Association of niacin intake with constipation in adult: result from the National Health and Nutrition Examination

Constipation is a common chronic gastrointestinal disease characterized by symptoms such as difficulty in defecation, reduced frequency of defecation, and incomplete evacuation after defecation, which can significantly affect patients' quality of life and psychological health [1]. Due to the complex etiology of constipation, the American Gastroenterological Association has classified constipation patients into three categories: normal transit constipation, slow transit constipation, and pelvic floor dysfunction or defecatory disorders, in order to better guide treatment [2]. Various risk factors related to constipation have been extensively studied, including selenium intake [3], energy intake [4], and liquid intake [5]. However, Werth [6] found that the existing evidences on most constipation risk factors are contradictory or insufficient, thus large-scale studies including a wide range of factors in a community environment are necessary to further understand the risk factors of constipation.

Niacin is an organic water-soluble compound primarily metabolized in the liver, with its main metabolites being uric acid and nicotinamide. Niacin may play a role in various diseases. By affecting immune cells and vascular endothelial cells through its receptor, niacin exerts its anti-atherosclerotic effects [7]. Even in patients with metabolic syndrome, the cardiovascular benefits of combined therapy with niacin and simvastatin outweigh the adverse effects on blood glucose [8]. Retrospective studies have also indicated a negative correlation between niacin intake and the incidence of pancreatic cancer [9]. Moreover, niacin and its derivatives have been found to play important roles in regulating inflammatory responses and maintaining intestinal health [10, 11]. However, there is currently no study evaluating the effect of niacin intake on constipation.

Therefore, this study aims to investigate the relationship between niacin intake and constipation by utilizing the National Health and Nutrition Examination Survey (NHANES) database, while adjusting for confounding factors such as age, gender, and others dietary intake.

This research examined the correlation between daily niacin intake and the incidence of constipation in adults. Constipation was defined in this study based on patients’ recollections of episodes experienced within the past year. The findings indicated a negative correlation between niacin intake and the incidence of constipation. An intake of 0–18 mg/day of niacin was identified as a risk factor for constipation, whereas intakes of 27–39 mg/day and > 39 mg/day did not significantly decrease the risk of constipation, as compared to an intake of 18–27 mg/day. It should be noted that adverse effects, such as vasodilation, may occur when niacin intake exceeds 50 mg/day [13]. Therefore, it is advisable to recommend the appropriate supplementation of niacin for constipation patients in clinical settings.

Given that the NHANES bowel questionnaire BHQ060 was built upon the well-established Bristol stool form scale [14], previous studies often relied upon this criterion for defining constipation [3, 4, 12]. However, individuals' perception of bowel movements and the actual form of feces might not align perfectly. Moreover, there was an increasing emphasis on patients' self-perceived symptoms. Thus, this study defined constipation based on self-reported symptoms. Prior research had demonstrated that the incidence of constipation varies depending on the definition used. When compared to other diagnostic criteria, self-reported symptoms lead to a higher incidence rate [15]. In this study, the incidence of constipation was found to be 22%, notably surpassing the rates obtained using the Rome I/II/III diagnostic criteria (10.1–15.3%). Additionally, the distribution of incidence between different genders appeared similar [16].

In previous studies of pellagra, researchers found that patients with niacin deficiency exhibited gastrointestinal symptoms, but the underlying mechanism remains unclear [17]. Singh et al. [18] discovered that niacin bound to GPR109A to promote the production of interleukin-10 (IL-10) in mouse macrophages and dendritic cells, further inducing T cell differentiation. Meanwhile, the expression of IL-18 was also regulated by GPR109A. Therefore, in mice with niacin deficiency, the repair function of intestinal mucosal barrier was impaired, making them more susceptible to intestinal inflammation. Maintaining the stability of the intestinal microecology was also considered an important way in which GPR109A promoted intestinal mucosal barrier repair [19], and research had shown that the use of antibiotics to induce gut microbiota depletion inhibited the expression of IL-23 and ILC3 in GPR109A knockout mice, reducing intestinal inflammation [20]. Coenzymes NAD + and NADP + , metabolites of niacin, played an important role in metabolism and energy release. Research found that raising the level of NAD + enhanced oxidative metabolism, providing protection against high-fat diet-induced metabolic abnormalities [21]. Similarly, Gomes et al. [22] found that increasing NAD + levels in elderly mice can restore mitochondrial function to the level of young mice. SIRT1 was a NAD + -dependent histone deacetylase that promoted the phosphorylation of S6K1, thereby increasing the number of intestinal stem cells [23]. Additionally, SIRT1 could prevent intestinal inflammation by regulating the gut microbiota [11]. Given the close relationship between niacin and intestinal function, it was necessary to evaluate the association between niacin intake and constipation. In addition, the research indicated that female participants had a higher risk of constipation, which was consistent with previous research results [4, 12]. However, further exploration is needed to elucidate the mechanism underlying gender differences in the risk of constipation. In further analysis, there was no interaction between niacin intake and gender.

This study has several limitations. Firstly, the NHANES database contains cross-sectional data, so this study cannot establish a causal relationship between constipation and niacin intake. Secondly, the use of recalled data may introduce potential recall bias. Thirdly, the NHANES database did not provide more detailed data, and there may be other potential confounding factors related to constipation that were not included in the study. Finally, the estimation of dietary intake elements through questionnaire-based calculations represents a coarse assessment. Furthermore, a subset of patients lacking follow-up information was excluded from the analysis, both of which inevitably contribute to confounding factors. On the other hand, this study has several strengths: (1) it includes a large nationally representative sample, which makes the results more convincing; (2) unlike other studies on constipation that used the NHANES database [3, 4, 12], this research used a definition of constipation derived from participants' self-reported symptoms, thereby placing a heightened emphasis on individuals who manifest constipation-related complaints despite yielding negative results on the Bristol Stool Scale assessment. (3) To the best of our knowledge, there is currently a lack of research on the relationship between daily niacin intake and constipation, so this study fills this gap.

In summary, our study suggests a potential association between low niacin intake and increased risk of constipation. Furthermore, we found no significant association between niacin intake in the range of 27–39 mg/day and > 39 mg/day and higher risk of constipation compared to the reference group (18–27 mg/day). Thus, optimal niacin intake should be considered for a healthy lifestyle. Further research is needed to confirm the potential benefits of appropriate niacin intake in improving constipation and to elucidate the underlying mechanisms.