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Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449].
Dancey, CP, Attree, EA, Brown, KF
Nutrition journal. 2006;5:16
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Plain language summary
Nucleotides are the building blocks of DNA and RNA. Dietary sources of nucleotides are found to varying degrees in many foods – lamb, liver, mushrooms (but not fruit and other vegetables) all are rich in nucleotides. Giving nucleotide supplements to infants has been shown to reduce the incidence and duration of diarrhoea, and animal studies show structural improvements in the intestines when nucleotide supplementation is given. The aim of this study was to test the hypothesis that nucleotide supplements would improve symptoms in people with Irritable Bowel Syndrome (IBS). Thirty-seven people with an IBS diagnosis took part in the study. Participants were asked to rate the severity of their IBS symptoms before and throughout the study period, and psychological measures (anxiety, depression, illness intrusiveness and general health) were also assessed. Participants were assigned to either placebo (56 days) followed by supplement (56 days) or the reverse. The supplement given was IntestAidIB which contained: nucleotides & RNA (concentrated extracts of Saccharomyces cerevisae), hydroxypropyl methylcellulose, FOS (fructo-oligosaccharides), Methionine, Glutamine, Inositol, Lysine, Pantothenic acid (Vitamin B5 as Calcium d-pantothenate), Sodium citrate, Riboflavin (Vitamin B2), Vanillin, Folic acid, and Biotin. The supplement improved the severity of all IBS symptoms, apart from diarrhoea, more than the placebo. Symptom improvement ranged from 4 - 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement and were statistically significant. The differences between groups for diarrhoea, bloating and flatulence were not significant. Although the improvements in symptoms were consistent, the effects were not strong, and the psychological measures showed no improvement. The authors concluded that dietary nucleotide supplementation improves some of the symptoms of IBS. Further studies need to replicate and extend these results, and clarify the mechanism by which improvements occur.
Abstract
BACKGROUND Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 - 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed.
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Dietary fructooligosaccharides affect intestinal barrier function in healthy men.
Ten Bruggencate, SJ, Bovee-Oudenhoven, IM, Lettink-Wissink, ML, Katan, MB, van der Meer, R
The Journal of nutrition. 2006;136(1):70-4
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Fructooligosaccharides (FOS) are nondigestible carbohydrates assumed beneficial because they stimulate the protective colonic microflora (bifidobacteria, lactobacilli) that produce organic acids that, in turn, increase host defence against invasive pathogens. However, studies show that FOS increases cytotoxicity of intestinal contents (fecal water), mucin excretion, and intestinal permeability in rats, reducing resistance to infection (since host defence depends on barrier function). This study aims to prove whether the adverse adverse effects of FOS that occurred before infection in rats would occur in humans. This is important because FOS has been added to a variety of products including dairy products and infant formulas. This is a double-blind, placebo-controlled crossover study design with 2 supplement periods of 2 wk. separated by 1 washout period of 2 wks. 34 healthy men were randomly divided in 2 groups. Subjects consumed either lemonade with 20g of FOS or 6g of sucrose (placebo) per day in 3 divided doses (morning, afternoon, and evening). They avoided dairy products and calcium rich foods (since FOS-induced adverse effects in rats is inhibited by calcium intake), foods high in fermentable nondigestible carbohydrates and pro- or prebiotics. Alcohol consumption was restricted. Habitual diet was otherwise maintained. The lemonade also contained the intestinal permeability marker chromium EDTA (CrEDTA). On the last 2 days of both supplement periods, quantitative food intake (self-reported) was measured, 24-h urine samples taken, and gastrointestinal symptoms rated (visual analogue scale). 24-h fecal samples were also collected. Dietary FOS consumption increased bifidobacteria, lactobacilli, lactic acid and decreased fecal pH. Cytotoxicity of fecal water and urinary and fecal CrEDTA excretion were not affected by FOS. Frequency of flatulence, bloating, abdominal pain and cramps were increased in the FOS period. The concept of stimulating endogenous microflora and intestinal organic acid production by rapid fermentation of nondigestible carbohydrates is beneficial for the intestinal barrier in humans is not supported.
Abstract
In contrast to most expectations, we showed previously that dietary fructooligosaccharides (FOS) stimulate intestinal colonization and translocation of invasive Salmonella enteritidis in rats. Even before infection, FOS increased the cytotoxicity of fecal water, mucin excretion, and intestinal permeability. In the present study, we tested whether FOS has these effects in humans. A double-blind, placebo-controlled, crossover study of 2 x 2 wk, with a washout period of 2 wk, was performed with 34 healthy men. Each day, subjects consumed lemonade containing either 20 g FOS or placebo and the intestinal permeability marker chromium EDTA (CrEDTA). On the last 2 d of each supplement period, subjects scored their gastrointestinal complaints on a visual analog scale and collected feces and urine for 24 h. Fecal lactic acid was measured using a colorimetric enzymatic kit. The cytotoxicity of fecal water was determined with an in vitro bioassay, fecal mucins were quantified fluorimetrically, and intestinal permeability was determined by measuring urinary CrEDTA excretion. In agreement with our animal studies, FOS fermentation increased fecal wet weight, bifidobacteria, lactobacilli, and lactic acid. Consumption of FOS increased flatulence and intestinal bloating. In addition, FOS consumption doubled fecal mucin excretion, indicating mucosal irritation. However, FOS did not affect the cytotoxicity of fecal water and intestinal permeability. The FOS-induced increase in mucin excretion in our human study suggests mucosal irritation in humans, but the overall effects are more moderate than those in rats.