Progress 10/01/05 to 09/30/06
Outputs
Progress 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? This five-year research plan represents a continuation of interest on the part of the Bone Metabolism Laboratory in improving the understanding of how diet impacts bone health in older men and women. Serum 25-hydroxy vitamin D [25(OH)D] is the best clinical measure of vitamin D status. One objective of the Bone Metabolism Laboratory is to define factors that influence the 25(OH)D concentrations achieved at a given vitamin D intake level in the wintertime. We will assess the effect of body mass index on the utilization of dietary vitamin D in 389 men and women age 65 and older who participated in a placebo-controlled calcium and vitamin D intervention study. We will also test the hypothesis that the increase in serum 25(OH)D in response to oral dosing with vitamin D is blunted at low
calcium intakes. This will be studied in a new randomized controlled trial in which 800 IU/day of vitamin D will be given to older subjects with high and low calcium intakes. We will also determine the impact of endogenous gonadal-hormone levels on 25(OH)D responses to supplemental vitamin D. Falls are a common source of serious injury, including fractures, in older subjects. Recent evidence suggests that low vitamin D levels may contribute to muscle weakness and increased risk of falling in this population. We will examine this possibility in the 389 older men and women who participated in our 3-year calcium and vitamin D intervention study. The impact of lean body mass, gonadal hormone levels, and usual activity levels on risk of falling will also be assessed. The vitamin D studies described above will improve the scientific basis for determining the vitamin D intake requirements for older men and women. A second research initiative of the Bone Metabolism Laboratory is to define
the impact of dietary protein and the acid-base balance of the diet on bone health. Several small protein intervention studies will be conducted to define the relative roles of protein, added aromatic or branched-chain L-amino acids, calcium, vitamin D, and alkaline foods (fruits and vegetables) or supplements, such as potassium bicarbonate, on short-term indices of bone metabolism including biochemical markers of bone turnover, calcium absorption, urinary calcium excretion, and insulin- like growth factor-1. A supplement (expected to contain protein, calcium, vitamin D, alkali, and perhaps added branched-chain amino acids) will be tested in a large longitudinal intervention trial in older men and women to determine its impact on rates of change in bone mineral density (BMD). This research falls under National Program 107 - Human Nutrition, and is related to component 4: Nutrient Requirements. 2. List by year the currently approved milestones (indicators of research progress)
Objective 1: Refine the approach to determining the vitamin D requirement for optimal musculoskeletal and dental health in men and women. Objective 2: Define the impact of dietary protein and the acid/base balance of the diet on musculoskeletal health in men and women. Objective 3: Define the impact of calcium and vitamin D intake on insulin resistance and risk of developing Type 2 diabetes in men and women. 2005 1. To determine the impact of body mass index on the serum 25(OH)D response to supplemental vitamin D. Objective 1 2. To determine the impact of calcium intake on the 25(OH)D response to supplemental vitamin D. Objective 1 3. To assess the long-term effect of vitamin D plus calcium on physical function and on the risk of falling in older men and women. Objective 1 2006 1. To determine the association between serum vitamin D levels and risk of gingivitis. Objective 1 2. To define and compare patterns of calcium and vitamin D supplement use in a random sample of women with and
without osteoporosis. Objective 1 3. To determine whether the level of calcium intake influences any association between the ratio of nitrogen to potassium in the urine and rates of bone loss in older men and women. Objective 2 4. To determine the association between the ratio of nitrogen to potassium in the urine, an index of the acidogenicity of the diet, and 3- year rates of bone loss in healthy older men and women. Objective 1 5. To determine the impact of stimulating the calcium sensor receptor on gastric acid secretion and calcium excretion. Objective 2 6. To determine the association between intakes of calcium and vitamin D and incidence of developing Type 2 diabetes. Objective 3 7. To determine and compare the effects of selected aromatic and branched-chain amino acids on urinary calcium excretion in healthy older men and women. Objective 2 2007 1. To study the association between endogenous gonadal hormone levels and physical function and risk of falling in elderly men and
women. Objective 1 2. Determine mechanisms by which vitamin D influences muscle strength and risk of falling. Objective 1 3. To determine whether alkalinization of the diet will attenuate the urine calcium losses induced by high protein diets. Objective 2 4. To determine the effect of supplementation with calcium and vitamin D on fasting insulin and glucose levels in healthy older men and women. Objective 3 2008 1. Define mechanisms by which specific amino acids affect intestinal calcium absorption. Objective 2 2. To begin a randomized, controlled longitudinal trial to determine whether alkalinization of the diet will lower the bone turnover rate, and thus lower risk of fracture, in healthy men and women who are being supplemented with calcium and vitamin D. Objective 2 2009 1. Continue the randomized, controlled longitudinal trial to determine whether alkalinization of the diet will lower the bone turnover rate, and thus lower risk of fracture, in healthy men and women who are being
