Citrulline and the Intestine

Citrulline, a non-protein amino acid, has been playing an important role in scientific research over the last few years. This thesis explores various aspects of citrulline with respect to intestinal disease, short bowel syndrome and intestinal failure. The first important finding was that citrulline as a term has been used at the end of the 19th century-beginning of the 20th century to describe an extract of the C. colocynthis, used as a subcutaneous laxative. Also, old sources have revealed that citrulline was first described as an amino acid by Koga and Ohtake (1914) and not by Wada (1930a). From the systematic review and meta-analysis, citrulline levels are strongly positively correlated with small bowel length in short bowel syndrome patients and strongly negatively correlated with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, mucositis, acute rejection in intestinal transplantation, but not Crohn’s disease). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and citrulline levels compared to controls were reduced by 10 μmol/L. These findings suggest that citrulline is a marker of possible acute intestinal injury or intestinal insufficiency. Next, an original five-by-five cross-over study was designed (Williams design) comparing post-absorptive amino acid concentrations after challenges with citrulline, arginine, glutamine, 3-methyl-hisitidine and placebo. Citrulline was the most potent stimulator for all other amino acids, contrary to beliefs of glutamine challenges. Citrulline challenges could be useful in intestinal failure but also in liver failure where urea cycle pathways including glutamine, arginine and ornithine are implicated. The final study was an investigation of quality of life in short bowel syndrome patients. The quality of life scale is highly reliable in short bowel syndrome patients (Cronbach’s alpha > 0.700) and the main causes of low quality of life are fatigue, diarrhoea/increased stomal output, lack of sleep, gastrointestinal symptoms, and muscle pains

Was citrulline first a laxative substance? The truth about modern citrulline and its isolation

Citrulline is a non-protein amino acid and is produced by the enterocytes of the small bowel. The isolation though of citrulline is generally ascribed to the 1930s. In the present article, we demonstrated that before 1930, there is was use of the term citrulline, signifying though a resin produced by Citrullus Colocynthis. This citrulline is different fomr modern citrulline. However, neither was modern citrulline isolated in 1930 but somewhat earlier. Reviewing the original manuscripts, Koga and Ohtake (1914) did indeed isolate citrulline for the first time and at least half a dozen other researchers cite their work. Even though their work didn’t lead to the determination of the structure and nature of citrulline, theirs was the first to isolate it. Our results have a certain historical and scientific significance and are discussed in extent

Perceived acceptability of partial enteral nutrition (PEN) using oral nutritional supplement drinks in adolescent and adult Crohn’s Disease outpatients: a feasibility study

BACKGROUND AND AIMS: Studies, mainly in Japanese cohorts, have shown that partial enteral nutrition (PEN) including oral nutritional supplement (ONS) drinks can prolong disease remission and increase drug effectiveness in Crohn’s disease (CD). Acceptability is a key feasibility parameter to determine whether PEN is a viable treatment option in UK CD patients. We report the results of a single centre cross-sectional feasibility study carried out to investigate perceived acceptability of PEN using ONS drinks and whether ONS preference varies with sex, nutritional status or phenylthiocarbamide (PTC) sensitivity. METHODS: Patients with a confirmed CD diagnosis were recruited using convenience sampling from an adult and adolescent gastroenterology outpatient clinic over 3 years. Blind taste testing of 5 polymeric ONS drinks was conducted using a validated 9-point hedonic rating scale followed by completion of the acceptability questionnaire based on the preferred ONS drink. A subset of patients took home the preferred ONS for a 7-day study. RESULTS: 105 CD patients (55 males), aged 34.9 (±15.4) years were recruited and 28 patients completed the 7-day ONS study. Overall impression scores did not significantly vary with nutritional status, sex, BMI, handgrip strength (HGS), mid-upper arm circumference (MUAC) or PTC sensitivity. Ensure plus™ milkshake rated highest for overall impression (6.5, p=<0.0001) and all other organoleptic properties (p<0.0001). The main perceived benefits of using ONS drinks as PEN related to assurance of nutrient intake (89.3%), convenience (85.7%), and improvement of gut symptoms (84.6%). The main perceived barriers related to reduction in pleasure from eating and drinking (55.6%), struggle with drink storage (53.6%) and increased tiredness than if eating 3 solid meals daily (52%%). 64.8% of patients would consider using PEN as a maintenance treatment option. 81.0% of patients felt confident about consuming ONS drinks daily as PEN for three months but this dropped to 63.8% and 37.1% at 6 and 12 months, respectively. There was a significant drop in perceived ease of use as PEN after the 7-day ONS study (P=0.01). CONCLUSION: Use of ONS drinks as PEN have high perceived benefits and appear to be a feasible option for short-term use of 3-6 months in CD patients. However, confidence in long-term use of ONS drinks as PEN is low mainly due to the perceived social impact. Future studies should assess longer trial periods and volume of ONS drinks to increase the validity of these findings

