Executive Summary
Evidence Report 15
- Chapter 1. Introduction
Background
Sources, metabolism and functions of vitamin D Sources, metabolism and functions of calcium Challenges for the DRI committees
Key Questions addressed in this report
- Chapter 2. Methods
Overview
Sponsoring Federal agencies
AHRQ Task Order Officer (TOO)
Technical Expert Panel (TEP)
EPC methodologists
Development of the analytic framework and refinement of key questions
Definitions
Vitamin D and calcium exposures
Clinical outcomes
Indicators of exposure (nutrient intake)
Surrogate outcomes Intermediate outcomes Life stages
Key questions
Literature search strategy Study selection
Abstract screening
Full text article eligibility criteria
Primary studies
Systematic reviews
Other specific eligibility criteria
Data extraction
Data analysis
Meta-analysis
Grading of studies analyzed in this evidence report
Critical appraisal and grading of primary studies
Additional considerations of methodological quality of primary studies for the
purpose of DRI decision making
Critical appraisal of systematic reviews
Reporting of the evidence
Evidence tables
Summary tables
Graphical presentation of dose-response relationship Grand summary tables (evidence map)
Units of measurement
Assay method
Sunlight exposure
Primary and secondary outcomes
Study quality
Organization of the Results Section
- Chapter 3. Results
Literature search results Vitamin D and health outcomes
Vitamin D and growth
Vitamin D and cardiovascular disease
Vitamin D and body weight
Vitamin D and cancer
Cancer from all causes and total cancer mortality
Prostate cancer Colorectal cancer Colorectal adenoma Breast cancer
Pancreatic cancer
Vitamin D and immunologic outcomes
Vitamin D and pregnancy-related outcomes
Preeclampsia
Other outcomes
Vitamin D and clinical outcomes of bone health
Rickets
Fractures, falls, or performance measures
Vitamin D and all-cause mortality
Vitamin D and hypertension and blood pressure Hypertension
Vitamin D and blood pressure
Vitamin D and bone mineral density or bone mineral content Calcium and health outcomes
Calcium and growth
Calcium and cardiovascular disease
Calcium and body weight
Calcium and cancer
Cancer from all cause and total cancer mortality
Prostate cancer Colorectal cancer Colorectal adenoma Breast cancer incidence
Breast Mammographic Density
Pancreatic cancer
Calcium and pregnancy-related outcomes
Preeclampsia
High blood pressure with or without proteinuria during pregnancy
Preterm birth
Small for gestational age infant
Calcium and all-cause mortality
Calcium and hypertension and blood pressure
Calcium and hypertension
Calcium and blood pressure
Combined vitamin D and calcium and health outcomes
Combined vitamin D calcium and growth
Combined vitamin D and calcium and cardiovascular disease
Combined vitamin D and calcium and body weight
Combined vitamin D and calcium and cancer
Cancer from all causes and total cancer mortality
Colorectal cancer
Colorectal adenoma
Breast cancer
Combined vitamin D and calcium and pregnancy-related outcomes
Preeclampsia
Other pregnancy-related outcomes
Combined vitamin D and calcium and clinical outcomes of bone health
Rickets, fractures, falls, or performance measures
Combined vitamin D and calcium and all-cause mortality
Combined vitamin D and calcium and hypertension and blood pressure
Combined vitamin D and calcium and hypertension
Combined vitamin D and calcium and blood pressure
Combined vitamin D and calcium and bone mineral density or bone mineral content How does dietary intake of vitamin D from fortified foods and vitamin D supplementation affect serum 25(OH)D concentrations (arrow 4)?
