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The synergistic effect of herbal medicine and probiotics in pediatric functional constipation: A systematic review and meta-analysis.
Kim, E, Chang, S, Nam, J, Park, N, Min, SY
Medicine. 2024;103(7):e36899
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Paediatric functional constipation (PFC) is a prevalent gastrointestinal disorder in children. The initial approach to managing PFC involves demystification, education, toilet training, and the use of laxatives. Using laxatives can lead to various adverse effects therefore, patients with functional constipation typically adopt a self-management approach and explore complementary and alternative therapies. The aim of this study was to analyse the synergistic effect of herbal medicine (HM) combined with probiotics in the treatment of PFC, by comparing it to the use of probiotics alone. This study was a systematic review and meta-analysis of twenty-two randomised controlled trials. Results showed that the combination of HM with probiotics may yield significantly greater benefits for total effective rate when compared to probiotics alone. Furthermore, HM combined with probiotics could potentially reduce the recurrence rate by 70% compared to probiotics alone. Authors concluded that HM could potentially offer advantages in enhancing the efficacy rate and Bristol faecal score, influencing gastrointestinal peptide hormones, decreasing inflammation indicators and lowering the recurrence rate among children with functional constipation.
Abstract
BACKGROUND Pediatric functional constipation (PFC) is a prevalent and persistent gastrointestinal disorder, that requires various treatments, including alternative approaches. This review assessed the synergistic efficacy of herbal medicine (HM) and probiotics for PFC. METHODS We conducted a comprehensive search of 11 databases, including English, Chinese, and Korean databases, until June 29, 2023. The inclusion criteria were randomized clinical trials (RCTs) comparing the intervention of HM with probiotics to that of the same probiotics. Statistical analyses included calculation of the mean difference (MD), standardized MD, risk ratio (RR) with a 95% confidence interval (CI), and assessment of risk of bias using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation rating system was used to evaluate evidence quality. Potential publication bias was assessed using funnel plots, Egger test, the fail-safe N test, and Duval and Tweedie trim and fill method. RESULTS A total of 22 RCTs involving 2228 patients were included in the meta-analysis. The HM and probiotics group exhibited superior outcomes compared to the probiotics alone group in various parameters: total effective rate (RR: 1.24, 95% CI: 1.19-1.29, P < .001), Bristol fecal Score (MD: 0.80, 95% CI: 0.71-0.89, P < .001), gastrointestinal peptide hormone (motilin) (MD: 35.37, 95% CI: 24.64-64.10, P < .001), inflammation indicator (nitrous oxide) (MD: -12.45, 95% CI: -15.12 to -9.77, P < .001), minimal sensitive volume of the rectum (MD: -8.7, 95% CI: -10.91 to -6.49, P < .001), and recurrence rate (RR: 0.30, 95% CI: 0.21-0.43, P < .001). CONCLUSION The combination of HM and probiotics may exhibit a synergistic effect on PFC. Nevertheless, it is imperative to undertake rigorously planned RCTs to comprehensively evaluate the synergistic efficacy of HM and probiotics.
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.
Ceballos-Rasgado, M, Lowe, NM, Mallard, S, Clegg, A, Moran, VH, Harris, C, Montez, J, Xipsiti, M
Advances in nutrition (Bethesda, Md.). 2022;13(6):2488-2518
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The upper limit of a nutrient’s intake has been defined as the maximum intake from food, water, and supplements that is unlikely to pose risk of adverse health effects to most individuals in the general population. The aim of this study was to determine the levels of zinc intake at which adverse effects are observed in children aged 0–3 years. This study is a systematic review and meta-analysis of fifty-eight articles from fifty-five studies. Almost all studies were randomised controlled studies (n=52) and the rest were quasi-experimental studies. Results show: - that zinc supplementation had a significant adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, haemoglobin, haematocrit, and the odds of anaemia in ≥1 of the subgroups of pooled data. - a significant reduction of the lactulose:mannitol ratio. - that there weren’t significant effects of zinc supplementation on c-reactive protein, erythrocyte superoxide dismutase [antioxidant enzyme], zinc protoporphyrin [chemical compound], blood cholesterol, or iron deficiency anaemia Authors conclude that the recommended maximum zinc doses might need to be adjusted for children at risk or recovering from iron or copper deficiency. Additionally, the study’s findings may be used to undertake dose–response modelling to estimate tolerable upper intake levels of zinc in children aged 0–3 years.
