Abstract
Background
Dietary adjustment has consistently been regarded as an effective and health way for both the prevention and treatment of constipation. Several researches suggest a significant correlation between dietary flavonoids intake and gut microbiota, while the relationship between dietary flavonoids and constipation has not been reported. The objective of this study is to investigate the relationship between flavonoids intake and constipation.
Methods
This cross-sectional analysis was based on data from the National Health and Nutrition Examination Survey (NHANES) collected from 2007 to 2010. The dietary flavonoid and subclasses intake value were obtained from the United States Department of Food and Nutrient Database for Dietary Studies (FNDDS), while constipation was defined using the stool consistency or frequency. Relationships between total and six main flavonoid subclasses intake constipation were investigated using weighted logistic regression approach.
Results
The study revealed a negative association between isoflavones, anthocyanidins, flavanones, flavones, flavonols, and total flavonoid intake and constipation, with significant p-trends of < 0.05. Following multivariate adjustment, decreased odds of constipation could still be observed in the highest quartiles of anthocyanidins compared with those in the reference quartiles (p-value = 0.03). Ln-transformed anthocyanidins exhibited a statistically significant nonlinear association with constipation, displaying an inverted U-shaped pattern. When anthocyanidins intake exceeded 0.92 mg, the rate of constipation trended downward with increases in anthocyanidins intake.
Conclusions
Our study demonstrated that higher dietary flavonoids intake can reduce the incidence of constipation in the adult US population. In addition, the negative association between anthocyanin intake and constipation was more stable compared to other subclasses.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-024-03551-x.
Keywords: Flavonoids, Anthocyanidins, Constipation, Gut microbiota, Intestinal health, NHANES
Introduction
Constipation is a prevalent gastrointestinal disorder, distinguished by reduced frequency of bowel movements, typically less than three times per week, and often accompanied by the presence of hardened, desiccated, or clumped stools [1]. Constipation significantly impacts patients’ quality of life and places a substantial strain on social and medical resources [2]. The global prevalence of constipation is estimated at 10.1% among adults, with a greater occurrence observed among females in comparison to males [3]. Constipation is a complex condition influenced by multiple factors, such as dietary intake, socio-economic status, lifestyle, drug use, and depression [4]. Among numerous factors, the association between dietary components and constipation has garnered considerable research interest. Recent research has indicated that increasing soluble fiber, lycopene, and certain microelements like selenium and magnesium intake may decrease the risk of constipation [5–7]. Therefore, dietary strategies exhibit substantial potential in the prevention and management of constipation.
Flavonoids are notable within the realm of natural phytochemicals for their possession of antioxidant, anti-inflammatory, anticancer, and various other biological activities [8, 9]. Fruit, vegetables, grain, tea, and other plant-based beverages are indispensable primary sources of flavonoids [10]. The structural backbone of flavonoids comprises two benzene rings linked by a heterocyclic pyran ring. According to the chemical composition, flavonoids can be subcategorized into several main subclasses, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols [11]. Previous research findings have suggested that dietary flavonoids intake can alleviate inflammation, increase the abundance of gut microbiota, enhance the protective effects of the gut barrier and regulate immune function, thereby improving colitis and reducing the risk of colon cancer [12]. These results suggest protective effects of flavonoids during the development of constipation. However, there is a scarcity of research investigating the relationship between flavonoids intake and constipation.
The primary objective of this study was to assessed the potential relationship between total flavonoids and subclasses intake and the risk of constipation in U.S. adults. The results of our research offer new insights into the dietary intake of flavonoids in the management of constipation among ethnically diverse populations.
Methods
Data source
The National Health and Nutrition Examination Survey (NHANES) is a national sample survey conducted by the National Center for Health Statistics (NCHS), aims to evaluate and assess the health and nutritional status of individuals in the United States. The participants’ data evaluated in this study were obtained from two cycles of NHANES (2007–2008, 2009–2010), as these individuals had both accessible flavonoids intake and bowel health questionnaire (BHQ) data. A total of 11,182 participants aged 20 years or older who had complete flavonoids intake and BHQ data were engaged in this study. Of these individuals, 55 who were taking laxatives and 109 who were pregnant were excluded, while the remaining 10,034 participants comprised the study population.
