Background
In the United States, nearly a third of adults older than 50 years have diverticulosis [
1], of whom around 4% will develop complications such as diverticulitis or diverticular bleeding [
2,
3]. Together, these complications resulted in over 216,000 admissions, nearly 2.7 million ambulatory visits, and around 2.2 billion dollars in inpatient costs in 2012 [
4].
Despite the increasing prevalence of diverticulosis and the potential for costly complications, the role of environmental factors in the pathogenesis of the disease remains poorly understood. Prior studies investigating dietary intake, specifically of fruit and vegetables, and risk of diverticulosis have yielded conflicting results. Early studies have suggested a protective role for dietary fiber in the development of diverticula [
5‐
7], while more recent studies have found either positive or no associations between fruit and vegetables and total fiber intake and the prevalence of diverticulosis [
8‐
11]. However, many of these results were based on dietary evaluations conducted after the detection of diverticula, either radiographically or by colonoscopy [
6‐
9], or were conducted in Asia where there are significant differences in the prevalence and location of diverticulosis, limiting the generalizability of these studies to the western population [
10,
11]. We therefore used dietary data in the Gastrointestinal Disease and Endoscopy Registry (GIDER) study to investigate the associations between fruit and vegetables consumption and the prevalence of diverticulosis.
Results
We confirmed diverticulosis in 245 participants (44.6%) among 549 enrolled in the GI Disease and Endoscopy Registry with a mean age of 61 years. Participants with diverticulosis were more likely to be older, male, smokers, and have a higher BMI than those without diverticula (Table
1). The rates of diverticulosis varied from 57% among those who consumed fruit and vegetables less than five times per week to 32% among those who consumed greater than one serving per day (Table
2). We found significant inverse associations between the intake of both fruit and vegetables and the prevalence of diverticulosis (P
trend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60–1.17) with five to seven servings per week and 0.62 (95%, 0.44–0.89) with greater than one serving per day. Similarly, we observed a lower prevalence of diverticulosis with five to seven servings of fruit per week (PR = 0.81; 95% CI, 0.58–1.11) and greater than one serving of fruit per day (PR = 0.60; 95% CI, 0.41–0.87) compared to participants with less than five servings per week even after adjusting for age, sex, BMI, smoking, physical activity, regular NSAID use, dietary pattern, and bowel movement frequency. We also created cross-classified categories of fruit and vegetables intake and observed that compared to individuals with less than or equal to one serving of fruit and vegetables per day, the multivariable-adjusted PR of diverticulosis was 0.58 (95% CI, 0.39–0.87) with greater than one serving per day.
Table 1
Baseline Characteristics of Participants According to Diagnosis of Diverticulosis
Age, years | 58.3 ± 9.6 | 65.1 ± 9.1 |
Gender, male | 125 (41.1) | 130 (53.1) |
Body Mass Index (kg/m2) | 26.4 ± 5.2 | 28.2 ± 5.8 |
Smoking History |
Current | 7 (2.3) | 9 (3.7) |
Past | 80 (26.3) | 94 (38.4) |
Never | 213 (70.1) | 139 (56.7) |
Physical activitya, MET/week | 40.3 ± 35.9 | 32.3 ± 37.1 |