RCTs on dietary intakes of vitamin D from fortified foods and serum 25(OH)D concentrations
RCTs on vitamin D supplementation and serum 25(OH)D concentrations
Outcomes for Tolerable Upper Intake Levels
Renal outcomes
Adverse events reported in RCTs
- Chapter 4. Discussion
Strengths of this report
DRI and the literature on vitamin D and calcium
Limitations of our methodological approach
Comments on the observational studies
Sources of heterogeneity and potential biases
Vitamin D intake and response in serum 25(OH)D concentration Considerations for future DRI committees
- Tables
Table 1. Number of primary studies on vitamin D intake or concentration and specific health outcomes that could be applicable to certain life stages
Table 2. Number of primary studies on calcium intake and specific health outcomes that could be applicable to certain life stages
Table 3. Number of primary studies on combined vitamin D and calcium intake and specific health outcomes that are relevant to certain life stages
Table 4. Vitamin D on growth outcome: Characteristics of interventional studies
Table 5. Vitamin D and growth outcomes: Characteristics of cohort studies
Table 6. Vitamin D and growth outcomes: Results of RCTs
Table 7. Vitamin D and growth outcomes: Results of cohort studies
Table 8. Vitamin D and cardiovascular outcomes: Characteristics of RCTs
Table 9. Vitamin D and cardiovascular outcomes: Results of RCTs
Table 10. Vitamin D and cardiovascular outcomes: Characteristics of cohort studies
Table 11. Vitamin D and cardiovascular outcomes: Results of cohort studies
Table 12. Vitamin D and weight: Characteristics of RCTs
Table 13. Vitamin D and weight: Results of RCTs
Table 14. Vitamin D and total cancer: Characteristics of RCTs
Table 15. Vitamin D and total cancer: Characteristics of cohort studies
Table 16. Vitamin D and total cancer: Results of RCTs
Table 17. Vitamin D and total cancer: Results of cohort studies
Table 18. Vitamin D and prostate cancer: Characteristics of nested case-control studies
Table 19. Vitamin D and prostate cancer: Results of nested case-control studies
Table 20. Vitamin D and colorectal cancer: Characteristics of RCTs
Table 21. Vitamin D and colorectal cancer: Results of RCTs
Table 22. Vitamin D and colorectal cancer: Characteristics of observational studiesA
Table 23. Vitamin D and colorectal cancer: Results of observational studies
Table 24. Vitamin D and colorectal adenoma: Characteristics of observational studies
Table 25. Vitamin D and colorectal adenoma: Results of observational studies
Table 26. Vitamin D and breast cancer: Characteristics of observational studies
Table 27. Vitamin D and breast cancer: Results of observational studies
Table 28. Vitamin D and pancreatic cancer: Characteristics of observational studies
Table 29. Vitamin D and pancreatic cancer: Results of observational studies
Table 30. Vitamin D (mother) and immunologic outcomes (offspring): Characteristics of cohort studies
Table 31. Vitamin D (mother) and immunologic outcomes (offspring): Results of cohort studies
Table 32. Vitamin D and preeclampsia: Characteristics of nested case-control studies
Table 33. Vitamin D and preeclampsia: Results of nested case-control studies
Table 34. Summary of systematic review of the effect of vitamin D on bone health
Table 35. Vitamin D and bone health: Characteristics of RCTs published after the Ottawa EPC report
Table 36. Vitamin D and bone health: Results of RCTs published after the Ottawa EPC report
Table 37. Summary of systematic review on vitamin D supplementation and all-cause mortality
Table 38. Vitamin D and all-cause mortality: Characteristics of cohort studies
Table 39. Vitamin D and all-cause mortality: Results of cohort studies
Table 40. Vitamin D and hypertension: Characteristics of cohort studies
Table 41. Vitamin D and hypertension: Results of cohort and nested case control studies
Table 42. Vitamin D and blood pressure: Characteristics of RCTs
Table 43. Vitamin D and blood pressure: Results of RCTs
Table 44. Vitamin D and bone mineral density: Characteristics of RCTs published after the Ottawa EPC report
Table 45. Vitamin D and bone mineral density or bone mineral contents: Results of RCTs published after the Ottawa EPC report
Table 46. Summary of systematic review of calcium on growth in children
Table 47. Calcium and growth: Characteristics of primary studies
Table 48. Calcium and growth: Results of primary studies
Table 49. Calcium and cardiovascular outcomes: Characteristics of cohort studiesB
Table 50. Calcium and cardiovascular outcomes: Results of cohort studies
Table 51. Systematic reviews of calcium supplementation and weight
Table 52. Calcium and weight: Characteristics of RCTs
Table 53. Calcium and weight: Results of RCTs
Table 54. Calcium and total cancer mortality: Characteristics of RCTs
Table 55. Calcium and total cancer incidence or mortality: Characteristics of cohort studies
Table 56. Calcium and total cancer mortality: Results of RCTs
Table 57. Calcium and total cancer incidence or mortality: Results of cohort studies 50-71, males
Table 58. Calcium and prostate cancer: Characteristics of observational studies
Table 59. Calcium and prostate cancer: Results of observational studies
Table 60. Systematic review of calcium supplementation and colorectal cancer incidence or adenoma recurrence
Table 61. Calcium and colorectal cancer: Characteristics of observational studies
Table 62. Calcium and colorectal cancer: Results of cohort studies
Table 63. Calcium and colorectal cancer: Results of nested case-control studies
Table 64. Calcium and colorectal adenoma: Characteristics of interventional studies
Table 65. Calcium and colorectal adenoma: Characteristics of cohort studies
Table 66. Calcium and colorectal adenoma recurrence: Results of RCTs
Table 67. Calcium and colorectal adenoma recurrence: Results of nonrandomized comparative study