Flavonoids intake assessment
The dietary flavonoids and subclasses intake values were obtained from the United States Department of Food and Nutrient Database for Dietary Studies (FNDDS), which is connected to the NHANES database. The levels of these flavonoid compounds’ were determined through one 24-hour dietary information interview. Consequently, appropriate weight was employed in the weighted analysis. The Flavonoid Database comprised 29 distinct flavonoid compounds categorized into 6 subclasses of flavonoids including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols. The daily intake of total flavonoids was determined by aggregating the quantities of 6 subclasses of flavonoids. The specific measurement method and equivalent conversion can be referred to Supplementary file 1.
Definition of constipation
Constipation was defined using the stool consistency or frequency in detailed BHQ from NHANES database. The assessment of stool consistency was conducted using the Bristol Stool Form Scale (BSFS), a classification system that categorizes stool consistency into seven distinct types. Constipation was defined by those participants whose “usual or most common” stool type was either BSFS type 1 (separate hard lumps) or type 2 (lumpy, sausage-like), whereas BSFS types 3–7 were indicative of the absence of constipation. Stool frequency was assessed based on participant responses to the question “How many times per week do you usually have a bowel movement?” Participants who reported answering less than three times per week were categorized as constipation, while those who answered three times or more per week were categorized as non-constipation. In this study, participants who satisfied either of the two conditions were clinically diagnosed with constipation.
Study covariates
Other participant information from the NHANES database that was assessed in the present study included age (years), sex (male, female), ethnicity (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, and other), family poverty to income ratio (PIR), educational status (< high school, high school, > high school), body mass index (BMI, kg/m2), total fiber intake(g), water intake(including total tap water and total bottled water intake, g), energy intake (kcal), total sugars intake(g), physical activity (including recreational activity and work activity), depression, diabetes mellitus, and hypertension. Considering that the majority of flavonoids are present as glycosides, conjugated with sugars, we included total sugars intake as a covariate in the present study [13]. Diabetes mellitus was defined according to self-reported diagnoses, the use of insulin or other antidiabetic agents, fasting blood glucose levels ≥ 126 mg/dL, HbA1c levels ≥ 6.5%, or serum glucose ≥ 200 mg/dL at 2 h after a 75 g oral glucose load. Hypertension was defined by systolic and/or diastolic blood pressure values ≥ 140 mmHg and ≥ 90 mmHg, respectively, self-reported diagnoses, or the use of antihypertensive medications. Depression was defined based on responses to the 9-item Patient Health Questionnaire 9 (PHQ-9), which is validated and publically available, with a score ≥ 10 being indicative of depression [14].
Statistical analyses
Categorical data were given as numbers (weighted percentages) and compared with chi-squared tests, whereas continuous variables were given as means ± standard error (SE) and compared using Student’s t-tests. Total and six flavonoid subclasses intake were categorized into quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed with univariate and multivariate-adjusted logistic regression analyses when assessing associations between flavonoids intake and constipation. Model 1 was unadjusted, whereas Model 2 was adjusted to account for age, sex, and ethnicity, and Model 3 was further adjusted for BMI [15], total fiber intake, water intake, energy intake, total sugars intake, physical activity, hypertension, depression, and diabetes mellitus. The potential nonlinearity relationships between ln-transformed flavonoids intake and constipation were assessed using restricted cubic spline (RCS) models. Subgroup analyses were additionally conducted based upon sex, ethnicity, education, physical activity, hypertension, diabetes mellitus, and depression. R (v 4.2.2) was utilized to conduct all analyses, using P < 0.05 as the threshold when defining significance.
Results
Participant characteristics
This study comprised 10,034 adult participants from the US, among whom 1,038 individuals were identified as being affected by constipation. Table 1 presents the characteristics of these subjects. There were significant differences observed in age, sex, PIR, BMI, ethnicity, educational status, total fiber, water, energy intake, physical activity, and depression between constipation and non-constipation group. Compared with the non-constipation group, participants with constipation exhibited a lower consumption of isoflavones, anthocyanidins, flavones, and flavonols, while no statistically significant differences were observed in flavan-3-ols, flavanones, and sum of flavonoids.
