2006 Annual Report 1.What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? Why does it matter? Osteoporosis is a major metabolic bone disease that affects at least 10 million Americans and costs over $14 billion annually in direct medical expenditures. The cause of this debilitating disease is known to be multifactorial with nutritional, genetic and hormonal components. It is recognized widely that manipulation of the diet to improve bone mineralization is the most cost-effective, practical approach in preventing osteoporosis. This approach calls for understanding all significant nutritional factors affecting bone mineral turnover. Such factors include, but are not limited to macronutrients (e.g. protein, lipids), minerals (e.g. calcium, magnesium, phosphorus, potassium, sodium, boron, copper, manganese, zinc), and vitamins (e.g., vitamins A, C, D, E, and K) which modulate such aspects of calcium homeostasis as intestinal absorption or renal excretion, hormone signals, and/or bone formation/bone resorption processes). Calcium intakes of postmenopausal women in the US are considered to be inadequate, but the National Academy of Science, Food and Nutrition Board (FNB) was unable to set an Recommended Dietary Allowance (RDA) due to the paucity of pertinent calcium retention data. Thus, the FNB called for both short- and long-term studies to determine the limits of physiologic adaptation to changes in calcium intake and recognized the need for information concerning dietary factors that affect calcium absorption and/or retention. This project will address these needs by investigating the effects of dietary protein and prebiotics, and by following up on our recent finding that copper and zinc can function synergistically with calcium to prevent bone loss. The FNB also called for better information on the influences of dietary boron on calcium and vitamin D metabolism as these influences relate to bone health. We address this need through controlled studies of boron, specifically to determine unequivocally whether it is a dietary essential and, in that context, whether it affects the need for or utilization of calcium. Last, the FNB called for further research on magnesium, particularly the interrelationships of inadequate dietary magnesium intakes, indicators of magnesium status, and bone health outcomes including osteoporosis. Animal and human experiments were conducted with the goal of establishing the calcium requirement and characterizing the modifying roles of animal proteins (in meat and milk), and zinc, copper, magnesium, and boron (as trace elements) on that requirement. Postmenopausal women and appropriate animal models (e.g., ovariectomized female rats) consumed varying amounts (low, adequate, and/or supranutritional) of calcium and the identified dietary factors while all other components of the diet remained constant. The response of the animals and humans to the dietary manipulations was ascertained by evaluating appropriate biochemical, physiological, and anatomical variables. The research undertaken fell under National Program 107, Human Nutrition, and addressed goal 3.1.1 (Human Nutrition Requirements). The challenge of this component is to identify essential nutrients, determine their effects on reproduction, development, function and longevity, and to provide information that will be used to develop standards to optimize human health, well-being, and genetic potential throughout the life cycle. All priority objectives, especially mechanism of action, biomarkers, function and performance, and nutrient interactions apply to the research program. Outcomes of the research was knowledge that will facilitate establishment of an RDA for calcium with due consideration of the dietary factors that have significant potential to modify that requirement. 2.List by year the currently approved milestones (indicators of research progress) Year 1 (FY 2005): 1. Enroll subjects and conduct study on estimating the Ca requirement by titration. 2. Conduct the first of a three year study on bone health and copper and zinc supplementation. 3. Complete in utero phase of boron essentiality study. 4. Initiate growth phase of three year study of boron essentiality. Year 2 (FY 2006): 1. Complete data analyses from study on estimating the Ca requirement by titration. 2. Enroll subjects and conduct study on bone health during weight loss. 3. Conduct the second of a three year study on bone health and copper and zinc supplementation. 4. Report findings from in utero phase of boron essentiality study. 5. Conduct the second of a three year study of boron essentiality. 6. Conduct study on whether dietary boron affects calcium absorption. 7. Enroll subjects and conduct study on whether dietary inulin affects calcium absorption. Year 3 (FY 2007): 1. Report on study on estimating the Ca requirement by titration. 2. Complete analyses from study on bone health during weight loss. 3. Conduct the third of a three year study on bone health and copper and zinc supplementation. 4. Conduct the third of a three year study of boron essentiality. 5. Conduct post-growth phase of boron essentiality study. 