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Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review
Author's Accepted Manuscript Evidence for the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review Catherine S. Bradley , Bradley A. Erickson , Emily E. Messersmith , Anne P. Cameron , H. Henry Lai , Karl J. Kreder , Claire C. Yang , Robert M. Merion , Tamara G. Bavendam , Ziya Kirkali PII: DOI: Reference:
S0022-5347(17)59390-8 10.1016/j.juro.2017.04.097 JURO 14733
To appear in: The Journal of Urology Accepted Date: 30 April 2017 Please cite this article as: Bradley CS, Erickson BA, Messersmith EE, Cameron AP, Lai HH, Kreder KJ, Yang CC, Merion RM, Bavendam TG, Kirkali Z, for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), Evidence for the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review, The Journal of Urology® (2017), doi: 10.1016/ j.juro.2017.04.097. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
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Evidence for the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review
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Catherine S. Bradley, MD, MSCE1, Bradley A. Erickson, MD, MS, FACS 1, Emily E. Messersmith, PhD2, Anne P. Cameron, MD3, H. Henry Lai, MD4, Karl J. Kreder, MD, MBA1, Claire C. Yang, MD5, Robert M. Merion, MD, FACS2, Tamara G. Bavendam, MD, MS6, Ziya Kirkali, MD6, for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) 1
University of Iowa Carver College of Medicine, Iowa City, IA Arbor Research Collaborative for Health, Ann Arbor, MI 3 University of Michigan, Ann Arbor, MI 4 Washington University School of Medicine, St. Louis, MO 5 University of Washington, Seattle WA 6 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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Author Emails [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]
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Running head: Lifestyle factors and lower urinary tract symptoms Key words: Lower urinary tract symptoms, systematic review
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Corresponding Author Catherine S. Bradley, MD, MSCE Professor of Ob-Gyn, Urology and Epidemiology Department of Obstetrics and Gynecology University of Iowa Hospitals & Clinics 200 Hawkins Drive Iowa City, IA 52242 [email protected]
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Source of Funding This is publication number 3 of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).
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This study is supported by the National Institute of Diabetes & Digestive & Kidney Diseases through cooperative agreements (grants DK097780, DK097772, DK097779, DK099932, DK100011, DK100017, DK097776, DK099879). Acknowledgement
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The following individuals were instrumental in the planning and conduct of this study at each of the participating institutions:
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Duke University, Durham, North Carolina (DK097780): PI: Cindy Amundsen, MD, Kevin Weinfurt, PhD; Co-Is: Kathryn Flynn, PhD, Matthew O. Fraser, PhD, Todd Harshbarger, PhD, Aaron Lentz, MD, Drew Peterson, MD, Nazema Siddiqui, MD, Alison Weidner, MD; Study Coordinators: Carrie Dombeck, MA, Robin Gilliam, MSW, Akira Hayes, Shantae McLean, MPH University of Iowa, Iowa City, IA (DK097772): PI: Karl Kreder, MD, MBA, Catherine S Bradley, MD, MSCE, Co-Is: Bradley A. Erickson, MD, MS, Susan K. Lutgendorf, PhD, Vince Magnotta, PhD, Michael A. O’Donnell, MD, Vivian Sung, MD; Study Coordinators: Ahmad Alzubaidi, Andrea Lopez, Linda Moss, RN, BSN, CCRC
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Northwestern University, Chicago, IL (DK097779): PI: David Cella, PhD; Co-Is: James Griffith, PhD, Kimberly Kenton, MD, MS, Christina Lewicky-Gaupp, MD, Todd Parrish, PhD, Jennie Yu Fan Chan, MD; Study Coordinators: Sarah Buono, Maria Corona, Beatriz Menendez, Alexis Siurek, Meera Tavathia, Veronica Venezuela NorthShore University Health System, Evanston, IL (DK097779): PI: Brian T. Helfand, MD, PhD; Study Coordinators: Jasmine Nero, Pooja Talaty
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University of Michigan Health System, Ann Arbor, MI (DK099932): PI: J Quentin Clemens, MD, FACS, MSCI; Co-Is: Mitch Berger, MD, PhD, John DeLancey, MD, Dee Fenner, MD, Rick Harris, MD, Steve Harte, PhD, Anne Pelletier-Cameron, MD, John Wei, MD; Study Coordinators: Morgen Barroso, Linda Drnek, Greg Mowatt, Julie Tumbarello University of Washington, Seattle Washington (DK100011): PI: Claire Yang, MD; Co-I: John L. Gore, MD, MS; Study Coordinators: Alice Liu, MPH, Brenda Vicars, RN Washington University in St. Louis, St. Louis Missouri (DK100017): PI: Gerald Andriole, MD, Henry Lai; Co-I: Joshua Shimony, MD, PhD; Study Coordinators: Susan Mueller, RN, BSN, Heather Wilson, LPN, Aleksandra Klim, RN, MHS, CCRC National Institute of Diabetes and Digestive and Kidney Diseases, Division of Kidney, Urology, and Hematology, Bethesda, MD: Project Scientist: Ziya Kirkali MD; Project Officer: John Kusek, PhD; NIH Personnel: Tamara Bavendam, MD, Robert Star, MD, Jenna Norton, MPH
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Arbor Research Collaborative for Health, Data Coordinating Center (DK097776 and DK099879): PI: Robert Merion, MD, FACS; Co-Is: Brenda Gillespie, PhD, Victor Andreev, PhD, DSc; Project Manager: Melissa Fava, MPA, PMP; Clinical Study Process Manager: Peg Hill-Callahan, BS, LSW; Clinical Monitor: Timothy Buck, BS, CCRP; Research Analysts: Margaret Helmuth, MA, Jon Wiseman, MS; Project Associate: Julieanne Lock, MLitt, BA
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Abstract Purpose: Foods, fluid intake, caffeine, alcohol, and tobacco may influence lower urinary tract symptoms (LUTS). Changes in these potentially modifiable non-urologic factors (NUF) are often suggested to improve
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LUTS. To better understand the relationship of NUFs with LUTS, we performed a systematic literature review to examine, grade, and summarize reported associations between LUTS and diet, fluid intake, caffeine,
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tobacco and alcohol use.
Materials and Methods: We performed PubMed searches for eligible articles providing evidence on
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associations between one or more NUF and LUTS. A modified Oxford system was used to grade the evidence.
Results: We reviewed 110 articles covering diet (n=28), fluid intake (n=21), caffeine (n=20), alcohol (n=26) and tobacco use (n=44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3; 59% level
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4). Fluid intake was associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with less likelihood of benign prostatic hyperplasia (BPH) diagnosis and fewer LUTS in men.
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LUTS associations with food, caffeine, and tobacco were inconsistent.
Conclusions: Evidence for associations between LUTS and diet, fluid intake, caffeine, alcohol and tobacco use
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is sparse and mostly observational. However, there is evidence of associations between increased fluid intake and urinary frequency/urgency, and between modest alcohol intake and decreased BPH diagnosis and LUTS. Given the importance of these NUF to daily life, and their perceived impact on LUTS, higher quality evidence is needed.
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Introduction
Lower urinary tract symptoms (LUTS) are common and bothersome, affecting 20-50% of men and women
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and negatively impacting health-related quality of life (QOL)1-3. Patients seeking care for LUTS are frequently instructed to modify daily behaviors to reduce symptoms. For example, providers may recommend patients change fluid intake, or use less caffeine or alcohol4. The quantity and quality of evidence to support such
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recommendations is unclear. While typically low risk, lifestyle changes may be obtrusive to patients’ lives and increase anxiety or stress. What patients eat, drink, and ingest depends on culture, region, employment,
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socioeconomic status, and other factors. These behaviors are part of the daily human experience, and as such, a better understanding of their impact on LUTS is critical.
The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-supported cooperative network with objectives to
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improve the measurement of LUTS and identify important LUTS subtypes5. In conceptualizing the scope of lower urinary tract dysfunction and its resultant symptoms, we considered multiple potential explanatory
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factors that may contribute to LUTS, including non-urologic factors (NUF), such as diet, fluid intake and
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caffeine, alcohol and tobacco use.
The objectives of this study were to identify, grade, and summarize peer-reviewed literature examining associations between diet, fluid intake, caffeine, alcohol and tobacco use and LUTS. In addition to identifying evidence-based associations between these factors and LUTS, results will help identify gaps where future efforts may be focused.
Methods
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This systematic review was designed to answer the question: “Are diet, fluid intake, and caffeine, alcohol and tobacco use associated with the prevalence and/or severity of LUTS in men and women?”. The review used findings from randomized clinical trial (RCT), cohort, case control, case series, and cross-sectional studies that
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could provide evidence related to these associations. Research focused on bladder pain and conditions such as interstitial cystitis/bladder pain syndrome were excluded. This systematic review was based on the
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Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines6.
PubMed searches were developed with assistance from a health science librarian. Five separate searches
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were performed to identify publications studying associations between LUTS and each of the five NUF. A search “string” was developed for LUTS and for each factor including MESH terms and key words for text searches and limited to English language publications (Supplemental Table 1).
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All citations and abstracts were screened using previously developed eligibility criteria (Table 1). When the initial screener was unsure whether a citation should be included, a second investigator reviewed it. If uncertainty persisted, the citation was included for additional review at the full text stage. Each article
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considered eligible after screening was reviewed (full text) by two investigators. All articles confirmed eligible were assigned a level of evidence by both reviewers, using a system based on the Oxford Centre for
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Evidence-based Medicine Level of Evidence scale (2009 version) and International Consultation on Urological Diseases, modified to include cross-sectional studies as level 4b evidence (Table 2)7, 8. If initial grades differed, investigators arrived at a grade by consensus.
Data from each article were reviewed and abstracted using a standard form. Information collated included study design, population, LUTS outcome (e.g. overactive bladder [OAB]), NUF exposure (e.g. caffeine), the
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summary measure of association and type of analysis performed. Meta-analyses were not performed given
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the heterogeneous study designs, outcomes and exposures identified.
Results
Electronic searches were performed through January 4, 2016. Results of the searches, screening and
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selection process, and reasons for exclusion are presented in Tables 1 and 3. We reviewed 110 unique articles in the areas of diet (n=28), fluid intake (n=21), caffeine (n=20), alcohol (n=26) and tobacco (n=44). Twenty-
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two articles contributed results on more than one factor. The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3, and 59% level 4). A summary of the publications reviewed and a synthesis of results related to the association of each NUF with LUTS are described below.
