake.
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From page 401... ...
American Journal of Clinical Nutrition 85(6)
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From page 402... ...
2006. A positive dose–response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention.
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