The effect of food, vitamin, or mineral supplements on chronic constipation in adults: A systematic review and meta‐analysis of randomized controlled trials

Over‐the‐counter supplements are commonly used to manage chronic constipation; however, their efficacy remains unclear. We aimed to investigate the effect of food, vitamin or mineral supplements on stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation via a systematic review and meta‐analysis of randomized controlled trials (RCTs).


| INTRODUC TI ON
Chronic constipation is a burdensome gastrointestinal disorder that affects 12% of adults. 1 Its diagnosis is based on patient-reported symptoms such as infrequent stools, hard/lumpy stool consistency, straining, and incomplete evacuation. 2 Chronic constipation impacts daily activities and adversely affects quality of life. 3,4Furthermore, it is responsible for substantial health care costs, ranging from $1912 to $11,991 per patient annually. 5,6ople with chronic constipation report high rates of dissatisfaction with current treatment options due to lack of efficacy and side effects. 7,8Healthcare professionals remain concerned with low response rates. 8This leaves an unmet need to be addressed by alternative treatment options.Over-the-counter (OTC) supplements are commonly used, with a survey of 1233 people with chronic constipation reporting trying an average of three OTC products before consulting their healthcare provider. 8Several types of OTC supplements are available, including probiotics, fiber and food, vitamin, and mineral supplements.

Systematic reviews and meta-analyses have been published
summarizing the effects of fiber supplements, probiotics, and synbiotics in chronic constipation. 9,10However, evidence is less well established on the use of other food supplements (e.g., fruit extracts or powders), and vitamin and mineral supplements, and these trials have not undergone meta-analysis to inform clinical care. 11e aim of this systematic review and meta-analysis was to investigate the effect of food, vitamin, or mineral supplements on response to treatment, stool output, gut transit time, symptoms, quality of life, adverse events, and compliance in adults with chronic constipation.

| MATERIAL S AND ME THODS
This systematic review and meta-analysis was conducted in line with the guidelines of the Cochrane Handbook and the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). 12,13The eligibility criteria, search strategy, methods of screening, data extraction, and analysis were specified in advance and published in a protocol on PROSPERO (CRD42021292029).

| Eligibility criteria
The eligibility criteria were developed using a patient, intervention, comparators, outcome, and study design (PICOS) approach and are outlined in Table 1.Briefly, the inclusion criteria were RCTs administering food supplements (e.g., fruit extract supplements), vitamin, or mineral supplements compared to placebo in adults with chronic constipation that measured constipation outcomes.Interventions were administered in supplement form (e.g., tablet, powder, capsule, or solution).Studies administering whole foods (e.g., fruits) were excluded from this systematic review.

| Search strategy
Studies were identified through a systematic search of electronic databases, a clinical trials register, conference abstracts, and backsearching reference lists of eligible studies and relevant review papers.

| Selection process
References were imported into a reference manager for assessment of eligibility (EndNote X9; Thomson Reuters).Two reviewers (AvdS and AC) independently screened titles and abstracts and then full text articles against the predefined inclusion and exclusion criteria.
Disagreements were resolved by a third and fourth reviewer (ED and KW).

| Data collection process
Two reviewers (AvdS and AC) independently extracted data from eligible studies onto a standardized form (Table 1).Extracted data were compared and discrepancies were resolved.Where an article provided insufficient data, authors were contacted to provide additional information.When trial reporting allowed, data were extracted as intention-to-treat analyses.For dichotomous data, dropouts were assumed to be treatment failures.When necessary, data were estimated from figures using Plot Digitizer software. 12

| Risk of bias assessment
Risk of bias was assessed independently by two reviewers (AvdS and AC). 14The Cochrane risk of bias 2 tool (RoB 2.0) assesses bias arising from randomization, deviations from intended interventions, missing outcome data, outcome measurement, and selective reporting.For TA B L E 1 Table of inclusion and exclusion criteria for participants, intervention, comparator, outcomes, and study designs.