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Diet and LUTS
Twenty-eight publications met criteria and provided information related to the association between diet and
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LUTS (Table 4). Diet was assessed by a food-frequency questionnaire (FFQ) in almost all studies. There were five interventional RCTs9-13. Only two specifically addressed adding a particular component to improve LUTS10, 13
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. The remaining studies analyzed diet and LUTS in the setting of interventions concerning diabetes
prevention9, constipation reduction11, and weight loss12, 14. (See detailed summary of publications in Supplemental Tables 2A-D.) Diet and BPH
Overall, there appears to be a weak association for diet and surgical BPH therapy. A myriad of food types, food groups, micronutrients and macronutrients were evaluated. Consumption of a high-calorie diet, high in
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starches and red meat may be weakly associated with BPH risk, while a lower-calorie diet, high in vegetables (specifically allium vegetables, e.g. onion and garlic), high in polyunsaturated fats (including specifically eicosapentanoic and docosahexanoic acids) and low in saturated fat may be associated with decreased risk1520
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. Studies on micronutrients have implicated carotene to decrease risk while zinc may increase risk21, 22.
Diet and Urinary Incontinence (UI)
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Many studies that assess diet and UI are indirectly evaluating diet through weight loss. The review found two RCTs in women, the first showing intensive lifestyle therapy (including a low calorie diet) decreased UI in pre-
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diabetic women9 and the second that modest weight reduction (mean 7.8 kg) can decrease stress urinary incontinence (SUI) episodes (but not urge)12, and that weight loss (5-10% of body weight) was sufficient to significantly decrease UI episodes14. Another RCT specifically looked at urgency incontinence episodes in nursing home patients and found when combined with toileting assistance, exercise and an increase in caloric intake, UI episodes decreased significantly11. Another RCT evaluated a diet rich in soy, hypothesized to
LUTS or UI.10
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increase circulating estrogens via phytoestrogens, showed no improvement versus a control diet on overall
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Studies looking at the association of dietary components and incontinence found consumption of saturated and monounsaturated fats and carbonated beverages may increase the risk of SUI while intake of
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breads/starches and vegetables may decrease the risk23, 24. Interestingly, similar to the association seen in BPH, zinc intake was associated with SUI in women as was vitamin B12.23, 24 Consumption of phytoestrogens did not affect SUI.
Diet and General Urinary Symptoms Validated questionnaire use was a common way to test associations between diet and LUTS. Most studies were cross-sectional, and thus, determining causality becomes more difficult given researchers believe
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lifetime exposure is more important for health than current diet. Clinically significant LUTS was associated with poor overall diet and dietary variety25, increase in total caloric intake (adjusting for weight),26, 27 and sodium intake in men26. Protein intake may decrease the risk in men25 but increases the risk of storage
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symptoms in women27. In elderly men, consumption of isoflavone (a phytoestrogen) showed a strong correlation with LUTS28. However, a single RCT evaluated the effects of flaxseed extract (high in
phytoestrogens) on LUTS and noted a dose-dependent and significant decrease in LUTS in men on flaxseed13.
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In a longitudinal cohort study, higher vitamin C intake at baseline was associated with less progression of storage LUTS but vitamin C supplementation was associated with worse LUTS at five-year follow-up in
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women29. Diet and OAB
Few studies have directly assessed OAB and diet. There appears to be a weak association with potato/starch consumption30. Evaluation of micronutrients suggests higher consumption of vitamin D, protein, and
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potassium may be protective of OAB in women31. High energy/caloric intake in the setting of high glycemic
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indices and low physical activity may also be a risk factor in women32.
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Fluid intake and LUTS
Table 5 summarizes the 21 publications reviewed with more details provided in Supplemental Tables 3A-D. Fluid Intake and BPH
It is unclear from the few published articles whether there is an association between fluid intake and BPH. In one RCT, 138 men with BPH were randomized to increase fluid intake by 1.5L per day versus placebo33. There was no difference in AUA-SI total, voiding and QOL scores between the groups at six months. However, AUASI storage scores were worse in those who increased fluid intake (effect size=1.3, p<0.001). In a non9
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randomized, uncontrolled study, AUA-SI increased from 7.9 to 8.9 (p=0.028) after subjects increased fluid intake by 2L per day for eight weeks34. However, the magnitude of symptom worsening was small and likely
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clinically insignificant. Fluid Intake and Nocturia
There is not a clear association between fluid intake and nocturia. In a large RCT35, 307 women were
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randomized to receive tolterodine versus tolterodine plus behavioral therapy, which included pelvic floor muscle exercise training, bladder control techniques, and fluid management. No difference in numbers of
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voids at night was found between treatment groups at 10 weeks. However, this RCT did not specifically examine fluid management, since other behavioral therapies were included and all subjects received general information to avoid excessive fluid intake. Similarly a large cohort study in men found no association between night-time fluids and incident nocturia36. In contrast, two uncontrolled case series showed fluid
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restriction improved nocturia37, 38. Fluid Intake and OAB Symptoms
Six out of seven studies on OAB symptoms reported a positive association between fluid intake and urinary
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frequency/urgency, including two small cross-over RCTs. One randomized 69 women to caffeine restriction plus daily fluid increase to 3L, compared to caffeine restriction plus fluid decrease to 750 mL daily39. Another
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included 24 men and women randomized to increase vs. decrease their daily fluid intake by 25% compared to their baseline40. Both trials found significantly increased frequency and urgency symptoms with fluid increase, and decreased frequency and urgency with fluid reductions. Fluid Intake and UI Fourteen articles had mixed results on association between fluid intake and UI: six showed positive, one showed negative and seven no correlations. In a small RCT, increasing fluid intake worsened weekly UI 10
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episodes, while decreasing fluid intake improved weekly incontinence. In contrast, the Zimmern RCT35 did not show any correlation. One RCT did not yield any useful results, since most patients were not able to adhere to the fluid protocols41. Two cohort studies examined new-onset UI: one found consumption of carbonated
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drinks was associated with new onset SUI,24 while another did not show an association between fluid intake
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and new UI42.
Caffeine Intake and LUTS
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Twenty articles on caffeine intake and LUTS are summarized in Table 6 (detailed summary found in Supplemental Tables 4A-E). Most were observational studies, but two small RCTs were reviewed. Most assessed caffeine intake as self-reported cups of coffee or milligrams of caffeine per day, estimated using a self-reported FFQ or other non-validated questions. Two studies in women focused on urodynamic test
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findings related to caffeine. One small study found detrusor pressure during filling increased (but other parameters were unchanged) after caffeine ingestion.43Another found detrusor overactivity in women with UI was associated with higher caffeine intake.44
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Caffeine and BPH
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It is unclear if caffeine intake and BPH are associated, and evidence reviewed was limited to coffee, not caffeine, intake. Three studies on caffeine intake in men with BPH had conflicting results. Two older case control studies of men with surgically-treated BPH found non-significant associations between coffee intake and BPH45, 46. A large, population-based, cross-sectional study found increasing coffee consumption positively associated with BPH47. Caffeine and Nocturia
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Coffee consumption was not associated with nocturia in men or women, as tested in a cohort study of men and a large cross-sectional study of women48, 49. In contrast, the same cross-sectional study found tea intake was associated with increasing nocturia, although the increased risk was small (OR 1.2) and only in women
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drinking three or more cups of tea daily. Another large cross sectional study found women with nocturia were less likely to drink caffeinated beverages after 6pm50. This finding highlights the limitations of crosssectional analyses, since women who have nocturia may be likely to avoid caffeinated beverages in the
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evening.
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Caffeine and OAB/LUTS
Small, randomized interventional studies provide limited evidence that caffeine reduction may decrease OAB symptoms in women. In two RCT (mostly women), caffeine reduction was associated with reduced urinary frequency, urgency, and OAB QOL scores51, 52. Caffeine restriction was not associated with changes in frequency/urgency in a third uncontrolled study39. Coffee consumption in a large cross-sectional study was
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not associated with urgency, but women reporting tea intake (three or more cups daily) were more likely to report urgency53. Fewer studies have evaluated caffeine and OAB in men, though one large, cross-sectional
Caffeine and UI
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study found caffeine intake was not associated with increased LUTS54.
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Overall evidence may suggest a weak positive association between caffeine and UI, but there are conflicting results for UI types, and studies in men are lacking. Four interventional studies (two randomized, two uncontrolled) found no impact for caffeine reduction on UI39, 51, 52, 55. A longitudinal study in women found caffeine associated with frequent UI and urgency urinary incontinence (UUI), but only in women with the greatest caffeine intake56. Caffeine intake was not associated with UI progression when analyzed in the same longitudinal data57. Mixed results were found in several large cross-sectional studies in women, with one finding coffee and tea intake associated with SUI, and tea intake with overall UI (but not UUI), while another 12
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found no association between tea or coffee consumption and any type of UI53, 58, 59. One large cross-sectional study of men found the highest level of caffeine intake associated with moderate to severe UI (but not with
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any UI)60.
Alcohol and LUTS
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Twenty-six articles on alcohol intake and LUTS were identified, reviewed and graded (Table 7). Study details are presented in Supplemental Tables 5A-E. Most publications assessed alcohol intake as self-reported drinks
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per day, week or month, or grams of alcohol consumed based on the subject’s self-report. Four articles analyzed alcohol type (beer, wine, spirits) as well as total consumption. Alcohol and BPH and LUTS in Men
Results for BPH and BPH surgery were consistent among seven of eight articles reviewed, with a decrease in
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BPH diagnosis or surgery in men who drank alcohol compared to non-drinkers. The association between alcohol intake and the reduction in BPH diagnosis and surgery was particularly strong for modest alcohol consumption (defined as 1-3 drinks per day), with this consumption level having the greatest BPH reduction
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compared to non-drinkers.
