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Directly measured free 25-hydroxy vitamin D levels show no evidence of vitamin D deficiency in young Swedish women with anorexia nervosa

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Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Purpose

Anorexia nervosa (AN) is an eating disorder characterized by low fat mass complicated by osteoporosis. The role of circulating vitamin D in the development of bone loss in AN is unclear. Fat mass is known to be inversely associated with vitamin D levels measured as serum levels of total, protein-bound 25-hydroxyvitamin D, but the importance of directly measured, free levels of 25(OH)D has not been determined in AN. The aim of this study was to investigate vitamin D status, as assessed by serum concentrations of total and free serum 25(OH)D in patients with AN and healthy controls.

Methods

In female AN patients (n = 20), and healthy female controls (n = 78), total 25(OH)D was measured by LC–MS/MS, and free 25(OH)D with ELISA. In patients with AN bone mineral density (BMD) was determined with DEXA.

Results

There were no differences between patients and controls in total or free S-25(OH)D levels (80 ± 31 vs 72 ± 18 nmol/L, and 6.5 ± 2.5 vs 5.6 ± 1.8 pg/ml, respectively), and no association to BMD was found. In the entire group of patients and controls, both vitamin D parameters correlated with BMI, leptin, and PTH.

Conclusions

The current study did not demonstrate a vitamin D deficiency in patients with AN and our data does not support vitamin D deficiency as a contributing factor to bone loss in AN. Instead, we observed a trend toward higher vitamin D levels in AN subjects compared to controls. Measurement of free vitamin D levels did not contribute to additional information.

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References

  1. Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A (1999) The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab 84(12):4489–4496

    CAS  PubMed  Google Scholar 

  2. Fonseca VA, D’Souza V, Houlder S, Thomas M, Wakeling A, Dandona P (1988) Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa. J Clin Pathol 41(2):195–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Olmos JM, Riancho JA, Amado JA, Freijanes J, Menéndez-Arango J, González-Macías J (1991) Vitamin D metabolism and serum binding proteins in anorexia nervosa. Bone 12(1):43–46

    Article  CAS  PubMed  Google Scholar 

  4. Aarskog D, Aksnes L, Markestad T, Trygstad O (1986) Plasma concentrations of vitamin D metabolites in pubertal girls with anorexia nervosa. Acta Endocrinol Suppl (Copenh) 279:458–467

    Article  CAS  Google Scholar 

  5. Van Binsbergen CJ, Odink J, Van den Berg H, Koppeschaar H, Coelingh Bennink HJ (1988) Nutritional status in anorexia nervosa: clinical chemistry, vitamins, iron and zinc. Eur J Clin Nutr 42(11):929–937

    PubMed  Google Scholar 

  6. Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K, Herzog D, Klibanski A (2000) Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Intern Med 133(10):790–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Haagensen AL, Feldman HA, Ringelheim J, Gordon CM (2008) Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa. Osteoporos Int 19(3):289–294. doi:10.1007/s00198-007-0476-z

    Article  CAS  PubMed  Google Scholar 

  8. Svedlund A, Pettersson C, Tubic B, Magnusson P, Swolin-Eide D (2016) Vitamin D status in young Swedish women with anorexia nervosa during intensive weight gain therapy. Eur J Nutr. doi:10.1007/s00394-016-1244-7 (Epub ahead of print)

  9. Veronese N, Solmi M, Rizza W, Manzato E, Sergi G, Santonastaso P, Caregaro L, Favaro A, Correll CU (2015) Vitamin D status in anorexia nervosa: a meta-analysis. Int J Eat Disord 48(7):803–813. doi:10.1002/eat.22370

    Article  PubMed  Google Scholar 

  10. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M (2014) Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol 144:132–137. doi:10.1016/j.jsbmb.2013.09.012

    Article  CAS  PubMed  Google Scholar 

  11. Bhan I, Powe CE, Berg AH, Ankers E, Wenger JB, Karumanchi SA, Thadhani RI (2012) Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 82(1):84–89. doi:10.1038/ki.2012.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26(7):1609–1616. doi:10.1002/jbmr.387

    Article  CAS  PubMed  Google Scholar 

  13. Mendel CM (1989) The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 10(3):232–274. doi:10.1210/edrv-10-3-232

    Article  CAS  PubMed  Google Scholar 

  14. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, Robins SJ et al (2010) Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes 59(1):242–248. doi:10.2337/db09-1011

    Article  CAS  PubMed  Google Scholar 

  15. Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J (2009) The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 29(9):3713–3720

    CAS  PubMed  Google Scholar 

  16. Shimizu H, Shimomura Y, Hayashi R, Ohtani K, Sato N, Futawatari T, Mori M (1997) Serum leptin concentration is associated with total body fat mass, but not abdominal fat distribution. Int J Obes Relat Metab Disord 21(7):536–541

    Article  CAS  PubMed  Google Scholar 

  17. Shah NR, Braverman ER (2012) Measuring adiposity in patients: the utility of body mass index (BMI), percent body fat, and leptin. PLoS One 7(4):e33308. doi:10.1371/journal.pone.0033308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen XX, Yang T (2015) Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab 33(5):474–485. doi:10.1007/s00774-014-0569-7

