Table 1.
Epidemiologic Studies of Vitamin D Levels in Existing Autoimmune Diseases
| Autoimmune Disease | Geographic | Study Design | Subjects | Controls | Hormones studied | Association | Results | Year | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Rheumatoid Arthritis | Turkey | Case-control | 65 RA | 40 Healthy controls | 25(OH) D | No | P = 0.94 No difference in RA subjects vs. healthy controls, but significant decrease in subgroup with highest disease activity | 2010 | Turnahoglu et al, (116) |
| Rheumatoid Arthritis | North America | Case-only | 266 early RA | - | 25(OH) D | No | No multivariate associations of 25(OH) D with any disease measures with the exception of borderline association with rheumatoid factor positivity at enrollment (p = 0.05) No significant associations with disease activity after multivariate analysis | 2010 | Craig et al, (117) |
| Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis | Israel | Case-control | 85 RA, 22 psoriatic arthritis, 14 AS | - | 25(OH) D and PTH | No | Association between vitamin D level and ethnic origin but not disease activity (among other factors) | 2009 | Braun-Moscovici et al, (210) |
| Rheumatoid Arthritis | North America | Case-control (Nested in high risk cohort) | 76 RA autoantibody positive, asymptomatic “at-risk” subjects | 154 RA autoantibody negative “at risk” controls | 25(OH) D | No | No association of autoantibody status and vitamin D level in individuals at high risk RA. | 2009 | Feser et al, (122) |
| Rheumatoid Arthritis | Italy, Estonia | Case-control | 64 female Estonian RA, 53 female Italian RA | 30 Estonian, 35 Italian age- and sex-matched | 25(OH) D | Yes | Inverse correlation between levels and DAS28 scores among Italian patients in summer (r = -0.57, P< 0.0001) and Estonian patients in winter (r = -0.40, p< 0.05) | 2007 | Cutolo et al, (211) |
| Inflammatory Polyarthritis | Great Britain | Case-only | 183 consecutive inflammatory polyarthritis < 6 months | - | 25(OH)D, 1,25(OH)2 D | Yes | Signficant inverse relationship between 25(OH)D level at baseline and tender joint count, DAS28*, CRP, and HAQ* and between baseline 1,25(OH)(2)D and HAQ*. | 2007 | Patel et al, (121) |
| Rheumatoid Arthritis | Germany | Case-only | 96 RA | - | 25(OH) D and PTH | Yes | P <0.001 (with glucocorticoids), P < 0.01 (without glucocorticoids) Inverse correlation between vitamin D level and disease activity | 1998 | Oelzner et al, (212) |
| Rheumatoid Arthritis | Denmark | Case-control | 29 RA, 21 SLE, 12 OA | 72 Healthy controls | 1,25(OH)2 D and 25(OH) D | No | No difference in vitamin D levels compared to controls | 1995 | Muller et al, (118) |
| Rheumatoid Arthritis | Finland | Case-only | 143 female RA patients | - | 1,25(OH)2 D 25(OH)D | Yes | 63% patients had levels below normal limit during summer | 1993 | Kroger et al, (213) |
| Rheumatoid Arthritis | Denmark | Case-control | 102 RA | 38 Healthy subjects | 25(OH) D; 24,25(OH) D; 25,26-OH D; 1,25(OH)2 D | Yes | P <0.01-0.001 (for 25(OH) D) 25(OH) D levels lower than in controls and significant inverse relation between level and functional class | 1987 | Als et al, (115) |
| Rheumatoid Arthritis | Great Britain | Case-control | 30 RA | 30 OA | 1,25(OH)2 D | No | No difference between RA and OA and 1,25(OH)2 D levels did not correlate either with articular index or with sedimentation rate | 1982 | Bird et al, (119) |
| Rheumatoid Arthritis | Great Britain | Case-control | 30 RA | 30 OA | 25(OH) D | No | No significant correlations between 25(OH) D and duration of arthritis or articular index | 1980 | Bird et al, (120) |
| Ankylosing Spondylitis and Psoriatic Arthritis | Germany | Case-only | 76 AS, 120 PsoA | - | 25(OH) D; 1,25(OH)2 D | Yes | P < 0.0005 for negative correlation between CRP and 25-OH D when combining AS and PsoA; P < 0.0005 for 25-OH level in PsoA versus AS | 2009 | Teichmann et al, (141) |
