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DRI Research Synthesis Database Overview and Sample Printout

DRI RESEARCH SYNTHESIS DATABASE OVERVIEW

The research recommendations from the following eight reports (Box D-1) on Dietary Reference Intakes (DRIs) have been entered into a database to provide ready access to this material.

Note that the database was derived from the DRI reports and does not contain new information. The database is in the form of a Microsoft1 Access file and a Microsoft Excel file; both files are available on the IOM project website (www.iom.edu/DRIresearch2006). The Access file contains all the research recommendations in ways that are easily accessible; the database can be searched easily by experienced Access users. The Excel file contains all the research recommendations plus other information (see below), but the accessibility of this information is limited by the capabilities of Excel.

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Dietary Reference Intakes Research Synthesis Workshop Summary D DRI Research Synthesis Database Overview and Sample Printout DRI RESEARCH SYNTHESIS DATABASE OVERVIEW The research recommendations from the following eight reports (Box D-1) on Dietary Reference Intakes (DRIs) have been entered into a database to provide ready access to this material. Note that the database was derived from the DRI reports and does not contain new information. The database is in the form of a Microsoft1 Access file and a Microsoft Excel file; both files are available on the IOM project website (www.iom.edu/DRIresearch2006). The Access file contains all the research recommendations in ways that are easily accessible; the database can be searched easily by experienced Access users. The Excel file contains all the research recommendations plus other information (see below), but the accessibility of this information is limited by the capabilities of Excel. 1 Microsoft Corporate Headquarters, Redmond, WA.

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Dietary Reference Intakes Research Synthesis Workshop Summary BOX D-1 DRI Reports Included in the Database A: IOM. 1997. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press. B: IOM. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press. C: IOM. 2000. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press. D: IOM. 2001. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press. E: IOM. 2002/2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. F: IOM. 2005. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: The National Academies Press. G: IOM. 2000. Dietary Reference Intakes: Applications in Dietary Assessment. Washington, DC: The National Academies Press. H: IOM. 2003. Dietary Reference Intakes: Applications in Dietary Planning. Washington, DC: The National Academies Press. Database Fields ID No—corresponds to the numerical order of total database entries ID Code—a code for internal use that corresponds to the code given to each database entry; the letter refers to the report (see later section “DRI Reports Included in the Database” Recommendation—full text of research recommendation Designation—determination made from wording in report and/or organization of the report Major Knowledge Gaps—research recommendation (knowledge gap) in the volume’s summary or whose wording indicated at least one of the following: it was critically needed, critically important, particularly needed, must, or

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Dietary Reference Intakes Research Synthesis Workshop Summary should be explored, merit(s) attention, is/are required. Location at the beginning of a section was also considered. Knowledge Gaps—other research recommendations Research Methods Priority Source—describes what text in the report led to the priority designation or the location of the recommendation in the report that led to the priority designation Keywords—main words from the text of the recommendation MeSH2 Terms Type of Rec (Type of Recommendation)—determination made from the original text of the recommendation General Research Recommendation Specific Research Recommendation Research Method Notes Exact Wording of Text—text pulled directly from original DRI report Page—page number where recommendation can be found in given DRI report Report Citation—citation of the relevant DRI report ISSB—corresponds to particular report on the National Academies Press (NAP) website Location/URL—link to exact page (full text) on the NAP website Downloading and Usage Instructions Website: http://www.iom.edu/DRIresearch2006. Click on the link for DRI Research Synthesis Database (on the right-hand side of the screen). On the DRI Research Synthesis Database screen: Save the files to your computer as follows: click each file; this takes you to a webpage for that file; click STARTDOWNLOAD; select the SAVE option; in the “Save As” pop-up window choose an appropriate place to save the files on your computer. You will probably want to save both the Access file (.mdb) and the Excel file (.xls). You may choose to download this Accompanying Text file (.pdf), as well. If you wish to view the database using Access: 2 Medical Subject Headings

