Women with higher intake of vitamin D are less likely to develop Crohn’s disease or ulcerative colitis, according to a study published in the March issue of Gastroenterology.
Vitamin D deficiency has been described in patients with inflammatory bowel diseases (IBD), and administration of vitamin D to mice with colitis alleviates their symptoms. However, no studies have determined vitamin D status in a large number of subjects and then followed them for the development of Crohn’s disease or ulcerative colitis.
Ashwin Ananthakrishnan et al. investigated whether vitamin D status affects later risk for developing these diseases using data from the Nurses’ Health Study. In 1986, 72,719 women completed questionnaires of diet and lifestyle and were assigned a 25-hydroxy vitamin D (25[OH]D) prediction score. Over the next 22 years, the authors collected information on which women developed Crohn’s disease or ulcerative colitis. This analysis avoided biases associated with nutritional deficiencies associated with preclinical symptoms.
They found that for each 1 ng/mL increase in predicted plasma level of 25(OH)D, there was a 6% relative reduction in risk of Crohn’s disease and a 4% (nonsignificant) reduction in risk of ulcerative colitis.
“Compared to women in the lowest predicted vitamin D quartile, women in the highest predicted vitamin D quartile (the best vitamin D status), had a 45% lower risk of developing Crohn’s disease”, says Ashwin Ananthakrishnan in a video abstract that accompanies the article.
For vitamin D intake from diet and supplements, each 100 IU/day increase in total vitamin D intake reduced the risk of ulcerative colitis by 10% and the risk of Crohn’s disease by 7%. How might vitamin D prevent these inflammatory disorders?
Vitamin D regulates the innate immune system and inflammatory response, which are involved in pathogenesis of these diseases. Acting through vitamin D receptors on T cells and antigen presenting cells, the active form of vitamin D suppresses proliferation of T-helper 1 cells and inhibits secretion of interleukin-2 and interferon-γ. Active vitamin D also induces proliferation of regulatory T cells that downregulate the inflammatory response, and inhibits differentiation of peripheral blood monocytes into dendritic cells.
Lower plasma levels of vitamin D from reduced solar ultraviolet-B radiation exposure could account for the North–South gradient of IBD incidence. There is a higher incidence of IBD at higher latitudes, where populations typically are exposed to less ultraviolet radiation, the greatest environmental determinant of plasma 25(OH)D level.
The prospective design of the study avoids the potential recall and selection biases of retrospective, case-control studies, which collect data on diet and lifestyle after subjects have been diagnosed. In the study of Ananthakrishnan et al., levels of 25(OH)D were determined 10–12 years before most study participants were diagnosed with Crohn’s disease or ulcerative colitis, so it is not likely features of early-stage disease affected vitamin D levels (reverse causation). Furthermore, all cases of these diseases were confirmed through medical record review—an advantage over studies that rely on self-report or discharge codes, which don’t always state the exact diagnosis.
Ananthakrishnan et al. state that these findings strengthen the rationale for considering vitamin D supplementation for treating active IBD or preventing disease flares. Despite the recognized prevalence of vitamin D deficiency in patients with Crohn’s disease, assessment of plasma 25(OH)D levels are not part of routine care.
Studies are needed to test the effects of vitamin D supplementation, particularly among deficient individuals, in patients with established Crohn’s disease. Patients with genetic risk factors for IBD might be screened for vitamin D deficiency.
More Information on IBD:
- The National Library of Medicine Website on Crohn’s Disease
- The National Library of Medicine Website on Ulcerative Colitis
- The National Institutes of Health Website on Vitamin D
Read the article online.
Ananthakrishnan AN, Khalili H, Higuchi LM, et al. Higher predicted vitamin D status is associated with reduced risk of crohn’s disease. Gastroenterology 2012;482–489.