Table 1.
Participants characteristics
| Non-constipation | Constipation | p value | |
|---|---|---|---|
| N = 8996 | N = 1038 | ||
| Isoflavones(mg) | 1.79(0.19) | 0.92(0.19) | 0.003 |
| Anthocyanidins(mg) | 12.99(0.98) | 8.60(1.00) | < 0.001 |
| Flavan-3-ols(mg) | 195.94(10.62) | 219.72(25.35) | 0.3 |
| Flavanones(mg) | 13.30(0.57) | 11.00(0.94) | 0.05 |
| Flavones(mg) | 0.96(0.05) | 0.68(0.03) | < 0.0001 |
| Flavonols(mg) | 20.37(0.53) | 18.08(1.17) | 0.03 |
| Sum of flavonoids(mg) | 245.36(11.18) | 259.01(26.73) | 0.57 |
| Total sugars intake(g) | 116.90(1.41) | 119.80(3.33) | 0.36 |
| Total fiber intake(g) | 17.20(0.26) | 13.88(0.36) | < 0.0001 |
| water intake(g) | 990.66(21.88) | 760.78(39.05) | < 0.0001 |
| energy intake(kcal) | 2117.26(18.01) | 1849.00(33.50) | < 0.0001 |
| Age(years) | 47.26(0.37) | 45.13(0.62) | < 0.001 |
| PIR | 3.09(0.06) | 2.59(0.08) | < 0.0001 |
| Body mass index(BMI, kg/m2) | 28.86(0.12) | 27.68(0.30) | 0.002 |
| Sex(%) | < 0.0001 | ||
| Female | 4303(49.02) | 713(71.92) | |
| Male | 4693(50.98) | 325(28.08) | |
| Ethnicity(%) | 0.01 | ||
| Mexican American | 1602(8.17) | 156(8.04) | |
| Non-Hispanic Black | 1648(10.41) | 246(15.71) | |
| Non-Hispanic White | 4441(71.31) | 463(64.59) | |
| Other Hispanic | 932(4.85) | 133(6.17) | |
| Other Race | 373(5.26) | 40(5.49) | |
| Educational status(%) | < 0.0001 | ||
| Less than high school | 1070(5.68) | 137(7.93) | |
| High school | 3573(36.11) | 489(45.26) | |
| More than high school | 4344(58.21) | 410(46.81) | |
| Physical activity(%) | 0.002 | ||
| No | 3131(27.35) | 422(34.07) | |
| Yes | 5865(72.65) | 616(65.93) | |
| Diabetes mellitus(%) | 0.24 | ||
| No | 7286(86.59) | 867(88.40) | |
| Yes | 1710(13.41) | 171(11.60) | |
| Hypertension(%) | 0.18 | ||
| No | 5116(62.97) | 626(65.76) | |
| Yes | 3879(37.03) | 412(34.24) | |
| Depression(%) | < 0.0001 | ||
| No | 8197(92.52) | 864(82.31) | |
| Yes | 790(7.48) | 172(17.69) |
PIR, family income to poverty ratio. Categorical data were given as numbers (weighted percentages) and compared with chi-squared tests.Continuous variables were given as means ± standard error (SE) and compared using Student’s t-tests
Relationships between flavonoids intake and constipation
Weighted logistic regression were conducted to assess the potential relationships between flavonoids intake and constipation (Table 2). In Model 1, a statistically significant negative correlation was observed between 5 flavonoids subclasses and total flavonoids intake and constipation (p for trend < 0.05). Despite the p-trend for flavan-3-ols being 0.06, the highest quintiles of flavan-3-ols exhibited a significantly decreased risk of constipation when compared to those in the reference quintiles (p = 0.04). After adjustment for age, sex, and ethnicity in Model 2, the highest quartile of anthocyanidins (OR: 0.63, 95%CI: 0.51,0.78), flavanones (OR: 0.74, 95%CI: 0.57,0.95), flavones (OR: 0.65, 95%CI: 0.52,0.81), flavonols (OR: 0.60, 95%CI: 0.49,0.73), and sum of flavonoids intake (OR: 0.71, 95%CI: 