supplemented with calcium and vitamin D. Objective 2 4a List the single most significant research accomplishment during FY 2006. Vitamin D, Calcium and Type 2 Diabetes Mellitus Higher intakes of vitamin D and calcium significantly lowered risk of developing type 2 diabetes mellitus in the Nurses' Health Study, a prospective cohort of 83,779 women age 30 to 55 years who were followed for 20 years. A combined daily intake of over 800 IU of vitamin D and 1200 mg of calcium was associated with a 33% lower risk of developing type 2 diabetes as compared with an intake of less than 200 IU and 600 mg of vitamin D and calcium, respectively. The results of this prospective cohort study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes. Type 2 diabetes mellitus is associated with considerable morbidity and mortality and its prevalence has been increasing in the United States and worldwide. Potentially modifiable environmental risk
factors for type 2 diabetes have been identified, the major one being obesity. However, although weight-loss (achieved by any means) has been shown to be successful in delaying diabetes, it is difficult to achieve and maintain long-term. Therefore, identification of weight-independent and easily modified dietary risk factors is urgently needed to prevent the increase in the incidence of type 2 diabetes. This research falls under National Program 107 - Human Nutrition, Component 1: Nutrient Requirements. 4b List other significant research accomplishment(s), if any. Vitamin D Supplementation Can Lower Fracture Risk A meta-analysis of randomized, controlled vitamin D intervention studies revealed that vitamin D lowers risk of fracture when the intervention is sufficient to raise the serum 25-hydroxyvitamin D level to 75 nmol/L or higher. Studies in which lower circulating levels of 25-hydroxyvitamin D were achieved, either because of administration of a lower dose of vitamin D or
because of non-compliance with the supplements, showed no effect of the vitamin on fracture risk. Vitamin D appears to lower fracture risk by increasing bone mass and by lowering risk of falling. Increasing intake of this vitamin is a safe and cost-effective approach to reducing fractures in elderly men and women. This research falls under National Program 107 Human Nutrition, Components 1: Nutrient Requirements. 5. Describe the major accomplishments to date and their predicted or actual impact. As we complete the second year of this 5-year program cycle, the main accomplishments of the Bone Metabolism Laboratory are the findings that supplementation with calcium and vitamin D lowers risk of falling in older subjects. Falls are common occurrences in the elderly 30% of subjects age 65 and 40 to 50% of those age 80 fall each year. These falls are a major precipitant of fractures. As expected, increasing vitamin D intake, by lowering risk of falling, can also lower risk of fracture
in older men and women. Dissemination of these findings in the scientific and medical community should lead to increases in vitamin D and calcium intakes and a reduction in falls and fractures in older men and women. This finding is related to Milestone 3, 2005: To assess the long-term effect of vitamin D plus calcium on physical function and on the risk of falling in older men and women. The second major finding is that increased intakes of calcium and vitamin D are associated with lower risk of developing type 2 diabetes. This provides a safe and easy approach to lowering risk of developing this devastating disease. This finding is related to Milestone 6 (2006): To determine the association between intakes of calcium and vitamin D and incidence of developing Type 2 diabetes. These findings are related to National Program 107 - Human Nutrition program component 4: Nutrient Requirements. 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? The finding that higher intakes of calcium and vitamin D reduce risk of developing type 2 diabetes has been presented at a scientific meeting and published in the peer-reviewed literature. This information will be useful in determining the calcium and vitamin D requirements. No intellectual property rights issues apply. 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). Environmental Nutrition Calcium and vitamin D help tame blood sugar (Dr. Dawson-Hughes findings on calcium, vitamin D , and risk of developing type 2 diabetes) June, 2006. National Public Radio interview Better bone health with more vitamin D, June 22, 2006. ABC World News Tonight Dr.
Dawson-Hughes view on the role of calcium in lowering fracture risk, Febuary 15, 2006. Good Morning America Dr. Dawson-Hughes view on the importance of calcium in bone health. Febuary 16, 2006. Bloomberg News Dr. Dawson-Hughes interpretation of the Womens Health Initiative study of calcium, vitamin D and fracture risk. Febuary 21, 2006. Washington Post - Dr. Dawson-Hughes interpretation of the optimal vitamin D intake for bone health. August 9, 2005.
