Cover Image

HARDBACK
$69.95



View/Hide Left Panel

6
Tolerable Upper Intake Levels: Calcium and Vitamin D

The Tolerable Upper Intake Level (UL) is not a recommended intake. Rather, it is intended to specify the level above which the risk for harm begins to increase, and is defined as the highest average daily intake of a nutrient that is likely to pose no risk of adverse health effects for nearly all persons in the general population. As intake increases above the UL, the potential risk for adverse effects increases. In short, the UL is a reference value intended to guide policy-makers and scientists charged with ensuring a safe food supply and protecting the health of the U.S. and Canadian populations. It applies to intakes on a chronic basis among free-living persons. Those responsible for determining the appropriate dosages of nutrients to be studied in carefully controlled experimental trials conducted in clinical or community settings have the opportunity to bring other considerations into play when deciding on the acceptable levels of nutrients that are appropriate for subjects taking part in such studies. ULs are not designed to address experimental protocols in which safety monitoring occurs.

This chapter is organized to include hazard identification (indicator review and selection) and hazard characterization (intake–response assessment and reference value specification), the first two steps of the general risk assessment approach for Dietary Reference Intake (DRI) development. Therefore, compared with the discussions presented in the two chapters on reference values for adequacy (Chapters 4 and 5), the discussions for ULs are contained in a single chapter. This chapter addresses adverse effects of excess intakes of calcium and vitamin D. Although adverse effects are also associated with deficiencies of calcium and vitamin D, those concerns are



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 403
6 Tolerable Upper Intake Levels: Calcium and Vitamin D The Tolerable Upper Intake Level (UL) is not a recommended intake. Rather, it is intended to specify the level above which the risk for harm begins to increase, and is defined as the highest average daily intake of a nutrient that is likely to pose no risk of adverse health effects for nearly all persons in the general population. As intake increases above the UL, the potential risk for adverse effects increases. In short, the UL is a reference value intended to guide policy-makers and scientists charged with ensuring a safe food supply and protecting the health of the U.S. and Canadian pop- ulations. It applies to intakes on a chronic basis among free-living persons. Those responsible for determining the appropriate dosages of nutrients to be studied in carefully controlled experimental trials conducted in clinical or community settings have the opportunity to bring other considerations into play when deciding on the acceptable levels of nutrients that are ap- propriate for subjects taking part in such studies. ULs are not designed to address experimental protocols in which safety monitoring occurs. This chapter is organized to include hazard identification (indicator review and selection) and hazard characterization (intake–response assess- ment and reference value specification), the first two steps of the general risk assessment approach for Dietary Reference Intake (DRI) development. Therefore, compared with the discussions presented in the two chapters on reference values for adequacy (Chapters 4 and 5), the discussions for ULs are contained in a single chapter. This chapter addresses adverse effects of excess intakes of calcium and vitamin D. Although adverse effects are also associated with deficiencies of calcium and vitamin D, those concerns are 403

OCR for page 403
404 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D incorporated into the previous discussions focused on establishing refer- ence values for adequacy. There are often ethical issues associated with conducting clinical trials designed to study the adverse effects of substances that can limit the types of data available for DRI development. For this reason, the derivation of ULs for DRI purposes necessarily relies more heavily on observational data and information derived from animal models than does the approach for the determination of levels of intake for nutritional adequacy. Thus, the emphasis on causality and strength of evidence needed for establishing reference values for adequacy is difficult to apply to the derivation of ULs. At the outset, it is important to distinguish between the relatively “acute” toxic effects of excess intake and the “chronic” adverse effects of high levels of intake that may manifest in other ways including disease risk. When the ULs for calcium and vitamin D were originally established in 1997, it was noted that the available data were limited relative to adverse outcomes and dose–response relationships (IOM, 1997). In that report, adverse effects from excess intakes of calcium and vitamin D were consid- ered primarily in terms of acute toxicity, which was defined as the condi- tion of hypercalcemia or, in some cases, hypercalciuria with or without hypercalcemia. The conditions associated with the intoxication syndrome for calcium and vitamin D are informative, but avoiding acute toxicity is not the ideal basis for a UL, a reference value with the larger purpose of public health protection over a life time of chronic intake. Although information con- cerning chronic excess intakes remains limited, data have emerged recently that may warrant caution about the levels of vitamin D that are consumed and raise questions about the long-term effects of high intakes that are less than those associated with toxicity and that may result in an increase in serum 25-hydroxyvitamin D (25OHD) levels into upper ranges previously considered physiological. Caution may also be warranted in comparing the effects at these high physiological levels of 25OHD achieved through supplementation versus sun exposure, and further research is needed to clarify the relative adverse effects of different sources of vitamin D. The model developed for UL derivation was summarized in 1998 (IOM, 1998), and it acknowledged that the lack of data would affect the ability to derive precise estimates. Specifically: “Several judgments must be made regarding the uncertainties and thus the uncertainty factor (UF) associated with extrapolating from the observed data to the general population.” Al- though a number of reports describe the underlying basis for uncertainty factors (Zielhuis and van der Kreek, 1979; Dourson and Stara, 1983), the strength of the evidence supporting the use of a specific UL undoubtedly varies. The summary of the 2007 workshop focused on enhancing DRI development (IOM, 2008) and pointed out the need for uncertainty fac-

OCR for page 403
405 TOLERABLE UPPER INTAKE LEVELS BOX 6-1 Potential Indicators of Adverse Outcomes for Excess Intake of Calcium and Vitamin D Calcium • Hypercalcemia • Hypercalciuria • Vascular and soft tissue calcification • Nephrolithiasis (kidney stones) • Prostate cancer • Interactions with iron and zinc • Constipation Vitamin D • Intoxication and related hypercalcemia and hypercalciuria • Serum calcium • Measures in infants: retarded growth, hypercalcemia • Emerging evidence for all-cause mortality, cancer, cardiovascular risk, falls and fractures tors, but also indicated that the scientific judgment involved should be described. In developing ULs for calcium and vitamin D, the limited nature of the data resulted in the committee using UFs to adjust for uncertainties in the data. These were necessarily qualitative adjustments rather than quantitative adjustments. As suggested repeatedly during the 2007 work- shop on DRIs (IOM, 2008), an educated guess for a reference value is more useful to stakeholders than the failure to set a reference value in the face of uncertainty. Discussions related to calcium ULs are provided first, and then vitamin D ULs are considered. At the start, the committee identified potential indi- cators to assess adverse effects for excess intakes of calcium and vitamin D based on the available literature, as described below. The potential indica- tors considered are presented in Box 6-1. CALCIUM UPPER LEVELS: REVIEW OF POTENTIAL INDICATORS AND SELECTION OF INDICATORS Excess calcium intake from foods alone is difficult if not impossible to achieve. Rather, excess intakes are more likely to be associated with the use of calcium supplements. However, the potential indicators for the adverse outcomes of excessive calcium intake are not characterized by a robust

