Micronutrient Deficiencies Predict Disease Outcomes in Patients With IBD

Jonathan Macdonald, MBChB

Credit: ResearchGate

Selenium and zinc deficiencies may predict adverse clinical outcomes in patients with inflammatory bowel disease (IBD) on biologic therapy, according to results from a new study.

“Although the underlying role of these deficiencies in causing disease exacerbation needs to be addressed within a randomized controlled trial, the clinical practitioner might be able to use these micronutrient levels in addition to other disease biomarkers to predict which patients are likely to experience a disease relapse and adapt disease management strategies accordingly,” wrote investigators.¹

Intestinal inflammation and other IBD-related complications can impact patients’ ability to properly digest food and absorb micronutrients. As a result, individuals with IBD are at greater risk for micronutrient deficiencies that can lead to other medical complications.²

A team of investigators led by Jonathan Macdonald, MBChB, of the Department of Gastroenterology in the Queen Elizabeth University Hospital in the United Kingdom, sought to explore associations between micronutrient status and frequently used markers of disease activity including C-reactive protein (CRP), serum albumin concentration, and fecal calprotectin (FCP). To do so, investigators collected clinical data from the electronic records of 216 patients with IBD in South Glasgow attending the hospital Medical Day Unit for infusions of infliximab or vedolizumab or injections of adalimumab or ustekinumab. Micronutrient status was audited from July-November 2020 and investigators extracted and analyzed clinical outcome data for 12 months after.¹

Micronutrients were assayed at the Scottish Trace Element and Micronutrient Diagnostic and Research Laboratory and were tested and calibrated against certified reference material. The between batch coefficient of variation of all methods was <10%. The most common deficiencies in the cohort were vitamin C (16.5%), ferritin (14.3%), folate (14.0%), and zinc (12.9%).¹

Investigators analyzed the relationships between each micronutrient and markers of disease activity/clinical outcomes using Spearman’s rank correlations. Significant associations were observed between CRP with the concentration of zinc, copper, and selenium in plasma; red blood cell (RBC) selenium; and vitamin K-to-triglyceride ratio, vitamin C, vitamin E-to-cholesterol ratio, vitamin A, and vitamin B1.¹

Investigators noted the concentration of serum albumin was significantly associated with plasma zinc, ferritin, selenium, and copper; RBC selenium and vitamin B2; and vitamin E-to-cholesterol ratio; and vitamin B1. FCP was significantly associated with plasma zinc, ferritin, copper, and selenium; RBC selenium; and vitamin E-to-cholesterol ratio, vitamin A, and vitamin B1.¹

Investigators pointed out during the 12-month follow up period, 22 patients developed 1 or more adverse clinical outcomes involving a clinical flare of disease or requirement for corticosteroids or surgical intervention. Logistic regression showed CRP, albumin, and FCP at the point of micronutrient status assessment were all significantly associated with adverse outcomes.¹

Investigators conducted further analysis in a subset of 48 patients in complete biochemical remission, defined as those with albumin >35 g/L, CRP <10 mg/L, and FCP <250 ug/g, to account for the influence of systemic inflammatory response on micronutrient level. Results showed no significant associations between micronutrient status and clinical outcomes.¹

Investigators further divided the subcohort based on clinical stability, defined as having no escalation or change in therapy for the preceding 3 months. In the stable ulcerative colitis (UC) cohort (n = 57), disease flare was observed in 11 patients and was significantly associated with high copper (P = .027). Among the 110 patients in the stable Crohn disease (CD) cohort, disease flare was experienced by 17 patients and was significantly associated with low Hb (P = .011).¹

When findings from the logistic regression were replicated using Kaplan-Meier survival analysis, investigators found patients with CD and zinc deficiency were significantly more likely to require surgery (P = .002) or induction treatment with steroids (P < .001) while patients with UC and selenium deficiency were significantly more likely to have a clinical flare of disease (P = .001). Of note, these findings were insignificant when investigators used Cox proportional hazards regression to account for confounders.¹

“This study offers important insights on the recommendation made by ESPEN on analysis of micronutrient status in IBD patients on a routine basis, but only after ruling out the effect that systemic inflammatory response may have on plasma micronutrient measurements. It also generates the research hypothesis that zinc and selenium supplementation may be used to improve disease outcomes in patients with CD and UC, respectively,” concluded investigators.¹

References

1. Brownson E, Saunders J, Jatkowska A, et al. Micronutrient status and prediction of disease outcome in adults with inflammatory bowel disease receiving biologic therapy. Inflammatory Bowel Diseases. Published online 2023. doi:10.1093/ibd/izad174
2. Crohn’s & Colitis Foundation. Malnutrition and IBD. Diet & Nutrition. Accessed August 28, 2023. https://www.crohnscolitisfoundation.org/diet-and-nutrition/malnutrition-and-ibd.