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List of Research Recommendations

The following research recommendations were generated from the database and are listed by ID Code.

DRI RECOMMENDATIONS

ID No.

ID CODE

RECOMMENDATION

DESIGNATION

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

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

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.

Major Knowledge

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

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



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Dietary Reference Intakes Research Synthesis Workshop Summary C List of Research Recommendations The following research recommendations were generated from the database and are listed by ID Code. DRI RECOMMENDATIONS ID No. ID CODE RECOMMENDATION DESIGNATION 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 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 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. Major Knowledge 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 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

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 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 7 A.I.08 Research is needed to assess methods for determining individual risk of chronic disease risk of chronic disease outcomes so that associations with nutrient status can be better understood. Major Knowledge 8 A.I.09 The potential relationship between allelic variation in the vitamin D receptor (VDR), bone 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 life-long calcium intake needs. Major Knowledge 9 A.I.10 For children ages 1 through 18 years, research is needed to evaluate the dietary intakes of 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 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 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 12 A.II.03 Adaptations to changes in the amount of dietary calcium should be followed within the same populations for short-term (2 months) to long-term (1 to 2 years) studies. Different experimental approaches will be needed to define the temporal response to changes in dietary calcium. Short-term studies may be conducted in a metabolic research unit whereas the longer-term studies will need to be carried out in confined populations (i. e., convalescent home patients) fed prescribed diets; human study cohorts followed carefully 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 surro Knowledge Gaps

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     gate markers of osteopenia could be used in epidemiological studies.   13 A.II.04 Investigations should include assessment of the effect of ethnicity and osteoporosis 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. 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 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 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. Major Knowledge 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 21 A.IV.02 Reliable data on population intakes of magnesium are required based on dietary Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     surveys that include estimates of intakes from food, water, and supplements in healthy populations in all life stages.   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 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 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 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 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. Major Knowledge 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. 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 Knowledge Gaps

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     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.   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. 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 (20ng/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 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. Research Method 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. Knowledge Gaps

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 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. Knowledge Gaps 38 B.I.01 Because of the difference in the bioavailability of food folate and the monoglutamate form of folate, it is recommended that both food folate and folic acid be included in tables and databases of food composition and in reports of intake. That is, the content or intake of naturally occurring food folate should be reported separately from that of folate provided by fortified foods and supplements. Research Method 39 B.I.02 To fill information gaps, studies designed specifically to estimate average requirements in apparently healthy humans should be conducted for some micronutrients. Major Knowledge 39.1 B.I.02.a See Recommendation ID Code B.I.02. Null 39.2 B.I.02.b See Recommendation ID Code B.I.02. Null 40 B.I.03 To fill information gaps, studies designed to generate usable data on the micronutrient needs of infants, children, adolescents, the elderly, and pregnant and lactating women should be conducted. Studies should use graded levels of nutrient intake and a combination of response indices. Major Knowledge 40.1 B.I.03.a See Recommendation ID Code B.I.03. Null 40.2 B.I.03.b See Recommendation ID Code B.I.03. Null 40.3 B.I.03.c See Recommendation ID Code B.I.03 Null 40.4 B.I.03.d See Recommendation ID Code B.I.03. Null 40.5 B.I.03.e See Recommendation ID Code B.I.03. Null 41 B.I.04 To fill information gaps, appropriately designed studies to determine the role of selected micronutrients in reducing the risk of certain chronic diseases should be conducted. Major Knowledge 41.1 B.I.04.a See Recommendation ID Code B.I.04. Null 41.2 B.I.04.b See Recommendation ID Code B.I.04. Null 42 B.I.05 To fill information gaps, appropriately designed studies to determine the role of choline in reducing the risk of certain chronic diseases should be conducted. Major Knowledge 43 B.I.06 To fill information gaps, studies designed to detect adverse effects of chronic high intakes of selected micronutrients should be conducted. Major Knowledge 43.1 B.I.06.a See Recommendation ID Code B.I.06. Null