Impacts
(N/A)
Publications
- Dawson-Hughes, B. 2005. Calcium throughout the life cycle - the later years. In: Calcium in Human Health. Weaver C, Heaney RP (eds). Humana Press, Inc., Totowa, NJ. p. 371-385.
- Dietrich, T., Nunn, M., Dawson-Hughes, B., Bischoff-Ferrari, H.A. 2005. Association between serum concentrations of 25-hydroxyvitamin d and gingival inflammation. American Journal of Clinical Nutrition. 82(3):575- 80.
- Bischoff-Ferrari, H.A., Orav, J.E., Dawson-Hughes, B. 2006. Effect of vitamin d plus calcium on falling in ambulatory older men and women: a 3- year randomized controlled trial. Archives of Internal Medicine. 166(4) :424-30.
- Pittas, A.G., Dawson-Hughes, B., Li, T., Van Dam, R.M., Willett, W.C., Manson, J., Hu, F.B. 2006. Vitamin d and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 29(3):650-6.
- Dawson-Hughes, B. 2006. Introduction to the supplement of the american journal of medicine's issue on "improving compliance and persistence with osteoporosis therapies". American Journal of Medicine. 119(4 Suppl 1):s1- s2.
- Jajoo, R., Rasmussen, H., Song, L., Dawson-Hughes, B. 2006. Dietary acid- base balance, bone resorption, and calcium excretion. Journal of the American College of Nutrition. 25(3):224-30.
- Bischoff-Ferrari, H., Giovannucci, E., Willett, W.C., Dietrich, T., Dawson- Hughes, B. 2006. Estimation of optimal serum concentrations of 25- hydroxyvitamin d for multiple health outcomes. American Journal of Clinical Nutrition. 84(1):18-28.
- Dawson-Hughes, B. 2005. How important is vitamin d for bone health? a clinical scientist's perspective. Endocrine News. 30(6):10-15.
- Dawson-Hughes B. 2005. Calcium and vitamin D. In: Kleerekoper M, Siris E, McClung M, ed(s). The Bone and Mineral Manual: A practical guide. San Diego, CA: Elsevier Inc. p. 93-96.
- Must, A., Naumova, E., Phillips, S., Blum, M., Dawson-Hughes, B., Rand, W. 2005. Childhood overweight and maturational timing in the development of adult overweight and fatness: the newton girls study and its follow-up. Journal of Pediatrics. 116(3):620-7.
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Progress 10/01/04 to 09/30/05
Outputs
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? What does it matter? This five-year research plan represents a continuation of interest on the part of the Bone Metabolism Laboratory in improving the understanding of how diet impacts bone health in older men and women. Serum 25-hydroxy vitamin D [25(OH)D] is the best clinical measure of vitamin D status. One objective of the Bone Metabolism Laboratory is to define factors that influence the 25(OH)D concentrations achieved at a given vitamin D intake level in the wintertime. We will examine the effect of body mass index on the utilization of dietary vitamin D. This will be studied in the 389 men and women age 65 and older who participated in a placebo-controlled calcium and vitamin D intervention study. We will also test the hypothesis that the increase in serum 25(OH)D in response to oral dosing with vitamin D is
blunted at low calcium intakes. This will be studied in a new randomized controlled trial in which 800 IU/day of vitamin D will be given to older subjects with high and low calcium intakes. We will also examine the impact of endogenous gonadal-hormone levels on 25(OH)D responses to supplemental vitamin D. Falls are a common source of serious injury, including fractures, in older subjects. Recent evidence suggests that low vitamin D levels may contribute to muscle weakness and increased risk of falling in this population. We will examine this possibility in the 389 older men and women who participated in our 3-year calcium and vitamin D intervention study. The impact of lean body mass, gonadal hormone levels, and usual activity levels on risk of falling will also be examined. The vitamin D studies described above will improve the scientific basis for determining the vitamin D intake requirements for older men and women. A second research initiative of the Bone Metabolism Laboratory
is to define the impact of dietary protein and the acid-base balance of the diet on bone health. Several small protein intervention studies will be conducted to define the relative roles of protein, added aromatic or branched-chain L-amino acids, calcium, vitamin D, and alkaline foods (fruits and vegetables) or supplements, such as potassium bicarbonate, on short-term indices of bone metabolism including biochemical markers of bone turnover, calcium absorption, urinary calcium excretion, and insulin-like growth factor-1. A supplement (expected to contain protein, calcium, vitamin D, alkali, and perhaps added branched- chain amino acids) will be tested in a large longitudinal intervention trial in older men and women to determine its impact on rates of change in bone mineral density (BMD). This research falls under National Program 107 - Human Nutrition, and is related to component 4: Nutrient Requirements. 2. List the milestones (indicators of progress) from your Project Plan.