Temperature dependence of the Brewer global UV measurements

Spectral measurements of global UV irradiance recorded by Brewer spectrophotometers can be significantly affected by instrument-specific optical and mechanical features. Thus, proper corrections are needed in order to reduce the associated uncertainties to within acceptable levels. The present study aims to contribute to the reduction of uncertainties originating from changes in the Brewer internal temperature, which affect the performance of the optical and electronic parts, and subsequently the response of the instrument. Until now, measurements of the irradiance from various types of lamps at different temperatures have been used to characterize the instruments' temperature dependence. The use of 50 W lamps was found to induce errors in the characterization due to changes in the transmissivity of the Teflon diffuser as it warms up by the heat of the lamp. In contrast, the use of 200 or 1000 W lamps is considered more appropriate because they are positioned at longer distances from the diffuser so that warming is negligible. Temperature gradients inside the instrument can cause mechanical stresses which can affect the instrument's optical characteristics. Therefore, during the temperature-dependence characterization procedure warming or cooling must be slow enough to minimize these effects. In this study, results of the temperature characterization of eight different Brewer spectrophotometers operating in Greece, Finland, Germany and Spain are presented. It was found that the instruments' response changes differently in different temperature regions due to different responses of the diffusers' transmittance. The temperature correction factors derived for the Brewer spectrophotometers operating at Thessaloniki, Greece, and Sodankylä, Finland, were evaluated and were found to remove the temperature dependence of the instruments' sensitivity.This article is based upon work from COST Action ES1207 “A European Brewer Network (EUBREWNET)”, supported by COST (European Cooperation in Science and Technology) and from the ENV59-ATMOZ (“Traceability for atmospheric total column ozone”) Joint Research Programme (JRP)

Exercise and redox status responses following alpha-lipoic acid supplementation in G6PD deficient individuals

G6PD deficiency renders cells more susceptible to oxidative insults, while antioxidant dietary supplementation could restore redox balance and ameliorate exercise-induced oxidative stress. To examine the effects of alpha-lipoic acid (ALA) supplementation on redox status indices in G6PD deficient individuals, eight male adults with G6PD deficiency (D) participated in this randomized double-blind placebo-controlled crossover trial. Participants were randomly assigned to receive ALA (600 mg/day) or placebo for 4 weeks separated by a 4-week washout period. Before and at the end of each treatment period, participants exercised following an exhaustive treadmill exercise protocol. Blood samples were obtained before (at rest), immediately after and 1h after exercise for later analysis of total antioxidant capacity (TAC), uric acid, bilirubin, thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC). ALA resulted in significantly increased resting TAC and bilirubin concentrations. Moreover, TAC increased immediately and 1h after exercise following both treatment periods, whereas bilirubin increased immediately after and 1h after exercise following only ALA. No significant change in uric acid, TBARS or PC was observed at any time point. ALA supplementation for 4 weeks may enhance antioxidant status in G6PD individuals; however, it does not affect redox responses to acute exercise until exhaustion or exercise performance

Refeeding syndrome in adults receiving total parenteral nutrition: An audit of practice at a tertiary UK centre