Characteristic Inclusion and exclusion criteria Data extracted
Participants Adults (≥18 years) with chronic idiopathic constipation identified by: (1) clinical diagnostic criteria (e.g., Rome); (2) author or clinician-defined criteria/diagnosis (3) participant-defined criteria (e.g., self-report); or (4) presence of ≥1 constipation symptoms: <3 bowel movements per week, hard/lumpy stools, sensation of incomplete evacuation, straining, manual maneuvers, physiological markers (e.g., slow gut transit time), or an evacuation disorder.No restrictions on age, sex, or ethnicity were applied.Community or outpatient settings were included.Studies were excluded if all participants had secondary constipation or belonged to specific clinical population groups (e.g., pregnant women or inpatients).However, a study was eligible if only a subset of the participants belonged to one of these groups.crossover studies, an additional domain on bias arising from period and carryover effects is assessed.Judgments were categorized as "low-risk", "some concerns" or "high-risk".Disagreements were resolved through discussion with a third reviewer (ED).

| Data synthesis
Meta-analysis was performed where data for the same outcome from two or more studies was obtained, using Review Manager Version 5.4 (The Cochrane Collaboration, 2020).Dichotomous outcomes were expressed as relative risk (RR) and 95% confidence intervals (CI).Mean difference (MD) was calculated for continuous outcomes that were measured using the same tool and reported in the same units.Standardized mean difference (SMD) was calculated for continuous outcomes that were measured or reported differently.Means and standard deviations (SD), sample size, and p values were used for the analysis.For studies that had multiple intervention arms administering different doses, each dose was compared to the control separately, and the sample size of the control group was divided by the number of intervention arms to reduce unit of analysis error. 12fferent types of supplements were analyzed separately in the data synthesis.Meta-analyses were performed using a randomeffects model.Statistical heterogeneity was assessed using the chisquared test and quantified using the I 2 statistic.Thresholds of 50% and 75% were considered to represent substantial and considerable heterogeneity, respectively. 12

| Kiwifruit supplements
[17] F I G U R E 1 PRISMA flow diagram of studies included in the systematic review.Stool consistency was measured using the Bristol Stool Form Scale (BSFS) in two studies, including 41 participants. 15,16Kiwifruit supplements did not significantly affect stool consistency compared to control (MD −0.11 points, 95% CI −0.31, 0.09, p = 0.29) and no significant heterogeneity was detected (I 2 = 0%, p = 0.97) (Figure 2B).
One study administering a kiwifruit supplement, including 32 participants, measured stool volume subjectively using a 5-point self-report scale (1 = very small to 5 = lots) and reported no significant difference compared to control (mean 2.72 vs. 2.66 units; p = 0.602). 16

| Gastrointestinal symptoms
One study administering a kiwifruit supplement, including 32 participants, measured integrative symptom scores using the Gastrointestinal Symptom Rating Scale and reported no significant difference compared to control (1.96 ± 1.36 vs. 2.06 ± 1.24; p = 0.124). 16 terms of individual gastrointestinal symptoms, one small crossover study administering three different kiwifruit supplements in nine participants, showed improvements in incomplete evacuation (MD −0.12, 95% CI −0.20, −0.04, p = 0.003, I 2 = 0%, p = 0.98) and abdominal pain (MD −0.14, 95% CI −0.19, −0.09, p < 0.00001; I 2 = 0%, p = 0.87) 15 (Figures S3 and S4).However, kiwifruit supplements had no effect on straining, use of manual maneuvers, bloating, or flatulence compared to control (Figures S5-S8).Details of the assessment tool used in this study were not reported.Another study, including 87 participants, reported data on abdominal discomfort, flatulence, bloating, or burping, but in a form that could not be included in the meta-analysis.This study reported no difference between the kiwifruit supplement and control group for these outcomes. 17ool ease was measured in one study administering a kiwifruit supplement, including 32 participants, using a 5-point scale (1 = very easy to 5 = difficult).There was no difference between the kiwifruit supplement and control group in stool ease (mean 3.10 vs. 3.10 units; p = 0.868). 16

| Quality of life
Quality of life was measured in one study administering kiwifruit supplements, including 32 participants, using the 12-item Short Form Health survey (SF-12).There was no difference between the kiwifruit supplement and control group in the physical (p = 0.781) and mental (p = 0.557) components of the SF-12. 16

| Adverse events and compliance
6][17] In one trial, seven adverse events occurred in the kiwifruit supplement group, of which five were considered possibly related to the intervention; three participants experienced flatulence and two experienced bloating and these were resolved "spontaneously without treatment".In the control group, there was one adverse event; however, no details were reported. 17In another trial, one participant experienced adverse events (mild bloating, nausea, and vomiting) leading to withdrawal and this resolved within 2 days of stopping treatment; however, the study did not report which intervention the participant was receiving. 16o trials assessed compliance by measuring the number of returned capsules. 15,16Compliance rates were 99% ± 8% and > 95% with no difference between kiwifruit supplement and control groups. 15,16One trial did not measure or report compliance rates. 17