| Ankylosing Spondylitis | Turkey | Case-control | 100 AS | 58 Healthy controls | 25(OH) D and PTH | No | P < 0.05 for 25(OH) D lower in cases than controls | 2010 | Mermerci Baskan et al, (137) |
| Ankylosing Spondylitis | Germany | Case-control | 58 AS | 58 matched healthy controls | 25(OH) D; 1,25(OH)2 D; PTH | Yes | P < 0.05 for negative correlation between 1,25(OH)2 D and disease activity and TNF-alpha | 2005 | Lange et al, (140) |
| Ankylosing Spondylitis | Germany | Case-control | 70 AS | 45 matched healthy controls | 25(OH) D; 1,25(OH)2 D; PTH | Yes | P < 0.01 for negative correlation between 1,25(OH)2 D and disease activity | 2001 | Lange et al, (139) |
| Ankylosing Spondylitis | Austria | Case-only | 73 AS | - | 25(OH) D and PTH | - | 18% with 25(OH) D < 8 ng/ml, 73% with 25(OH) D less than 20 ng/ml | 2001 | Falkenbach et al, (214) |
| Ankylosing Spondylitis | Germany | Case-only | 14 AS at entry and 15 months later | - | 25(OH) D; 1,25(OH)2 D and PTH | No | Vitamin D levels did not differ significantly between baseline and follow-up in AS patients | 1997 | Lee et al, (215) |
| Ankylosing Spondylitis | Germany | Case-control | 38 AS | 52 controls | 1,25(OH)2 D and PTH | No | No significant difference | 1993 | Franck et al, (138) |
| Systemic Lupus Erythematosus | Poland | Case-control | 45 SLE | 49 controls | 25(OH) D | Yes | Lower 25(OH)D in cases than controls p = 0.0005, and antibodies to 1,25 (OH) D detected in 4 pts (8.9%, NS). | 2010 | Bogaczewicz et al, (127) |
| Systemic Lupus Erythematosus | Europe and Israel | Case-only | 378 SLE | - | 25(OH) D | Yes | R= -0.12, P = 0.018 for vitamin D levels and disease activity scores Negative correlation between 25(OH) D levels and disease activity in SLE patients | 2010 | Amital et al, (129) |
| Systemic Lupus Erythematosus | South Korea | Case-control | 104 SLE | 49 controls | 25(OH) D | Yes | P = 0.03 for vitamin D insufficiency in SLE compared to controls, but did not correlate with SLE disease activity. | 2010 | Kim et al, (123) |
| Systemic Lupus Erythematosus | North America | Case-only | 198 SLE | - | 25(OH) D | Yes | R = -0.234, P = 0.002 for inverse correlation of vitamin D with disease activity | 2010 | Ben-Zvi et al, (128) |
| Systemic Lupus Erythematosus | Canada | Case - only | 124 female SLE | - | 25(OH) D and 1,25(OH)2 D | No | No significant association between low vitamin D levels and disease activity; 25(OH) D levels associated with season, glucocorticoid exposure, and serum creatinine | 2010 | Toloza et al, (132) |
| Systemic Lupus Erythematosus | Saudi Arabia | Case-control | 165 SLE | 214 volunteers | 25(OH) D | Yes | P < 0.0001 for vitamin D deficiency in SLE versus controls | 2009 | Damanhouri, (124) |
| Systemic Lupus Erythematosus | North America | Case-only | 181 SLE | - | 25(OH) D | Yes | P = 0.018 for negative correlation between low 25(OH) D and SLE disease activity index (adjusted for age, season and white race) | 2009 | Wu et al, (130) |
| Systemic Lupus Erythematosus | North America | Case-only | 38 pediatric SLE | 207 healthy controls | 25(OH) D; 1,25(OH)2 D; iPTH | Yes | P = 0.01 for low 25(OH) D low level and disease activity index scores | 2009 | Wright et al, (125) |
| Systemic Lupus Erythematosus | Brazil | Case-control | 36 SLE | 26 controls | 25(OH) D; 1,25(OH)2 D; PTH | Yes | R = -0.65; P < 0.001 for 25(OH) D level and negative correlation with disease activity index | 2009 | Borba et al, (126) |
| Systemic Lupus Erythematosus | Spain | Case-only | 92 SLE | - | 25(OH) D | No | P = 0.08 for fatigue and vitamin D deficiency; no significant association with disease activity | 2008 | Ruiz-Irastorza et al, (133) |
