Download PDF
Semin Thromb Hemost 2023; 49(05): 453-470
DOI: 10.1055/s-0042-1756701
Review Article

Is Vitamin D Deficiency Prothrombotic? A Systematic Review

Isabella Hangaard Rüdiger‡   *
1   Department of Obstetrics and Gynecology, Regional Hospital of Randers, Randers, Denmark
,
Matilde Kanstrup Andersen‡   *
1   Department of Obstetrics and Gynecology, Regional Hospital of Randers, Randers, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Anna Louise Vestergaard
1   Department of Obstetrics and Gynecology, Regional Hospital of Randers, Randers, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Pinar Bor
3   Department of Biomedicine, Aarhus University, Aarhus, Denmark
,
Agnete Larsen
4   Department of Regional Health Research, Thrombosis Research, University of Southern Denmark, Odense, Denmark
5   Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
,
Mustafa Vakur Bor
4   Department of Regional Health Research, Thrombosis Research, University of Southern Denmark, Odense, Denmark
5   Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms behind this association are uncertain. This systematic review explores if there is an association between decreased vitamin D levels and a prothrombotic profile. The systematic literature search initially identified 3,214 studies (published until December 21, 2021) investigating the relationship between vitamin D and numerous hemostatic parameters. After the screening process, 18 observational and intervention studies fulfilled the inclusion criteria and were included in this systematic review. Parameters of primary hemostasis, secondary hemostasis, and fibrinolysis were investigated in six, thirteen, and fifteen of these studies, respectively. Most of the eligible studies did not identify significant associations between decreased vitamin D levels and hemostatic parameters. Some conflicting results were found between decreased vitamin D levels and thrombin generation parameters and the tissue factor pathway inhibitor. Conflicting results were also found between decreased vitamin D levels and fibrinolytic parameters, although the evidence may point toward weak associations with some regulators of fibrinolysis, mostly decreased tissue type plasminogen activator. Overall, our systematic review did not identify any definitive link between vitamin D deficiency and a prothrombotic profile, which might otherwise help explain the observed association between vitamin D deficiency and increased risk of thrombotic events. Moreover, there is no clinical evidence to confirm or refute a possible antithrombotic effect of vitamin D. Larger high-quality randomized controlled trials are needed to better elucidate the link between vitamin D deficiency and a prothrombotic risk profile.

Keywords

vitamin D deficiency - hemostasis - prothrombotic profile

* These authors contributed equally to this work.


Supplementary Material



Publication History

Article published online:
29 September 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 2017; 18 (02) 153-165
    CrossrefPubMedGoogle Scholar
  • 2 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357 (03) 266-281
    CrossrefPubMedGoogle Scholar
  • 3 Pludowski P, Holick MF, Pilz S. et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev 2013; 12 (10) 976-989
    CrossrefPubMedGoogle Scholar
  • 4 Wan J, Yuan J, Li X. et al. Association between serum vitamin D levels and venous thromboembolism (VTE): a systematic review and meta-analysis of observational studies. Rev Complement Therap Med 2020; 54: 102579
    CrossrefPubMedGoogle Scholar
  • 5 Epstein D, Kvanta A, Lindqvist PG. Seasonality and incidence of central retinal vein occlusion in Sweden: a 6-year study. Ophthalmic Epidemiol 2015; 22 (02) 94-97