0.56,0.92), with the exception of isoflavones and flavan-3-ols, exhibited inverse relationships with constipation. After further adjustment for BMI, total fiber, water, energy, and sugars intake, physical activity, hypertension, depression, and diabetes mellitus in Model 3, decreased odds of constipation were only observed in the highest quartiles of anthocyanidins (OR: 0.76, 95%CI: 0.59,0.97), compared with those in the reference quartiles. The p-trend for anthocyanins being 0.06, which is only marginally above the conventional significance level of 0.05. However, there were no statistical associations observed in other subclasses and sum flavonoids intake. Additionally, we utilized RCS to investigate the non-linear relationships between ln-transformed anthocyanidins and the occurrence of constipation. Figure 1 shows that ln-transformed anthocyanidins showed a statistically significant nonlinear association with constipation (non-line p value = 0.0442), displaying an inverted U-shaped pattern. At anthocyanidins intake exceeded 0.92 mg (ln-transformed anthocyanidins = -0.083), the rate of constipation trended downward with increases in anthocyanidins intake. When these levels below 0.92 mg, the rate of constipation gradually trended upwards.
Table 2.
Logistic regression analyses of the relationships between total and six flavonoid subclasses intake and constipation status
| Model 1 | Model 2 | Model 3 | ||||
|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | |
| Isoflavones | ||||||
| Quartile 1 (0 mg) | ref | ref | ref | |||
| Quartile 2 (0 mg) | ref | ref | ref | |||
| Quartile 3 (0-0.03 mg) | 0.65(0.50,0.84) | 0.002 | 0.66(0.51,0.85) | 0.002 | 0.75(0.57,0.97) | 0.03 |
| Quartile 4 (0.03-421.02 mg) | 0.78(0.60,1.02) | 0.07 | 0.81(0.62,1.06) | 0.11 | 1.01(0.75,1.36) | 0.93 |
| p for tend | 0.04 | 0.06 | 0.84 | |||
| Anthocyanidins | ||||||
| Quartile 1 (0 mg) | ref | ref | ref | |||
| Quartile 2 (0-0.92 mg) | 0.76(0.60,0.97) | 0.03 | 0.74(0.58,0.95) | 0.02 | 0.79(0.58,1.06) | 0.10 |
| Quartile 3 (0.92-5.49 mg) | 0.79(0.62,1.02) | 0.07 | 0.79(0.60,1.03) | 0.07 | 0.91(0.67,1.23) | 0.51 |
| Quartile 4 (5.49-1497.9 mg) | 0.65(0.54,0.79) | < 0.0001 | 0.63(0.51,0.78) | < 0.001 | 0.76(0.59,0.97) | 0.03 |
| p for tend | < 0.001 | < 0.001 | 0.06 | |||
| Flavan-3-ols | ||||||
| Quartile 1 (0-2.51 mg) | ref | ref | ref | |||
| Quartile 2 (2.51-10.17 mg) | 0.85(0.66,1.10) | 0.21 | 0.92(0.72,1.18) | 0.51 | 1.09(0.85,1.39) | 0.48 |
| Quartile 3 (10.17-30.23 mg) | 0.80(0.59,1.09) | 0.16 | 0.89(0.65,1.20) | 0.42 | 1.13(0.78,1.65) | 0.50 |
| Quartile 4 (30.23-17363.77 mg) | 0.77(0.60,0.99) | 0.04 | 0.84(0.66,1.08) | 0.16 | 1.03(0.76,1.40) | 0.82 |
| p for tend | 0.06 | 0.21 | 0.86 | |||
| Flavanones | ||||||
| Quartile 1 (0 mg) | ref | ref | ref | |||
| Quartile 2 (0-0.22 mg) | 0.90(0.70,1.15) | 0.39 | 0.83(0.62,1.11) | 0.19 | 0.91(0.66,1.27) | 0.57 |
| Quartile 3 (0.22-7.93 mg) | 0.72(0.59,0.89) | 0.004 | 0.70(0.57,0.87) | 0.002 | 0.87(0.67,1.14) | 0.29 |
