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By David Kiefer, MD
Clinical Assistant Professor, Department of Family Medicine, University of Wisconsin (Madison); Clinical Assistant Professor of Medicine, Arizona Center for Integrative Medicine, University of Arizona, Tucson
Dr. Kiefer reports no financial relationships relevant to this field of study.
• This was a randomized, double-blind, placebo-controlled trial in 64 people with mild-to-moderate ulcerative colitis.
• The ginger group received 500 mg capsules of dried ginger rhizome and was instructed to take two capsules twice daily.
• There was no intention-to-treat analysis, and data in 46 of the remaining participants showed via symptom questionnaires and blood tests a mixture of no difference from the placebo group to a slight improvement in symptoms and serum estimates of oxidation.
SYNOPSIS: For people with mild-to-moderate ulcerative colitis and who have symptoms and serum markers of inflammation and oxidation, some preliminary findings demonstrate both benefit and no difference when using 2 grams of ginger daily for 12 weeks vs. placebo.
SOURCE: Nikkhah-Bodaghe M, Maleki I, Agah S, et al. Zingiber officinale and oxidative stress in patients with ulcerative colitis: A randomized, placebo-controlled, clinical trial. Complement Ther Med 2019;43:1-6.
The scientific community does not often see clinical trials studying common herbs with a long history of traditional use. There is less of a financial incentive to invest in an expensive research study if positive results lead to people simply purchasing plants from a grocery store or local herbal market or pharmacy. Yet, plants such as ginger long have had promising anecdotal results, and fitting physiological benefits as well. Add these together, and it is exciting to see the efforts of this research group examining the effects of orally dosed powdered ginger on patients with mild-to-moderate ulcerative colitis.
The use of ginger in this capacity dovetails with accumulating thought that ginger has anti-inflammatory effects and the pathophysiology of ulcerative colitis initiation and flares, as cited by the authors.1 To explore this possible therapeutic effect, the investigators enrolled 64 people in the study and randomly allocated half to a control group and half to a ginger therapy group. Adults with mild-to-moderate ulcerative colitis (as per histopathology) were recruited from three gastroenterology clinics in Iran.
Possible participants were excluded from the trial if they were pregnant or lactating; had cancer, any other intestinal diseases, or infections; or had “… other inflammatory … autoimmune …” diseases, although the latter were not specified. Patients also were excluded from the study if they were taking pharmaceuticals, such as antihistamines, blood thinners, calcium channel blockers, non-steroidal anti-inflammatory drugs, or birth control pills, in the month prior to study’s inception.
As the study progressed, if participants had a disease flare necessitating hospitalization or participants failed to consume at least 90% of the capsules, they also were excluded. Statistically, it is unclear if the later exclusions were still included in the final data analysis as intention-to-treat. Although the authors stated the study was double-blind, they did not detail the specifics of that blinding.
Culinary ginger rhizome (Zingiber officinale) was harvested from a farm, dried, and powdered; 500 mg was then put into each capsule for use in this study. The treatment group was instructed to consume two capsules with breakfast and two capsules with dinner over the course of the 12-week study. The placebo capsules contained maltodextrin. No commentary was made about whether the participants were able to guess which group they were in — that is, the similarity of the placebo and ginger capsules.
The study participants were visited at baseline (time = 0), six weeks, and 12 weeks, and were asked to not change their diet or their activity level significantly during that 12-week period. The authors measured height and weight and administered questionnaires at three times during the study. (See Table 1.) Of note, the Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ) was the primary outcome variable. In addition, laboratory tests were taken and analyzed for total serum antioxidant activity, serum malondialdehyde (MDA) (this compound is a byproduct of omega-6 fatty acid lipid peroxidation and can indicate the presence of oxidative stress in the body), and possibly cholesterol, the latter being mentioned in a table but not specifically discussed in the text.
There were a significant number of dropouts from the study. In the control group, of the 32 original participants, four dropped out at the six-week mark (two refused to continue, one had constipation, and one had bloody diarrhea). In the treatment group, there were eight dropouts (five refused to continue, one had heartburn, and two had bloody diarrhea). In the ensuing six weeks, an additional four and two people refused to continue, respectively.