Abstract
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial.
Zhang, X, Chen, S, Zhang, M, Ren, F, Ren, Y, Li, Y, Liu, N, Zhang, Y, Zhang, Q, Wang, R
Nutrients. 2021;13(7)
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Constipation is a common complaint among people with depression and may negatively affect their quality of life. In association with this, previous studies have shown a correlation between the reduction of Lactobacillus or Bifidobacterium strains in the gut of patients with major depressive disorder. Thus, this two-arm, parallel-design, randomised, double-blinded, placebo-controlled trial examined the effects of supplementing fermented milk with Lacticaseibacillus paracasei Strain Shirota or LcS (previously known as Lactobacillus casei strain Shirota) on constipation in people with depression. Symptoms of constipation, stool problems, and depressive symptoms improved after 9 weeks of consuming fermented milk containing LcS. The abundance of Adlercreutzia, Megasphaera, and Veillonella increased significantly in the intervention group. In contrast, the abundance of bacteria related to mental disorders such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter significantly decreased after the intervention. After 9 weeks of intervention with LcS, a significant reduction in serum proinflammatory cytokines such as IL-1β, IL-6, and TNF-α was observed in patients with depression. The intervention group also showed a decrease in inflammation-causing bacteria, Surrerella, which correlated with a reduction in proinflammatory cytokines. The mechanisms driving the changes in gut microbial composition, depression, and gastrointestinal symptoms after LcS intervention need to be evaluated in more robust studies. Healthcare professionals can use the results of the study to better understand how probiotics can reduce constipation and depression and improve gut microbial composition.
Abstract
Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
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An algorithm for differentiating food antigen-related gastrointestinal symptoms.
Rostami, K, Bold, J, Ismail Ali, J, Parr, A, Dieterich, W, Zopf, Y, Htoo, A, Rostami-Nejad, M, Danciu, M
Gastroenterology and hepatology from bed to bench. 2021;14(1):8-16
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Irritable bowel syndrome (IBS) is a collection of gastrointestinal symptoms. Due to multiple etiologies, the pathogenesis of IBS is poorly understood. The aim of this audit was to assess the outcomes achieved using a lactose and gluten-free diet clinical intervention in patients traditionally diagnosed with IBS. This study was an audit of outcomes from the records of 149 patients presenting with IBS symptoms at secondary and tertiary Gastroenterology outpatients in two UK hospitals. This audit has demonstrated that more than 70% of patients presenting with IBS symptoms improved by following a diet eliminating lactose and gluten containing grains (improvement for >30% in their symptoms). The success of the elimination diet did not seem to be correlated with the body mass index (BMI). The best outcome was recorded in patients with normal BMI and also in the overweight group. Patients with higher BMI >30 or low below 18 also responded well to nutrition therapy. In conclusion, multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
Abstract
AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
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Probiotic Lactobacillus casei: Effective for Managing Childhood Diarrhea by Altering Gut Microbiota and Attenuating Fecal Inflammatory Markers.
Lai, HH, Chiu, CH, Kong, MS, Chang, CJ, Chen, CC
Nutrients. 2019;11(5)
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Acute diarrhoea caused by pathogens may induce gastroenteritis (inflammation of the stomach and intestines), bloody stool, or severe intra-abdominal infections that establish disease and increase the economic burden, especially among infantile and childhood populations. The aim of the study was to determine whether probiotics (Lactobacilluscasei) inhibited gastrointestinal infection and reduced the associated inflammatory response. The study is a prospective, randomized, case-controlled study which enrolled 81 children aged between 6 months and 6 years. The participants were divided into 2 groups (Lactobacilluscasei variety rhamnosus treatment and a no probiotic control). Study results indicate that probiotics can reduce the severity and duration of diarrhoea. Furthermore, probiotic colonisation improved bowel habits and reduced abdominal pain or colic and bloating. Authors conclude that the efficacy of probiotic preparations for the treatment of acute childhood diarrhoea is related to individual bacteria strains. Thus, the population and modulation of intestinal gut/probiotic bacteria can be restored through the reduction of intestinal inflammatory reactions.