    Article  CAS  PubMed  Google Scholar 

  19. Carlsson M, Nilsson I, Brudin L, Von SP, Wanby P (2017) Erythrocyte fatty acid composition does not influence levels of free, bioavailable, and total 25-hydroxy vitamin D. Scand J Clin Lab Invest 77(1):45–52. doi:10.1080/00365513.2016.1258724

    Article  CAS  PubMed  Google Scholar 

  20. Hind K, Oldroyd B, Truscott JG (2010) In vivo precision of the GE Lunar iDXA densitometer for the measurement of total-body, lumbar spine, and femoral bone mineral density in adults. J Clin Densitom 13(4):413–417. doi:10.1016/j.jocd.2010.06.002

    Article  PubMed  Google Scholar 

  21. Tian XQ, Chen TC, Matsuoka LY, Wortsman J, Holick MF (1993) Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin. J Biol Chem 268(20):14888–14892

    CAS  PubMed  Google Scholar 

  22. Wacker M, Holick MF (2013) Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 5(1):111–148. doi:10.3390/nu5010111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 33(3):456–492. doi:10.1210/er.2012-1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A (2017) Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord 22(1):27–41. doi:10.1007/s40519-016-0312-6

    Article  PubMed  Google Scholar 

  25. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281. doi:10.1056/NEJMra070553

    Article  CAS  PubMed  Google Scholar 

  26. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA et al (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(1):53–58. doi:10.1210/jc.2010-2704

    Article  CAS  PubMed  Google Scholar 

  27. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH (2011) Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(12):1911–1930. doi:10.1210/jc.2011-0385

    Article  CAS  PubMed  Google Scholar 

  28. Modan-Moses D, Levy-Shraga Y, Pinhas-Hamiel O, Kochavi B, Enoch-Levy A, Vered I, Stein D (2015) High prevalence of vitamin D deficiency and insufficiency in adolescent inpatients diagnosed with eating disorders. Int J Eat Disord 48(6):607–614. doi:10.1002/eat.22347

    Article  PubMed  Google Scholar 

  29. Hotta M (2015) High prevalence of vitamin D insufficiency and deficiency among patients with anorexia nervosa in Japan. Osteoporos Int 26(3):1233. doi:10.1007/s00198-014-2957-1

    Article  CAS  PubMed  Google Scholar 

  30. Spedding S (2014) Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 6(4):1501–1518. doi:10.3390/nu6041501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Toffanello ED, Sergi G, Veronese N, Perissinotto E, Zambon S, Coin A, Sartori L et al (2014) Serum 25-hydroxyvitamin d and the onset of late-life depressive mood in older men and women: the Pro.V.A. study. J Gerontol A Biol Sci Med Sci 69(12):1554–1561. doi:10.1093/gerona/glu081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Umhau JC, George DT, Heaney RP, Lewis MD, Ursano RJ, Heilig M, Hibbeln JR et al (2013) Low vitamin D status and suicide: a case-control study of active duty military service members. PLoS One 8(1):e51543. doi:10.1371/journal.pone.0051543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hughes EK, Goldschmidt AB, Labuschagne Z, Loeb KL, Sawyer SM, Le Grange D (2013) Eating disorders with and without comorbid depression and anxiety: similarities and differences in a clinical sample of children and adolescents. Eur Eat Disord Rev 21(5):386–394. doi:10.1002/erv.2234

    Article  PubMed  Google Scholar 

  34. Aloia J, Mikhail M, Dhaliwal R, Shieh A, Usera G, Stolberg A, Ragolia L et al (2015) Free 25(OH)D and the Vitamin D Paradox in African Americans. J Clin Endocrinol Metab 100(9):3356–3363. doi:10.1210/JC.2015-2066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Szabó B, Tabák ÁG, Toldy E, Szekeres L, Szili B, Bakos B, Balla B, et al (2015) The role of serum total and free 25-hydroxyvitamin D and PTH values in defining vitamin D status at the end of winter: a representative survey. J Bone Miner Metab. doi:10.1210/JC.2015-2066 (Epub ahead of print)

  36. Altinova AE, Ozkan C, Akturk M, Gulbahar O, Yalcin M, Cakir N, Toruner FB (2016) Vitamin D-binding protein and free vitamin D concentrations in acromegaly. Endocrine 52(2):374–379. doi:10.1007/s12020-015-0789-1

    Article  CAS  PubMed  Google Scholar 

  37. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72(3):690–693

    Article  CAS  PubMed  Google Scholar 

  38. Winston AP (2012) The clinical biochemistry of anorexia nervosa. Ann Clin Biochem 49(Pt 2):132–143. doi:10.1258/acb.2011.011185

    Article  CAS  PubMed  Google Scholar 

  39. Estecha Querol S, Fernandez Alvira JM, Mesana Graffe MI, Nova Rebato E, Marcos Sanchez A, Moreno Aznar LA (2016) Nutrient intake in Spanish adolescents SCOFF high-scorers: the AVENA study. Eat Weight Disord 21(4):589–596. doi:10.1007/s40519-016-0282-8

