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Objective: Current studies on the association between constipation and depression is still insufficient. In this study, we investigated the detailed association between constipation and major depression among American adults.

Methods: In this cross-sectional study, 12,352 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005–2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week. For the assessment of major depression, the validated Patient Health Questionnaire-9 was used. Adjusted odds ratios (ORs) were calculated using multivariate logistic regression models. A subgroup analysis was carried out to ensure that the results were stable.

Results: Of the 12,352 participants, 430 reported constipation, with a prevalence of 3.5%. Depression was reported in 1030 cases, indicating a prevalence rate of 8.3%. Patients with constipation were significantly more likely to have major depression (20.9%) than those without it (7.9%, p < 0.001). After adjusting for age, sex, race/ethnicity, marital status, education level, body mass index, vigorous physical activity, alcohol consumption, smoking status, poverty income ratio, diabetes, selective serotonin reuptake inhibitor use, liver disease, heart disease, pulmonary disease, hypertension, arthritis, cancer, dietary fiber intake, moisture intake, total fat intake, carbohydrates intake, and protein intake, constipation is significantly associated with major depression (OR: 2.20, 95%CI: 1.68–2.87, p < 0.001). Subgroup analyses by age, sex, dietary intake, risk behaviors, and common complications showed no statistically significant interactions (p > 0.05).

Conclusion: In conclusion, this study showed that constipation were significantly associated with depression. When treating patients with constipation, it is necessary for clinicians to screen and evaluate depression, and provide timely and effective intervention for patients with depression to avoid further deterioration of the condition.

Baseline characteristics: In Table 1, we compared the characteristics of participants in the constipated and normal groups. Among these participants, 430 reported constipation, with a prevalence of 3.5%. Patients with constipation had a higher incidence of being younger, female, White, divorced, separated or widowed, never married, under/normal weight, smokers, with a lower education level, and PIR. Constipated individuals consumed less fiber, fat, protein, carbohydrates, and water in their diets. Constipation was associated with a greater likelihood of heart disease and pulmonary disease among patients with comorbidities. 1,030 reported depression, with a prevalence of 8.3%. Patients with constipation were significantly more likely to have major depression (20.9%) than those without it (7.9%, p < 0.001).

In Table 2, we compared the characteristics of the participants in the depressed and non-depressed groups. Patients with major depression had a higher incidence of being younger, female, black, hispanic, divorced, separated or widowed, never married, obese, smokers, SSRI use, with a lower education level, PIR, and percentage of vigorous physical activity practicing. Patients with major depression consumed less fiber, fat, protein, carbohydrates, and water in their diets. Among patients with comorbidities, major depression was more likely to be associated with diabetes, liver disease, heart disease, pulmonary disease, hypertension, and arthritis. Patients with major depression were significantly more likely to have constipation (8.7%) than those without it (3.0%, p < 0.001).

Association between constipation and major depression: Based on univariate logistic regression analysis, race and ethnicity, sex, age, marital status, education level, PIR, BMI, smoking status, dietary intake, vigorous physical activity, SSRI use, and comorbidities (except cancer) were significantly related to major depression (all p < 0.05) (Table 3). In Table 4, the logistic regression results for the association between constipation and major depression are presented. The unadjusted model (Model I) showed an increased risk of major depression related to constipation (OR: 3.09, 95%CI: 2.43–3.94, p < 0.001). After controlling for sex and age (Model II), constipation and major depression were still associated (OR: 2.60, 95%CI: 2.03–3.32, p < 0.001). After adjusting for covariates in Model II and race/ethnicity, marital status, education level, PIR, BMI, vigorous physical activity, smoking status, SSRI use and alcohol consumption (Model III), constipation was still significantly positively associated with major depression (OR: 2.42, 95%CI: 1.86–3.14, p < 0.001). After controlling for covariates in Model III and diabetes, hypertension, arthritis, heart disease, pulmonary disease, liver disease, and cancer (Model IV), the results did not change significantly (OR: 2.29, 95%CI: 1.76–2.99, p < 0.001). Even after further adjusting for covariates in Model IV and dietary fiber, moisture, total fat, carbohydrate, and protein intake (Model V), constipation and major depression remained significantly associated (OR: 2.20, 95%CI: 1.68–2.87, p < 0.001).

A subgroup analysis of the data is presented in Figure 2 and Supplementary Figure 1. Subgroup analyses by age, sex, dietary intake, risk behaviors, SSRI use, and common complications showed no statistically significant interactions (p > 0.05). We found that the association between constipation and depression was relatively stable in every subgroup.