    CrossrefPubMedGoogle Scholar
  • 6 Lindqvist PG, Epstein E, Olsson H. Does an active sun exposure habit lower the risk of venous thrombotic events? A D-lightful hypothesis. J Thromb Haemost 2009; 7 (04) 605-610
    CrossrefPubMedGoogle Scholar
  • 7 Dehghani K, Nowrouzi A, Pourdavood AH, Rahmanian Z. Effect of vitamin D deficiency in lower extremity and pulmonary venous thromboembolism. Biomed Res Ther 2019; 6 (04) 3107-3112
    CrossrefPubMedGoogle Scholar
  • 8 Korkmaz UTK, Ersoy S, Yuksel A. et al. Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study. Sao Paulo Med J 2021; 139 (03) 279-284
    CrossrefPubMedGoogle Scholar
  • 9 Huang J, Wang Z, Hu Z, Jiang W, Li B. Association between blood vitamin D and myocardial infarction: a meta-analysis including observational studies. Clin Chim Acta 2017; 471: 270-275
    CrossrefPubMedGoogle Scholar
  • 10 Shi H, Chen H, Zhang Y. et al. 25-Hydroxyvitamin D level, vitamin D intake, and risk of stroke: a dose-response meta-analysis. Clin Nutr 2020; 39 (07) 2025-2034
    CrossrefPubMedGoogle Scholar
  • 11 Su C, Jin B, Xia H, Zhao K. Association between vitamin D and risk of stroke: a PRISMA-compliant systematic review and meta-analysis. Eur Neurol 2021; 84 (06) 399-408
    CrossrefPubMedGoogle Scholar
  • 12 Targher G, Pichiri I, Lippi G. Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost 2012; 38 (01) 114-124
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988; 67 (02) 373-378
    CrossrefPubMedGoogle Scholar
  • 14 O'Neill CM, Kazantzidis A, Ryan MJ. et al. Seasonal changes in vitamin D-effective UVB availability in Europe and associations with population serum 25-hydroxyvitamin D. Nutrients 2016; 8 (09) E533
    CrossrefPubMedGoogle Scholar
  • 15 Holick MF, Matsuoka LY, Wortsman J. Age, vitamin D, and solar ultraviolet. Lancet 1989; 2 (8671): 1104-1105
    CrossrefPubMedGoogle Scholar
  • 16 Cutillas-Marco E, Fuertes-Prosper A, Grant WB, Morales-Suárez-Varela M. Vitamin D deficiency in South Europe: effect of smoking and aging. Photodermatol Photoimmunol Photomed 2012; 28 (03) 159-161
    CrossrefPubMedGoogle Scholar
  • 17 Kassi EN, Stavropoulos S, Kokkoris P. et al. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones (Athens) 2015; 14 (02) 245-250
    PubMedGoogle Scholar
  • 18 Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev 2015; 16 (04) 341-349
    CrossrefPubMedGoogle Scholar
  • 19 Holick MF, Binkley NC, Bischoff-Ferrari HA. et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (07) 1911-1930
    CrossrefPubMedGoogle Scholar
  • 20 Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab 2011; 25 (04) 585-591
    CrossrefPubMedGoogle Scholar
  • 21 Wang L, Song Y, Manson JE. et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes 2012; 5 (06) 819-829
    CrossrefPubMedGoogle Scholar
  • 22 Zakhary CM, Rushdi H, Hamdan JA. et al. Protective role of vitamin D therapy in diabetes mellitus type II. Cureus 2021; 13 (08) e17317
    PubMedGoogle Scholar
  • 23 Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens 2009; 27 (10) 1948-1954
    CrossrefPubMedGoogle Scholar
  • 24 Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients 2020; 12 (07) E2097
    CrossrefPubMedGoogle Scholar
  • 25 Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007; 179 (03) 1634-1647
    CrossrefPubMedGoogle Scholar
  • 26 Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia 1999; 42 (01) 51-54
    CrossrefPubMedGoogle Scholar
  • 27 Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358 (9292): 1500-1503
    CrossrefPubMedGoogle Scholar
  • 28 Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296 (23) 2832-2838