OCR for page 403
406 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D data set that clearly provides a basis for a dose–response relationship. The measures available are confounded by a range of variables including other dietary factors and pre-existing disease conditions. The “classic” toxicity state of hypercalcemia is seen with either calcium or vitamin D excess, although it appears that the symptoms of hypercal- cemia are manifested at relatively lower intake of calcium compared with vitamin D, for which high intakes are required to reach a toxic state. In the discussions below, hypercalcemia, as well as, hypercalciuria is described first as general conditions associated with the toxicity of either nutrient, followed by a discussion of adverse outcomes associated with excess calcium intake. The Toxic Condition of Hypercalcemia and Hypercalciuria Hypercalcemia occurs when serum calcium levels are 10.5 mg/dL (also expressed as 2.63 mmol/L) or greater depending on normative laboratory values. It can be induced by excess intake of calcium or vitamin D, but it is more commonly caused by conditions such as malignancy and primary hyperparathyroidism (Moe, 2008). Clinical signs and symptoms of hyper- calcemia may vary depending on the magnitude of the hypercalcemia and the rapidity of its elevation; they often include anorexia, weight loss, polyuria, heart arrhythmias, fatigue, and soft tissue calcifications (Jones, 2008). When serum calcium levels rise above 12 mg/dL, the kidney’s abil- ity to reabsorb calcium is often limited; in turn, hypercalciuria can occur, particularly with increased calcium or vitamin D intake. Hypercalciuria is present when urinary excretion of calcium exceeds 250 mg/day in women or 275-300 mg/day in men. Often, urinary calcium excretion is expressed as the ratio of calcium to creatinine excreted in 24 hours (milligrams of calcium per milligram of creatinine). Values above 0.3 mg/mg creatinine are considered to be within the hypercalcuric range. Hypercalcemia, in addition to leading to hypercalciuria, can cause re- nal insufficiency, vascular and soft tissue calcification including calcinosis leading to nephrocalcinosis, and nephrolithiasis. Nephrolithiasis, often referred to as kidney stones, can also be caused by hypercalciuria. Hyper- calciuria may occur in the absence of hypercalcemia and is related to either hyperabsorption of calcium in the gut or a renal leak whereby calcium excretion is enhanced. Both etiologies can lead to nephrocalcinosis. In the North American population, as many as 30 percent of persons ages 60 years or older have some degree of renal insufficiency (Coresch et al., 2005; Szczech et al., 2009). Decreased renal functioning may make persons more sensitive or susceptible to the effects of excess calcium or vitamin D intake. Urinary calcium excretion decreases in older adults, although it is not clear the extent to which this may be due to decreased

OCR for page 403
407 TOLERABLE UPPER INTAKE LEVELS calcium intake as compared to decreased renal function. However, if due to decreased renal function, older persons may be at higher risk for adverse effects derived from excess intakes. Moreover, decreased renal function simultaneously increases cardiovascular disease (CVD) risk and impairs cal- ciuric responses and calcium and phosphate homeostasis. Likewise, those using thiazide-based diuretics—a sizeable proportion of older adults—are more readily challenged by excess calcium and vitamin D due to reduction in calcium excretion from the kidney (Medarov, 2009). Excess Calcium and Hypercalcemia Leading to Renal Insufficiency Prior to the introduction of histamine-2 blockers and proton pump inhibitors, liquid formulations that contained high calcium levels and absorbable alkali were used to treat gastric and duodenal ulcers. High intake of these formulations, however, caused a variety of adverse effects including hypercalcemia and renal failure. The syndrome became known as “milk-alkali syndrome” or MAS (Hardt and Rivers, 1923; Burnett et al., 1949) and was originally associated with men with peptic ulcer disease. In this context, hypercalcemia causes emesis and natriuresis, which result in significant drops in extracellular blood volume. This contraction worsens the hypercalcemia. Decreases in blood volume also induce an alkalotic state that causes an increase in proximal tubular bicarbonate resorption. Also, high serum calcium levels worsen the alkalosis through suppression of parathyroid hormone (PTH), which physiologically enhances bicarbon- ate excretion. Although the availability of absorbable alkali in the diet may enhance the alkalotic state, it is not the major pathogenic factor in MAS. Recently, Patel and Goldfarb (2010) suggested renaming MAS as “calcium-alkali syndrome” to better reflect the current understanding of the disorder, which now has shifted to be more prevalent in other groups including postmenopausal women. The earlier MAS presented with hyper- phosphatemia after prolonged ingestion of phosphorus-containing milk with cream (Patel and Goldfarb, 2010). In contrast, the modern version of the syndrome is associated with hypophosphatemia or low-normal serum phosphorus levels as a result of the phosphorus-binding properties of cal- cium carbonate. The hypophosphatemia is more pronounced in elderly patients or those with eating disorders, who tend to have relatively low consumption of protein and therefore phosphorus (Picolos et al., 2005; Felsenfeld and Levine, 2006; Medarov, 2009). Confounding this, however, is the chronic renal insufficiency that often accompanies MAS; in that case, serum phosphorus levels may be normal or high. Available case reports tend to provide only serum calcium levels and do not specify calcium in- takes per se, or serum phosphate, associated with the condition. As shown in Table 6-1, a number of recent case reports have been iden-

OCR for page 403
TABLE 6-1 Case Reports of Calcium-Alkali Syndrome 408 Patient Gender/Age Calcium Carbonate Serum Calcium Level Creatinine Level Reference (years) Intake (mg/day) Duration (mmol/L) mg/dL (µmol/L) mg/dL Javed et al., 2007 Male/70 1 year (3.43) 13.7 (344.8) 3.9 > 1,000 Nabhan et al., 2004 Female/61 1,500 + 600 IU Several years (6.43) 25.7 (106.1) 1.2 vitamin D Caruso et al., 2007 Male/60 NR (3.08) 12.3 (530.4) 6.0 > 2,000 + 800 IU vitamin D Gordon et al., 2005 Female/35 3,000 1 month (2.64) 10.6 (190.0) 2.1 Shah et al., 2007 Female/47 3,000 + 200 IU NR (4.13) 16.5 (362.4) 4.1 vitamin D Kaklamanos and Perros, Female/76 5,500 2 years (3.45) 13.8 (124.0) 1.4 2007 Grubb et al., 2009 Female/51 7,200 NR (5.70) 22.8 (185.6) 2.1 Ulett et al., 2010 Male/46 NR (3.98) 15.9 (406.6) 4.6 > 7,500 Irtiza-Ali et al., 2008 Case 1: Female/48 Case 1: ~ 8,000 Case 1: 19 years Case 1: (3.25) 13.0 Case 1: (737) 8.3 Case 2: Male/74 Case 2: ~ 18,000 Case 2: several weeks Case 2: (3.31) 13.2 Case 2: (245) 2.8 Case 3: Male/51 Case 3: ~ 44,000 Case 3: NR Case 3: (2.97) 11.9 Case 3: (1,013) 11.5 Jousten and Guffens, 2008 Male/66 ~ 10,000 Several months (4.15) 16.6 (459.7) 5.2 Bailey et al., 2008 Female/40 ~ 11,000 NR (4.71) 18.8 (164.0) 1.9 Waked et al., 2009 Male/81 ~ 12,500 NR (3.65) 13.8 (733.7) 8.3 NOTE: To convert mmol/L to mg/dL, multiply by 0.25; IU = International Units; NR = not reported.

OCR for page 403
409 TOLERABLE UPPER INTAKE LEVELS tified for calcium-alkali syndrome. For these individuals, a calcium intake of 3,000 mg/day was associated with the onset of hypercalcemia. However, in every case except one, all outcomes were found in individuals with im- paired renal function and high serum creatinine levels. The one exception (Nabhan et al., 2004) was a patient who was using hydrochlorothiazide as a diuretic and was hypoparathyroid. Although these data cannot be ap- plied directly to the normal, free-living population, they are informative and indicate that calcium levels of 3,000 mg/day are problematic for these compromised persons. Patel and Goldfarb (2010) suggested that the incidence of calcium- alkali syndrome is growing as a result of the widespread use of over-the- counter calcium and vitamin D supplements, particularly among older persons. The basis for the suggestion is that while healthy younger adults rely on the bone reservoir to buffer excess calcium, the net flux of calcium is out of the bone for older persons, thereby making the bone less func- tional as a reservoir. These older persons are more susceptible to the syn- drome when they begin taking supplemental calcium. Patel and Goldfarb (2010) also noted that the excess ingestion of calcium with or without vitamin D is an integral feature of this syndrome, making it potentially relevant to the consideration of upper levels of calcium intake. Excess Calcium and Soft Tissue Calcification Associated with Hypercalcemia Calcification of soft tissues—calcinosis—occurs as a result of long- standing hypercalcemia, increased serum phosphate levels, or local abnor- mality in the affected tissues. Clinically, the condition is linked to metabolic disorders such as hyperparathyroidism, sarcoidosis, or connective tissue disease such as scleroderma.1 Calcification of kidney tissues, or nephrocalcinosis, results in symptoms similar to those of renal dysfunction, ranging from painful and frequent urination to nausea, vomiting, and swelling. Although nephrocalcinosis has been reported to be induced by calcium intake in rats (Peterson et al., 1996), no data link calcium intake or the use of calcium supplements in humans to the onset of nephrocalcinosis. Nephrocalcinosis may be associ- ated with calcium nephrolithiasis under particular conditions (Vervaet et al., 2009). Relative to hypercalcemia and calcification of vascular tissue, there is 1Soft tissue calcifications are more severe in hypocalcemic disorders such as hypoparathy- roidism and renal failure, but in such cases it is the associated hyperphosphatemia that is causing the calcifications.