6. Enroll subjects and conduct study on whether magnesium status affects calcium retention and bone resorption. 7. Complete analyses from study on whether dietary inulin affects calcium absorption. Year 4 (FY 2008): 1. Report on study of whether bone health is affected by weight loss. 2. Complete analyses on study on bone health and copper and zinc supplementation. 3. Report findings from growth phase of boron essentiality study. 4. Report findings from post-growth phase of boron essentiality study. 5. Complete analyses on study whether magnesium status affects calcium retention and bone resorption. 6. Report findings from dietary inulin and calcium absorption study 4a.List the single most significant research accomplishment during FY 2006. New Estimation of the Magnesium Requirement for Men and Women: Magnesium is an element that may be a risk factor for osteoporosis and current recommendations regarding the amount of magnesium needed to support health and optimal biological function are based on sparse balance data. ARS scientists at Grand Forks, ND, established a new estimation of the average magnesium requirement of healthy men and women by conducting secondary analyses of magnesium balance data generated in 27 human controlled feeding studies at the Grand Forks Human Nutrition Research Center over the last three decades. The findings suggest a magnesium requirement for healthy men and women (165 mg/d) that is lower than that estimated previously. This work will be very useful in setting the next Dietary Reference Intake for magnesium. This accomplishment was conducted under National Program 107 Human Nutrition; goal 4 of IMPROVING THE NATION’S NUTRITION AND HEALTH; and part of performance standard 4.1.2 related to defining human requirements for known classes of nutrients. 4b.List other significant research accomplishment(s), if any. Boron Promotes Bone Healing After Tooth Extraction: Slow or poor bone formation slows recovery time or healing after injury such as that which occurs with tooth extraction. A cooperative study between scientists at the Grand Forks Human Nutrition Research Center, University of Buenos Aires, and National Research Council of Argentina, showed that a diet low in boron affected bone healing after tooth extraction in mice and rats. Boron deprivation compared to usual intakes of boron resulted in markedly impaired alveolar bone healing after tooth extraction because of reduced bone formation (osteogenesis). This accomplishment is important because it shows that bone healing can be enhanced with a diet containing boron-rich foods (fruits, vegetables and pulses). This accomplishment was conducted under National Program 107 Human Nutrition; goal 4 of IMPROVING THE NATION’S NUTRITION AND HEALTH; and part of performance standard 4.1.2 related to defining functions for emerging classes of nutrients. Dietary Boron May Help Maintain Body Weight Children that experience a rapid weight gain during infancy have been shown to be at greater risk for becoming obese during childhood. Dietary boron reduces body weight in adolescent rats while maintaining indicators of good health. ARS scientists at Grand Forks, ND conducted a study with pregnant rat dams to determine whether boron nutrition early in development is important for body weight of female offspring during late adolescence. They found that rat pups were lighter and had lower cholesterol and triglyceride levels in their blood if their dams consumed usual amounts of boron during pregnancy and lactation. This finding may be of importance in human nutrition where excess body weight is associated with a low intake of fruits and vegetables. These foods are good sources of dietary boron. This accomplishment was conducted under National Program 107 Human Nutrition; goal 4 of IMPROVING THE NATION’S NUTRITION AND HEALTH; and part of performance standard 4.1.2 related to defining functions for emerging classes of nutrients. Boron and Insulin Secretion High levels of insulin in the blood over a long time cause the pancreas to become “exhausted” and to stop secreting insulin after awhile, a situation that results in diabetes. Scientists at the Grand Forks Human Nutrition Research Center, in cooperation with scientists at North Dakota State University, Fargo, ND, have shown that dietary boron reduced the amount of insulin in the blood by about 25% while maintaining the proper amount of glucose in male rats. This finding may be of importance in human nutrition where a decreased risk of developing a glucose tolerance abnormality is associated with frequent consumption of dairy products and fruits and vegetables and low alcohol intake. Fruits and vegetables are good sources of dietary boron. This accomplishment was conducted under National Program 107 Human Nutrition; goal 4 of IMPROVING THE NATION’S NUTRITION AND HEALTH; and part of performance standard 4.1.2 related to defining functions for emerging classes of nutrients. 