Table 68. Calcium and colorectal adenoma: Results of cohort studies
Table 69. Calcium and breast cancer: Characteristics of cohort studies
Table 70. Calcium and breast cancer: Results of cohort studies
Table 71. Calcium and breast mammography density: Characteristics of cohort studies
Table 72. Calcium and breast cancer: Results of cohort studies
Table 73. Calcium and pancreatic cancer: Characteristics of cohort studies
Table 74. Calcium and pancreatic cancer: Results of cohort studies
Table 75. Summary table of systematic review on calcium supplementation and preeclampsia, small for gestational age, preterm birth
Table 76. Calcium and preeclampsia and other pregnancy outcomes: Characteristics of cohort studies
Table 77. Calcium and preeclampsia and other pregnancy outcomes: Results of cohort studies
Table 78. Calcium intake and all-cause mortality: Characteristics of cohort studies
Table 79. Calcium intake and all-cause mortality: Results of cohort studies
Table 80. Calcium and hypertension incidence: Characteristics of cohort studies
Table 81. Calcium and hypertension incidence: Results of cohort studies
Table 82. Summary of systematic reviews of calcium and blood pressure
Table 83. Calcium and blood pressure: Characteristics of RCTs
Table 84. Calcium and blood pressure: Results of RCTs
Table 85. Combined vitamin D and calcium and cardiovascular outcomes: Characteristics of RCTs
Table 86. Combined vitamin D and calcium and cardiovascular outcomes: Results of RCTs
Table 87. Combined vitamin D and calcium and weight: Characteristics of RCTs
Table 88. Combined vitamin D and calcium and weight: Results of RCTs
Table 89. Combined vitamin D and calcium and total cancer incidence: Characteristics of RCTs
Table 90. Combined vitamin D and calcium and total cancer incidence: Results of RCTs
Table 91. Combined vitamin D with calcium and colorectal cancer: Characteristics of RCTs
Table 92. Combined vitamin D with calcium and colorectal cancer: Results of RCTs
Table 93. Combined vitamin D and calcium and breast cancer outcomes: Characteristics of RCTs
Table 94. Combined vitamin D and calcium and breast cancer outcomes: Results of RCTs
Table 95. Combined vitamin D and calcium and preeclampsia: Characteristics of RCTs
Table 96. Combined vitamin D and calcium and preeclampsia: Results of RCTs
Table 97. Combined vitamin D and calcium and bone health: Characteristics of RCTs published after the Ottawa EPC report
Table 98. Combined vitamin D and calcium and bone health: Results of RCTs published after the Ottawa EPC report (stress fracture)
Table 99. Combined vitamin D and calcium and bone health: Results of RCTs published after the Ottawa EPC report (performance measures)
Table 100. Combined vitamin D and calcium and incident hypertension: Characteristics of RCTs
Table 101. Combined vitamin D and calcium and incident hypertension: Results of RCTs
Table 102. Combined vitamin D and calcium and blood pressure: Characteristics of RCTs
Table 103. Combined vitamin D and calcium and blood pressure: Results of RCTs
Table 104. Combined vitamin D and calcium and bone mineral density/content: Characteristics of RCTs published after the Ottawa EPC report
Table 105. Combined vitamin D and calcium and bone mineral density/content: Results of RCTs published after the Ottawa EPC report
Table 106. The relationship between vitamin D3 daily doses and changes in 25(OH)D concentrations in RCTs
Table 107. Adverse events reported in RCTs
- Figures
Figure 1. Summary of the vitamin D endocrine system
Figure 2. Generic analytic framework to assist formulation of key questions for the development of DRIs
Figure 3. Analytic framework for vitamin D and/or calcium EARs
Figure 4. Analytic framework for vitamin D and/or calcium ULs
Figure 5. Literature flow in this report
Figure 6. Cardiovascular outcomes risk stratified by vitamin D concentration
Figure 7. Prostate cancer risk stratified by vitamin D concentration
Figure 8. Colorectal cancer risk stratified by vitamin D concentration
Figure 9. Colon cancer risk stratified by vitamin D concentration
Figure 10. Rectal cancer risk stratified by vitamin D concentration
Figure 11. Cardiovascular outcomes risk stratified by calcium intake
Figure 12. Stroke risk stratified by calcium intake
Figure 13. Prostate cancer risk stratified by calcium intake
Figure 14 Colorectal cancer risk in both sexes stratified by calcium intake
Figure 15 Colorectal cancer risk in men stratified by calcium intake
Figure 16 Colorectal cancer risk in women stratified by calcium intake Figure 17 Colon cancer risk stratified by calcium intake
Figure 18. Rectal cancer risk stratified by calcium intake
Figure 19. Colorectal adenomatous polyp risk stratified by calcium intake
Figure 20. Breast cancer risk stratified by calcium intake
Figure 21. Hypertension risk stratified by calcium intake
Figure 22. Forest plot of trials of combined vitamin D and calcium supplementation and effects on all-cause mortality
Figure 23. Relationship between doses of Vitamin D3 supplementation and net changes in serum 25(OH)D concentrations in RCTs
Figure 24. Relationship between doses of Vitamin D3 supplementation and net changes in serum 25(OH)D concentrations in RCTs by baseline vitamin D status among adults
Figure 25. Relationship between doses of Vitamin D3 supplementation and net changes in serum 25(OH)D concentrations in RCTs by duration of supplementation among adults
- Appendixes
Appendix A. Search Strategy for Primary Studies Appendix B. Search Strategy for Systematic Reviews Appendix C. Evidence Tables
Appendix D. Existing Systematic Reviews
Appendix E. Blank Data Extraction Form and Quality Assessment Checklists Appendix F. Excluded Studies With Reasons
Appendixes and Evidence Tables for this report are provided electronically at http://www.ahrq.gov/downloads/pub/evidence/pdf/vitadcal/vitadcal.pdf.