Objective 1: Refine the approach to determining the vitamin D requirement for optimal musculoskeletal and dental health in men and women Objective 2: Define the impact of dietary protein and the acid/base balance of the diet on musculoskeletal health in men and women Objective 3: Define the impact of calcium and vitamin D intake on insulin resistance and risk of developing Type 2 diabetes in men and women 2005 1. To determine the impact of body mass index on the serum 25(OH)D response to supplemental vitamin D. Objective 1 2. To determine the impact of calcium intake on the 25(OH)D response to supplemental vitamin D. Objective 1 3. To assess the long-term effect of vitamin D plus calcium on physical function and on the risk of falling in older men and women. Objective 1 2006 1. To determine the association between serum vitamin D levels and risk of gingivitis. Objective 1 2. To define and compare patterns of calcium and vitamin D supplement use in a random sample of women with and
without osteoporosis. Objective 1 3. To determine whether the level of calcium intake influences any association between the ratio of nitrogen to potassium in the urine and rates of bone loss in older men and women. Objective 2 4. To determine the association between the ratio of nitrogen to potassium in the urine, an index of the acidogenicity of the diet, and 3- year rates of bone loss in healthy older men and women. Objective 1 5. To determine the impact of stimulating the calcium sensor receptor on gastric acid secretion and calcium excretion. Objective 2 6. To determine the association between intakes of calcium and vitamin D and incidence of developing Type 2 diabetes. Objective 3 7. To determine and compare the effects of selected aromatic and branched-chain amino acids on urinary calcium excretion in healthy older men and women. Objective 2 2007 1. To study the association between endogenous gonadal hormone levels and physical function and risk of falling in elderly men and
women. Objective 1 2. Determine mechanisms by which vitamin D influences muscle strength and risk of falling. Objective 1 3. To determine whether alkalinization of the diet will attenuate the urine calcium losses induced by high protein diets. Objective 2 4. To determine the effect of supplementation with calcium and vitamin D on fasting insulin and glucose levels in healthy older men and women. Objective 3 2008 1. Define mechanisms by which specific amino acids affect intestinal calcium absorption. Objective 2 2. To begin a randomized, controlled longitudinal trial to determine whether alkalinization of the diet will lower the bone turnover rate, and thus lower risk of fracture, in healthy men and women who are being supplemented with calcium and vitamin D. Objective 2 2009 1. Continue the randomized, controlled longitudinal trial to determine whether alkalinization of the diet will lower the bone turnover rate, and thus lower risk of fracture, in healthy men and women who are being
supplemented with calcium and vitamin D. Objective 2 3a List the milestones that were scheduled to be addressed in FY 2005. For each milestone, indicate the status: fully met, substantially met, or not met. If not met, why. 1. Bone Metabolism Laboratory Milestone # 1 To determine the impact of body mass index on the serum 25(OH)D response to supplemental vitamin D. Milestone Fully Met 2. Bone Metabolism Laboratory Milestone # 2 To determine the impact of calcium intake on the 25(OH)D response to supplemental vitamin D. Milestone Fully Met 3. Bone Metabolism Laboratory Milestone # 3 To assess the long-term effect of vitamin D plus calcium on physical function and on the risk of falling in older men and women. Milestone Fully Met 3b List the milestones that you expect to address over the next 3 years (FY 2006, 2007, and 2008). What do you expect to accomplish, year by year, over the next 3 years under each milestone? 2006 1. To determine the association between serum vitamin D
levels and risk of gingivitis. Objective 1 Anticipated Results: We expect to find that adults with optimal 25(OH)D concentrations are at decreased risk for gingivitis compared with those with lower levels. 2. To define and compare patterns of calcium and vitamin D supplement use in a random sample of women with and without osteoporosis. Objective 1 Anticipated Results: We expect to find that patterns of calcium and vitamin D supplement use differ between women with and without osteoporosis and that the differences are influenced by their medical treatment. 3. To determine whether the level of calcium intake influences any association between the ratio of nitrogen to potassium in the urine and rates of bone loss in older men and women. Objective 2 Anticipated Results: We expect to find that a higher nitrogen to potassium ratio is less strongly associated with bone loss in older men and women with high calcium intakes than in those with low calcium intakes. 4. To determine the
association between the ratio of nitrogen to potassium in the urine, an index of the acidogenicity of the diet, and 3- year rates of bone loss in healthy older men and women. Objective 2 Anticipated Results: We expect to find that a high ratio of nitrogen to potassium predicts increased rates of bone loss in older men and women. 5. To determine the impact of stimulating the calcium sensor receptor on gastric acid secretion and calcium excretion. Objective 2 Anticipated Results: We expect to find that a calcimimetic agent will increase gastric acid secretion and urinary calcium excretion compared with placebo. 6. To determine the association between intakes of calcium and vitamin D and incidence of developing Type 2 diabetes. Objective 3 Anticipated Results: We expect to find that poor intakes of both calcium and vitamin D and a low 25(OH)D level is associated with a higher incidence of type 2 diabetes. 7. To determine and compare the effects of selected aromatic and branched-chain