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 43.2 B.I.06.b See Recommendation ID Code B.I.06. Null 43.3 B.I.06.c See Recommendation ID Code B.I.06. Null 44 B.I.08 Conduct studies to provide the basic data for constructing risk curves and benefit curves across the exposures to food folate and to folate (folic acid) added to foods and taken as a supplement. Such studies would provide estimates of the risk of developing neural tube defects, vascular disease, and neurological complications in susceptible individuals consuming different amounts of folate. With the new U.S. regulations on the fortification of cereal grains with folate, it is now possible to investigate the health effects, both positive and negative, of folate fortification on folate intake and health status. Major Knowledge 44.1 B.I.08.a See Recommendation ID Code B.I.08. Null 44.2 B.I.08.b See Recommendation ID Code B.I.08. Null 45 B.I.09 Conduct investigations of the magnitude of the effect of intake of folate, vitamin B6, vitamin B12, and related nutrients for preventing vascular disease and other chronic degenerative diseases. Possible mechanisms for the influence of genetic variation should also be investigated. Major Knowledge 45.1 B.I.09.a See Recommendation ID Code B.I.09. Null 45.2 B.I.09.b See Recommendation ID Code B.I.09. Null 46 B.I.10 Conduct studies to overcome the methodological problems in the analysis of folate, including the development of sensitive and specific deficiency indicators and of practical, improved methods for analyzing the folate content of foods and determining its bioavailability. Major Knowledge 47 B.I.11 Conduct studies to develop economical, sensitive, and specific methods to assess the prevalence, causes, and consequences of vitamin B12 malabsorption and deficiency and to prevent and treat these conditions. One reason these methods are especially needed is because it appears that vitamin B12 deficiency greatly increases the potential of folate to cause adverse effects. Major Knowledge 47.1 B.I.11.a See Recommendation ID Code B.I.11. Null 48 B.I.12 Investigate how folate and related nutrients influence normal cellular differentiation and development, including embryogenesis and neoplastic transformation. Major Knowledge 49 B.I.13 Investigate vitamin B12 requirements of the elderly and how they may be met. These investigations appear to be a priority from a public health perspective. Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 49.1 B.I.13.a See Recommendation ID Code B.I.13. Null 50 B.I.14 Investigate whether the folate requirement varies substantially by trimester of pregnancy. These investigations appear to be a priority from a public health perspective. Major Knowledge 50.1 B.I.14.a See Recommendation ID Code B.I.14. Null 50.2 B.I.14.b See Recommendation ID Code B.I.14. Major Knowledge 51 B.I.15 Develop indicators on which to base vitamin B6 requirements. Major Knowledge 52 B.II.01 Priority should be given to studies useful for setting Estimated Average Requirements (EARs) for thiamin for children, adolescents, pregnant and lactating women, and the elderly. Future studies should be designed around the Estimated Average Requirement (EAR) paradigm, use graded levels of thiamin intake with clearly defined cutoff values for clinical adequacy and inadequacy, and be conducted for a sufficient duration. To do this, close attention should be given to the identification of indicators on which to base thiamin requirements. Major Knowledge 53 B.II.02 If studies are designed to test high doses of thiamin for possible beneficial effects, the design should also provide for the careful investigation of possible adverse effects. Research Method 54 B.III.01 Priority should be given to studies useful for setting Estimated Average Requirements (EARs) for riboflavin for children, adolescents, pregnant and lactating women, and the elderly. Future studies should be designed specifically around the Estimated Average Requirement (EAR) paradigm, use graded levels of riboflavin intake and clearly defined cutoff values for clinical adequacy and inadequacy, and be conducted for a sufficient duration. Major Knowledge 55 B.III.02 Develop another functional test for riboflavin status to corroborate and augment the presently used flavin–adenine dinucleotide-dependent erythrocyte glutathione reductase (e.g., a test using a flavin mononucleotide-dependent erythrocyte enzyme such as the pyridoxine [pyridoxamine] 5′-phosphate oxidase). Knowledge Gaps 56 B.III.03 Examine the effects of physical activity on the requirement for riboflavin. Knowledge Gaps 57 B.IV.01 For niacin, data useful for setting the Estimated Average Requirement (EAR) for children, adolescents, pregnant women, and lactating women are scanty. To fill information gaps, additional research on niacin requirements is desired for children, adolescents, pregnant women, and lactating women. Knowledge Gaps 58 B.IV.02 Priority should be given to investigation of the niacin requirement to satisfy nicoti Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     namide adenine dinucleotide (NAD) needs for increased adenosine diphosphate (ADP) ribosylation resulting from oxidant– deoxyribonucleic acid (DNA) damage.   59 B.IV.03 Priority should be given to development of sensitive and specific blood measures of niacin status. Current assessments of niacin status and requirement are based solely on urinary metabolite measures; measurements of plasma metabolites such as the 2-pyridone derivatives may be productive. Two recent experimental studies have suggested erythrocyte nicotinamide adenine dinucleotide (NAD) as a functional blood measure of niacin status [Fu CS, Swendseid ME, Jacob RA, McKee RW. 1989. Biochemical markers for assessment of niacin status in young men: Levels of erythrocyte niacin coenzymes and plasma tryptophan. J Nutr 119(12):1949-1955; Ribaya-Mercado J, Russell R, Rasmussen H, Crim M, Perrone- Petty G, Gershoff S. 1997. Effect of niacin status on gastrointestinal function and serum lipids. FASEB J 11: A179. Abstract.], but further work is needed in clinical populations. Major Knowledge 60 B.V.01 Priority should be given to studies useful for setting Estimated Average Requirements (EARs) for vitamin B6 for children, adolescents, pregnant and lactating women, and the elderly. Future studies should be designed around the Estimated Average Requirement (EAR) paradigm, use graded levels of nutrient intake and clearly defined cutoff values for clinical adequacy and inadequacy, and be conducted for a sufficient duration. To do this, close attention should be given to the identification of indicators on which to base vitamin B6 requirements. Major Knowledge 60.1 B.V.01.a See Recommendation ID Code B.V.01. Null 61 B.VI.01 Investigations should be conducted to determine the mechanisms and magnitude of relationships of folate intake with risk reduction for the occurrence of neural tube defects (NTDs) and vascular disease and the influence of related factors (including genetic polymorphism) on these relationships. Targeted intervention programs need a clearer understanding of the mechanisms by which adequate folate intake ensures normal embryogenesis and may reduce vascular disease risk. Major Knowledge 62 B.VI.02 Investigations should be conducted to estimate folate requirements in high-risk groups for which data are limited and for which public health problems may result from deficiencies. These groups include children, adolescents, women of reproductive age (including pregnant women by trimester and lactating women), and the elderly. These studies should identify and use new folate status indicators that are Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     linked to metabolic function and traditional indices of folate status.   63 B.VI.03 Develop more precise and reproducible methods of analysis for the estimation of both blood and food folate and for the estimation of folate bioavailability. Improved methods would allow for comparison of status indicators among laboratories, revision of the food folate databases, and improved estimation of how dietary requirements are influenced by the food matrix and the source of folate (food or synthetic). Research Method 64 B.VI.04 Identify and quantify adverse effects of high intakes of folate. Further investigation is needed on the effect of increasing folate intake from supplements and fortified foods on the onset and progression of vitamin B12 deficiency. Major Knowledge 65 B.VI.05 Determine the mechanisms by which maternal folate sufficiency reduces the occurrence of neural tube defect (NTD) in the infant, including the establishment of which genes are responsible for the heritability and folate-responsiveness of NTD. Knowledge Gaps 66 B.VI.06 Determine the effect of folate fortification on folate intake and occurrence of neural tube defect (NTD) and vascular disease. With the new U. S. regulations on the fortification of cereal grains with folate, it is now possible to investigate the health effects, both positive and negative, of folate fortification on folate intake and health status. Major Knowledge 66.1 B.VI.06.a See Recommendation ID Code B.VI.06. Null 67 B.VI.07 Determine whether folate status affects the risk of birth defects other than neural tube defect (NTD) and of chronic diseases other than vascular disease (e.g., cancer). With the new U. S. regulations on the fortification of cereal grains with folate, it is now possible to investigate the health effects, both positive and negative, of folate fortification on folate intake and health status. Major Knowledge 67.1 B.VI.07.a See Recommendation ID Code B.VI.07. Null 68 B.VII.01 Investigate the prevalence of vitamin B12 deficiency as diagnosed by biochemical, neurological, or hematological abnormalities (e.g., methylmalonic acid and holotranscobalamin II). Major Knowledge 69 B.VII.02 Develop improved, economical, and sensitive methods to detect vitamin B12 malabsorption and deficiency before adverse neurological and hematological changes occur. Major Knowledge 70 B.VII.03 Develop effective methods to reduce the risk of suboptimal vitamin B12 status resulting from vitamin B12 malabsorption or vegetarian diets. For elderly persons Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     with food- bound malabsorption, research is needed on the form and amount of vitamin B12 that can normalize and maintain vitamin B12 stores. For vegetarians, information is needed about the absorption of vitamin B12 from dairy products, algae, and fortified food products.   71 B.VII.04 Investigate the feasibility, potential benefits, and adverse effects of fortification of cereal grain foods with vitamin B12 considering stability, identity of any degradation products, and bioavailability for normal individuals and those who malabsorb protein-bound vitamin B12. Knowledge Gaps 72 B.VII.05 Investigate the contribution of bacterial overgrowth to elevated serum methylmalonic acid, to determine the variability of this indicator of vitamin B12 status. Knowledge Gaps 73 B.VIII.01 To fill information gaps, further investigations about pantothenic acid as a nutrient are needed. Information gaps include human requirements, intake, bioavailability, toxicity, and metabolic effects. Research to date has indicated little cause for concern about the adequacy of pantothenic acid intake for healthy people; deficiency states can be produced only by actively interfering with the absorption or bacterial production pantothenic acid. Major Knowledge 73.1 B.VIII.01.a See Recommendation ID Code B.VIII.01. Null 73.2 B.VIII.01.b See Recommendation ID Code B.VIII.01. Null 74 B.VIII.02 Investigate pantothenic acid requirements of different age groups, especially infants, children, and the elderly. Major Knowledge 75 B.VIII.03 Investigate bioavailability of pantothenic acid from different foods and mixed diets and of the extent to which synthesis by intestinal bacteria contributes to meeting the requirement. Major Knowledge 76 B.VIII.04 Using newer methods, such as high-pressure liquid chromatography, analyze pantothenic acid in foods. At present, pantothenic acid intakes are not calculated in national surveys such as the Third National Health and Nutrition Examination Survey (NHANES III) because of a lack of information on the pantothenic acid content of foods. Major Knowledge 77 B.VIII.05 To fill information gaps, expand the food composition databases used for the national surveys to include pantothenic acid. This would allow pantothenic acid intakes to be calculated in national surveys such as the Third National Health and Nutrition Examination Survey (NHANES III). Research Method