OCR for page 403
410 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D experimental evidence in humans and laboratory animals indicating that hypercalcemia can lead to vascular calcification in the setting of renal in- sufficiency as a result of elevated calcium and phosphate concentrations (Reynolds et al., 2004; Yang et al., 2004; Cozzolino et al., 2005). However, this has not been demonstrated clinically. Associated with Calcium Supplements Calcification of vascular tissues has been reported with high calcium intake (Goodman et al., 2000; Asmus et al., 2005; Block et al., 2005; Raggi et al., 2005); however, the reports are based on individuals with compro- mised kidney function. No link has been clearly established for a general population. Bolland et al. (2008), in a recent randomized, placebo-controlled trial, found that cardiovascular events may be slightly more prevalent in older women on calcium supplementation. Reid and Bolland (2008), in a subsequent companion publication, suggested among other possibilities that vascular calcification may be relevant to their finding of an upward trend in cardiovascular event rates in healthy postmenopausal women supplemented with calcium. These findings were contrary to the purported benefits of calcium supplementation and CVD. A more recent meta-analysis conducted by Bolland et al. (2010) ex- amined 11 randomized controlled trials of calcium supplements in 12,000 older patients and found that there was a 30 percent increased risk of heart attack independent of age, gender, and type of supplement. Although this report is of concern, there are several relevant limitations. The studies included are small, the event frequency is low, and most outcomes have confidence intervals (CIs) that overlap. Moreover, cardiovascular events were not a primary outcome, the events may not have been well adjudi- cated, and renal function was not considered as a covariate. Many of the studies supplemented with 1,000 to 1,200 mg of calcium per day and did not report the total calcium intake (supplement plus diet). The events may therefore be associated with intakes higher than the supplemented dose, perhaps 2,000 mg of calcium per day or more, as reported, for example, by Jackson et al. (2006). Under these circumstances, it is difficult to conclude that calcium intakes per se in the range of 1,000 to 1,200 mg/day can be associated with cardiovascular events. In addition, some questions remain as to whether the addition of this amount of calcium to a baseline diet as a calcium supplement may have adverse consequences. Excess Calcium and Nephrolithiasis (Kidney Stones) More than 12 percent of men and 6 percent of women in the general population will develop kidney stones (Stamatelou et al., 2003). The mor-

OCR for page 403
411 TOLERABLE UPPER INTAKE LEVELS bidity of kidney stones is not limited to the pain of stone passage; stones increase the risk of renal and urinary tract infections as well as renal insuffi- ciency. A contributing factor in stone formation is hypercalciuria from any cause; another is hyperabsorption of calcium from the gut. Hypercalciuria increases the risk for nephrolithiasis (Pak and Holt, 1976). Hypercalciuria can be present in the absence of hypercalcemia and may reflect routine excretion of excess calcium intake. Incidence rates for kidney stones vary by age and gender. The rates are highest in men, rising after age 20, peaking between 40 and 60 years, and then beginning to decline (Johnson et al., 1979; Hiatt et al., 1982; Curhan et al., 1993). For women, incidence rates seem to be higher in the late 20s, decreasing by age 50, and then remaining relatively constant (Johnson et al., 1979; Hiatt et al., 1982; Curhan et al., 1997, 2004). Although calcium is present in approximately 80 percent of kidney stones (Coe et al., 1992), the role of calcium and other nutrients, acting alone or in concert as risk factors, is not completely understood and may be a function of physiological context. Various dietary and non-dietary fac- tors are associated with stone formation, making data difficult to interpret. Rodent models that have been used to explore the effect of dietary factors on the propensity to form calcium oxalate and calcium phosphate stones suggest that the role of supplemental calcium in determining risk for neph- rolithiasis varies by interaction with a given dietary component. One study in rats compared renal oxalate crystallization relative to the consumption of calcium-supplemented or oxalate-rich diets as well as control diets. The study found that rats fed the calcium-supplemented diet had enhanced calcium and oxalate accumulation as well as crystallization in renal tissues, even though urinary oxalate and citrate excretion was not significantly different in rats fed the control diet (Mourad et al., 2006). In this study, measures of renal function, including glomerular filtration rate, fractional excretion of urea, and fractional reabsorption of water and magnesium were not affected by the calcium-supplemented diet, and calciuria was only slightly increased. Nephrolithiasis in Adults Recently, a study using data from the Women’s Health Initiative (WHI) trial, which recruited more than 36,000 post-menopausal women ages 50 to 79 years (mean age 62 years), reported findings on the incidence of kidney stones (Jackson et al., 2006). Participants were randomly assigned to receive a placebo or 1,000 mg of elemental calcium (calcium carbon- ate) per day with 400 International Units (IU) of vitamin D3. The primary outcome focus was fractures and measures of bone density. Mean baseline intake of calcium was approximately 1,100 mg/day and the supplement added another 1,000 mg/day, for a total average calcium intake of about

OCR for page 403
412 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D 2,100 mg/day for the experimental group. The mean baseline intake for vitamin D was about 365 IU/day, which, when combined with the vitamin D supplement, resulted in an approximate vitamin D intake of 765 IU/day for the experimental group. The rate of adherence (defined as use of 80 percent or more of the assigned study supplements) ranged from 60 to 63 percent during the first 3 years of follow-up, with an additional 13 to 21 percent of the participants taking at least half of their study pills. At the end of the trial, 76 percent were still taking the study supplements, and 59 percent were taking 80 percent or more of the supplements. Among the healthy postmenopausal women in the WHI study, the doses of calcium and vitamin D resulted in an increased risk (17 percent) of kidney stones. Kidney stones were reported by 449 women in the supple- mented group, compared with 381 women in the placebo group. With respect to the intention to treat, the reported hazard ratio (HR) was 1.17 (95% CI: 1.02–1.34). Although this study did not focus on calcium intake alone, the total vitamin D intakes were around 800 IU/day, a level that is not associated with either hypercalcemia or hypercalciuria. Therefore, it is reasonable to consider the possibility that total calcium intake of 2,100 mg per day were associated with increased kidney stones in this popula- tion. Although the kidney stone events were not adjudicated specifically, adjudication problems should be randomly distributed and thus not a contributing factor to the outcome. The WHI reflects a large, well-designed cohort study. There is also a re- port from a small, short trial (covering 4 years) of 236 elderly women with a baseline calcium intake of 800 mg/day and with calcium supplementation of 1,600 mg/day for 1 year (total calcium intake of approximately 2,400 mg/day) (Riggs et al., 1998). In this study, 50 percent of subjects receiv- ing supplemental calcium and 8 percent of placebo controls had urinary calcium levels exceeding 350 mg/day, but no subjects in the calcium group experienced nephrolithiasis, nephrocalcinosis, or a decrease in glomerular filtration rate. Other smaller trials among older subjects have shed little light on the issue of nephrolithiasis and calcium intake, either because the doses were relatively low or because subjects were recruited on the basis of having had previous incidence of kidney stones (Levine et al., 1994; Williams et al., 2001; Borghi et al., 2002). Curhan et al. (1997) examined the risk for kidney stones in women 34 to 59 years of age, using data from the Nurses’ Health Study (NHS), a nota- bly younger group of subjects than those included in the WHI study. They reported an inverse association between calcium intake from foods, but a positive relationship between risk and intake of calcium from supplements (Curhan et al., 1997). In a 2004 study, Curhan and colleagues (Curhan et al., 2004) prospectively examined data again from the NHS for an 8-year period relative to dietary factors and the risk for kidney stones in women 27 to 44 years of age. In this analysis, the inverse relationship between calcium