    CrossrefPubMedGoogle Scholar
  • 29 Lee YH, Bae SC. Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol 2016; 34 (05) 827-833
    PubMedGoogle Scholar
  • 30 Kamen D, Aranow C. Vitamin D in systemic lupus erythematosus. Curr Opin Rheumatol 2008; 20 (05) 532-537
    CrossrefPubMedGoogle Scholar
  • 31 Aibana O, Huang CC, Aboud S. et al. Vitamin D status and risk of incident tuberculosis disease: a nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med 2019; 16 (09) e1002907
    CrossrefPubMedGoogle Scholar
  • 32 Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, Landry ML. Serum 25-hydroxyvitamin D and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One 2010; 5 (06) e11088
    CrossrefPubMedGoogle Scholar
  • 33 Martineau AR, Jolliffe DA, Hooper RL. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583
    CrossrefPubMedGoogle Scholar
  • 34 Mercola J, Grant WB, Wagner CL. Evidence regarding vitamin D and risk of COVID-19 and its severity. Nutrients 2020; 12 (11) E3361
    CrossrefPubMedGoogle Scholar
  • 35 Brøndum-Jacobsen P, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. 25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18,791 participants. J Thromb Haemost 2013; 11 (03) 423-431
    CrossrefPubMedGoogle Scholar
  • 36 Wajda J, Świat M, Owczarek AJ, Brzozowska A, Olszanecka-Glinianowicz M, Chudek J. Severity of vitamin D deficiency predicts mortality in ischemic stroke patients. Dis Markers 2019; 2019: 3652894
    CrossrefPubMedGoogle Scholar
  • 37 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93 (01) 327-358
    CrossrefPubMedGoogle Scholar
  • 38 Wells GA, Shea B, O'Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. The Ottawa Hospital Research Institute. Accessed June 10, 2022 at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
    PubMedGoogle Scholar
  • 39 Julian PT, Higgins JS, Page MJ, Sterne JAC. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). J Clin Epidemiol 2019; 126: 37-44
    PubMedGoogle Scholar
  • 40 NIH. Study Quality Assessment Tools. Updated July 2021. Accessed June 10, 2022 at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
    PubMedGoogle Scholar
  • 41 Aleva FE, Tunjungputri RN, van der Vorm LN. et al. Platelet integrin αIIbβ3 activation is associated with 25-hydroxyvitamin D concentrations in healthy adults. Thromb Haemost 2020; 120 (05) 768-775
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Blondon M, Cushman M, Jenny N. et al. Associations of serum 25-hydroxyvitamin D with hemostatic and inflammatory biomarkers in the Multi-Ethnic Study of Atherosclerosis. J Clin Endocrinol Metab 2016; 101 (06) 2348-2357
    CrossrefPubMedGoogle Scholar
  • 43 Witham MD, Dove FJ, Khan F, Lang CC, Belch JJ, Struthers AD. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction–a randomised controlled trial. Int J Cardiol 2013; 167 (03) 745-749
    CrossrefPubMedGoogle Scholar
  • 44 Elbers LPB, Wijnberge M, Meijers JCM. et al. Coagulation and fibrinolysis in hyperparathyroidism secondary to vitamin D deficiency. Endocr Connect 2018; 7 (02) 325-333
    CrossrefPubMedGoogle Scholar
  • 45 Moin ASM, Sathyapalan T, Butler AE, Atkin SL. Vitamin D association with coagulation factors in polycystic ovary syndrome is dependent upon body mass index. J Transl Med 2021; 19 (01) 239
    CrossrefPubMedGoogle Scholar
  • 46 Hyppönen E, Berry D, Cortina-Borja M, Power C. 25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: a cross sectional analysis in the 1958 British Birth Cohort. PLoS One 2010; 5 (05) e10801
    CrossrefPubMedGoogle Scholar
  • 47 Jorde R, Haug E, Figenschau Y, Hansen JB. Serum levels of vitamin D and haemostatic factors in healthy subjects: the Tromsø study. Acta Haematol 2007; 117 (02) 91-97
