P658 Is vitamin D deficiency related to fat malabsorption or inflammation in Inflammatory Bowel Disease? Preliminary results from the Fat-D study

Background Vitamin D deficiency is highly prevalent in patients with inflammatory bowel disease (IBD). The question of whether vitamin D status is a contributory factor or a consequence of IBD, or maybe both, remains unanswered, and is confounded by the complexity of inflammation, IBD and vitamin D. Fat malabsorption has been proposed as a possible reason for deficiencies of vitamin D in IBD. The aim of this study was to further understanding of vitamin D deficiency in IBD by investigating possible causal relationships of fat malabsorption and inflammation on vitamin D levels in this complex context. Methods In a comparative, cross-sectional study in IBD patients, 25(OH)D was analysed by LCMS/MS. Serum β-carotene levels were used as a biomarker for fat malabsorption. Vitamin K1, another fat-soluble vitamin, was used to affirm a possible causative relation between β-carotene and vitamin D in case of fat malabsorption. β-carotene and vitamin K were measured in serum by HPLC. Inflammation was characterised by serum hsCRP<5mg/L. Results 51 IBD patients (30f;20CD/18UC;45.3±16.3y; 21 with inflammatory activity) were enrolled. In patients with vs. without inflammation, serum 25(OH)D levels were significantly lower (26.5±14.6ng/mL vs. 36.8±12.6ng/mL, p<0.05), while serum vitamin K1 (1.4±0.5µg/L vs. 1.2±0.4µg/L) and β-carotene (28.5±0.6.0µg/dL vs. 35.9±5.4µg/dL) levels were similar (p>0.05). 36/51 of the patients had low serum β-carotene levels, indicating steatorrhoea. Neither 25(OH)D (32.1.5±13.8ng/mL vs. 33.6±15.8ng/mL) nor vitamin K1 (1.3±0.5µg/L vs. 1.2±0.4µg/L) levels differed according to the presence vs. absence of steatorrhoea (p>0.05). Similarly, no correlation was found for 25(OH)D (r=0.024, p=0.875) or serum vitamin K1 (r=0.111, p=0.462) with β-carotene levels. On the other hand, 25(OH)D levels were significantly inversely correlated with hsCRP (r=-0.338, p=0.015), whereas vitamin K1(r=0.050, p=0.731) and β-carotene (r=-0.118, p=0.438) did not show a similar relation. Conclusion Vitamin D levels were confirmed to be related to inflammation in IBD. A lack of correlation with fat malabsorption, as indicated by β-carotene levels, or with steatorrhoea, was found for vitamin D and confirmed by measuring and comparing serum levels of an additional fat-soluble vitamin, K1. We conclude that low vitamin D levels in patients with IBD are related to inflammation rather than fat malabsorption.

From Congenital Disorders of Fat Malabsorption to Understanding Intra-Enterocyte Mechanisms Behind Chylomicron Assembly and Secretion

During the last two decades, a large body of information on the events responsible for intestinal fat digestion and absorption has been accumulated. In particular, many groups have extensively focused on the absorptive phase in order to highlight the critical “players” and the main mechanisms orchestrating the assembly and secretion of chylomicrons (CM) as essential vehicles of alimentary lipids. The major aim of this article is to review understanding derived from basic science and clinical conditions associated with impaired packaging and export of CM. We have particularly insisted on inborn metabolic pathways in humans as well as on genetically modified animal models (recapitulating pathological features). The ultimate goal of this approach is that “experiments of nature” and in vivo model strategy collectively allow gaining novel mechanistic insight and filling the gap between the underlying genetic defect and the apparent clinical phenotype. Thus, uncovering the cause of disease contributes not only to understanding normal physiologic pathway, but also to capturing disorder onset, progression, treatment and prognosis.

Early Diagnosis and Intervention in Cystic Fibrosis: Imagining the Unimaginable

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of cystic fibrosis lung disease, and primary prevention may be achievable.

Effect of Fat-Soluble Vitamins A, D, E and K on Vitamin Status and Metabolic Profile in Patients with Fat Malabsorption with and without Urolithiasis

Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF; n = 10) than in non-stone formers (NSF; n = 41) but decreased significantly in SF patients after supplementation. Plasma vitamin D and E concentrations increased significantly and to a similar extent in both groups during intervention. While plasma vitamin D concentrations did not differ between the groups, vitamin E concentrations were significantly lower in the SF group than the NSF group before and after ADEK supplementation. Although vitamin D concentration increased significantly in both groups, urinary calcium excretion was not affected by ADEK supplementation. The decline in plasma AST activity in patients with urolithiasis might be attributed to the supplementation of ADEK. Patients with fat malabsorption may benefit from the supplementation of fat-soluble vitamins ADEK.