The purpose of this study was to examine whether intestinal beta-carotene cleavage activity, measured with the dioxygenase assay, is affected by vitamin A intake and whether this in vitro activity is a determinant of beta-carotene cleavage in vivo, measured in lymph-cannulated rats. Six groups of 10-20 rats were fed a diet with a low, normal or high retinyl palmitate concentration (120 RE, 1200 RE and 12,000 RE per kg, respectively) for 14 to 18 wk, either supplemented or not with 50 mg beta-carotene/kg in the last 6 wk. Intestinal dioxygenase activity was 90% higher (P < 0.05) in the animals fed the unsupplemented low vitamin A diet than in the animals fed the unsupplemented high vitamin A diet, whereas in beta-carotene-supplemented rats intestinal dioxygenase activity was significantly lower than in unsupplemented rats. The molar ratio between retinyl esters and beta-carotene in lymph collected over 8 h after a single intestinal dose of beta-carotene (250 micrograms) to beta-carotene-unsupplemented rats fed the three levels of vitamin A was correlated with intestinal dioxygenase activity (r = 0.66, P = 0.003). Dioxygenase activity in the liver was not affected by the vitamin A concentration of the diet but was 70% higher in the beta-carotene-supplemented rats. Based on the difference in liver vitamin A contents between beta-carotene-supplemented and unsupplemented rats we estimated beta-carotene conversion factors of 9:1 for the rats fed the high vitamin A diet and 4:1 for the rats fed the normal and low vitamin A diets. Intestinal beta-carotene cleavage activity is higher in vitamin A-deficient rats than in rats with a high intake of either vitamin A or beta-carotene. The intestinal dioxygenase activity as measured in vitro is an adequate indicator of in vivo beta-carotene cleavage activity.
SummaryBackgroundThere are plausible mechanisms for how dietary docosahexaenoic acid (DHA), an n−3 polyunsaturated fatty acid, could prevent Crohn's disease (CD).AimTo conduct a prospective study to investigate the association between increased intake of DHA and risk of CD.MethodsOverall, 229 702 participants were recruited from nine European centres between 1991 and 1998. At recruitment, dietary intakes of DHA and fatty acids were measured using validated food frequency questionnaires. The cohort was monitored through to June 2004 to identify participants who developed incident CD. In a nested case–control analysis, each case was matched with four controls; odds ratios (ORs) were calculated for quintiles of DHA intake, adjusted for total energy intake, smoking, other dietary fatty acids, dietary vitamin D and body mass index.ResultsSeventy‐three participants developed incident CD. All higher quintiles of DHA intake were inversely associated with development of CD; the highest quintile had the greatest effect size (OR = 0.07; 95% CI = 0.02–0.81). The OR trend across quintiles of DHA was 0.54 (95% CI = 0.30–0.99, Ptrend = 0.04). Including BMI in the multivariate analysis, due to its correlation with dietary fat showed similar associations. There were no associations with the other dietary fatty acids studied.ConclusionThere were inverse associations, with a biological gradient between increasing dietary docosahexaenoic acid intakes and incident Crohn's disease. Further studies in other populations should measure docosahexaenoic acid to determine if the association is consistent and the hypothesis tested in randomised controlled trials of purely docosahexaenoic acid supplementation.
Summary
Background
Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions.
Aim
To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD
Methods
In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24.
Results
We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8–22) and 6 weeks (IQR 5–10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005).
Conclusions
Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.
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