Background: Chronic constipation is a prevalent disorder that remains challenging to treat. Studies suggest increasing fiber intake may improve symptoms, although recommendations on the fiber type, dose, and treatment duration are unclear.

Objectives: We investigated the effects of fiber supplementation 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).

Methods: Studies were identified using electronic databases, backward citation, and hand searches of abstracts. RCTs reporting administration of fiber supplementation in adults with chronic constipation were included. Risks of bias (RoB) was assessed with the Cochrane RoB 2.0 tool. Results were synthesized using risk ratios (RRs), mean differences, or standardized mean differences (SMDs) and 95% CIs using a random-effects model.

Results: Sixteen RCTs with 1251 participants were included. Overall, 311 of 473 (66%) participants responded to fiber treatment and 134 of 329 (41%) responded to control treatment [RR: 1.48 (95% CI: 1.17, 1.88; P = 0.001); I2 = 57% (P = 0.007)], with psyllium and pectin having significant effects. A higher response to treatment was apparent in fiber groups compared to control groups irrespective of the treatment duration, but only with higher fiber doses (>10 g/d). Fiber increased stool frequency [SMD: 0.72 (95% CI: 0.36, 1.08; P = 0.0001); I2 = 86% (P < 0.00001)]; psyllium and pectin had significant effects, and improvement was apparent only with higher fiber doses and greater treatment durations (≥4 weeks). Fiber improved stool consistency (SMD: 0.32; 95% CI: 0.18, 0.46; P < 0.0001), particularly with higher fiber doses. Flatulence was higher in fiber groups compared to control groups(SMD: 0.80; 95% CI: 0.47, 1.13; P < 0.00001).

Conclusions: Fiber supplementation is effective at improving constipation. Particularly, psyllium, doses >10 g/d and treatment durations of at least 4 weeks appear optimal, though caution is needed when interpreting the results due to considerable heterogeneity. These findings provide promising evidence on the optimal type and regime of fiber supplementation, which could be used to standardize recommendations to patients. The protocol for this review is registered at PROSPERO as CRD42020191404.

A total of 7356 nonduplicated records were identified, of which 93 were deemed to be potentially eligible (Figure 1). Of these, 77 records were excluded (Supplemental Table 1). One completed but unpublished trial (NCT01847950) was confirmed to be eligible after contact with the principal investigator; however, the data could not be shared due to a confidentiality agreement. In total, 16 RCTs fulfilled the criteria for inclusion in the review, involving 1251 participants with chronic constipation. Table 2 displays the characteristics of the included studies. Twelve studies were in English, 2 were in Spanish, 1 was in Korean, and 1 was in Chinese. There were 14 parallel RCTs and 2 crossover RCTs. For 1 crossover study, data from the first period only were extracted due to an inadequate washout period. There was variability in the fiber type (e.g., psyllium, polydextrose), dose (4 to 40 g/d), and treatment duration (2 to 8 weeks) studied. Authors of all studies were contacted for further information. Of these, 7 replied and 1 provided data for inclusion in the analyses.

Outcomes: The outcomes of the meta-analysis are reported in Table 3. Forest plots for subgroup analyses on fiber type, prebiotic status, doses, and treatment durations for each outcome are found in Supplemental Figures 1–22.

Response to treatment: Response to treatment, measured as symptomatic improvement, was reported as dichotomous data in 9 studies including 802 participants. Overall, 311 of 473 (66%) participants responded to fiber treatment and 134 of 329 (41%) responded to control treatment (RR: 1.48; 95% CI: 1.17, 1.88; P = 0.001), with substantial heterogeneity between studies (I2 = 57%; P = 0.007). Subgroup analyses showed significantly greater responses to treatment in the 3 trials of psyllium supplementation, with no significant heterogeneity [RR: 1.82 (95% CI: 1.51, 2.20; P < 0.00001); I2 = 0% (P = 0.98)] and in 1 trial of pectin supplementation (RR: 3.71; 95% CI: 1.83, 7.56; P = 0.0003) (Figure 2). Nonprebiotics increased response to treatment [RR: 1.46 (95% CI: 1.08, 1.97; P = 0.01); I2 = 69% (P = 0.002)], while prebiotics and mixtures of prebiotics and nonprebiotics did not; however, no significant subgroup differences were detected (P = 0.97). A significant effect was shown for high fiber doses (>10 g/d) [RR: 1.72 (95% CI: 1.35, 2.18; P < 0.0001); I2 = 41% (P = 0.09)], but not low fiber doses (≤10 g/d), with a statistically significant subgroup effect (P = 0.005); however, only a low number of studies contributed data to the low-dose subgroup. All treatment durations (less than or greater than 4 weeks) were effective at increasing response to treatment (Supplemental Figure 1).

