purehealth research

Leaky Gut Revitalize



Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions


In addition to its important role in digestion, absorption and secretion, the gastrointestinal epithelium serves as a barrier to the diffusion of toxins, allergens and pathogens from the luminal contents into the interstitial tissue. Barrier disruption and diffusion of noxious substances are known to induce mucosal inflammation and tissue injury. In fact, the disruption of gut barrier function plays a crucial role in the pathogenesis of numerous gastrointestinal diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease and infectious enterocolitis. The specialized junctional complexes called tight junctions provide the intestinal epithelial barrier function. Loss of tight junction integrity and increased intestinal permeability to macromolecules are associated with the pathogenesis of IBD, IBS and celiac disease. Mucosal protective factors such as growth factors and nutrients preserve the gut barrier integrity and are beneficial in the treatment of various gastrointestinal diseases. L-Glutamine the most abundant amino acid in blood plays a vital role in the maintenance of mucosal integrity. Glutamine is traditionally termed as a nonessential amino acid, is now considered a “conditionally essential” amino acid. Its consumption in small bowel mucosa exceeds the rate of production during catabolic stress such as trauma, sepsis and post surgery [1, 2]. In the small bowel mucosa, glutamine is an unique nutrient providing fuel for metabolism, regulating cell proliferation, repair and maintaining the gut barrier functions [3]. The focus of this article is on the role of L-glutamine in the preservation of gut barrier function and the epithelial tight junction integrity and gut barrier function.

Source: RadhaKrishna Rao, Geetha Samak, “Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions” Journal of Epithelial Biology and Pharmacology, (2012), 5, (Suppl 1-M7) 47-54.

Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial


Background: Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn's disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP.

Aim: We evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD.

Methods: In a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5 g/kg ideal body weight/day for 2 months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system.

Results: Patients (age 34.5 ± 10.5 years; 20 males) were assigned to the GG (n = 15) or ACG (n = 15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2 months was 0.029 (0.006-0.090) and 0.033 (0.009-0.077), respectively, with P = 0.6133. IP normalized in 8 (57.1%) patients in each group (P = 1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2 months was 2.68 (1.02) and 2.49 (0.67), respectively, (P = 0.347). At the end of 2 months LMR improved significantly in GG from 0.071 (0.041-0.254) to 0.029 (0.006-0.090) (P = 0.0012) and in ACG from 0.067 (0.040-0.136) to 0.033 (0.009-0.077) (P = 0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P = 0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P = 0.009).

Conclusions: Intestinal permeability and morphology improved significantly in both glutamine and ACG.

Source: Benjamin J, Makharia G, Ahuja V, Anand Rajan KD, Kalaivani M, Gupta SD, Joshi YK. “Glutamine and whey protein improve intestinal permeability and morphology in patients… a randomized controlled trial.” Digestive Diseases and Sciences. (2012 Apr) 57(4):1000-1012.

Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner


Purpose: To examine the dose–response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat.

Methods: Ten recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg−1 of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of V˙O2max in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise.

Results: Relative to placebo, L:R was likely lower following 0.25 g kg−1 (mean difference: − 0.023; ± 0.021) and 0.5 g kg−1 (− 0.019; ± 0.019) and very likely following 0.9 g kg− 1 (− 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation.

Discussion: Acute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg−1, although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity.

Source: Pugh, J. N., Sage, S., Hutson, M., Doran, D. A., Fleming, S. C., Highton, J., Morton, J. P., & Close, G. L. “Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner.” European journal of applied physiology, (2017) 117(12), 2569–2577. https://doi.org/10.1007/s00421-017-3744-4

l-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer


Role of l-glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. l-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, l-aspargine, l-arginine, l-lysine, or l-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-l-norleucine failed to affect the l-glutamine-mediated protection of barrier function. l-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and β-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and β-catenin from the actin cytoskeleton, and this effect was reduced by l-glutamine. l-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of l-glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor. These results indicate that l-glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.

Source: A. Seth, S. Basuroy, P. Sheth, R. K. Rao. “l-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.” American Journal of Physiology (2004) Volume 287, Issue 3.


Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells


Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin, apigenin, chrysin, and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Source: Pearce FL, Befus AD, Bienenstock J. “Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells.” The Journal of Allergy and Clinical Immunology (1984 Jun);73(6):819-23. doi: 10.1016/0091-6749(84)90453-6. PMID: 6202731.

Dietary polyphenols modulate intestinal barrier defects and inflammation in a murine model of colitis


Some polyphenols have been shown to promote the tight junction (TJ) barrier in intestinal cells. The present study investigated the ameliorative effects of polyphenols, curcumin, quercetin, naringenin or hesperetin, on experimental colitis with a particular focus on the TJ barrier in mice. Administration of dextran sulphate sodium (DSS) caused severe colon damage, indicated by body weight loss, clinical scores, and colon shortening, and TJ barrier impairment, indicated by FITC-dextran permeability. Supplemental feeding of polyphenols (0.3% (w/w)), curcumin, quercetin, naringenin or hesperetin, partially restored these symptoms although the levels of amelioration differed among the polyphenols tested. Feeding naringenin led to more effective restoration. The feeding of each polyphenol restored the expression of TJ proteins, such as zonula occludens-1, occludin, junctional adhesion molecule-A, and claudin-3, impaired by DSS administration. The colon barrier integrity correlated closely with the level of inflammation. Collectively, supplemental feeding of these polyphenols restores DSS-induced colitis, at least in part, through regulation of the colonic TJ barrier.

Source: Mizuki Shigeshiro, Soichi Tanabe, Takuya Suzuki. “Dietary polyphenols modulate intestinal barrier defects and inflammation in a murine model of colitis.” Journal of Functional Foods (2013), Vol 5, Issue 2. 949-955

Zinc Carsonine

Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes


Background: Zinc carnosine (ZnC) is a health food product claimed to possess health‐promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited.

Aim: To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial.

Methods: In vitro studies used pro‐migratory (wounded monolayer) and proliferation ([3H]‐thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small‐intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration.

Results: ZnC stimulated migration and proliferation of cells in a dose‐dependent manner (maximum effects in both assays at 100 µmol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small‐intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered.

Conclusion: ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.

Source: Mahmood, A., FitzGerald, A. J., Marchbank, T., Ntatsaki, E., Murray, D., Ghosh, S., & Playford, R. J. “Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes.” Gut (2007), 56(2), 168–175.

A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders


Zinc-L-carnosine (ZnC), also called polaprezinc known as PepZin GI™, is a chelated compound that contains L-carnosine and zinc. It is a relatively new molecule and has been associated with multiple health benefits. There are several studies that support ZnC’s benefits in restoring the gastric lining, healing other parts of the gastrointestinal (GI) tract, improving taste disorders, improving GI disorders, and enhancing skin and liver. Oral mucositis is a common complication of cytotoxic radiotherapy and/or chemotherapy. It occurs in almost every person with head and neck cancer who receive radiotherapy. It is often overlooked because it is not considered life threatening. However, mucositis often leads to a decreased quality of life and cessation of treatment, ultimately decreasing positive outcomes. Therefore, solutions to address it should be considered. The primary mechanisms of action are thought to be localized and related to ZnC’s anti-inflammatory and antioxidant functions. Therefore, the purpose of this review is to discuss the research related to ZnC and to explore its benefits, especially in the management of conditions related to damaged epithelial cells, such as oral mucositis. Evidence supports the safety and efficacy of ZnC for the maintenance, prevention, and treatment of the mucosal lining and other epithelial tissues. The research supports its use for gastric ulcers (approved in Japan) and conditions of the upper GI and suggests other applications, particularly for oral mucositis.

Source: Hewlings, S., & Kalman, D. “A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders.” Nutrients (2020), 12(3), 665.