| Quartile 4 (7.93-1181.25 mg) | 0.74(0.58,0.95) | 0.02 | 0.74(0.57,0.95) | 0.02 | 0.81(0.59,1.11) | 0.18 |
| p for tend | 0.003 | 0.002 | 0.14 | |||
| Flavones | ||||||
| Quartile 1 (0-0.04 mg) | ref | ref | ref | |||
| Quartile 2 (0.04-0.26 mg) | 0.91(0.72,1.15) | 0.41 | 0.88(0.67,1.15) | 0.33 | 0.93(0.69,1.25) | 0.61 |
| Quartile 3 (0.26-0.78 mg) | 0.62(0.48,0.81) | < 0.001 | 0.62(0.47,0.80) | < 0.001 | 0.75(0.55,1.01) | 0.06 |
| Quartile 4 (0.78-87.93 mg) | 0.60(0.48,0.76) | < 0.0001 | 0.65(0.52,0.81) | < 0.001 | 0.85(0.66,1.09) | 0.19 |
| p for tend | < 0.0001 | < 0.0001 | 0.1 | |||
| Flavonols | ||||||
| Quartile 1 (0-3.66 mg) | ref | ref | ref | |||
| Quartile 2 (3.66-8.51 mg) | 0.69(0.48,0.99) | 0.05 | 0.73(0.51,1.06) | 0.09 | 0.81(0.55,1.19) | 0.25 |
| Quartile 3 (8.51-17.91 mg) | 0.59(0.43,0.81) | 0.002 | 0.64(0.47,0.88) | 0.01 | 0.78(0.57,1.06) | 0.11 |
| Quartile 4 (17.91-620.16 mg) | 0.50(0.40,0.62) | < 0.0001 | 0.60(0.49,0.73) | < 0.0001 | 0.79(0.61,1.02) | 0.07 |
| p for tend | < 0.0001 | < 0.001 | 0.1 | |||
| Sum of flavonoids | ||||||
| Quartile 1 (0-14.54) | ref | ref | ref | |||
| Quartile 2 (14.54-39.3 mg) | 0.61(0.46,0.81) | 0.002 | 0.67(0.51,0.88) | 0.01 | 0.84(0.61,1.16) | 0.26 |
| Quartile 3 (39.3-109.82 mg) | 0.65(0.51,0.82) | < 0.001 | 0.70(0.55,0.89) | 0.01 | 0.95(0.73,1.23) | 0.68 |
| Quartile 4 (109.82-17991.79 mg) | 0.64(0.50,0.83) | 0.001 | 0.71(0.56,0.92) | 0.01 | 0.88(0.66,1.17) | 0.34 |
| p for tend | 0.01 | 0.04 | 0.55 | |||
Model 1 had no covariate-adjusted
Model 2 adjusted age, sex, and ethnicity
Model 3 adjusted age, gender, ethnicity, BMI, total fiber intake, water intake, energy intake, total sugars intake, physical activity, hypertension, depression, and diabetes mellitus
Fig. 1.
RCS curves corresponding to the associations between ln-transformed anthocyanidins intake and the occurrence of constipation
Subgroup analysis
According to the results presented in Table 3, a significant inverse association was observed between anthocyanidins intake and constipation in female (p for trend < 0.0001), Non-Hispanic White (p for trend = 0.01), other Hispanic (p for trend = 0.005), those with more than a high school educational status (p for trend = 0.001), those with more than a high school educational status, and those who engage in physical activity (p for trend = 0.01). This association was also observed in participants without diabetes mellitus (p for trend < 0.0001), hypertension (p for trend < 0.0001), and depression (p for trend = 0.01). There was no observed interaction between the covariates and anthocyanidins intake in relation to the risk of constipation (p for interaction > 0.05). Notably, the effect of flavanones intake on the prevalence of constipation was moderated by depression (p for interaction = 0.01, Supplementary Table S4). Sex, ethnicity, educational statue, hypertension, diabetes mellitus, physical activity, and depression did not modify the effect of isoflavones, anthocyanidins, flavan-3-ols, flavones, flavonols, and sum of flavonoids intake on the risk of constipation.