OCR for page 403
413 TOLERABLE UPPER INTAKE LEVELS intake from foods and the risk of kidney stone formation remained, but there was no apparent relationship between supplement use and risk. In a study of 50,000 men 40 to 75 years of age (Curhan et al., 1993), the same relationship was evident: reduced risk with increased intake of calcium from food sources, but no association with use of calcium supplements. The suggested discrepancy between the risks from food sources of calcium and from calcium supplements may in part be due to the timing of the supplement intake (Curhan et al., 2007). Calcium present in the food will bind oxalate, a known contributor to kidney stone formation, and prevent its absorption. If taken between meals, the calcium would have less opportunity to bind oxalate, and so oxalate absorption would be increased. These observations suggest that taking calcium supplements with meals should reduce the formation of kidney stones, but this has not been tested. Overall, the data indicate that the calcium content of foods does not cause stone formation, but may be protective against it. On the other hand, calcium supplements are emerging as a concern based on observa- tional data, at least for some groups under certain circumstances. Further, individuals with a history of kidney stones are at increased risk if they obtain their calcium from supplements rather than food sources. There is, however, limited evidence from small, short-term trials suggesting that supplemental calcium in moderate doses may not increase risk for stone recurrence. The most important evidence to date is from the WHI trial (Jackson et al., 2006), which indicated that a mean calcium intake from foods and supplements that totaled about 2,150 mg/day—plus a vitamin D supplement of 400 IU/day, a level low enough to avoid potential con- founding effects for adverse events given the mean total vitamin D intake of approximately 750 IU/day—resulted in a 17 percent increased incidence of kidney stones among postmenopausal women, regardless of whether the subjects had experienced previous clinical events related to urinary calculi formation. Nephrolithiasis in Children Hypercalciuria, as a secondary outcome to high calcium intake, can occur in children as well as in adults. However, the incidence of kidney stones in children is rare. There is limited evidence concerning high cal- cium intakes in young children relative to calcium excretion. In a study of children ages 1 to 6 years and designed to test the effects of 1,800 mg/day total calcium (supplementation adjusted on the basis of dietary calcium questionnaire), the calcium intake of 1,800 mg/day calcium did not cause urinary calcium/creatinine ratios to differ significantly from those of pla- cebo controls (Markowitz et al., 2004). A study by Sargent et al. (1999) provides information relevant to infants and calcium excretion. This study supplemented the formula of full-term

OCR for page 403
446 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D ULs for Pregnancy and Lactation Pregnant or Lactating 14 Through 18 Years of Age Pregnant or Lactating 19 Through 30 Years of Age Pregnant or Lactating 31 Through 50 Years of Age UL 4,000 IU (100 µg)/day Vitamin D The available data do not indicate a basis for deriving a UL for preg- nant and lactating women or adolescents that is different from those for their non-pregnant and non-lactating counterparts. REFERENCES Adams, J. S. and G. Lee. 1997. Gains in bone mineral density with resolution of vitamin D intoxication. Annals of Internal Medicine 127(3): 203-6. Aloia, J. F., M. Patel, R. Dimaano, M. Li-Ng, S. A. Talwar, M. Mikhail, S. Pollack and J. K. Yeh. 2008. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. American Journal of Clinical Nutrition 87(6): 1952-8. Ames, S. K., B. M. Gorham and S. A. Abrams. 1999. Effects of high compared with low cal- cium intake on calcium absorption and incorporation of iron by red blood cells in small children. American Journal of Clinical Nutrition 70(1): 44-8. Anthoni, S., E. Savilahti, H. Rautelin and K. L. Kolho. 2009. Milk protein IgG and IgA: the association with milk-induced gastrointestinal symptoms in adults. World Journal of Gastroenterology 15(39): 4915-8. Asmus, H. G., J. Braun, R. Krause, R. Brunkhorst, H. Holzer, W. Schulz, H. H. Neumayer, P. Raggi and J. Bommer. 2005. Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrology, Dialysis, Trans- plantation 20(8): 1653-61. Bailey, C. S., J. J. Weiner, O. M. Gibby and M. D. Penney. 2008. Excessive calcium ingestion leading to milk-alkali syndrome. Annals of Clinical Biochemistry 45(Pt 5): 527-9. Bajwa, G. S., L. M. Morrison and B. H. Ershoff. 1971. Induction of aortic and coronary athero- arteriosclerosis in rats fed a hypervitaminosis D, cholesterol-containing diet. Proceedings of the Society for Experimental Biology and Medicine 138(3): 975-82. Barger-Lux, M. J. and R. P. Heaney. 2002. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. Journal of Clinical Endocrinology and Metabolism 87(11): 4952-6. Baron, J. A., M. Beach, K. Wallace, M. V. Grau, R. S. Sandler, J. S. Mandel, D. Heber and E. R. Greenberg. 2005. Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiology, Biomarkers & Prevention 14(3): 586-9. Binkley, N., R. Novotny, D. Krueger, T. Kawahara, Y. G. Daida, G. Lensmeyer, B. W. Hollis and M. K. Drezner. 2007. Low vitamin D status despite abundant sun exposure. Journal of Clinical Endocrinology and Metabolism 92(6): 2130-5. Blank, S., K. S. Scanlon, T. H. Sinks, S. Lett and H. Falk. 1995. An outbreak of hypervitamin- osis D associated with the overfortification of milk from a home-delivery dairy. American Journal of Public Health 85(5): 656-9.

OCR for page 403
447 TOLERABLE UPPER INTAKE LEVELS Block, G. A., D. M. Spiegel, J. Ehrlich, R. Mehta, J. Lindbergh, A. Dreisbach and P. Raggi. 2005. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney International 68(4): 1815-24. Bolland, M. J., P. A. Barber, R. N. Doughty, B. Mason, A. Horne, R. Ames, G. D. Gamble, A. Grey and I. R. Reid. 2008. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. British Medical Journal 336(7638): 262-6. Bolland, M. J., A. Avenell, J. A. Baron, A. Grey, G. S. MacLennan, G. D. Gamble and I. R. Reid. 2010. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. British Medical Journal 341: 3691-9. Borghi, L., T. Schianchi, T. Meschi, A. Guerra, F. Allegri, U. Maggiore and A. Novarini. 2002. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercal- ciuria. New England Journal of Medicine 346(2): 77-84. Brannon, P. M., E. A. Yetley, R. L. Bailey and M. F. Picciano. 2008. Vitamin D and health in the 21st century: an update. Proceedings of a conference held September 2007 in Bethesda, Maryland, USA. American Journal of Clinical Nutrition 88(2): 483S-592S. Bransby, E. R., W. T. Berry and D. M. Taylor. 1964. Study of the vitamin-D intakes of infants in 1960. British Medical Journal 1(5399): 1661-3. British Paediatric Association. 1956. Hypercalcaemia in infants and vitamin D. British Medical Journal 2(4985): 149. British Paediatric Association. 1964. Infantile hypercalcaemia, nutritional rickets, and infan- tile scurvy in Great Britain. British Medical Journal 1(5399): 1659-61. Burnett, C. H., R. R. Commons and et al. 1949. Hypercalcemia without hypercalcuria or hypophosphatemia, calcinosis and renal insufficiency; a syndrome following prolonged intake of milk and alkali. New England Journal of Medicine 240(20): 787-94. Byrne, P. M., R. Freaney and M. J. McKenna. 1995. Vitamin D supplementation in the elderly: review of safety and effectiveness of different regimes. Calcified Tissue International 56(6): 518-20. Caruso, J. B., R. M. Patel, K. Julka and D. C. Parish. 2007. Health-behavior induced disease: return of the milk-alkali syndrome. Journal of General Internal Medicine 22(7): 1053-5. Cauley, J., et al. 2009. Serum 25 hydroxyvitamin (OH)D and fracture risk in multi-ethnic women: The Women’s Health Initiative (WHI). Presented at ASBMR 31st Annual Meet- ing. Denver, CO. Chan, J. M., P. Pietinen, M. Virtanen, N. Malila, J. Tangrea, D. Albanes and J. Virtamo. 2000. Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland). Cancer Causes and Control 11(9): 859-67. Chan, J. M., M. J. Stampfer, J. Ma, P. H. Gann, J. M. Gaziano and E. L. Giovannucci. 2001. Dairy products, calcium, and prostate cancer risk in the Physicians’ Health Study. Ameri- can Journal of Clinical Nutrition 74(4): 549-54. Chiricone, D., N. G. De Santo and M. Cirillo. 2003. Unusual cases of chronic intoxication by vitamin D. Journal of Nephrology 16(6): 917-21. Chlebowski, R. T., K. C. Johnson, C. Kooperberg, M. Pettinger, J. Wactawski-Wende, T. Rohan, J. Rossouw, D. Lane, M. J. O’Sullivan, S. Yasmeen, R. A. Hiatt, J. M. Shikany, M. Vitolins, J. Khandekar and F. A. Hubbell. 2008. Calcium plus vitamin D supplementation and the risk of breast cancer. Journal of the National Cancer Institute 100(22): 1581-91. Chung M., E. M. Balk, M. Brendel, S. Ip, J. Lau, J. Lee, A. Lichtenstein, K. Patel, G. Raman, A. Tatsioni, T. Terasawa and T. A. Trikalinos. 2009. Vitamin D and calcium: a systematic review of health outcomes. Evidence Report No. 183. (Prepared by the Tufts Evidence- based Practice Center under Contract No. HHSA 290-2007-10055-I.) AHRQ Publication No. 09-E015. Rockville, MD: Agency for Healthcare Research and Quality.