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Dietary Reference Intakes Research Synthesis Workshop Summary If you are an experienced Access user: Open the Access file that you have just saved to your computer. Under “Objects/Tables” open the DRI Recommendations table, which is the database. Then use the functions of Access to view the data. We have created common Queries and Reports that you may wish to view as described below. If you come across a Research Recommendation ID Code that is not in the Access database, look in the DRI-Other Text tab in the Excel file as described below. If you are a novice Access user: Open the Access File that you have just saved to your computer. Under “Objects/Reports” you will see numerous lists we created for common queries. Open or print any of these lists to view the selected data. Since we created over 100 lists, you may wish to use the “Groups” function to view lists in specific categories. This is the easiest way to view databaseentries. To view all the research recommendations related to calcium, for example, click on the Report named “Calcium List;” to view all of the Major Knowledge Gaps related to calcium, click on the Report named “Calcium List, Major.” For any list you can right-click and choose print, or double-click to open and view the list. If you wish to view the database using Excel: Open the Excel file that you have just saved to your computer. The first tab (DRI Recommendations) is the database, and you can view the entries using the functions of Excel. Note that there is not a convenient way to print this tab using Excel, however the other tabs are designed to print easily. Access provides the best way to view and print the database entries as reports. Special features of the database, accessible only through Excel in the current version: DRI-Other Text tab includes any other text from the DRI Reports that pertains to the research recommendations but was not actually used as a research recommendation. At present, printing this information from the Excel file is limited to specific data fields.

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Dietary Reference Intakes Research Synthesis Workshop Summary Glossary (DRI Recommendations) tab lists definitions of acronyms, words, and terms used in the DRI Recommendations tab. Glossary (DRI Reports) tab lists definitions of acronyms, words, and terms used in any of the eight DRI reports. Keywords tab lists the keywords that were used to categorize the research recommendations. This field affects how queries in Access categorize the research recommendations. MeSH tab lists some of the Medical Subject Headings terms that will be used to categorize the research recommendations. This field affects how queries in Access categorize the research recommendations. Glossary (MeSH) tab lists some definitions used in applying the MeSH terms. Numbers tab gives some data about the database. Some of this information is listed in Box D-2. BOX D-2 Numbers of Ders of Dietary Reference Intakes Research Recommendations Total number of research recommendations: 459 Number of records by designation Major knowledge gaps: 212 (46.2%) Knowledge gaps: 199 (43.4%) Research methods: 48 (10.4%) Priority Setting The DRI panels were charged with developing prioritized research agendas to address research needs in scientific areas related to the DRIs. These research recommendations were not intended to provide a basis for public policy decisions and should not be interpreted as priorities for federal funding of research, which must consider a wide range of research needs in many scientific areas.

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Dietary Reference Intakes Research Synthesis Workshop Summary The individual DRI panels were guided in the task of priority setting by the following text from each report. The following major research areas are considered the highest priority in order to more accurately determine the DRIs for calcium, phosphorus, magnesium, vitamin D, and fluoride in future reports. The Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (DRI Committee) agreed to assign highest priority to research that has potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. In the judgment of the DRI Committee and its panel and subcommittees, highest priority should be given to research that has potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. Highest priority is thus given to research that has potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. Highest priority is given to research that has the potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. Highest priority is given to research that has the potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. Highest priority is given to research that has the potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences.

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Dietary Reference Intakes Research Synthesis Workshop Summary SAMPLE PRINTOUT PRODUCED BY MICROSOFT ACCESS A-DRI Report on Calcium and Related Nutrients, List of All Research Recommendations List of all research recommendations from the DRI Report on Calcium and Related Nutrients (v3; version 3 of the database). Designation ID No ID Code RECOMMENDATION Major Knowledge Gaps 1 A.I.02 Epidemiological research that evaluates the impact of habitual (lifetime) nutrient intake on functional outcomes related to specific diseases is urgently needed in order to optimize nutrient recommendations. Major Knowledge Gaps 2 A.I.03 Epidemiological research that evaluates the impact of habitual (lifetime) dietary calcium intake on peak bone mass and fracture risk is urgently needed in order to optimize calcium recommendations. Major Knowledge Gaps 3 A.I.04 Epidemiological research that evaluates the impact of habitual (lifetime) dietary calcium intake on prostate cancer is urgently needed in order to optimize calcium recommendations.

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Dietary Reference Intakes Research Synthesis Workshop Summary Major Knowledge Gaps 4 A.I.05 Epidemiological research that evaluates the impact of habitual (lifetime) dietary calcium intake on renal stones is urgently needed in order to optimize calcium recommendations. Major Knowledge Gaps 5 A.I.06 Epidemiological research that evaluates the impact of habitual (lifetime) exposure to fluoride from all sources on prevention of dental caries and risk of fluorosis is urgently needed in order to optimize fluoride recommendations. Major Knowledge Gaps 6 A.I.07 Epidemiological research that evaluates the role of habitual (lifetime) dietary magnesium intake in the development of hypertension, cardiovascular disease, and diabetes is urgently needed in order to optimize magnesium recommendations. Major Knowledge Gaps 7 A.I.08 Research is needed to assess methods for determining individual risk of chronic disease outcomes so that associations with nutrient status can be better understood. Major Knowledge Gaps 8 A.I.09 The potential relationship between allelic variation in the vitamin D receptor (VDR), bone mineral density, and osteoporosis within and between population groups requires further elucidation in order to determine if VDR polymorphisms are a variable influencing lifelong calcium intake needs.

