Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32231
Combinatory Nutrition Supplementation: A Case of Synergy for Increasing Calcium Bioavailability

Authors: Daniel C. S. Lim, Eric Y. M. Yeo, W. Y. Tan


This paper presents an overview of how calcium interacts with the various essential nutrients within an environment of cellular and hormonal interactions for the purpose of increasing bioavailability to the human body. One example of such interactions can be illustrated with calcium homeostasis. This paper gives an in-depth discussion on the possible interactive permutations with various nutrients and factors leading to the promotion of calcium bioavailability to the body. The review hopes to provide further insights into how calcium supplement formulations can be improved to better influence its bioavailability in the human body.

Keywords: Bioavailability, environment of cellular and hormonal interactions, combinative nutrition, nutrient synergy.

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 973


[1] Turnlund, J.R. 1999, ‘Nutrition in health and disease’. 9th ed. Baltimore: Williams & Wilkins Publ., pp. 241–252.
[2] Coxam, V. 2007, ‘Current data with inulin-type fructans and calcium, targeting bone health in adults’, The Journal of Nutrition, vol 137, no. 11 (Suppl), pp. 2527S-2533S.
[3] Lindsay, R., Christiansen, C., Einhorn, T.A., Hart, D.M., Ljunghall, S., Mautalen, C.A., Meunier, P.J., Morii, H., Mundy, G.R., Rapado, A. and Stevenson, J. 1997, ‘Who are candidates for prevention and treatment for osteoporosis?’, Osteoporosis International, vol 7, no. 1, pp.1-6.
[4] Yergey, A.L., Abrams, S.A., Vieira, N.E., Aldroubi, A., Marini, J. and Sidbury, J.B. 1994, ‘Determination of fractional absorption of dietary calcium in humans’, Journal of Nutrition, vol 124, no. 5, pp.674-682.
[5] Tanrattana, C., Charoenphandhu, N., Limlomwongse, L. and Krishnamra, N. 2004, ‘Prolactin directly stimulated the solvent drag-induced calcium transport in the duodenum of female rats’, Biochimica et Biophysica Acta (BBA)-Biomembranes, vol 1665, no. 1, pp.81-91.
[6] Pansu, D., Bellaton, C., Roche, C. and Bronner, F. 1983, ‘Duodenal and ileal calcium absorption in the rat and effects of vitamin D’, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol 244, no. 6, pp.G695-G700.
[7] Cummings, J.H., Macfarlane, G.T. and Englyst, H.N. 2001, ‘Prebiotic digestion and fermentation’, The American Journal of Clinical Nutrition, vol 73, no. 2, pp.415s-420s.
[8] Cashman K. 2003, ‘Prebiotics and calcium bioavailability’, Current Issues In Intestinal Microbiology, vol 4, no. 1, pp.21–32.
[9] Cashman, K.D. 2002, ‘Calcium intake, calcium bioavailability and bone health’, British journal of Nutrition, vol 87, S2, pp.S169-S177.
[10] Cashman, K.D. 2006, ‘A prebiotic substance persistently enhances intestinal calcium absorption and increases bone mineralization in young adolescents’, Nutrition Reviews, vol 64, no. 4, pp.189-196.
[11] Remesy, C., Levrat, M.A., Gamet, L. and Demigné, C. 1993, ‘Cecal fermentations in rats fed oligosaccharides (inulin) are modulated by dietary calcium level’, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol 264, no. 5, pp.G855-G862.
[12] Ohta, A., Ohtsuki, M., Baba, S., Adachi, T., Sakata, T. and Sakaguchi, E. 1995, ‘Calcium and magnesium absorption from the colon and rectum are increased in rats fed fructo-oligosaccharides’, The Journal of Nutrition, vol 125, no. 9, pp. 2417-2424.
[13] Lutz, T. and Scharrer, E. 1991, ‘Effect of short‐chain fatty acids on calcium absorption by the rat colon’, Experimental Physiology, vol 76, no. 4, pp.615-618.