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LUTS, UI and nocturia in men alone were assessed in 14 articles and had relatively consistent findings with modest drinking associated with fewer symptoms compared to non-drinkers in all but two articles. Heavy alcohol consumption (defined as self-reported alcoholism, >72g/day [>5.1 drinks a day] or >40g/day [>2.9 drinks a day]), however, appears to have a negative effect with an increase in incontinence, obstructive and irritative LUTS61. This “J-shaped” association of alcohol intake and LUTS was most clearly seen in a crosssectional study of 30,196 Korean men participating in a comprehensive health examination, where the odds
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of moderate or severe AUA-SI scores were lowest among modest drinkers (0-10g/day) compared to nondrinkers and highest in men who drank >40g/day62.
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Alcohol and Nocturia Only two articles assessed nocturia. In a group with both genders, no association was found between alcohol intake and nocturia63, whereas in a single article including only men, modest alcohol intake had the lowest
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risk of moderate or severe nocturia48.
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Alcohol and OAB/UI
Among three articles assessing OAB there were inconsistent results. Results from the BACH study showed inconsistent findings by intake level and symptom subtype with few groups achieving statistical significance64, whereas an interview study of 833 elderly individuals found greater odds of urgency and frequency among current drinkers compared to non-drinkers, but not ex-drinkers65. In four articles assessing UI no association
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Tobacco and LUTS
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was found between any type of UI and alcohol intake.
Forty-four articles on tobacco use and LUTS were systematically reviewed (Table 8). Most were cross-
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sectional, but some cohort and case-controls studies were reviewed. Tobacco use was almost always studied as self-reported current cigarette smoking. Tobacco and BPH
Eight of 12 articles reported no association between BPH and tobacco. Four found a negative association between heavy or current smoking and BPH, but no trend in the association with quantity of cigarettes smoked47, 66-68. 14
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Tobacco and Nocturia Evidence regarding nocturia was inconsistent. Of six studies, one showed a positive association between
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current smoking and nocturia in women50, two showed a negative association in women69 and men68, one showed a negative association with heavy current smoking (but not lighter current smoking) in a sample of men and women70. Two studies showed no association48, 71.
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Tobacco and OAB
Within the broad category of evidence for OAB or LUTS in general, there are some consistent and some
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inconsistent findings. A small amount of evidence suggests former and/or current smoking is related to frequency in women. Two studies showed a positive association between urgency and current tobacco use,71, 72
while two did not69, 73. A single study each showed no association with irritative symptoms in men61 or
voiding symptoms in men and women74, but a positive association with obstructive symptoms in men61 and
most inconsistent results. Tobacco and UI
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storage symptoms in women74. LUTS in general was the most common outcome in this category but had the
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We found no evidence to review regarding UI in men. In women, studies reported inconsistent results. Some
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studies provided evidence of a positive association between tobacco use and SUI75, 76, UUI and mixed incontinence77, motor incontinence75, and incontinence of any (unspecified) type59, 77, 78. Six studies showed no associations69, 71, 73, 79-81, and one showed a negative association between occasional UI and current smoking78. In addition, Hannested 200359 showed mixed results between current, former, and heavy smoking and various measures of incontinence. The two studies that examined severe UI showed a positive association59, 78. Tobacco and Other LUTS Measures 15
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A few studies focused on other parameters. Single studies showed positive associations between smoking and women’s maximum cough spike82, cough leak point pressure and maximal intravesical pressures generated by cough83, and men’s estradiol levels84. Two studies showed evidence that male smokers were at
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lower risk of low urinary flow rates85, 86, but another found no association84. No associations were found between tobacco use and women’s maximum closure pressure, mean pressure transmission ratio, degree of urethral axis with stress82, or men’s testosterone, dehydroepiandrosterone (DHEA), or DHEA-S levels or
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prostate weight.84
Key Point Summary
• Expert consensus of the reviewed literature suggests a balanced low-calorie/low-saturated fat diet in a physically active, non-obese person will decrease the lifetime likelihood of developing LUTS and/or BPH,
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but current evidence for associations between diet and individual dietary constituents and LUTS is mixed and suggests associations, if present, are weak.
• Fluid intake is associated with urinary frequency and urgency in men and women and the association is
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bi-directional. Evidence supports the use of fluid reduction to manage urinary urgency (as in the AUA Guideline on OAB)4. Given potential risks from dehydration, recommendations that patients reduce their
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fluid intake by 25%, providing they do not drink <1 L/day, seem reasonable87. Relationships between UI, nocturia and fluid intake are less conclusive. • We found inconsistent associations between caffeine intake and BPH and nocturia. Mixed evidence suggests caffeine reduction may reduce urinary frequency and urgency in women (small effects). Conflicting results related to caffeine and overall UI and UI types suggests any association if present is weak. The small number of studies focused on caffeine and LUTS in men (particularly OAB and UI symptoms) made it difficult to interpret these results. 16
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• Moderate/modest alcohol consumption in men is associated with a reduced risk of BPH and BPH surgery, as well as decreased LUTS compared to non-drinkers, however excessive alcohol intake above the recommended threshold of healthy consumption is associated with worse LUTS in men. These results are
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consistent with the U.S. Department of Health and Human Services’ recommendation on alcohol consumption for men (two drinks or less/day)88. In contrast, we found no evidence for women that avoidance of alcohol reduces the risk of UI or LUTS.
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• We did not find strong evidence that smoking increases UI. Indeed, we found mixed, and therefore weak, evidence for any associations between tobacco use and LUTS. There was perhaps a positive association
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between smoking and urinary frequency in women, based on limited evidence.
Discussion
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We systematically reviewed the literature studying associations between LUTS and daily behaviors, including diet, fluid intake, and caffeine, alcohol and tobacco use. We identified 110 articles meeting our eligibility criteria, graded their evidence, and summarized these findings by population and LUTS condition studied.
low.
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Overall, relatively few, largely observational studies were eligible (< 50 per factor) and evidence quality was
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Based on our review, few definitive conclusions about associations could be made. In observational studies of men, modest alcohol use (compared to non-use) was associated with less likelihood of a BPH diagnosis and fewer LUTS. As alcohol intake of this level falls within federal recommendations, this might be considered a reasonable recommendation in clinical practice. Fluid intake was positively associated with urinary frequency and urgency symptoms in men and women in two small interventional studies and in observational studies of mixed quality. These findings support the inclusion of fluid management within the behavioral strategies
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recommended as first-line treatments for OAB4. In other areas of our review, inconsistent results or lack of evidence precluded conclusions about associations between NUF and LUTS.
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Strengths of this effort include our standardized protocol used for screening citations, determining eligibility for inclusion and abstracting study results. We used an accepted and widely-used system for grading the evidence of the included studies. When possible, we attempted to synthesize results to help clarify clinical
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usefulness of the literature.
One study limitation is that most of the evidence was from observational studies, and we did not attempt
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meta-analyses due to the heterogeneous search results. Few studies in any single area included similar enough outcomes and exposures that statistical integration would be useful or valid. Given our results included lower evidence levels, caution must be taken in making clinical recommendations based on these findings89, 90. However, systematic review of observational studies may be an important alternative when RCTs cannot produce the evidence needed or would be unethical90. For example, a dietary factor may require
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an extended duration of exposure to cause LUTS, which could not be feasibly assessed in an RCT. In another example, RCTs measuring the impact of tobacco on LUTS would be unethical.
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Another weakness to much of the evidence included in this review is the use of self-report measurement to assess exposures. Most of the reviewed articles assessed exposures using self-report, often by interview or
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questionnaire. Thus, the associations between the NUF and LUTS summarized here are subject to limitations of participants’ memory and social desirability effects. Other measurement tools, such as electronic diaries or biomarkers, may provide more valid assessment of exposure in future studies. However, any research in lifestyle factors is likely to face challenges obtaining accurate and unbiased measurements of these factors. The challenges in performing research on lifestyle factors may partially explain the lack of higher quality evidence available. Despite this (or perhaps because of this), we feel a systematic review of this observational data is important to summarize the evidence available (even if lower quality) and to highlight the lack of 18
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evidence in this important topic area. We hope results from this review will spur additional research on lifestyle changes that may modify and/or prevent LUTS. On the other hand, we also acknowledge that strong evidence may never exist for some of these research questions. In these cases, LUTS providers should make a
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practical assessment of the evidence available and consider the individual situation of each patient in making clinical recommendations.
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Conclusions
Systematic literature review revealed that evidence supporting associations between LUTS and diet, fluid
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intake, and caffeine, alcohol and tobacco use is sparse. The data available are largely observational and generally lower quality. Given these factors are often modifiable and are frequently included in management recommendations by LUTS care providers, more and higher quality evidence is needed to better understand
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their impact on LUTS.
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References* 1. Kupelian V, Wei JT, O'Leary MP et al: Prevalence of lower urinary tract symptoms and effect on quality of life in a racially and ethnically diverse random sample: the Boston Area Community Health (BACH) Survey. Arch Intern Med 2006; 166: 2381. 2. Coyne KS, Sexton CC, Thompson CL et al: The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int 2009; 104: 352. 3. Coyne KS, Wein AJ, Tubaro A et al: The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS. BJU Int, suppl., 2009; 103: 4. 4. Gormley EA, Lightner DJ, Burgio KL et al: Diagnosis and treatment of overactive bladder (nonneurogenic) in adults: AUA/SUFU guideline. J Urol, suppl., 2012; 188: 2455. 5. Yang CC, Weinfurt KP, Merion RM et al: Symptoms of Lower Urinary Tract Dysfunction Research Network. J Urol ; 196: 146. 6. Moher D, Liberati 2016A, Tetzlaff J et al: Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med 2009; 6: e1000097. 7. Oxford Centre for Evidence-based Medicine: Oxford Centre for Evidence-based Medicine—Levels of Evidence (March 2009). Available at http://www.cebm.net/oxford-centre-evidence-based-medicinelevels-evidence-march-2009/. 8. Abrams P and Khoury S: International Consultation on Urological Diseases: Evidence-based medicine overview of the main steps for developing and grading guideline recommendations. Neurourol Urodyn 2010; 29: 116. 9. Brown JS, Wing R, Barrett-Connor E et al: Lifestyle intervention is associated with lower prevalence of urinary incontinence: the Diabetes Prevention Program. Diabetes Care 2006; 29: 385. 10. Manonai J, Songchitsomboon S, Chanda K et al: The effect of a soy-rich diet on urogenital atrophy: a randomized, cross-over trial. Maturitas 2006; 54: 135. 11. Schnelle JF, Leung FW, Rao SS et al: A controlled trial of an intervention to improve urinary and fecal incontinence and constipation. J Am Geriatr Soc 2010; 58: 1504. 12. Subak LL, Wing R, West DS et al: Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med 2009; 360: 481. 13. Zhang W, Wang X, Liu Y et al: Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J Med Food 2008; 11: 207. 14. Wing RR, Creasman JM, West DS et al: Improving urinary incontinence in overweight and obese women through modest weight loss. Obstet Gynecol 2010; 116: 284. 15. Araki H, Watanabe H, Mishina T et al: High-risk group for benign prostatic hypertrophy. Prostate 1983; 4: 253. 16. Bravi F, Bosetti C, Dal Maso L et al: Food groups and risk of benign prostatic hyperplasia. Urology 2006; 67: 73. 17. Chyou PH, Nomura AM, Stemmermann GN et al: A prospective study of alcohol, diet, and other lifestyle factors in relation to obstructive uropathy. Prostate 1993; 22: 253. 18. Galeone C, Pelucchi C, Talamini R et al: Onion and garlic intake and the odds of benign prostatic hyperplasia. Urology 2007; 70: 672. 19. Kristal AR, Arnold KB, Schenk JM et al: Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol 2008; 167: 925. 20. Suzuki S, Platz EA, Kawachi I et al: Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia. Am J Clin Nutr 2002; 75: 689. 20
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27. 28. 29. 30. 31. 32. 33.
