Benign prostatic hyperplasia (BPH), a disease characterized by uncontrolled overgrowth of epithelial and smooth muscle cells located in the transition zone of the urethra, is one of the most common diagnoses made by urologists (1). BPH mainly manifests as lower urinary tract symptoms (LUTS), and its incidence has been on the rise in recent years. Epidemiological surveys have reported that this disease affects over 15 million men, particularly those over the age of 50, and is a considerable economic burden on society (2). However, the specific mechanism of BPH is unclear, as multifactorial disease, age, androgen and estrogen interactions, obesity, diabetes, hypertension, hypogonadism, unhealthy lifestyle factors such as smoking, and alcohol consumption may be potential risk factors for the development of BPH (3). Among these factors, dietary factors were found to be associated with BPH (4–9).

Currently, coffee is one of the most frequently consumed drinks worldwide, with caffeine being its primary pharmacologically active compound (10). A survey by the National Coffee Association indicated that nearly 64% of American adults consume coffee daily, amounting to approximately 517 million cups each day (11). This widespread consumption has heightened concerns about caffeine’s potential effects on human health. Epidemiological studies have shown that habitual consumption of coffee can prevent and reduce the incidence and prevalence of type 2 diabetes (12), liver disease (13, 14), depression (15), cardiovascular disease (CVD) (16), and cancer (17, 18). However, drinking coffee can also have negative consequences, such as sleep disturbances, anxiety, and adverse pregnancy outcomes (19). The findings from various epidemiological studies on the connection between coffee intake and BPH remain inconclusive. Two earlier case–control studies of men with BPH who underwent surgery showed no significant relationship between coffee intake and BPH (20, 21). A comprehensive, cross-sectional population-based study revealed that increased coffee intake was positively correlated with BPH (22). However, these studies were limited to coffee intake rather than caffeine intake. A previous experimental study suggested that caffeine is associated with BPH and that caffeine may stimulate cell proliferation by increasing androgen signaling in ventral prostate epithelial cells (4). However, it is unclear whether caffeine intake is linked to the development of BPH in the population.

Given this gap in the literature, we conducted a cohort study with data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES) to explore the link between caffeine intake and BPH.

This study, which revealed a positive correlation between caffeine intake and BPH, is the first to focus on the relationship between caffeine intake and BPH. From the NHANES database, we used a comprehensive, nationally representative sample of 2,374 participants, and after adjusting for a range of potential confounders, we found that participants with higher caffeine intake was associated with an increased risk of developing BPH.

Caffeine is very common in the global diet (35), and numerous studies have shown that caffeine is associated with a reduced risk of depression, Parkinson’s disease, liver disease, and cardiovascular mortality, among others (13–16). However, the relationship between caffeine intake and BPH remains controversial (22, 36–38). In our study, we found that caffeine intake was positively associated with BPH. Interestingly, subgroup analysis revealed a significant association between caffeine intake and BPH in subgroups with lower education levels, a PIR between 1.3 and 3.5, former smokers, married/living with partner individuals, individuals with uric acid levels between 5.5 and 6.6 mg/dL, those with hypertension, and those without CVD. For instance, in the T3 caffeine intake group, participants with lower education levels, hypertension, and no CVD had a higher prevalence of BPH. This may be puzzling. Here, we provide a plausible explanation: individuals with lower education levels may not pay attention to healthy lifestyles and habits, and choose more high-caffeine drinks, such as sugary drinks and energy drinks; hypertensive patients’ blood vessels already endure greater pressure, and long-term caffeine intake may lead to sustained vasoconstriction, potentially affecting blood supply to the prostate and resulting in abnormal prostate tissue growth; for participants with CVD, the lack of a significant association could be due to the fact that they were taking relevant therapeutic drugs, which led to a bias in the results.

In vitro and animal studies, caffeine has been shown to have biological effects that may affect prostate epithelial cell proliferation. Wu et al. (39) found that caffeine can induce Ca2+ transients in primary prostate stromal cells, which may be associated with the regulation of prostate stromal cell proliferation. Other experimental animal studies have indicated that caffeine raises plasma testosterone levels by stimulating testicular interstitial cells sympathetically, but it also leads to testicular atrophy and impaired spermatogenesis. Moreover, caffeine may promote androgen-dependent prostate hyperplasia by interfering with androgen circulation (40, 41). Sarobo et al. (4) reported that caffeine intake increased plasma testosterone and dihydrotestosterone levels in Wistar rats and promoted the proliferation of epithelial cells and enhanced androgen receptor expression in the ventral prostatic lobe. Additionally, it has been proposed that caffeine may contribute to BPH through the stimulation of the sympathetic nervous system (42). Consistent with this hypothesis, Huang et al. (43) reported that chronic stress-induced sympathetic overactivity led to hyperplasia in the ventral lobe of Wistar rats, with the dorsolateral lobe mostly unaffected, and no hyperplasia was observed after chemical sympathectomy during stress. Another study on Sprague–Dawley rats revealed that unilateral sympathectomy reduced the ventral prostate weight and DNA and protein content on the lesioned side, while unilateral parasympathectomy increased these parameters on the intact side (44). Based on the above findings, we speculate that caffeine may promote BPH by stimulating the sympathetic nervous system and modulating androgen signaling pathways.

