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 have demonstrated that administration of potassium bicarbonate, a compound that neutralizes the acid load of the diet, has favorable effects on muscle performance and bone turnover markers over a 3-month period. However, the amount of potassium bicarbonate needed for maximal benefit to muscle and bone is unknown. We are now conducting a randomized, placebo-controlled dose-finding trial to identify the dose of potassium bicarbonate that is most favorable to short-term indicators of muscle and bone health in 276 older men and women. Recruitment is on schedule and the last subject is due to complete the study in July 2015. Once the optimal dose is determined, it will be tested for its effects on longer-term important clinical endpoints including muscle strength and power, risk of falling, and rates of bone loss in healthy older men and women. Safe and low cost strategies are urgently needed to curb the current epidemic of type 2 diabetes. After two years of planning, we have received a grant from the NIH to test the possibility that supplementation with vitamin D, compared with placebo, will retard the progression to type 2 diabetes in high risk adults (adults with pre-diabetes). This trial, due to begin recruitment in the fall will enroll 2,382 men and women from 20 centers around the US. Subjects will take either 4000 IU of vitamin D or placebo daily for up to 4 years. The numbers of subjects meeting our criteria for type 2 diabetes will be compared in the placebo and vitamin D treated subjects. An issue that complicates the process of correcting vitamin D deficiency is that individual serum 25OHD responses to a given dose of the vitamin vary widely. Recent work in our laboratory suggests that the type of fat in the diet influences the absorbability of vitamin D. We are currently conducting a study in 60 healthy older men and women to determine and compare the absorption of vitamin D when the vitamin is taken with a meal with a high mono-unsaturated fatty acid/poly-unsaturated fatty acid (MUFA/PUFA) ratio, a meal with a low MUFA/PUFA ratio, or with no meal (after no food for 12 hours). This research may lead to a more effective strategy to achieve and maintain vitamin D repletion.
1. Vitamin D in adequate amounts lowers fracture risk in older adults. Increasing intake of vitamin D is one strategy to prevent fractures but the amount needed is uncertain. ARS funded researchers at JMUSDA-HNRCA at Tufts University at Boston, Massachusetts examined evidence from 31,022 participants in randomized controlled vitamin D trials and found that an intake of at least 800 IU per day is needed to prevent fractures. Since most older adults in the US consume less than 800 IU per day, increasing vitamin D intake appears to be an effective strategy to lower fracture risk.
2. Vitamin D may build muscle mass via a muscle-specific receptor. Vitamin D affects muscle tissue, but it is not clear how it does so. ARS funded researchers at JMUSDA-HNRCA at Tufts University at Boston, Massachusetts gave 4000 IU/d vitamin D supplements or placebos to frail older women and looked at changes in their muscle tissue. Vitamin D increased the size of muscle fibers by 10% and increased the number of cell nuclei found positive for vitamin D receptors by 30%. This research has demonstrated a direct effect of vitamin D on muscle cells and is an important step in developing targeted strategies for preserving muscle mass in the frail elderly.
3. Meal conditions affect vitamin D absorption. It is often assumed that dietary fat is required for vitamin D absorption, but this has not been demonstrated in controlled experiments. ARS funded researchers at JMUSDA-HNRCA at Tufts University at Boston, Massachusetts randomly assigned healthy older men and women to take a monthly dose of 50,000 IU vitamin D with no meal, a low-fat meal, or a high-fat meal for three months. Vitamin D was absorbed under all three meal conditions, but absorption was highest when vitamin D was taken with the low-fat meal. However, higher absorption did not result in a greater increase in the form of vitamin D that is stored in the blood. The practical implications of meal conditions for vitamin D nutrition now warrant further investigation based on this study.