Aloe Vera

In vitro activity of Aloe vera inner gel against Helicobacter pylori strains


Aloe barbadensis Miller (Aloe vera) is a herbal remedy widely used for a variety of illnesses; A. vera leaf extracts have been promoted for detoxification, cure constipation, help flush out toxins and wastes from the body, promote digestion and are used in the treatment of peptic ulcer for cytoprotective action. The aim of this study was to evaluate the antibacterial activity of A. vera inner gel against both susceptible and resistant Helicobacter pylori strains isolated in Abruzzo region, Italy. The inner gel of leaves of a 5‐year‐old plant of A. vera was extracted, homogenized and tested from 800 to 1·56 mg ml−1 against 14 clinical strains and one reference strain of H. pylori using the broth microdilution methodology. Furthermore, the sample of A. vera was investigated for the chemical fingerprint of anthraquinones. The inhibitory concentrations of A. vera inner gel were similar to the bactericidal ones, with values ranging from 6·25 to 800 mg ml−1. Fifty per cent of the detected strains, independently of their susceptibility profile, were inhibited in their growth at 100 mg ml−1. Aloe vera inner gel expresses antibacterial properties against H. pylori and, therefore, in combination with antibiotics, could represent a novel strategy for the treatment of the infection of H. pylori, especially in cases of multiresistance.

Source: L. Cellini S. Di Bartolomeo E. Di Campli S. Genovese M. Locatelli M. Di Giulio. “n vitro activity of Aloe vera inner gel against Helicobacter pylori strains.” Letter in Applied Microbiology (2014), Vol. 59, Issue 1.


Methylsulfonylmethane is effective against gastric mucosal injury


Methylsulfonylmethane (MSM) is a natural organosulfur compound has been widely used as a dietary supplement. MSM has protective effects against various disorders through its anti-inflammatory and antioxidant properties however the effect of MSM on gastric mucosal injury remains unclear. The aim of the present study is to determine whether MSM has beneficial effects on ethanol/HCl-induced gastric ulcer in mice. Macroscopic and histopathological evaluation of gastric mucosa revealed that ethanol/HCl administration produced apparent mucosal injuries, while pretreatment with MSM (200 and 400mg/kg, orally) could effectively protect gastric mucosa against the injuries caused by acidified ethanol. MSM significantly increased the levels of glutathione (GSH), catalase (CAT) and prostaglandin E2 (PGE2), and decreased the levels of malondialdehyde (MDA), myeloperoxidase (MPO), carbonyl protein, and nitric oxide (NO) in gastric tissues compared with those in the ethanol group. MSM suppressed gastric inflammation by reducing the levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9. Moreover, pretreatment of mice with MSM decreased the expression of nuclear factor kappa B (NF-κB) as a key regulator of inflammation in gastric mucosa. Taken together, these data suggest that MSM is able to decrease the severity of ethanol/HCl-induced gastric mucosal injury through inhibition of oxidative stress and inflammation.

Source: Amirshahrokhi K, Khalili AR. “Methylsulfonylmethane is effective against gastric mucosal injury.” European Journal of Pharmacology (2017);811:240-248.

Cat’s Claw

Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content


Cat's claw is an herbal medicine from the Amazon that is used widely to treat inflammatory disorders. The purpose of this study was to characterize the antioxidative and antiinflammatory properties of cat's claw, Uncaria tomentosa (UT) and Uncaria guianensis (UG). Alkaloids and flavanols were determined using reversed-phase HPLC; scavenging of 1,1-diphenyl-2-picrilhydrazyl (DPPH), hydroxyl radicals, and lipid peroxidation by spectrophotometry; and TNFalpha production by ELISA. Anti-inflammatory activity was assessed in vitro by inhibition of TNFalpha and nitrite production from RAW 264.7 cells exposed to LPS (50 ng/ml) and in vivo using the indomethacin-induced gastritis model. Apoptosis was assessed using the TUNEL technique and TNFalpha mRNA by in situ RT-PCR. In each of the antioxidant assays tested, UG was more potent than UT (P < 0.01). The total oxindole and pentacyclic alkaloid content of UT was 35-fold > UG. The IC50 value for inhibition of TNFalpha production was significantly (P < 0.01) higher for UT (14.1 ng/ml) vs UG (9.5 ng/ml), yet at concentrations that were considerable lower than that required for antioxidant activity. Non-alkaloid HPLC fractions from UT decreased LPS-induced TNFalpha and nitrite production in RAW 264.7 cells (P < 0.01) at a concentration range comparable to the parent botanical. Oral pretreatment for 3 d with UT protected against indomethacin-induced gastritis, and prevented TNFalpha mRNA expression and apoptosis. These results indicate that while both species of cat's claw provide effective antioxidant and anti-inflammatory activities, U. guianensis is more potent. In conclusion, the presence of oxindole or pentacyclic alkaloids did not influence the antioxidant and anti-inflammatory properties of cat's claw.