The etiology of BPH is complex and diverse, involving multiple factors such as genetics, hormones, inflammation and lifestyle. It has been suggested that caffeine may contribute to the development and progression of BPH through interactions with these factors. Caffeine metabolism is significantly influenced by genetic factors, particularly in association with CYP1A2 gene polymorphisms (45). These genetic differences may lead to individual differences in the rate of caffeine metabolism and thus influence the physiological status of the prostate gland. Androgens play a critical role in the pathogenesis of BPH, previous studies have found that caffeine can increase plasma testosterone levels by stimulating sympathetic activity in Leydig cells (40, 41), which may promote androgen-dependent BPH. In addition, inflammation is considered to be one of the important pathological mechanisms of BPH (46). Caffeine has been shown to modulate the balance of proinflammatory and anti-inflammatory factors in vivo, such as the concentrations of interleukin 6 and interleukin 10 (47), which may alter the inflammatory microenvironment of the prostate and thus further participate in the development of BPH. Additionally, caffeine impacts lifestyle-related metabolic diseases, such as obesity and diabetes, which are important risk factors for BPH by regulating metabolic activity or fluid balance (48–50). Previous studies have suggested that sleep disorders are risk factors for BPH (51, 52), and given caffeine’s well-documented effects on sleep quality, its role in BPH may be partly mediated through these sleep disturbances.

Caffeine, as a bioactive compound, has a variety of pharmacological effects, which can promote sympathetic activation leading to smooth muscle contraction, which in turn promotes BPH, and sympathetic activation can also modulate testosterone levels and prostatic blood supply (4, 42), and these factors play an important role in the pathogenesis of BPH (53). In addition, caffeine may exacerbate BPH by altering local inflammatory status and oxidative stress levels in the prostate. These properties may make the effect of caffeine on BPH different from other dietary factors. In contrast, it has been shown that the association of high-calorie diets and red meat intake with BPH is mainly indirectly influenced through systemic metabolic pathways, for example, promoting the development of obesity and metabolic syndrome (6). On the other hand, vegetable may offer protective effects against BPH due to its anti-inflammatory and antioxidant properties (54).

Our study found that caffeine is more directly associated with BPH, particularly in the high caffeine intake group (T3), where the risk increased significantly (OR = 1.52, 95% CI: 1.01–2.27). In contrast, the increased risk in the medium intake group (T2) did not reach statistical significance. This suggests that caffeine may have a dose-dependent effect, with a more significant promoting effect on BPH once a certain threshold is exceeded. Future research should further clarify the safe threshold for caffeine intake and its dose–response relationship. Our subgroup analysis revealed that the association between high caffeine intake and increased BPH risk was more pronounced in specific subgroups, such as individuals with hypertension (OR = 2.05, 95% CI: 1.34–3.13). Therefore, we recommend that future BPH management guidelines explore the potential effects of caffeine intake on high-risk subgroups (e.g., those with hypertension) and assess dietary interventions based on broader research evidence. Furthermore, metabolic syndrome is well-established as an important risk factor for BPH (55, 56). Caffeine may indirectly influence the development of BPH by modulating components of metabolic syndrome. For example, caffeine may alter blood glucose levels, insulin sensitivity, and lipid metabolism (57, 58), and these metabolic changes could exacerbate obesity and chronic inflammation, thereby increasing the risk of BPH. In our study, we adjusted for key components of metabolic syndrome (such as BMI, hypertension, and diabetes), but future studies should further explore the potential mediating role of caffeine in the relationship between metabolic syndrome and BPH.

We explored the relationship between caffeine intake and BPH with a relatively large sample size extracted from the NHANES, a comprehensive, nationally representative database, which supports the generalizability of our findings among adults in the United States. In addition, we performed subgroup analyses to identify the relationship between caffeine intake and BPH across different populations. This study also has several limitations. First, as a cross-sectional study, a causal relationship between caffeine intake and BPH could not be established. To better understand the relationship between caffeine intake and BPH, future studies should include prospective designs and randomized controlled trials. Second, although we adjusted for potential confounders affecting BPH, some confounding factors may remain unconsidered, such as sleep quality and sleep duration. Third, dietary intake data were collected via 24-h dietary recalls, which may not adequately reflect long-term dietary habits. However, some studies suggest that two 24-h recalls can sufficiently assess daily dietary intake (59). Fourth, the sources of caffeine are diversified, and this study did not analyze the effects of different caffeine sources on BPH. In future research, we plan to explore the impact of various caffeine sources on BPH using more detailed data, addressing this limitation of the current study. Fifth, in this study, BPH diagnosis was based solely on questionnaire data, without objective clinical measures (such as imaging tests or laboratory markers), which may be some classification error, in future studies we will add objective clinical data on BPH to further clarify the relationship between caffeine intake and BPH.

Our study is the first national cross-sectional survey to explore the association between caffeine intake and BPH, and the current study provides preliminary evidence that there may be a positive association between caffeine intake and BPH. We aspire for this study to offer insights for future research into the biological mechanisms underlying the effects of caffeine on BPH.