amino acids on urinary calcium excretion in healthy older men and women. Objective 2 Anticipated Results: We expect to find that aromatic L-amino acids have a greater calciuric effect than branched chain L-amino acids in healthy older men and women. 2007 1. To study the association between endogenous gonadal hormone levels and physical function and risk of falling in elderly men and women. Objective 1 Anticipated Results: We expect to find that elderly men and women who have higher levels of endogenous gonadal hormones have better physical function and fall less often that those with lower levels. 2. Determine mechanisms by which vitamin D influences muscle strength and risk of falling. Objective 1 Anticipated Results: We expect to find that vitamin D increases muscle strength and reduces falling by influencing vitamin D signaling in muscle tissue. 3. To determine whether alkalinization of the diet will attenuate the urine calcium losses induced by high protein diets. Objective 2
Anticipated Results: We expect to find that neutralizing the acid load will reduce urinary calcium losses associated with a high protein diet. 4. To determine the effect of supplementation with calcium and vitamin D on fasting insulin and glucose levels in healthy older men and women. Objective 3 Anticipated Results: We expect to find that supplementation with vitamin D and calcium will reduce fasting insulin and glucose levels in healthy older men and women, consistent with improved glucose control and insulin sensitivity. 2008 1. Define mechanisms by which specific amino acids affect intestinal calcium absorption. Objective 2 Anticipated Results: We expect to find differences between branched- chain L-amino acids and aromatic L-amino acids in their effects on biochemical factors that regulate intestinal calcium absorption. 2. To begin a randomized, controlled longitudinal trial to determine whether alkalinization of the diet will lower the bone turnover rate, and thus lower risk of
fracture, in healthy men and women who are being supplemented with calcium and vitamin D. Objective 2 Anticipated Results: We expect to find that neutralizing the acid load will lower the bone turnover rate and reduce fracture risk in healthy men and women. 4a What was the single most significant accomplishment this past year? Vitamin D, Calcium and Falls Supplementation with vitamin D and calcium in frequently recommended amounts significantly lowered risk of falling in our cohort of 389 healthy older men and women. Relatively sedentary women appeared to have the greatest risk reduction with supplementation. Falls are the largest single cause of injury in the elderly and 90% of fractures result from falls. In our placebo-controlled calcium and vitamin D intervention trial, information on falls was acquired every 6 months for 3 years and fall rates in the supplemented and placebo groups were compared. Broad-based increases in vitamin D and calcium intake have the potential to
substantially reduce fractures and other injuries in the elderly by lowering the risk for falling. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. As we complete the first year of this 5-year program cycle, the main accomplishment of the Bone Metabolism Laboratory is finding that supplementation with calcium and vitamin D lowers risk of falling in older subjects. Falls are common occurrences in the elderly 30% of subjects age 65 and 40 to 50% of those age 80 will fall in 1 year and falls are a major precipitant of fractures. Dissemination of this finding in the scientific and medical community should lead to increases in vitamin D and calcium intakes and a reduction in falls and fractures in older men and women. This finding is related to Milestone #3: To assess the long-term effect of vitamin D plus calcium on physical function and on the risk of falling in older men and women, and to National Program 107 - Human
Nutrition program component 4: Nutrient Requirements, and ARS Strategic Plan Performance Measure 4.1.2.: Improve Human Health by Better Understanding the Nutrient Requirements of Individuals and the Nutritional Value of Foods. 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? The finding that the calcium intake does not influence the increase in serum 25(OH)D that occurs with vitamin D supplementation (Milestone 2) has been presented at a scientific meeting and published in the peer- reviewed literature. This information will be useful in determining the calcium and vitamin D requirements. No intellectual property rights issues apply. 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). Journal of American Medical Association Better osteoporosis management a priority; (describing Dr. Dawson-Hughes views on vitamin D and Bone health) May 25, 2005. US News World Report National Issues Briefing, Bone Health and Osteoporosis (Calcium and vitamin D in the diet); October 20, 2004.
Impacts
(N/A)
Publications
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