Table 3.
Subgroup analyses focused on the relationship between anthocyanidins intake and the incidence of constipation
| Anthocyanidins | Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | p for trend | p for interaction |
|---|---|---|---|---|---|---|
| Sex | 0.67 | |||||
| Female | ref | 0.73(0.53,0.99) | 0.71(0.52,0.95) | 0.57(0.46,0.71) | < 0.0001 | |
| Male | ref | 0.67(0.45,0.99) | 0.90(0.56,1.44) | 0.63(0.41,0.96) | 0.06 | |
| Ethnicity | 0.76 | |||||
| Other Race | ref | 0.60(0.18,1.99) | 1.28(0.37,4.38) | 0.62(0.19,2.06) | 0.71 | |
| Non-Hispanic White | ref | 0.78(0.57,1.08) | 0.77(0.54,1.09) | 0.64(0.47,0.88) | 0.01 | |
| Mexican American | ref | 0.93(0.51,1.67) | 1.01(0.58,1.77) | 0.96(0.60,1.54) | 0.95 | |
| Non-Hispanic Black | ref | 0.86(0.52,1.43) | 0.79(0.53,1.18) | 0.87(0.56,1.35) | 0.29 | |
| Other Hispanic | ref | 0.52(0.29,0.93) | 0.47(0.29,0.77) | 0.49(0.28,0.87) | 0.005 | |
| Educational status | 0.26 | |||||
| Less than high school | ref | 1.10(0.53,2.32) | 0.90(0.48,1.69) | 1.00(0.54,1.85) | 0.86 | |
| High school | ref | 0.70(0.43,1.13) | 1.02(0.62,1.68) | 0.84(0.60,1.19) | 0.59 | |
| More than high school | ref | 0.80(0.60,1.07) | 0.64(0.43,0.95) | 0.57(0.41,0.80) | 0.001 | |
| Diabetes mellitus | 0.77 | |||||
| No | ref | 0.74(0.56,0.98) | 0.78(0.61,0.99) | 0.66(0.55,0.79) | < 0.001 | |
| Yes | ref | 0.94(0.51,1.75) | 0.92(0.52,1.65) | 0.63(0.33,1.18) | 0.18 | |
| Hypertension | 0.07 | |||||
| No | ref | 0.60(0.44,0.80) | 0.75(0.55,1.02) | 0.57(0.46,0.71) | < 0.0001 | |
| Yes | ref | 1.17(0.80,1.73) | 0.89(0.59,1.35) | 0.85(0.56,1.29) | 0.29 | |
| Physical activity(%) | 0.98 | |||||
| No | ref | 0.81(0.53,1.26) | 0.77(0.49,1.22) | 0.66(0.43,1.01) | 0.07 | |
| Yes | ref | 0.75(0.54,1.04) | 0.81(0.61,1.08) | 0.67(0.51,0.88) | 0.01 | |
| Depression | 0.42 | |||||
| No | ref | 0.85(0.64,1.13) | 0.80(0.60,1.07) | 0.71(0.56,0.90) | 0.01 | |
| Yes | ref | 0.42(0.18,1.00) | 0.85(0.41,1.73) | 0.68(0.35,1.30) | 0.32 |
Discussion
To our knowledge, our study first investigated the association between the intake of flavonoids and constipation among US adults based on NHANES 2007–2010. The results demonstrated that dietary flavonoids intake was associated with constipation. After controlling for potential confounding factors, only individuals with the highest intake of anthocyanidins had a significantly lower risk of constipation compared to those with lower intake. A potential nonlinear relationship was observed between anthocyanidins and constipation risk in further RCS analysis. Furthermore, the protective impact of anthocyanidins on constipation was pronounced among female, non-hispanic white, other hispanic, more than high school educational status, and individuals with physical activity, without depression, diabetes mellitus, and hypertension. There was an interaction between depression subgroup and flavanones intake against constipation. These results reveal that increasing certain flavonoid, especially anthocyanidins through dietary modification may be a potential prevention and treatment approach for constipation.