OCR for page 403
448 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Coe, F. L., J. H. Parks and D. R. Webb. 1992. Stone-forming potential of milk or calcium- fortified orange juice in idiopathic hypercalciuric adults. Kidney International 41(1): 139-42. Coresh, J., D. Byrd-Holt, B. C. Astor, J. P. Briggs, P. W. Eggers, D. A. Lacher and T. H. Hostet- ter. 2005. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. Journal of the American Society of Nephrology 16(1): 180-8. Cozzolino, M., D. Brancaccio, M. Gallieni and E. Slatopolsky. 2005. Pathogenesis of vascular calcification in chronic kidney disease. Kidney International 68(2): 429-36. Cranney A., T. Horsley, S. O’Donnell, H. A. Weiler, L. Puil, D. S. Ooi, S. A. Atkinson, L. M. Ward, D. Moher, D. A. Hanley, M. Fang, F. Yazdi, C. Garritty, M. Sampson, N. Barrowman, A. Tsertsvadze and V. Mamaladze. 2007. Effectiveness and safety of vitamin D in relation to bone health. Evidence Report/Technology Assessment No. 158. (Pre- pared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021.) AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. Curhan, G. C., W. C. Willett, E. B. Rimm and M. J. Stampfer. 1993. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. New England Journal of Medicine 328(12): 833-8. Curhan, G. C., W. C. Willett, F. E. Speizer, D. Speigelman and M. J. Stampfer. 1997. Compari- son of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Annals of Internal Medicine 126(7): 497-504. Curhan, G. C., W. C. Willett, E. L. Knight and M. J. Stampfer. 2004. Dietary factors and the risk of incident kidney stones in younger women: Nurses’ Health Study II. Archives of Internal Medicine 164(8): 885-91. Curhan, G. C. 2007. Epidemiology of stone disease. Urologic Clinics of North America 34(3): 287-93. Dalton, M. A., J. D. Sargent, G. T. O’Connor, E. M. Olmstead and R. Z. Klein. 1997. Calcium and phosphorus supplementation of iron-fortified infant formula: no effect on iron status of healthy full-term infants. American Journal of Clinical Nutrition 65(4): 921-6. Davie, M. W., D. E. Lawson, C. Emberson, J. L. Barnes, G. E. Roberts and N. D. Barnes. 1982. Vitamin D from skin: contribution to vitamin D status compared with oral vitamin D in normal and anticonvulsant-treated subjects. Clinical Science 63(5): 461-72. Davies, M. and P. H. Adams. 1978. The continuing risk of vitamin-D intoxication. Lancet 2(8090): 621-3. Deluca, H. F. 2009. Vitamin D toxicity. Paper prepared for the Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Washington, DC. Dourson, M. L. and J. F. Stara. 1983. Regulatory history and experimental support of uncer- tainty (safety) factors. Regulatory Toxicology and Pharmacology 3(3): 224-38. Faupel-Badger, J. M., L. Diaw, D. Albanes, J. Virtamo, K. Woodson and J. A. Tangrea. 2007. Lack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in Finnish men. Cancer Epidemiology, Biomarkers & Prevention 16(12): 2784-6. Felsenfeld, A. J. and B. S. Levine. 2006. Milk alkali syndrome and the dynamics of calcium homeostasis. Clinical Journal of the American Society of Nephrology 1(4): 641-54. Fiscella, K. and P. Franks. 2010. Vitamin D, race, and cardiovascular mortality: findings from a national US sample. Annals of Family Medicine 8(1): 11-8. Fomon, S. J., M. K. Younoszai and L. N. Thomas. 1966. Influence of vitamin D on linear growth of normal full-term infants. Journal of Nutrition 88(3): 345-50.

OCR for page 403
449 TOLERABLE UPPER INTAKE LEVELS Freedman, B. I., L. E. Wagenknecht, K. G. Hairston, D. W. Bowden, J. J. Carr, R. C. Hightower, E. J. Gordon, J. Xu, C. D. Langefeld and J. Divers. 2010. Vitamin D, adiposity, and calci- fied atherosclerotic plaque in African-Americans. Journal of Clinical Endocrinology and Metabolism 95(3): 1076. Ginde, A. A., R. Scragg, R. S. Schwartz and C. A. Camargo, Jr. 2009. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. Journal of the American Geriatrics Society 57(9): 1595-603. Giovannucci, E., E. B. Rimm, A. Wolk, A. Ascherio, M. J. Stampfer, G. A. Colditz and W. C. Willett. 1998. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Research 58(3): 442-7. Giovannucci, E., Y. Liu, M. J. Stampfer and W. C. Willett. 2006a. A prospective study of cal- cium intake and incident and fatal prostate cancer. Cancer Epidemiology, Biomarkers & Prevention 15(2): 203-10. Giovannucci, E., Y. Liu and W. C. Willett. 2006b. Cancer incidence and mortality and vitamin D in black and white male health professionals. Cancer Epidemiology, Biomarkers & Prevention 15(12): 2467-72. Goodman, W. G., J. Goldin, B. D. Kuizon, C. Yoon, B. Gales, D. Sider, Y. Wang, J. Chung, A. Emerick, L. Greaser, R. M. Elashoff and I. B. Salusky. 2000. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. New England Journal of Medicine 342(20): 1478-83. Gordon, M. V., L. P. McMahon and P. S. Hamblin. 2005. Life-threatening milk-alkali syn- drome resulting from antacid ingestion during pregnancy. Medical Journal of Australia 182(7): 350-1. Graham, S. 1959. Idiopathic hypercalcemia. Postgraduate Medicine 25(1): 67-72. Grant, W. B. 1999. An ecologic study of dietary links to prostate cancer. Alternative Medicine Review 4(3): 162-9. Grant, W. B. 2010. Critique of the U-shaped serum 25-hydroxyvitamin D level-disease response relation. Dermato-Endocrinology 1(6): 289. Grubb, M., K. Gaurav and M. Panda. 2009. Milk-alkali syndrome in a middle-aged woman after ingesting large doses of calcium carbonate: a case report. Cases Journal 2: 8198. Haddad, J. G. 1980. Competitive protein-binding radioassays for 25-OH-D; clinical applica- tions. In Vitamin D, Volume 2, edited by Norman. New York: Marcel Dekker, Inc. Pp. 587. Hardt, L. L. and A. B. Rivers. 1923. Toxic manifestations following the alkaline treatment of peptic ulcer. Archives of Internal Medicine 31(2): 171-80. Harmeyer, J. and C. Schlumbohm. 2004. Effects of pharmacological doses of vitamin D3 on mineral balance and profiles of plasma vitamin D3 metabolites in horses. Journal of Steroid Biochemistry and Molecular Biology 89-90(1-5): 595-600. Harrington, D. D. and E. H. Page. 1983. Acute vitamin D3 toxicosis in horses: case reports and experimental studies of the comparative toxicity of vitamins D2 and D3. Journal of the American Veterinary Medical Association 182(12): 1358-69. Hathcock, J. N., A. Shao, R. Vieth and R. Heaney. 2007. Risk assessment for vitamin D. Ameri- can Journal of Clinical Nutrition 85(1): 6-18. Heaney, R. P., K. M. Davies, T. C. Chen, M. F. Holick and M. J. Barger-Lux. 2003. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. American Journal of Clinical Nutrition 77(1): 204-10. Hiatt, R. A., L. G. Dales, G. D. Friedman and E. M. Hunkeler. 1982. Frequency of urolithiasis in a prepaid medical care program. American Journal of Epidemiology 115(2): 255-65. Honkanen, R., E. Alhava, M. Parviainen, S. Talasniemi and R. Monkkonen. 1990. The neces- sity and safety of calcium and vitamin D in the elderly. Journal of the American Geriatrics Society 38(8): 862-6.