34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44.
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Lagiou P, Wuu J, Trichopoulou A et al: Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999; 54: 284. Tavani A, Longoni E, Bosetti C et al: Intake of selected micronutrients and the risk of surgically treated benign prostatic hyperplasia: a case-control study from Italy. Eur Urol 2006; 50: 549. Dallosso H, Matthews R, McGrother C et al: Diet as a risk factor for the development of stress urinary incontinence: a longitudinal study in women. Eur J Clin Nutr 2004; 58: 920. Dallosso HM, McGrother CW, Matthews RJ et al: The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int 2003; 92: 69. Erickson BA, Vaughan-Sarrazin M, Liu X et al: Lower urinary tract symptoms and diet quality: findings from the 2000-2001 National Health and Nutrition Examination Survey. Urology 2012; 79: 1262. Maserejian NN, Giovannucci EL and McKinlay JB: Dietary macronutrients, cholesterol, and sodium and lower urinary tract symptoms in men. Eur Urol 2009; 55: 1179. Maserejian NN, McVary KT, Giovannucci EL et al: Dietary macronutrient intake and lower urinary tract symptoms in women. Ann Epidemiol 2011; 21: 421. Wong SY, Lau WW, Leung PC et al: The association between isoflavone and lower urinary tract symptoms in elderly men. Br J Nutr 2007; 98: 1237. Curto TM, Giovannucci EL, McKinlay JB et al: Associations between supplemental or dietary intake of vitamin C and severity of lower urinary tract symptoms. BJU Int 2015; 115: 134. Dallosso HM, Matthews RJ, McGrother CW et al: The association of diet and other lifestyle factors with the onset of overactive bladder: a longitudinal study in men. Public Health Nutr 2004; 7: 885. Dallosso HM, McGrother CW, Matthews RJ et al: Nutrient composition of the diet and the development of overactive bladder: a longitudinal study in women. Neurourol Urodyn 2004; 23: 204. McGrother CW, Donaldson MM, Thompson J et al: Etiology of overactive bladder: a diet and lifestyle model for diabetes and obesity in older women. Neurourol Urodyn 2012; 31: 487. Spigt M, van Schayck O, Knipschild P et al: Is it possible to improve elderly male bladder function by having them drink more water? A randomized trial of effects of increased fluid intake/urine output on male lower urinary tract function. Urology 2006; 68: 1031. Spigt MG, Knottnerus JA, van de Beek C et al: Short-term effects of increased urine output on male bladder function and lower urinary tract symptoms. Urology 2004; 64: 499. Zimmern P, Litman HJ, Mueller E et al: Effect of fluid management on fluid intake and urge incontinence in a trial for overactive bladder in women. BJU Int 2010; 105: 1680. Johnson TM 2nd, Sattin RW, Parmelee P et al: Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults. J Am Geriatr Soc 2005; 53: 1011. Soda T, Masui K, Okuno H et al: Efficacy of nondrug lifestyle measures for the treatment of nocturia. J Urol 2010; 184: 1000. Tani M, Hirayama A, Torimoto K et al: Guidance on water intake effectively improves urinary frequency in patients with nocturia. Int J Urol 2014; 21: 595. Swithinbank L, Hashim H and Abrams P: The effect of fluid intake on urinary symptoms in women. J Urol 2005; 174: 187. Hashim H and Abrams P: How should patients with an overactive bladder manipulate their fluid intake? BJU Int 2008; 102: 62. Dowd TT, Campbell JM and Jones JA: Fluid intake and urinary incontinence in older communitydwelling women. J Community Health Nurs 1996; 13: 179. Townsend MK, Jura YH, Curhan GC et al: Fluid intake and risk of stress, urgency, and mixed urinary incontinence. Am J Obstet Gynecol 2011; 205: 73. Creighton SM and Stanton SL: Caffeine: does it affect your bladder? Br J Urol 1990; 66: 613. Arya LA, Myers DL and Jackson ND: Dietary caffeine intake and the risk for detrusor instability: a casecontrol study. Obstet Gynecol 2000; 96: 85.
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48. 49. 50.
Morrison AS: Prostatic hypertrophy in greater Boston. J Chronic Dis 1978; 31: 357. Morrison AS: Risk factors for surgery for prostatic hypertrophy. Am J Epidemiol 1992; 135: 974. Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002; 90: 649. Shiri R, Hakama M, Häkkinen J et al: The effects of lifestyle factors on the incidence of nocturia. J Urol 2008; 180: 2059. Tettamanti G, Nyman-Iliadou A, Pedersen NL et al: Influence of smoking, coffee, and tea consumption on bladder pain syndrome in female twins. Urology 2011; 77: 1313. Asplund R and Aberg HE: Nocturia in relation to body mass index, smoking and some other life-style factors in women. Climacteric 2004; 7: 267.
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* References 51 to 125 for this article can be obtained at http://jurology.com/.
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Table 1. Criteria for excluding article from the systematic review Number* 158
No relevant LUTS or LUT condition (including prostate cancer)
83
LUTS studied as treatment result or adverse effect (e.g. post-prostatectomy incontinence)
24
Sample size < 25 (unless RCT design)
3
Editorial, commentary, non-systematic review
76
Non-relevant research type (e.g. qualitative studies, instrument development)
6
Pregnant population
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Pediatric population
9
5 1
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Not human subjects research
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No relevant non-urologic factor studied
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Reason for Exclusion
*More than one reason for exclusion may be listed for an individual article
1
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Level
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Table 2. Levels of evidence used in grading the articles (modified from the 2009 Oxford Centre for Evidence-based Medicine Levels of Evidence and the International Consultation on Urological Diseases)7, 8 Study Design or Type Systematic review of RCTs
1b
Individual RCT (good quality)
2a
Systematic review of cohort studies
2b
Individual cohort study, low quality RCT
3a
Systematic review of case control studies
3b
Individual case control study
4a
Good quality case-series, poor quality cohort or case control study
4b
Cross-sectional study
5
Expert opinion
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RCT – Randomized controlled trial
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1a
2
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Table 3. Numbers of publications obtained in each PubMed search and included in review Additional article identified during review
Diet
128
31
28
0
Fluid Intake
207
30
19
2
Caffeine
36
22
19
Alcohol
66
30
26
Tobacco
126
45
44
TOTAL
563
158
136
Total Publications included in Systematic Review
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Publications eligible after full text review
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Publications eligible after screening citation/abstract
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Citations from PubMed Search
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Non-urologic Factor
28
21
1
20
0
26
0
44
3
110*
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*Some publications provided results for more than one non-urologic factor; specifically 15 and 7 publications contributed results for 2 and 3 factors, respectively.
Table 4. Overview of search results for diet and LUTS Number articles
Study Design
Population
Results Summary*
Comments
BPH15-22, 91, 92
9
2-Cohort
All Men
Mixed results:
Diet may indirectly affect prostate growth through influences on androgens. Low caloric intake high in polyunsaturated fats may
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LUTS Condition Studied
6-Case-control 1 -Cross-
7 - S, + 7 - S, -
3
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9
be protective. Most effects from diet came indirectly through weight alteration.
4- RCT
8 – Women
Mixed results:
4 - Cohort
1– Men/Women
6 - S, +
14, 23, 24, 93, 94
1 - Crosssectional
3 - S, 5 - NS
7
1 – RCT
5 – Men
Mixed results:
1 – Cohort
1 – Women
3 - S, +
5 – Crosssectional
1– Men/Women
2 - S, -
29, 95
2 - NS
3
3 - Cohort
2 –Women
Mixed results:
1 – Men
1 - S, +
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OAB30-32
2 - S, -
3 – NS
Weak associations noted, mostly indirect through weight gain/loss. Some evidence for effects on OAB through diabetes mechanism (neurovascular)
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EP
Overall weak associations. Low caloric intake, high in polyunsaturated fats and high in vegetables may be protective from LUTS. Vit C may be protective when obtained from food.
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Non-Specific Urinary Symptoms13, 25-
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Incontinence 9-12,
7 – NS
SC
sectional
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association * Studies that tested more than one association may be counted more than once in this column.
4
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Table 5. Overview of search results for fluid intake and LUTS Number articles
Study Design
Population
Results Summary
Comments
BPH33, 34, 96
3
1 - RCT
3 - Men
Mixed results:
Fluid intake worsens storage symptoms with no impact on voiding symptoms.
1 - Outcome research
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1 - S, +
1 - Crosssectional 1 – RCT
3- Men
1- Cohort study
2 - Men & Women
2 - Outcome research
7
3 - RCT
1 - Cohort study
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35, 39, 40, 97-99
1- Women
EP
2 - Crosssectional OAB/LUTS (non-UI)24,
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6
2 - NS
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Nocturia35-38, 96, 97
3 - Crosssectional
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LUTS Condition Studied
5 - Women 2 - Men & Women
Mixed results: 2 - S, + 4 - NS
Positive association in most studies: 6 - S, + 1 - NS
Evidence was inconclusive whether fluid restriction reduces nocturia.