Regular NSAID Use in Past 2 Years (> 2 tablets/week) | 74 (24.3) | 72 (30.2) |
Dietary Pattern |
Western standard | 164 (54.4) | 141 (57.6) |
Low red meat (< 3 times/month) | 104 (34.2) | 78 (31.8) |
No red meat | 23 (7.6) | 23 (9.4) |
Number of bowel movements |
> 1/day | 61 (20.1) | 31 (12.7) |
1/day | 151 (49.8) | 135 (55.1) |
< 1/day | 86 (28.3) | 76 (31.0) |
Table 2
Consumption of Fruit, and Vegetables and Prevalence of Diverticulosis
Vegetables |
Total subjects | 126 | 160 | 215 | |
No. of cases, n (%) | 72 (57.1) | 82 (51.3) | 69 (32.1) | |
Age-adjusted | 1.00 | 0.85 (0.62–1.17) | 0.58 (0.42–0.81) | 0.001 |
Model 2a | 1.00 | 0.85 (0.61–1.19) | 0.65 (0.46–0.92) | 0.015 |
Model 3b | 1.00 | 0.84 (0.60–1.17) | 0.62 (0.44–0.89) | 0.008 |
Fruits |
Total subjects | 200 | 152 | 139 | |
No. of cases, n (%) | 102 (51.0) | 69 (45.4) | 47 (33.8) | |
Age-adjusted | 1.00 | 0.83 (0.61–1.13) | 0.61 (0.43–0.87) | 0.006 |
Model 2a | 1.00 | 0.82 (0.59–1.13) | 0.64 (0.44–0.92) | 0.015 |
Model 3b | 1.00 | 0.81 (0.58–1.11) | 0.60 (0.41–0.87) | 0.007 |
We also explored the association between red and processed meat and prevalent diverticulosis. Compared to individuals who reported no consumption, the multivariable-adjusted PRs of diverticulosis with 2 or more servings per week were 1.03 (95% CI: 0.62–1.71) for red meat and 0.97 (95% CI 0.68–1.40) for processed meat, respectively.
Finally, we examined the associations between the consumption of fruit and vegetables and the prevalence of diverticulosis according to strata defined by potential risk factors and found no evidence for effect modification by age, BMI, smoking, and red meat intake (All P
interaction > 0.055) (Tables
3 and
4).
Table 3
Risk of diverticulosis according to vegetables consumption by strata
Vegetables |
Age | | | | 0.128 |
< 60 years |
No. of cases | 21/51 | 20/60 | 19/98 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.81 (0.44–1.49) | 0.45 (0.24–0.85) | |
Multivariable-adjusted | 1.00 | 0.81 (0.42–1.57) | 0.53 (0.27–1.01) | |
≥60 years |
No. of cases | 51/75 | 62/100 | 50/117 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.88 (0.61–1.28) | 0.64 (0.43–0.95) | |
Multivariable-adjusted | 1.00 | 0.87 (0.59–1.29) | 0.70 (0.46–1.05) | |
BMI (kg/m2) | | | | 0.842 |
< 25 |
No. of cases | 20/42 | 22/50 | 25/95 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.96 (0.53–1.76) | 0.62 (0.34–1.12) | |
Multivariable-adjusted | 1.00 | 1.02 (0.54–1.92) | 0.72 (0.39–1.34) | |
≥25 |
No. of cases | 52/84 | 60/110 | 44/120 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.82 (0.57–1.19) | 0.60 (0.40–0.90) | |
Multivariable-adjusted | 1.00 | 0.82 (0.55–1.21) | 0.65 (0.43–0.99) | |
Smoking | | | | 0.778 |
Current or past |
No. of cases | 27/40 | 31/42 | 19/58 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 1.06 (0.65–1.72) | 0.59 (0.35–0.99) | |
Multivariable-adjusted | 1.00 | 1.05 (0.63–1.75) | 0.67 (0.39–1.16) | |
Never |
No. of cases | 33/63 | 32/79 | 29/103 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.72 (0.47–1.11) | 0.58 (0.37–0.89) | |
Multivariable-adjusted | 1.00 | 0.73 (0.47–1.13) | 0.64 (0.41–1.01) | |
Red Meat Intake | | | | 0.938 |
< 2 times/week |
No. of cases | 27/46 | 23/40 | 17/68 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 1.11 (0.68–1.80) | 0.55 (0.33–0.94) | |
Multivariable-adjusted | 1.00 | 1.04 (0.63–1.74) | 0.59 (0.34–1.02) | |
≥2 times/week |
No. of cases | 28/45 | 41/79 | 28/84 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.66 (0.42–1.04) | 0.56 (0.35–0.88) | |