    Article  PubMed  Google Scholar 

  40. Chandran JJ, Anderson G, Kennedy A, Kohn M, Clarke S (2015) Subacute combined degeneration of the spinal cord in an adolescent male with avoidant/restrictive food intake disorder: a clinical case report. Int J Eat Disord 48(8):1176–1179. doi:10.1002/eat.22450

    Article  PubMed  Google Scholar 

  41. Achamrah N, Coeffier M, Rimbert A, Charles J, Folope V, Petit A et al (2017) Micronutrient status in 153 patients with anorexia nervosa. Nutrients. doi:10.3390/nu9030225

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kobayashi S, Asakura K, Suga H, Sasaki S (2017) Three-generation Study of Women on D, Health Study G. Living status and frequency of eating out-of-home foods in relation to nutritional adequacy in 4017 Japanese female dietetic students aged 18–20 years: a multicenter cross-sectional study. J Epidemiol. doi:10.1016/j.je.2016.07.002

    Article  PubMed  PubMed Central  Google Scholar 

  43. Misra M, Klibanski A (2014) Anorexia nervosa and bone. J Endocrinol 221(3):R163–R176. doi:10.1530/JOE-14-0039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Misra M, Klibanski A (2014) Endocrine consequences of anorexia nervosa. Lancet Diabetes Endocrinol 2(7):581–592. doi:10.1016/S2213-8587(13)70180-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Idolazzi L, El Ghoch M, Dalle Grave R, Bazzani PV, Calugi S, Fassio S et al (2016) Bone metabolism in patients with anorexia nervosa and amenorrhoea. Eat Weight Disord. doi:10.1007/s40519-016-0337-x

    Article  PubMed  Google Scholar 

  46. Miller KK (2011) Endocrine dysregulation in anorexia nervosa update. J Clin Endocrinol Metab 96(10):2939–2949. doi:10.1210/jc.2011-1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lawson EA, Klibanski A (2008) Endocrine abnormalities in anorexia nervosa. Nat Clin Pract Endocrinol Metab 4(7):407–414. doi:10.1038/ncpendmet0872

    Article  PubMed  Google Scholar 

  48. Lawson EA, Miller KK, Bredella MA, Phan C, Misra M, Meenaghan E, Rosenblum L, Donoho D, Gupta R, Klibanski A (2010) Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa. Bone 46(2):458–463. doi:10.1016/j.bone.2009.09.005

    Article  CAS  PubMed  Google Scholar 

  49. Gatti D, El Ghoch M, Viapiana O, Ruocco A, Chignola E, Rossini M, Giollo A, Idolazzi L, Adami S, Dalle Grave R (2015) Strong relationship between vitamin D status and bone mineral density in anorexia nervosa. Bone 78:212–215. doi:10.1016/j.bone.2015.05.014

    Article  CAS  PubMed  Google Scholar 

  50. Ramnemark A, Norberg M, Pettersson-Kymmer U, Eliasson M (2015) Adequate vitamin D levels in a Swedish population living above latitude 63 & #xB0;N: the 2009 Northern Sweden MONICA study. Int J Circumpolar Health 74:27963. doi:10.3402/ijch.v74.27963

    Article  PubMed  Google Scholar 

  51. Degerud E, Hoff R, Nygård O, Strand E, Nilsen DW, Nordrehaug JE, Midttun Ø et al (2016) Cosinor modelling of seasonal variation in 25-hydroxyvitamin D concentrations in cardiovascular patients in Norway. Eur J Clin Nutr 70(4):517–522. doi:10.1038/ejcn.2015.200

    Article  CAS  PubMed  Google Scholar 

  52. Klingberg Eva, Oleröd Göran, Konar Jan, Petzold Max, Hammarsten Ola (2015) Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort. Endocrine 49(3):800–808. doi:10.1007/s12020-015-0548-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by a grant from the Medical Research Council of Southeast Sweden (FORSS).We are also indebted to nurse Susanne Petersen and biomedical scientist Siv-Pingh Von, for their excellent assistance.

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Authors and Affiliations

  1. Department of Clinical Chemistry, County Hospital of Kalmar, Kalmar, Sweden

    Martin Carlsson

  2. Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden

    Martin Carlsson

  3. Department of Clinical Physiology, County Hospital of Kalmar, Kalmar, Sweden

    Lars Brudin

  4. Department of Medicine and Health Sciences, University Hospital Linkoping, Linköping, Sweden

    Lars Brudin

  5. Section of Endocrinology, Department of Internal Medicine, County Hospital of Kalmar, SE 391 85, Kalmar, Sweden

    Pär Wanby

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  1. Martin Carlsson
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Correspondence to Pär Wanby.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Regional Ethical Committee, Linköping, Sweden.

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Informed consent was obtained from all individual participants included in the study.

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Carlsson, M., Brudin, L. & Wanby, P. Directly measured free 25-hydroxy vitamin D levels show no evidence of vitamin D deficiency in young Swedish women with anorexia nervosa. Eat Weight Disord 23, 247–254 (2018). https://doi.org/10.1007/s40519-017-0392-y

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