Most studies showed positive association between fluid intake and frequency and/or urgency
5
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symptoms. 14
5 - RCT
10 - Women
2 - Cohort study
1 - Men
1 – Case series
3 - Men & Women
97, 99-101
6 - Crosssectional
Mixed results: 6 - S, + 1 - S, -
Results were inconclusive for an association between fluid intake and UI.
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UI11, 24, 35, 39-42, 55, 58, 60,
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SC
7 - NS
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
Table 6. Overview of search results for caffeine intake and LUTS Study Design
BPH45-47
2- Case-control
Results Comments Summary*
3- Men
Mixed results:
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3
Population
TE D
LUTS Condition Studied Number articles
Nocturia48, 50, 53
3
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1- Cross-sectional
2- NS, -, + 1- S, +
1- Cohort
1- Men
2- Cross-sectional
2- Women
Mixed results: 1- S, +
Unclear if caffeine or other coffee constituents might influence BPH. Tea (but not coffee) intake associated with nocturia.
6
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2- NS, + and +/OAB/LUTS (non-UI)39, 51-
5
2- RCT
3-Women
1- Case series
1- Men & Women
2- Cross-sectional
2- NS, +/-
2- RCT
9-Women
2- Cohort
2- Men & Women
1- Case series
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12
3- S, +
1-Men
Mixed results: 5- S, +
2- NS, +
2
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EP
7- Cross-sectional
Urodynamic parameters43, 44
Caffeine restriction associated with small improvements in frequency and urgency in women.
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1- Men
UI39, 49, 51, 52, 55-60, 102, 103
Mixed results:
SC
54
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1- S, -
1- Case series
1- Cross-sectional
2-Women
4- NS, +/1- NS, -
2- S, +
Overall evidence may suggest weak positive association between caffeine and UI, but conflicting results for UI types. Studies in men are lacking. Positive results but conflicting findings (varying endpoints)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association * Studies that tested more than one association may be counted more than once in this column. 7
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Table 7. Overview of search results for alcohol and LUTS Number articles
Study Design
Population
Results Summary
Comments
BPH17, 46, 47, 68, 104-108
9
2- Cohort
10- Men
Consistent results:
Decrease in BPH diagnosis surgery in men who drank alcohol compared to non-drinkers (all but one study)
3- Case control
1- Metaanalysis 10
2- Cohort
9- Men
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8- Cross sectional
Consistent results:
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109-113
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1- NS
SC
8- S +
3- Cross sectional
Male LUTS19, 54, 61, 62, 95,
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LUTS Condition Studied
7- S+ (negative associations with modest alcohol, positive with heavy alcohol use) 2- NS
Modest drinking associated with fewer symptoms compared to non-drinkers (all but two articles). Alcoholism has negative effect on urinary symptoms.
1- variable results
9
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1- Cohort
1- Men
1- Crosssectional
1- Women and Men
Inconsistent results: 1- 1 subgroup S+ 1- NS
3
3- Women and Men
1- Cohort 2- Crosssectional
Inconsistent results: 2- NS
1- S only for subgroup
5
3- Crosssectional
1- Men 3-Women
2- NS, +
1- Women and Men
2- NS, +/-
No significant association noted
EP
1- Case series
1- S+
TE D
UI59, 63, 95, 112, 114
Inconsistent findings for association between alcohol and urinary symptoms
M AN U
OAB/LUTS (non-UI)63-65
Inconsistent results for alcohol and nocturia
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2
SC
Nocturia48, 63
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S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
10
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Table 8. Overview of search results for tobacco use and LUTS Number articles
Study Design
Population
Results Summary
BPH17, 45-47, 66-68, 85, 86, 115-117
12
4-Cohort
All Men
Mixed results: 7NS
Some evidence for negative association, more evidence for no association
SC
6-Crosssectional
Comments
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LUTS Condition Studied
1- NS, S, + 2-Casecontrol
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2- NS, S, 2- S, -
Nocturia48, 50, 68-71
6
5-Crosssectional
3-Women
Mixed results:
Inconsistent results
85, 86, 95, 109, 111, 113, 118-123
EP
19
18-Crosssectional
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OAB/LUTS (non-UI)54, 61, 69, 71-74,
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2-Men 1-Cohort
6-Women 11-Men
2- NS
1- NS, S, 1- S, + 2- S, Mixed results: 7NS
1-Cohort
2- Women and Men
3- NS, S, + 7- S, +
Some evidence for a positive association, other evidence shows no association
2- not 11
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reported 13
2-Casecontrol
All Women
Some evidence for a positive association, other evidence 1- NS, S, +/- shows no association 3- S, +
SC
11-Crosssectional
Mixed results: 6NS
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UI59, 69, 71, 73, 75-81, 118, 124
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1- S, +/-
2- not reported
Other- UDS parameters & plasma levels82-86
5
1-Case control
2-Women
Mixed results:
3- Men
2- NS, S, + 1- S, + 2- S, -
EP
3-Crosssectional
TE D
1-Case series
Outcomes varied, some evidence of associations
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S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
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Abbreviation Key
AUA-SI: American Urological Association Symptom Index
DHEA: dehydroepiandrosterone FFQ: food-frequency questionnaire LURN: Symptoms of Lower Urinary Tract Dysfunction Research Network LUTS: lower urinary tract symptoms NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases
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NUF: non-urologic factors
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BPH: benign prostatic hyperplasia
OAB: overactive bladder
QOL: quality of life RCT: randomized clinical trial SUI: stress urinary incontinence UI: urinary incontinence
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UUI: urgency urinary incontinence
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PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Bradley et al. Evidence for the Impact of Diet
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Supplemental Table 1. Terms used in PubMed literature search. Terms for each topic were combined into search strings, and each search performed by combining the search string for LUTS with the string for one of the non-urologic factors. Searches were further limited to human studies, adult study populations and English language publications, and to publications not labeled as case reports, editorials and letters.
MESH Terms
Complete Search String
Alcohol intake
Alcohol drinking
"Alcohol Drinking"[Mesh] OR "Alcoholic Intoxication"[Mesh] OR "Alcoholism"[Mesh] OR “Binge Drinking”[Mesh]
SC
Alcohol intoxication Alcoholism
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Binge drinking Caffeine intake
"Caffeine"[Mesh] OR "Coffee"[Mesh] OR "Coffea"[Mesh] OR "Energy Drinks"[Mesh]
Caffeine Coffee Coffea
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Energy Drinks Diet
Diet
"Diet"[Mesh] OR "Eating"[Mesh:NoExp] OR "Nutritional Status"[Mesh]
EP
Nutritional status
Drinking Drinking behavior
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Eating Fluid intake
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Search Topic
"Water-Electrolyte Balance"[Mesh] OR "Drinking Behavior"[Mesh:NoExp] OR "Drinking"[Mesh] OR fluid intake [title/abstract]
Water/electrolyte balance Fluid Intake*
1
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Lower Urinary Tract Symptoms Prostatic Hyperplasia
LUTS
"Lower Urinary Tract Symptoms"[Mesh] OR "Prostatic Hyperplasia"[Mesh] OR "Urination Disorders"[Mesh:NoExp] OR "Urethral Obstruction"[Mesh] OR “enuresis”[Mesh] OR “urinary retention”[Mesh] OR urinary hesitanc*[Title/Abstract] OR post void dribbl*[Title/Abstract] OR post-void dribbl*[Title/Abstract] OR postvoid dribbl*[Title/Abstract] OR underactive bladder*[Title/Abstract] OR under-active bladder*[Title/Abstract] OR under active bladder*[Title/Abstract]
Urination Disorders
RI PT
Urethral Obstruction Enuresis Urinary retention
SC
Urinary hesitancy*
Tobacco use
M AN U
Post void dribble* Underactive bladder*
"Tobacco Products"[Mesh] OR "Tobacco"[Mesh] OR "Smoking"[Mesh] OR "Nicotine"[Mesh] OR "Tobacco Use Cessation Products"[Mesh]
Smoking Nicotine Tobacco
TE D
Tobacco Products Tobacco Use Cessation Products
EP
*Terms searched as text words (limited to the title or abstract). Text words were used in search strings when MESH terms were not sufficient.