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     as whether and at what point adaptation occurs.   399 F.V.07 Conduct survey studies comparing high versus low sulfate water ingestion from public water supplies that appropriately control for other causes of intestinal disturbances. Knowledge Gaps 400 F.V.08 Conduct studies to evaluate whether chronic exposure to high sulfur (both cystine and sulfate) ingestion predisposes individuals to ulcerative colitis. Investigate the role of hydrogen sulfide in the etiology of ulcerative colitis. Knowledge Gaps 401 F.V.09 Assess the relationship between increased sulfate intake and risk of inflammatory bowel disease. Conduct studies to determine how much of the sulfate produced via turnover in metabolism reenters the bowel and thus may serve asan irritant or oxidant. The risk of inflammatory bowel disease might be addressed in the setting of a case-control study or possibly a large, prospective observational study. Major Knowledge 401.1 F.V.09.a See Recommendation ID Code F.V.09. Null 401.2 F.V.09.b See Recommendation ID Code F.V.09. Null 402 F.V.10 Conduct absorption studies using acute and chronic sulfate doses. Knowledge Gaps 403 F.V.11 Conduct analytical studies to determine sulfate, as well as total sulfur content, of foods. Knowledge Gaps 404 F.VI.12 For water, plasma or serum osmolality is an acceptable indicator of hydration status; however, trials that rigorously control and test different levels of total water intake, rather than allowing ad libitum intakes, have not been performed. These studies should be performed. Major Knowledge 405 F.VI.14 For water, potassium, and sodium, useful data are lacking for setting requirements for infants, children, adolescents, pregnant and lactating women, and the elderly. Studies to collect these data should be conducted. Major Knowledge 406 F.VI.15 There is a paucity of data on the relationship of dietary sodium and potassium intakes early in life on blood pressure and markers of bone health during adulthood. Studies to collect these data should be conducted. Major Knowledge 407 F.VI.16 For water, potassium, and sodium, useful data are lacking for setting requirements for infants, children, adolescents, pregnant and lactating women, and the elderly. For water, research studies commonly tested the effects of inadequate intake in men of military age, but not in broad populations. These types of studies should be conducted. Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 408 F.VI.17 Develop improved methods for the accurate measurement of total body water and electrolytes in free-living persons. Research Method 409 F.VI.18 Develop improved methods for the accurate measurement of dietary intake of water and electrolytes in free-living persons. Potential sources of error in self-reported intake data include underreporting of portion sizes and frequency of intake, omission of foods and beverages, and use of food composition tables and databases. Research Method 410 F.VI.19 Food composition tables and databases need to be continuously updated and expanded to include new foods and beverages and reformulated products. Inclusion of water and electrolytes in food composition tables and databases is important. Research Method 411 F.VI.20 Develop practical tools to estimate sodium intake. For several reasons, assessment of sodium intake is problematic. Substantial additions can occur post-processing. In fact, many diet collection methods do not collect information on the salt (sodium chloride) added during cooking or eating. More importantly, there is large day-to-day variation in sodium intake. The most accurate method to assess dietary sodium is to measure several timed urinary collections. However, this approach is cumbersome and prone to collection errors. Hence, practical tools to estimate sodium intake are needed. Research Method 412 F.VI.22 There is some evidence that increased dietary sodium intake and inadequate potassium intake increase urinary calcium excretion and affect calcium balance; to fill in knowledge gaps, additional investigations of effects of sodium and potassium intake on subclinical and clinical outcomes, such as bone mineral density and osteoporosis, are needed. Major Knowledge 413 F.VI.32 Conduct studies that test the effects of reduced sodium and increased potassium intake, alone and combined, on clinical outcomes (e.g., stroke, bone mineral density, and kidney stones). To the extent possible, clinical trials should be conducted. A formal assessment of the feasibility of a sodium reduction trial with clinical cardiovascular outcomes should be undertaken. In the absence of trials, methodologically rigorous observational studies that concomitantly collect electrolyte intake, other dietary information, and genetic information should be conducted. There is some evidence that increased dietary sodium intake and inadequate potassium intake increase urinary calcium excretion and affect calcium balance. Major Knowledge 413.1 F.VI.32.a See Recommendation ID Code F.VI.32. Null

