Research - Dyspepsia / Gastroesophogeal reflux/GERD
Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies
Mehdi Salehi, MD,1 Hossein Karegar-Borzi, MD,1 Mehrdad Karimi, MD, PhD,1 and Roja Rahimi, PharmD, PhD2
Abstract
Objectives: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects.
Methods: Medline, Scopus, and Cochrane Central Register of Controlled Trials were searched for animal or human studies. The data collected covered January 1966–October 2015.
Results: A total of 22 studies were included in this review, of which nine were animal studies and 13 were human studies. Ceratonia siliqua as a medicinal plant and rikkunshito as a multicomponent herbal preparation were the most frequently studied herbal medicines in GERD. Antioxidant and anti-inflammatory activities were the main mechanisms demonstrated in animal studies for ameliorating the effects of medicinal plants in GERD. Other mechanisms include downregulation of genes encoding inflammatory proteins, improvement of barrier function and gastric mucus, a decrease in gastric acid, and induction of tonic contractions of the lower esophageal sphincter. All herbal preparations used in human studies have led to the alleviation of symptoms related to GERD. Myrtus communis and Cydonia oblonga showed marked reduction in GERD symptoms comparable to omeprazole. The therapeutic effect of Cydonia oblonga persisted after discontinuation of the drug. Tongjlang and rikkunshito showed therapeutic effects for non-erosive reflux disease (NERD) where PPIs failed to show a promising effect. Studies on Ceratonia siliqua have been solely focused on regurgitation in infants, and a remarkable decrease in the number of regurgitations was demonstrated.
Conclusion: The multiple mechanisms of action of medicinal plants in GERD other than anti-secretory properties appear to provide more efficient treatment and helped to manage the histopathological changes associated with this disorder. Further studies are needed to understand the effects of medicinal plants on GERD better.
Source : Journal of Alternative and Complementary Medicine
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Comparing the Effect of Psyllium Seed on Gastroesophageal Reflux Disease With Oral Omeprazole in Patients With Functional Constipation
Mousalreza Hosseini,1 Roshanak Salari,1 Mina Akbari Rad,1 Maryam Salehi,1 Batul Birjandi,1 andMasoumeh Salari, MD
Abstract
Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases. Several studies have been carried out on the treatment of symptoms associated with GERD. The present study aimed to compare the effect of Psyllium seed and oral omeprazole on GERD in patients with functional constipation. In this trial, 132 patients were divided into 2 groups. The impact of omeprazole and Psylliumseed on the treatment and recurrence of GERD was studied. Among the patients, the rate of response to treatment was 89.2% (n = 58) in the Psyllium seed group, while in omeprazole group, it was 94% (n = 63; P = .31). The recurrence rates of Psyllium seed and omeprazole groups were 24.1% (n =14) and 69.8% (n = 44), respectively (P < .001). The results showed that treatment of functional constipation by Psyllium seed in patients with GERD leads to improvement of GERD and its recurrences in comparison with omeprazole.
Source : Journal Evidence Based Integrative Medicine
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Safety and Efficacy of Ferula asafoetida in Functional Dyspepsia: A Randomized, Double-Blinded, Placebo-Controlled Study
K. N. Mala,1 Jestin Thomas,2 Das S. Syam,3 Balu Maliakel,3 and I. M.Krishnakumar
Abstract
Despite the availability of various synthetic drugs for the treatment of functional dyspepsia (FD), the side effects and their cost have always created a great interest in the search for novel natural alternatives for the management of gut disorders. The present contribution reports the safety and efficacy of the kitchen spice asafoetida (Ferula asafoetida) in FD for the first time. In the double-blinded, placebo-controlled study, 43 subjects diagnosed to have moderate to severe discomforts of nonulcer FD were randomized to receive hard-shell capsules (250 mg × 2/day) of either placebo (n=22) or a food-grade formulation of asafoetida (Asafin) (n=21) for 30 days. When evaluated by a set of validated indexing tools (GSRS, GDSS, and NDI), almost 81% in the Asafin group showed significant (p < 0.01) improvement in the overall score and quality of life as compared to the placebo. At the end of the study, 66% of subjects in the Asafin group remained symptoms-free. Although the symptoms score improved significantly in both the groups (from -5.67 to -25.29 in Asafin group versus -1.55 to -6.0 in the placebo; p ≤ 0.001), the relative percentage of subjects in the Asafin group with more than 80% reduction in various symptoms were: bloating (58%), appetite (69%), postprandial fullness (74%) motion sickness (75%), and digestion (77%) as compared to less than 10% nonspecific improvement in the placebo group. All the subjects remained safe with no adverse events or variations in haematological and biochemical parameters.
