Abstract
Purpose
This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women.
Methods
Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D3, 5 μg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined.
Results
Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes.
Conclusions
Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 μg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.
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References
Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87:1080S–1086S
Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501
Laird E, Ward M, McSorley E, Strain JJ, Wallace J (2010) Vitamin D and bone health: potential mechanisms. Nutrients 2:693–724. doi:10.3390/nu2070693
Holick MF (2010) Vitamin D: extraskeletal health. Endocrinol Metab Clin North Am 39:381–400. doi:10.1016/j.ecl.2010.02.016
McGillivray G, Skull SA, Davie G, Kofoed SE, Frydenberg A, Rice J, Cooke R, Carapetis JR (2007) High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate. Arch Dis Child 92:1088–1093
Sim JJ, Lac PT, Liu IL, Meguerditchian SO, Kumar VA, Kujubu DA, Rasgon SA (2010) Vitamin D deficiency and anemia: a cross-sectional study. Ann Hematol 89:447–452. doi:10.1007/s00277-009-0850-3
Toxqui L, Pérez-Granados AM, Blanco-Rojo R, Wright I, González-Vizcayno C, Vaquero MP (2013) Intake of an iron or iron an vitamin D-fortified skimmed milk and iron metabolism in women. Ann Nutr Metab (in press)
Blanco-Rojo R, Perez-Granados AM, Toxqui L, Zazo P, de la Piedra C, Vaquero MP (2013) Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron-fortified food. Eur J Nutr 52:695–703. doi:10.1007/s00394-012-0375-8
Tuderman L, Myllyla R, Kivirikko KI (1977) Mechanism of the prolyl hydroxylase reaction.1. Role of co-substrates. Eur J Biochem 80:341–348
Diaz-Castro J, Lopez-Frias MR, Campos MS, Lopez-Frias M, Alferez MJ, Nestares T, Ojeda ML, Lopez-Aliaga I (2012) Severe nutritional iron-deficiency anaemia has a negative effect on some bone turnover biomarkers in rats. Eur J Nutr 51:241–247. doi:10.1007/s00394-011-0212-5
Katsumata S, Tsuboi R, Uehara M, Suzuki K (2006) Dietary iron deficiency decreases serum osteocalcin concentration and bone mineral density in rats. Biosci Biotechnol Biochem 70:2547–2550
Katsumata S, Katsumata-Tsuboi R, Uehara M, Suzuki K (2009) Severe iron deficiency decreases both bone formation and bone resorption in rats. J Nutr 139:238–243
Harris MM, Houtkooper LB, Stanford VA, Parkhill C, Weber JL, Flint-Wagner H, Weiss L, Going SB, Lohman TG (2003) Dietary iron is associated with bone mineral density in healthy postmenopausal women. J Nutr 133:3598–3602
Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281
Gonzalez-Molero I, Morcillo S, Valdes S, Perez-Valero V, Botas P, Delgado E, Hernandez D, Olveira G, Rojo G, Gutierrez-Repiso C, Rubio-Martin E, Menendez E, Soriguer F (2011) Vitamin D deficiency in Spain: a population-based cohort study. Eur J Clin Nutr 65:321–328
Vaquero MP, Sanchez-Muniz FJ, Carbajal A, Garcia-Linares MC, Garcia-Fernandez MC, Garcia-Arias MT (2004) Mineral and vitamin status in elderly persons from Northwest Spain consuming an Atlantic variant of the Mediterranean diet. Ann Nutr Metab 48:125–133
Mata-Granados JM, Luque de Castro MD, Quesada Gomez JM (2008) Inappropriate serum levels of retinol, alpha-tocopherol, 25 hydroxyvitamin D3 and 24,25 dihydroxyvitamin D3 levels in healthy Spanish adults: simultaneous assessment by HPLC. Clin Biochem 41:676–680. doi:10.1016/j.clinbiochem.2008.02.003
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B (2009) Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005. Public Health Nutr 12:444–454. doi:10.1017/S1368980008002401
Lips P (2010) Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol 121:297–300. doi:10.1016/j.jsbmb.2010.02.021
