Assessment of the use of vitamin C and E supplements concomitantly to antibiotic treatment against Helicobacter pylori: A systematic review and meta-analysis

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In developing countries, the prevalence ranges from 75% to 86%, unlike developed countries, which report rates of 39.6% in Japan and 17.1% in the United States.<a class="elsevierStyleCrossRefs" href="#bib0230">1,2</a> Studies carried out in different countries around the world describe the following risk factors: low socio-economic level, high population density, inadequate hygiene habits and difficult access to education and health services.<a class="elsevierStyleCrossRef" href="#bib0240">3</a>The clinical importance of H. pylori infection lies in its relationship with the development of a broad spectrum of gastrointestinal diseases such as: gastritis, dyspepsia, peptic ulcer, mucosal-associated lymphoid tissue (MALT) lymphoma and gastric cancer.<a class="elsevierStyleCrossRef" href="#bib0230">1</a> Under the circumstances, pharmacological treatment strategies have been developed for said infection. Some international guidelines describe standard triple therapies that include a proton pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole.<a class="elsevierStyleCrossRefs" href="#bib0245">4–6</a> Other alternatives have proposed a quadruple therapy based on bismuth salts with metronidazole and tetracycline, and even third and fourth generation quinolones are recommended for said treatment.<a class="elsevierStyleCrossRef" href="#bib0260">7</a>However, resistance rates of H. pylori have been increasing since the beginning of the XXI century. For example, in 2004, the percentage of resistance in the United States was 13%, increasing to 18% in 2015.<a class="elsevierStyleCrossRef" href="#bib0265">8</a> In northern India, Gehlot et al. evaluated strains isolated from 68 patients where they described a resistance percentage of 70.6%, including 48.5% resistance to metronidazole, 17.6% to amoxicillin, 16.2% to tetracycline and 11.8% to clarithromycin.<a class="elsevierStyleCrossRef" href="#bib0270">9</a> In France, Ducournanu et al. documented 115 patients with H. pylori, with a resistance of 73.9% for clarithromycin and 78.3% for metronidazole.<a class="elsevierStyleCrossRef" href="#bib0275">10</a>There are some alternatives for the treatment of this infection currently under investigation, which include: vaccines, prebiotics grown from fermented milk, phytotherapy and vitamin C and E supplements.<a class="elsevierStyleCrossRefs" href="#bib0280">11,12</a> The use of prebiotics proved to be effective in eradication, according to the meta-analysis conducted by Guo et al., as long as it was administered with the standard treatment. Despite the foregoing, prebiotics do not reduce drug-related adverse reactions.<a class="elsevierStyleCrossRef" href="#bib0290">13</a> Phytotherapy was evaluated in in vitro and in vivo studies, where some components are effective in the eradication of bacteria and prevention of gastric cancer but produce undesirable effects in animal models.<a class="elsevierStyleCrossRef" href="#bib0295">14</a>In the same way, in vitro studies have been carried out with antioxidant compounds such as vitamin C and E supplements in states of chronic inflammation (which precedes the formation of neoplasms in the gastric mucosa), which exerted a cytoprotective effect. In murine models, the consumption of vitamins C and E generated a hostile environment for the microorganism and facilitated its elimination by antimicrobials, reducing strains that can enter bacterial gene material for resistance acquisition.<a class="elsevierStyleCrossRef" href="#bib0300">15</a> Poplawski et al. evaluated in vitro the effects of vitamin C in the context of infection by H. pylori observing a genotoxicity reduction in heterocyclic amines in the above-mentioned environment.<a class="elsevierStyleCrossRef" href="#bib0305">16</a>In the year 2011, Li et al. reported a meta-analysis evaluating vitamin C and E supplements in the eradication of H. pylori. It included 6 studies where they compared the use of vitamins C and E. However, they omitted to consider the number of antibiotics used. Based on this study, new research was conducted in Turkey, which may provide new perspectives for the study of this phenomenon.<a class="elsevierStyleCrossRef" href="#bib0310">17</a> Therefore, the present study aims to perform a systematic review of the literature, evaluating the efficacy and safety of the use of vitamin C and E supplements or just vitamin C supplement with antibiotic therapy for the eradication of H. pylori.MethodologyRegistryWe followed the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the development of systematic reviews and meta-analyzes.<a class="elsevierStyleCrossRef" href="#bib0315">18</a>Eligibility criteriaRandomized double-blind, single-blind, or open-label clinical trials evaluating vitamin C and E supplementation were selected, attached to triple or quadruple antibiotic therapy in H. pylori infection diagnosed by the urease test method, biopsy or culture. The main outcome was the eradication of the infection, defined as a negative urea breath test or a negative histological finding after treatment and the secondary outcome was adverse reactions. Cohort studies, in vitro studies or cases-control studies were excluded. Conference summaries found in the databases selected in the reports of academic events were also considered.Information sourcesMedLine (PubMed), Embase and Cochrane Central Register of Clinical Trials (CENTRAL) databases. The search was conducted between May 12 and June 12, 2016. In case of expanding some information, we tried to contact the authors.SearchThe following were used as search criteria: (acid, ascorbic OR L-ascorbic acid OR vitamin C OR sodium ascorbate) OR (vitamin E OR tocopherols OR alpha-tocopherol OR beta-tocopherol OR gamma-tocopherol) AND (Helicobacter pylori OR H pylori OR infection Helicobacter pylori). No restrictions were made regarding time or language.Study selectionThe records reported by the databases were reviewed by 2 authors, independently, and in case of any discrepancy, a third reviewer was consulted. The summaries of the manuscripts were obtained according to the title and summary that, in the context of patients infected by H. pylori, enunciated the antibiotic treatment with vitamin C or E supplementation. The results obtained were recorded in a database. Subsequently, the search of the articles was carried out “in extenso”, to verify the inclusion and exclusion criteria in the systematic review. The diagnostic and eradication method of H. pylori infection, pharmacological treatment and its doses were verified in the database, in addition, vitamin C and E doses were recorded.Data collection processFrom the selected studies, the search for extensive documents was started, evaluating the following variables: diagnostic method for H. pylori infection; dosage of antibiotics and vitamin C or E supplementation, follow-up of patients in treatment and post-treatment H. pylori infection evaluation. In addition, the method to establish eradication was recorded in the database. The evaluation of biases was made according to the guidelines presented by Higgins and Green in the Cochrane Handbook of systematic intervention reviews of the Cochrane collaboration,<a class="elsevierStyleCrossRef" href="#bib0320">19</a> taking into account selection, information and analysis biases.Analysis of dataThe association measure for the main outcome was the odds ratio (OR) with a confidence interval of 95% (95% CI). An analysis was made by the random-effects method due to the variability in dosage, antibiotics used, time of treatment and after-treatment progression, under the statistical method of Mantel-Haenszel. The proposed analyses were: use of vitamin C or its combination with vitamin E along with antimicrobial therapy without considering the number of antibiotics. Subsequently, the number of drugs in antibiotic therapy was evaluated in a discriminatory manner. The data report was evaluated by “intention to treat”, taking into account the methodological failures of some studies to determine the events related to the loss of patients.<a class="elsevierStyleCrossRef" href="#bib0325">20</a> Statistical heterogeneity was calculated considering the I2, according to Higgins et al.<a class="elsevierStyleCrossRef" href="#bib0330">21</a>; and so high heterogeneity was defined for the manuscripts if they presented an I2 greater than 30%, or in case of finding a p-value less than 0.10 for the Chi-square heterogeneity test. Finally, an analysis of publication biases was performed using the Egger test, considering it to be of high risk of bias if it was significant (p<0.1).<a class="elsevierStyleCrossRef" href="#bib0335">22</a> The analysis was developed using the STATA 14 software and the graphical component of the bias analysis of the feature provided by Review Manager 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark).ResultsStudy selection2441 records were obtained (Medline, 269 studies, Embase, 818 studies and CENTRAL, 1354 studies). We selected 42 studies that would potentially meet our study's criteria. When reviewing all the complete manuscripts, 28 records were discarded, because several were duplicated (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). 14 studies were the evaluated in depth, out of which 3 were excluded. Yoshinaga et al. only compared the use of vitamin C supplement versus treatment with omeprazole, Tümgör et al. only compared the use of vitamin E, and Correa et al. contrasted the treatment with vitamin C supplement against beta-carotenes for one year.<a class="elsevierStyleCrossRefs" href="#bib0340">23–25</a> Of the 11 studies obtained, we found several published manuscripts derived from the same sample. In the case of Sezikli et al., 3 articles were found: the first one described the antioxidant capacity, which was discarded for not complying with the results considered in this review, and the other 2 papers compared triple and quadruple therapy.<a class="elsevierStyleCrossRefs" href="#bib0355">26–28</a> In the case of Chuang et al., there were 2 articles where they mentioned a management difference with or without clarithromycin.