Chronic obstructive pulmonary disease (COPD) is a severe chronic respiratory illness characterized by irreversible and persistent airflow limitation in the airways, thus posing a significant global health challenge (1, 2). With a high disability rate and ranking as the third leading cause of death globally, COPD imposes a considerable burden on clinical healthcare systems and public health (3, 4). COPD not only increases overall mortality but is also closely linked to the risk of cardiovascular disease (CVD) death (5). Pathophysiological changes in COPD patients, including systemic inflammation, vascular dysfunction, and hypoxia, accelerate atherosclerosis, thereby increasing the risk of cardiovascular events like myocardial infarction and stroke, and ultimately leading to higher CVD-related mortality (6). COPD has multiple risk factors, including smoking, genetic predisposition, environmental conditions, and dietary habits (2, 7). It is noteworthy that COPD is strongly associated with chronic inflammation, which may deteriorate during acute exacerbations, thereby posing a substantial threat to patients’ health (8). Hence, identifying effective methods to counteract abnormal inflammatory mechanisms in the lungs is pivotal for the prevention and early treatment of COPD.

In recent years, scholars have increasingly devoted attention to examining the correlation between dietary habits and COPD (9, 10). Specifically, the consumption of specific vitamins is believed to positively impact the maintenance of respiratory function and the alleviation of COPD symptoms. Owing to their antioxidant properties, these vitamins have the potential to facilitate cell repair and reduce inflammation, thereby potentially playing a pivotal role in both the prevention and management of COPD.

Niacin, alternatively referred to as vitamin B3, serves as a crucial nutrient participating in diverse physiological processes, such as energy metabolism, DNA repair, and cell signaling (11). Insufficient dietary intake of niacin may negatively impact oxidative phosphorylation, subsequently compromising mitochondrial respiratory function (12). However, controversy exists concerning niacin’s effects on human health. On one hand, studies indicated that niacin significantly decreases coronary events and overall mortality (13, 14). Conversely, certain research suggested that niacin may not be effective in preventing cardiovascular diseases and could potentially increase all-cause mortality (15–17). Furthermore, high dietary niacin intake has been positively associated with diabetes in US adults (18). Nevertheless, another study found that increasing dietary niacin intake improves glucose homeostasis in adults over 40 years old (19). Dietary niacin intake has also been linked to reduce all-cause and cardiac-related mortality in patients with chronic kidney disease (CKD) (20). Moreover, have revealed a notable correlation between niacin intake and forced expiratory volume in 1 s (FEV1) (21). This finding indicates a possible role of niacin in improving lung function. Another study has uncovered an inverse relationship between dietary niacin intake and the incidence of COPD among adults in the United State (22). A comparable correlation has been noted in the Korean populace as well (23). Nevertheless, the precise connection between dietary niacin intake and mortality in individuals with COPD remains obscure.

We hypothesize that there is a potential association between dietary niacin intake and COPD mortality. To test this hypothesis, we conducted a cohort study. The aim of this study is to explore the potential relationship between dietary niacin intake and mortality in COPD patients, providing scientific evidence to support nutritional interventions and treatments for COPD patients.

To the best of current knowledge, this is the first prospective study exploring the relationship between dietary niacin intake and all-cause and CVD mortality among individuals with COPD. The study reveals that higher dietary niacin intake is associated with a reduced risk of all-cause and CVD mortality. This association is independent of traditional risk factors, including dietary and lifestyle factors, as well as comorbidities. Various stratified analyses and sensitivity analyses demonstrate the robustness of the results.

Niacin possesses various crucial biological functions, among which its antioxidant properties are particularly significant for human health (32). However, the association between niacin and mortality risk has been inconsistent across different populations. Previous studies have found that niacin can significantly reduce coronary events and overall mortality (13, 14, 33). Nevertheless, some research has also suggested that niacin therapy offers limited benefits in preventing cardiovascular events (15, 16), and sole supplementation with niacin may increase all-cause mortality (17, 34). In a prospective cohort of 660 stable renal transplant recipients, a lower niacin status was associated with a higher risk of all-cause premature death (35). An American study involving 3,504 cancer patients indicated a negative correlation between niacin intake and mortality outcomes among cancer patients (36). This correlation persisted across various subgroups, including sex, age, and BMI. Another cohort study, encompassing 4,315 participants with nonalcoholic fatty liver disease (NAFLD), revealed that higher dietary niacin intake might be associated with a lower risk of all-cause mortality in NAFLD patients, although no significant negative correlation was observed with CVD mortality (37).

In the field of COPD research, the role of niacin has garnered attention. A nutritional epidemiological study involving 2,337 American smokers found a significant association between niacin and FEV1, suggesting that niacin may contribute to improving lung function (21). Another study, encompassing 7,055 American adults, revealed a negative correlation between dietary niacin intake and the incidence of chronic obstructive pulmonary disease (22). Similar conclusions were drawn by Shi, Yushan et al. in a study of 7,170 middle-aged and elderly individuals (38). A cross-sectional study conducted in Korea, involving 22,948 participants, discovered a significant association between niacin intake and reduced COPD severity among elderly men (aged ≥ 60) (23). Furthermore, a study of 7,615 Korean women indicated a negative correlation between lower niacin content in refined diets and predicted forced vital capacity levels (FVC) and FEV1 (39). These findings suggest that niacin may have some positive impact on lung function.