[14] Zafar, T.A., Weaver, C.M., Zhao, Y., Martin, B.R. and Wastney, M.E. 2004, ‘Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats’, The Journal of Nutrition, vol 134, no. 2, pp.399-402.
[15] Scholz-Ahrens, K.E., Schaafsma, G., van den Heuvel, E.G. and Schrezenmeir, J. 2001, ‘Effects of prebiotics on mineral metabolism’, The American Journal of Clinical Nutrition, vol 73, no. 2, pp.459s-464s.
[16] Blaine, J., Chonchol, M. and Levi, M. 2014, ‘Renal control of calcium, phosphate and magnesium homeostasis’, Clinical Journal of the American Society of Nephrology, vol 10, no. 7, pp.1257-1272.
[17] Kopic, S and Geibel, JP. 2013, ‘Gastric acid, calcium absorption and their impact on bone health’, Physiological Reviews, vol 93, no. 1, pp. 189-268.
[18] Nguyen, T.M., Lieberherr, M., Fritsch, J., Guillozo, H., Alvarez, M.L., Fitouri, Z., Jehan, F. and Garabédian, M. 2004, ‘The rapid effects of 1, 25-dihydroxyvitamin D3 require the vitamin D receptor and influence 24-hydroxylase activity: studies in human skin fibroblasts bearing vitamin D receptor mutations’, Journal of Biological Chemistry, vol 279, no. 9, pp.7591-7597.
[19] Sone, T., Kerner, S. and Pike, J.W. 1991, ‘Vitamin D receptor interaction with specific DNA association as a 1, 25-dihydroxyvitamin D3-modulated heterodimer’, Journal of Biological Chemistry, vol 266, no. 34, pp.23296-23305.
[20] Sheikh, M.S., Ramirez, A., Emmett, M., Santa Ana, C., Schiller, L.R. and Fordtran, J.S. 1988, ‘Role of vitamin D-dependent and vitamin D-independent mechanisms in absorption of food calcium’, Journal of Clinical Investigation, vol 81, no. 1, p.126.
[21] Mee, A.P., Hoyland, J.A., Braidman, I.P., Freemont, A.J., Davies, M. and Mawer, E.B. 1996, ‘Demonstration of vitamin D receptor transcripts in actively resorbing osteoclasts in bone sections’, Bone, vol 18, no. 4, pp.295-299.
[22] Koshihara, Y., Hoshi, K., Ishibashi, H. and Shiraki, M. 1996, ‘Vitamin K2 promotes 1α,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts’, Calcified Tissue International, vol 59, no. 6, pp.466-473.
[23] Kumar, R., Schaefer, J., Grande, J.P. and Roche, P.C. 1994, ‘Immunolocalization of calcitriol receptor, 24-hydroxylase cytochrome P-450, and calbindin D28k in human kidney’, American Journal of Physiology-Renal Physiology, vol 266, no. 3, pp.F477-F485.
[24] Hoenderop, J.G., van der Kemp, A.W., Hartog, A., van de Graaf, S.F., van Os, C.H., Willems, P.H. and Bindels, R.J. 1999, ‘Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia’, Journal of Biological Chemistry, vol 274, no. 13, pp.8375-8378.
[25] Mundy, G.R. and Guise, T.A. 1999, ‘Hormonal control of calcium homeostasis’, Clinical Chemistry, vol 45, no. 8, pp.1347-1352.
[26] Kraenzlin, M.E. and Meier, C. 2011, ‘Parathyroid hormone analogues in the treatment of osteoporosis’, Nature Reviews Endocrinology, vol 7, no. 11, pp.647-656.
[27] Fraser, D.R. and Kodicek, E. 1973, ‘Regulation of 25-hydroxycholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone’, Nature, vol 241, no. 110, pp.163-166.
[28] Van Abel, M., Hoenderop, J.G., van der Kemp, A.W., Friedlaender, M.M., van Leeuwen, J.P. and Bindels, R.J. 2005, ‘Coordinated control of renal Ca2+ transport proteins by parathyroid hormone’, Kidney International, vol 68, no. 4, pp.1708-1721.
[29] Huang, J.C., Sakata, T., Pfleger, L.L., Bencsik, M., Halloran, B.P., Bikle, D.D. and Nissenson, R.A. 2004, ‘PTH differentially regulates expression of RANKL and OPG’, Journal of Bone and Mineral Research, vol 19, no. 2, pp.235-244.