4c.List significant activities that support special target populations. None 4d.Progress report. None 5.Describe the major accomplishments to date and their predicted or actual impact. This report is the first for this CRIS project (certified in 2005), thus the accomplishments for the life of the project are incorporated in sections 4a and 4b. 6.What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end-user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? Information about the nutritional of beneficial aspects of ultratrace and trace elements as it became available was routinely transferred to a variety of customers. The customers included nutritional risk assessment groups through direct contact or organized meetings and workshops; the public through web pages of professional organizations, via the popular media; and other scientists through presentations at national and international meetings and professional publications. 7.List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below). Information was transferred to the public through a local public lecture and through the local newspaper (Grand Forks Herald) that was also placed on the Grand Forks Human Nutrition Research Center Home Page. Dr. Nielsen wrote an article entitled, “Nutrients Keeps Immune System in Balance.” Dr. Hunt wrote an article entitled, Don't overlook importance of breast-feeding” and presented the lecture entitled “The bricks (calcium) or the mortar (everything else): which is more important in a healthy bone?” for the Spring 2006 Medical School for the Public seminar series, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND. Review Publications Hunt, C., Butte, N.F., Johnson, L.K. 2005. Boron concentrations in milk from mothers of exclusively breast-fed healthy full-term infants are stable during the first four months of lactation. Journal of Nutrition. 135:2383-86. Nielsen, F.H. 2006. A mild magnesium deprivation affects calcium excretion but not bone strength and shape, including changes induced by nickel deprivation, in the rat. Biological Trace Element Research. 110:133-149. Hunt, C. 2006. Dietary boron: evidence for essentiality and homeostatic control in humans and animals. In: Fangsen Xu, Heiner E. Goldback, Patrick H. Brown, Richard W. Bell, Toru Fujiwars, Curtiss D. Hunt, Sabine Goldberg, Lei Shi, editors. Advances in Plant and Animal Boron Nutrition. Boron 2005, September 10-13, 2005, Wuhan, China. p. 230-246. Nielsen, F.H., Stoecker, B.J., Penland, J.G. 2006. Boron as a dietary factor for bone microarchitecture and central nervous system function. In: Fangsen Xu, Heiner E. Goldback, Patrick H. Brown, Richard W. Bell, Toru Fujiwars, Curtiss D. Hunt, Sabine Goldberg, Lei Shi, editors. Advances in Plant and Animal Boron Nutrition. Boron 2005, September 10-13, 2005, Wuhan, China. p. 255-268. Nielsen, F.H. 2006. Silicon. In: Klasing, K.C., editor. Mineral Tolerance of Animals. 2ndd Revised Edition. Washington DC; National Academies Press. p. 348-356. Friel, J., Hunt, C. 2005. Boron and molybdenum content in infant formulas [abstract]. 12th International Symposium on Trace Elements in Man and Animals. p. 93. Hunt, C. 2005. Dietary boron: evidence for essentiality and homeostatic control in humans and animals [abstract]. Presented at Boron 2005, Wuhan, China, September 10-13, 2005. Hunt, C., Johnson, L.K. 2006. Estimation of magnesium requirements in men and women by cross-sectional statistical analyses of metabolic magnesium balance data [abstract]. FASEB J. 20(4):A182. Nielsen, F.H. 2005. Effect of dietary silicon on bone turnover and the inflammatory response may be through an immune response involving osteopontin [abstract]. Journal of Dairy Science. 83(Suppl. 1):333. Nielsen, F.H., Stoecker, B. 2006. Dietary boron and fish oil have desirable effects on vertebra microarchitecture and strength [abstract]. FASEB J. 20(4):A561. Gorustovich, A.A., Steimetz, T., Nielsen, F.H., Guglielmotti, M.B. 2006. A histomorphometric study of alveolar bone healing in rats fed a boron-deficient diet [abstract]. FASEB J. 20(4):A24. Gorustovich, A.A., Steimetz, T., Nielsen, F.H., Guglielmotti, M.B. 2006. A histomorphometric study of alveolar bone modeling and remodeling in mice fed a boron-deficient diet [abstract]. FASEB J. 20(4):A195. Nielsen, F.H. 2006. Dietary magnesium deprivation confirmed by balance induces biochemical and functional changes including calcium balance in postmenopausal women [abstract]. International Symposium on Health Aspects of Calcium and Magnesium in Drinking Water, Program and Abstracts. p. 43-44. Combs, Jr., G.F., Hassan, N. 2005. The Chakaria food system study: household level, case-control study to identify risk factor for rickets in Bangladesh. European Journal of Clinical Nutrition. 59:1291-1301. Nielsen, F.H., Stoecker, B.J., Penland, J.G. 2005. Boron as a dietary factor for bone microarchitechture and central nervous system function [abstract]. Abstract Book, The Third International Symposium on All Aspects of Plant and Animal Boron Nutrition, September 9-13, 2005, Huazhong Agricultural University, Wuhan, China, p 52. Turner, K.K., Nielsen, B.D., O'Connor, C.I., Rosenstein, D.S., Schott, H., Womack, C.J., Nielsen, F.H., Orth, M.W. 2006. Sodium zeolite A supplementation to dairy calves [abstract]. Journal American Science. vol. 84, Suppl. 1/Journal Dairy Science. vol. 89, Suppl. 1. p.436-437.