Abstract
BACKGROUND Acute diarrhea is a major cause of childhood morbidity and an economic burden for families. The aim of this study is to explore the effect of probiotics on clinical symptoms, intestinal microbiota, and inflammatory markers during childhood diarrhea. METHODS Children (n = 81) aged six months to six years (mean age 2.31 years) hospitalized for acute diarrhea were randomized to receive probiotics (Lactobacillus casei variety rhamnosus; n = 42) or no probiotics (n = 39) orally twice daily for seven days. Feces samples were also collected to evaluate microbial content using a traditional agar plate and next-generation sequencing. Immunoglobulin A (IgA), lactoferrin, and calprotectin were determined by enzyme-linked immunosorbent assay (ELISA) and compared in different groups. Other clinical symptoms or signs, including fever, vomiting, diarrhea, abdominal pain, bloated abdomen, daily intake, appetite, and body weight were also assessed. RESULTS Data were collected from 81 individuals across three different time points. Total fecal IgA levels in fecal extracts of the probiotics group were higher than those in the control group, reaching statistical significance (p < 0.05). Concentrations of fecal lactoferrin and calprotectin were significantly downregulated in patients with probiotic Lactobacillus casei variety rhamnosus (Lc) consumption compared to those of the control (p < 0.05). Probiotic Lc administration may be beneficial for gut-microbiota modulation, as shown by the data collected at one week after enrollment. Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotic group. Appetite and oral intake, body-weight gain, abdominal pain, bloating, as well as bowel habits (diarrhea) were much better in children receiving probiotics compared with those in the control group. CONCLUSION Fecal IgA increased during acute diarrhea under Lc treatment; in contrast, fecal lactoferrin and calprotectin were downregulated during acute diarrhea under Lc treatment. Probiotic Lc may be a useful supplement for application in children during acute diarrhea to reduce clinical severity and intestinal inflammatory reaction.
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Systematic review: probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.
Hungin, APS, Mitchell, CR, Whorwell, P, Mulligan, C, Cole, O, Agréus, L, Fracasso, P, Lionis, C, Mendive, J, Philippart de Foy, JM, et al
Alimentary pharmacology & therapeutics. 2018;47(8):1054-1070
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The role of the gut microbiota in health and disease is far reaching and there is a growing body of evidence on the therapeutic potential of probiotics in gastrointestinal (GI) disease. Patients with GI disease present with a variety of symptoms and current evidence suggests probiotics may play a role in ameliorating these adverse symptoms. The purpose of this review is to update the previous systematic review and incorporate new findings on the role of probiotics in adult patients presenting with a variety of GI symptoms. Based on the updated evidence, this study confirms the finding that specific probiotics are beneficial for certain lower GI problems. According to this review, the author deems this study useful for clinicians when recommending probiotics to patients.
Abstract
BACKGROUND In 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems. AIM: To update the consensus with new evidence. METHODS A systematic review identified randomised, placebo-controlled trials published between January 2012 and June 2017. Evidence was graded, previously developed statements were reassessed by an 8-expert panel, and agreement was reached via Delphi consensus. RESULTS A total of 70 studies were included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea associated with Helicobacter pylori eradication therapy, 7; other conditions, 16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8 reported significant benefits of probiotics vs placebo. Consensus statements with 100% agreement and "high" evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy, and have favourable safety. Statements with 70%-100% agreement and "moderate" evidence indicated that, in some patients with IBS, specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency. CONCLUSIONS This updated review indicates that specific probiotics are beneficial in certain lower GI problems, although many of the new publications did not report benefits of probiotics, possibly due to inclusion of new, less efficacious preparations. Specific probiotics can relieve lower GI symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori eradication therapy, and show favourable safety. This study will help clinicians recommend/prescribe probiotics for specific symptoms.
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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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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.