A five year longitudinal study published in the American Journal of Gastroenterology found that low vitamin D status was associated with worse pain, disease activity scores and quality of life among patients with inflammatory bowel disease.
Inflammatory bowel disease (IBD) primarily refers to ulcerative colitis and Crohn’s disease. Ulcerative colitis causes inflammation and ulcers in the innermost lining of the large intestine and rectum; whereas, Crohn’s disease can affect all layers of the bowel wall and any part of the GI tract.
Both ulcerative colitis and Crohn’s disease are caused by an irregular response by the immune system. In people with IBD, the immune system mistakes food and bacteria among other normal components of the GI tract as invading substances, leading the body to send white blood cells to the intestines. The white blood cells produce proteins that cause inflammation, known as proinflammatory cytokines.
Researchers have hypothesized that vitamin D plays a role in IBD by regulating the immune system. Vitamin D increases the production of anti-inflammatory cytokines, while reducing proinflammatory cytokines. Research has also shown that vitamin D may help patients with IBD by modulating the gut microbiome.
Cross-sectional and epidemiological studies have supported this hypothesis by showing an inverse relationship of both UVB exposure and vitamin D status with the development of IBD. Recently, researchers conducted the first long-term prospective study to evaluate the association between vitamin D status and the clinical course of IBD. In order to do this, the researchers included nearly one thousand IBD patients (61.9% with Crohn’s disease and 38.1% with ulcerative colitis) from the Inflammatory Bowel Disease Center at the University of Pittsburgh Medical Center.
The researchers wanted to know the role vitamin D plays in disease severity, health related quality of life, medication use, health care utilization and markers of inflammation.
Here is what they found:
- At baseline, 42% of patients were considered to have low vitamin D status as defined by levels less than 30 ng/ml.
- At the study conclusion, 28.5% of patients were considered to have low vitamin D levels. Of those who received vitamin D supplements, 67.9% achieved normal vitamin D levels at the study conclusion.
- Over the 5 year study period, significantly more patients with low vitamin D status required pain medications compared to the number of patients of normal vitamin D status (p = 0.04).
- The patients with low vitamin D received more frequent computed tomography scan imaging, ED visits, hospitalizations and surgeries than those with normal vitamin D levels.
- There was no difference in C – reactive protein levels, an indicator of inflammation, between the low and normal vitamin D groups.
- Pain scores were significantly worse among IBD patients with low vitamin D levels, indicating more frequent abdominal pain, compared to those with normal vitamin D levels (p < 0.0001).
- Patients with low vitamin D status had worse disease activity, as indicated with higher (Harvey–Bradshaw index and UC disease activity index scores (p < 0.0001, 0.01).
- Patients with low vitamin D levels had worse quality of life (p = 0.06 and 0.002 for Crohn’s disease and ulcerative colitis, respectively).
- Those with low vitamin D levels had nearly double the risk of being affected by the active disease (opposed to remission) compared to those with sufficient vitamin D (p = 0.0003, 0.0375 for patients with Crohn’s disease and ulcerative colitis).
The researchers also compared patients with low vitamin D levels who did not receive vitamin D supplementation to those who did. They found that those who did not receive supplementation had lower vitamin D levels, and they used the health care system more often.
The researchers concluded,
“IBD patients with low mean vitamin D levels have worse disease activity, worse pain, higher need for biologics, steroids and narcotics, and increased health-care utilization. Vitamin D status is an independent risk factor for worse IBD outcomes.
They went on to state,
“Vitamin D supplementation also appears to be associated with improvement in health-care utilization, which is reflective of improved overall health.”
While the observational design is insufficient to prove a cause-effect relationship, conducting a well-designed clinical trial may be impossible according to David Binion, MD, a researcher of the longitudinal study.
“This type of prospective, observational registry data is essential, as a clinical trial which fails to correct vitamin deficiency detected in participants would be impossible, as with-holding vitamin treatment would be unethical,” he stated.
The study possessed several limitations worth acknowledging. First, many patients in the study lacked available endoscopic findings for the researchers to investigate the association between vitamin D and inflammation. The results may be due to reverse causation, meaning IBD causes low vitamin D levels. Lastly, one might expect for low vitamin D levels and poor outcomes to be caused by non-compliance with medical treatment, including vitamin D supplementation. However, the researchers found that subjects with low vitamin D status made the same number of phone calls and clinic visits compared to those with sufficient vitamin D status, indicating a similar level of concern.
The Vitamin D Council recommends that patients with IBD take 5,000 IU of vitamin D3 daily with their largest meal of the day. After two months of supplementing, patients should check their vitamin D levels to see if they are within the ideal vitamin D range of 40-80 ng/ml. If not, they should adjust their supplementation regimen accordingly. As always, it’s best to work with your doctor.
Tovey, A. & Cannell, JJ. New study shows low vitamin D levels may be associated with worse outcomes in patients with inflammatory bowel disease. The Vitamin D Council Blog & Newsletter, 2016.