1a. Objectives (from AD-416)
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.
1b. Approach (from AD-416)
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 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.
3. Progress Report
We recently found that short-term administration of potassium bicarbonate, a compound that neutralizes the acid load of the diet, had favorable effects on short-term indicators of bone and muscle health. A weaker response to the bicarbonate in the men suggests that men may need a higher dose than women. In the future, it will be important to conduct a large, long-term potassium bicarbonate intervention trial to determine whether the favorable bone and muscle effects persist over the long term. Before this is done, however, it is first necessary to identify the dose of potassium bicarbonate that is optimal for men and women. A dose-finding study is now underway. In this study we are evaluating doses up to twice the amount we administered previously and basing the doses on body weight. Once the dose that is most effective and safe over the short-term has been identified, we will seek funding to conduct a large, long-term trial to fully evaluate the effects of potassium bicarbonate on musculoskeletal health. Vitamin D is known to affect muscle tissue, but the mechanism(s) for its effect have not been delineated. Enrollment into this study is currently ongoing. At the same time we have been developing the methods needed to determine how vitamin D affects muscle. This method development work has been successful and we have recently had a manuscript describing the details of tissue staining and analysis accepted for publication. The method is being applied to the human muscle biopsy tissue specimens that are being collected in the study. The study to determine the association between serum 25-hydroxyvitamin D (25OHD) levels and risk of developing type 2 diabetes in the Harvard Nurses’ Health Study is underway. The cases and controls have been selected and the serum 25OHD levels in the baseline samples have been measured. Data analyses are currently in progress. On schedule, we have completed enrollment into the randomized, controlled trial in which we are examining the effects of calcium, vitamin D, and the combination, versus placebo on blood sugar levels and insulin sensitivity in adults with prediabetes, defined as fasting blood sugars between 100 and 120 mg/dl. The samples are currently being analyzed in the laboratory. Data analyses will follow. All subject visits have been completed on the randomized controlled trial to assess the effect of 2000 IU of supplemental vitamin D per day, compared with placebo, on progression of knee osteoarthritis. The blood samples collected during this trial are currently being analyzed. The randomized controlled trial of 4000 IU/d vitamin D to improve insulin sensitivity and glucose control in overweight, pre-diabetic African Americans is in the second of three study years. It is ahead of schedule in recruitment of subjects and completion of study visits. Laboratory measurements have been begun. Data analyses will begin next year. For publications related to project, see parent project #1950-51000-069-00D.