| Systemic Lupus Erythematosus | U.S. | Case-only | 37 SLE | - | 25(OH)D | Yes | 65% < 80 nmol/L and 20% <47.7 nmol/L. Above normal level correlated with low disease activity, but also with significantly higher dsDNA antibodies. | 2008 | Thudi et al, (131) |
| Systemic Lupus Erythematosus | Canada | Case-only | 25 SLE | - | 25(OH) D; 1,25(OH)2 D; PTH | No | 1,25-OH lower in SLE patients using hydroxychloroquine compared to nonusers | 2001 | Huisman et al, (135) |
| Systemic Lupus Erythematosus | Denmark | Case-control | 21 SLE, 29 RA, 12 OA | 72 Healthy controls | 1,25(OH)2 D and 25(OH) D | Yes | P = 0.0008 for decreased 25(OH) levels in SLE versus controls; no correlation with anti-DNA antibodies, sedimentation rate, or blood counts. | 1995 | Muller et al, (118) |
| Systemic Lupus Erythematosus and Dermatomyositis and Juvenile RA | North America | Case-only | 17 pediatric SLE, 13 juvenile dermatomyositis, 83 JRA | - | 25(OH) D; 1,25(OH)2 D; PTH | No | No significant differences between active and inactive stages of pediatric SLE with regards to vitamin D levels | 1990 | Reed et al, (134) |
| Undifferentiated Connective Tissue Disease | Hungary | Case-only | 161 UCTD | 59 controls | 25(OH)D | Yes | 25(OH)D significantly lower than in controls in summer and winter. Significant associations of low 25(OH)D with active manifestations and with evolution to diagnosed connective tissue disease within 2.3 years. | 2008 | Zold et al, (136) |
| Scleroderma | Italy | Case-only | 108 scleroderma | - | 25(OH) D | Yes | Vitamin D deficiency is associated with more severe disease P = 0.026 for longer disease duration, P = 0.014 for lower diffusing lung capacity, P = 0.037 for higher pulmonary artery pressure | 2010 | Carameschi et al, (147) |
| Scleroderma | Brazil | Case-control | 10 juvenile scleroderma | 10 matched controls | 25(OH) D, iPTH | Yes | P = 0.04 for lower vitamin D levels compared with controls | 2010 | Shinjo et al, (143) |
| Scleroderma | Italy | Case-control | 60 Scleroderma | 60 controls | 25(OH) D | Yes | P < 0.001 for lower vitamin D levels compared with controls, but no associations with disease features or skin score | 2009 | Calzolari et al, (142) |
| Scleroderma | France and Italy | Case-only | 90 scleroderma | - | 25(OH) D and iPTH | Yes | R = -0.17 (P = 0.04) for negative correlation between low vitamin D and disease activity score | 2009 | Vacca et al, (148) |
| Scleroderma | Israel | Case-only | 60 scleroderma | - | 25(OH) D, PTH | - | 46% of scleroderma patients are vitamin D deficient | 2008 | Braun-Moscovici et al, (179) |
| Scleroderma | North America | Case-control | 8 scleroderma | 8 matched healthy controls | 25(OH) D; 1,25(OH)2 D | No | Similar levels in cases and controls. | 1991 | Matsuoka et al, (144) |
| Scleroderma | Holland | Case-control | 20 scleroderma | - | 25(OH) D; 1,25(OH)2 D; 24-25(OH) D | No | Normal 25(OH) D and 24,25(OH) D levels in scleroderma; lower 1,25(OH)2 D in a subgroup with calcinosis | 1985 | Serup et al, (145) |
| Scleroderma | Holland | Case-control | 25 scleroderma | 92 controls | 1,25(OH)2 D | No | P < 0.001 for higher 1,25(OH)2 D in scleroderma compared to controls | 1984 | Serup et al, (146) |
| Type I Diabetes Mellitus | India | Case-control | 50 children within 1 week of diagnosis of T1D* | 50 healthy children | 25(OH) D | Yes | P < 0.009 for lower vitamin D in new onset diabetics | 2009 | Borkar et al, 8 (149) |
| Type I Diabetes Mellitus | North America | Case-control | 46 new-onset T1D*, 110 established T1D, | 153 control subjects; 106 first-degree relatives | 25(OH) D | No | P = 0.87 No significant associations of reduced vitamin D level and T1D | 2009 | Bierschenk et al, (158) |