Author /Year
Araki15
Oxford Level
3b
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Supplemental Table 2A. BPH and Diet- Detailed Summary of Articles Study Design, Duration Followup
Population, N
Case-
Men, 100 BPH and
LUTSOutcome(s)
BPH (diagnosis confirmed by hx,
Diet Variable
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Rice, wheat, seafood, meat, milk, green & yellow
milk OR=2.25 vegetables OR=3.91
NS rice, wheat,
No 2
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3b
Bravi16 2006
3b
100 controls
digital palpitation, transrectal ultrasonotomog raphy, x-ray, and biopsy)
vegetables, pickles (FFQ, 5point scale)
Casecontrol
Men, 1369 BPH, 1451 controls
BPH (surgically treated, dx ≤ 1yr before)
(daily g, FFQ) Proteins --Vegetable proteins --Animal proteins Sugars Starch Total fats --Vegetable fats --Animal fats Saturated fatty acids Monounsaturated fatty acids Polyunsaturated fatty acids Oleic acid Linoleic acid Linolenic acid Other polyunsat fatty acids Cholesterol (mg)
Quintiles 2-5 (ref: 1) 1.04 1.01 1.21 1.04 1.31 1.15 1.13 1.09 1.02 1.13 1.01 1.07 0.82 0.84 0.88 0.87 1.31 1.19 1.35 1.51 1.00 1.03 0.94 0.94 1.05 0.97 1.05 0.95 0.92 1.11 0.84 0.85 1.01 0.95 0.94 0.91 0.89 1.10 1.09 1.06 0.95 0.80 0.67 0.72 0.91 1.13 1.05 1.10 0.97 0.78 0.67 0.73 0.95 1.07 0.86 0.71 0.98 1.05 0.98 1.02 1.13 1.16 1.20 1.00
Casecontrol
Men, 1369 BPH, 1451 controls
(weekly servings, FFQ)
Quintiles 2-5 (ref: 1) 0.89 1.11 1.11 1.11 0.69 0.86 0.94 0.96 1.12 1.42 1.60 1.55 1.08 1.26 1.59 1.69 1.68 1.43 1.43 1.30 1.03 0.96 0.93 0.74 1.53 1.43 n/a n/a
pickles OR=1.99
AC C
EP
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M AN U
SC
Bravi91, 2006
control
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1983
BPH (surgically treated, dx ≤ 1yr before)
Milk & diary Coffee & tea Cereals
seafood, meat; S+ milk, vegetables, pickles
Yes NS NS NS NS S+ NS NS NS NS NS SNS SSNS NS Yes NS NS S+ S+ NS SS+ 3
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Bread Pasta & rice
Poultry Red meat Fish
M AN U
Cheese
SC
Eggs
RI PT
Soups
1.03 1.52 1.40 1.39 0.90 0.89 0.95 0.75 1.18 1.00 1.11 1.13 1.02 0.85 0.91 0.88 0.88 0.74 n/a n/a 1.07 1.16 0.97 1.07 1.02 0.83 0.67 0.66 0.97 0.95 0.88 0.81 0.97 0.86 0.90 n/a 1.02 0.66 0.79 0.82 1.05 0.71 1.06 1.04 0.86 0.85 0.86 0.94 1.06 1.08 1.02 0.97
S+ NS NS NS SNS SNS NS SNS NS NS
Pulses
Raw vegetables
Cooked vegetables
TE D
Total vegetables Potatoes
EP
Citrus fruit
Chyou17 1993
4b
Crosssectional
Men,
AC C
Other fruit
846 BPH and 5735 no
BPH (tissueconfirmed)
Total fruit Desserts
Beef Chicken Wieners Spam/lunchmeat
Low, high (ref: none) 1.06 1.25 0.89 0.98 1.01 0.79 0.91 1.01
Yes S+ NS NS NS 4
ACCEPTED MANUSCRIPT
1.06 1.03 0.98 0.96 0.94 0.92 1.01 0.69 0.98 0.99 1.09 0.91 1.06 0.93 0.59 0.92 1.01 1.08 0.87 1.00 0.76 0.92 1.03 0.94 1.20 1.04 1.16 1.14 1.26 1.08 1.12 1.04 1.05 0.99 0.99 1.09 0.91 0.79 1.07 1.06 0.79 1.07 0.99 1.04 0.95 0.82 1.00 1.21 1.09 1.12
NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS
Onion <4/wk 0.94 (0.80 -1.11), >=4 per wk 0.41 (0.24-0.72) Garlic intermediate use 0.89 (0.75-1.06), high
Onion and garlic, both significant inverse association
Galeone 18 2007
3b
Casecontrol
AC C
EP
TE D
M AN U
SC
RI PT
Vienna/pork sausage Bacon Eggs Char siu Shrimp Raw fish Dried fish Dried cuttlefish Fish cake Tofu Rice Miso soup Saimin/udon Corn, on the cob Corn, whole kernel Tomatoes, sliced Tomato juice Lettuce Celery Salted cabbage Pickled turnip Pickled plum Tsukudani Milk Fruit drinks (g/week)
BPH
Men (age <75), 1369 cases, 1451 controls
Surgical admission BPH
FFQ - onion intake (nonusers, infrequent users [fewer than 4 portions per week], regular users [4 or more portions per week])
Yes- age, site, BMI, education, calorie intake, 5
ACCEPTED MANUSCRIPT
Incident BPHmedical or surgical treatment or repeated elevation (>14) on AUA-SI
new surgically treated BPHhistologically confirmed, dx within 1 yr
FFQ- intake assessed in quintiles
Surgery for BPH (n=1589) or AUASI score of 15-35 (n=1934)
131 item validated FFQ
Lagiou21 1999
3b
Casecontrol
Men, 184 cases, 246 controls
Suzuki20 2002
2b
Prospecti ve cohort,
Men, 3523 BPH and 24388 no BPH
8 year
M AN U
7 year follow-up
FFQ - Macronutrients, micronutrients, diet supplements, food groups
with BPH
activitylevel , smoking, EtOH
Fat intake (highest vs lowest quintile) HR 1.31 (1.05, 1.63), Polyunsat fats (high v. low quintile) HR 1.27 (1.03, 1.57), Zinc (high vs low quintile) 0.69 (0.50-0.96), Vegetables ( 4 vs <1 /day) HR 0.68 (.50-.92), Red meat daily (vs. <1/week) HR 1.38 (1.01-1.88)
Total Energy NS, Total and polyunsaturat ed fats S, Antioxidants NS, Total and dietary Zinc S, Lycopene/Zinc /Vit D S (weak), Red meat S, Vegetables S
Yes- age, race, waist/hip ratio, TEI
Fruits OR per quintile increase 0.84 (0.72– 0.97), Added lipids OR per quintile 1.28 (1.111.48), Zinc OR per daily increase 1.89 (1.03– 3.46)
Fruits S-, added lipids S+, zinc S+
Yes- age, height, BMI, education, TEI
TEI, highest vs. lowest quintile for BPH
S+
Yes
SC
Men (age > 54), 4770
TE D
Prospecti ve cohort,
EP
2b
AC C
Kristal19 2008
use 0.72 (0.57 -0.91) per week], regular users [4 or more portions per week]) and garlic use (none or low, intermediate, high)
RI PT
and garlic use (none or low, intermediate, high)
S+ OR: 1.29; 95% CI: 1.14, 1.45; and BPH
NS 6
ACCEPTED MANUSCRIPT
symptoms OR: 1.43; (95%CI 1.23, 1.66)
follow-up
S+
3b
Casecontrol
Men, 1369 cases, 1451 controls
Surgery for BPH (BPH defined as need for surgery)
AC C
Tavani22 2006
EP
TE D
M AN U
SC
RI PT
Energy-adjusted total protein intake with total BPH (OR 1.18; 1.05, 1.33) and BPH surgery (1.26; 1.06, 1.49).
FFQ - structured
Energy-adjusted total fat intake - not associated with BPH
Eicosapentaenoic, docosahexaenoic, and arachidonic acids – associated with moderate increase in BPH Carotene - OR 0.8 a-carotene - OR 0.83 b-carotene - OR 0.82 CisBCarotene - OR 0.82 Sodium - OR 1.3 Zinc
Variable
Yes
BPH: benign prostatic hyperplasia, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, FFQ = Food frequency questionnaire, OR = Odds ratio, TEI = Total energy intake, RR = Relative risk, HR = Hazard ratio 7
ACCEPTED MANUSCRIPT
Supplemental Table 2B. Incontinence and Diet - Detailed Summary of Articles Population, N
RCT,
Women (overweigh t, prediabetic), 1957
UI 1+/week,
Women, 4592
SUI at least several times/ month
2b
Prospecti ve cohort, 1 year follow-up
Diet Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted?
OR 0.76 (0.61-0.95) OR 0.80 (0.64-1.01) OR weekly urge not reported
SNS NS
Yes
SC
SUI 1+/week,
Intervention of a low-fat diet and 150 min/week of moderate-intensity physical activity
RI PT
Comments
UUI 1+/week, ; (Q)
M AN U
2.9 year mean follow-up
LUTSOutcome(s)
per day Protein (g) Total fat (g) Monounsaturated fatty acids (g) Saturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrates (g) Starch (g) Sugars (g) Cholesterol (mg) Fiber (g) Retinol (μg) Carotene (μg) Thiamin (mg) Riboflavin (mg) Niacin (mg)
TE D
Dallosso23 2004
1b
Study Design, Duration Followup
EP
Brown9 2006
Oxford Level
AC C
Author /Year
Quintiles (2-5 vs 1) 1.33 1.35 1.73 1.23 1.38 1.35 1.27 2.02
NS S+
1.10 1.52 1.55 1.57
NS
1.08 1.46 1.08 2.02
S+
1.22 1.11 1.16 0.95 0.95 0.68 0.59 0.73 0.87 0.93 0.68 0.85 1.22 0.94 0.74 0.70 1.09 1.24 1.34 2.09 1.09 0.88 1.02 0.76 1.28 1.12 1.60 1.60 0.96 1.02 0.86 1.07
NS S- (p=0.05) NS SS+ NS NS NS
Yes
8
ACCEPTED MANUSCRIPT
NS NS NS NS S+ NS NS NS NS NS NS NS S+ NS NS NS NS NS
OAB
OAB S-
SC
RI PT
0.92 0.99 1.12 0.82 0.84 1.07 0.92 0.93 1.10 1.31 1.08 0.92 1.12 0.71 1.12 0.92 1.52 1.27 1.84 1.66 0.84 0.62 0.76 0.82 0.99 1.03 1.23 1.20 1.10 1.13 1.13 0.73 0.73 0.73 0.81 0.81 0.79 0.93 1.12 0.85 0.86 0.94 0.99 0.90 0.95 0.98 0.82 0.80 1.40 1.57 1.89 0.52 0.78 1.04 1.15 1.14 1.20 1.10 0.91 1.05 1.17 1.18 0.98 0.94 1.07 0.82 0.83 0.82 0.99 0.93 1.03 1.00
Prospecti ve cohort, 1 year follow-up
Women, 5873 (OAB analyses), 5682 (SUI analyses)
OAB at least several times/ month; SUI at least several times/ month
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (daily) Dairy & eggs (5-7, 8-9, 10-12, 13+/week)
EP
2b
AC C
Dallosso24 2003
TE D
M AN U
Vitamin B6 (mg) Vitamin B12 (μg) Vitamin C (mg) Vitamin D (μg) Vitamin E (mg) Total folate (μg) Calcium (mg) Iron (mg) Potassium (mg) Zinc (mg) Sodium (mg) Selenium (μg) Iodine (μg) Magnesium (mg) Copper (mg)
No
0.61 0.71 0.64 0.88
0.98 0.92 0.96 0.88 0.86 1.07
0.94 1.02 1.05 1.00 0.89 0.85
NS NS
NS NS
NS 1.05 0.98
9
ACCEPTED MANUSCRIPT
NS
1.13 1.03 0.89 1.11
NS
1.18 1.11 1.41 0.65
NS S-
0.75 0.62 0.78 0.80
NS SUI NS
SC
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (daily) Dairy & eggs (5-7, 8-9, 10-12, 13+/week) Milk (280-424ml, 425567ml, 568+ml/day) Bread (>daily) Sweets & snacks (1, 2, 34, 5+/day)
1.00
RI PT
Milk (280-424ml, 425567ml, 568+ml/day) Bread (> daily) Sweets & snacks (1, 2, 34, 5+/day)
AC C
EP
TE D
M AN U
SUI 0.99 0.81 0.96 0.81
1.16 1.22 0.95 0.79 0.57 0.78
0.96 1.02 1.27 1.30 1.06 0.96
NS S-
NS NS
NS 0.99 0.87 NS 0.86 NS 1.10 0.86 0.88 0.93
1.21 1.09 1.36 0.73
NS S-
10
ACCEPTED MANUSCRIPT
Maserejian 93 2010
4b
Schnelle11 2010
1b
Subak12 2009
1b
Crosssectional
RCT,
Soy-free diet (control) vs. Soy-rich diet
Women, 2060
UI, modsevere (Sandvik Index)
TEI, Carbohydrate, Protein, total fat, saturated: polyunsaturated fat ratio (FFQ)
TEI - quintile 5 vs 1
UI episodes
Toileting assistance, exercise, choice of food/snack/fluid every 2 hour for 8 hours/day for 3 months
n/a
All other NS
Men & Women in nursing homes, 112
TEI S+, Carbs NS, Protein NS, total fat NS, SFA:PUFA ratio S+
Yes
Intervention - increase in fluid intake, caloric intake and weight
more fluid = more UI
No
Mean weekly number of UI episodes decreased by 47% in intervention group, compared with 28% control group (P=0.01).