Stool frequency: Stool frequency was measured in 15 studies; however, 1 study did not report data in a form that could be included in the meta-analysis, and these data were not obtained on request. Fourteen studies including 1040 participants were included in the meta-analysis. Stool frequency was reported in various units, such as bowel movements/week and days between bowel movements. Fiber significantly increased stool frequency compared to control (SMD: 0.72; 95% CI: 0.36, 1.08; P = 0.0001); however, considerable heterogeneity was detected (I2 = 86%; P < 0.00001). Subgroup analyses showed that psyllium significantly increased stool frequency [SMD: 1.13 (95% CI: 0.39, 1.88; P = 0.003); I2 = 67% (P = 0.05)], as did pectin and wheat bran. However, polydextrose, inulin-type fructans, and galacto-oligosaccharides (GOS) did not impact stool frequency (Figure 3). Prebiotics and nonprebiotics were effective at increasing stool frequency when administered individually but not as mixtures; however, no significant subgroup differences were detected (P = 0.73). High fiber doses (>10 g/d) significantly increased stool frequency [SMD: 0.93 (95% CI: 0.49, 1.38; P < 0.0001); I2 = 86% (P < 0.00001)], but low fiber doses (≤10 g/d) did not, with a statistically significant subgroup effect (P = 0.06). Greater treatment durations (≥4 weeks) significantly increased stool frequency [SMD: 1.13 (95% CI: 0.50, 1.76; P = 0.0001); I2 = 89% (P < 0.00001)], but shorter durations (<4 weeks) did not, with a statistically significant subgroup effect (P = 0.03) (Supplemental Figure 2). Heterogeneity remained high between studies within each subgroup. No significant funnel plot asymmetry was detected (Supplemental Figure 23).

A sensitivity analysis was conducted to include studies that measured and reported stool frequency using the same methods and units (bowel movements/week), and a MD was calculated. In 12 studies including 966 participants, fiber significantly increased stool frequency by +1.19 bowel movements/week (95% CI: 0.59, 1.78 bowel movements/week; P < 0.0001) compared to control; however, heterogeneity remained considerable (I2 = 80%; P < 0.00001) (Supplemental Figure 3). Psyllium significantly increased stool frequency by +3.08 bowel movements/week [95% CI: 0.61, 5.54 bowel movements/week; P = 0.01; I2 = 90% (P < 0.0001)] and GOS significantly increased stool frequency by +0.71 bowel movements/week [95% CI: 0.07, 1.34 bowel movements/week; P = 0.03; I2 = 68% (P = 0.04)]. High fiber doses (>10 g/d) increased stool frequency [MD: +1.60 bowel movements/week (95% CI: 0.71, 2.48 bowel movements/week; P = 0.0004); I2 = 85% (P < 0.00001)], but low fiber doses (≤10 g/d) did not, with a significant subgroup effect (P = 0.07). Greater treatment durations (≥4 weeks) increased stool frequency [MD: +1.33 bowel movements/week (95% CI: 0.62, 2.03 bowel movements/week; P = 0.0002); I2 = 81% (P < 0.00001)], but shorter durations (<4 weeks) did not; however, no significant subgroup differences were detected (P = 0.59). Heterogeneity remained high between studies within each subgroup (Supplemental Figure 3).

Stool consistency: Stool consistency was measured in 11 studies; however, 1 study did not report data, and these data were not obtained on request. Ten studies including 918 participants were included in the meta-analysis. The methods of measuring stool consistency varied, with most studies using the Bristol Stool Form Scale or a modified version of it. Fiber significantly improved stool consistency compared to control (SMD: 0.32; 95% CI: 0.18, 0.46; P < 0.0001), and no significant heterogeneity was detected (I2 = 0%; P = 0.56). Subgroup analyses showed that psyllium [SMD: 0.52 (95% CI: 0.25, 0.78; P = 0.0002); I2 = 0% (P = 0.46)] and inulin-type fructans [SMD: 0.36 (95% CI: 0.03, 0.70; P = 0.03); I2 = 0% (P = 0.38)] significantly improved stool consistency, but polydextrose and GOS did not; however, no significant subgroup differences were detected (P = 0.40 ) (Figure 4). Nonprebiotic interventions significantly improved stool consistency [SMD: 0.35 (95% CI: 0.16, 0.53; P = 0.0002); I2 = 0% (P = 0.46)], while prebiotics or mixtures did not; however, no significant subgroup differences were detected (P = 0.65). High fiber doses (>10 g/d) improved stool consistency (SMD: 0.42; 95% CI: 0.26, 0.59; P < 0.00001), but low fiber doses (≤10 g/d) did not, with a significant subgroup effect (P = 0.02). All durations (less than or greater than 4 weeks) were effective at improving stool consistency. There was no significant heterogeneity detected between studies within each subgroup (Supplemental Figure 4). Funnel plot asymmetry was detected (Supplemental Figure 24).