OCR for page 403
450 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Hruska, K. A., S. Mathew, R. J. Lund, I. Memon and G. Saab. 2009. The pathogenesis of vascu- lar calcification in the chronic kidney disease mineral bone disorder: the links between bone and the vasculature. Seminars in Nephrology 29(2): 156-65. Hughes, M. R., D. J. Baylink, W. A. Gonnerman, S. U. Toverud, W. K. Ramp and M. R. Haussler. 1977. Influence of dietary vitamin D3 on the circulating concentration of its active metabolites in the chick and rat. Endocrinology 100(3): 799-806. Hunt, R. D., F. G. Garcia and R. J. Walsh. 1972. A comparison of the toxicity of ergocalciferol and cholecalciferol in rhesus monkeys (Macaca mulatta). Journal of Nutrition 102(8): 975-86. Ilich-Ernst, J. Z., A. A. McKenna, N. E. Badenhop, A. C. Clairmont, M. B. Andon, R. W. Nah- has, P. Goel and V. Matkovic. 1998. Iron status, menarche, and calcium supplementation in adolescent girls. American Journal of Clinical Nutrition 68(4): 880-7. IOM (Institute of Medicine). 1997. Dietary Reference Intakes for Calcium, Phosphorus, Mag- nesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press. IOM. 1998. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper In- take Levels for Nutrients. Washington, DC: National Academy Press. IOM. 2008. The Development of DRIs 1994-2004: Lessons Learned and New Challenges: Workshop Summary. Washington, DC: The National Academies Press. Irtiza-Ali, A., S. Waldek, E. Lamerton, A. Pennell and P. A. Kalra. 2008. Milk alkali syndrome associated with excessive ingestion of Rennie: case reports. Journal of Renal Care 34(2): 64-7. Jackson, R. D., A. Z. LaCroix, M. Gass, R. B. Wallace, J. Robbins, C. E. Lewis, T. Bassford, S. A. Beresford, H. R. Black, P. Blanchette, D. E. Bonds, R. L. Brunner, R. G. Brzyski, B. Caan, J. A. Cauley, R. T. Chlebowski, S. R. Cummings, I. Granek, J. Hays, G. Heiss, S. L. Hendrix, B. V. Howard, J. Hsia, F. A. Hubbell, K. C. Johnson, H. Judd, J. M. Kotchen, L. H. Kuller, R. D. Langer, N. L. Lasser, M. C. Limacher, S. Ludlam, J. E. Manson, K. L. Margolis, J. McGowan, J. K. Ockene, M. J. O’Sullivan, L. Phillips, R. L. Prentice, G. E. Sarto, M. L. Stefanick, L. Van Horn, J. Wactawski-Wende, E. Whitlock, G. L. Anderson, A. R. Assaf and D. Barad. 2006. Calcium plus vitamin D supplementation and the risk of fractures. New England Journal of Medicine 354(7): 669-83. Javed, R. A., M. A. Rafiq, K. Marrero and J. Vieira. 2007. Milk-alkali syndrome: a reverberation of the past. Singapore Medical Journal 48(4): 359-60. Jeans, P. C. and G. Stearns. 1938. The effect of vitamin D on linear growth in infancy: II. The effect of intakes above 1,800 U.S.P. units daily. Journal of Pediatrics 13(5): 730-40. Jia, X., L. S. Aucott and G. McNeill. 2007. Nutritional status and subsequent all-cause mortal- ity in men and women aged 75 years or over living in the community. British Journal of Nutrition 98(3): 593-9. Johnson, C. M., D. M. Wilson, W. M. O’Fallon, R. S. Malek and L. T. Kurland. 1979. Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney International 16(5): 624-31. Johnson, K. R., J. Jobber and B. J. Stonawski. 1980. Prophylactic vitamin D in the elderly. Age and Ageing 9(2): 121-7. Jones, G. 2008. Pharmacokinetics of vitamin D toxicity. American Journal of Clinical Nutri- tion 88(2): 582S-6S. Jousten, E. and P. Guffens. 2008. Milk-alkali syndrome caused by ingestion of antacid tablets. Acta Clinica Belgica 63(2): 103-6. Kaklamanos, M. and P. Perros. 2007. Milk alkali syndrome without the milk. British Medical Journal 335(7616): 397-8. Kamio, A., T. Taguchi, M. Shiraishi, K. Shitama, K. Fukushima and S. Takebayashi. 1979. Vitamin D sclerosis in rats. Acta Pathologica Japonica 29(4): 545-62.

OCR for page 403
451 TOLERABLE UPPER INTAKE LEVELS Klontz, K. C. and D. W. Acheson. 2007. Dietary supplement-induced vitamin D intoxication. New England Journal of Medicine 357(3): 308-9. Koh, K. A., H. D. Sesso, R. S. Paffenbarger, Jr. and I. M. Lee. 2006. Dairy products, calcium and prostate cancer risk. British Journal of Cancer 95(11): 1582-5. Kristal, A. R., J. L. Stanford, J. H. Cohen, K. Wicklund and R. E. Patterson. 1999. Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention 8(10): 887-92. Kurahashi, N., M. Inoue, M. Iwasaki, S. Sasazuki and A. S. Tsugane. 2008. Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiology, Biomarkers and Prevention 17(4): 930-7. Levine, B. S., J. S. Rodman, S. Wienerman, R. S. Bockman, J. M. Lane and D. S. Chapman. 1994. Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis. American Journal of Clinical Nutrition 60(4): 592-6. Linden, V. 1974. Vitamin D and myocardial infarction. British Medical Journal 3(5932): 647-50. Littledike, E. T. and R. L. Horst. 1982a. Vitamin D3 toxicity in dairy cows. Journal of Dairy Science 65(5): 749-59. Littledike, E. T. and R. L. Horst. 1982b. Metabolism of vitamin D3 in nephrectomized pigs given pharmacological amounts of vitamin D3. Endocrinology 111(6): 2008-13. Markowitz, M. E., M. Sinnett and J. F. Rosen. 2004. A randomized trial of calcium supplemen- tation for childhood lead poisoning. Pediatrics 113(1 Pt 1): e34-9. McKenna, A. A., J. Z. Ilich, M. B. Andon, C. Wang and V. Matkovic. 1997. Zinc balance in adolescent females consuming a low- or high-calcium diet. American Journal of Clinical Nutrition 65(5): 1460-4. Medarov, B. I. 2009. Milk-alkali syndrome. Mayo Clinic Proceedings 84(3): 261-7. Melamed, M. L., E. D. Michos, W. Post and B. Astor. 2008. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Archives of Internal Medicine 168(15): 1629-37. Mitrou, P. N., D. Albanes, S. J. Weinstein, P. Pietinen, P. R. Taylor, J. Virtamo and M. F. Leitzmann. 2007. A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). International Journal of Cancer 120(11): 2466-73. Moe, S. M. 2008. Disorders involving calcium, phosphorus, and magnesium. Primary Care; Clinics in Office Practice 35(2): 215-37, v-vi. Mourad, B., N. Fadwa, T. Mounir, E. Abdelhamid, N. Mohamed Fadhel and S. Rachid. 2006. Influence of hypercalcic and/or hyperoxalic diet on calcium oxalate renal stone forma- tion in rats. Scandinavian Journal of Urology and Nephrology 40(3): 187-91. Nabhan, F. A., G. W. Sizemore and P. M. Camacho. 2004. Milk-alkali syndrome from inges- tion of calcium carbonate in a patient with hypoparathyroidism. Endocrine Practice 10(4): 372-5. Narang, N. K., R. C. Gupta and M. K. Jain. 1984. Role of vitamin D in pulmonary tuberculosis. Journal of the Association of Physicians of India 32(2): 185-8. Pak, C. Y. and K. Holt. 1976. Nucleation and growth of brushite and calcium oxalate in urine of stone-formers. Metabolism 25(6): 665-73. Park, S. Y., S. P. Murphy, L. R. Wilkens, A. M. Nomura, B. E. Henderson and L. N. Kolonel. 2007a. Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic Cohort Study. American Journal of Epidemiology 165(7): 784-93. Park, S. Y., S. P. Murphy, L. R. Wilkens, D. O. Stram, B. E. Henderson and L. N. Kolonel. 2007b. Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Mul- tiethnic Cohort Study. American Journal of Epidemiology 166(11): 1259-69.