Source : Evidence Based Complementary and Alternative Medicine
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Individualized Acupuncture for Symptom Relief in Functional Dyspepsia: A Randomized Controlled Trial.
Ko SJ1, Kuo B2, Kim SK1, Lee H3, Kim J1, Han G1, Kim J1, Kim SY3, Jang S1, Son J1, Kim M1, Lee H3, Yeo I4, Joo KR5, Park JW1.
Abstract
OBJECTIVES:This study was implemented to evaluate the effect of individualized acupuncture treatment (AT) on functional dyspepsia (FD).
METHODS:A randomized, waitlist-controlled, two-center trial was performed. Seventy-six patients with FD were enrolled in the trial with partially individualized AT in a more realistic clinical setting performed twice a week for 15 minutes a session over 4 weeks. The participants were randomly allocated to a group receiving 8 sessions of AT for 4 weeks or a waitlist control group. After 4 consecutive weeks, the AT group was followed up without AT and the control group received the identical AT. The proportion of responders with adequate symptom relief, Nepean Dyspepsia Index (NDI), FD-related quality of life, Beck Depression Inventory, State-Trait Anxiety Inventory, Acupuncture Belief Scale, and acupuncture credibility test were assessed.
RESULTS:After the first 4 weeks, the proportion of responders significantly improved (59% in AT group [n = 37] versus 3% in control group [n = 39]; p < 0.001). The difference was no longer significant at 8 weeks, at which point the waitlist control group showed similar improvement after receiving AT (68% in the AT group versus 79% in the control group). Total NDI scores were significantly reduced in the AT group compared with the waitlist group (p = 0.03). Among NDI items, discomfort (p = 0.01), burning (p = 0.02), fullness after eating (p = 0.02), and burping (p = 0.02) were significantly improved in the AT group compared with the control group. No significant differences were observed between groups in other secondary variables.
CONCLUSION:Individualized AT adequately relieves symptoms in patients with FD, and this effect may persist up to 8 weeks.
Source : Sci-Hub via Journal Alternative and Complementary Medicine
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Efficacy and Safety of a Natural Remedy for the Treatment of Gastroesophageal Reflux: A Double-Blinded Randomized-Controlled Study
Umberto Alecci,1 Francesco Bonina,2 Andrea Bonina,3 Luisa Rizza,3 Santi Inferrera,1 Carmen Mannucci,4 and Gioacchino Calapai4
Abstract
Gastroesophageal reflux (GER) is a common, chronic, relapsing symptom. Often people self-diagnose and self-treat it even though health-related quality of life is significantly impaired. In the lack of a valid alternative approach, current treatments focus on suppression of gastric acid secretion by the use of proton pump inhibitors (PPIs), but people with GER have a significantly lower response rate to therapy. We designed a randomized double-blinded controlled clinical study to evaluate the efficacy and the safety of a formulation based on sodium alginate/bicarbonate in combination with extracts obtained from Opuntia ficus-indica andOlea europaea associated with polyphenols (Mucosave®; verum), on GER-related symptoms. Male/female 118 (intention to treat) subjects with moderate GER and having at least 2 to 6 days of GER episodes/week were treated with verum (6 g/day) or placebo for two months. The questionnaires Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQoL) and Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) were self-administered by participants before the treatment and at the end of the treatment.Verum produced statistically significant reduction of GERD-HRQoL and GSAS scores, −56.5% and −59.1%, respectively, in comparison to placebo. Heartburn and acid regurgitation episodes for week were significantly reduced by verum (p<0.01)). Results indicate that Mucosave formulation provides an effective and well-tolerated treatment for reducing the frequency and intensity of symptoms associated with gastroesophageal reflux.