| Risk of bias
One study administering kiwifruit supplements was judged to be at "high-risk" of bias for each outcome due to selective reporting, as the analysis plan was changed.However, all other domains were "low-risk". 15Two studies were judged to be of "some concerns". 16,17 one study, there were some concerns due to selective reporting as there was no prespecified analysis plan; however, all other domains were "low-risk". 17In another study, there were some concerns as only a per protocol analysis was presented; however, all other domains were "low-risk". 16Risk of bias for each outcome for kiwifruit supplements is presented in Figures S1-S8.

| Ziziphus jujuba (Chinese date) extract supplement
Ziziphus jujuba extract was administered in one study included in this review; therefore, this study was not included in a meta-analysis and is instead presented narratively below. 18ziphus jujuba significantly decreased stool frequency from baseline to week 4 (2.5 ± 1.0-1.0± 0.   Analysis includes a crossover study of three interventions and a control group with a total sample size of 9 (15).When included in the meta-analysis, each intervention is assigned to a sample size of 9 and the control was assigned a sample size of 3 to account for unit of analysis error. d Analysis includes a crossover study with a total sample size of 32 (16).
In the Ziziphus jujuba group, two out of 18 participants withdrew from the study early due to persistence or worsening of constipation compared with 16 out of 19 participants in the control group.It was reported that those who completed the trial (19 out of 37 participants) adhered to the intervention as reflected in the used vials returned on visits; however, a value for compliance was not provided.

| Risk of bias
The study administering Ziziphus jujuba was judged to be at "highrisk" of bias overall as an intention-to-treat analysis was not conducted, and there was bias due to missing data with 18 out of 37 (49%) participants dropping out.Bias due to the randomization process and measurement of outcomes was "low-risk", while bias due to selective reporting was "some concerns".
In one study administering senna, a significant difference in stool consistency was observed between the senna and control groups at week 4, measured using the BSFS (4.5 ± 1.2 vs. 3.4 ± 1; p < 0.01). 19

| Gut transit time
In one study administering senna, gut transit time was measured using the radio-opaque marker method and slow transit constipation (STC) was defined as expulsion of <80% markers after 120 h.
There was no difference in the proportion of participants with STC in the senna and control group after 8 weeks of intervention (48% vs. 64%, p = 0.251). 20I G U R E 2 Forest plot of (A) stool frequency (bowel movements/week) (n = 123) and (B) stool consistency (Bristol Stool Form Scale) (n = 41) in randomized controlled trials comparing kiwifruit supplements with control in adults with chronic constipation.Values were calculated as mean difference (95% CIs) using a random-effects model.CI, confidence interval; IV, inverse variance; SD, standard deviation.

| Gastrointestinal symptoms
The severity of gastrointestinal symptoms was reported in both studies administering senna; however, these could not be combined for meta-analysis as studies used different measurement scales (5or 7-point), and data were not reported in sufficient detail for an SMD to be calculated. 19,20 one study, senna (1 g/day) improved the severity of constipation symptoms (4.9 ± 3.2 vs. 1.0 ± 3.2 points using the Constipation Scoring System (CSS); p < 0.01), straining (p < 0.001), incomplete evacuation (p < 0.01), and bloating (p < 0.05) compared to control.

| Quality of life
Quality of life was measured in both studies administering senna; however, these could not be combined for meta-analysis as one study reported a global PAC-QoL score, 19 whereas the other reported scores for eight individual domains of SF-36 but not a global score. 20obal PAC-QoL scores were improved in the senna group compared to control (p < 0.05). 19Improvements were shown in the physical and satisfaction domains, but not psychosocial or worries and concerns domains. 19In the study that reported quality of life SF-36 scores, both the senna and control group had worsened scores on the emotional domain after treatment compared to baseline (p = 0.03). 20In the senna group, scores in the vitality domain improved (p = 0.01), whereas the physical domain worsened (p = 0.04).In the control group, none of the other domains were different from baseline. 20

| Adverse events and compliance
Most participants tolerated senna, and no serious adverse events were reported.One study reported that in the senna group, two participants dropped out due to stomachache and headache and five dropped out due to "unsatisfactory effects", whereas in the control group eight dropped out due to "unsatisfactory effects". 20e other study reported that the most common treatment-related adverse events were mild abdominal pain and diarrhea; however, the study did not report which intervention groups these occurred in. 19One study administering senna measured compliance and reported that 93.5% participants consumed ≥80% scheduled doses; however, values were not reported for the senna and control groups separately. 20

| Risk of bias
One study administering senna was judged to be at "high-risk" of bias across outcomes due to missing data, as 10 out of 97 participants dropped out in the senna group and 14 out of 97 dropped out in the control group; however, all other domains were "low-risk". 20Another study was judged to be of "some concerns" in selective reporting; however, all other domains were "low-risk". 19Risk of bias for each outcome for senna is presented in Figures S9 and S10.