Patients with COPD not only suffer from declined lung function but also frequently suffer from systemic inflammation and vascular dysfunction (5), which accelerate atherosclerosis and increase the risk of cardiovascular events such as myocardial infarction and stroke (6). Smoking habits and low oxygen levels in COPD patients impose an additional burden on the heart, potentially promoting heart failure (40). Studies indicate that some COPD patients exhibit altered cardiac repolarization, potentially increasing the risk of arrhythmias and sudden cardiac death (41). Additionally, acute exacerbations of COPD (AECOPD) are a major cause of hospitalization and mortality in these patients (42).

Through a large-scale, long-term follow-up multi-ethnic cohort study, we found a negative correlation between dietary niacin intake and all-cause and CVD mortality among COPD patients. This association may be attributed to the various biological activities of niacin. The lungs of COPD patients suffer from chronic inflammation and oxidative stress damage over the long term, which are significant factors contributing to decreased lung function and disease progression (43, 44). Niacin, as an effective antioxidant, plays a crucial role in maintaining mitochondrial function (32). A lack of niacin in the diet may affect the oxidative phosphorylation process, thereby disrupting mitochondrial respiration (11). Animal experiments have shown that high doses of niacin significantly reduce lung inflammation, decrease the production of proinflammatory cytokines, and alleviate lung tissue damage by regulating the NF-κB signaling pathway (45). Furthermore, niacin plays a crucial role in regulating the production and release of inflammatory mediators. Niacin may modulate the production and release of inflammatory mediators, reducing lung inflammation and improving respiratory function and overall health status (46). In COPD patients, systemic and pulmonary inflammation are significant contributors to disease progression and increased CVD risk. Through its anti-inflammatory effects, niacin may help alleviate pulmonary inflammatory responses and decrease systemic inflammation levels, thereby reducing the risk of CVD. Additionally, niacin regulates the function of vascular endothelial cells, promoting the synthesis and release of nitric oxide, which improves endothelial function and mitigates vascular aging (47). Vascular dysfunction is a key factor that accelerates the development of atherosclerosis in COPD patients (48). By enhancing vascular endothelial function, niacin may help reduce vascular damage and lower the risk of CVD. As nicotinamide adenine dinucleotide (NAD), niacin participates in various adenosine diphosphate (ADP)-ribosylation reactions, influencing immune system stability (49). Immune dysfunction is a major contributor to disease progression and increased CVD risk in COPD patients (50). Moreover, chronic inflammation and oxidative stress can lead to DNA damage in COPD patients (51). In this regard, NAD plays a key role in the DNA repair mechanism. Substantial evidence suggests that NAD is involved in the repair of DNA damage through the base excision repair pathway, which is crucial for maintaining genomic stability and normal cellular function (52). This reduces cellular apoptosis and necrosis, lowering the risk of CVD. However, further research is needed to confirm these findings and explore the potential mechanisms underlying niacin’s beneficial effects in COPD patients.

This long-term follow-up prospective cohort study offers significant advantages. Primarily, it is the first to evaluate the relationship between dietary niacin intake and both all-cause and CVD mortality in a sample of adult individuals with COPD in the United States. Furthermore, the meticulous adjustment for various potential confounding factors, such as diet, lifestyle, and comorbidities, ensures the reliability and validity of the findings. However, the study also has its limitations. Firstly, due to its observational nature, it cannot definitively establish a causal link between dietary niacin intake and mortality rates; it can only identify associations. Secondly, the use of 24-h dietary recall questionnaires as the primary assessment tool may not fully capture the dynamic fluctuations in niacin intake over time, thereby limiting the ability to assess time-varying associations. Additionally, the NHANES database lacked consistent and comprehensive information on breastfeeding status among female participants. Given that the recommended dietary allowance for niacin differs between breastfeeding and non-breastfeeding women, the failure to account for this could introduce bias into our results. Finally, and most importantly in the context of this study, the lack of detailed data on the severity of COPD is a substantial constraint. As the NHANES database did not provide FEV1 predicted% data, we were unable to stratify our analysis according to COPD severity stages as recommended by the GOLD guidelines. This lack of stratification restricts a deeper understanding of the potential differential effects of dietary niacin intake on mortality across different stages of COPD progression. It also limits our ability to draw more precise conclusions about the role of niacin in the context of varying disease severities. Future research is strongly encouraged to address these limitations. Specifically, studies should aim to collect more comprehensive and longitudinal dietary data to better capture the time-varying nature of niacin intake. Moreover, future investigations should prioritize the inclusion of detailed COPD severity data, such as FEV1 predicted%, to enable a more nuanced analysis of the relationship between dietary niacin intake and disease progression, as well as mortality. This will ultimately contribute to the formulation of more accurate and personalized nutritional guidelines for COPD patients.

We observed that a higher dietary intake of niacin was associated with lower all-cause and CVD mortality among individuals with COPD. These findings suggest that optimizing niacin intake may have beneficial effects on COPD outcomes and patient safety. However, since our analysis did not account for COPD severity, these results should be interpreted cautiously as preliminary assumptions. Further studies incorporating disease severity assessment are required to confirm and expand upon these findings.