1a. Objectives (from AD-416)
LAB: Bone Health 1. Conduct clinical studies to determine the effects of vitamin D in the prevention of physical dysfunction, oral disease, and diabetes, and other chronic diseases in older adults. 2. Conduct clinical studies to determine the effects of dietary protein and dietary acid-base balance on bone and muscle metabolism and function, respectively, in older adults. 3. Determine the role and mechanisms of action for calcium, magnesium, and other dietary components in the maintenance of bone health and the progression of related diseases. LAB: Vitamin K 1. Determine the amounts of individual dietary forms of vitamin K in nationally representative samples of frequently consumed U.S. foods and dietary supplements. 2. Characterize the effects of dietary and non-dietary factors, such as age, lipid profile and body fat, on the bioavailability and utilization of different forms of vitamin K in humans. 3. Identify mechanisms of action for vitamin K, other than its classic role as an enzyme cofactor, using cellular and animal models.
1b. Approach (from AD-416)
LAB: Bone Health The Bone Metabolism Laboratory uses a variety of approaches to carry out its clinical and translational research program. Observational studies such as the publicly available cross-sectional National Health and Nutrition Examination Survey will be used to examine associations of vitamin D with bone mineral density. Longitudinal cohort studies, such as the Nurses Health Study, will be used to link vitamin D levels to risk of several chronic diseases. We will employ diet-controlled metabolic studies to define address several research goals. For example, we will examine the impact of a dietary alkaline load on muscle tissue changes and on indices of bone metabolism in healthy older subjects on both low and high protein diets. Information learned from this metabolic study will be helpful in the design of a large randomized controlled trial to determine the long term effects of lowering the dietary acid load on muscle performance and mass and on rates of bone turnover and bone loss. The Bone Metabolism Laboratory has a strong network of collaborations, both internal, exemplified by our work on multiple projects with the Nutrition, Exercise Physiology and Sarcopenia Laboratory, and external. These collaborations allow us to expand our reach to examine the effect of vitamin D on risk of other chronic diseases such as periodontal disease and diabetes. They also allow us access to basic research technologies, such as gene array analysis, that enable us to identify mechanisms by which nutrients affect bone and muscle. LAB: Vitamin K Laboratory analysis of different forms of vitamin K will be conducted in selected foods obtained through collaboration with the USDA Nutrient and Data Laboratory (NDL), as part of the Food and Nutrient Analysis Program. Priorities for food analysis will include dietary supplements, food purchased in family style restaurants, foods common to the Hispanic/Latino diet, and foods associated with high calorie diets. Food composition data will be transferred to the NDL for entry into national food composition databases. To identify dietary and non-dietary factors that determine how much vitamin K obtained from foods is utilized, we will apply stable isotope techniques to measures of vitamin K metabolism. Data obtained from ongoing metabolic studies in men and women, in addition to pilot feasibility studies, will be used to refine the study design to test the response of these measures to intake of different vitamin K-rich food sources. Animal models will be used to identify tissue-specific effects of interactions between vitamin K and other fat-soluble vitamins, with an emphasis on vitamins A and D. To identify mechanisms of action for vitamin K other than its classic role as an enzyme cofactor, urinary and serum levels of vitamin K metabolites will be measured in response to vitamin K supplementation using archived samples from human and animal studies. We will then focus on the role of different forms of vitamin K in inflammation through the inactivation of nuclear receptors in macrophages.
3. Progress Report
This progress report includes the work of 2 subordinate projects at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-069-01S (Musculoskeletal Health in the Elderly) and 1950-51000-069-02S (Vitamin K: Food Composition, Bioavailability and its Role in Human Health).
1. LAB: Bone Health. Vitamin D improves beta cell function in adults at high risk for diabetes. Evidence from animal studies, observational studies, and small experimental studies suggests that both calcium and vitamin D may influence the risk for type 2 diabetes by improving the ability of pancreatic beta cells to produce insulin. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, in collaboration with scientists at Tufts Medical Center, Boston, MA, and Harvard University, Cambridge, MA, conducted a randomized controlled trial to compare the effects of calcium and vitamin D, separately and together, on beta cell function and other outcomes related to diabetes risk. The study showed no effect of calcium supplementation, but 2000 international units per day (IU/d) of vitamin D improved beta cell function over sixteen weeks. This finding provides strong support for improving vitamin D status among adults who are at risk for type 2 diabetes.
2. LAB: Bone Health. Vitamin D improves insulin secretion in African Americans with prediabetes. Compared with others in the U.S. population, African Americans have much higher rates of both vitamin D deficiency and type 2 diabetes, but the possibility that correcting vitamin D deficiency in this group can reduce their risk for diabetes has not been investigated. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, in collaboration with scientists at Tufts Medical Center, Boston, MA, conducted a randomized controlled trial to examine the effect of a 4000 international units per day (IU/d) dose of vitamin D on insulin secretion and related measures in overweight and obese African Americans with prediabetes. Vitamin D supplementation resulted in a six-fold improvement in insulin secretion over the 12-week supplementation period. This finding suggests that correcting widespread vitamin D deficiency among African-Americans may reduce the racial disparity in the incidence of type 2 diabetes.
3. LAB: Bone Health. Vitamin D lowers fracture risk in seniors when the dose is at least 800 IU/d. Compelling evidence suggests that supplemental vitamin D reduces the risk for fractures among seniors, but the minimum vitamin D dose needed for fracture prevention has not been well defined. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, in collaboration with scientists from multiple sites in the United States and Europe, analyzed data from 30,011 individuals aged 65 years and older who had participated in prior clinical trials of vitamin D supplementation to prevent fractures. Fracture reduction was demonstrated only at vitamin D doses of 800 international units per day (IU/d) or higher and consisted of a 30% reduction in hip fractures and a 14% reduction in all non-vertebral fractures. This finding provides important guidance for clinical decision making and policy development.
4. LAB: Vitamin K. Importance of dietary intake of vitamin K in younger and older adults. Vitamin K is a nutrient that is essential for health, yet is consumed in low amounts by the elderly. To understand the benefits of an increased consumption of vitamin K on human health, ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, studied the effects of dietary and non-dietary factors, including age, sex, blood lipids and body fat, on the utilization of vitamin K. Dietary restriction of vitamin K caused a decline in vitamin K status, which was rapidly reversed by high vitamin K intake. Elderly men and women benefited from vitamin K intake as well as young men and women. These data suggest that individuals with low vitamin K intake will benefit from increased consumption, regardless of their age or sex.
Looker, A.C., Dawson-Hughes, B., Tosteson, A.N., Johansson, H., Kanis, J.A., Melton Iii, J.L. 2011. Hip fracture risk in older US adults by treatment eligibility status based on new National Osteoporosis Foundation Guidance. Osteoporosis International. 22(2):541-549.