<a class="elsevierStyleCrossRefs" href="#bib0370">29,30</a> Finally, we evaluated 10 articles for the meta-analysis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Characteristics of the studiesThe use of vitamin C and E supplement in antibiotic therapy was evaluated in 6 studies.<a class="elsevierStyleCrossRefs" href="#bib0355">26,27,30–33</a> The manuscripts of Sezikli et al. published between 2009 and 2012 were considered separately.<a class="elsevierStyleCrossRefs" href="#bib0355">26,27</a> The same was done with that of Demirci et al., since they evaluated different patients in each arm of the study, with variation in triple or quadruple therapy.<a class="elsevierStyleCrossRef" href="#bib0385">32</a> 973 patients were obtained in the management of vitamin C and E supplement versus antibiotic therapy (424 of antibiotic therapy vs 549 of therapy with supplementation). Within the characteristics of the studies, Chuang et al., Babu et al., and Kaboli et al. do not describe sample characteristics such as the age and the number of male patients who were part of the studied population.<a class="elsevierStyleCrossRefs" href="#bib0370">29,31,34</a> The studies of Chuang et al. evaluated the group of younger patients<a class="elsevierStyleCrossRef" href="#bib0375">30</a>; almost all studies evaluated eradication with the use of the urea breath test (UBT), with the exception of Babu et al. and Everett et al.<a class="elsevierStyleCrossRefs" href="#bib0380">31,33</a> The other elements are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Therapy with only vitamin C supplement was evaluated in 4 studies,<a class="elsevierStyleCrossRefs" href="#bib0370">29,34–36</a> with 702 patients (347 of antibiotic therapy vs 355 of therapy with supplement); almost all studies evaluated eradication using UBT, except for Koçkar et al., who made a histological diagnosis.<a class="elsevierStyleCrossRef" href="#bib0405">36</a>Quality evaluationThe studies were evaluated according to the Cochrane Collaboration guidelines. Of the 10 clinical trials, 9 studies had a high risk of bias.<a class="elsevierStyleCrossRefs" href="#bib0355">26,27,29–32,34–36</a> Although all the studies were described as randomized, they did not describe the randomization method or sequence and the integrity of concealment of the randomization is not very clear either. Blinding was only reported by the Everett et al. study, as double blind, however, there is uncertainty about the follow-up.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> A conference summary was included, which reports only the main outcome information.<a class="elsevierStyleCrossRef" href="#bib0380">31</a> Therefore, the studies show biases in selection and information (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Antibiotic therapy with vitamin C and E supplementNot counting the number of antibiotics used in the therapy of each study, it was estimated that there is no statistically significant relationship between the use of vitamin C and E supplement in antibiotic therapy (OR: 1.98 [95% CI: 0.91–4.28], p=0.08), with high heterogeneity but no publication bias (I2=84%, p<0.01; Egger test: 0.30) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Triple therapyOf the studies evaluated, 5 used triple therapy,<a class="elsevierStyleCrossRefs" href="#bib0355">26,30–33</a> 4 used PPIs with antibiotics, except for Everett et al., who used bismuth. Regarding the antibiotic therapy, Sezikli et al. and Demirci et al. used amoxicillin 1000mg TD (twice a day) and clarithromycin 500mg TD,<a class="elsevierStyleCrossRefs" href="#bib0355">26,32</a> while Chuang et al. and Babu et al. treated with amoxicillin 1000mg and metronidazole 400–500mg, with differences in the dosage between these 2 studies.<a class="elsevierStyleCrossRefs" href="#bib0375">30,31</a> Everett et al. used metronidazole 400mg TDD (3 doses per day) and tetracycline 500mg FDD (4 doses per day). The doses of vitamin C and E supplement showed important differences; Sezikli et al. administered 1000mg day, and the other studies used 500mg or less a day of vitamin C. Sezikli et al. and Babu et al. administered 400UI a day of vitamin E, while others used lower doses. Almost all the regimens lasted at least 14 days with additional supplement therapy in 4 studies for almost 30 days,<a class="elsevierStyleCrossRefs" href="#bib0355">26,31,32</a> except Everett et al., who only administered the therapy for 14 days.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> The meta-analysis of these studies found that the effect of antibiotic therapy with vitamins C and E supplement is not statistically significant in eradication if triple therapy is administered (OR 1.80 [95% CI: 0.64–5.08], p=0.26), with the studies showing high heterogeneity, but without publication bias (I2=85%, p<0.01; Egger test: 0.33) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>B).Quadruple therapyTwo studies used quadruple therapy<a class="elsevierStyleCrossRefs" href="#bib0360">27,32</a>; both used PPI plus bismuth, although the study by Demirci et al. administered a total of 800mg/day, while Sezikli et al. used 1200mg/day of bismuth; both used the same antibiotic dose of amoxicillin 1000 mg TD and clarithromycin 500mg TD. The dose of vitamin C supplement was higher in the paper by Sezikli et al. with 1000mg/day and also that of vitamin E with 400UI/day versus 100UI/day. The treatment follow-up time was equal to 14 days and a 30-day supplement. According to the meta-analysis, in quadruple therapy there is no effect on H. pylori eradication with vitamin C and E supplement therapy (OR: 2.84 [95% CI: 0.51–15.56], p=0.22). However, it shows high heterogeneity (I2=89.6%; p<0.01) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>C).Antibiotic therapy with vitamin C supplementWe obtained 4 studies that evaluated only vitamin C supplement<a class="elsevierStyleCrossRefs" href="#bib0370">29,34–36</a>; 3 used triple therapy, all used PPI and antibiotic, amoxicillin 1000mg and clarithromycin 500mg.<a class="elsevierStyleCrossRefs" href="#bib0370">29,34,36</a> Only Zojaji et al. administered PPI and bismuth, along with antibiotic therapy of amoxicillin and metronidazole.<a class="elsevierStyleCrossRef" href="#bib0400">35</a> The dose of vitamin C supplement was higher in the Chuang et al. and Koçkar et al. studies with 1000mg/day<a class="elsevierStyleCrossRefs" href="#bib0370">29,36</a>; the treatment time was the same for all, except for Chuang et al. who implemented the therapy for 7 days. According to the meta-analysis, the use of vitamin C combined with triple or quadruple therapy has no effect on the eradication of H. pylori (OR: 1.17 [IC95%: 0.58–2.31], p=0.65) with high heterogeneity, without publication bias (I2=67.6%, p=0.02; Egger test, p=0.96) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Safety4 studies reported adverse reactions. Zojaji et al. reported the presence of persistent nausea and headaches.<a class="elsevierStyleCrossRef" href="#bib0400">35</a> The studies by Sezikli et al. documented nausea and persistent metallic taste<a class="elsevierStyleCrossRefs" href="#bib0355">26,27</a>; Koçkar et al. evaluated adverse reactions and reported that no adverse effect was observed in their study.<a class="elsevierStyleCrossRef" href="#bib0405">36</a>DiscussionThe purpose of this research is to search for new or complementary therapeutic alternatives to the management of H. pylori infection, considering the high prevalence of this microorganism and the earlier detection since this infection is associated with the development of gastric cancer. The present study, which included 10 studies, shows considerable heterogeneity due to the methodological designs of the open-label clinical trials; aspects such as blinding of randomization and patient follow-up are not consistent in some studies. In addition, it is worth mentioning that the research conducted in this area has been mainly carried out in countries like Turkey and Taiwan, which are not related to other areas where the prevalence of gastric cancer associated with H. pylori infection is high, as the Andean region in South America and some regions in Asia.<a class="elsevierStyleCrossRefs" href="#bib0355">26,27,29–32,34–36</a>In the specific evaluation of clinical trials there is no difference in H. pylori eradication in patients treated with the common eradication regimen (triple therapy) compared to patients who received this treatment regimen plus vitamins C and E.<a class="elsevierStyleCrossRefs" href="#bib0355">26,30–33</a> Similarly, there is no statistically significant benefit in combining quadruple therapy with the supplement of the 2 vitamins<a class="elsevierStyleCrossRefs" href="#bib0360">27,32</a>; neither when using the eradication therapy regimen accompanied only by vitamin C.<a class="elsevierStyleCrossRefs" href="#bib0370">29,34–36</a> On the other hand, it is worth mentioning that in the studies analyzed, the vitamin doses were variable; this is particularly important in the Sezikli et al. study, in which vitamins C and E were administered, the first at a dose of 1000mg per day (with the vitamin C dose being the highest of all the studies), finding more encouraging results for the eradication of H. pylori than in the other studies.<a class="elsevierStyleCrossRef" href="#bib0360">27</a>Contrary to the results of the clinical trials in question, we highlight that in the last 15 years, numerous studies have been published internationally, addressing the effect of nutritional supplements such as trace elements or vitamins for the eradication of H. pylori.<a class="elsevierStyleCrossRefs" href="#bib0410">37,38</a> In this way, the antioxidant effect of vitamins C and E avoids some of the adverse reactions of prolonged use of antibiotics, among which are: chronic gastritis, preneoplastic lesions and the increase of bacterial resistance to antibiotic treatment.<a class="elsevierStyleCrossRef" href="#bib0420">39</a> Zhang et al. found that high concentrations of vitamin C have a pH-dependent effect, radically inhibiting bacterial growth.<a class="elsevierStyleCrossRef" href="#bib0425">40</a> On the other hand, studies in animal models show that a diet rich in vitamin C greatly reduces the load of H. pylori on the gastric mucosa of mice and guinea pigs.<a class="elsevierStyleCrossRefs" href="#bib0430">41,42</a>Some cohort studies suggest vitamin C intake in patients infected with H. pylori, like Mard et al. who found through serial ultrasound evaluation that vitamin C intake affects the microenvironment of H. pylori and therefore decreases the harmful effect of reactive oxygen species on the gastric mucosa.