The main sources of dietary flavonoids include fruits, vegetables, grain, and tea. However, each flavonoid subclass has distinct sources. Isoflavones predominantly originate from soy-based products; anthocyanidins originate from berries, vegetables, and cereals, like bananas; flavan-3-ols originate from tea, flavanones originate from citrus fruit; flavones originate from tea and sweet peppers; flavonols originate from tea, beer, and onions [10]. Obviously, the predominant flavonoid subclasses present in fruits and vegetables encompass anthocyanins, flavanones, flavones, flavonols. Prior research have elucidated the impact of fruit and vegetables intake on the occurrence of constipation. According to the most recent Healthy Eating Index (2015) published by the Dietary Guidelines for Americans team determined that higher fruit and vegetables intake was related to lower constipation risk [16]. Stricter adherence to a Mediterranean diet rich in fruit and vegetable is significantly associated with lower rates of constipation [17]. In our study, after adjustment for age, sex, and ethnicity, an increased intake of anthocyanins, flavanones, flavones, and flavonols, primarily sourced from fruits and vegetables, exhibited beneficial effects in improving constipation, aligning with prior investigations. This relationship between fruit and vegetable intake and constipation may be related to other nutrients they contain, such as fiber, and water, as well as trace elements like magnesium and selenium [18–20]. However, in the fully adjusted model, the highest intake of anthocyanins remained associated with constipation. Therefore, we believe that flavonoids, especially anthocyanins, play an indispensable role in the relationship between vegetables and fruits and constipation.
Indeed, the impact of flavonoids on gastrointestinal function have garnered significant attention in academic research. After ingestion, approximately 90% of flavonoids are transported to the colon as non-absorbed or non-metabolized form without absorption in the small intestine [21]. They affect the composition, growth and activity of gut microbiota. The dietary flavonoids could be metabolized by gut microbe enzyme in the colon via glycoside elimination to produce flavonoid aglycones, which were further catabolized into active low-weight molecules [22]. It is noteworthy that these catabolites lower molecular weight produces may in turn the regulate gut microbiota composition. Hence, the effects of flavonoids intake on gastrointestinal function partly depend on the interaction between flavonoids and the gut microbiota [23]. A greater proportion of Lactobacillus was observed in the group of Lewis rats that were orally administered hesperidin, the major of flavanones [24]. Apigenin, a member of the flavones class, has the potential to alter the composition of the intestinal flora [25]. Many studies have demonstrated that the consumption of anthocyanins causes an increase in probiotics, like Lactobacilli and Bifidobacteria [26, 27]. The generation of short-chain fatty acids (SCFA) through the process of anthocyanin catabolism represents a mechanism fosters a favorable microbial habitat, thereby promoting the proliferation of beneficial bacteria [28, 29]. In fact, the observed positive effects resulting from following intake of all flavonoids including anthocyanins may in part be attributed to the modulation of gut microbiota [30]. Mounting lines of research suggested that the increase of the gut microbiota abundance and diversity promoted the mitigation of intestinal inflammation [31]. Bifidobacterium could alleviate colitis through regulating Treg cell homeostasis [32]. Lactobacillus exhibits a beneficial effect on colitis via increasing the population of CD4+,CD25+,Foxp3 + Treg cell [33]. B. adolescentis could regulate Treg/Th2 response to ameliorates chronic colitis [34]. Meanwhile, the gut microbiota can augment the anti-inflammatory and antioxidant efficacy of flavonoids through degrading and metabolizing flavonoids, thereby safeguarding intestine health [12]. Quercetin, secondary metabolite of quercitrin (a member of flavonol class), exhibits enhanced anti-inflammatory activity by inhibiting the NF-κB pathway, surpassing the effectiveness of quercitrin [35]. Lactic acid bacteria could metabolize isoflavone into equol, the more active molecule with greater potent antioxidant effects [36]. Clostridium butyricum could metabolize eriodictyol, which belongs to flavanones category, to produce more active forms with antioxidant properties [37]. The microbial metabolites, SCFA, enhances colonic homeostasis and health via the regulation of colonic Treg cell homeostasis [38].