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 414 F.VI.33 Conduct studies to assess the potential for increased potassium intake to mitigate the adverse consequences of excess sodium intake and, vice versa, the potential for a reduced sodium intake to mitigate the adverse consequences of inadequate potassium intake. Potential outcomes include blood pressure, salt sensitivity, bone demineralization, and decreased bone mineral density. There is some evidence that increased dietary sodium intake and inadequate potassium intake increase urinary calcium excretion and affect calcium balance. Major Knowledge 414.1 F.VI.33.a See Recommendation ID Code F.VI.33. Null 415 F.VI.34 Conduct studies on the adverse effects of chronic, low-grade metabolic acidosis that results from an inadequate intake of potassium and its bicarbonate precursors. Potential clinical outcomes include decreased bone mineral density, osteoporosis, and kidney stones. Major Knowledge 415.1 F.VI.34.a See Recommendation ID Code F.VI.34.   416 F.VI.35 Conduct water, sodium, and potassium balance studies that enroll broad populations and that vary climate and physical activity levels. Populations of particular interest are children, as well as older persons with chronic, but stable, illnesses. Major Knowledge 417 G.I.04 To fill knowledge gaps, conduct further investigations and collect better data on requirements for nutrients currently with an Adequate Intake (AI) (for age groups older than infants). Additional applications are possible when data are sufficient to allow Adequate Intakes (AIs) to be replaced with Estimated Average Requirements (EARs) (and thus Recommended Dietary Allowances [RDAs] can be set). Estimated Average Requirements (EARs) (rather than Adequate Intakes [AIs]) present more possibilities for assessing individual and group prevalence of inadequacy. Major Knowledge. 417.1 G.I.04.a See Recommendation ID Code G.I.04. Null 417.2 G.I.04.b See Recommendation ID Code G.I.04. Null 418 G.I.05 For nutrients with an Adequate Intake (AI) for age groups older than infants (vitamin D, vitamin K, pantothenic acid, biotin, choline, calcium, chromium, fluoride, manganese, potassium, sodium, chloride, water, dietary fiber, linoleic acid, and alpha-linolenic acid), new research and better data that allow replacement of the Adequate Intakes (AIs) with Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) will greatly aid the assessment of nutrient adequacy. Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 419 G.I.06 Collect better information on the distribution of requirements so that the appropriate method for assessing the prevalence of inadequacy for groups can be determined (EAR [Estimated Average Requirement] cut-point method versus full probability approach). Null 419.1 G.I.06.a See Recommendation IDCode G.I.06. Major Knowledge 420 G.I.07 Research should be undertaken to allow Tolerable Upper Intake Levels (ULs) to be set for all nutrients. Establishment of Tolerable Upper Intake Levels (ULs) provides an opportunity to evaluate the risk of adverse effects for individuals and populations, and is an extremely important step forward in assessing intakes. Research to allow ULs to be set should be undertaken in carefully controlled settings.   420.1 G.I.07.a See Recommendation ID Code G.I.07. Null 420.2 G.I.07.b See Recommendation ID Code G.I.07. Null 421 G.I.08 Research should be undertaken to generate information on ways to identify and conceptualize the risk of exceeding the Tolerable Upper Intake Level (UL). Information on the distribution of adverse effects via dose-response data (i.e., risk curves) would allow greatly expanded applications of ULs, particularly for population groups. Major Knowledge 421.1 G.I.08.a See Recommendation ID Code G.I.08. Null 421.2 G.I.08.b See Recommendation ID Code G.I.08. Null 422 G.I.10 Develop new initiatives and innovative methods for the estimation and management of bias (such as underreporting or overreporting of food intake) during analysis of dietary intake data. This is a very high priority area of investigation. Research Method 422.1 G.I.10.a See Recommendation ID Code G.I.10. Null 423 G.I.11 Advances are needed in behavioral research to determine why people underreport food intake. Major Knowledge 424 G.I.12 Following advances in behavioral research to determine why people underreport food intake, develop improved dietary data collection tools that would not trigger this behavior. Research Method 425 G.I.13 Following advances in behavioral research todetermine why people underreport food intake, derive statistical tools to correct the bias associated with this phenomenon. Research Method 426 G.I.14 To enhance estimates of nutrient inadequacy and estimates of nutrient intakes above Research Method