| Malva Sylvestris L. flower (MSL) extract supplement
Malva Sylvestris L. flower (MSL) extract syrup was administered in one study only, therefore this study was not included in a metaanalysis and is instead presented narratively below. 21significantly higher stool frequency was found in the MSL group compared to control (7 ± 3.95 vs. 5.14 ± 2.74 bowel movements/week; p < 0.001), and a lower proportion of participants experienced hard stools measured using the BSFS (45.4% vs. 9.1%, p < 0.001).A lower frequency of straining (p < 0.001) and incomplete evacuation (p < 0.001) were found in the MSL group compared to control, measured using a 3-point frequency scale.There was no difference between groups for use of manual maneuvers (p = 0.177).
In the MSL group, 14 mild adverse events were reported including diarrhea, acid regurgitation, and nausea.In the control group, six adverse events were reported including worse constipation and dry mouth.However, there was no difference in the number adverse events between groups (p > 0.05).Compliance was not measured or reported.

| Risk of bias
The study administering MSL extract was judged to be "high-risk" overall.This was due to inadequate detail on the methods of randomization and differences in baseline characteristics of the study groups, missing data with 66 out of 110 (60%) participants dropping out, and the possibility of recall bias in the measurement of outcomes.Bias due to the deviation from intended interventions and selective reporting were judged to be of "some concerns".

| Gut transit time
One study administering magnesium oxide supplements, including 34 participants, measured gut transit time using the radio-opaque marker method. 22Gut transit time significantly decreased from baseline to week 4 in the magnesium oxide group (75.5 ± 37.3 h-41.6 ± 30.5 h, p < 0.001); however, no change was found in the control group (46.4 ± 36.9 h-31.6 ± 25.5 h, p = 0.109). 22ere was no analysis comparing the intervention to control at week 4.
The severity of individual gastrointestinal symptoms was measured in both studies using a 5-point scale, with a higher score denoting more severe symptoms.

| Adverse events and compliance
Adverse events were measured in one study administering magnesium oxide. 19The most common treatment-related adverse events were mild abdominal pain and diarrhea, and no severe adverse events were encountered; however, the study did not report which intervention groups these occurred in. 19Compliance was not measured in studies administering magnesium oxide supplements.

| Risk of bias
Bias in one study administering magnesium oxide supplements was judged to be of "some concerns" across outcomes in selective reporting; however, all other domains were "low-risk". 19In another study, bias was judged to be "high-risk" in the randomization process due to differences in baseline characteristics of the study groups and inadequate detail on the methods of randomization and allocation concealment. 22Bias in selective reporting was judged to be "some concerns", while all other domains were "lowrisk". 22Risk of bias for each outcome is presented in Figures S11-S19; Table 3.