Source: Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ. “Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content.” Phytomedicine. (2002 May);9(4):325-37.

Marshmallow Root

Herbal Medicine in the Treatment of Ulcerative Colitis


Ulcerative colitis (UC) is a refractory, chronic, and nonspecific disease occurred usually in the rectum and the entire colon. The etiopathology is probably related to dysregulation of the mucosal immune response toward the resident bacterial flora together with genetic and environmental factors. Several types of medications are used to control the inflammation or reduce symptoms. Herbal medicine includes a wide range of practices and therapies outside the realms of conventional Western medicine. However, there are limited controlled evidences indicating the efficacy of traditional Chinese medicines, such as aloe vera gel, wheat grass juice, Boswellia serrata, and bovine colostrum enemas in the treatment of UC. Although herbal medicines are not devoid of risk, they could still be safer than synthetic drugs. The potential benefits of herbal medicine could lie in their high acceptance by patients, efficacy, relative safety, and relatively low cost. Patients worldwide seem to have adopted herbal medicine in a major way, and the efficacy of herbal medicine has been tested in hundreds of clinical trials in the management of UC. The evidences on herbal medicine are incomplete, complex, and confusing, and certainly associated with both risks and benefits. There is a need for further controlled clinical trials of the potential efficacy of herbal medicine approaches in the treatment of UC, together with enhanced legislation to maximize their quality and safety.

Source: Ke, F., Yadav, P. K., & Ju, L. Z. “Herbal medicine in the treatment of ulcerative colitis.” Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association (2012), 18(1), 3–10.

Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats

Background: Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats.

Materials and Methods: Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg).

Results: Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study.

Conclusion: These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release.

Source: Zaghlool, S. S., Shehata, B. A., Abo-Seif, A. A., & Abd El-Latif, H. A. “Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats.” Journal of natural science, biology, and medicine (2015), 6(2), 421–428.

Slippery Elm

Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study


Objective: The study objective was to assess the effects and tolerability of two novel natural medicine formulations in improving bowel habit and abdominal symptoms in patients with irritable bowel syndrome (IBS). The DA-IBS formula was designed to treat diarrhea-predominant and alternating bowel habit IBS, and the C-IBS formula was designed to treat constipation-predominant IBS.

Design: This was a two arm, open-label, uncontrolled pilot study.

Settings/location: Subjects were recruited from the greater Lismore area (NSW, Australia) in 2001.

Subjects: The study included 31 patients who fulfilled the Rome II criteria for IBS. Twenty-one (21) patients were classified as suffering from diarrhea-predominant or alternating bowel habit IBS and 10 patients were classified with constipation-predominant IBS.

Interventions: The DA-IBS formula consisted of a mixture of dried, powdered bilberry fruit, slippery elm bark, agrimony aerial parts, and cinnamon quills. The C-IBS formula consisted of a mixture of dried powdered slippery elm bark, lactulose, oat bran, and licorice root. The aim of each formula was to normalize stool frequency and stool consistency.

Results: Ingestion of the DA-IBS formula was associated with a small, but significant increase in bowel movement frequency (p = 0.027). Subjects in the DA-IBS group also experienced reductions in straining (p = 0.004), abdominal pain (p = 0.006), bloating (p < 0.0001), flatulence (p = 0.0001), and global IBS symptoms (p = 0.002) during the treatment phase of the trial. Subjects in the C-IBS group experienced a 20% increase in bowel movement frequency (p = 0.016) and significant reductions in straining (p < 0.0001), abdominal pain (p = 0.032), bloating (p = 0.034), and global IBS symptom severity (p = 0.0005), as well as improvements in stool consistency (p < 0.0001). Both formulas were well-tolerated.

Conclusions: The DA-IBS formula was not effective in improving bowel habit in individuals with diarrhea-predominant or alternating bowel habit IBS, although it did significantly improve a number of IBS symptoms. The C-IBS formula significantly improved both bowel habit and IBS symptoms in patients with constipation-predominant IBS. Further research is warranted on C-IBS, as a potentially useful therapeutic formula.

Source: Hawrelak JA, Myers SP. “Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study.” Journal of Alternative and Complementary Medicine (2010);16(10):1065-71.

