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United States Department of Agriculture

Agricultural Research Service

Research Project: MUSCULOSKELETAL HEALTH IN THE ELDERLY
2012 Annual Report


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 two 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)


4.Accomplishments
1. LAB: Muscuolosketal Health in the elderly: Vitamin D improves glucose tolerance in adults at high risk for type 2 diabetes. Adults with lower blood levels of vitamin D are thought to be at increased risk of developing type 2 diabetes. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA,, in collaboration with scientists at Tufts Medical Center in Boston, MA conducted a study to examine the effect of 2000 IU of vitamin D per day compared with placebo on insulin secretion and insulin sensitivity in a group of mainly Caucasian adults at high risk for developing type 2 diabetes. Over a 16-week period, supplementation significantly improved glucose tolerance, mainly by increasing insulin secretion. This study suggests a favorable effect of vitamin D on glucose handling and it provides the evidence needed to justify a large trial to determine whether longer-term supplementation with vitamin D will in fact lower risk of risk of developing type 2 diabetes in high-risk adults.

2. LAB: Muscuolosketal Health in the elderly: Vitamin D does not change the pathophysiology of prediabetes in African Americans. African-Americans have low vitamin D levels and a high incidence of type 2 diabetes. Prior evidence from this laboratory suggested that vitamin D supplementation can mitigate the progression from prediabetes to type 2 diabetes in Caucasian individuals, but it was unknown whether a similar effect would be observed in African Americans. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, 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. Supplementation successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on blood sugar levels. Thus, vitamin D supplementation for three months did not change the risk for progressing to diabetes in overweight and obese African Americans.

3. LAB: Muscuolosketal Health in the elderly: Dietary fat may influence the bioavailability of dietary vitamin D. The process of vitamin D replacement is complicated by the fact that the increase in the blood level of vitamin D in response to a given dose of the vitamin varies greatly from person to person. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, recently analyzed data from an intervention trial, and found that the increase in the blood level of vitamin D 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 monounsaturated fatty acids (MUFAs) and decreased by poly-unsaturated fatty acids (PUFAs). Understanding the nature of nutrient-nutrient interactions with vitamin D may lead to guidance on how to increase the bioavailability of this important vitamin.

4. LAB: Vitamin K: Vitamin K status in U.S. adults differs according to race and ethnicity. Vitamin K is a nutrient that is essential for health, but little is known about racial and/or ethnic differences in vitamin K status. To address this gap in knowledge, ARS-Funded scientists from Tufts University in Boston, MA in collaboration with scientists from Wake Forest Medical Center, studied the racial and ethnic differences in circulating vitamin K concentrations of adults participating in the Multiethnic Study of Atherosclerosis. Very few of the Chinese Americans had low concentrations of circulating vitamin K. In comparison, about one-third of African Americans and Hispanics had low concentrations of circulating vitamin K, which is related to increased risk of abnormal coronary artery calcification and osteoarthritis. These findings suggest that vitamin K status differs by race and ethnicity in U.S. adults, which may partially explain the observed racial and ethnic differences in health outcomes related to vitamin K.


Review Publications
Wang, T., Feng, Z., Richards, B., Kestenbaum, B., Van Meurs, J., Berry, D., Kiel, D., Streeten, E., Ohlsson, C., Koller, D., Jarvelin, M., Cooper, J., O'Reilly, P., Houston, D., Glazer, N., Vandenput, L., Peacock, M., Shi, J., Rivadeneira, F., Mccarthky, M., Anneli, P., De Boer, I., Mangino, M., Kato, B., Smyth, D., Booth, S., Jacques, P., Burke, G., Goodarzi, M., Cheung, C., Wolf, M., Rice, K., Goltzman, D., Hidiroglou, N., Ladouceur, M., Hui, S., Wareham, N., Hocking, L., Hart, D., Arden, N., Copper, C., Malik, S., Fraser, W., Hartikainen, A., Zhai, G., Macdonald, H., Forouhinita G, Loos, R., Reid, D., Hakim, A., Dennison, E., Liu, Y., Power, C., Stevens, H., Jaana, L., Vasan, R., Soranzo, N., Bojunga, J., Pstay, B., Lorentzon, M., Foroud, T., Harris, T., Hofman, A., Jansson, J., Cauley, J., Uitterlinden, A., Gibson, Q., Palotie, L., Karasik, D., Econs, M., Kritchevskyk, S., Florez, J., Todd, J., Dupuis, J., Hypponen, E., Spector, T. 2010. Common genetic determinants of vitamin D insufficiency: the sunlight consortium. Lancet. 376(9736):180-188.

Santos, R.D., Miname, M.H., Martinez, L.R., Rochitte, C.E., Chacra, A.P., Nakandakare, E.R., Chen, D., Schaefer, E. 2008. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography. Atherosclerosis. 197(2):910-915.

Bischoff-Ferrari, H., Willett, W., Orav, E.J., Lips, P., Lyons, R., Flicker, L., Wark, J., Jackson, R., Cauley, J., Meyer, H., Pfeifer, M., Sanders, K., Staehelin, H., Theiler, R., Meunier, P., Dawson-Hughes, B. 2012. A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors. New England Journal of Medicine. 367(1):40-49.