OCR for page 403
452 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Patel, A. M. and S. Goldfarb. 2010. Got calcium? Welcome to the calcium-alkali syndrome. Journal of the American Society of Nephrology 21(9): 1440-3. Peterson, C. A., D. H. Baker and J. W. Erdman, Jr. 1996. Diet-induced nephrocalcinosis in female rats is irreversible and is induced primarily before the completion of adolescence. Journal of Nutrition 126(1): 259-65. Pettifor, J. M., D. D. Bikle, M. Cavaleros, D. Zachen, M. C. Kamdar and F. P. Ross. 1995. Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity. Annals of Internal Medicine 122(7): 511-3. Picolos, M. K., V. R. Lavis and P. R. Orlander. 2005. Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients. Clinical Endocrinology 63(5): 566-76. Prince, R. L., A. Devine, S. S. Dhaliwal and I. M. Dick. 2006. Effects of calcium supplementa- tion on clinical fracture and bone structure: results of a 5-year, double-blind, placebo- controlled trial in elderly women. Archives of Internal Medicine 166(8): 869-75. Raggi, P., G. James, S. K. Burke, J. Bommer, S. Chasan-Taber, H. Holzer, J. Braun and G. M. Chertow. 2005. Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis. Journal of Bone and Mineral Research 20(5): 764-72. Raimondi, S., J. B. Mabrouk, B. Shatenstein, P. Maisonneuve and P. Ghadirian. 2010. Diet and prostate cancer risk with specific focus on dairy products and dietary calcium: a case–control study. Prostate 70(10):1054-65. Reid, I. R. and M. J. Bolland. 2008. Calcium supplementation and vascular disease. Climacteric 11(4): 280-6. Reynolds, J. L., A. J. Joannides, J. N. Skepper, R. McNair, L. J. Schurgers, D. Proudfoot, W. Jahnen-Dechent, P. L. Weissberg and C. M. Shanahan. 2004. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracel- lular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. Journal of the American Society of Nephrology 15(11): 2857-67. Riggs, B. L., W. M. O’Fallon, J. Muhs, M. K. O’Connor, R. Kumar and L. J. Melton, 3rd. 1998. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. Journal of Bone and Mineral Research 13(2): 168-74. Rizzoli, R., C. Stoermann, P. Ammann and J. P. Bonjour. 1994. Hypercalcemia and hyper- osteolysis in vitamin D intoxication: effects of clodronate therapy. Bone 15(2): 193-8. Roborgh, J. R. and T. de Man. 1960. The hypercalcemic activity of dihydrotachysterol-2 and dihydrotachysterol-3 and of the vitamins D2 and D3 after intravenous injection of the aqueous preparations. 2. Comparative experiments on rats. Biochemical Pharmacology 3: 277-82. Rodriguez, C., M. L. McCullough, A. M. Mondul, E. J. Jacobs, D. Fakhrabadi-Shokoohi, E. L. Giovannucci, M. J. Thun and E. E. Calle. 2003. Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States men. Cancer Epidemiology, Biomarkers & Prevention 12(7): 597-603. Rohrmann, S., E. A. Platz, C. J. Kavanaugh, L. Thuita, S. C. Hoffman and K. J. Helzlsouer. 2007. Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study. Cancer Causes and Control 18(1): 41-50. Sambrook, P. N., J. S. Chen, L. M. March, I. D. Cameron, R. G. Cumming, S. R. Lord, J. Schwarz and M. J. Seibel. 2004. Serum parathyroid hormone is associated with increased mortality independent of 25-hydroxy vitamin d status, bone mass, and renal function in the frail and very old: a cohort study. Journal of Clinical Endocrinology and Metabolism 89(11): 5477-81.

OCR for page 403
453 TOLERABLE UPPER INTAKE LEVELS Sambrook, P. N., C. J. Chen, L. March, I. D. Cameron, R. G. Cumming, S. R. Lord, J. M. Simpson and M. J. Seibel. 2006. High bone turnover is an independent predictor of mortality in the frail elderly. Journal of Bone and Mineral Research 21(4): 549-55. Sanders, K. M., A. L. Stuart, E. J. Williamson, J. A. Simpson, M. A. Kotowicz, D. Young and G. C. Nicholson. 2010. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Journal of the American Medical Association 303(18): 1815-22. Sargent, J. D., M. A. Dalton, G. T. O’Connor, E. M. Olmstead and R. Z. Klein. 1999. Random- ized trial of calcium glycerophosphate-supplemented infant formula to prevent lead absorption. American Journal of Clinical Nutrition 69(6): 1224-30. Schmidt-Gayk, H., J. Goossen, F. Lendle and D. Seidel. 1977. Serum 25-hydroxycalciferol in myocardial infarction. Atherosclerosis 26(1): 55-8. Schuurman, A. G., P. A. van den Brandt, E. Dorant and R. A. Goldbohm. 1999. Animal prod- ucts, calcium and protein and prostate cancer risk in The Netherlands Cohort Study. British Journal of Cancer 80(7): 1107-13. Schwartzman, M. S. and W. A. Franck. 1987. Vitamin D toxicity complicating the treatment of senile, postmenopausal, and glucocorticoid-induced osteoporosis. Four case reports and a critical commentary on the use of vitamin D in these disorders. American Journal of Medicine 82(2): 224-30. Selby, P. L., M. Davies, J. S. Marks and E. B. Mawer. 1995. Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate. Clinical Endocrinology 43(5): 531-6. Semba, R. D., D. K. Houston, L. Ferrucci, A. R. Cappola, K. Sun, J. M. Guralnik and L. P. Fried. 2009. Low serum 25-hydroxyvitamin D concentrations are associated with greater all- cause mortality in older community-dwelling women. Nutrition Research 29(8): 525-30. Shah, B. K., S. Gowda, H. Prabhu, J. Vieira and H. C. Mahaseth. 2007. Modern milk alkali syndrome—a preventable serious condition. New Zealand Medical Journal 120(1262): U2734. Shephard, R. M. and H. F. Deluca. 1980. Plasma concentrations of vitamin D3 and its metabo- lites in the rat as influenced by vitamin D3 or 25-hydroxyvitamin D3 intakes. Archives of Biochemistry and Biophysics 202(1): 43-53. Skinner, H. G., D. S. Michaud, E. Giovannucci, W. C. Willett, G. A. Colditz and C. S. Fuchs. 2006. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiology, Biomarkers & Prevention 15(9): 1688-95. Smith, H., F. Anderson, H. Raphael, P. Maslin, S. Crozier and C. Cooper. 2007. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology 46(12): 1852-7. Stamatelou, K. K., M. E. Francis, C. A. Jones, L. M. Nyberg and G. C. Curhan. 2003. Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney International 63(5): 1817-23. Stamp, T. C., J. G. Haddad and C. A. Twigg. 1977. Comparison of oral 25-hydroxycholecalcif- erol, vitamin D, and ultraviolet light as determinants of circulating 25-hydroxyvitamin D. Lancet 1(8026): 1341-3. Stearns, G. 1968. Fifty years of experience in nutrition and a look to the future: III. Early stud- ies of vitamin D requirement during growth. American Journal of Public Health and the Nations Health 58(11): 2027-35. Stephenson, D. W. and A. N. Peiris. 2009. The lack of vitamin D toxicity with megadose of daily ergocalciferol (D2) therapy: a case report and literature review. Southern Medical Journal 102(7): 765-8.