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     the Tolerable Upper Intake Levels (UL), better ways to quantify the intake of dietary supplements are needed. This information is relevant to the nutrient status of a large proportion of the population in the United States and Canada. Investigation of better methods of quantifying dietary supplement intakes is a high-priority research area.   426.1 G.I.14.a See Recommendation ID Code G.I.14. Null 426.2 G.I.14.b See Recommendation ID Code G.I.14. Null 427 G.I.15 Food composition databases need to be updated to include the forms and units that are specified by the Dietary Reference Intakes (DRIs). Research Method 428 G.I.16 Develop chemical methodology to facilitate analysis of various forms of certain nutrients (e.g., alpha-tocopherol versus gamma-tocopherol) to allow comparison to the Dietary Reference Intakes (DRIs). Research Method 429 G.I.17 Investigate methods for developing standard errors for prevalence estimates (such as those associated with requirement estimates). Research Method 430 G.I.20 Further research is needed to apply the recommended assessment methods to estimate differences in the prevalence of in adequacy between subgroups, after controlling for other factors that affect nutrient intake. Major Knowledge 431 G.I.21 Investigate ways to assess the performance ofmethods to estimate prevalence of inadequacy. Major Knowledge 432 G.I.22 Conduct detailed investigations of the effects of violating assumptions for the EAR (Estimated Average Requirement) cut-point method. These investigations would best be done using well-designed, well-planned, and well-implemented simulation studies. Results of such studies would permit identification of recommendations as to the best approach to be used in assessments for each nutrient and would provide an estimate of the expected bias in prevalence estimates when the conditions for application of the EAR cut-point method are not ideal. Assumptions in applying the EAR cut–pointmethod include: (a) intakes and requirements are not correlated or exhibit only low correlation; (b) the distribution of requirements in the population is approximately symmetrical; and (c) the variability of intakes is larger than the variability of requirements. Major Knowledge 432.1 G.I.22.a See Recommendation ID Code G.I.22. Null 432.2 G.I.22.b See Recommendation ID Code G.I.22. Null

