The nutritional state in adults Crohn’s Disease remission

Abstract

Crohn’s Disease (CD) is characterised by a dysregulated intestinal immune response to an altered host microbiota, leading to intestinal inflammation, accumulated tissue injury, and constitutional malaise. Treatment aims to suppress the immune system and induce and maintain clinical and endoscopic remission. Effective medications are available to alter the disease course. However, the response is variable; the benefit may be short-lived, and poor quality of remission may remain due to residual disease activity and symptom burden. A third of remission cohorts report severe fatigue. Fatigue is poorly understood and has limited effective treatment options. Untreated Crohn’s disease may alter the nutritional state through loss of appetite, food-related symptoms, increased loss through diarrhoea and alerted requirements through inflammation. The existing literature on the nutritional state of CD is from mixed populations with variable disease activity, often from a time before effective medical therapies.
The central hypothesis of the work described in this thesis was that adults with Crohn’s disease in clinical remission may have an under-diagnosed and underappreciated poor nutritional state and those with a poor nutritional state will have a greater degree of disease-related fatigue and worse health-related quality of life.
The systematic review on micronutrient status in adults with CD in remission found nine eligible studies reporting low circulating levels of Vitamins B6, B12, C, D, and Magnesium and Selenium. There was insufficient information to determine the likely prevalence of micronutrient deficiency from blood biochemistry, nor to understand the causes and clinical consequences of the micronutrient blood tests. The first experimental chapter describes a time-limited trial of a nutritional intervention, Exclusive Enteral Nutrition, in 24 adults with CD in clinical and biochemical remission (faecal calprotectin <250µg/g). The nutritional and clinical state was assessed at 3 time-points, from the perspectives of intake (food diary analysis), micronutrient status and body composition (using anthropometry and bioelectrical impedance) before (assessment 1) and after (2) the intervention and on return to the free diet (3).
Assessment 1 identified inadequacies of micronutrient intake in habitual diet, abnormal micronutrient biochemistry, sarcopenia, reduced phase angle (bioelectrical impedance measurement, which when reduced has been correlated to poor outcomes and nutritional risk), and excess fatigue among the study subjects. At Assessment 2 (after the nutritional intervention), there were statistically significant improvements in intake, micronutrient biochemistry, Phase Angle, and a trend towards improving fatigue (SF36 vitality scores). The study suggested that nutritional issues are present in CD remission, and nutritional and fatigue may be amenable to nutritional intervention. This was followed by an observational cohort study in 200 patients with CD in remission to explore the relationship between nutritional state and the quality of remission (as marked by FACIT-F). Complete data was available for 194 subjects. Severe fatigue was evident in 26% of patients; FACIT-F scores correlated with SF36 vitality scores. Conventional screening tools identified very few patients at nutritional risk, whereas more detailed assessments revealed nutritional concerns. Food diary analysis showed that dietary inadequacies were common, most obviously in those with dietary impact factors and food-related symptoms, which were worse among those with severe fatigue. Excess adiposity (18%) and a lack of lean mass (14%) were evident, and the Standardised Phase Angle was reduced. Phase Angle was lower, and excess adiposity was higher in those with severe fatigue. Blood micronutrient biochemistry analysis was inconclusive without reference ranges but revealed a weak correlation between liposoluble antioxidant Vitamins and FACIT-F.
This thesis shows that adults with Crohn’s disease may have a variable quality of remission, including excessive fatigue and altered nutritional state. CD remission can have a burden of residual symptoms, and these may be related to the patient's nutritional state and may be amenable to intervention. Future appropriately powered studies into nutritional interventions have the potential to demonstrate a novel avenue of treatment for improving CD remission.

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