Intake of Caffeinated, Carbonated, or Citrus Beverage Types and Development of Lower Urinary Tract Symptoms in Men and Women

Discussion

In this observational study, coffee and caffeine intake were associated with LUTS progression, greater symptom scores, and urgency in men. In women, increases in coffee consumption between baseline and follow-up were associated with progression of urgency symptoms, although baseline coffee intake itself was not. Women who drank more soda at follow-up, particularly caffeinated diet soda, or increased their soda intake over time, were more likely to report a variety of LUTS or progression of symptoms. Consumption of orange or grapefruit juice was associated with protection from LUTS progression in men.

A strength of this study was the use of various measures to examine longitudinal relationships with habitual beverage intake and changes in intake levels, as well as short-term relationships between recent beverage intakes and recent symptoms. LUTS can be a seemingly constant problem in some persons, but most studies, including BACH, show remission and progression in symptoms over time.^[2,16,17] Thus, analyses of LUTS as a chronic condition, using longitudinal data with long time spans between assessment measures, might miss acute associations that exist in a temporally brief causal pathway. Certain lifestyle behaviors (e.g., physical activity, smoking) and medical factors (e.g., depression) could contribute to LUTS over the long term.^[28,29] Other factors can lead to LUTS relatively quickly, through immediate effects on nervous system activity^[30] or as chemical irritants to the bladder. It is plausible that components of beverages have both direct effects on the bladder and systemic effects that contribute to LUTS. Thus, our multimode analyses provided different yet complementary information.

The finding that total fluid intake was associated with LUTS acutely, but not longitudinally, is evidence of the validity of our analysis of proximate associations. There is little reason to believe that long-term average fluid intake levels lead to pathophysiological changes causing LUTS. However, drinking large amounts of fluids acutely causes greater frequency, urgency, and voiding volumes,^[18,31] as we observed. Given that reverse causation is possible in a cross-sectional analysis, we considered results of the BACH qualitative interviews and did not analyze beverage types that participants mentioned while discussing symptom management: herbal tea (participants generally increased consumption to improve health) and water (some increased water intake to improve health, whereas others decreased intake to avoid frequent urination).^[18] Overall, the nature of the acute associations observed in the present analysis does not implicate reverse causation. One exception is noncaffeinated soda consumption among men, which was associated with LUTS acutely, whereas caffeinated soda consumption was not. It is possible that men with LUTS chose noncaffeinated soda to avoid caffeine.

Interestingly, in BACH qualitative interviews, participants with LUTS generally did not mention avoidance of caffeine. Similarly, in a small study in the United Kingdom, men with LUTS were unaware of caffeine's possible effects and consumed large amounts of caffeinated drinks; only 13% of men with LUTS believed caffeine affected their symptoms.^[32] Caffeine has long been anecdotally implicated in contributing to LUTS, but data supporting the link have been limited. Our results are consistent with the findings of small clinical studies in which caffeine intake led to detrusor instability, urgency, and frequency.^[12,33] Caffeine could act by directly stimulating the detrusor muscle via increased sympathetic nervous activity, increased production of nitric oxide, or diuretic effects.^[34–37]

It should be noted that our analysis of recent intake showed similar findings for caffeinated and decaffeinated coffee, even after adjustment for total fluid intake and other confounding factors. Changes in total coffee intake also showed similar associations between increased or decreased intakes and LUTS (with the exception of urgency symptoms, which were associated only with increased total coffee intake). In a clinical crossover trial that substituted decaffeinated for caffeinated coffee, no difference in detrusor overactivity was found.^[31] It is possible that other components of coffee also contribute to LUTS (in one small trial, decaffeinated coffee increased sympathetic nervous activity in nonhabitual drinkers), but most studies have attributed such effects to caffeine.^[37,38]

