Abstract
Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0.72, 0.96); type 1 diabetes (HR = 0.95, 95 % CI 0.88, 1.02), multiple sclerosis (HR = 0.89, 95 % CI 0.74, 1.07), iridocyclitis (HR = 1.00, 95 % CI 0.86, 1.17); Crohn’s disease (HR = 0.95, 95 % CI 0.80, 1.13), ulcerative colitis (HR = 0.88, 95 % CI 0.75, 1.04); psoriasis vulgaris (HR = 0.99, 95 % CI 0.86, 1.13); seropositive rheumatoid arthritis (HR = 0.97, 95 % CI 0.89, 1.07), and polymyalgia rheumatica (HR = 0.94, 95 % CI 0.83, 1.06). We found statistically significant inverse associations between vitamin D status and development of any autoimmune disease and thyrotoxicosis in particular. Our findings suggest a possible protective role of a higher vitamin D status on autoimmune disease but warrant further studies to clarify causality.
Similar content being viewed by others
References
M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007)
T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and cause-specific mortality: a general population study. PLoS One 7, e52423 (2012)
T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population. Cardiology 123, 62–70 (2012)
T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, K. Rasmussen et al., Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population. Endocrine 44, 473–480 (2013)
T. Skaaby, L.L. Husemoen, T. Martinussen, J.P. Thyssen, M. Melgaard, B.H. Thuesen et al., Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach. PLoS One 8, e57647 (2013)
T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43, 618–625 (2013)
T. Skaaby, L.L. Husemoen, A. Borglykke, T. Jorgensen, B.H. Thuesen, C. Pisinger et al., Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 47, 213–220 (2013)
T. Skaaby, L.L. Husemoen, B.H. Thuesen, C. Pisinger, T. Jorgensen, N. Roswall et al., Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer. Cancer Epidemiol. Biomarkers Prev. 23, 1220–1229 (2014)
T. Skaaby, L.L. Husemoen, B.H. Thuesen, C. Pisinger, T. Jorgensen, R.V. Fenger et al., Vitamin D status and chronic obstructive pulmonary disease: a prospective general population study. PLoS One 9, e90654 (2014)
M. Hewison, An update on vitamin D and human immunity. Clin. Endocrinol. (Oxf) 76, 315–325 (2012)
A. Latina, D. Gullo, F. Trimarchi, S. Benvenga, Hashimoto’s thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer. PLoS One 8, e55450 (2013)
Y. Arnson, H. Amital, Y. Shoenfeld, Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann. Rheum. Dis. 66, 1137–1142 (2007)
P. Pludowski, M.F. Holick, S. Pilz, C.L. Wagner, B.W. Hollis, W.B. Grant 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. 12, 976–989 (2013)
P. Szodoray, B. Nakken, J. Gaal, R. Jonsson, A. Szegedi, E. Zold et al., The complex role of vitamin D in autoimmune diseases. Scand. J. Immunol. 68, 261–269 (2008)
K.L. Munger, S.M. Zhang, E. O’Reilly, M.A. Hernan, M.J. Olek, W.C. Willett et al., Vitamin D intake and incidence of multiple sclerosis. Neurology 62, 60–65 (2004)
K.L. Munger, L.I. Levin, B.W. Hollis, N.S. Howard, A. Ascherio, Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296, 2832–2838 (2006)
A. Ascherio, K.L. Munger, R. White, K. Kochert, K.C. Simon, C.H. Polman et al., Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 71, 306–314 (2014)
C. Mathieu, C. Gysemans, A. Giulietti, R. Bouillon, Vitamin D and diabetes. Diabetologia 48, 1247–1257 (2005)
G.G. Song, S.C. Bae, Y.H. Lee, Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin. Rheumatol. 31, 1733–1739 (2012)
M. Osler, A. Linneberg, C. Glumer, T. Jorgensen, The cohorts at the Research Centre for Prevention and Health, formerly ‘The Glostrup Population Studies’. Int. J. Epidemiol. 40, 602–610 (2011)
C.B. Pedersen, The Danish Civil Registration System. Scand. J. Public Health 39, 22–25 (2011)
T.F. Andersen, M. Madsen, J. Jorgensen, L. Mellemkjoer, J.H. Olsen, The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan. Med. Bull. 46, 263–268 (1999)
N.M. Nielsen, T. Westergaard, M. Frisch, K. Rostgaard, J. Wohlfahrt, N. Koch-Henriksen et al., Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch. Neurol. 63, 1001–1004 (2006)
M. Aadahl, S.L. von Huth, C. Pisinger, U.N. Toft, C. Glumer, K. Borch-Johnsen et al., Five-year change in physical activity is associated with changes in cardiovascular disease risk factors: the Inter99 study. Prev. Med. 48, 326–331 (2009)
