Vitamin D in Systemic Lupus Erythematosus

Diane Kamen; Cynthia Aranow


Curr Opin Rheumatol. 2008;20(5):532-537. 

In This Article

Clinical Studies of Vitamin D and Systemic Lupus Erythematosus

There is a growing body of epidemiologic data linking low levels of serum 25D with autoimmune diseases, including MS[43,44] rheumatoid arthritis (RA),[45] type 1 diabetes mellitus[46] and inflammatory bowel disease.[47] Additional studies associating a higher dietary intake of vitamin D with protection from autoimmune disease have also been published and include a report that the offspring of pregnant women who are bearing children at high risk for development of type 1 diabetes mellitus are at a lower risk of developing diabetes-associated autoantibodies with higher maternal vitamin D intake[48] in addition to multiple studies showing a reduction in the risk for type 1 diabetes mellitus with high dietary intake.[49,50,51] A prospective study of the risk of RA and vitamin D intake similarly found that a higher vitamin D intake at baseline provided significant protection from subsequent development of the disease.[45] However, these findings in RA could not be replicated in a study published this year, which used comparable methods in a different cohort.[52] This large prospective study additionally examined baseline vitamin D intake and later development of SLE and found no association. Measurements of 25D were not performed.

Initial insights into the prevalence of vitamin D deficiency in SLE came from studies of bone health. The first study measuring levels of vitamin D in SLE reported a deficiency of 1,25D in seven of 12 corticosteroid-receiving adolescents.[53] Subsequent studies measuring vitamin D in the context of either bone mineral density (BMD) or fractures or both included a study documenting severe 25D deficiency (<25 nmol/l or 1 ng/ml) in 8% of 107 consecutive patients from the Netherlands.[54] A second study examining BMD in patients with newly diagnosed SLE, established SLE on corticosteroids and age-matched controls reported mean 25D levels of 27.2 ± 10.05, 19.6 ± 11.9, and 40.45 ± 18 (respectively) with statistically lower 25D levels in patients with established SLE compared with controls.[55]

A cross-sectional study specifically of vitamin D in SLE from Copenhagen reported statistically lower levels of 25D in 21 patients with SLE (mean 13 ng/ml) in comparison with 29 patients with RA (mean 24 ng/ml), patients with osteoarthritis (mean, 32 ng/ml) and 24 controls (mean, 27 ng/ml).[56] There was no difference in levels of 1,25D. A second cross-sectional Canadian study of 25 Caucasian patients with SLE reported that over 50% were vitamin D deficient (using a cutoff of <50 nmol/l or 20 ng/ml). However, this was not statistically different from a control group of patients with fibromyalgia that was similarly low (SLE mean, 46.5 nmol/l; fibromyalgia mean, 51.5 nmol/l).[57]

A recent cross-sectional study published this year has confirmed these results in patients from Shanghai. Levels of 25D were significantly lower in patients with SLE (11.5 ng/ml) than in patients with RA (54.6 ng/ml) or controls (59.2 ng/ml).[15] Another study published this year from Israel determined 25D levels in a number of autoimmune diseases including MS, myositis, RA, autoimmune thyroid disease and SLE. The mean 25D levels for all diseases were below 20 ng/ml. Patients with SLE (n = 138) had a mean 25D level of 11.9 ± 11.1 ng/ml, which was significantly lower than the mean of 21.6 ng/ml in European controls.[58]

Vitamin D deficiency is more prevalent in patients with darker skin pigmentation due to a reduced ability of UVB to convert 7-dehydrocholesterol to vitamin D cutaneously in these individuals. In recent years, vitamin D status has been evaluated in non-Caucasian SLE populations. In one study of 123 recently diagnosed patients with SLE and 240 controls, the mean 25D levels were significantly lower among African-Americans (15.5 ng/ml; SD, 9.4) than among Caucasians (31.3 ng/ml; SD, 4.9). Overall, 67% of patients with SLE were vitamin D deficient. Caucasian patients had statistically lower vitamin D levels than controls, and there was a trend for all patients toward lower 25D levels. Severe deficiency (<10 ng/ml) was noted in about 18% of patients and was associated with renal disease and photosensitivity.[59]

A smaller study comparing vitamin D levels in SLE and incomplete lupus (patients with 1-3 American College of Rheumatology criteria) in 12 Caucasians, 12 African-Americans and 13 Hispanics noted that Caucasians had statistically higher 25D levels than either Hispanics or African-American patients. Quality of life measurements were worse in vitamin D-deficient patients suggesting a poorer general health status among patients most deficient in vitamin D.[60]

A comparison of 25D levels in 101 Gullah African-American patients with SLE from the Sea Islands and 86 population controls without SLE did not find a significant difference in 25D levels. However, an alarming 95% of patients were vitamin D deficient (<30 ng/ml) with a mean 25D level of 13.3 ± 8 ng/ml.[61]

We have recently analyzed 25D levels in 200 patients with SLE of different ethnicities (142 African-American, 42 Hispanic, 10 Caucasian and six Asian). The 25D levels in African-American and Hispanics were statistically lower than in Caucasians or Asians. Furthermore, there were a significant number of African-Americans and Hispanics with severe deficiency (<10 ng/ml) (unpublished data).

Many studies, but not all, have documented an association between higher disease activity and a low level of vitamin D. A significant negative correlation between 25D and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and European Consensus Lupus Activity Measurement (ECLAM) scores was noted in European patients;[62] another study using data from three centers documented a significant difference in SLEDAI scores between patients with severe deficiency and those who were less deficient.[63] However, the previously mentioned study of Shanghai patients described a correlation between active disease and low 1,25D but not 25D levels,[15] and no association between disease activity and 25D was observed in the study from Israel.[58]


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