Our finding that carbonated sodas were associated with urgency and worse symptom scores in women is consistent with a prior epidemiologic study of 1-year incidence of urgency symptoms in women in the United Kingdom. Dallosso et al.^[14] found that those who drank soda at least once per day, versus those who drank soda less than once per week, were 70% more likely to develop urgency than were nondrinkers, but specific types of sodas were not assessed; thus the reason for the association was unclear. Carbonated beverages (i.e., sodas, soft drinks) commonly have various components suspected to contribute to LUTS: caffeine, artificial sweeteners or high levels of sugar, colorants, and preservatives (e.g., citric acid).^[10,11] Our data, which showed the strongest associations for caffeinated diet sodas, support findings from a small clinical crossover trial that caffeine and artificial sweeteners together could contribute to LUTS in women.^[13] In experiments in rodents, low concentrations of artificial sweeteners increased detrusor muscle contraction via modulation of L-type calcium channels.^[10] Similar results were found for low levels of ascorbic acid and citric acid, common soda preservatives.^[11] Given small effect sizes, the authors noted that ascorbic or citric acids alone are unlikely to have effects on normal bladder contraction; however, when combined with artificial sweeteners and other constituents of popular sodas, the contractile response was considerably greater.^[11]

Citrus juice was of particular interest in our analysis because of the contrasting possibilities of adverse acidic effects on the bladder and beneficial effects on systemic inflammation and oxidative stress.^[39,40] Orange juice is a primary dietary source of vitamin C and contains various beneficial compounds. Analyses of baseline BACH data showed that high doses of supplemental vitamin C were associated with greater odds of LUTS, but similar associations were not found for vitamin C from dietary sources such as juice.^[41,42] Orange juice reduces inflammation and oxidative stress and improves endothelial function.^[39,40] These effects could help prevent benign prostatic hyperplasia, a common cause of LUTS in men. Thus, a systemic pathway toward improved health and prevention of LUTS with habitual intake over time is consistent with our longitudinal findings in men, which were not apparent in women.

Acute associations for citrus juice and LUTS were observed in both men and women, but these were generally weaker and statistically significant only for moderate citrus juice intake. The sample size for citrus juice analysis was limited to those who returned the follow-up FFQ, which lowered power and could result in nonresponse bias, as well as residual confounding by healthy lifestyle.^[43]

Limitations of this study include possible nonresponse bias to the FFQ or follow-up and confounding by unmeasured factors that are associated with beverage intakes and LUTS. Although the FFQ and interview provided complementary information, the baseline FFQ was limited by lack of data on noncola sodas (e.g., lemon-lime, ginger ale), and the BACH interview did not assess artificially sweetened sodas. Thus, comparing results of the longitudinal and proximate analyses is difficult. Furthermore, differences in the format of questions asked at baseline and follow-up limited analyses of changes in beverage intake to total coffee or total soda.

The focus of our longitudinal analysis was on progression of symptoms for clinical relevance; however, many participants reported symptom remission, which was not specifically taken into account. Our definition of progression was based on a clinical study of patient-reported outcomes, where a 3-point change in IPSS was perceived by men as a global worsening of their condition.^[44] Thresholds for meaningful IPSS changes have not been established in women, although prior studies support the use of the same threshold, given similar scores and associations with quality of life.^[25,26] Additional research, particularly studies with clinical assessments repeatedly measured over follow-up, is needed to verify our findings.

In summary, the present study adds evidence that not only the volume but also the types of beverages consumed can be associated with urological symptoms. A novel finding was that benefits of orange and grapefruit juice could extend to LUTS, particularly for men. Thus, more rigorous evidence is needed to substantiate recommendations to limit intake of acidic beverages that are generally healthful and commonly enjoyed, such as 100% orange juice. Although coffee has been associated with benefits for other health outcomes,^[45] our data support recommendations to limit caffeinated beverage intake for LUTS. Further clinical research is warranted on sodas containing various artificial flavorings, sweeteners, and preservatives, to determine their precise role in bladder sensations and urological function.

Am J Epidemiol. 2013;177(12):1399-1410. © 2013 Oxford University Press