Moreiras O, Carbajal A, Cabrera L, Cuadrado C (2009) Ingestas recomendadas de energía y nutrientes para la población española. In: Tablas de composición de alimentos. Pirámide, Grupo Anaya, SA, Madrid, pp 227–230
Institute of Medicine (2001) Iron. In: Institute of Medicine and Food and Nutrition Board (ed) Dietary Reference Intakes for Vitamin A, Vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academic Press, Washington, DC, pp 290–393
Ross AC, Taylor CL, Yaktine AL, Del Valle HB (2011) Dietary Reference Intakes for Calcium Vitamin D. The National Academic Press, Washington, D.C
Ferrar L, van der Hee RM, Berry M, Watson C, Miret S, Wilkinson J, Bradburn M, Eastell R (2011) Effects of calcium-fortified ice cream on markers of bone health. Osteoporos Int 22:2721–2731. doi:10.1007/s00198-010-1513-x
D’Amelio P, Cristofaro MA, Tamone C, Morra E, Di Bella S, Isaia G, Grimaldi A, Gennero L, Gariboldi A, Ponzetto A, Pescarmona GP, Isaia GC (2008) Role of iron metabolism and oxidative damage in postmenopausal bone loss. Bone 43:1010–1015. doi:10.1016/j.bone.2008.08.107
Medeiros DM, Stoecker B, Plattner A, Jennings D, Haub M (2004) Iron deficiency negatively affects vertebrae and femurs of rats independently of energy intake and body weight. J Nutr 134:3061–3067
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58. doi:10.1210/jc.2010-2704
van Schoor NM, Lips P (2011) Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 25:671–680. doi:10.1016/j.beem.2011.06.007S1521-690X(11)00071-6
Rodriguez Sangrador M, Beltran de Miguel B, Cuadrado Vives C, Moreiras Tuny O (2010) Influence of sun exposure and diet to the nutritional status of vitamin D in adolescent Spanish women: the five countries study (OPTIFORD Project). Nutr Hosp 25:755–762
Groba MV, Miravalle A, Gonzalez-Rodriguez E, García-Santana S, Gonzalez-Padilla E, Saavedra P, Soria A, Sosa M (2010) Factors related to vitamin D deficiency in medical students in Gran Canaria. Revista de osteoporosis y metabolismo mineral 2:11–18
Federación Española de Sociedades de Nutrición Alimentación y Dietética (FESNAD) (2010) Ingestas Dietéticas de Referencia (IDR) para la población española. EUNSA, Navarra
Vinas BR, Barba LR, Ngo J, Gurinovic M, Novakovic R, Cavelaars A, de Groot LC, van’t Veer P, Matthys C, de Majem LS (2011) Projected prevalence of inadequate nutrient intakes in Europe. Ann Nutr Metab 59:84–95. doi:10.1159/000332762
Vaquero MP, Navarro MP (2013) Minerales. Libro blanco de la nutrición en España. Fundación Española de Nutrición, Madrid, pp 157–163
Kemi VE, Kärkkäinen MU, Lamberg-Allardt CJ (2006) High phosphorus intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females. Br J Nutr 96:545–552
Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM (2013) Vitamin D metabolism, functions and needs: from science to health claims. Eur J Nutr 52:429–441. doi:10.1007/s00394-012-0430-5
Blanco-Rojo R, Perez-Granados AM, Toxqui L, Gonzalez-Vizcayno C, Delgado MA, Vaquero MP (2011) Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women. Br J Nutr 105:1652–1659. doi:10.1017/S0007114510005490
Acknowledgments
This study was financed by Project AGL2009-11437. LT and RBR were supported by a JAE-predoc grant from CSIC and European Social Fund. The authors are grateful to the volunteers who participated in the study. CAPSA (Spain) is acknowledged for providing the dairy products.
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Toxqui, L., Pérez-Granados, A.M., Blanco-Rojo, R. et al. Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women. Eur J Nutr 53, 441–448 (2014). https://doi.org/10.1007/s00394-013-0544-4
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DOI: https://doi.org/10.1007/s00394-013-0544-4