Cosman, F., Dawson-Hughes, B., Wan, X., Krege, J. 2012. Changes in vitamin D metabolites during teriparatide treatment. Bone. 50(6):1368-1371.

Truong, J., Fu, X., Saltzman, E., Al Rajabi, A., Dallal, G., Gundberg, C., Booth, S. 2012. Age,group,or sex do not influence responses of vitamin K biomarkers to changes in dietary vitamin K. Journal of Nutrition. 142(5):936-941.

Shea, M., Booth, S., Nettleton, J., Burke, G., Chen, H., Kritchevsky, S. 2012. Circulating phylloquinone concentrations of adults in the United States differs according to race/ethnicity. Journal of Nutrition. 111:154278.

Shea, K.M., O'Donnell, C.J., Vermeer, C., Magdeleyns, E., Crosier, M.D., Gundberg, C.M., Ordovas, J.M., Kritchevsky, S.B., Booth, S.L. 2011. Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. Journal of Nutrition. 141(8):1529-1534.

Rajabi, A., Booth, S., Peterson, J., Choi, S., Suttie, J., Shea, M., Miao, B., Grusak, M.A., Fu, X. 2012. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats. Journal of Nutrition. 142(5):841-845.

Rienstra, M., Cheng, S., Larson, M., Mccabe, E., Booth, S., Jacques, P., Lubitz, S., Yin, X., Levy, D., Magnani, J., Ellinor, P., Benjamin, E., Wang, T. 2011. Vitamin D status is note related to development of atrial fibrillation in the community. American Heart Journal. 162(3):538-541.

Suttie, J., Booth, S.L. 2011. Vitamin K. Advances in Nutrition. 2:440-441.

Fu, X., Booth, S. 2012. Vitamin K. In: Nollet, L., Toldra, F., editors. Handbook of Analysis of Active Compounds in Functional Foods. Boca Raton, FL: CRC Press Taylor & Francis Group. p. 133-147.

Booth, S. 2012. Vitamin K: food composition and dietary intakes. Food and Nutrition Research. 56:5505.

Gundberg, C.M., Lian, J.B., Booth, S.L. 2012. Vitamin K-dependent carboxylation of osteocalcin: friend or foe?. Advances in Nutrition. 3:149-157.

Shearer, M.J., Fu, X., Booth, S.L. 2012. Vitamin K nutrition, metabolism and requirements: current concepts and future research. Advances in Nutrition. 3:182-195.

Harris, S. 2011. Does vitamin D deficiency contribute to increased rates of cardiovascular disease and type 2 diabetes among African Americans?. American Journal of Clinical Nutrition. 93(5):1175S-1178.

Niramitmahapanya, S., Harris, S., Dawson-Hughes, B. 2011. Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Journal of Clinical Endocrinology and Metabolism. DOI: 10.1210/jc.2011-1518.

Wang, T.J., Feng, Z., Richards, B., Kestenbaum, B., Van Meurs, J.B., Berry, D., Kiel, D., Streeten, E.A., Ohlsson, C., Koller, D.L., Jarvelin, M., Cooper, J.D., O'Reilly, P.F., Houston, D.K., Glazer, N.L., Vandenput, L., Peacock, M., Shi, J., Rivadeneira, F., Mccarthy, M.I., Anneli, P., De Boer, I.H., Mangino, M., Kato, B., Smyth, D.J., Booth, S.L., Jacques, P.F., Burke, G.L., Goodarzi, M., Cheung, C., Wolf, M., Rice, K., Goltzman, D., Hidiroglou, N., Ladouceur, M., Hui, S.L., Wareham, N.J., Hocking, L.J., Hart, D., Arden, N.K., Copper, C., Malik, S., Fraser, W.D., Hartikainen, A., Zhai, G., Macdonald, H., Forouhi, N.G., Loos, R.J., Reid, D.M., Hakim, A., Dennison, E., Liu, Y., Power, C., Stevens, H.E., Jaana, L., Vasan, R.S., Soranzo, N., Bojunga, J., Pstay, B.M., Lorentzon, M., Foroud, T., Harris, T.B., Hofman, A., Jansson, J., Cauley, J.A., Uitterlinden, A.G., Gibson, Q., Palotie, L., Karasik, D.S., Econs, M.J., Kritchevsky, S.B., Florez, J.C., Todd, J.A., Dupuis, J., Hypponen, E., Spector, T.D. 2010. Common genetic determinants of vitamin D insufficiency: the sunlight consortium. Lancet. 376(9736):180-188.

Ceglia, L., Morais, M.D., Park, L., Morris, E., Harris, S.S., Bischoff-Ferrari, H., Fielding, R., Dawson-Hughes, B. 2011. Hip fracture risk in older US adults by treatment eligibility status based on new National Osteoporosis Foundation Guidance. Journal of Molecular Biology. 22(2):541-549.

Last Modified: 10/30/2014
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