Stool weight: Stool weight was reported in 3 studies including 59 participants. Fiber did not affect stool weight compared to control (MD: 31.93 g/d; 95% CI: −3.74, 67.60 g/d; P = 0.08), and there was no significant heterogeneity (I2 = 46%; P = 0.15) (Supplemental Figure 5).

Gut transit time: Whole GTT was reported in 7 studies including 485 participants. All studies measured transit time using the radio-opaque marker method. Fiber had no significant effect on whole GTT (MD: −7.5 hours; 95% CI: −18.1, 3.1 hours; P = 0.17), and considerable heterogeneity was detected (I2 = 81%; P < 0.00001) (Supplemental Figure 6). The effect of higher doses of fiber (>10 g/d) in decreasing whole GTT approached conventional statistical significance [MD: −12.3 hours (95% CI: −25.1, 0.5 hours; P = 0.06); I2 = 83% (P < 0.00001)], but low fiber doses (≤10 g/d) did not impact whole GTT, with a significant subgroup effect (P = 0.05). Greater treatment durations (≥4 weeks) significantly decreased whole GTT by −18.4 hours [95% CI: −31.5, –5.4 hours; P = 0.006; I2 = 77% (P = 0.001)], but shorter durations (<4 weeks) did not, with a significant subgroup effect (P = 0.003) (Supplemental Figure 6).

Regional GTT was reported in 2 studies. Fiber had no significant impact on right, left, or rectosigmoid transit time compared to control (Supplemental Figure 7).

Integrative symptom scores: Various questionnaires were used to measure integrative symptom scores in 5 studies including 531 participants. Fiber had no significant effect on integrative symptom scores [SMD: −0.15 (95% CI: −0.39, 0.08; P = 0.20); I2 = 37% (P = 0.12)]. Fiber doses higher or lower than 10 g/d had no effect on symptom scores. Greater treatment durations (≥4 weeks) led to significant improvements in symptom scores [SMD: −0.42 (95% CI: −0.77, −0.06; P = 0.02); I2 = 32% (P = 0.22)] but shorter durations (<4 weeks) did not, with a significant subgroup effect (P = 0.04). However, low numbers of studies contributed data in each subgroup (Supplemental Figure 8).

A sensitivity analysis was conducted for studies that measured and reported integrative symptom scores using the PAC-SYM questionnaire, and a MD was calculated. In 3 studies including 428 participants, fiber had no impact on PAC-SYM global scores [MD: −0.10 scale points (95% CI: −0.31, 0.11 scale points; P = 0.35); I2 = 48% (P = 0.07); a lower score denotes less severe symptoms]. In addition, fiber had no impact on the abdominal, rectal, or stool subscales of PAC-SYM (Supplemental Figures 9–12). All 3 studies measured 1 other integrative symptom score—2 measured the CCCS and 1 measured the Bowel Function Index —and reported no difference between intervention and control groups.

Individual gastrointestinal symptoms: The effect of fiber supplementation on the severity of individual symptoms was widely reported in various studies (Supplemental Figures 13–17).

Severity of straining was reported in 4 studies including 489 participants. Fiber significantly improved straining severity compared to control [SMD: −0.32 (95% CI: −0.59, −0.04; P = 0.02); I2 = 46% (P = 0.10)]. Subgroup analyses showed that only psyllium significantly improved straining severity [SMD: −0.65 (95% CI: −0.91, −0.39; P < 0.00001); I2 = 0% (P = 0.67)], while polydextrose and inulin-type fructans did not (Figure 5). High fiber doses (>10 g/d) improved straining severity [SMD: −0.45 (95% CI: −0.73, −0.16; P = 0.002); I2 = 34% (P = 0.002)], but low fiber doses (≤10 g/d) did not, with a significant subgroup effect (P = 0.09). However, a low number of studies contributed data in each subgroup (Supplemental Figure 13).