Source : Evidence Based Complementary and Alternative Medicine
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Efficacy and Safety of Acupuncture for the Treatment of Functional Dyspepsia: Meta-Analysis
Weimei Zhou, MS, Jiewen Su, MS, and Hongjie Zhang, PhD
Abstract
Objectives: Functional dyspepsia (FD) is a common gastrointestinal disorder. Currently, no established optimal treatment is available. The aim of this study was to assess the efficacy of acupuncture in relieving symptoms and improving quality of life in patients with FD.
Methods: PubMed, MEDLINE, Web of Science, Sino-Med, China National Knowledge Infrastructure, VIP databases, and Google Scholar engine were searched from inception through April 2014 to identify randomized controlled trials of acupuncture therapy that reported on overall FD symptoms or FD-related quality of life as a primary outcome. The Cochrane Collaboration's risk of bias tool, RevMan 5.0, and Stata 12.0 software were used for meta-analysis. Data were pooled to calculate relative risk (RRs) and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data using random-effects models.
Results: Twenty-four English- and Chinese-language articles describing randomized, placebo-controlled, clinical trials involving 3097 patients were included. Acupuncture significantly improved FD symptoms in studies reporting outcomes using dichotomous (RR, 1.19; 95% CI, 1.12–1.27; p < 0.001) and continuous (standardized MD [SMD], −0.78; 95% CI, −1.21 to −0.35; p = 0.0004) variables. Pooled analyses showed that acupuncture improved FD-related (weighted MD [WMD], 5.97; 95% CI, 3.14–8.80; p = 0.0002) and health-related (WMD, 6.83; 95% CI, 3.02–10.65; p = 0.004) quality of life, without serious adverse events. However, acupuncture failed to increase plasma motilin concentration (SMD, 0.67; 95% CI, −0.07 to 1.42; p = 0.08).
Conclusions: Acupuncture appears to be efficacious in relieving FD symptoms and improving quality of life.
Source : Journal of Alternative and Complementary Medicine
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Efficacy and safety of Aloe vera syrup for the treatment of gastroesophageal reflux disease: a pilot randomized positive-controlled trial Abstract
ObjectiveTo investigate the use of Aloe vera (A. vera) for the treatment of gastroesophageal reflux disease (GERD) symptoms and compare its effects with those of omeprazole and ranitidine.
Methods In this pilot, randomized controlled trial, 79 subjects were allocated to A. vera syrup (standardized to 5.0 mg polysaccharide per mL of syrup) at a dose of 10 mL/d, omeprazole capsule (20 g/d) or ranitidine tablet (150 mg in a fasted state in the morning and 150 mg 30 min before sleep at night) for a period of 4 weeks. The frequencies of eight main symptoms of GERD (heartburn, food regurgitation, flatulence, belching, dysphagia, nausea, vomiting and acid regurgitation) were assessed at weeks 2 and 4 of the trial.
Results A. vera was safe and well tolerated and reduced the frequencies of all the assessed GERD symptoms, with no adverse events requiring withdrawal.
Conclusion A. vera may provide a safe and effective treatment for reducing the symptoms of GERD.
Source : Journal of Traditional Chinese Medicine
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The Effect of Ginger (Zingiber officinalis) and Artichoke (Cynara cardunculus) Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and Placebo-Controlled Clinical Trial
Attilio Giacosa,1 Davide Guido,2 Mario Grassi,2 Antonella Riva,3 Paolo Morazzoni,3 Ezio Bombardelli,3 Simone Perna,4 Milena A. Faliva,4 and Mariangela Rondanelli4
1Department of Gastroenterology, Policlinico di Monza, 20900 Milan, Italy
2Section of Biostatistics, Neurophysiology and Psychiatry, Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
3Research and Development Unit, Indena, 20139 Milan, Italy
4Section of Human Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Azienda di Servizi alla Persona, 27100 Pavia, Italy
Discussion
The main result of this study is that the supplementation with ginger and artichoke extracts is efficacious in the short-term treatment of FD. This effect appears to be statistically significant when compared to placebo. It is interesting to note that the efficacy appears quickly, that is, within 14 days, and afterwards it is maintained until the 28th day of intervention. The intervention group shows treatment efficacy in 86.2% of cases after 28 days of supplementation, with marked reduction of dyspepsia intensity (grades 2 + 3 of the considered scale) in 63.1% of the treated cases, while only 52.5% of the control group patients showed a positive effect of placebo and only 24.6% of the placebo treated patients had a marked reduction of symptoms (grades 2 and 3).