The strong correlation between dietary flavonoids and gut microbiota, as well as their impact on intestinal inflammation, provides evidence supporting their potential benefits in alleviating constipation. We found a significant association between isoflavones, anthocyanins, flavanones, flavones, flavonols, total flavonoids intake, and constipation in both models 1 and 2, except for flavan-3-ols. However, prior researches have revealed that flavan-3-ols are metabolized in colonic and the metabolites are beneficial for intestinal health [39, 40]. These evidences provide support for the association flavan-3-ols intake and constipation. After further adjustment for BMI, total fiber, water, energy, and other covariates, the relationship between flavonoids and subclasses intake and constipation showed no statistically significant differences. However, the highest quartiles of anthocyanidins intake were related to constipation, compared with those in the reference quartiles. The relationship between anthocyanins and constipation appears to be more stable than other subclasses. Mounting evidence indicates the potential benefits of anthocyanins for intestinal disorders [41]. Anthocyanins can regulate intestinal dysfunction and inflammation through protecting the intestinal epithelial barrier, modulating the immune system, acting as antioxidants, and influencing gut microbiota metabolism [26, 42–45]. The RCS analysis further indicated a negative association between anthocyanidins intake and constipation when intake > 0.92 mg. A gradual upward trend was observed when anthocyanidins intake < = 0.92 mg. Therefore, it is necessary to consume sufficient anthocyanins to effectively protect the intestines. In subgroup analysis, we observed a negative association between anthocyanin intake and constipation in the female population, but no statistically significant difference in the male population. Indeed, female had a significantly higher anthocyanidins (berries) intake compared with male in the US population [46]. Furthermore, the prevalence of constipation was higher in female compared to male [47]. Therefore, the intake of anthocyanins has a more significant improvement effect on constipation in women.
This study possesses several noteworthy strengths. By utilizing NHANES datasets, which encompass a large-scale sample population that is nationally representative, the reliability of these findings is significantly enhanced. This study represents the inaugural report that specifically investigates the impact of flavonoids intake on constipation. Our study still have some limitations. For one, the reliance on 24-hour recall interviews to obtain dietary data introduces the possibility of recall bias. Secondly, the long-term dietary patterns, seasonal, and intermittent intake data of participants were not included in the database. Third, the patients in this study classified as constipated did not meet the Rome IV diagnostic criteria for functional constipation, potentially biasing the analysis results. In addition, despite attempts to control for covariates, this study did not account for other potential confounding variables that could have impacted the outcomes of the analyses. Lastly, the cross-sectional nature of the data prevents the assessment of causal relationships.
Conclusion
Our study demonstrated that higher dietary flavonoids intake can reduce the incidence of constipation in the adult US population. In addition, the negative association between anthocyanin intake and constipation was more stable compared to other subclasses. Together, the findings of our study provide valuable insights on the formulation of dietary management strategies for improving symptoms of constipation.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
We would like to thank the NHANES team for providing the data.
Author contributions
All authors contributed to the study conception and design. YJS, CYJ—data collection and analysis; YJS, JYL, and CYJ—wrote and revised the manuscript. All authors contributed to the article and approved the submitted version.
Funding
This research received no external funding.
Data availability
Publicly available datasets were analyzed in this study. This data can be found here: https://www.cdc.gov/nchs/nhanes.
Declarations
Ethics approval and consent to participate
The studies involving human participants were reviewed and approved by The National Center for Health Statistics Research Ethics Review Board. All methods were carried out in accordance with relevant guidelines and regulations (Declaration of Helsinki).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Chenyu Jiang and Jingyao Luo contributed equally to this work.
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Associated Data
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Supplementary Materials
Data Availability Statement
Publicly available datasets were analyzed in this study. This data can be found here: https://www.cdc.gov/nchs/nhanes.