Multivariable-adjusted | 1.00 | 0.71 (0.44–1.13) | 0.64 (0.40–1.04) | |
Table 4
Risk of diverticulosis according to fruit consumption by strata
Fruit |
Age | | | | 0.055 |
< 60 years |
No. of cases | 35/93 | 15/60 | 7/51 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.66 (0.36–1.21) | 0.36 (0.16–0.80) | |
Multivariable-adjusted | 1.00 | 0.62 (0.33–1.15) | 0.33 (0.14–0.81) | |
≥60 years |
No. of cases | 67/107 | 54/92 | 40/88 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.92 (0.64–1.31) | 0.72 (0.49–1.06) | |
Multivariable-adjusted | 1.00 | 0.92 (0.63–1.36) | 0.77 (0.51–1.17) | |
BMI (kg/m2) | | | | 0.317 |
< 25 |
No. of cases | 29/63 | 22/57 | 15/62 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.75 (0.43–1.30) | 0.49 (0.26–0.92) | |
Multivariable-adjusted | 1.00 | 0.75 (0.41–1.37) | 0.57 (0.29–1.09) | |
≥25 |
No. of cases | 73/137 | 47/95 | 32/77 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.89 (0.61–1.28) | 0.72 (0.47–1.09) | |
Multivariable-adjusted | 1.00 | 0.85 (0.58–1.26) | 0.70 (0.45–1.09) | |
Smoking | | | | 0.473 |
Current or past |
No. of cases | 39/60 | 20/37 | 17/41 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.95 (0.58–1.54) | 0.69 (0.42–1.14) | |
Multivariable-adjusted | 1.00 | 0.91 (0.55–1.51) | 0.72 (0.42–1.23) | |
Never |
No. of cases | 45/97 | 32/80 | 12/60 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.77 (0.51–1.15) | 0.55 (0.34–0.90) | |
Multivariable-adjusted | 1.00 | 0.74 (0.48–1.14) | 0.58 (0.35–0.97) | |
Red Meat Intake | | | | 0.925 |
< 2 times/week |
No. of cases | 35/67 | 19/39 | 12/47 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.92 (0.57–1.52) | 0.65 (0.39–1.09) | |
Multivariable-adjusted | 1.00 | 0.83 (0.49–1.41) | 0.68 (0.39–1.17) | |
≥2 times/week |
No. of cases | 45/79 | 31/75 | 18/52 | |
Prevalence Ratio (95% CI) |
Age adjusted | 1.00 | 0.71 (0.47–1.08) | 0.63 (0.39–1.02) | |
Multivariable-adjusted | 1.00 | 0.72 (0.47–1.12) | 0.65 (0.39–1.09) | |
Discussion
In this colonoscopy-based cohort, fruit and vegetables consumption was significantly associated with a lower prevalence of diverticulosis even after adjusting for common risk factors. Conversely, no associations were observed between red and processed meat intake and the risk of prevalent diverticulosis. Furthermore, we did not observe any effect modification by age, BMI, smoking, or red meat intake on the association between fruit and vegetables intake and prevalent diverticulosis.
Our finding of a lower risk of prevalent diverticulosis among participants with a higher fruit and vegetables intake is supported by several prior studies. In a large cohort nested within the Health Professionals Follow-up Study, Aldoori and colleagues [
19] found high-fiber diet to be protective against symptomatic diverticular disease. In a case-control study in Greece, Manousos et al.
6 observed a significant inverse association between vegetables intake and prevalence of symptomatic diverticular disease. Similarly, a study of diet and diverticulosis restricted to asymptomatic patients found that vegetarians had a lower prevalence of diverticulosis compared to non-vegetarians [
20]. However, these studies either focused on symptomatic diverticulosis [
6,
19] or failed to fully account for other lifestyle and confounding factors [
20]. Therefore, our study, which carefully adjusts for known and putative risk factors for diverticulosis, significantly extends these findings.