| Type I Diabetes Mellitus | Great Britain | Case-control | 40 T1D,* 40 T2D* | 41 non-diabetic controls | 1,25(OH)2 D, PTH, Erythropoietin | Yes | P = 0.001 for median vitamin D level in cases vs. controls. Tubulointerstitial damage associated with low 1,25(OH)2 D | 2009 | Singh et al, (150) |
| Type I Diabetes Mellitus | North America | Case-only | 128 Pediatric T1D* | - | 25(OH) D | - | 61% Vitamin D insufficient; 15% Vitamin D deficient | 2009 | Svoren et al, (216) |
| Type I Diabetes Mellitus | Qatar | Case-control | 170 pediatric T1D* | 170 healthy controls | 25(OH) D, PTH | Yes | P = 0.009 for mean vitamin D level; 28.8% versus 17.1% severe vitamin D deficiency | 2008, 2009 | Bener et al, (217, 151) |
| Type I Diabetes Mellitus | Australia | Case-only | 64 pediatric new-onset T1D* | - | 25(OH) D | - | P = 0.001 (for associate acidosis) Low vitamin D in 42% with acidosis versus 5.6% without acidosis Acidosis may alter vitamin D metabolism or low vitamin D may contribute to presenting with ketoacidosis | 2009 | Huynh et al, (160) |
| Type I Diabetes Mellitus | Australia | Case-control | 47 pediatric T1D* | 94 Healthy controls | 25(OH) D, 1,25(OH)2 D | Yes | P = 0.002 for 25(OH) D deficiency | 2007 | Greer et al, (152) |
| Type I Diabetes Mellitus | Sweden | Case-control | 459 T1D* at diagnosi, 138 8 years later | 208 - matched controls | 25(OH) D | Yes | P < 0.0001 for vitamin D level at diagnosis; P = 0.04 for vitamin D level 8 years later | 2006 | Littorin et al, (155) |
| Type I Diabetes Mellitus | North America | Case-control | 50 T1D* | 63 T2D* | 25(OH) D | No | P = 0.01 for lower 25-OH-D levels in T2D versus T1D* (adjusted for body mass index and age) | 2006 | Di Cesar et al, (156) |
| Type I Diabetes Mellitus | Italy | Case-control | 46 T1D* | 24 healthy controls | 25(OH) D; 1,25(OH)2 D; PTH | Yes | P < 0.01 for vitamin D levels Lower vitamin D level in incipient nephropathy/microalbuminuria | 1999 | Verrotti et al, (157) |
| Type I Diabetes Mellitus | Germany | Case-control | 49 new onset T1D* | 42 healthy controls | 25(OH) D; 1,25(OH)2 D | Yes | P < 0.01 for 1,25(OH)2 D at onset of T1D | 1991 | Baumgartl et al, (153) |
| Type I Diabetes Mellitus | Mexico | Case-only | 22 T1D* | - | 25(OH) D | Yes | P < 0.001 for low 25(OH) D in poorly controlled T1D* | 1990 | Arreola et al, PMID 2103709 (159) |
| Type I Diabetes Mellitus | Norway | Case-control | 46 pubertal T1D* | 191 Healthy controls | 25(OH) D; 1,25(OH)2 D; 24,25(OH) D | Yes | P < 0.05 for 1,25(OH)2 D Relative decrease in 1,25(OH)2 D and increased 24,25(OH) D levels in T1D at puberty | 1985 | Rodland et al, (154) |
| Type I Diabetes Mellitus | Denmark | Case-only | 74 T1D* | - | 25(OH) D; 1,25(OH)2 D; 24,25(OH) D | - | P < 0.02 for 1,25-OH level during ketoacidosis; P < 0.01 for 25(OH) D in T1D groups with diabetic nephropathy | 1983 | Storm et al, (161) |
| Multiple Sclerosis | Holland | Case-control | 36 MS | 20 Healthy controls | 25(OH) D | - | R= -0.359, P = 0.048 25(OH) D negative correlation with IgG index in MS | 2010 | Vogt et al, (162) |
| Multiple Sclerosis | Norway | Case-control | 36 MS | 38 other neurologic diseases | Serum and cerebrospinal fluid 25(OH) D | Yes | P = 0.0012 and 0.041 for cerebrospinal fluid-to-vitamin D serum ratio (lower in MS compared with other neurological diseases) | 2010 | Holmoy et al, (164) |
| Multiple Sclerosis | North America | Case-control | 173 MS +9 transverse myelitis, | 16 other neurologic diseases | 25(OH) D | - | 84% of all patients had insufficient levels Large numbers of patients with MS and transverse myelitis are deficient in vitamin D | Hiremath et al, (165) | |