Our results show the advantage of the supplementation, as compared to placebo, with a significant amelioration of 0.85 units on the MCA severity scale (of range 0–3) at 14 days. This result is adjusted for baseline symptoms and typologies of dyspepsia, and it persists until the end of the study (28th day). On raw data, the percentage difference between the intervention product and placebo approached 34%. This therapeutic gain is greater than what has been observed in previous studies with antisecretory and gastrokinetic drugs [23], as well as with artichoke extracts [13]: in all these cases the advantage was in the range of 15%. Therefore, it seems that the association between ginger and artichoke extracts may increase the treatment efficacy on FD as compared to what was observed with artichoke extract alone or with antisecretory and gastrokinetic drugs.
The mechanisms involved in the pathophysiology of FD are multifactorial. As a matter of fact, a number of potential abnormalities have been reported in patients with FD including impaired fundic accommodation, gastric hypersensitivity to distention, abnormal duodenojejunal motility, duodenal motor and sensory dysfunction, duodenal hypersensitivity to lipids or acid, and Helicobacter pylori infection [24]. In the present study the highest prevalence of FD subtype was represented by dysmotility-like FD and unspecified FD, while ulcer-like FD was present in very few cases of both the intervention and placebo groups, as shown in Table 1. Therefore, a prevalence of symptoms related to motility disorders was observed in the recruited patients. Most studies in animals have demonstrated that ginger root extracts increase gastric emptying and gastrointestinal transit [25]. Micklefield et al. demonstrated a significant increase of the interdigestive motility after intervention with ginger extracts and Wu et al. showed that ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers [11, 26]. Animal emesis models likewise have shown reduced emesis with the administration of ginger. Gingerols and shogaols seem to be the active components [27].
Nausea, vomiting, and hypomotility involve a temporary dysfunction of the complex integrated network of cholinergic M3 and serotonergic 5-HT3/5-HT4 receptors. In this respect, major chemical constituents of the ginger roots lipophilic extracts such as
[6]-gingerol, [8]-gingerol, [10] -gingerol, and [6]-shogaol have been shown in several experimental models to modulate with a differentiated potency all these receptors. In particular, the capacity of ginger to reduce nausea and eventually vomiting seems to correlate with the effectiveness of these active ingredients to weakly inhibit M3 and 5-HT3 receptors. On the contrary, 5-HT4 receptors, which also play a role in gastroduodenal motility, do not seem to be involved in the effects of these compounds [11, 12].
Artichoke leaf extracts (ALE) have been used since long time, in traditional medicine, to treat dyspepsia and in 2003 Holtmann et al. [13] confirmed this effect in patients with FD. ALE increase bile flow and exert hepatoprotective [28], serum cholesterol lowering [29], and antioxidant and antispasmodic effects [30–32]. The bitter compounds of ALE and particularly cynaropicrin are responsible for the digestive beneficial effects [33, 34]. Holtmann et al. [13] showed that ALE were significantly better than placebo in reducing symptoms and improving the disease-specific quality of life in patients with functional dyspepsia. Anyhow the present study shows that the association of ginger extracts and ALE increases the efficacy on functional dyspepsia treatment with a 16.9% advantage as compared to the data found by Holtmann et al. [13] with ALE alone.
Of great interest appears the evaluation of the effect of ginger and artichoke supplementation on specific symptoms of functional dyspepsia. In this study the intervention was associated with a reduction of severity of epigastric pain, epigastric fullness, nausea, bloating, and early satiety: this decrease appears statistically significant for nausea and epigastric pain, over the observation time of 28 days. The only symptom which did not change was vomiting. On the contrary, in the placebo group, the statistical analysis shows that all symptoms have an increasing slope, which means an increase of symptom intensity with a statistically significant worsening for vomiting.