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Dietary Reference Intakes Research Synthesis Workshop Summary Major Knowledge Gaps 9 A.I.10 For children ages 1 through 18 years, research is needed to evaluate the dietary intakes of calcium, phosphorus, magnesium, and vitamin D required to optimize bone mineral accretion, especially in relation to changing age ranges for the onset of puberty and growth spurts. Major Knowledge Gaps 10 A.I.11 With respect to dietary intake needs for vitamin D, information is required by geographical and racial variables that reflect the mix of the Canadian and United States populations and the influence of sunscreens on intake requirements. Major Knowledge Gaps 15 A.II.06 Investigations should include epidemiological studies of the interrelationships between calcium intake and fracture risk, osteoporosis, prostate cancer, and hypertension must be pursued to determine if calcium intake is an independent determinant of any of these health outcomes. Control of other factors potentially associated as other risk factors for these health problems is essential (for example, fat intake in relation to cancer and cardiovascular disease; weight-bearing activity; and dietary components such as salt, protein, and caffeine in relation to osteoporosis). Such epidemiological studies need to be conducted in middle- aged as well as older adult men and women. Major Knowledge Gaps 18 A.III.01 The model that relates absorbed phosphorus intake to serum phosphorus must be evaluated in clinical studies using oral phosphorus intakes, and investigated in children and adolescents as well as adults.

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Dietary Reference Intakes Research Synthesis Workshop Summary Major Knowledge Gaps 21 A.IV.02 Reliable data on population intakes of magnesium are required based on dietary surveys that include estimates of intakes from food, water, and supplements in healthy populations in all life stages. Major Knowledge Gaps 22 A.IV.03 Biochemical indicators that provide an accurate and specific marker(s) of magnesium status must be investigated in order to assess their ability to predict functional outcomes that indicate adequate magnesium status over prolonged periods. Major Knowledge Gaps 23 A.IV.04 Basic studies need to be initiated in healthy individuals, including experimental magnesium depletion studies that measure changes in various body magnesium pools. Major Knowledge Gaps 24 A.IV.05 Investigations should be conducted to determine the most valid units to use in expressing estimates of magnesium requirements (body weight, fat- free mass, or total body unit). Major Knowledge Gaps 26 A.IV.07 Investigations are needed to assess the interrelationships between dietary magnesium intakes, indicators of magnesium status, and possible health outcomes that may be affected by inadequate magnesium intakes. Possible health outcomes include hypertension, hyperlipidemia, atherosclerotic vascular disease, altered bone turnover, and osteoporosis.

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Dietary Reference Intakes Research Synthesis Workshop Summary Knowledge Gaps 12 A.II.03 Adaptations to changes in the amount of dietary calcium should be followed within the same populations for short- (2 months) to long-term (1 to 2 years). Different experimental approaches are needed to define the temporal response to changes in dietary calcium. Short-term studies may be conducted in metabolic research units whereas the longer- term studies need to be carried out in confined populations (i.e., convalescent home patients) fed prescribed diets; human study cohorts followed for years with frequent, thorough estimates of dietary intakes; or metabolic studies of individuals fed their usual diets who typically consume a wide range of calcium intakes. All studies should include a comprehensive evaluation of biochemical measures of bone mineral content or metabolism. Bone mineral content and density should be evaluated in long-term studies. Good surrogate markers of osteopenia could be used in epidemiologic studies. Knowledge Gaps 13 A.II.04 Investigations should include assessment of the effect of ethnicity and osteoporosis phenotype on the relationship between dietary calcium, desirable calcium retention, bone metabolism, and bone mineral content. Knowledge Gaps 14 A.II.05 Investigations should include evaluation of the independent impact of diet, lifestyle (especially physical activity), and hormonal changes on the utilization of dietary calcium for bone deposition and growth in children and adolescents. These studies need to be done in populations for which the usual calcium intakes range from low to above adequate.