S+ (UI)
n/a
OR 2.86 (1.56-5.23); SFQ:PUFA ratio (quintile 5 vs 1) OR 2.48 (1.22-5.06)
RCT
AC C
EP
3 month follow-up
UUI- S,
UUI, SUI, Urgency, Frequency
RI PT
12 week follow-up for each intervent ion
Soy-free control diet: increased UUI (22.2 vs 11.1, p< 0.05)
Women (peri/post menopausa l), 36
SC
Small crossover RCT,
NS
M AN U
2b
TE D
Manonai10 2006
0.77 0.99 1.03 1.07
Women, 226 weight loss program, 112 controls
UI, SUI, UUI after 6 months
Standard reduced calorie diet (1200 to 1500 kcal/day) - no more than 30% of calories from fat; Increase physical activity
11
ACCEPTED MANUSCRIPT
Compared with control group, intervention group had greater decrease in frequency of SUI (P=0.02), but not UUI (P=0.14).
UI
Prospecti ve, nonrandomiz ed Cohort (analysis using RCT
Baseline dietary phytoestrogen
Women, 226 weight loss program, 112 controls
Total UI, SUI and UUI episodes/wk (D)
AC C
2b
SC
Women, 1459
10 year follow-up Wing14 2010
M AN U
Prospecti ve cohort,
NS (UUI)
OR all NS
S+ (UI, SUI, UUI) NS
Yes
TE D
2b
S+ (SUI)
Higher proportion of intervention group than control group had >=70% reduction in frequency of all UI (P<0.001), SUI (P=0.009), and UUI (P=0.04).
EP
Waetjen94 2013
RI PT
(Interventio n group had mean weight loss 8.0% (7.8 kg), compared with 1.6% (1.5 kg) in control group (P<0.001)).
24h urine loss (pad
Weight loss program: Calorie and fat restricted diet of 1,200 - 1,800 kcal/day; < 30% of calories from fat
Yes
Ref: Weight gain <5% weight loss – no change
5-10% weight loss – 5-10% weight loss
53-63% fewer total UI/wk at 6/12/18 months (p<0.05)
5-10% weight loss 12
ACCEPTED MANUSCRIPT
data),
test)
>=10% weight loss
at 6/12/18 months:
43-56% fewer Urge UI/wk at 6/12/18 mo (p<=.001, .02 and .06)
S+ Total
RI PT
18 month follow-up
68-70% fewer Stress UI/wk at 6/12/18 mo (p<=0.05)
SC
50-56% less urine loss on pad test at 6/12/18 mo (p>.05)
S+ Stress S+ Urge (except NS at 18 mo) Pad test NS
M AN U
>10% weight loss – 52-66% fewer total UI/wk at 6/12/18 months (p<0.001)
AC C
EP
TE D
74-77% fewer Stress UI/wk at 6/12/18 mo (p<.02) 30-62% fewer Urge UI/wk at 6/12/18 mo (p<.01) 55-56% less urine loss on pad test at 6/12/18 mo (p=.01, .02, .10)
>10% weight loss at 6/12/18 months: S+ Total S+ Stress S+ Urge Pad test NS (borderline S+ p~0.05 at 13
ACCEPTED MANUSCRIPT
12/18 mo)
AC C
EP
TE D
M AN U
SC
RI PT
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, OAB = Overactive bladder, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial, TEI = Total energy intake
14
ACCEPTED MANUSCRIPT
Supplemental Table 2C. OAB/LUTS (non-UI) and Diet- Detailed Summary of Articles Populatio n, N
Prospecti ve cohort,
Women, 5816
LUTSOutcome(s)
Diet Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted?
PER DAY Protein (g) Total fat (g) Monounsaturated fatty acids (g) Saturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrates (g) Starch (g) Sugars (g) Cholesterol (mg) Fiber (g) Retinol (μg) Total carotene (μg) Thiamin (mg) Riboflavin (mg) Niacin (mg) Vitamin B6 (mg) Vitamin B12 (μg) Vitamin C (mg) Vitamin D (μg) Vitamin E (mg) Total folate (μg) Calcium (mg)
Quintiles (2-5 vs 1) 0.95 0.56 0.86 0.87 0.80 0.95 1.23 0.78
SC
OAB at least several times/month
RI PT
Comments
Yes NS NS
0.71 0.76 0.97 0.80 0.77 0.79 1.27 0.93
NS NS
0.82 0.85 0.86 0.72 1.19 1.31 1.01 1.22 1.18 0.88 1.11 0.82 0.94 0.89 1.31 1.33 0.87 0.96 1.05 0.85 1.22 0.96 0.88 1.24 0.63 1.13 0.83 0.94 0.89 1.05 0.97 0.95 0.68 0.74 0.65 0.72 1.02 0.74 1.08 1.22 0.66 0.67 0.65 0.70 0.72 0.93 0.62 0.98 0.75 0.91 0.75 0.98 1.25 1.15 1.05 1.33 0.99 0.73 0.51 0.75 1.09 1.09 1.11 1.01
NS NS NS NS NS NS NS NS NS NS NS NS NS NS SNS NS
M AN U
1 year follow-up
TE D
2b
Study Design, Duration Followup
EP
Dallosso30 2004
Oxford Level
AC C
Author /Year
15
ACCEPTED MANUSCRIPT
SC
Men, 4382
OAB at least several times/month
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (>=daily) Dairy & eggs (5-7, 8-9, 1012, 13+/week) Milk (280-424ml, 425567ml, 568+ml/day) Bread (more than daily) Sweets & snacks (1, 2, 3-4, 5+/day)
1.13 1.15 0.91 1.15
M AN U
Prospecti ve cohort,
TE D
1 year follow-up
EP
2b
AC C
Dallosso31 2004
0.90 0.94 0.76 1.01 1.11 0.90 0.99 1.29 0.89 0.83 0.81 0.96 0.69 0.60 0.83 0.99 0.87 0.63 0.85 0.90 0.82 0.77 0.72 0.80 0.66 0.89 0.80 0.67 0.94 0.96 1.02 1.36 0.85 0.84 0.65 0.99 0.91 0.89 0.94 1.05
RI PT
Iron (mg) Potassium (mg) Zinc (mg) Sodium (mg) Selenium (μg) Iodine (μg) Magnesium (mg) Copper (mg)
NS NS S- (P=0.05) NS NS NS NS NS NS
NS
1.05 1.40 0.77 1.08 0.99 0.94
S+ (p=0.05) NS
0.84 0.95 1.17 1.38 1.03 0.91
NS NS
1.19 1.08 0.86
NS
1.04
NS
1.19 0.93 0.93 1.04
NS
1.09 1.12 0.96 1.06
NS NS
No
16
ACCEPTED MANUSCRIPT
McGrother 32 2012
2b
Prospecti ve cohort,
Women age >39), 3411
Incident OAB (Q)
Dietary GI, TEI (FFQ)
NS
No direct relationship between total energy index or GI with new OAB (no numbers)
NS; NS
RI PT
1 year follow-up
0.82 0.80 1.02 0.99
2b
Study Design, Duration Followup
Population, N
Prospecti ve cohort,
Men and Women, 2825
4b
Crosssectional
AC C
Erickson25 2012
AUA-SI scores
Diet Variable(s)
Men, 1385
"LUTS" - difficulty voiding and/or bladder does not feel empty
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Baseline Vit C intake and Followup Vit C intake (FFQ)
Q4 v Q1 - 0.63 (progression of disease); Men: Recent Vit C intake = improved symptoms. Women: recent Vit C intake = worse storage symptoms (OR 1.66 (1.18 2.35)
Baseline Vit C = decreased progression; Current Vit C = decreased symptoms in men, increased in women
Yes
Overall dietary quality - 3 tertiles from HEI score; Poor diet (lowest vs. highest tertile) . Source: USDA Healthy Eating Index (HEI)-
Poor diet- OR 1.7 (95% CI 1.05-2.90)
LUTS- poor diet quality, S+
Yes
EP
5 year follow-up
LUTSOutcome(s)
M AN U
Curto29 2015
Oxford Level
TE D
Author /Year
SC
OAB = Overactive bladder, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, GI = Glycemic index, TEI = Total energy intakeSupplemental Table 2D. General Urinary Symptoms and Diet - Detailed Summary of Articles
17
ACCEPTED MANUSCRIPT
derived from 24 hr diet recall
Crosssectional
Men, 1545
"Moderate to severe Prostatism" = AUA-SI >=8)
Questionnaire/int erview - 24 hr recall - daily consumption calories, fat, protein, carbohydrate
Moderate to severe LUTS (>=8 AUA-SI), voiding symptoms (>=5), storage symptoms (>=4)
TEI, Carbohydrate, Protein, total fat, fat types, sodium (FFQ)
Crosssectional
Women, 2060
EP
4b
Moderate to severe LUTS (>=8 AUA-SI), voiding symptoms (>=5), storage symptoms (>=4)
AC C
Maserejian27 2011
No numbers given
Calories NS,
No
Fat NS,
RI PT
Men (age >49), 514
SC
4b
Crosssectional
Greater TEI assoc with higher LUTS score (continuous) and storage symptoms (p trend <0.01);
Protein NS, Carbohydrate NS
Carbohydrate NS,
Yes
Total fat NS, Protein intake S - (voiding sx)
Protein (quintile 5 vs 1) OR 0.35 (0.17-74);
TE D
Maserejian26 2009
4b
M AN U
Lee95 1997
TEI, Carbohydrate, Protein, total fat, fat types, sodium (FFQ)
weak association polyunsaturated fat with storage symptoms. Sodium (quintile 5 vs 1) OR 2.25 (1.26-4.03) LUTS: TEI- quintile 5 vs 1 OR 1.77 (1.01-3.09); Post micturition sx: Saturated fats (quintle 5 vs 1) 3.94 (1.57-9.89)
TEI S+
Yes
Monounsat fat NS Carbohydrates NS Sodium NS Protein S + (nocturia)
18
ACCEPTED MANUSCRIPT
Wong28 2007 4b
Crosssectional