| Multiple Sclerosis | Argentina | Case-control | 132 MS-various forms | 60 Healthy controls | 1,25(OH)2 D, 25(OH) D | Yes | P < 0.00001 for 25(OH) D and 1,25(OH)2 D levels (lower in relapsing-remitting MS during exacerbation compared with remission | 2009 | Correale et al, (167) |
| Multiple Sclerosis | Holland | Case-control | 103 MS | 110 Healthy controls | 1,25(OH)2 D, 25(OH) D | Yes | Among women: for every 10 nmol/L increase in serum 25(OH)D level the odds of MS decreased 19% (OR = 0.81; 95% CI 0.69-0.95) for dose-dependent decreased odds of MS among women); r= -0.29; P = 0.02 for negative correlation between disability status and 25(OH) D levels in women only | 2009 | Kragt et al, (166) |
| Multiple Sclerosis | Finland | Case-control | 23 MS | 23 Healthy controls | 25(OH) D and iPTH every 3 months for 1 year | Yes | P = 0.012 for inverse relationship between serum vitamin D level and MS clinical activity | 2008 | Soilu-Hanninen et al, (218) |
| Multiple Sclerosis | Great Britain | Case-control twin study | 40 monozygotic and 59 dizygotic twins with MS | 40 monozygotic and 59 dizygotic twins without MS | 25(OH) D | No | No association with having MS (P = 0.4) | 2008 | Orton et al, (170) |
| Multiple Sclerosis | Holland | Case-control | 267 MS | - | 25(OH) D, 1,25(OH)2 D | Yes | P = 0.043 for high 25(OH) D and chance of remaining relapse-free | 2008 | Smolders et al,(172) |
| Multiple Sclerosis | Ireland | Case-control | 29 MS | 22 age- and sex-matched controls | 25(OH) D; 1,25(OH)2 D; PTH | No | No differences between cases and controls | 2007 | Barnes et al, (169) |
| Multiple Sclerosis | Australia | Case-control | 136 MS | 272 controls | 25(OH) D | Yes | OR = 3.07 (95% CI 1.37-6.90) for disability and vitamin D insufficiency | 2007 | van der Mei et al, (163) |
| Multiple Sclerosis | Finland | Case-control | 40 MS | 40 Controls | 25(OH) D | Yes | P = 0.03 for lower vitamin D level during relapse versus remission | 2005 | Soilu-Hanninen et al, (171) |
| Multiple Sclerosis | Germany | Case-control | 53 MS | 415 Controls | 25(OH) D | Yes | R2 = 0.8491 for vitamin D level; R2 = 0.7931 for brain lesions (two-fitted, third-order polynomial curves corresponding closely when 25(OH) D data lagged 2 months) Inverse correlation of gadolinium-enhancing lesions on MRI and vitamin D levels following seasonal fluctuations | 2000 | Embry et al, (168) |
| Hashimoto's Thyroiditis | India | Case-only | 642 healthy individuals | - | 25(OH) D | - | r - 0.08, P = 0.04 for vitamin D level inverse correlation with anti-thyroid antibodies | 2009 | Goswami et al, (177) |
| Crohn's disease | India | Case-control | 34 Crohn's | 34 irritable bowel syndrome controls | 25(OH) D | Yes | Correlation coefficient -0.484, significance P<0.004 Lower vitamin D levels in Crohn's disease and association with severe disease activity | 2009 | Joseph et al, (173) |
| Crohn's disease and Ulcerative colitis | America | Case-only | 130 young Crohn's, and UC* | - | 25(OH) D, iPTH | No | P =0.97 in multiple regression for vitamin D level and disease activity | 2006 | Pappa et al, (176) |
| Crohn's disease | Japan | Case-control | 33 Crohn's | 15 healthy controls | 25(OH) D, iPTH | Yes | P = 0.04 for vitamin D and disease activity in logistic regression | 2004 | Tajika et al(174) |
| Crohn's disease | Great Britain | Case-only | 40 Crohn's | - | 25(OH) D, 24,25(OH) D, 1,25(OH)2 D, PTH | Yes | P < 0.05 for low 25(OH) D levels in active disease | 1985 | Harries et al (175) |
| Vitiligo | Great Britain | Case-only | 45 Vitiligo | - | 25(OH)D | Yes | 55.6% were insufficient (<30 ng/mL), and 13.3% were very low (<15 ng/mL). | 2007 | Silverberg, et al.(178) |
*
DAS28= Disease Activity Score 28 joint assessment; HAQ= Health Assessment Questionnaire; PsOA= psoriatic arthritis; T1D= type 1 diabetes; T2D= type 2 diabetes; UC= ulcerative colitis