<a class="elsevierStyleCrossRef" href="#bib0440">43</a> Tümgör et al. published a similar design study carried out in the paediatric population and concluded that the continuous intake of vitamin C improves the prognosis of H. pylori gastritis.<a class="elsevierStyleCrossRef" href="#bib0345">24</a> With similar results, Kim et al. claimed, in a prospective cohort that included 295 individuals, that continuous vitamin C intake can beneficially modify the causal relationship between H. pylori and the development of gastric cancer.<a class="elsevierStyleCrossRef" href="#bib0445">44</a>The use of vitamins C and E for this purpose have been the subject of clinical trials since 2002, with the first steps taken by Everett et al.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> and Chuang et al.<a class="elsevierStyleCrossRef" href="#bib0375">30</a> in England and Taiwan, respectively. Our meta-analysis is preceded by another conducted by Li et al., in 2011, who obtained 6 clinical trials in their search: Sezikli et al.,<a class="elsevierStyleCrossRef" href="#bib0360">27</a> Everett et al.,<a class="elsevierStyleCrossRef" href="#bib0390">33</a> Zojaji et al.,<a class="elsevierStyleCrossRef" href="#bib0400">35</a> Koçkar et al.<a class="elsevierStyleCrossRef" href="#bib0405">36</a> and the 2 studies by Chuang et al.<a class="elsevierStyleCrossRefs" href="#bib0370">29,30</a> The meta-analysis of Li et al. includes the information search algorithm, however, our research provides 4 other studies published after the Li et al. study. In the bias assessment, there is uncertainty regarding the randomization mechanism or the follow-up of patients in each study included in this meta-analysis.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> It should be noted that there is uncertainty on why the studies were compared without taking into account the differences according to type of triple or quadruple empirical therapy, doses, antibiotics administered and follow-up time. Li et al. do not evaluate the subgroups in isolation, considering the effect of vitamin C and E supplement, or vitamin C only, along with conventional triple or quadruple therapy.<a class="elsevierStyleCrossRef" href="#bib0310">17</a>This meta-analysis has as strengths the sensitivity and completeness of the bibliographic search, the separate analysis of whether the standard antibiotic therapy was triple or quadruple and the effect of vitamin C in isolation. All the clinical trials analyzed are randomized and evaluated according to subgroups. The analysis showed that none of the comparisons showed publication bias. On the other hand, it is necessary to mention the limitations of this manuscript; the main obstacle found was the heterogeneity of the manuscripts, since the trials considered were unequal in terms of the population selection parameters, the diagnostic method, the antibiotics used, the management of PPI vs bismuth salts administered, the vitamin doses, the duration of the treatment and the time of follow-up; this hinders statistical analysis and the consolidation of results, which means, in part, that the statistical result associated with the methodological heterogeneity of the studies taken into account is not so reliable. We emphasize that no study describes an adequate method by which the randomization allocation sequence is blinded; in addition, only one of the studies mentions the blinding method for participants and investigators, but does not describe it.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> Finally, the study by Babu et al.,<a class="elsevierStyleCrossRef" href="#bib0380">31</a> being a scientific conference summary, reports incomplete results because there is no selective information report. For all the above-mentioned reasons, we encourage future research by conducting a randomized clinical trial based on international guidelines, to clarify the information and answer the question on the therapeutic use indication of vitamin C and E supplements in the eradication of H. pylori in patients with acid-peptic disease.In conclusion, this study seems to indicate that there is no statistical relationship between vitamin C and E supplementation or vitamin C combined with antibiotic therapy against H. pylori infection. However, the studies included have several methodological biases. Nevertheless, there are studies that indicate that the addition of vitamin C supplements at doses greater than 1000mg a day and vitamin E of 400mg per day for a month, together with antibiotic therapy, is more effective in the treatment against H. pylori infection.<a class="elsevierStyleCrossRef" href="#bib0450">45</a>Conflict of interestsThe authors declare no conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1063457" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1011661" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1063458" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1011660" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methodology" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Registry" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Eligibility criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Information sources" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Search" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Study selection" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Data collection process" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Analysis of data" ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Study selection" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Characteristics of the studies" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Quality evaluation" ] 3 => array:3 [ "identificador" => "sec0070" "titulo" => "Antibiotic therapy with vitamin C and E supplement" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Triple therapy" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Quadruple therapy" ] ] ] 4 => array:2 [ "identificador" => "sec0085" "titulo" => "Antibiotic therapy with vitamin C supplement" ] 5 => array:2 [ "identificador" => "sec0090" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0095" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflict of interests" ] 9 => array:2 [ "identificador" => "xack359941" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-04-13" "fechaAceptado" => "2017-09-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1011661" "palabras" => array:5 [ 0 => "Helicobacter pylori" 1 => "Ascorbic acid" 2 => "Vitamin E" 3 => "Vitamin C" 4 => "Meta-analysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1011660" "palabras" => array:5 [ 0 => "Helicobacter pylori" 1 => "Ácido ascórbico" 2 => "Vitamina E" 3 => "Vitamina C" 4 => "Metaanálisis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionHelicobacter pylori infections affect almost 50% of the world population, constituting a risk factor for benign and malignant gastrointestinal diseases. The increased resistance to antibiotic treatment against this infection represents a dilemma in the search of other therapeutic alternatives. ObjectiveTo determine the efficacy of the use of vitamin C and E supplements concomitantly to antibiotic treatment against H. pylori infections. MethodsWe performed a systematic review on the MedLine (PubMed), Embase and Cochrane Central Register of Clinical Trials (CENTRAL) databases, searching for studies evaluating the efficacy of vitamin C and/or E supplements in the antibiotic treatment of H. pylori infections. The primary outcome was eradication of the infection. The secondary outcome was the adverse effects. The meta-analysis was conducted using the random effects method. ResultsTen studies were included and analyzed in two groups. The first group, which was comprised by 973 patients, compared the use of supplementation with vitamin C and E, showing that, without discriminating the number of antibiotics used, there was no relationship with the eradication of the infection (OR: 1.98 [95% CI: 0.92–4.29], p=0.08). The triple or quadruple antibiotic therapy had no effect on eradication rates either (OR 1.80 [95% CI: 0.64–5.08], p=0.26 and OR: 2.84 [95% CI: 0.51–15.56], p=0.22, respectively). No effect on the eradication rates was observed either in the group that only assessed the use of vitamin C, comprised by 702 patients (OR: 1.17 [95% CI: 0.58–2.31], p=0.65). Only four studies reported adverse effects, the most common one being nausea. ConclusionsSupplementation with vitamin C and E in the antibiotic treatment against H. pylori has no effect. However, the reviewed studies had several biases and differences in the dosage of the supplements and antibiotics administered." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa prevalencia de la infección por Helicobacter pylori afecta casi al 50% de la población mundial, siendo un factor de riesgo para enfermedades benignas y malignas gastrointestinales. El aumento de la resistencia al tratamiento antibiótico contra esta infección ha presentado un dilema en el abordaje de otras alternativas en la terapéutica. ObjetivoDeterminar la eficacia del suplemento de vitaminas C y E añadido al tratamiento antibiótico en la erradicación de la infección por H. pylori. MétodosSe realizó una revisión sistemática en las bases de datos de MedLine, Embase y Cochrane Central Register of Clinical Trials (CENTRAL), para estudios que evaluaran la eficacia del suplemento de vitaminas C y/o E en el tratamiento antibiótico de infección por H. pylori. El resultado principal fue erradicación de la infección y el secundario fueron efectos adversos. El metaanálisis fue elaborado mediante el método de efectos aleatorios. ResultadosSe incluyeron 10 estudios y se hicieron 2 grupos. El primero comparó el uso de suplemento de vitaminas C y E incluyendo 973 pacientes, en el cual sin discriminar el número de antibióticos no se obtuvo una relación con la erradicación de la infección (OR: 1,98 [IC95%: 0,92-4,29], p=0,08). La terapia triple o cuádruple antibiótica no tuvo un efecto sobre la erradicación (OR: 1,80 [IC95%: 0,64-5,08], p=0,26, y OR: 2,84 [IC95%: 0,51-15,56], p=0,22, respectivamente). En el grupo en que solo se evaluó el uso de vitaminaC se incluyeron 702pacientes, pero no se obtuvo un efecto sobre la erradicación (OR: 1,17 [IC95%: 0,58-2,31], p=0,65). Los efectos adversos solo fueron reportados en 4 estudios, siendo el más frecuente las náuseas. ConclusionesEl suplemento de vitaminas C y E en la terapia antibiótica contra H. pylori no tuvo ningún efecto. Sin embargo, los estudios presentaron bastantes sesgos y diferencias en la posología de los suplementos y antibióticos." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Caicedo Ochoa EY, Quintero Moreno CO, Méndez Fandiño YR, Sánchez Fonseca SC, Cortes Motta HF, Guio Guerra SA. Evaluación del suplemento de vitaminas C y E en el tratamiento antibiótico contra Helicobacter pylori: revisión sistemática y metaanálisis. Med Clin (Barc). 2018;151:45–52." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2157 "Ancho" => 2216 "Tamanyo" => 206584 ] ] "descripcion" => array:1 [ "en" => "Flow chart of the selection process." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3080 "Ancho" => 1342 "Tamanyo" => 344274 ] ] "descripcion" => array:1 [ "en" => "Evaluation of biases in the studies selected." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3022 "Ancho" => 1505 "Tamanyo" => 280837 ] ] "descripcion" => array:1 [ "en" => "Efficacy of vitamin C and E supplementation as adjuvant in the antibiotic treatment of Helicobacter pylori. (A) Without discrimination regarding number of antibiotics. (B) Triple therapy. (C) Quadruple therapy." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1338 "Ancho" => 2083 "Tamanyo" => 113333 ] ] "descripcion" => array:1 [ "en" => "Efficacy of vitamin C supplement as adjuvant in the antibiotic treatment of Helicobacter pylori." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "FD: 4 times a day; TD: twice a day; RCT: randomized clinical trial; NA: data not available; BT: breath test; TDD: 3 doses per day; RUT: rapid urease test; OD: once a day" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Year \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Place \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Design \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Antibiotics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Supplement \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Treatment time \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Antibiotics</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Supplement</th><th class="td" title="table-head " align="left" valign="top" scope="col">Diagnostic test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Test to confirm eradication \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients (n) and gender (male/female) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients (n) and gender (male/female) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="13" align="left" valign="top">Vitamins C and E supplementation</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sezikli et al.<a class="elsevierStyleCrossRef" href="#bib0360">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT-open label \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lansoprazole 30mg TD; amoxicillin 1000mg TD; clarithromycin 500mg TD; bismuth subcitrate 300mg FD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg TD, vitamin E 200UI TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80 (28/52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44±10<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80 (24/56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43±11<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sezikli et al.<a class="elsevierStyleCrossRef" href="#bib0355">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT-open label \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lansoprazole 30mg TD; amoxicillin 1000mg TD; clarithromycin 500mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg TD, vitamin E 200UI TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 (13/27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.7±10.8<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160 (53/107) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39.7±19<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Everett et al.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">United Kingdom \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT-double blind study, controlled \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bismuth subcitrate 120mg OD; metronidazole 400mg TDD; tetracycline 500mg FD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 200mg TD, vitamin E 50mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 (13/12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 (17–75)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (15/9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49 (22–65)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological and culture \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chuang et al.<a class="elsevierStyleCrossRef" href="#bib0375">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Taiwan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lansoprazole 30mg OD; amoxicillin 1000mg OD; metronidazole 500mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 250mg, vitamin E 200mg TD for one week; then, vitamin C 250mg, vitamin E 200mg OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 days of antibiotic treatment, then 6 weeks with supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49 (19/30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35.6±14.3<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 (21/34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.9±13.6<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological and culture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT or histological \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Babu et al.<a class="elsevierStyleCrossRef" href="#bib0380">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT-open label \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxicillin 1000mg TD; metronidazole 400mg FD; Omeprazole 40mg OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg OD, vitamin E 200UI TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days of antibiotic treatment and 28 days with supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Demirci et al.<a class="elsevierStyleCrossRef" href="#bib0385">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxicillin 1000mg TD; clarithromycin 500mg TD; Lansoprazole 30mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg OD, vitamin E 100UI OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (53/47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 (26–66)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (59/41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 (21–65)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Demirci et al.<a class="elsevierStyleCrossRef" href="#bib0385">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxicillin 1000mg TD; clarithromycin 500mg TD; Lansoprazole 30mg TD; bismuth subcitrate 400mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg OD, vitamin E 100UI OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (52/48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 (24–66)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (60/40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38 (22–65)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="13" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="13" align="left" valign="top">Vitamin C supplement</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Zojaji et al.<a class="elsevierStyleCrossRef" href="#bib0400">35</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxicillin 500mg TD; metronidazole 500mg TD; subcitrate of bismuth240mg TD; omeprazole 20mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">162 (40/122) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150 (36/114) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kaboli et al.<a class="elsevierStyleCrossRefs" href="#bib0240">3,4</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Omeprazole 20mg TD; Amoxicillin 1000mg TD; clarithromycin 500mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 250mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">114 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological, RUT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chuang et al.<a class="elsevierStyleCrossRef" href="#bib0370">29</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Taiwan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Omeprazole 20mg OD; Amoxicillin 1000mg OD; clarithromycin 250mg OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 500mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 days of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61 (NA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Koçkar et al.<a class="elsevierStyleCrossRef" href="#bib0405">36</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Turkey \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lansoprazole 30mg TD; clarithromycin500mg TD; amoxicillin 1000mg TD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vitamin C 1000mg OD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 days of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.9±10<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (14/16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40±10<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Histological \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1813184.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Mean±standard deviation." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Median (confidence interval)." ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of included studies." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0230" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Helicobacter pylori infection: an overview of bacterial virulence factors and pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.-Y. 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Original article

Assessment of the use of vitamin C and E supplements concomitantly to antibiotic treatment against Helicobacter pylori: A systematic review and meta-analysis

Evaluación del suplemento de vitaminas C y E en el tratamiento antibiótico contra Helicobacter pylori: revisión sistemática y metaanálisis

Edgar Yaset Caicedo Ochoaa,

Corresponding author

grab.uptc@gmail.com

Corresponding author.

