Salem EM, Yar T, Bamosa AO, et al. Comparative study of Nigella sativa and triple therapy in eradication of Helicobacter pylori in patients with non-ulcer dyspepsia. Saudi J Gastroenterol. Jul-Sep 2010;16(3):207-214.
Helicobacter pylori (HP) is a gram-negative bacterium linked to chronic active gastritis, peptic ulcer, gastric cancer, and gastric mucosa-associated-lymphoid tissue (MALT)-lymphoma. Gastric HP infections are difficult to eradicate due to emerging drug resistance, the low pH of the stomach, and the bacteria's adherence to the gastric mucosa layer. The conventional treatment is triple therapy (TT) with two antibiotics and one proton pump inhibitor, and it is not effective for all patients. The purpose of this randomized, open clinical trial was to compare the effectiveness of nigella (Nigella sativa) seed with TT in the eradication of HP in patients with non-ulcer dyspepsia. Nigella has a long history of food and medicinal use. Its biological activities include potent in vitro antibacterial effects against HP and drug-resistant bacteria.
Between March 2007 and August 2008, researchers at the gastroenterology endoscopy unit of King Fahd Hospital of the University (Al-Khobar, Saudi Arabia) enrolled patients with dyspeptic symptoms and HP infection confirmed by histopathology and rapid urease test. Patients with peptic ulcers, gastric cancer, or gastrointestinal bleeding were excluded. Patients were also excluded if they had taken bismuth, proton pump inhibitors, or antibiotics during the 4 weeks prior to endoscopy. They were randomized to 4 groups using the alternate subject method. All 4 groups took 40 mg omeprazole once daily for 4 weeks. Group 1 also received TT, which consisted of 500 mg clarithromycin and 1 g amoxicillin twice daily for 1 week. Groups 2, 3, and 4 took 1 g/day nigella seed [BioExtract (Pvt.) Ltd.; Sri Lanka], 2 g/day nigella seed, and 3 g/day nigella seed for 4 weeks, respectively. The nigella seed was provided as 500 mg capsules of ground seed that were taken after meals (groups 2 and 3: 2 divided doses, group 4: 3 divided doses).
Every patient received esophagogastroduodenoscopy (EGD) according to standard protocol, and mucosal biopsies were taken from the patients' stomach (antrum and body). Gastroesophageal reflux disease (GERD) was diagnosed according to the Los Angeles (LA) classification. The researchers assessed the mucosal states of the patients' esophagus, stomach, and duodenum, and they diagnosed gastritis and duodenitis endoscopically, which was later confirmed by histology. The presence or absence of HP antigen in the patients' stool was analyzed 4 weeks after the end of treatment with a rapid monoclonal immunochromatographic method. The patients were interviewed and received physical examinations. The researchers used a questionnaire to collect demographic data and information about any other illnesses. An adapted form of the Short-form Leeds Dyspepsia Questionnaire was used to evaluate the patients' gastrointestinal symptoms, including epigastric pain and reflux symptoms. The following parameters were rated for each symptom: frequency (0: less than 3 times/week, 1: most days of the week), relief of symptoms (0: spontaneously relieved, 1: relieved by medication), and the effect on quality of life (0: no effect, 1: presence of effect). The symptoms were also rated on a scale of 0 (no symptoms) to 3 (severe symptoms).
Out of 110 patients, 88 (32 men, 56 women, age: 18-65 years) completed the study and were included in the data analysis. The reasons for withdrawal included antibiotic use (n=10), travel abroad or loss of contact (n=11), and noncompliance (n=1). None of the drop-outs were related to adverse effects. At baseline, there were no statistically significant inter-group differences in demographics and clinical characteristics, including endoscopic findings. There were no significant differences in compliance between the groups, and over 98% of patients took all doses correctly.
Following 4 weeks of treatment, the HP antigen stool test showed that the HP eradication rate was not significantly different between TT and 2 g/day nigella seed (82.6% and 66.7%, respectively, P=0.384). Nigella seed at 1 and 3 g/day were significantly less active than TT (47.6%, P=0.033, 95% confidence interval [CI] 0.068 – 0.569 and 47.8%, P=0.030, 95% CI 0.072 – 0.561, respectively). Compared to baseline values, epigastric pain and reflux symptoms improved in all groups (P<0.001 for all). These dyspeptic symptoms did not worsen in any of the patients. There were no significant inter-group differences in post-treatment scores. The authors noted that adverse effects "were minor, similar, most related to gastrointestinal irritation and did not persist for long." Further details, including the numbers and types of adverse effects, were not reported. There were 2 patients who did not respond to TT, but they were negative for HP after treatment with omeprazole plus nigella seed. It is possible that nigella seed is active against drug-resistant HP strains. Nigella seed may have a role in reducing the emergence of antibiotic resistance in HP strains and improve the efficacy of antibiotic drugs, but more research is needed for confirmation.
This is the first clinical trial to show that nigella seed (2 g/day) is effective in treating HP infections and is comparable to the effectiveness of TT. The 3 g/day dose was less effective than the 2 g/day dose. An explanation for this could be that the antisecretory effects of nigella, coupled with omeprazole, lowered gastric pH enough to allow HP to spread from the antrum to the rest of the stomach. More research is needed to determine nigella's mechanism of action. The improvements in dyspeptic symptoms that were observed in all of the groups were most likely due to the effects of omeprazole, although animal studies have shown that an aqueous nigella suspension and nigella seed have antisecretory and protective effects on gastric mucosa. Additional clinical studies are needed to confirm these results and determine if nigella seed is effective in treating dyspeptic symptoms.—Marissa Oppel-Sutter, MS