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION 433 G.II.10 Research on the factors that can alter nutrient requirements or upper limits is needed to enable more accurate applications of the Dietary Reference Intakes (DRIs) to specific individuals and populations. Adjustment factors for considerations such as body size, physical activity, and intakes of energy and other nutrients may be appropriate but are often unknown. Knowledge Gaps 434 G.II.16 Develop and maintain a database of dietary supplement composition. This is difficult due to the rapidly changing market; however, investigation of better methods of quantifying dietary supplement intakes is a high-priority research area. Intake distribution from dietary supplements usually cannot be adjusted because the current data do not permit the estimation of the day-to-day variability in dietary supplement intake. Research Method 435 G.II.20 Enhance food composition databases to separate nutrients inherent in foods from those provided by fortification, particularly when intakes are compared to the Tolerable Upper Intake Level (UL) for nutrients such as niacin. Research Method 436 G.II.21 Modify food composition databases to change the units of measurement to those specified by the Dietary Reference Intakes (DRIs) (e. g., dietary folate equivalents [DFEs], as suggested for folate; milligrams of alpha-tocopherol, as suggested for vitamin E in place of alpha-tocopherol equivalents; and new biological conversion rates for beta-carotene to vitamin A as suggested for retinol activity equivalents in place of retinol equivalents). Research Method 436.1 G.II.21.a See Recommendation ID Code G.II.21. Null 436.2 G.II.21.b See Recommendation ID Code G.II.21. Null 436.3 G.II.21.c See Recommendation ID Code G.II.21. Null 437 G.II.23 Research is needed to permit calculation of the standard deviation of daily intake for each individual. It is well known that the standard deviation of daily intake is typically heterogeneous across individuals. Conduct research to devise methods to allow the adjustment of a pooled standard deviation estimate to better reflect an individual's daily variability in intakes. Research Method 438 G.II.24 Conduct research to devise methods for quantitatively assessing individual intakes when the distribution of daily intakes is not symmetrical around the individual's usual intake. The approach for testing whether usual intake is greater than requirements (or greater than the Adequate Intake [AI] or less than the Tolerable Upper Research Method