Data were analyzed for 22 people in the ginger treatment group and 24 people in the placebo group — the numbers left after the dropouts and intrastudy exclusions as described above. Among these 46 people, baseline measurements were equal and remained similar over the course of the study — with one exception. People in the control group significantly decreased their fiber intake over the 12 weeks. Blood testing revealed no difference in serum total antioxidant activity between the two groups at baseline or after the 12 weeks.
In contrast, although the serum MDA levels were similar for the ginger group and placebo group at baseline (8.33 and 7.88, respectively), after 12 weeks, the ginger group’s level of MDA had decreased significantly (3.87, P < 0.001), whereas the control group’s level was not significantly lower (6.38). Comparatively, too, these 12-week values were different from each other (P < 0.001).
With respect to the questionnaires, the overall Inflammatory Bowel Disease Questionnaire-9 (IBDQ-9) score was unchanged over the 12 weeks for each group, and there was no significant difference between the ginger and control groups. When subsets of the IBDQ-9 were analyzed, the stool frequency score and the bowel distress and cramp score were slightly better in the ginger group at 12 weeks compared to the control group (P = 0.041 and 0.029, respectively). Gas excretion of bowel scores and flatulence scores were similar between the two groups. The SCCAIQ score is detailed in Table 2, essentially showing some improvement in the ginger group vs. the control group, but only at the 12-week mark.
There was no information provided about adverse effects other than the symptoms that developed in some of the participants who dropped out of the study.
This study had huge potential. The intervention (ginger) was compelling and tied into the pathophysiology of ulcerative colitis. The herbal dose (1g to 4 g mentioned in the literature for upper gastrointestinal symptoms) and form (rhizome) were correct, and the sample size and statistical power seemed appropriate.2
It is disappointing, then, to see that it is likely that the final analysis was done on the 46 people who completed the trial, not the 64 enrolled. The failure to use an intention-to-treat statistical analysis on the original 64 represents an important failure in the methodology, especially for such a small study. Essentially, whether they meant to, the authors “cherry picked” data, so we do not know if the study underestimated or overestimated the final results. We can read between the lines of these results, but it will take a repeat of the protocol, and better statistics, to really ferret out ginger’s effect on ulcerative colitis.
The authors concluded that this dose of ginger for 12 weeks benefited people with ulcerative colitis in some inflammatory parameters and clinical outcomes. They ascribed the lack of benefit in other variables because of inadequate dose and treatment duration. Alternatively, it also is possible that ginger does not actually work for this diagnosis regardless of the dose or time period. The structure of this study just does not permit us to comment definitively on the primary outcome, the SCCAIQ results, or any of the secondary variables detailed.
The results are interesting, though. If we believe the anti-inflammatory effect of the MDA test, it seems likely that the total serum antioxidant level also would have changed. A repeat of this examination, with stronger methodology, would be compelling. If ginger has such systemic effects, it truly might be useful for an inflammatory condition such as ulcerative colitis. In that line of thinking, the next study needs to more specifically detail the allopathic treatments being used in the study cohort that are more typical of inflammatory bowel disease, such as oral (or intravenous) steroids and topical/oral preventive medications.
Long-term use of ginger, if it bears out to be significantly anti-inflammatory, may have additive effects with those pharmaceuticals. And the heartburn and bloody diarrhea (although there also was one case of bloody diarrhea in the control group) could be considered adverse effects or simply ulcerative colitis pathology. Better tracking of adverse effects and plant-
pharmaceutical interactions are imperative as clinicians attempt to learn a risk-benefit approach for using phytomedicinals.
In summary, there were some preliminary findings of both benefit and no difference for the use of 2 g of ginger daily for 12 weeks vs. placebo in people with mild-to-moderate ulcerative colitis, specifically on symptoms and serum markers of inflammation and oxidation.
Ginger is a culinary spice and plant with a long history of use for a variety of conditions (mostly gastrointestinal). For this reason, providers could consider using ginger in therapeutic doses (provided there are no pharmaceutical interactions) for people with ulcerative colitis until more methodologically sound research corroborates or disproves the findings of this study.
Financial Disclosure: Integrative Medicine Alert’s Physician Editor Suhani Bora, MD; Peer Reviewer Eugene Lee, MD; Associate Editor Mike Gates; Editor Jason Schneider; Relias Media Editorial Group Manager Leslie Coplin; and Accreditations Director Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.