Less Inflammatory Bowel Disease Seen in Southern Latitudes

Women living in the southern latitudes of the United States have significantly lower rates of Inflammatory Bowel Disease (IBD) than those living in the country's northern regions, according to new research published online January 11, 2012, in Gut.
Similar trends have been reported in Europe in the past; however, this is the first study to evaluate the role of latitude on IBD incidence in the United States.
To investigate the issue, Hamed Khalili, MD, from the Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues evaluated data on 175,912 women enrolled in the Nurses' Health Study I (NHS) in 1976, and in the NHS II in 1989.
The data included information on the women's state of residence at birth, at age 15 years, and at age 30 years. The states were categorized as being in the northern, middle, or southern tiers of each of the 4 time zones (eastern, central, mountain, and pacific).
Follow-up data taken in 2003 identified 257 cases of Crohn's disease and 313 cases of ulcerative colitis among the women, with the incidence of each disease increasing significantly according to increased latitude (P _trend < .01).
The residence at age 30 years showed the strongest association with risk for Inflammatory Bowel Disease.
The multivariate-adjusted hazard ratio for women residing in southern latitudes compared with those residing at northern latitudes at age 30 years was 0.48 (95% confidence interval, 0.30 - 0.77) for Crohn's disease and 0.62 (95% confidence interval, 0.42 - 0.90) for ulcerative colitis. The multivariate analysis was adjusted for age, body mass index, ancestry (Southern European, Scandinavian, other white, nonwhite), smoking, and oral contraceptive and hormone therapy use.
"In two large prospective cohorts of US women, the incidence of [ulcerative colitis and Crohn's disease] was significantly lower among women who resided in the southern latitudes, particularly in later life (age 30 years), than in those residing in the northern latitudes," Dr. Khalili and colleagues write.
"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations."
The authors hypothesize that the main explanation for the reductions in southern latitudes is related to greater levels of sun exposure and to the higher levels of plasma vitamin D that are associated with ultraviolet (UV) radiation.
"UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the authors write.
"The role of vitamin D in the pathogenesis of IBD is further supported by the observation that animal models of colitis have more severe inflammation in vitamin D receptor knock out animals or animals deficient in 1,25(OH)₂ vitamin D."
In addition, UV radiation is associated with regulation of T cells, as well as the production of interleukin (IL) 4 and IL-10, and the inhibition of IL-12, which suppresses the inflammatory response, they note.
Bincy P. Abraham, MD, an assistant professor of medicine in the Inflammatory Bowel Disease Program at Baylor College of Medicine in Houston, Texas, said that vitamin D, or a lack thereof, has been recognized as a potential risk factor for IBD, but its role is not entirely understood.
"Theoretically, vitamin D can play a role in inflammation: low levels may contribute to inflammation, and thus can be explained by the general north–south gradient of inflammatory bowel disease we have seen historically in the US, as well as Europe," Dr. Abraham told Medscape Medical News.
"However, knowing the vitamin D levels in both groups of patients is important in order to clarify this," added Dr. Abraham, who was not involved in the study. "This is because there could be other confounders — other environmental causes that we do not know about."
In her own research on Inflammatory Bowel Disease, Dr. Abraham found high levels of abnormal bone density among patients with IBD and vitamin D deficiency, but that research was also inconclusive regarding the vitamin's influence.
"It was difficult for us to determine a correlation of IBD disease activity and vitamin D levels due to too many confounding variables," she said, noting that, among potential variables, there is even a theory that refrigeration of food may increase the risk for Inflammatory Bowel Disease.
"My general sense is that [a correlation with vitamin D] is quite possible," Dr. Abraham concludes. "We may need to do additional, larger-scale studies of vitamin D levels and their association in contributing to the development of Inflammatory Bowel Disease."
The study received support from the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. The authors included a clinical investigator for the Damon Runyon Cancer Research Foundation, and one author is supported by a career development award from the IBD Working Group and the Crohn's and Colitis Foundation of America. Dr. Abraham has disclosed no relevant financial relationships.