| DISCUSS ION
This systematic review and meta-analysis demonstrates that magnesium oxide supplements are effective in the management of chronic constipation, and that there is insufficient evidence to recommend other food supplements, such as kiwifruit supplements and vitamin supplements for this condition.This is the first systematic review and meta-analysis showing that magnesium oxide supplements are effective at improving a range of constipation outcomes and increase the likelihood of response to treatment by 332% compared to control.Magnesium oxide supplements are osmotic agents that act by retaining water in the intestinal lumen, resulting in bulking and softening stool. 23gnesium oxide increased stool frequency by 3.72 CSBM/week, which is above the threshold considered to be a clinically meaningful change in people with constipation. 24Magnesium oxide softened stool consistency by 1 point on the BSFS.The Rome criteria describes the predominant symptoms in chronic constipation as difficult, infrequent, or incomplete defecation, therefore improvements in CSBMs and stool consistency are considered clinically important. 2The dose of magnesium oxide administered in studies was 1.5 g/day; however, in one study half of participants required a dose reduction, possibly due to reported side effects such as diarrhea, suggesting that a gradual increase in dose up to tolerance may be required. 19Overall, the clinically significant effects of magnesium oxide suggest that it may be an appropriate first-line OTC treatment option in chronic constipation, unless otherwise contraindicated.
Kiwifruit supplements, administered as freeze-dried powders, 6][17] However, studies show beneficial effects of whole, fresh kiwifruit in people with constipation. 25,26There are several proposed mechanisms by which kiwifruit may affect the gut. 27The fiber within the fruit has a high water holding capacity, thus softening stools. 280][31] The lack of effect of freeze-dried powders may be the result of differences in the nutrient composition, as well as the food matrix and form.For example, it has been previously shown that solid food induces higher rates of intestinal contraction than other food forms. 32Additionally, dose is likely to play a role as of the three trials of kiwifruit supplementation (0.6, 1, 2.4, and 5.5 g/day), the only study showing a significant benefit in constipation outcomes was with the highest dose (5.5 g/day). 17erefore, higher doses of freeze-dried powder may be required to have a beneficial impact in constipation, though this remains to be confirmed by future research.
Senna supplements were found to be ineffective at improving symptoms of chronic constipation.This was a surprising finding as senna is an anthraquinone stimulant laxative that is commonly used in clinical practice for the treatment of constipation, and its use has been recommended previously in clinical guidelines. 33Despite the fact that the two placebo-controlled RCTs included in our review both individually reported a beneficial effect of senna on constipation outcomes compared to placebo, when meta-analyzed, there was no longer a significant effect on response to treatment or stool frequency.This might be explained by the two trials reporting vastly different effect sizes for these outcomes, contributing to a large confidence interval in the meta-analysis. 19,20There is a lack of RCTs that assess the effect of senna alone, compared to placebo, in chronic constipation.5][36] Future placebo-controlled RCTs are needed to establish its effectiveness in chronic constipation.
In accordance with the findings of this systematic review, a recent survey reported that two thirds of people with chronic constipation who had tried senna had discontinued treatment, mainly due to insufficient relief of bowel symptoms and side effects. 37dominal pain and diarrhea were reported in studies administering senna (15 mg or 1 g/day). 19,20In the study administering the higher dose (1 g/day), 80% of participants required a dose reduction, highlighting the low tolerance levels of such dose. 19Further RCTs are needed to establish the tolerance of senna in chronic constipation, as well as the appropriate regime.

Ziziphus jujuba (chinese date) and MSL extract supplements
have been investigated in one study each.The study administering Ziziphus jujuba did not report analyses between the intervention and control groups, and had a large dropout rate in the control group (84%) compared with the intervention group (11%). 18Similarly, the study administering MSL extract reported a dropout rate of 60%. 21th aforementioned trials had considerable methodological limitations and were at high-risk of bias, and thus any data must be interpreted with caution.
No RCTs administering vitamin supplements in chronic constipation were identified amongst the literature.Anecdotally, vitamin C supplements have been hypothesized to improve constipation symptoms.This originates from scarce evidence that high doses of vitamin C may lead to diarrhea, and hence may have a laxative effect that could be beneficial in constipation. 38However, this systematic review highlights that there is complete lack of evidence to support their use, and RCTs are needed to explore the effect of vitamin C supplements in chronic constipation.In addition, chronic constipation has also been linked to certain micronutrient deficiencies, for example, vitamin D deficiency. 39It is therefore also possible that correcting micronutrient deficiencies through supplementation may improve constipation, and this would be valuable to investigate in the future.
The findings of this review have important implications for clinical practice.A previous systematic review on the efficacy of OTC products for chronic constipation reported good evidence for senna, and moderate evidence for fruit-based and magnesiumbased supplements; however, no meta-analysis was performed. 11r meta-analysis has provided further insight into the efficacy of these products, highlighting that although magnesium oxide is beneficial in constipation, there is no evidence that kiwifruit and senna supplements are effective compared to placebo.This is crucial as a recent survey found that 70% of people with chronic constipation have tried more than one OTC product and report discontinuing treatment due to insufficient symptom relief or side effects, suggesting patients may be cycling through many OTC products without experiencing relief. 37This contributes not only to high rates of dissatisfaction with the effectiveness of OTC products, but may also unnecessarily delay effective treatment and increase the financial burden for patients who resort to trying multiple unsuccessful products. 37This meta-analysis highlights that magnesium oxide may be an appropriate treatment option that provides satisfactory relief of constipation symptoms, which could prevent treatment cycling.
Although previous systematic reviews demonstrated that other types of dietary supplements, such as fiber and probiotic supplements, may be beneficial in chronic constipation, this is the first systematic review and meta-analysis to investigate the effect of food, vitamin, or mineral supplements in chronic constipation. 9,10This review followed a rigorous methodology, adhering to recommendations from the Cochrane handbook and PRISMA guidelines, and incorporating searches of grey literature with no language restrictions, in order to reduce publication bias.Additionally, six of eight RCTs diagnosed constipation using the Rome criteria, thus leading to a relatively homogeneous population being studied.Limitations of this review include the small numbers of studies and participants included, the heterogeneity of doses administered for some intervention types (kiwifruit and senna supplements), and the fact that no studies in this review were at low-risk of bias.

