Reviewed: Shakeri A, Hashempur MH, Mojibian M, Aliasl F, Bioos S, Nejatbakhsh F. A comparative study of ranitidine and quince (Cydonia oblonga Mill) sauce on gastroesophageal reflux disease (GERD) in pregnancy: a randomised, open-label, active-controlled clinical trial [Published online March 19, 2018]. J Obstet Gynaecol. doi: 10.1080/01443615.2018.1431210.
Gastroesophageal reflux disease (GERD) can occur in men and women at any age but is most common in pregnant women. GERD usually presents as heartburn and may be treated with diet and lifestyle changes. In addition, histamine-2 receptor antagonists (H2RAs) like ranitidine (Zantac®; Chattem Inc.; Chattanooga, Tennessee) may also be prescribed. Ranitidine is the only H2RA whose efficacy in pregnancy-related GERD has been established, but concerns remain about its safety in this population. Traditional Iranian medicine (TIM) offers other approaches to pregnancy-related GERD as symptomatically described in TIM literature. Ibn Sina (Avicenna; ca. 980-1037) and other early TIM practitioners used quince (Cydonia oblonga, Rosaceae), or safarjal, in formulas for GERD. In TIM, quince is used as a gastric tonic, appetite enhancer, and remedy for nausea, vomiting, and epigastric pain. Quince also is said to have a protective effect on the fetus and is used specifically for pregnant women in other traditional medicine systems.
The authors conducted a two-phase, randomized, active-controlled, open-label, parallel group clinical trial that compared ranitidine to quince sauce (QS; a concentrated quince fruit extract) in pregnant women with GERD. This is the first study of the efficacy of QS in pregnant women with GERD, according to the authors. The first phase included 229 pregnant women aged 18-35 years with gestational age of 12-34 weeks and who had at least one GERD symptom more than once weekly for four weeks, and attended the Mojibian Outpatient Clinic (Yazd, Iran) between April 2015 and January 2016. Participants received 15-minute lessons on lifestyle and diet changes from a trained general practitioner and were assessed at baseline and two weeks. No additional details about the lifestyle or diet modifications were provided. A General Symptom Score (GSS) and Major Symptom Score (MSS) were computed for each woman based on symptom severity, intensity, and frequency. Patient responses to treatment were analyzed by calculating a Symptom Score Reduction Ratio (SSRR). “Complete” responders were defined as having an SSRR of at least 75% by the end of the study, and “fair” responders were defined as having an SSRR between 25% and 49% by the end of the study. After two weeks, 79 women (34.5%) had responded completely or fairly to the lifestyle modifications.
The second phase included patients who did not respond to lifestyle modifications after two weeks (SSRR less than 25%), were experiencing heartburn, and had not received any GERD medication for a week before beginning the second-phase study protocol. Thirteen initial subjects were lost to follow-up before randomization, leaving 137 to be randomized as follows: 68 received 150 mg of ranitidine twice daily and 69 received 10 mg of QS* after each meal daily for four weeks.
QS was prepared from fruit purchased at a Tehran market by the Faculty of Pharmacy at Tehran University of Medical Sciences in Iran. Preparation involved heating quince juice pressed from fresh pulp. QS was standardized for its total polyphenols (3.16 mg/1 g QS) as gallic acid equivalents (GAEs). Quality control measures included screening for heavy metals and bacterial contamination. QS was refrigerated during the study. Baseline demographic and clinical characteristics of the two study groups were similar; however, baseline GSSs were somewhat worse in the ranitidine group. During the study, eight participants in the ranitidine group were lost to follow-up and four discontinued participation (three because of adverse events [AEs]). Data from 56 were analyzed. In the QS group, three participants were lost to follow-up and two discontinued treatment (one because of worsening symptoms). Data from 64 were analyzed.
GSS values in both study groups improved during the study. At the two-week data collection point, there was a significant difference in GSS favoring QS (P = 0.036). At four weeks, the difference between groups was not significant (P = 0.074). When major symptoms were analyzed individually, heartburn in those who received QS was significantly lower at two weeks (P = 0.03) and four weeks (P = 0.04) compared to those who received ranitidine. Other major symptoms showed no significant between-group differences at any time point. After two weeks of treatment, a significantly greater percentage of subjects in the QS group responded completely compared to the ranitidine group (P = 0.03). At week two, 28.1% of patients in the QS group had attained complete response compared to 12.5% of those taking ranitidine. However, the difference between groups at week four was not significant (P = 0.37). There were slightly fewer non-responders at the end of the study in the ranitidine group than the QS group. QS was well-tolerated, and no AEs were reported.
QS previously has been compared to omeprazole (Prilosec OTC®; Procter & Gamble; Cincinnati, Ohio), a proton pump inhibitor used for GERD, in pediatric patients with similar results as this study. In this study, QS performed as well as ranitidine and worked more rapidly. QS is inexpensive and can be used easily at home. Studies with a longer follow-up period and objective outcome measures are recommended.
* A reviewer of this article noted that the QS dosage used in this study appears to be unusually small. The authors of the journal article did not respond to requests to confirm the dosage.