OCR for page 403
454 DIETARY REFERENCE INTAKES FOR CALCIUM AND VITAMIN D Stolzenberg-Solomon, R. Z., R. Vieth, A. Azad, P. Pietinen, P. R. Taylor, J. Virtamo and D. Albanes. 2006. A prospective nested case–control study of vitamin D status and pancre- atic cancer risk in male smokers. Cancer Research 66(20): 10213-9. Stolzenberg-Solomon, R. Z. 2009. Vitamin D and pancreatic cancer. Annals of Epidemiology 19(2): 89-95. Stolzenberg-Solomon, R. Z., E. J. Jacobs, A. A. Arslan, D. Qi, A. V. Patel, K. J. Helzlsouer, S. J. Weinstein, M. L. McCullough, M. P. Purdue, X. O. Shu, K. Snyder, J. Virtamo, L. R. Wilkins, K. Yu, A. Zeleniuch-Jacquotte, W. Zheng, D. Albanes, Q. Cai, C. Harvey, R. Hayes, S. Clipp, R. L. Horst, L. Irish, K. Koenig, L. Le Marchand and L. N. Kolonel. 2010. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consor- tium Vitamin D Pooling Project of Rarer Cancers. American Journal of Epidemiology 172(1): 81-93. Szczech, L. A., W. Harmon, T. H. Hostetter, P. E. Klotman, N. R. Powe, J. R. Sedor, P. Smedberg and J. Himmelfarb. 2009. World Kidney Day 2009: problems and challenges in the emerging epidemic of kidney disease. Journal of the American Society of Nephrol- ogy 20(3): 453-5. Tangpricha, V., A. Turner, C. Spina, S. Decastro, T. C. Chen and M. F. Holick. 2004. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. American Journal of Clinical Nutrition 80(6): 1645-9. Taussig, H. B. 1966. Possible injury to the cardiovascular system from vitamin D. Annals of Internal Medicine 65(6): 1195-200. Tominaga, S. and T. Kuroishi. 1997. An ecological study on diet/nutrition and cancer in Japan. International Journal of Cancer (Suppl 10): 2-6. Towler, D. 2009. Adverse health effects of excessive vitamin D and calcium intake: consid- erations relevant to cardiovascular disease and nephrocalcinosis. A white paper com- missioned for the Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Washington, DC. Trivedi, D. P., R. Doll and K. T. Khaw. 2003. Effect of four monthly oral vitamin D3 (cho- lecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. British Medical Journal 326(7387): 469. Tryfonidou, M. A., M. A. Oosterlaken-Dijksterhuis, J. A. Mol, T. S. van den Ingh, W. E. van den Brom and H. A. Hazewinkel. 2003. 24-hydroxylase: potential key regulator in hy- pervitaminosis D3 in growing dogs. American Journal of Physiology, Endocrinology, and Metabolism 284(3): E505-13. Tseng, M., R. A. Breslow, B. I. Graubard and R. G. Ziegler. 2005. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. American Journal of Clinical Nutrition 81(5): 1147-54. Tuohimaa, P., L. Tenkanen, M. Ahonen, S. Lumme, E. Jellum, G. Hallmans, P. Stattin, S. Harvei, T. Hakulinen, T. Luostarinen, J. Dillner, M. Lehtinen and M. Hakama. 2004. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case–control study in the Nordic countries. International Journal of Cancer 108(1): 104-8. Ulett, K., B. Wells and R. Centor. 2010. Hypercalcemia and acute renal failure in milk-alkali syndrome: a case report. Journal of Hospital Medicine 5(2): E18-20. Vervaet, B. A., A. Verhulst, P. C. D’Haese and M. E. De Broe. 2009. Nephrocalcinosis: new in- sights into mechanisms and consequences. Nephrology, Dialysis, Transplantation 24(7): 2030-5. Vieth, R. 1990. The mechanisms of vitamin D toxicity. Bone and Mineral 11(3): 267-72.

OCR for page 403
455 TOLERABLE UPPER INTAKE LEVELS Vieth, R., T. R. Pinto, B. S. Reen and M. M. Wong. 2002. Vitamin D poisoning by table sugar. Lancet 359(9307): 672. Vieth, R. 2007. Vitamin D toxicity, policy, and science. Journal of Bone and Mineral Research 22(Suppl 2): V64-8. Vik, B., K. Try, D. S. Thelle and O. H. Forde. 1979. Tromso Heart Study: vitamin D metabolism and myocardial infarction. British Medical Journal 2(6183): 176. Visser, M., D. J. Deeg, M. T. Puts, J. C. Seidell and P. Lips. 2006. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. American Journal of Clinical Nutrition 84(3): 616-22; quiz 671-2. Wagner, C. L. and F. R. Greer. 2008. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 122(5): 1142-52. Waked, A., A. Geara and B. El-Imad. 2009. Hypercalcemia, metabolic alkalosis and renal failure secondary to calcium bicarbonate intake for osteoporosis prevention—“modern” milk alkali syndrome: a case report. Cases Journal 2: 6188. Wang, T. J., M. J. Pencina, S. L. Booth, P. F. Jacques, E. Ingelsson, K. Lanier, E. J. Benjamin, R. B. D’Agostino, M. Wolf and R. S. Vasan. 2008. Vitamin D deficiency and risk of car- diovascular disease. Circulation 117(4): 503-11. WCRF (World Cancer Research Fund)/AICR (American Institute for Cancer Research). 2007. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR. Webb, A. R., B. R. DeCosta and M. F. Holick. 1989. Sunlight regulates the cutaneous produc- tion of vitamin D3 by causing its photodegradation. Journal of Clinical Endocrinology and Metabolism 68(5): 882-7. Williams, C. P., D. F. Child, P. R. Hudson, G. K. Davies, M. G. Davies, R. John, P. S. Anandaram and A. R. De Bolla. 2001. Why oral calcium supplements may reduce renal stone disease: report of a clinical pilot study. Journal of Clinical Pathology 54(1): 54-62. Yang, H., G. Curinga and C. M. Giachelli. 2004. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney International 66(6): 2293-9. Yetley, E. A., D. Brule, M. C. Cheney, C. D. Davis, K. A. Esslinger, P. W. Fischer, K. E. Friedl, L. S. Greene-Finestone, P. M. Guenther, D. M. Klurfeld, M. R. L’Abbe, K. Y. McMurry, P. E. Starke-Reed and P. R. Trumbo. 2009. Dietary reference intakes for vitamin D: jus- tification for a review of the 1997 values. American Journal of Clinical Nutrition 89(3): 719-27. Zielhuis, R. L. and F. W. van der Kreek. 1979. Calculation of a safety factor in setting health based permissible levels for occupational exposure. II. Comparison of extrapolated and published permissible levels. International Archives of Occupational and Environmental Health 42(3-4): 203-15.

OCR for page 403