Background & aims: The key to preventing refeeding syndrome (RS) is identifying and appropriately managing patients at risk. We evaluated our clinical management of RS risk in patients starting total parenteral nutrition (TPN). / Methods: Patients commencing TPN at University College London Hospital between January and July 2015 were prospectively followed-up for 7-days. Eighty patients were risk assessed for RS and categorized into risk groups. High and low risk RS groups were compared focussing on the onset of biochemical features of RS (hypophosphatemia, hypokalaemia and hypomagnesemia) and initial clinical assessment. Statistical analysis was conducted using t-tests and Mann–Whitney U tests. / Results: Sixty patients (75%) were identified as high-risk for RS and received lower initial calories (12.8 kcal/kg/day, p < 0.05). All high-risk patients received a high potency vitamin preparation compared to 35% in the low risk group (p < 0.05). Daily phosphate, magnesium and potassium plasma levels were monitored for seven days in 25%, 30% and 53.8% of patients, respectively. Hypophosphatemia developed in 30% and hypomagnesaemia and hypokalaemia in 27.5% of all patients. Approximately 84% of patients had one or more electrolyte abnormalities, which occurred more frequently in high-risk RS patients (p < 0.05). Low risk patients developed mild hypophosphatemia at a much lower percentage than high-risk RS (20% vs 33.3%, respectively). / Conclusion: A significant proportion of patients commencing TPN developed biochemical features of RS (but no more serious complications) despite nutritional assessment, treatment, and follow up in accordance with national recommendations. High vs low risk RS patients were more likely to have electrolyte abnormalities after receiving TPN regardless of preventative measures. Additional research is required to further optimise the initial nutritional approach to prevent RS in high-risk patients

Enteral Nutrition in Adult Crohn’s Disease: Toward a Paradigm Shift

Medical and surgical treatments for Crohn’s disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn’s disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn’s disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed

Joint Hypermobility Syndrome Affects Response to a Low Fermentable Oligosaccharide, Disaccharide, Monosaccharide and Polyol Diet in Irritable Bowel Syndrome Patients: A Retrospective Study

Background: The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet causes significant clinical improvement in patients with irritable bowel syndrome (IBS). Joint hypermobility syndrome (JHS), defined as musculoskeletal symptoms in a hypermobile individual in the absence of systemic rheumatological disease, may be associated with functional gastrointestinal symptoms, including IBS. The aim of this study is to examine whether JHS can affect the response to the low FODMAP diet in patients with IBS. Methods: In this retrospective study, we included patients with IBS according to Rome III criteria who had followed a low FODMAP diet. Symptoms scores were measured before and after the low FODMAP diet. Results: A total of 165 patients (130 females, age 44 ± 14 years) were included. Diarrhea predominant IBS (IBS-D) was present in 40.6% of our patients while JHS was present in 21.2%. The score for abdominal pain was higher for JHS compared to non-JHS prior to intervention (P = 0.011). Symptoms improved in both groups of patients after a low FODMAP diet (P < 0.0001). The largest effects were shown with significant decreases of the average score and bloating. When broken down by JHS and IBS type, a low FODMAP diet significantly improved pain, bloating, diarrhea, constipation, and the average score with the largest effect in JHS/constipation predominant IBS (IBS-C), JHS/mixed IBS and unclassified IBS (IBS-M), JHS/IBS-D, non-JHS/IBS-C and JHS/IBS-M, respectively. Conclusions: Our study suggests that a low FODMAP diet has a greater effect on IBS symptoms in JHS than non-JHS patients

Clinical and Nutritional Care Pathways of Patients with Malignant Bowel Obstruction: A Retrospective Analysis in a Tertiary UK Center

We describe a retrospective cohort study of patients with malignant bowel obstruction to examine their nutritional care pathways between 1.1.16 and 31.12.16 with readmissions until 31.12.17. Data were analyzed by comparing patients who were referred (R) and not referred (NR) for PN. We identified 72 patients with 117 MBO admissions (mean ± SD age:63.1 ± 13.1yrs, 79% female). 24/72 patients were in R group. Predominant primary malignancies were gynaecological and lower-gastrointestinal cancers (76%). 83% patients had metastases (61% sub-diaphragmatically). All patients were at high-risk of malnutrition and baseline mean weight loss was 7%. Discussion of PN at multidisciplinary team meeting (MDT) (22% vs.5%, P = 0.02) and dietetic contact (94% vs. 41%, P < 0.0001) were more likely to occur in the R group. In 13/69 MBO admissions in NR group, reasons for non-referral were unclear. Median baseline and follow-up weight was similar (55–55.8 kg). Overall survival was 4.7 (1.4–15.2)months, with no differences by referral groups. We compared a sub-sample of patients who ‘may have’ required PN (n = 10) vs. those discharged on home PN (n = 10) and found greater survival in the HPN group (323vs.91 day, P < 0.01). Our findings highlight disparity in care pathways suggesting that nutritional care should be integrated into clinical management discussion(s) at MDT to ensure equal access to nutritional services