| CON CLUS ION
In conclusion, magnesium oxide is effective at improving response to treatment, stool frequency, stool consistency, gastrointestinal symptoms, and quality of life, which highlights its potential to be used in clinical practice for the management of chronic constipation.Based on evidence from placebo-controlled RCTs, there is currently insufficient evidence to recommend kiwifruit supplements and senna supplements in chronic constipation.Our review provides insight into the efficacy of certain OTC supplements which could prevent individuals with constipation cycling through several treatments without obtaining relief, ultimately improving clinical care and treatment.

AUTH O R CO NTR I B UTI O N S
AvdS, KW, and ED designed the systematic review protocol.AvdS conducted the searches.AvdS and AC independently reviewed studies against inclusion and exclusion criteria.AvdS and AC The following databases were searched: MEDLINE(1946 to February 2022; OvidSP), EMBASE (1974 to February 2022; OvidSP), and The Cochrane Central Register of Controlled Trials (all years; The Cochrane Library).The final search date was February 18, 2022.Search strategies are presented in Appendix S1.No restrictions were applied to language or publication date.The US National Institute of Health clinical trials register (www.clinicaltr ials.gov/) was searched in February 2022 to identify unpublished trials.The following annual conferences were hand-searched: American Gastroenterology Association Digestive Diseases Week (2011-2021; Gastroenterology), British Dietetic Association (2011-2020; J Hum Nutr Diet), British Society of Gastroenterology (2011-2021; Gut), and European Society for Clinical Nutrition and Metabolism (2011-2021; Clin Nutr; Clin Nutr Supp, e-SPEN).

c
Study administered two active interventions (senna and MaziRenwan) and control; however, only senna (n = 97) and control (n = 97) groups were eligible and analyzed in this review(20).d Several outcomes were assessed; however, the intervention was administered in one study only, therefore the study was not included in a meta-analysis and is instead presented narratively.TA B L E 2 (Continued)TA B L E 3 Results of meta-analyses comparing kiwifruit, senna, or magnesium oxide supplements with placebo for response to treatment, stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation.

E 3
Forest plot of (A) response to treatment; (B) stool frequency (complete spontaneous bowel movements/week); (C) stool consistency (Bristol Stool Form Scale); (D) integrative symptom scores (Constipation Scoring System) in randomized controlled trials comparing magnesium oxide supplements with control in adults with chronic constipation (n = 94).Values were calculated as relative risk (95% CIs) or mean difference (95% CIs) using a random-effects model.CI, confidence interval; IV, inverse variance; M-H, Mantel-Haenszel; RR, relative risk; SD, standard deviation.

range) a Constipation diagnosis Intervention Dose Form Duration Comparator Outcomes included in meta-analysis
Characteristics of randomized controlled trials investigating the effect of food or mineral supplements on chronic constipation in adults.
2 bowel movements/day, p < 0.001), and there was no change in the control group.Ziziphus jujuba reduced overall constipation symptom severity (p < 0.001), difficult evacuation (p < 0.01), bloating (p < 0.01), abdominal pain (p < 0.03), and quality of life using the SF-36 (p < 0.003) from baseline to week 4; however, no change in these parameters was found in the control group.For each outcome, there was no analysis comparing the intervention to control at week 4.TA B L E 2

range) a Constipation diagnosis Intervention Dose Form Duration Comparator Outcomes included in meta-analysis
Abbreviations: CSBM, complete spontaneous bowel movements; NR, not reported; QoL, quality of life.Ref, reference.a Values for whole study population unless values per group are specified.b Study administered two active interventions (senna and magnesium oxide) and control, with each group having a sample size of n = 30 and being analyzed separately (19).