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
Recently found that short-term administration of potassium bicarbonate, a compound that neutralizes the acid load of the diet, had favorable effects on indicators of bone and muscle health. In the future, it will be important to conduct a long-term trial to determine whether the favorable bone and muscle effects persist. First, however, it is necessary to identify the dose of potassium bicarbonate that is optimal for men and women. NIH will fund a large dose-finding potassium bicarbonate trial in 276 older men and women that is scheduled to begin in late 2011. Vitamin D affects muscle tissue, but the mechanism(s) have not been delineated. Enrollment into this study was recently completed and muscle tissue is currently being analyzed for fiber number and area, vitamin D receptor number, protein kinase activity, and gene array analyses. The study to determine the association between serum 25-hydroxyvitamin D (25OHD) and risk of developing type 2 diabetes in the Harvard Nurses’ Health Study has been completed. The study included 608 cases of incident type 2 diabetes and 569 controls. Serum 25OHD levels were inversely associated with the development of type 2 diabetes, independent of known diabetes risk factors, including age, BMI and race. All subject visits have been completed on the randomized controlled trial to assess the effect of 2000 IU of vitamin D per day, compared with placebo, on progression of knee osteoarthritis. The data are currently being analyzed. In a secondary analysis of our STOP/IT trial study, we noted that the serum 25OHD increment in response to 700 IU per day of vitamin D was influenced by the fat composition of the diet. The increment was enhanced by dietary mono-unsaturated fatty acids (MUFAs) and decreased by poly-unsaturated fatty acids (PUFAs). We plan to examine this possibility further in prospective studies. One study currently underway will indicate whether the amount of fat is important and another study (pending funding) will directly assess the effect of the dietary MUFA:PUFA ratio on vitamin D absorption.
1. 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 over 16 weeks the 2000 international units per day (IU/d) of vitamin D improved function of the cells that regulate insulin production and thus glood glucose level. This finding provides strong support for improving vitamin D status among adults who are at risk for type 2 diabetes.
2. 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. 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.