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     Intake Level [UL]) makes the critical assumption that daily intakes for an individual are normally distributed. No alternative methodology exists for the many instances in which this assumption is untenable.   439 G.II.26 Investigate methods for developing standard deviations for prevalence estimates (sometimes referred to as the standard error of the estimate) for use in assessing dietary intakes of groups. Research Method 440 G.II.29 Investigate methods for developing an estimate of the standard deviation for the prevalence of nutrient inadequacy for use in assessing dietary intakes of groups. This concept combines two sources of uncertainty, the standard deviation of the Estimated Average Requirement (EAR) and the standard deviation of the usual intake distribution. Research Method 441 G.II.30 Conduct research on ways to better match the biomarkers used to set requirements with the effect of dietary intake on those same biomarkers. Knowledge Gaps 442 G.II.31 Conduct research on the appropriate biochemical data to collect so that these data can be combined with dietary intake data in assessment. Biomarker and other biochemical data are usually too expensive, time-consuming, or both, to collect on large numbers of individuals. However, when this information is available, it can be used in combination with intake data to give a more accurate estimate of the probability of inadequacy. Knowledge Gaps 443 G.II.35 Conduct research in how to estimate differences in the prevalence of inadequacy between subgroups, after controlling for other factors that also affect nutrient intake. For example, a possible approach to addressing this issue based on multiple regression analysis has been described [see IOM, 2000, Dietary Reference Intakes: Applications in Dietary Assessment, Chapter 7]. Research is needed to apply this approach to existing survey data sets such as the Continuing Survey of Food Intakes by Individuals (CSFII) and the National Health and Nutrition Examination Surveys (NHANES). Knowledge Gaps 444 G.II.39 Develop a wider variety of software that can assist users of the Dietary Reference Intakes (DRIs) in correctly applying the recommended methods. Research Method 445 G.II.40 Upgrade software used currently in dietary assessment to incorporate the recommended statistical methodology. Research Method 446 H.I.02 Pilot test the proposed approaches to dietary planning to achieve a low group preva Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     lence of inadequate nutrient intakes. Before large-scale implementation of these approaches, practical pilot testing will be useful to assess whether a low prevalence of inadequacy can be achieved while meeting other important goals (e.g., avoiding excessive consumption of energy, maintaining nutrient intakes below the Tolerable Upper Intake Level [UL], and avoiding unnecessary food waste).   446.1 H.I.02.a See Recommendation ID Code H.I.02. Null 446.2 H.I.02.b See Recommendation ID Code H.I.02. Null 447 H.I.03 Determine how different nutrition interventions affect intake distributions. It cannot be assumed that an intervention designed to increase the intake of a nutrient will result in a simple upward shift in nutrient intakes without changing the shape of the intake distribution or the between-person variation in usual nutrient intake. Different types of nutritional interventions may have very different effects on both the magnitude and shape of the intake distribution. Examination and publication of intake distributions before and after an intervention, with a systematic collection of this type of data, would allow a more informed selection of methods for planning a dietary intervention. Major Knowledge 447.1 H.I.03.a See Recommendation ID Code H.I.03. Null 448 H.I.04 Determine the intake distributions of specific population groups. Although data on dietary intakes may be available either from national population surveys or surveys of large groups, often such information has not been reported in a manner that facilitates the estimation of variations in the usual intake of individuals. Major Knowledge 449 H.I.05 Determine the relationship between foods offered and nutrient intake in the context of group planning. Research is needed to determine how food offerings relate to food and nutrient intakes, and how the relationship between food offered and intake varies according to planning context. Major Knowledge 450 H.I.06 Develop and evaluate dietary planning strategies for heterogeneous groups, including a nutrient-density approach to dietary planning. Research is needed to determine the practical usefulness of planning for a target nutrient density, determine if the applicability of the nutrient density approach is limited to situations with predetermined food allocations or restricted food choices (e. g., emergency relief rations), and determine if this approach would be practical in situations offering a wide variety of food choices, where the nutrient density is more dependent on food selection Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     than on total food access to meet energy needs.   451 H.I.10 Review and, where necessary, revise existing food guides. Changes in recommended intakes of various nutrients, combined with rapid changes in the amount and number of nutrients and types of foods that are fortified (particularly in the United States), necessitate review of existing food guides and continuation of the periodic review of dietary guidance such as the Dietary Guidelines for Americans and Canada's Guidelines for Healthy Eating. Major Knowledge 451.1 H.I.10.a See Recommendation ID Code H.I.10. Null 452 H.I.11 Develop technical tools for the professional. There is a need to develop analytical tools that support implementation of recommendations for using the Dietary Reference Intakes (DRIs) for professional dietary assessment and planning, as well as for general guidelines for professionals to evaluate such tools. Industry and academia should explore development and production of accurate and convenient tools, expanding on the availability and use of sophisticated hand- held calculators and computers and easy Internet access to a spectrum of data and software. Major Knowledge 452.1 H.I.11.a See Recommendation ID Code H.I.11. Null 453 H.I.12 Communicate with and educate nutrition professionals about correct uses of the Dietary Reference Intakes (DRIs). For full implementation and use of the DRIs, communication strategies are needed to effectively educate nutrition professionals on how the DRI recommendations can be practically and effectively applied. There is a need to formally examine how to best integrate this information into the education of nutrition professionals. Major Knowledge 453.1 H.I.12.a See Recommendation ID Code H.I.12. Null 454 H.I.13 Assess application of the Dietary Reference Intakes (DRIs) for food and supplement labeling. The DRIs provide updated nutrient intake recommendations with scientific justification and extensive documentation. For some nutrients (e. g., folate and vitamin B12), the need to evaluate appropriate labeling information in both the United States and Canada is recognized to convey the recommendation for synthetic sources. Developing and testing a labeling format that conveys the meaning and use of the Tolerable Upper Intake Level (UL) may be especially helpful to consumers. Major Knowledge 454.1 H.I.13.a See Recommendation ID Code H.I.13. Null 455 H.I.14 Develop and evaluate food guides for group planning. Planning for groups to have a Major Knowledge