Licorice Root

Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides


Background: The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease.

Methods: This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31) were treated with pantoprazole and a formula (Mirgeal®) containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32) were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10). Side effects, tolerability, and compliance were also assessed.

Results: Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B) completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the two groups.

Conclusion: Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening tolerability or compliance.

Source: Di Pierro, F., Gatti, M., Rapacioli, G., & Ivaldi, L. “Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides.” Clinical and experimental gastroenterology (2013), 6, 27–33.

Prevention of symptoms of gastric irritation (GERD) using two herbal formulas: An observational study


Background: Acid-suppressive drugs are commonly used to treat gastric irritation and GERD. These drugs have been associated with a number of adverse effects and caution may be needed in recommending their use. The purpose of this observational study was to compare the efficacy of two herbal formulas in the reduction of the symptoms of GERD and some other gastrointestinal diseases without the need to substantially lower gastric acid.

Methods: Fifty eight people who suffered from one or more symptoms of gastric irritation and GERD for more than 6 months took part in this two-year observation study. The symptoms and conditions studied included gastric reflux, unspecified burning sensations in the gastric area (heart burn), confirmed gastric or duodenal ulcer, irritable bowel syndrome and Crohn's disease. This study examined the use of two non-antacid herbal formulas: Formula 1, containing Ulmus fulva (slippery elm) and Mentha piperita (peppermint oil) and Formula 2 with the addition of deglycyrrhizinated liquorice (DGL). Symptoms were self-evaluated by patients using a questionnaire that was completed before and after the study.

Results: The results showed that the both herbal formulas were associated with significant improvement in symptoms of gastric and intestinal irritation and that these improvements were consistently reported as better than commonly used antacids.

Conclusion: A herbal formula designed to sooth and protect the gastric mucosa may be a better alternative than acid-suppressive drugs for people suffering with gastric irritation and GERD.

Source: Setright, Russell, “Prevention of symptoms of gastric irritation (GERD) using two herbal formulas: An observational study.” Journal of the Australian Traditional-Medicine Society (2017) Volume 23, Issue 2.

Prune Fruit

Systematic review: the effect of prunes on gastrointestinal function


Background: Prunes (dried plums) are high in fibre and are perceived to promote healthy gastrointestinal (GI) function.

Aim: To assess the effect of prunes on GI function through a systematic review of randomised controlled trials (RCTs).

Methods: Sixteen electronic databases were searched, a hand search was performed and key opinion leaders were contacted. RCTs investigating the effect of prunes on GI function were included. Two reviewers independently screened relevant articles, extracted data and assessed risk of bias.

Results: Four trials met the inclusion criteria, one in constipation and three in non-constipated subjects. In constipation, 3 weeks of prune consumption (100 g/day) improved stool frequency (3.5 vs. 2.8 CSBM per week, P = 0.006) and stool consistency (3.2 vs. 2.8 on Bristol stool form scale, P = 0.02) compared with psyllium (22 g/day). In non-constipated subjects, prunes softened stool consistency in one trial and increased stool weight (628 g vs. 514 g/72 h wet weight, P = 0.001) in another trial, compared with control. No trials found differences in GI symptoms between prunes and comparator. Meta-analysis was not appropriate due to heterogeneity in populations and methods. Two of the trials were limited by unclear risk of bias.

Conclusions: In constipation, prunes appear superior to psyllium for improving stool frequency and consistency, however, the evidence for other outcomes and the effects in non-constipated subjects is weak. Although prunes may be a promising intervention for the management of constipation and increasing stool weight, this needs to be confirmed by further rigorous research.

Source: Lever E, Cole J, Scott SM, Emery PW, Whelan K. “Systematic review: the effect of prunes on gastrointestinal function.” Alimentary Pharmacology and Therapeutics (2014) ;40(7):750-8.


Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial


Background: Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects.

Purpose: To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse.

Methods: Outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at ClinicalTrials.gov, identifier NCT01072344.

Results: Between March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20-1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates.

Conclusions: Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, but did not significantly reduce rate of relapse. Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding. Possible chamomile superiority over placebo requires further examination in large-scale studies.

Source: Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. “Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial.” Phytomedicine (2016) ;23(14):1735-1742.


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