, César Orlando Quintero Morenoa, Yardany Rafael Méndez Fandiñoa,b, Sofía Catalina Sánchez Fonsecaa, Héctor Fabio Cortes Mottaa, Santiago Alejandro Guio Guerraa

a Grupo de Investigación en Análisis de Resistencia Bacteriana de Boyacá (GRAB), Escuela de Medicina, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Boyacá, Colombia

b Departamento de Medicina Interna, Hospital Regional de Duitama, Duitama, Boyacá, Colombia

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Helicobacter pylori</span> infection has been documented as one of the most prevalent in the world&#59; approximately half of the world&#39;s population is infected with this microorganism&#46; In developing countries&#44; the prevalence ranges from 75&#37; to 86&#37;&#44; unlike developed countries&#44; which report rates of 39&#46;6&#37; in Japan and 17&#46;1&#37; in the United States&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#44;2</span></a> Studies carried out in different countries around the world describe the following risk factors&#58; low socio-economic level&#44; high population density&#44; inadequate hygiene habits and difficult access to education and health services&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The clinical importance of <span class="elsevierStyleItalic">H&#46; pylori</span> infection lies in its relationship with the development of a broad spectrum of gastrointestinal diseases such as&#58; gastritis&#44; dyspepsia&#44; peptic ulcer&#44; mucosal-associated lymphoid tissue &#40;MALT&#41; lymphoma and gastric cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">1</span></a> Under the circumstances&#44; pharmacological treatment strategies have been developed for said infection&#46; Some international guidelines describe standard triple therapies that include a proton pump inhibitor &#40;PPI&#41;&#44; clarithromycin&#44; and amoxicillin or metronidazole&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">4&#8211;6</span></a> Other alternatives have proposed a quadruple therapy based on bismuth salts with metronidazole and tetracycline&#44; and even third and fourth generation quinolones are recommended for said treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; resistance rates of <span class="elsevierStyleItalic">H&#46; pylori</span> have been increasing since the beginning of the <span class="elsevierStyleSmallCaps">XXI</span> century&#46; For example&#44; in 2004&#44; the percentage of resistance in the United States was 13&#37;&#44; increasing to 18&#37; in 2015&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">8</span></a> In northern India&#44; Gehlot et al&#46; evaluated strains isolated from 68 patients where they described a resistance percentage of 70&#46;6&#37;&#44; including 48&#46;5&#37; resistance to metronidazole&#44; 17&#46;6&#37; to amoxicillin&#44; 16&#46;2&#37; to tetracycline and 11&#46;8&#37; to clarithromycin&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">9</span></a> In France&#44; Ducournanu et al&#46; documented 115 patients with <span class="elsevierStyleItalic">H&#46; pylori</span>&#44; with a resistance of 73&#46;9&#37; for clarithromycin and 78&#46;3&#37; for metronidazole&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There are some alternatives for the treatment of this infection currently under investigation&#44; which include&#58; vaccines&#44; prebiotics grown from fermented milk&#44; phytotherapy and vitamin C and E supplements&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">11&#44;12</span></a> The use of prebiotics proved to be effective in eradication&#44; according to the meta-analysis conducted by Guo et al&#46;&#44; as long as it was administered with the standard treatment&#46; Despite the foregoing&#44; prebiotics do not reduce drug-related adverse reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">13</span></a> Phytotherapy was evaluated in in vitro and in vivo studies&#44; where some components are effective in the eradication of bacteria and prevention of gastric cancer but produce undesirable effects in animal models&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the same way&#44; in vitro studies have been carried out with antioxidant compounds such as vitamin C and E supplements in states of chronic inflammation &#40;which precedes the formation of neoplasms in the gastric mucosa&#41;&#44; which exerted a cytoprotective effect&#46; In murine models&#44; the consumption of vitamins C and E generated a hostile environment for the microorganism and facilitated its elimination by antimicrobials&#44; reducing strains that can enter bacterial gene material for resistance acquisition&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a> Poplawski et al&#46; evaluated in vitro the effects of vitamin C in the context of infection by <span class="elsevierStyleItalic">H&#46; pylori</span> observing a genotoxicity reduction in heterocyclic amines in the above-mentioned environment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">16</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the year 2011&#44; Li et al&#46; reported a meta-analysis evaluating vitamin C and E supplements in the eradication of <span class="elsevierStyleItalic">H&#46; pylori</span>&#46; It included 6 studies where they compared the use of vitamins C and E&#46; However&#44; they omitted to consider the number of antibiotics used&#46; Based on this study&#44; new research was conducted in Turkey&#44; which may provide new perspectives for the study of this phenomenon&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a> Therefore&#44; the present study aims to perform a systematic review of the literature&#44; evaluating the efficacy and safety of the use of vitamin C and E supplements or just vitamin C supplement with antibiotic therapy for the eradication of <span class="elsevierStyleItalic">H&#46; pylori&#46;</span></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methodology</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Registry</span><p id="par0035" class="elsevierStylePara elsevierViewall">We followed the criteria of the <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews and Meta-Analyses</span> &#40;PRISMA&#41; guidelines for the development of systematic reviews and meta-analyzes&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Eligibility criteria</span><p id="par0040" class="elsevierStylePara elsevierViewall">Randomized double-blind&#44; single-blind&#44; or open-label clinical trials evaluating vitamin C and E supplementation were selected&#44; attached to triple or quadruple antibiotic therapy in <span class="elsevierStyleItalic">H&#46; pylori</span> infection diagnosed by the urease test method&#44; biopsy or culture&#46; The main outcome was the eradication of the infection&#44; defined as a negative urea breath test or a negative histological finding after treatment and the secondary outcome was adverse reactions&#46; Cohort studies&#44; in vitro studies or cases-control studies were excluded&#46; Conference summaries found in the databases selected in the reports of academic events were also considered&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Information sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">MedLine &#40;PubMed&#41;&#44; Embase and <span class="elsevierStyleItalic">Cochrane Central Register of Clinical Trials</span> &#40;CENTRAL&#41; databases&#46; The search was conducted between May 12 and June 12&#44; 2016&#46; In case of expanding some information&#44; we tried to contact the authors&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Search</span><p id="par0050" class="elsevierStylePara elsevierViewall">The following were used as search criteria&#58; &#40;acid&#44; ascorbic OR L-ascorbic acid OR vitamin C OR sodium ascorbate&#41; OR &#40;vitamin E OR tocopherols OR alpha-tocopherol OR beta-tocopherol OR gamma-tocopherol&#41; AND &#40;<span class="elsevierStyleItalic">Helicobacter pylori</span> OR <span class="elsevierStyleItalic">H pylori</span> OR infection <span class="elsevierStyleItalic">Helicobacter pylori</span>&#41;&#46; No restrictions were made regarding time or language&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Study selection</span><p id="par0055" class="elsevierStylePara elsevierViewall">The records reported by the databases were reviewed by 2 authors&#44; independently&#44; and in case of any discrepancy&#44; a third reviewer was consulted&#46; The summaries of the manuscripts were obtained according to the title and summary that&#44; in the context of patients infected by <span class="elsevierStyleItalic">H&#46; pylori</span>&#44; enunciated the antibiotic treatment with vitamin C or E supplementation&#46; The results obtained were recorded in a database&#46; Subsequently&#44; the search of the articles was carried out &#8220;in extenso&#8221;&#44; to verify the inclusion and exclusion criteria in the systematic review&#46; The diagnostic and eradication method of <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#44; pharmacological treatment and its doses were verified in the database&#44; in addition&#44; vitamin C and E doses were recorded&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Data collection process</span><p id="par0060" class="elsevierStylePara elsevierViewall">From the selected studies&#44; the search for extensive documents was started&#44; evaluating the following variables&#58; diagnostic method for <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#59; dosage of antibiotics and vitamin C or E supplementation&#44; follow-up of patients in treatment and post-treatment <span class="elsevierStyleItalic">H&#46; pylori</span> infection evaluation&#46; In addition&#44; the method to establish eradication was recorded in the database&#46; The evaluation of biases was made according to the guidelines presented by Higgins and Green in the <span class="elsevierStyleItalic">Cochrane Handbook of systematic intervention reviews</span> of the Cochrane collaboration&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">19</span></a> taking into account selection&#44; information and analysis biases&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Analysis of data</span><p id="par0065" class="elsevierStylePara elsevierViewall">The association measure for the main outcome was the odds ratio &#40;OR&#41; with a confidence interval of 95&#37; &#40;95&#37; CI&#41;&#46; An analysis was made by the random-effects method due to the variability in dosage&#44; antibiotics used&#44; time of treatment and after-treatment progression&#44; under the statistical method of Mantel-Haenszel&#46; The proposed analyses were&#58; use of vitamin C or its combination with vitamin E along with antimicrobial therapy without considering the number of antibiotics&#46; Subsequently&#44; the number of drugs in antibiotic therapy was evaluated in a discriminatory manner&#46; The data report was evaluated by &#8220;intention to treat&#8221;&#44; taking into account the methodological failures of some studies to determine the events related to the loss of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">20</span></a> Statistical heterogeneity was calculated considering the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>&#44; according to Higgins et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a>&#59; and so high heterogeneity was defined for the manuscripts if they presented an <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> greater than 30&#37;&#44; or in case of finding a <span class="elsevierStyleItalic">p</span>-value less than 0&#46;10 for the Chi-square heterogeneity test&#46; Finally&#44; an analysis of publication biases was performed using the Egger test&#44; considering it to be of high risk of bias if it was significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">22</span></a> The analysis was developed using the STATA 14 software and the graphical component of the bias analysis of the feature provided by Review Manager 5&#46;3 &#40;<span class="elsevierStyleItalic">The Nordic Cochrane Centre</span>&#44; Copenhagen&#44; Denmark&#41;&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Study selection</span><p