    CrossrefPubMedGoogle Scholar
  • 48 Da Porto A, Cavarape A, Catena C, Colussi G, Casarsa V, Sechi LA. Interactions between vitamin D levels, cardiovascular risk factors, and atherothrombosis markers in patients with symptomatic peripheral artery disease. Vasc Med 2021; 26 (03) 315-316
    CrossrefPubMedGoogle Scholar
  • 49 Topaloglu O, Arslan MS, Karakose M. et al. Is there any association between thrombosis and tissue factor pathway inhibitor levels in patients with vitamin D deficiency?. Clin Appl Thromb Hemost 2015; 21 (05) 428-433
    CrossrefPubMedGoogle Scholar
  • 50 Clark P, Cockburn F, Cowan RA. et al. Artificial ultraviolet whole-body radiation does not modify serum lipoprotein, plasma fibrinogen, plasminogen or antithrombin III concentrations in post-myocardial infarction patients. Atherosclerosis 1994; 107 (01) 65-69
    CrossrefPubMedGoogle Scholar
  • 51 Saliba W, Awad K, Ron G, Elias M. The effect of vitamin D supplementation on thrombin generation assessed by the calibrated automated thrombogram. Clin Appl Thromb Hemost 2016; 22 (04) 340-345
    CrossrefPubMedGoogle Scholar
  • 52 Jorde R, Sneve M, Torjesen P, Figenschau Y, Hansen JB. Parameters of the thrombogram are associated with serum 25-hydroxyvitamin D levels at baseline, but not affected during supplementation with vitamin D. Thromb Res 2010; 125 (05) e210-e213
    CrossrefPubMedGoogle Scholar
  • 53 Stricker H, Tosi Bianda F, Guidicelli-Nicolosi S, Limoni C, Colucci G. Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Eur J Vasc Endovasc Surg 2012; 44 (03) 307-312
    CrossrefPubMedGoogle Scholar
  • 54 Kebapcilar AG, Kulaksizoglu M, Ipekci SH. et al. Relationship between mean platelet volume and low-grade systemic coagulation with vitamin D deficiency in primary ovarian insufficiency. Arch Gynecol Obstet 2013; 288 (01) 207-212
    CrossrefPubMedGoogle Scholar
  • 55 Blondon M, Biver E, Braillard O, Righini M, Fontana P, Casini A. Thrombin generation and fibrin clot structure after vitamin D supplementation. Endocr Connect 2019; 8 (11) 1447-1454
    CrossrefPubMedGoogle Scholar
  • 56 Amarasekera AT, Assadi-Khansari B, Liu S. et al. Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults. PLoS One 2017; 12 (05) e0174435
    CrossrefPubMedGoogle Scholar
  • 57 Sinha-Hikim I, Duran P, Shen R, Lee M, Friedman TC, Davidson MB. Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D. Horm Metab Res 2015; 47 (04) 280-283
    PubMedGoogle Scholar
  • 58 Witham MD, Adams F, Kabir G, Kennedy G, Belch JJ, Khan F. Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK–a randomised controlled trial. Atherosclerosis 2013; 230 (02) 293-299
    CrossrefPubMedGoogle Scholar
  • 59 Horvath B, Hegedus D, Szapary L. et al. Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases. Exp Clin Cardiol 2004; 9 (01) 31-34
    PubMedGoogle Scholar
  • 60 Aihara K, Azuma H, Akaike M. et al. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 2004; 279 (34) 35798-35802
    CrossrefPubMedGoogle Scholar
  • 61 Sultan M, Twito O, Tohami T, Ramati E, Neumark E, Rashid G. Vitamin D diminishes the high platelet aggregation of type 2 diabetes mellitus patients. Platelets 2019; 30 (01) 120-125
    CrossrefPubMedGoogle Scholar
  • 62 Kant R, Perry CG, Lewis JP. et al. Vitamin D inhibits human platelet aggregation: implications for hypercoagulable state in diabetes. . [Conference Abstract] Diabetes 2014; 63: A569
    PubMedGoogle Scholar
  • 63 Koyama T, Shibakura M, Ohsawa M, Kamiyama R, Hirosawa S. Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous leukemia cells and monocytes. Blood 1998; 92 (01) 160-167
    CrossrefPubMedGoogle Scholar
