Chronic constipation is a significant global public health issue that severely impacts patients' quality of life and overall health. Dietary adjustments are fundamental in the prevention and treatment of chronic constipation. Exploring the association between antioxidant-rich diets and constipation may address this widespread health problem. The Comprehensive Dietary Antioxidant Index (CDAI) is a novel index that quantifies and evaluates the overall antioxidant capacity of a diet by measuring the intake of multiple antioxidants. Previous studies have found that higher CDAI scores are associated with reduced incidences of stroke, kidney stones, and depression(12, 13).
In this NHANES cross-sectional study, we included 10,904 participants, with an overall constipation prevalence of approximately 10.86%. Among these participants, 27.70% were male and 72.30% were female, consistent with previous findings that constipation prevalence is significantly higher in women(14).The results indicated a negative correlation between CDAI and constipation after adjusting for all confounders (OR = 0.958 [0.929, 0.987]). The reduction in constipation prevalence was particularly significant in the highest CDAI quartile compared to the lowest quartile (OR = 0.704 [0.535, 0.927], ptrend < 0.05). This negative correlation was more pronounced in younger males, possibly due to more efficient nutrient absorption and utilization in younger individuals. As individuals age, the gastrointestinal neuromuscular system gradually deteriorates, leading to weakened peristaltic function in the elderly. Consequently, even with the support of a high CDAI diet, the protective effect against constipation is less pronounced in older adults compared to younger individuals(15, 16).Similar patterns were observed in subgroups of individuals who consumed alcohol and those who smoked. Smoking and alcohol consumption can damage the intestinal mucosa, impairing absorption and motility functions. Antioxidants can protect the intestinal mucosa, promote cellular repair, and maintain normal intestinal function(17). Smoking and drinking increase oxidative stress in the body, producing a large number of free radicals that damage cells and tissues. The antioxidants in a high CDAI diet can neutralize these free radicals, mitigating the negative effects of oxidative stress(18). Therefore, the negative correlation between CDAI and constipation is more pronounced among smokers and drinkers.Additionally, in the non-drinking group, there is a complex nonlinear relationship between the CDAI and constipation. When the CDAI exceeds 1.08, there is a significant negative correlation between CDAI levels and the incidence of constipation. Conversely, when the CDAI is below 1.08, the relationship between CDAI levels and constipation incidence is positive. This might be because alcohol can enhance the bioavailability of antioxidants, allowing them to act more quickly(19). In the non-drinking group, low levels of CDAI have a lesser impact on the gut, leading to an unstable effect. As the CDAI increases, the protective effects of antioxidants gradually become evident. To further understand the relationship between CDAI and constipation in non-drinking populations, more large-scale prospective studies are needed.
Dietary antioxidants, including vitamins, carotenoids, and minerals such as zinc and selenium, play a crucial role in maintaining human health and preventing diseases. They neutralize free radicals and protect cells from oxidative damage, thereby reducing the risk of diseases related to oxidative stress(20).Numerous studies have shown that dietary antioxidants are associated with a reduced incidence of cardiovascular, urinary, endocrine diseases, and certain types of cancer(21). Additionally, antioxidants help enhance immune function, improve skin health, slow down the aging process, and prevent neurodegenerative diseases(22).
Vitamins, carotenoids, and selenium act as cofactors for antioxidant enzymes, working together with superoxide dismutase and glutathione peroxidase to eliminate free radicals and prevent them from transforming into intracellular molecules, thereby reducing oxidative stress(23). Vitamin A is crucial for maintaining normal vision, immune function, and skin health, but few studies have examined its relationship with constipation. Our study shows a negative correlation between high levels of vitamin A and constipation, possibly because vitamin A helps maintain the integrity of the intestinal mechanical barrier and promotes healthy and functional intestinal epithelial cells, enhancing motility and normal defecation. The intestinal mechanical barrier, composed of tight junction proteins such as ZO-1, occludin, and claudin, regulates intestinal permeability. Vitamin A can induce these tight junction proteins, protecting the barrier function. Additionally, vitamin A deficiency exacerbates intestinal dysbiosis, while supplementation promotes a healthy gut microbiome and alleviates intestinal disease symptoms(24, 25).
Carotenoids are natural antioxidants, including lycopene, α-carotene, β-carotene, and lutein, found in various fruits and vegetables. Lycopene activates antioxidant response elements (ARE), promoting the synthesis of cellular enzymes to eliminate reactive oxygen species. It also regulates inflammatory mediator signaling pathways and activates antioxidant gene expression to exert anti-inflammatory effects(26). A study based on NHANES data found that higher dietary lycopene intake significantly reduced the risk of chronic constipation in men, while increased dietary α-carotene intake reduced the risk in women. These differences may be related to hormonal and metabolic differences between genders(27). Notably, lycopene's antioxidant effect is dose-dependent; it acts as a potent antioxidant at low doses but becomes a pro-oxidant at high doses, potentially increasing oxidative stress. Therefore, it is crucial to control lycopene supplement doses to avoid adverse effects(28). Ahn et al.(29) found that lutein and zeaxanthin reduce pro-inflammatory cytokines like IL-1β, IL-6, and IFN-γ and increase anti-inflammatory cytokines like IL-10, thereby inhibiting intestinal inflammation, alleviating constipation symptoms, and improving overall gut health. Zinc and selenium are essential trace elements for intestinal health and immune function, but there are few studies on their relationship with constipation. Our study did not observe significant associations between individual zinc or selenium intake and constipation. Previous research suggests interactions between antioxidants, where lycopene combined with resveratrol and vitamin E significantly enhances its stability(30). Vitamin C can regenerate the chromanoxyl radical of vitamin E, restoring its antioxidant activity(31). Zinc and vitamin A synergistically maintain intestinal epithelial tissue stability, and animal studies indicate that vitamin E and selenium together can upregulate serum vitamin A levels(32, 33). These synergistic effects among antioxidants significantly enhance the body's resistance to oxidative stress, aligning with our findings that CDAI, rather than individual antioxidants, is more significantly associated with reduced constipation risk.
Our study highlights the potential positive role of dietary antioxidants in reducing constipation risk. However, solely relying on antioxidant intake to improve constipation is not advisable. A diet rich in high-fiber foods and reduced intake of high-sugar, high-fat processed foods can improve various intestinal issues, including constipation(34). Beyond dietary factors, physical activity, lifestyle habits, and psychological factors also significantly influence constipation, and managing these aspects can help improve intestinal health(35). Overall health management is crucial for preventing and alleviating constipation.
Our study has several strengths. We utilized all available continuous NHANES data, providing a large, nationally representative sample, enhancing the reliability and generalizability of our results. The CDAI comprehensively considers multiple antioxidants, effectively reflecting overall dietary antioxidant intake and improving result accuracy. This study is the first to identify a significant association between CDAI and reduced constipation incidence, offering new insights into the potential role of dietary antioxidants in the pathophysiology of constipation and emphasizing the importance of dietary factors in gut health management.
However, our study also has limitations. As a cross-sectional study, it can only demonstrate an association between CDAI and reduced constipation incidence; further prospective studies or intervention trials are needed to establish causality. The data are based on self-reported information, which may be subject to recall or reporting biases. Dietary nutrient intake was averaged from two 24-hour dietary recalls, which may not accurately reflect long-term dietary habits. Finally, the results are primarily applicable to the U.S. population, and dietary habits, environmental factors, and socioeconomic conditions in different countries or regions may affect constipation prevalence, limiting the generalizability of our findings.