[30] Locklin, R.M., Khosla, S., Turner, R.T. and Riggs, B.L. 2003, ‘Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone’, Journal of Cellular Biochemistry, vol 89, no. 1, pp.180-190.
[31] Brown, E.M. and MacLeod, R.J. 2001, ‘Extracellular calcium sensing and extracellular calcium signaling’, Physiological Reviews, vol 81, no. 1, pp.239-297.
[32] Rodríguez-Ortiz, M.E., Canalejo, A., Herencia, C., Martínez-Moreno, J.M., Peralta-Ramírez, A., Perez-Martinez, P., Navarro-González, J.F., Rodríguez, M., Peter, M., Gundlach, K. and Steppan, S. 2013, ‘Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration’, Nephrology Dialysis Transplantation, vol 29, no. 2, pp.282-289.
[33] Quinn, J.M.W., Morfis, M., Lam, M.H.C., Elliott, J., Kartsogiannis, V., Williams, E.D., Gillespie, M.T., Martin, T.J. and Sexton, P.M. 1999, ‘Calcitonin receptor antibodies in the identification of osteoclasts’, Bone, vol 25, no. 1, pp.1-8.
[34] Suzuki, H., Nakamura, I., Takahashi, N., Ikuhara, T., Matsuzaki, K., Isogai, Y., Hori, M. and Suda, T. 1996, ‘Calcitonin-induced changes in the cytoskeleton are mediated by a signal pathway associated with protein kinase A in osteoclasts’, Endocrinology, vol 137, no. 11, pp.4685-4690.
[35] Chambers, T.J. and Magnus, C.J. 1982, ‘Calcitonin alters behaviour of isolated osteoclasts’, The Journal of Pathology, vol 136, no. 1, pp.27-39.
[36] Zhong, Y., Armbrecht, H.J. and Christakos, S. 2009, ‘Calcitonin, a regulator of the 25-hydroxyvitamin D3 1α-hydroxylase gene’, Journal of Biological Chemistry, vol 284, no. 17, pp.11059-11069.
[37] Chen, R.A. and Goodman, W.G. 2004, ‘Role of the calcium-sensing receptor in parathyroid gland physiology’, American Journal of Physiology-Renal Physiology, vol 286, no. 6, pp.F1005-F1011.
[38] Nemeth, E.F., Steffey, M.E., Hammerland, L.G., Hung, B.C., Van Wagenen, B.C., DelMar, E.G. and Balandrin, M.F. 1998, ‘Calcimimetics with potent and selective activity on the parathyroid calcium receptor’, Proceedings of the National Academy of Sciences, vol 95, no. 7, pp.4040-4045.
[39] Tfelt-Hansen, J. and Brown, E.M. 2005, ‘The calcium-sensing receptor in normal physiology and pathophysiology: a review’, Critical Reviews in Clinical Laboratory Sciences, vol 42, no. 1, pp.35-70.
[40] Bourdeau, A., Souberbielle, J.C., Bonnet, P., Herviaux, P., Sachs, C. and Lieberherr, M. 1992, ‘Phospholipase-A2 action and arachidonic acid metabolism in calcium-mediated parathyroid hormone secretion’, Endocrinology, vol 130, no. 3, pp.1339-1344.
[41] Garfia, B., Cañadillas, S., Canalejo, A., Luque, F., Siendones, E., Quesada, M., Almadén, Y., Aguilera-Tejero, E. and Rodríguez, M. 2002, ‘Regulation of parathyroid vitamin D receptor expression by extracellular calcium’, Journal of the American Society of Nephrology, vol 13, no. 12, pp.2945-2952.
[42] Zofková, I. and Kancheva, R.L. 1995, ‘The relationship between magnesium and calciotropic hormones’, Magnesium Research, vol 8, no. 1, pp.77-84.
[43] Raggi, P., Callister, T.Q. and Shaw, L.J. 2004, ‘Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy’, Arteriosclerosis, Thrombosis, and Vascular Biology, vol 24, no. 7, pp.1272-1277.
[44] 2010, ‘Cellular technology to establish nutritional requirements for trace minerals and other nutrients, Acu-Cell, USA, .
[45] Heaney, R.P. 2004, ‘Phosphorus nutrition and the treatment of osteoporosis’, Mayo Clinic Proceedings, vol 79, no. 1, pp. 91-97.
[46] Riccardi, D. and Martin, D. 2008, ‘The role of the calcium-sensing receptor in the pathophysiology of secondary hyperparathyroidism’, Nephrology Dialysis Transplantation, vol 1, no.1 (Suppl), pp. i7-i11.