  • 64 Ohsawa M, Koyama T, Yamamoto K, Hirosawa S, Kamei S, Kamiyama R. 1Alpha,25-dihydroxyvitamin D(3) and its potent synthetic analogs downregulate tissue factor and upregulate thrombomodulin expression in monocytic cells, counteracting the effects of tumor necrosis factor and oxidized LDL. Circulation 2000; 102 (23) 2867-2872
    CrossrefPubMedGoogle Scholar
  • 65 Lipets EN, Ataullakhanov FI. Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk. Thromb J 2015; 13 (01) 4
    CrossrefPubMedGoogle Scholar
  • 66 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 67 Fukumoto S, Allan EH, Martin TJ. Regulation of plasminogen activator inhibitor-1 (PAI-1) expression by 1,25-dihydroxyvitamin D-3 in normal and malignant rat osteoblasts. Biochim Biophys Acta 1994; 1201 (02) 223-228
    CrossrefPubMedGoogle Scholar
  • 68 Barbosa EM, Nonogaki S, Katayama ML, Folgueira MA, Alves VF, Brentani MM. Vitamin D3 modulation of plasminogen activator inhibitor type-1 in human breast carcinomas under organ culture. Virchows Arch 2004; 444 (02) 175-182
    CrossrefPubMedGoogle Scholar
  • 69 Wu-Wong JR, Nakane M, Ma J. Vitamin D analogs modulate the expression of plasminogen activator inhibitor-1, thrombospondin-1 and thrombomodulin in human aortic smooth muscle cells. J Vasc Res 2007; 44 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 70 Sakkinen PA, Wahl P, Cushman M, Lewis MR, Tracy RP. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000; 152 (10) 897-907
    CrossrefPubMedGoogle Scholar
  • 71 Folsom AR. Fibrinolytic factors and atherothrombotic events: epidemiological evidence. Ann Med 2000; 32 (Suppl 1): 85-91
    PubMedGoogle Scholar
  • 72 Manson JE, Cook NR, Lee IM. et al; VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2019; 380 (01) 33-44
    CrossrefPubMedGoogle Scholar
  • 73 Scragg R, Stewart AW, Waayer D. et al. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol 2017; 2 (06) 608-616
    CrossrefPubMedGoogle Scholar
  • 74 Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother 2012; 3 (02) 118-126
    PubMedGoogle Scholar
  • 75 Mogire RM, Mutua A, Kimita W. et al. Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis. Lancet Glob Health 2020; 8 (01) e134-e142
    CrossrefPubMedGoogle Scholar
  • 76 Saliba W, Rennert HS, Kershenbaum A, Rennert G. Serum 25(OH)D concentrations in sunny Israel. Osteoporos Int 2012; 23 (02) 687-694
    CrossrefPubMedGoogle Scholar
  • 77 Schleicher RL, Sternberg MR, Looker AC. et al. National estimates of serum total 25-hydroxyvitamin D and metabolite concentrations measured by liquid chromatography-tandem mass spectrometry in the US population during 2007-2010. J Nutr 2016; 146 (05) 1051-1061
    CrossrefPubMedGoogle Scholar
  • 78 Jiang Z, Pu R, Li N. et al. High prevalence of vitamin D deficiency in Asia: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 2021; 1-10 DOI: 10.1080/10408398.2021.1990850.
    CrossrefPubMedGoogle Scholar
  • 79 Sarafin K, Durazo-Arvizu R, Tian L. et al. Standardizing 25-hydroxyvitamin D values from the Canadian Health Measures Survey. Am J Clin Nutr 2015; 102 (05) 1044-1050
    CrossrefPubMedGoogle Scholar
  • 80 Eloi M, Horvath DV, Szejnfeld VL. et al. Vitamin D deficiency and seasonal variation over the years in São Paulo, Brazil. Osteoporos Int 2016; 27 (12) 3449-3456
    CrossrefPubMedGoogle Scholar
  • 81 Cashman KD, Dowling KG, Škrabáková Z. et al. Vitamin D deficiency in Europe: pandemic?. Am J Clin Nutr 2016; 103 (04) 1033-1044
    CrossrefPubMedGoogle Scholar
  • 82 Daly RM, Gagnon C, Lu ZX. et al. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin Endocrinol (Oxf) 2012; 77 (01) 26-35
    CrossrefPubMedGoogle Scholar