Severity of flatulence was reported in 3 studies including 153 participants. Fiber significantly worsened flatulence severity compared to control (SMD: 0.80; 95% CI: 0.47, 1.13; P < 0.00001), and there was no significant heterogeneity (I2 = 0%; P = 0.84). Subgroup analysis indicated that 2 studies administering inulin-type fructans significantly worsened flatulence severity [SMD: 0.79 (95% CI: 0.44, 1.14; P < 0.00001); I2 = 0% (P = 0.60) (Figure 5; Supplemental Figure 14)]. Fiber had no significant impact on severity of incomplete evacuation, bloating, or abdominal pain or discomfort (Supplemental Figures 15–17).

The frequency of individual symptoms was less commonly reported amongst studies, and suitable data could not be obtained for more than 1 study; therefore, a meta-analysis was not performed.

Several other individual symptoms were reported in the same way by only 1 study each and, therefore, meta-analyses were not possible. These outcomes were occurrence of hard stools, pain with defecation, sensation of anal obstruction, use of manual maneuvers, defecation difficulties, ease of passage, time spent on the toilet, and borborygmi. Of note, in 1 study administering an unspecified type of fiber, the frequency of sensation of anal obstruction was significantly lower in the fiber group compared to the control group (P = 0.032). In a study administering pectin, the time spent on the toilet was significantly lower in the fiber group compared to the control group(P < 0.05).

Quality of life: Two studies including 296 participants reported overall quality of life (QoL) measurements using the Patient Assessment of Constipation Quality of Life (PAC-QoL) global score. Both studies administered polydextrose and found that it did not impact QoL scores (MD: −0.04 scale points; 95% CI: −0.19, 0.10 scale points; P = 0.54; a higher score indicates more severe), and heterogeneity was not significant (I2 = 37%; P = 0.17). Fiber doses higher or lower than 10 g/d had no impact on PAC-QoL. Greater treatment durations (≥4 weeks) significantly improved global scores [MD: −0.25 scale points (95% CI: −0.48, −0.03 scale points; P = 0.03); I2 = 0% (P = 0.66)], while shorter durations (<4 weeks) did not, with a significant subgroup effect (P = 0.03). However, these data derive from 2 intervention groups of the same study (Supplemental Figure 18). Fiber had no impact on QoL subscales for satisfaction, physical discomfort, worries and concerns, or psychosocial discomfort (Supplemental Figures 19–22).

Laxative use: Two studies measured laxative use; however, data were only reported for 1 study. In this study, pectin supplementation significantly reduced the number of days participants took laxatives compared to control [mean: 1.4 days (SD: 1.0 days) compared with 1.9 days (SD: 1.2 days), respectively; P < 0.01].

Adverse events: Adverse events were reported in 12 studies including 1089 participants. In 1 study administering polydextrose, 18 events were considered to be related to the intervention and 10 events were considered to be related to the control treatment. These were all mild to moderate, except for 1 event in the polydextrose group that was severe (nausea). Another study administering polydextrose reported events such as abdominal pain, but there was no link identified between treatment groups and the occurrence of adverse events. One study administering psyllium reported that 2 participants (18%) in the intervention group had abdominal pain, compared to none in the control group. Another study administering psyllium reported that 3 participants withdrew from the intervention group and 5 from the control group, for reasons related to the reported treatment side effects. A study administering wheat bran reported participant withdrawal due to “unbearable” abdominal pain. Two studies reported that while adverse events did occur, none interfered with the trial process. Finally, 2 studies administering psyllium, 1 administering pectin, and 2 administering GOS reported no serious adverse events associated with the fiber products.

Compliance: Compliance was measured in 7 studies, but reported in only 3. Of those that counted returned sachets, 1 study reported >98% compliance and another reported >95% compliance in each group. One study reported that compliance was equally satisfactory in both groups; however, no data were provided. Another 2 of the 7 studies reported the numbers of participants excluded for noncompliance only: in the first RCT, 3 participants were excluded in the fiber group and none were excluded in the control group; and in the other, 4 participants were excluded, but the group they belonged to was not dislosed.

Risk of bias at the outcome and study levels: No study was at low RoB across all domains. Bias due to the randomization process was judged to have low risk in 3 studies and some concerns in 13 studies due to inadequate details on the methods used in the generation of the randomization sequence or for concealment of allocation. Bias due to deviations from the intended interventions was judged to have low risk in 6 studies, some concerns in 2 studies, and high risk in 8 studies; as although all but 2 studies were double-blinded, many did not follow an intention-to-treat analysis. Bias across other domains varied at the outcome level (Supplemental Figures 1–22A).