In contrast to our findings, two studies conducted in South Korea and Taiwan found no significant associations between the consumption of fruit and vegetables and risk of diverticulosis [
10,
11]. However, the prevalence of diverticulosis in East Asian countries varies from 8 to 25%, an estimate that is significantly lower than those reported by us and others in Western populations [
8‐
11,
20‐
22]. In addition, diverticulosis predominately affects the right colon in Asia compared to the left in the West, likely due to distinct risk factors and mechanisms of development [
10]. In the U.S., a cross-sectional, colonoscopy-based study observed no associations between the intake of fiber from fruit and vegetables and risk of diverticulosis, while total fiber intake was found to be associated with a higher prevalence of diverticulosis [
8]. Similarly, a more recent study by the same research group found no associations between the consumption of fruit and vegetables fiber and total fiber and the prevalence of diverticulosis [
9]. However, dietary information was collected up to three to 4 months after colonoscopy in both studies and participants may have been aware of their diagnoses at the time of diet collection, increasing the likelihood of recall bias [
8,
9]. Thus, misclassification of exposures may account for the lack of association between intake of fiber from fruit and vegetables and risk of prevalent diverticulosis.
The mechanism by which fruit and vegetables consumption influences the development of diverticulosis is currently unknown. Nearly fifty years ago, Painter postulated that low-fiber diets produce increased colonic pressures. Along with segmentation of the colon, these higher pressures cause the mucosa to herniate through weak areas in the muscle wall and form diverticula [
5]. However, this hypothesis was based on ecological observations comparing the prevalence of diverticulosis in the West to that of native Africans, which failed to account for confounding variables and did not confirm the presence of diverticula in participants. The interaction between diet and the gut microbiota may mediate this process. In a recent study, Barbara et al. [
23] observed a depletion of
Clostridium cluster IV in the gut microbiota of asymptomatic diverticulosis cases compared to controls without diverticula.
Clostridium cluster IV includes many anti-inflammatory bacterial species that primarily function through the release of butyrate, the preferred energy source for colonocytes and a key contributor to the integrity of the colonic epithelial barrier [
24]. In turn, increased intake of fruit and vegetables has been shown to significantly increase the abundance of
Clostridium cluster IV in the gut microbiome [
25]. Thus, fruit and vegetables consumption through its effect on Clostridium cluster IV could decrease the risk of diverticula formation. Nevertheless, further studies are needed to better examine this complex relationship between diet, gut microbiota, and diverticulosis.
Our study has several strengths. First, all cases of diverticulosis were confirmed through complete colonoscopy. Second, our study population was drawn from a longitudinal cohort in which dietary and lifestyle data were collected prior to colonoscopy, averting the potential for recall bias. Third, we accounted for multiple risk factors that could impact our observed associations, including age, BMI, smoking history, bowel movement frequency, dietary pattern, regular NSAID use, and physical activity.
The present study has several potential weaknesses that are worth highlighting. First, the participants were from a single center and predominately white, which may reduce the generalizability of our observations. Specifically, out of 549 participants enrolled in the cohort, 511 (93.1%) identified as Caucasian, 19 identified as Asian (3.5%), 13 identified as African-American (2.4%), 3 (0.5%) identified as Pacific Islander or Native Hawaiian, and 3 (0.5%) identified as Native American. Second, we based our brief dietary questionnaire on the SFFQ; however, our validation showed a moderate to good correlation between the two measures. In addition, adjusting for measurement errors would likely strengthen our observed association. Third, our dietary questionnaire did not distinguish between different types of fruit and vegetables. Therefore, we were unable to evaluate the relationship between individual foods in these groups and the prevalence of diverticulosis. Lastly, although dietary data were collected prior to the colonoscopy, diverticula were likely present for many years, preventing us from demonstrating a clear temporal association between fruit and vegetables consumption and risk of diverticulosis. However, medium-term studies on patterns of dietary intake over time have demonstrated remarkable stability [
26]. Additionally, some participants may have known about their diagnosis of diverticulosis from prior colonoscopies (~ 40% had 2 or more colonoscopies prior to enrollment).
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