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Dietary Reference Intakes Research Synthesis Workshop Summary Knowledge Gaps 16 A.II.07 Carefully controlled studies are needed to determine the strength of the causal association between calcium intake vis-à-vis the intake of other nutrients and kidney stones in healthy individuals. Knowledge Gaps 17 A.II.08 Because of their potential to increase the risk of mineral depletion in vulnerable populations, calcium– mineral interactions should be the subject of additional studies. Knowledge Gaps 19 A.III.02 Bone mineral mass as a function of dietary phosphorus intake should be investigated at all stages of the life cycle. Knowledge Gaps 20 A.III.03 The practical effect of phosphate-containing food additives on trace mineral status (iron, copper, and zinc) should be evaluated. Knowledge Gaps 27 A.IV.08 Based on the evidence of abnormal magnesium status and health outcomes [from research in Recommendation ID Code A. IV. 07 (pg. 249)], intervention studies to improve magnesium status and to assess its impact on specific health outcomes would be appropriate. Possible health outcomes include hypertension, hyperlipidemia, atherosclerotic vascular disease, altered bone turnover, and osteoporosis. Knowledge Gaps 28 A.IV.09 The toxicity of pharmacological doses of magnesium requires further investigation.

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Dietary Reference Intakes Research Synthesis Workshop Summary Knowledge Gaps 29 A.V.01 Research is needed to evaluate how geographical and racial variables (that reflect the mix of the Canadian and American population) affect vitamin D status at various levels of vitamin D intake throughout the lifespan. Knowledge Gaps 30 A.V.02 Research is needed to evaluate the influence of sunscreens on vitamin D status. Knowledge Gaps 31 A.V.03 Regarding puberty and adolescence, research is needed to evaluate the effect of various intakes of vitamin D on circulating concentrations of 25-hydroxyvitamin D [25(OH) D] and 1,25-dihydroxyvitamin D [1,25(OH) 2D] during winter at a time when no vitamin D comes from sunlight exposure. During this time, the body adapts by increasing the renal metabolism of 25-hydroxyvitamin D [25(OH) D] to 1,25-dihydroxyvitamin D [1,25(OH) 2D] and the efficiency of intestinal calcium absorption, thereby satisfying the increased calcium requirement by the rapidly growing skeleton. Knowledge Gaps 32 A.V.04 It is very difficult to determine the reference values for vitamin D in healthy young adults aged 18 through 30 and 31 through 50 years in the absence of sunlight exposure because of their typically high involvement in outdoor activity and the unexplored contribution of sunlight to vitamin D stores. More studies are needed that evaluate various doses of vitamin D in young and middle-aged adults in the absence of sunlight exposure.

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Dietary Reference Intakes Research Synthesis Workshop Summary Knowledge Gaps 33 A.V.05 A major difficulty in determining how much vitamin D is adequate for the body's requirement is that a normal range for serum 25-hydroxyvitamin D [25(OH) D] is 25 to 137.5 nmol/ liter (10 to 55 ng/ ml) for all gender and life stage groups. However, there is evidence, especially in the elderly, that in order for the parathyroid hormone (PTH) to be at the optimum level, a 25-hydroxyvitamin D [25(OH) D] of 50 nmol/ liter (20 ng/ml) or greater may be required. Therefore, more studies are needed to evaluate other parameters of calcium metabolism as they relate to vitamin D status including circulating concentrations of parathyroid hormone (PTH). Knowledge Gaps 35 A.VI.01 Epidemiological studies (especially analytical studies) of the relationships among fluoride exposures from all major sources and the prevalence of dental caries and enamel fluorosis at specific life stages should continue for the purposes of detecting trends and determining the contribution of each source to the effects demonstrated. Knowledge Gaps 36 A.VI.02 Epidemiological and basic laboratory studies should further refine our understanding of the effects of fluoride on the quality and biomechanical properties of bone and on the calcification of soft tissue.

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Dietary Reference Intakes Research Synthesis Workshop Summary Knowledge Gaps 37 A.VI.03 Studies are needed to define the effects of metabolic and environmental variables on the absorption, excretion, retention, and biological effects of fluoride. Such variables would include the composition of the diet (for example, calcium content), acid- base balance, and the altitude of residence. Research Method 11 A.II.02 Calcium balance studies should be augmented with stable or radioactive tracers of calcium to estimate aspects of calcium homeostasis with changes in defined intakes (i.e., fractional absorption, bone calcium balance, and bone turnover rates). Research Method 25 A.IV.06 Magnesium balance studies might be one indicator utilized as a marker of magnesium status. In magnesium balance studies, strict adherence to criteria suggested (IOM. 1997. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press. Chapter 6— Magnesium) would improve their application to dietary recommendations. Research Method 34 A.V.06 The development of methodologies to assess changes in body stores of vitamin D is needed to accurately assess requirements in the absence of exposure to sunlight. Such work would markedly assist in the estimation of reference values for all life stage groups.

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