id="par0070" class="elsevierStylePara elsevierViewall">2441 records were obtained &#40;Medline&#44; 269 studies&#44; Embase&#44; 818 studies and CENTRAL&#44; 1354 studies&#41;&#46; We selected 42 studies that would potentially meet our study&#39;s criteria&#46; When reviewing all the complete manuscripts&#44; 28 records were discarded&#44; because several were duplicated &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; 14 studies were the evaluated in depth&#44; out of which 3 were excluded&#46; Yoshinaga et al&#46; only compared the use of vitamin C supplement versus treatment with omeprazole&#44; T&#252;mg&#246;r et al&#46; only compared the use of vitamin E&#44; and Correa et al&#46; contrasted the treatment with vitamin C supplement against beta-carotenes for one year&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">23&#8211;25</span></a> Of the 11 studies obtained&#44; we found several published manuscripts derived from the same sample&#46; In the case of Sezikli et al&#46;&#44; 3 articles were found&#58; the first one described the antioxidant capacity&#44; which was discarded for not complying with the results considered in this review&#44; and the other 2 papers compared triple and quadruple therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#8211;28</span></a> In the case of Chuang et al&#46;&#44; there were 2 articles where they mentioned a management difference with or without clarithromycin&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;30</span></a> Finally&#44; we evaluated 10 articles for the meta-analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Characteristics of the studies</span><p id="par0075" class="elsevierStylePara elsevierViewall">The use of vitamin C and E supplement in antibiotic therapy was evaluated in 6 studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;27&#44;30&#8211;33</span></a> The manuscripts of Sezikli et al&#46; published between 2009 and 2012 were considered separately&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;27</span></a> The same was done with that of Demirci et al&#46;&#44; since they evaluated different patients in each arm of the study&#44; with variation in triple or quadruple therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a> 973 patients were obtained in the management of vitamin C and E supplement versus antibiotic therapy &#40;424 of antibiotic therapy vs 549 of therapy with supplementation&#41;&#46; Within the characteristics of the studies&#44; Chuang et al&#46;&#44; Babu et al&#46;&#44; and Kaboli et al&#46; do not describe sample characteristics such as the age and the number of male patients who were part of the studied population&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;31&#44;34</span></a> The studies of Chuang et al&#46; evaluated the group of younger patients<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a>&#59; almost all studies evaluated eradication with the use of the urea breath test &#40;UBT&#41;&#44; with the exception of Babu et al&#46; and Everett et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">31&#44;33</span></a> The other elements are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Therapy with only vitamin C supplement was evaluated in 4 studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;34&#8211;36</span></a> with 702 patients &#40;347 of antibiotic therapy vs 355 of therapy with supplement&#41;&#59; almost all studies evaluated eradication using UBT&#44; except for Ko&#231;kar et al&#46;&#44; who made a histological diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Quality evaluation</span><p id="par0080" class="elsevierStylePara elsevierViewall">The studies were evaluated according to the Cochrane Collaboration guidelines&#46; Of the 10 clinical trials&#44; 9 studies had a high risk of bias&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;27&#44;29&#8211;32&#44;34&#8211;36</span></a> Although all the studies were described as randomized&#44; they did not describe the randomization method or sequence and the integrity of concealment of the randomization is not very clear either&#46; Blinding was only reported by the Everett et al&#46; study&#44; as double blind&#44; however&#44; there is uncertainty about the follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> A conference summary was included&#44; which reports only the main outcome information&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a> Therefore&#44; the studies show biases in selection and information &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Antibiotic therapy with vitamin C and E supplement</span><p id="par0085" class="elsevierStylePara elsevierViewall">Not counting the number of antibiotics used in the therapy of each study&#44; it was estimated that there is no statistically significant relationship between the use of vitamin C and E supplement in antibiotic therapy &#40;OR&#58; 1&#46;98 &#91;95&#37; CI&#58; 0&#46;91&#8211;4&#46;28&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#44; with high heterogeneity but no publication bias &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>84&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#59; Egger test&#58; 0&#46;30&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Triple therapy</span><p id="par0090" class="elsevierStylePara elsevierViewall">Of the studies evaluated&#44; 5 used triple therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;30&#8211;33</span></a> 4 used PPIs with antibiotics&#44; except for Everett et al&#46;&#44; who used bismuth&#46; Regarding the antibiotic therapy&#44; Sezikli et al&#46; and Demirci et al&#46; used amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD &#40;twice a day&#41; and clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;32</span></a> while Chuang et al&#46; and Babu et al&#46; treated with amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg and metronidazole 400&#8211;500<span class="elsevierStyleHsp" style=""></span>mg&#44; with differences in the dosage between these 2 studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">30&#44;31</span></a> Everett et al&#46; used metronidazole 400<span class="elsevierStyleHsp" style=""></span>mg TDD &#40;3 doses per day&#41; and tetracycline 500<span class="elsevierStyleHsp" style=""></span>mg FDD &#40;4 doses per day&#41;&#46; The doses of vitamin C and E supplement showed important differences&#59; Sezikli et al&#46; administered 1000<span class="elsevierStyleHsp" style=""></span>mg day&#44; and the other studies used 500<span class="elsevierStyleHsp" style=""></span>mg or less a day of vitamin C&#46; Sezikli et al&#46; and Babu et al&#46; administered 400<span class="elsevierStyleHsp" style=""></span>UI a day of vitamin E&#44; while others used lower doses&#46; Almost all the regimens lasted at least 14 days with additional supplement therapy in 4 studies for almost 30 days&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;31&#44;32</span></a> except Everett et al&#46;&#44; who only administered the therapy for 14 days&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> The meta-analysis of these studies found that the effect of antibiotic therapy with vitamins C and E supplement is not statistically significant in eradication if triple therapy is administered &#40;OR 1&#46;80 &#91;95&#37; CI&#58; 0&#46;64&#8211;5&#46;08&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;26&#41;&#44; with the studies showing high heterogeneity&#44; but without publication bias &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>85&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#59; Egger test&#58; 0&#46;33&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Quadruple therapy</span><p id="par0095" class="elsevierStylePara elsevierViewall">Two studies used quadruple therapy<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">27&#44;32</span></a>&#59; both used PPI plus bismuth&#44; although the study by Demirci et al&#46; administered a total of 800<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; while Sezikli et al&#46; used 1200<span class="elsevierStyleHsp" style=""></span>mg&#47;day of bismuth&#59; both used the same antibiotic dose of amoxicillin 1000 <span class="elsevierStyleHsp" style=""></span>mg TD and clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#46; The dose of vitamin C supplement was higher in the paper by Sezikli et al&#46; with 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day and also that of vitamin E with 400<span class="elsevierStyleHsp" style=""></span>UI&#47;day versus 100<span class="elsevierStyleHsp" style=""></span>UI&#47;day&#46; The treatment follow-up time was equal to 14 days and a 30-day supplement&#46; According to the meta-analysis&#44; in quadruple therapy there is no effect on <span class="elsevierStyleItalic">H&#46; pylori</span> eradication with vitamin C and E supplement therapy &#40;OR&#58; 2&#46;84 &#91;95&#37; CI&#58; 0&#46;51&#8211;15&#46;56&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#41;&#46; However&#44; it shows high heterogeneity &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>89&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C&#41;&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Antibiotic therapy with vitamin C supplement</span><p id="par0100" class="elsevierStylePara elsevierViewall">We obtained 4 studies that evaluated only vitamin C supplement<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;34&#8211;36</span></a>&#59; 3 used triple therapy&#44; all used PPI and antibiotic&#44; amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg and clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;34&#44;36</span></a> Only Zojaji et al&#46; administered PPI and bismuth&#44; along with antibiotic therapy of amoxicillin and metronidazole&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> The dose of vitamin C supplement was higher in the Chuang et al&#46; and Ko&#231;kar et al&#46; studies with 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;36</span></a>&#59; the treatment time was the same for all&#44; except for Chuang et al&#46; who implemented the therapy for 7 days&#46; According to the meta-analysis&#44; the use of vitamin C combined with triple or quadruple therapy has no effect on the eradication of <span class="elsevierStyleItalic">H&#46; pylori</span> &#40;OR&#58; 1&#46;17 &#91;IC95&#37;&#58; 0&#46;58&#8211;2&#46;31&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;65&#41; with high heterogeneity&#44; without publication bias &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>67&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#59; Egger test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;96&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Safety</span><p id="par0105" class="elsevierStylePara elsevierViewall">4 studies reported adverse reactions&#46; Zojaji et al&#46; reported the presence of persistent nausea and headaches&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> The studies by Sezikli et al&#46; documented nausea and persistent metallic taste<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;27</span></a>&#59; Ko&#231;kar et al&#46; evaluated adverse reactions and reported that no adverse effect was observed in their study&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a></p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">The purpose of this research is to search for new or complementary therapeutic alternatives to the management of <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#44; considering the high prevalence of this microorganism and the earlier detection since this infection is associated with the development of gastric cancer&#46; The present study&#44; which included 10 studies&#44; shows considerable heterogeneity due to the methodological designs of the open-label clinical trials&#59; aspects such as blinding of randomization and patient follow-up are not consistent in some studies&#46; In addition&#44; it is worth mentioning that the research conducted in this area has been mainly carried out in countries like Turkey and Taiwan&#44; which are not related to other areas where the prevalence of gastric cancer associated with <span class="elsevierStyleItalic">H&#46; pylori</span> infection is high&#44; as the Andean region in South America and some regions in Asia&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;27&#44;29&#8211;32&#44;34&#8211;36</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In the specific evaluation of clinical trials there is no difference in <span class="elsevierStyleItalic">H&#46; pylori</span> eradication in patients treated with the common eradication regimen &#40;triple therapy&#41; compared to patients who received this treatment regimen plus vitamins C and E&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26&#44;30&#8211;33</span></a> Similarly&#44; there is no statistically significant benefit in combining quadruple therapy with the supplement of the 2 vitamins<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">27&#44;32</span></a>&#59; neither when using the eradication therapy regimen accompanied only by vitamin C&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;34&#8211;36</span></a> On the other hand&#44; it is worth mentioning that in the studies analyzed&#44; the vitamin doses were variable&#59; this is particularly important in the Sezikli et al&#46; study&#44; in which vitamins C and E were administered&#44; the first at a dose of 1000<span class="elsevierStyleHsp" style=""></span>mg per day &#40;with the vitamin C dose being the highest of all the studies&#41;&#44; finding more encouraging results for the eradication of <span class="elsevierStyleItalic">H&#46; pylori</span> than in the other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Contrary to the results of the clinical trials in question&#44; we highlight that in the last 15 years&#44; numerous studies have been published internationally&#44; addressing the effect of nutritional supplements such as trace elements or vitamins for the eradication of <span class="elsevierStyleItalic">H&#46; pylori</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">37&#44;38</span></a> In this way&#44; the antioxidant effect of vitamins C and E avoids some of the adverse reactions of prolonged use of antibiotics&#44; among which are&#58; chronic gastritis&#44; preneoplastic lesions and the increase of bacterial resistance to antibiotic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">39</span></a> Zhang et al&#46; found that high concentrations of vitamin C have a pH-dependent effect&#44; radically inhibiting bacterial growth&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">40</span></a> On the other hand&#44; studies in animal models show that a diet rich in vitamin C greatly reduces the load of <span class="elsevierStyleItalic">H&#46; pylori</span> on the gastric mucosa of mice and guinea pigs&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">41&#44;42</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Some cohort studies suggest vitamin C intake in patients infected with <span class="elsevierStyleItalic">H&#46; pylori</span>&#44; like Mard et al&#46; who found through serial ultrasound evaluation that vitamin C intake affects the microenvironment of <span class="elsevierStyleItalic">H&#46; pylori</span> and therefore decreases the harmful effect of reactive oxygen species on the gastric mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">43</span></a> T&#252;mg&#246;r et al&#46; published a similar design study carried out in the paediatric population and concluded that the continuous intake of vitamin C improves the prognosis of <span class="elsevierStyleItalic">H&#46; pylori gastritis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">24</span></a> With similar results&#44; Kim et al&#46; claimed&#44; in a prospective cohort that included 295 individuals&#44; that continuous vitamin C intake can beneficially modify the causal relationship between <span class="elsevierStyleItalic">H&#46; pylori</span> and the development of gastric cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">44</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The use of vitamins C and E for this purpose have been the subject of clinical trials since 2002&#44; with the first steps taken by Everett et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> and Chuang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a> in England and Taiwan&#44; respectively&#46; Our meta-analysis is preceded by another conducted by Li et al&#46;&#44; in 2011&#44; who obtained 6 clinical trials in their search&#58; Sezikli et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a> Everett et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Zojaji et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> Ko&#231;kar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a> and the 2 studies by Chuang et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">29&#44;30</span></a> The meta-analysis of Li et al&#46; includes the information search algorithm&#44; however&#44; our research provides 4 other studies published after the Li et al&#46; study&#46; In the bias assessment&#44; there is uncertainty regarding the randomization mechanism or the follow-up of patients in each study included in this meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> It should be noted that there is uncertainty on why the studies were compared without taking into account the differences according to type of triple or quadruple empirical therapy&#44; doses&#44; antibiotics administered and follow-up time&#46; Li et al&#46; do not evaluate the subgroups in isolation&#44; considering the effect of vitamin C and E supplement&#44; or vitamin C only&#44; along with conventional triple or quadruple therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">This meta-analysis has as strengths the sensitivity and completeness of the bibliographic search&#44; the separate analysis of whether the standard antibiotic therapy was triple or quadruple and the effect of vitamin C in isolation&#46; All the clinical trials analyzed are randomized and evaluated according to subgroups&#46; The analysis showed that none of the comparisons showed publication bias&#46; On the other hand&#44; it is necessary to mention the limitations of this manuscript&#59; the main obstacle found was the heterogeneity of the manuscripts&#44; since the trials considered were unequal in terms of the population selection parameters&#44; the diagnostic method&#44; the antibiotics used&#44; the management of PPI vs bismuth salts administered&#44; the vitamin doses&#44; the duration of the treatment and the time of follow-up&#59; this hinders statistical analysis and the consolidation of results&#44; which means&#44; in part&#44; that the statistical result associated with the methodological heterogeneity of the studies taken into account is not so reliable&#46; We emphasize that no study describes an adequate method by which the randomization allocation sequence is blinded&#59; in addition&#44; only one of the studies mentions the blinding method for participants and investigators&#44; but does not describe it&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Finally&#44; the study by Babu et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a> being a scientific conference summary&#44; reports incomplete results because there is no selective information report&#46; For all the above-mentioned reasons&#44; we encourage future research by conducting a randomized clinical trial based on international guidelines&#44; to clarify the information and answer the question on the therapeutic use indication of vitamin C and E supplements in the eradication of <span class="elsevierStyleItalic">H&#46; pylori</span> in patients with acid-peptic disease&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study seems to indicate that there is no statistical relationship between vitamin C and E supplementation or vitamin C combined with antibiotic therapy against <span class="elsevierStyleItalic">H&#46; pylori infection&#46;</span> However&#44; the studies included have several methodological biases&#46; Nevertheless&#44; there are studies that indicate that the addition of vitamin C supplements at doses greater than 1000<span class="elsevierStyleHsp" style=""></span>mg a day and vitamin E of 400<span class="elsevierStyleHsp" style=""></span>mg per day for a month&#44; together with antibiotic therapy&#44; is more effective in the treatment against <span class="elsevierStyleItalic">H&#46; pylori infection</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conflict of interests</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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                  "titulo" => "Triple therapy"
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              "titulo" => "Antibiotic therapy with vitamin C supplement"
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    "fechaRecibido" => "2017-04-13"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Helicobacter pylori</span> infections affect almost 50&#37; of the world population&#44; constituting a risk factor for benign and malignant gastrointestinal diseases&#46; The increased resistance to antibiotic treatment against this infection represents a dilemma in the search of other therapeutic alternatives&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the efficacy of the use of vitamin C and E supplements concomitantly to antibiotic treatment against <span class="elsevierStyleItalic">H&#46; pylori</span> infections&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We performed a systematic review on the MedLine &#40;PubMed&#41;&#44; Embase and Cochrane Central Register of Clinical Trials &#40;CENTRAL&#41; databases&#44; searching for studies evaluating the efficacy of vitamin C and&#47;or E supplements in the antibiotic treatment of <span class="elsevierStyleItalic">H&#46; pylori</span> infections&#46; The primary outcome was eradication of the infection&#46; The secondary outcome was the adverse effects&#46; The meta-analysis was conducted using the random effects method&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ten studies were included and analyzed in two groups&#46; The first group&#44; which was comprised by 973 patients&#44; compared the use of supplementation with vitamin C and E&#44; showing that&#44; without discriminating the number of antibiotics used&#44; there was no relationship with the eradication of the infection &#40;OR&#58; 1&#46;98 &#91;95&#37; CI&#58; 0&#46;92&#8211;4&#46;29&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#46; The triple or quadruple antibiotic therapy had no effect on eradication rates either &#40;OR 1&#46;80 &#91;95&#37; CI&#58; 0&#46;64&#8211;5&#46;08&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;26 and OR&#58; 2&#46;84 &#91;95&#37; CI&#58; 0&#46;51&#8211;15&#46;56&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#44; respectively&#41;&#46; No effect on the eradication rates was observed either in the group that only assessed the use of vitamin C&#44; comprised by 702 patients &#40;OR&#58; 1&#46;17 &#91;95&#37; CI&#58; 0&#46;58&#8211;2&#46;31&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;65&#41;&#46; Only four studies reported adverse effects&#44; the most common one being nausea&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Supplementation with vitamin C and E in the antibiotic treatment against <span class="elsevierStyleItalic">H&#46; pylori</span> has no effect&#46; However&#44; the reviewed studies had several biases and differences in the dosage of the supplements and antibiotics administered&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de la infecci&#243;n por <span class="elsevierStyleItalic">Helicobacter pylori</span> afecta casi al 50&#37; de la poblaci&#243;n mundial&#44; siendo un factor de riesgo para enfermedades benignas y malignas gastrointestinales&#46; El aumento de la resistencia al tratamiento antibi&#243;tico contra esta infecci&#243;n ha presentado un dilema en el abordaje de otras alternativas en la terap&#233;utica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Determinar la eficacia del suplemento de vitaminas C y E a&#241;adido al tratamiento antibi&#243;tico en la erradicaci&#243;n de la infecci&#243;n por <span class="elsevierStyleItalic">H&#46; pylori</span>&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una revisi&#243;n sistem&#225;tica en las bases de datos de MedLine&#44; Embase y <span class="elsevierStyleItalic">Cochrane Central Register of Clinical Trials</span> &#40;CENTRAL&#41;&#44; para estudios que evaluaran la eficacia del suplemento de vitaminas C y&#47;o E en el tratamiento antibi&#243;tico de infecci&#243;n por <span class="elsevierStyleItalic">H&#46; pylori</span>&#46; El resultado principal fue erradicaci&#243;n de la infecci&#243;n y el secundario fueron efectos adversos&#46; El metaan&#225;lisis fue elaborado mediante el m&#233;todo de efectos aleatorios&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 10 estudios y se hicieron 2 grupos&#46; El primero compar&#243; el uso de suplemento de vitaminas C y E incluyendo 973 pacientes&#44; en el cual sin discriminar el n&#250;mero de antibi&#243;ticos no se obtuvo una relaci&#243;n con la erradicaci&#243;n de la infecci&#243;n &#40;OR&#58; 1&#44;98 &#91;IC95&#37;&#58; 0&#44;92-4&#44;29&#93;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;08&#41;&#46; La terapia triple o cu&#225;druple antibi&#243;tica no tuvo un efecto sobre la erradicaci&#243;n &#40;OR&#58; 1&#44;80 &#91;IC95&#37;&#58; 0&#44;64-5&#44;08&#93;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;26&#44; y OR&#58; 2&#44;84 &#91;IC95&#37;&#58; 0&#44;51-15&#44;56&#93;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;22&#44; respectivamente&#41;&#46; En el grupo en que solo se evalu&#243; el uso de vitamina<span class="elsevierStyleHsp" style=""></span>C se incluyeron 702<span class="elsevierStyleHsp" style=""></span>pacientes&#44; pero no se obtuvo un efecto sobre la erradicaci&#243;n &#40;OR&#58; 1&#44;17 &#91;IC95&#37;&#58; 0&#44;58-2&#44;31&#93;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;65&#41;&#46; Los efectos adversos solo fueron reportados en 4 estudios&#44; siendo el m&#225;s frecuente las n&#225;useas&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El suplemento de vitaminas C y E en la terapia antibi&#243;tica contra <span class="elsevierStyleItalic">H&#46; pylori</span> no tuvo ning&#250;n efecto&#46; Sin embargo&#44; los estudios presentaron bastantes sesgos y diferencias en la posolog&#237;a de los suplementos y antibi&#243;ticos&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Caicedo Ochoa EY&#44; Quintero Moreno CO&#44; M&#233;ndez Fandi&#241;o YR&#44; S&#225;nchez Fonseca SC&#44; Cortes Motta HF&#44; Guio Guerra SA&#46; Evaluaci&#243;n del suplemento de vitaminas C y E en el tratamiento antibi&#243;tico contra <span class="elsevierStyleItalic">Helicobacter pylori</span>&#58; revisi&#243;n sistem&#225;tica y metaan&#225;lisis&#46; Med Clin &#40;Barc&#41;&#46; 2018&#59;151&#58;45&#8211;52&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Evaluation of biases in the studies selected&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Efficacy of vitamin C and E supplementation as adjuvant in the antibiotic treatment of <span class="elsevierStyleItalic">Helicobacter pylori</span>&#46; &#40;A&#41; Without discrimination regarding number of antibiotics&#46; &#40;B&#41; Triple therapy&#46; &#40;C&#41; Quadruple therapy&#46;</p>"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">FD&#58; 4 times a day&#59; TD&#58; twice a day&#59; RCT&#58; randomized clinical trial&#59; NA&#58; data not available&#59; BT&#58; breath test&#59; TDD&#58; 3 doses per day&#59; RUT&#58; rapid urease test&#59; OD&#58; once a day</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Place&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Antibiotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Supplement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Treatment time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Antibiotics</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Supplement</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Diagnostic test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Test to confirm eradication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46; of patients &#40;<span class="elsevierStyleItalic">n</span>&#41; and gender &#40;male&#47;female&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46; of patients &#40;<span class="elsevierStyleItalic">n</span>&#41; and gender &#40;male&#47;female&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="13" align="left" valign="top"><span class="elsevierStyleItalic">Vitamins C and E supplementation</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sezikli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT-open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg TD&#59; amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; bismuth subcitrate 300<span class="elsevierStyleHsp" style=""></span>mg FD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg TD&#44; vitamin E 200<span class="elsevierStyleHsp" style=""></span>UI TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80 &#40;28&#47;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80 &#40;24&#47;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sezikli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT-open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg TD&#59; amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg TD&#44; vitamin E 200<span class="elsevierStyleHsp" style=""></span>UI TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 &#40;13&#47;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">160 &#40;53&#47;107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Everett et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT-double blind study&#44; controlled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bismuth subcitrate 120<span class="elsevierStyleHsp" style=""></span>mg OD&#59; metronidazole 400<span class="elsevierStyleHsp" style=""></span>mg TDD&#59; tetracycline 500<span class="elsevierStyleHsp" style=""></span>mg FD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 200<span class="elsevierStyleHsp" style=""></span>mg TD&#44; vitamin E 50<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25 &#40;13&#47;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52 &#40;17&#8211;75&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;15&#47;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;22&#8211;65&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological and culture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chuang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg OD&#59; amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg OD&#59; metronidazole 500<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 250<span class="elsevierStyleHsp" style=""></span>mg&#44; vitamin E 200<span class="elsevierStyleHsp" style=""></span>mg TD for one week&#59; then&#44; vitamin C 250<span class="elsevierStyleHsp" style=""></span>mg&#44; vitamin E 200<span class="elsevierStyleHsp" style=""></span>mg OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 days of antibiotic treatment&#44; then 6 weeks with supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;19&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;3<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55 &#40;21&#47;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological and culture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT or histological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Babu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT-open label&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; metronidazole 400<span class="elsevierStyleHsp" style=""></span>mg FD&#59; Omeprazole 40<span class="elsevierStyleHsp" style=""></span>mg OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg OD&#44; vitamin E 200<span class="elsevierStyleHsp" style=""></span>UI TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days of antibiotic treatment and 28 days with supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Demirci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg OD&#44; vitamin E 100<span class="elsevierStyleHsp" style=""></span>UI OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 &#40;53&#47;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41 &#40;26&#8211;66&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 &#40;59&#47;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 &#40;21&#8211;65&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Demirci et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg TD&#59; bismuth subcitrate 400<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg OD&#44; vitamin E 100<span class="elsevierStyleHsp" style=""></span>UI OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days on antibiotic treatment and 30 days on supplement therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 &#40;52&#47;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42 &#40;24&#8211;66&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 &#40;60&#47;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38 &#40;22&#8211;65&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="13" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="13" align="left" valign="top"><span class="elsevierStyleItalic">Vitamin C supplement</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Zojaji et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amoxicillin 500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; metronidazole 500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; subcitrate of bismuth240<span class="elsevierStyleHsp" style=""></span>mg TD&#59; omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">162 &#40;40&#47;122&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">150 &#40;36&#47;114&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Kaboli et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;4</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg TD&#59; Amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 250<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">114 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&#44; RUT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chuang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg OD&#59; Amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg OD&#59; clarithromycin 250<span class="elsevierStyleHsp" style=""></span>mg OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 500<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 days of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61 &#40;NA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ko&#231;kar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lansoprazole 30<span class="elsevierStyleHsp" style=""></span>mg TD&#59; clarithromycin500<span class="elsevierStyleHsp" style=""></span>mg TD&#59; amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg TD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vitamin C 1000<span class="elsevierStyleHsp" style=""></span>mg OD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 days of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;14&#47;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Histological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0230"
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                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Helicobacter pylori</span> infection&#58; an overview of bacterial virulence factors and pathogenesis"
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                        0 => array:2 [
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                          "autores" => array:3 [
                            0 => "C&#46;-Y&#46; Kao"
                            1 => "B&#46;-S&#46; Sheu"
                            2 => "J&#46;-J&#46; Wu"
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                      "doi" => "10.1016/j.bj.2015.06.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biomed J"
                        "fecha" => "2016"
                        "volumen" => "39"
                        "paginaInicial" => "14"
                        "paginaFinal" => "23"
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