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Dietary Reference Intakes Research Synthesis Workshop Summary ID No. ID CODE RECOMMENDATION DESIGNATION     low prevalence of inadequate dietary intakes involves methods different from those used in planning for a low risk of dietary inadequacy for individuals. However, in both cases, the emphasis should be on food sources of nutrients. In the United States food-based menu planning guides have long been part of specifications for professionals to use in planning the food offered in various nutrition programs such as the National School Lunch Program. Convenient-to-use, food-based guidelines for menu planning for specific groups should be developed to assist professionals in planning for a low group prevalence of inadequate or excessive intakes.   455.1 H.I.14.a See Recommendation ID Code H.I.14. Null 455.2 H.I.14.b See Recommendation ID Code H.I.14. Null 456 H.I.18 Identify factors that can alter the upper intake levels that can be tolerated biologically. For example, the nutrient source (such as a dietary supplement) can affect the potential risk of nutrient intakes that exceed the Tolerable Upper Intake Level (UL). Major Knowledge 456.1 H.I.18.a See Recommendation ID Code H.I.18. Null 457 H.II.08 For situations in which nutrient density approaches are deemed useful, further development of data and methods is needed to estimate the median and distribution associated with nutrient requirements when expressed as a proportion of energy, either by statistical derivation from the present Estimated Average Requirements (EARs), or as a goal for future revisions of the Dietary Reference Intakes (DRIs). Knowledge Gaps 458 H.II.09 Conduct further research to determine how intake distributions for all nutrients are affected when plans for heterogeneous groups involve targeting the aggregate or average requirement of specific nutrients for all individuals within a group versus targeting the maximum individual requirement for the whole group. Develop criteria to determine when to apply each of these approaches based upon current knowledge used to derive the Estimated Average Requirements (EARs) and Tolerable Upper Intake Levels (ULs), studies of intake distributions, and the effects of interventions. These criteria should consider the impact of such goal setting on the food supply and resulting distribution of intakes. Knowledge Gaps 459 H.II.26 Studies to evaluate nutrient requirements or adverse effects of nutrient intakes should provide individual data where possible to allow estimation of their distributions. Knowledge Gaps

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