L. Ambye, S. Rasmussen, M. Fenger, T. Jorgensen, K. Borch-Johnsen, S. Madsbad et al., Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome. Diabetes Res. Clin. Pract. 67, 175–179 (2005)
T. Jorgensen, K. Borch-Johnsen, T.F. Thomsen, H. Ibsen, C. Glumer, C. Pisinger, A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur. J. Cardiovasc. Prev. Rehabil. 10, 377–386 (2003)
J.P. Thyssen, A. Linneberg, B.C. Carlsen, J.D. Johansen, K. Engkilde, T. Hansen et al., A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study. BMJ Open 1, e000062 (2011)
G.S. Cooper, B.C. Stroehla, The epidemiology of autoimmune diseases. Autoimmun. Rev. 2, 119–125 (2003)
R.L. Rabin, A.I. Levinson, The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature. Clin. Exp. Immunol. 153, 19–30 (2008)
A. Misharin, M. Hewison, C.R. Chen, V. Lagishetty, H.A. Aliesky, Y. Mizutori et al., Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology 150, 1051–1060 (2009)
H. Yamashita, S. Noguchi, K. Takatsu, E. Koike, T. Murakami, S. Watanabe et al., High prevalence of vitamin D deficiency in Japanese female patients with Graves’ disease. Endocr. J. 48, 63–69 (2001)
T. Yasuda, Y. Okamoto, N. Hamada, K. Miyashita, M. Takahara, F. Sakamoto et al., Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine 42, 739–741 (2012)
H. Czernobilsky, S. Scharla, H. Schmidt-Gayk, R. Ziegler, Enhanced suppression of 1,25(OH)2D3 and intact parathyroid hormone in Graves’ disease as compared to toxic nodular goiter. Calcif. Tissue Int. 42, 5–12 (1988)
T. Kawakami-Tani, E. Fukawa, H. Tanaka, Y. Abe, I. Makino, Effect of 1 alpha-hydroxy vitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves’ disease. Metabolism 46, 1184–1188 (1997)
M.A. Pani, K. Regulla, M. Segni, S. Hofmann, M. Hufner, A.M. Pasquino et al., A polymorphism within the vitamin D-binding protein gene is associated with Graves’ disease but not with Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 87, 2564–2567 (2002)
C.E. Jennings, C.J. Owen, V. Wilson, S.H. Pearce, A haplotype of the CYP27B1 promoter is associated with autoimmune Addison’s disease but not with Graves’ disease in a UK population. J. Mol. Endocrinol. 34, 859–863 (2005)
E.R. Lopez, O. Zwermann, M. Segni, G. Meyer, M. Reincke, J. Seissler et al., A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and type 1 diabetes mellitus in Germans. Eur. J. Endocrinol. 151, 193–197 (2004)
G. Effraimidis, K. Badenhoop, J.G. Tijssen, W.M. Wiersinga, Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur. J. Endocrinol. 167, 43–48 (2012)
P.B. Wilson, Serum 25-hydroxy vitamin D status in individuals with psoriasis in the general population. Endocrine 44, 537–539 (2013)
J.F. Merola, J. Han, T. Li, A.A. Qureshi, No association between vitamin D intake and incident psoriasis among US women. Arch. Dermatol. Res. 306, 305–307 (2014)
P. Gisondi, M. Rossini, C.A. Di, L. Idolazzi, S. Farina, G. Beltrami et al., Vitamin D status in patients with chronic plaque psoriasis. Br. J. Dermatol. 166, 505–510 (2012)
J. Orgaz-Molina, A. Buendia-Eisman, M.A. Arrabal-Polo, J.C. Ruiz, S. Arias-Santiago, Deficiency of serum concentration of 25-hydroxy vitamin D in psoriatic patients: a case-control study. J. Am. Acad. Dermatol. 67, 931–938 (2012)
A.A. Levin, S. Aleissa, N. Dumont, F. Martinez, C. Donovan, S.C. Au et al., A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis. J. Drugs Dermatol. 13, 922–926 (2014)
I. Heier, E. Soyland, A.L. Krogstad, C. Rodriguez-Gallego, M.S. Nenseter, F.L. Jahnsen, Sun exposure rapidly reduces plasmacytoid dendritic cells and inflammatory dermal dendritic cells in psoriatic skin. Br. J. Dermatol. 165, 792–801 (2011)
A. Shah, The pathologic and clinical intersection of atopic and autoimmune disease. Curr. Allergy Asthma Rep. 12, 520–529 (2012)
Ethics standards
The studies were approved by the Ethics Committee of Copenhagen and the Danish Data Protection Agency, and the recommendations of the Declaration of Helsinki were followed. Participants gave their informed written consent.
Conflict of interest
The authors declare that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Skaaby, T., Husemoen, L.L.N., Thuesen, B.H. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine 50, 231–238 (2015). https://doi.org/10.1007/s12020-015-0547-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-015-0547-4