Dietary Reference Intakes for Calcium and Vitamin D

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Table of Contents
Front Matter R1-R16
Summary 1-14
1 Introduction 15-34
2 Overview of Calcium 35-74
3 Overview of Vitamin D 75-124
4 Review of Potential Indicators of Adequacy and Selection of Indicators: Calcium and Vitamin D 125-344
5 Dietary Reference Intakes for Adequacy: Calcium and Vitamin D 345-402
6 Tolerable Upper Intake Levels: Calcium and Vitamin D 403-456
7 Dietary Intake Assessment 457-478
8 Implications and Special Concerns 479-512
9 Information Gaps and Research Needs 513-522
Appendix A: Acronyms, Abbreviations, and Glossary 523-536
Appendix B: Issues and Interests Identified by Study Sponsors 537-538
Appendix C: Methods and Results from the AHRQ-Ottawa Evidence-Based Report on Effectiveness and Safety of Vitamin D in Relation to Bone Health 539-724
Appendix D: Methods and Results from the AHRQ-Tufts Evidence-Based Report on Vitamin D and Calcium 725-1012
Appendix E: Literature Search Strategy 1013-1018
Appendix F: Evidence Maps 1019-1024
Appendix G: Cases Studies of Vitamin D Toxicity 1025-1034
Appendix H: Estimated Intakes of Calcium and Vitamin D from National Surveys 1035-1044
Appendix I: Proportion of the Population Above and Below 40 nmol/L Serum 25-Hydroxyvitamin D Concentrations and Cumulative Distribution of Serum 25-Hydroxyvitamin D Concentrations: United States and Canada 1045-1058
Appendix J: Workshop Agenda and Open Session Agendas 1059-1064
Appendix K: Biographical Sketches of Committee Members 1065-1074
Index 1075-1102
Summary Tables: Dietary Reference Intakes 1103-1116

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Author (year) Duration (Timepoints for Toxicity Assessment)	% Vitamin D Deficient Population Exclusion Criteria Ethnicity (country)	Sample Size	Intervention Compliance	Followup Serum 25(OH)D (nmol/L) Assay	Safety Outcomes
Lips (1988)²⁰⁹	79 % (serum 25(OH)D <30 nmol/L) 35% < 20 nmol/L	IG1: 70 IG2: 72	IG1: 400 IU vit D₃/d IG2: 800 IU vit D₃/d	increased to > 40 nmol/L in all subjects (means (SD) presented in graph only)	Hypercalcemia: IG1: 0 IG2: 1 (associated with thiazide use)
1 year	79 % (serum 25(OH)D <30 nmol/L) 35% < 20 nmol/L		IG1: 400 IU vit D₃/d IG2: 800 IU vit D₃/d
(2, 3 and every 3 mo thereafter)	Men and women living in two different levels of institutional care; mean age (SD): 81 (9) y nursing home); 84 (6) y (senior home)	Completers: nursing home: 50/72 (69%) seniors home: 59/70 (84%)			Ca/Cr ratio: fasting urinary Ca excretion increased ~ 15% unrelated to treatment in all groups, NS serum Cr: increase of ~ 4% in all groups (significant increase from baseline)
			Compliance NR
	Excluded subjects with hypercalcemia, active urolithiasis, or chronic renal failure			CPBA	Mortality: IG1: 223/1291 (17.2%) CG: 251/1287 (19.5%)
	NR (The Netherlands)
Mastaglia (2006)²¹²	NR median 36.25 (range 27.5-48.12)	IG1 13 IG2 13 CG 12	IG1: D₂ 5,000 IU/d + Ca 500 mg IG2: D₂ 10,000 IU/d + Ca 500 mg CG: Ca 500 mg	25(OH)D median (25-75th percentile):	Hypercalcemia: IG1: 0; IG2: 0 (increase in mean serum Ca at 2 mo but WNL) CG: 0
3 mo	Post menopausal osteopenic/osteoporotic women aged 50 - 70 y presenting for bone mass evaluation
				IG1 77.5 (66.2-156.2) IG2 97.7 (79.3-123.1) CG: 55.0 (72.5-68.0)
(0, 1, 2 and 3 mo)
					Hypercalciuria: IG1: 1 (urinary Ca excretion increased from 99.0 (69.5-147.5) to 152 (102-204) mg/24 h, p<0.05, at 3 mo); IG2: 1 (urinary calcium excretion increased from 121 (88.7-140) mg/24h to 149 (120.7-225.7) mg/24h, p<0.05, at 3 mo); CG: 1 (urinary Ca excretion not increased)
			Compliance (pill and drop counts): 89 (11)-92 (10)%
	Excluded subjects treated with vitamin D or drugs known to affect bone or vitamin D metabolism		Compliance (pill and drop counts): 89 (11)-92 (10)%
				RIA (Diasorin)
	NR (Argentina)
					no urinary Ca/Cr ratio >0.37mg/dL
oral route of administration unless otherwise specified; ² measured at 2 wks and 6 mo post dose; ³ measured at 2 wks post 1st and 2nd dose, and 3 mo after each of the three doses Ca, calcium; CG, control group; CPBA, competitive protein binding assay; Cr, creatinine; d, day; D, vitamin D, isoform not specified in publication; dL, deciliter; GI, gastrointestinal; HRT, hormonal replacement therapy; IG, intervention group; IQR, interquartile range; IU, international units: mo, month(s); mg, milligram; mo, month(S); ND, not done: NR, not reported; RIA, radioimmunoassay; WNL, within normal limits;

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