Adverse gastrointestinal effects of arginine and related amino acids

Oral supplements of arginine and citrulline increase local nitric oxide (NO production in the small intestine and this may be harmful under certain circumstances. Gastrointestinal toxicity was therefore reviewed with respect to the intestinal physiology of arginine, citrulline, ornithine, and cystine (which shares the same transporter) and the many clinical trials of supplements of the dibasic amino acids or N-acetylcysteine (NAC. The human intestinal dibasic amino acid transport system has high affinity and low capacity. L-Arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion that is mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue at high levels. The action of many laxatives is NO mediated and there are reports of diarrhea following oral administration of arginine or ornithine ihine. The clinical data cover a wide span of arginine intakes f rom 3 g/d to > 100 g/d, but the standard of reporting adverse effects (e.g. nausea, vomiting, and diarrhea) was variable. Single doses of 3-6 g rarely provoked side effects and healthy athletes appeared to be more susceptible than diabetic patients to gastrointestinal symptoms at individual doses >9 g. This may relate to an effect of disease on gastrointestinal motility and pharmacokinetics. Most side effects of arginine and NAC occurred at single doses of >9 g in adults >140 mg/kg) often when part of a daily regime of similar to>30 g/d (>174 mmol/d). In the case of arginine, this compares with the laxative threshold of the nonabsorbed disaccharide alcohol, lactitol (74 g or 194 mmol). Adverse effects seemed dependent on the dosage regime and disappeared if divided doses were ingested (unlike lactitol). Large single doses of poorly absorbed amino acids seem to provoke diarrhea. More research is needed to refine dosage strategies that reduce this phenomenon. It is suggested that dipeptide forms of arginine may meet this criterion.

Physiological and bifidogenic effects of prebiotic supplements in infant formulae

This randomized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides (GOS), oligofructose and long-chain inulin (FOS) in formula. Subjects were randomized to Orafti Synergy1 (50 oligofructose: 50 FOS) 0.4g/dl or 0.8g/dl, GOS:FOS (90:10) 0.8g/dl or a standard formula according to Good Clinical Practise (GCP) guidelines. A breast-fed group was included for comparison. Outcome parameters were weight, length, intake, stool characteristics, crying, regurgitation, vomiting, adverse events and fecal bacterial population counts. Statistical analyses used non-parametric tests. During the first month of life weight, length, intake and crying increased significantly in all groups. Regurgitation and vomiting scores were low and similar. Stool frequency decreased significantly and similarly in all formula groups but was lower than in the breast-fed. All prebiotic groups maintained soft stools, only slightly harder than those of breast-fed infants. The standard group had significantly harder stools at wks 2 and 4 compared to 1 (P<0.001 & P=0.0279). The total number of fecal bacteria increased in all prebiotic groups (9.82, 9.73 and 9.91 to 10.34, 10.38 and 10.37, respectively, log10 cells/g feces, P=0.2298) and resembled more the breast-fed pattern. Numbers of lactic acid bacteria, bacteroides and clostridia were comparable. In the SYN1 0.8 g/dl and GOS:FOS groups Bifidobacterium counts were significantly higher at D14 & 28 compared to D3 and comparable to the breast-fed group. Tolerance and growth were normal. In conclusion, stool consistency and bacterial composition of infants taking SYN1 0.8 g/dl or GOS:FOS supplemented formula was closer to the breast-fed pattern. There was no risk for dehydration.

A double-blind, placebo-controlled, randomized human study assessing the capacity of a novel galacto-oligosaccharide mixture in reducing travellers' diarrhoea.

Background/Objectives: Prebiotics have attracted interest for their ability to positively affect the colonic microbiota composition, thus increasing resistance to infection and diarrhoeal disease. This study assessed the effectiveness of a prebiotic galacto-oligosaccharide mixture (B-GOS) on the severity and/or incidence of travellers' diarrhoea (TD) in healthy subjects. Subjects/Methods: The study was a placebo-controlled, randomized, double blind of parallel design in 159 healthy volunteers, who travelled for minimum of 2 weeks to a country of low or high risk for TD. The investigational product was the B-GOS and the placebo was maltodextrin. Volunteers were randomized into groups with an equal probability of receiving either the prebiotic or placebo. The protocol comprised of a 1 week pre-holiday period recording bowel habit, while receiving intervention and the holiday period. Bowel habit included the number of bowel movements and average consistency of the stools as well as occurrence of abdominal discomfort, flatulence, bloating or vomiting. A clinical report was completed in the case of diarrhoeal incidence. A post-study questionnaire was also completed by all subjects on their return. Results: Results showed significant differences between the B-GOS and the placebo group in the incidence (P<0.05) and duration (P<0.05) of TD. Similar findings occurred on abdominal pain (P<0.05) and the overall quality of life assessment (P<0.05). Conclusions: Consumption of the tested galacto-oligosaccharide mixture showed significant potential in preventing the incidence and symptoms of TD.

Rodents as carriers of disease: preliminary studies in the United Kingdom

The University of Reading has conducted some preliminary work on the prevalence of Campylobacter spp., Salmonella spp. and Arenavirus in Norway rats trapped from farms and semi-urban areas in central southern England. Campylobacter is the cause of a notificable disease in the UK, with 57,772 cases reported for England and Wales in 2009. Transmission to humans is believed to be primarily through undercooked meat, from contaminated water, and through contact with pets; and symptoms include a high temperature, severe diarrhoea, vomiting and abdominal pain. Ninety-seven per-cent of sporadic cases have been attributed to farm animals, and in particular the meat and poultry industry. There are eighteen species of Campylobacter, eleven of which can be pathogenic to humans; although the principal species that cause gastrointestinal disease in humans are C. jejuni and C. coli; although C. lari, C. helveticus and C. upsaliensis are also involved. Salmonella species also causes a gastrointestinal disease, and in the UK, is common in chicken and has been linked to egg production. Species are typed using antigen specific agglutination tests, or by their susceptibility to specific bacteriophage. Some strains are known to be linked with human disease (eg. S. enteritidis PT4).

Parent-reported gastro-intestinal symptoms in children with autism spectrum disorders

The objective of this study is to investigate whether parentally-reported gastro-intestinal (GI) symptoms are increased in a population-derived sample of children with autism spectrum disorders (ASD) compared to controls. Participants included 132 children with ASD and 81 with special educational needs (SEN) but no ASD, aged 10-14 years plus 82 typically developing (TD) children. Data were collected on GI symptoms, diet, cognitive abilities, and developmental histories. Nearly half (weighted rate 46.5 %) of children with ASD had at least one individual lifetime GI symptom compared with 21.8 % of TD children and 29.2 % of those with SEN. Children with ASD had more past and current GI symptoms than TD or SEN groups although fewer current symptoms were reported in all groups compared with the past. The ASD group had significantly increased past vomiting and diarrhoea compared with the TD group and more abdominal pain than the SEN group. The ASD group had more current constipation (when defined as bowel movement less than three times per week) and soiling than either the TD or SEN groups. No association was found between GI symptoms and intellectual ability, ASD severity, ASD regression or limited or faddy diet. Parents report more GI symptoms in children with ASD than children with either SEN or TD children but the frequency of reported symptoms is greater in the past than currently in all groups.