Considering the entity of the efficacy on the secondary outcomes, the supplementation shows a greatest efficacy on nausea, followed by a positive effect on epigastric fullness, epigastric pain, and bloating, after statistical adjustment for type of dyspepsia. The effect on nausea and on epigastric fullness could mainly be due to the ginger component and to its activity on gastric motility: this confirms what was previously observed in other clinical settings such as in nausea associated with pregnancy, chemotherapy, and motion sickness [12,35–37].
The effects on bile secretion that have been found in previous trials with artichoke extracts [38] may partially contribute to our results. The increase in bile acid secretion, observed after supplementation with ALE, is suitable to accelerate gastrointestinal transit and thus may alleviate bloating and fullness. The well-known antispasmodic feature of ALE may also increase both effects [38].
The treatment with the ginger and ALE supplement used in this study did not show any relevant side effect. This observation is of great importance when compared with the critical role of traditional prokinetic drugs such as domperidone, levosulpiride, or metoclopramide, frequently used in FD therapy. The treatment with these drugs is frequently associated with neurologic or endocrinologic side effects [39]. In addition to this, a severe warning has been reported for domperidone treatment due to the sudden risk of cardiac death observed at doses of more than 30 mg per day in the elderly [40–43].
In conclusion, the association between ginger and artichoke leaf extracts appears efficacious in the treatment of functional dyspepsia and could represent a promising and safe treatment strategy for this frequent disease, even though additional studies are needed to confirm these results.
Source : Journal Alternative and Complementary Medicine
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An Extract of Glycyrrhiza glabra (GutGard) Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study
Kadur Ramamurthy Raveendra, 1 Jayachandra, 2 Venkatappa Srinivasa, 3 Kadur Raveendra Sushma, 1 Joseph Joshua Allan, 4 * Krishnagouda Shankargouda Goudar, 4 Hebbani Nagarajappa Shivaprasad, 4 Kudiganti Venkateshwarlu, 4 Periasamy Geetharani, 4 Gopalakrishna Sushma, 4 and Amit Agarwal 4
Abstract
A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of GutGard, an extract of Glycyrrhiza glabra, in patients with functional dyspepsia. The primary outcome variables of the study were the change in the severity symptoms and the global assessment of efficacy. The quality of life was evaluated as a secondary outcome measure. The patients received either placebo or GutGard (75mg twice daily) for 30 days. Efficacy was evaluated in terms of change in the severity of symptoms (as measured by 7-point Likert scale), the global assessment of efficacy, and the assessment of quality of life using the short-form Nepean Dyspepsia Index. In comparison with placebo, GutGard showed a significant decrease (P ≤ .05) in total symptom scores on day 15 and day 30, respectively. Similarly, GutGard showed marked improvement in the global assessment of efficacy in comparison to the placebo. The GutGard group also showed a significant decrease (P ≤ .05) in the Nepean dyspepsia index on day 15 and 30, respectively, when compared to placebo. GutGard was generally found to be safe and well-tolerated by all patients. GutGard has shown significant efficacy in the management of functional dyspepsia.
Source : Evid Based Complement Alternat Med. 2012; 2012: 216970.
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Effect of Ginger on patients with functional dyspepsia.
Hu ML, Wu KL, Chuah SK et al.
Nine patients with functional dyspepsia were studied on separate two days in a randomised, double-blind design.
Following a fast of 8 hours the patients took capsules containing a total of 1.2 g of ginger (Zingiber officinale) root powder or placebo. One hour later they consumed 500 mL of low-nutrient soup. Antral area (bottom of stomach, nearthe duodenum), fundus area (top, near the oesophagus) and diameter, and the frequency of antral contractions were then measured using ultrasound at intervals over 90 minutes. The gastric half-emptying time was calculated from the change in antral area. Serum peptides (glucagon-like peptide-1, motilin, ghrelin) were also measured.
The following results were found:
• Gastric half-emptying time was significantly less after ginger than placebo (11.9 minutes vs 21.1 minutes), and the frequency of antral contractions was significantly greater. Antral area decreased more rapidly.
• There was no difference in fundus dimensions, serum peptides or gastrointestinal symptoms.
Conclusions
Ginger accelerated gastric emptying and stimulated antral contractions in patients with functional dyspepsia in a preliminary investigation.
Source : J Gastroenterol Hepatol 2009; 24(Suppl 1): A31
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See also side effects of Antacids
FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)
FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors