Faten N. Aberra, MD, MSCE
Assistant Professor of Medicine
Division of Gastroenterology
Perelman School of Medicine at the University of Pennsylvania
Hospital of the University of Pennsylvania
Penn Tower – 9th Floor, 1 Convention Ave
Philadelphia, PA 19104
215-615-4951/ 215-662-6530 (FAX)
Faten.aberra@uphs.upenn.edu
“Vitamin D Deficiency is Associated with Ulcerative Colitis Disease Activity,”
Dig Dis Sci, 2013 Jun;58(6):1698-702. 50283 (2/2014)
Kirk Hamilton: Can you please share with us your educational background and current position?
Faten N. Aberra: I graduated from Swarthmore College with a Bachelor of Arts degree in Biochemistry in 1993 and graduated from Dartmouth Medical School in 1997. I completed residency training in internal medicine in 2000 and a gastroenterology fellowship at the University of Pennsylvania in 2003. I also received a Masters in Science degree in Clinical Epidemiology and Biostatistics in 2004 from the University of Pennsylvania. I am an Assistant Professor of Medicine in the Division of Gastroenterology at Perelman School of Medicine at the University of Pennsylvania and Associate Director of the CHOP-Penn Transitional IBD Center. My clinical expertise is in the evaluation and treatment of inflammatory bowel diseases. I am extensively involved in several research areas that range from identifying risk factors for developing inflammatory bowel disease to medical therapy trials that are multicenter.
KH: What got you interested in studying the role of vitamin D (VD) in ulcerative colitis (UC)?
FNA: My interest developed when I came across research that linked Vitamin D as an immune modulator for T Helper 17 cells. Increased T Helper 17 cells are associated with immunedysregulatory disorders. A north-south gradient in the prevalence of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has been observed in several countries in the northern hemisphere (such as the United States, Canada and France). Sun exposure contributes to vitamin D production and low vitamin D levels are more likely to occur in colder and less sun exposed climates. Since it appears that IBD may occur more often in less sun exposed locations, I felt I should investigate whether vitamin D deficiency may be associated with increased disease activity in inflammatory bowel disease. I decided not to evaluate Crohn’s since our study would be retrospective and it would be difficult to adjust for malabsorption which can occur in some Crohn’s patients and cause low vitamin D. Our study was to assess if low vitamin D levels were associated with more active ulcerative colitis.
KH: What is the biochemistry of VD, especially the immunobiochemistry, that might alter the pathophysiology of UC?
FNA: Vitamin D has been shown to inhibit the differentiation of monocytes to dendritic cells, thereby reducing the number of antigen presenting cells available to stimulate T cells. There are also studies that have shown 1,25 (OH)2D3 inhibits Th1 and Th17 cell proliferation and stimulates T regulatory cell activity. So low vitamin D may increase Th1 and Th17 which are stimulated in inflammatory bowel diseases (ulcerative colitis and Crohn’s disease)
KH: What do you define as VD deficiency, insufficiency, adequacy, and/or optimal levels of VD, especially with regards to UC progression and severity?
FNA: There are studies that suggest a 25-OH vitamin D level of >30 ng/ml is needed for immune system homeostasis. In our study we used a level >30 as sufficient; 20-30 insufficient; < 20 deficient. It is unclear as of yet what are optimum serum levels.
KH: Can you tell us about your study and the basic results?
FNA: We performed a retrospective cross-sectional study, comparing vitamin D deficiency in patients with active disease to patients with inactive ulcerative colitis. There were more patients with clinically active disease in the vitamin D deficient group (68%) compared to the sufficient group (32%), (p=0.04). Vitamin D deficient patients were statistically more likely to be prescribed steroids, with 47% of the vitamin D deficient cohort taking steroids compared to only 7% of their vitamin D sufficient counterparts (p=0.02). However, there was no statistically significant association among the other immunesuppresants.
KH: Is there any evidence that supplementation with VD can alter UC progression and pathophysiology? Or actually reverse the disease?
FNA: This is not yet known for ulcerative colitis.
KH: If so what have been the daily doses used in IU/d of VD in UC patients? Or what is the target serum level of VD3 as some kind of therapeutic goal in UC patients?
FNA: It’s not yet known, but I speculate it will be a dose needed to keep levels >30 ng/ml.
KH: Are there any side effects with the VD therapy at doses used in clinical trials? What is your upper level of comfort with VD supplementation in IUs/day or serum levels of VD3?
FNA: In a clinical trial for Crohn’s there were no side effects appreciated with oral intake of 1200 IU per day of oral vitamin D3.
KH: Who is a candidate for VD therapy? All subjects with UC? Only those with serum levels below ??
20, 30, 40 ng/ml…? Why not just give 5000 IU of VD to all UC patients routinely, and supplement with more if they don’t achieve your therapeutic target levels?
FNA: There is a theoretical risk of hypercalcemia if levels are “too” high. In patients with underlying hypercalcemia, vitamin D may need to be avoided until the hypercalcemia is corrected. For now I would only recommend supplementation in patients that are deficient. A randomized study is needed in ulcerative colitis to determine if supplementation works to prevent active disease and maintain remission and to determine which level of 25-OH vitamin D is optimal.
KH: From this work do you think VD is a cause or a result of UC pathophysiology or both?
FNA: From our study, it cannot be excluded that patients with active disease minimized vitamin D containing products in their diet due to a disease flare. Therefore, a randomized study is needed that could control for potential confounders.
KH: How can the public or health professionals use this information?
FNA: For now, I check vitamin 25(OH)D3 levels in my patients and supplement if they are insufficient or deficient (i.e. level >30 as sufficient, 20-30 insufficient, <20 deficient).