Men, 2000
Chinese AUA-SI
Dietary total isoflavone (mg) (FFQ)
Ref: <5.1mg
S-
5.1 to 9.5 mg: OR 0.59 (95 % CI 0.44, 0.80)
(subjects with dietary total isoflavone of more than 5.1 mg were significantly less likely to suffer from more severe LUTS)
RI PT
9.6 to 14.3 mg: OR 0.81 (95% CI 0.61, 1.09) 14.4 to 21.7 mg: OR 0.68 (95% CI 0.51, 0.92)
Yes - TEI
AUA-SI Uroflowmetry
Randomized to placebo vs. 300 or 600 mg/day secoisolariciresino l diglucoside (SDG)
AUA-SI score changed: -3.67 +/- 1.56, -7.33 +/- 1.18, and 6.88 +/- 1.43 (mean +/- SE; P = .10, < .001, and < .001 compared to baseline)
M AN U
4 month follow-up
Men, 78
TE D
RCT,
EP
1b
AC C
Zhang13 2008
SC
>=21.8 mg: OR 0.73 (95% CI 0.54, 0.98) S(secoisolariciresinol diglucoside use associated with fewer LUTS)
No
Quality of Life score improved by -0.71 +/- 0.23, 1.48 +/- 0.24, and -1.75 +/0.25 (mean +/- SE; P = .16 and .012 compared to placebo and P = .10, < .001, and < .001 compared to baseline)
Number of subjects with LUTS change from "moderate/severe" to 19
ACCEPTED MANUSCRIPT
"mild" increased by 3, 6, and 10 (P = .19, .03, and .01 compared to baseline)
RI PT
Maximum urinary flows and postvoid volumes NS
Population, N
4b
Crosssectional
Men, 23 BPH, 11 controls
Spigt34 2004
4a
Case series,
Men, 44
2 month follow-up
Spigt33 2006
1b
RCT,
LUTS vs. no LUTS
AUA-SI total score, QOL
AC C
Matthiesen96 1999
LUTSOutcome(s)
Men, 138
Fluid intake Variable(s)
AUA-SI total score, AUA-SI
Results: OR, RR, other
M AN U
Study Design, Duration Follow-up
Results: Significance, Direction
Analyses adjusted? Comments
24-hour fluid intake (exclude fluid in food) (D)
No difference in 24hour fluid intake between patients with LUTS vs. controls without LUTS.
Subjects were asked to increase fluid intake by 2L per day for 8 weeks
Score increased from S, + 7.9 to 8.9 (p = 0.028) after increase in fluid intake. QOL decreased by 0.2 (p=0.30). No comparison group.
No
Subjects randomized
No difference in total score, voiding
No
TE D
Oxford Level
EP
Author/Year
SC
American Urological Association Symptom Index = (AUA-SI), LUTS = Lower urinary tract symptoms, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, TEI = Total energy intakeSupplemental Table 3A. BPH and Fluid Intake- Detailed Summary of Articles
NS
NS (total scores)
No
20
ACCEPTED MANUSCRIPT
QOL, AUA-SI storage symptoms, and voiding symptoms
to increase fluid intake by 1.5L per day for 6 months, versus placebo
score, and QOL between groups. AUA-SI storage scores worse in subjects who increased fluid intake (effect size=1.3, p<0.001).
S, + (storage scores)
RI PT
6 month follow-up
4b
Study Design, Duration Follow-up
Population ,N
Crosssectional
Men & Women, 128
LUTSOutcome(s)
Nocturnal micturition (nocturia)
Fluid intake Variable(s)
1) Daily fluid intake 2) Evening fluid intake
Johnson36 2005
2b
Prospectiv e cohort, 2 year follow-up
AC C
EP
Griffiths97 1993
Oxford Level
TE D
Author/Year
M AN U
Supplemental Table 3B. Nocturia and Fluid Intake- Detailed Summary of Articles
Men, 1289
2-year Incident nocturia
SC
BPH: benign prostatic hyperplasia, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, D = Diary, American Urological Association Symptom Index = (AUA-SI), OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial
Nighttime fluid intake (y/n), amount of nighttime
Results: OR, RR, other
1) Positive correlation between daily fluid intake and nocturia (0.21, p<0.02),
Results: Significance, Direction
Analyses adjusted? Comments
1) S, +
No
2) NS
2) No correlation between evening fluid intake and nocturia (0.17, p>0.05). Fluids at bedtime
NS
0.97 (0.76-1.25)
NS
Yes
21
ACCEPTED MANUSCRIPT
intake
Amount bedtime fluids 1.05 (0.96, 1.15)
Men with BPH, 23; Controls 11
Soda37 2010
4a
Case series,
24-hour fluid intake (exclude fluid in food) (D)
No statistical difference (but positive trend) in 24hour fluid intake and nocturnal polyuria
NS
No
Nocturia indices (nocturnal frequency, nocturnal urine volume, nocturia index, nocturnal polyuria index, nocturnal bladder capacity index), Urinary frequency
Fluid intervention (restriction of fluid intake) and subjects asked to refrain from excessive hours in bed keep bed warm, and perform moderate exercise
Fluid restriction (plus other interventions) associated with reduction of nocturnal frequency (p<0.001), nocturnal urine volume (p<0.001), nocturia index (p<0.001), nocturnal polyuria index (p=0.004), nocturnal bladder capacity index (p=0.002), and urinary frequency (p=0.007). No comparison group. The effect of fluid restriction could not be isolated from other interventions.
S, +
No
Subjects asked to reduce water and food intake so urine output
Nocturia decreased from mean 4.1 to 3.1/night, p<0.0001.
S, +
No
Tani38 2014
4a
Case series, 1 month follow-up
AC C
EP
TE D
4 week follow-up
Men & Women, 47 men and 9 women
Presence vs. absence of nocturnal polyuria
Men, 65
Numbers of nocturnal voids (nocturia)
RI PT
Crosssectional
SC
4b
M AN U
Matthiesen96 1999
22
ACCEPTED MANUSCRIPT
reduced to 30 mL/kg. 1b
RCT, 10 week follow-up
Women, 307
Nocturnal voids (nocturia)
Daily fluid intake (D)
None of the changes in the variable outcomes differed by treatment
NS
Yes
RI PT
Zimmern35 2009
group at 10 weeks.
AC C
EP
TE D
M AN U
SC
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, D = Diary, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial
23
ACCEPTED MANUSCRIPT
Supplemental Table 3C- OAB/LUTS (non-UI) and Fluid Intake- Detailed Summary of Articles Population, N
Prospective cohort,
Women, 6424
LUTSOutcome(s)
Incident OAB (Q)
1 year follow-up
Crosssectional
Results: OR, RR, other
Men & Women, 128
Diurnal micturition (daytime frequency)
S, +
1) Daily fluid intake
1) Positive correlation for daily fluid intake and diurnal micturition (0.33, p<0.002),
S, +
2) Evening fluid intake
Cross-over RCT, 4 day follow-up per each interventio
Men & Women, 24
Frequency, Urgency, Nocturia (D)
Fluid total increased by 25% and 50% and decreased by 25% and 50%
Analyses adjusted? Comments
Carbonated drinks associated with new OAB (OR 1.41, 95% CI 1.021.95), comparing
EP 1b
AC C
Hashim40 2008
Results: Significance, Direction
Consumption of various fluid (carbonated drinks, water, tea, coffee, wine, beer, port & spirits, fruit juices) (FFQ)
TE D
Griffiths97 1993 4b
Fluid intake Variable(s)
RI PT
2b
Study Design, Duration Follow-up
SC
Dallosso24 2003
Oxford Level
M AN U
Author/Year
Yes
NS
No
S, +
2) Positive correlation for evening fluid intake and diurnal micturition (0.29, p<0.002). Frequency, urgency and nocturia all decreased with 25% (all p<.001) and 50% reduction (all p<0.05) in fluid intake Frequency increased with
Fluid reduction: S, + (frequency, urgency,
No; Small numbers, especially in 50% fluid reduction 24
ACCEPTED MANUSCRIPT
25% (p=0.03) and 50% (p=0.002) increase in fluid intake
n
nocturia)
(12) or increase (14)
1) Daily total fluid intake
Positive correlation for urinary frequency and daily total fluid intake, p=0.04 (but not for daily caffeinated fluid intake)
S, +
No
SC
Urinary frequency
2) Daily caffeinated fluid intake
M AN U
Women with UI (urgency, stress, mixed), 256
TE D
Crosssectional
(frequency)
EP
4b
S, +
AC C
Segal99 2011
RI PT
Fluid increase:
25
ACCEPTED MANUSCRIPT
4b
Crosssectional
Women, 2244
1) Urinary frequency
1) Women with frequency 2.5 times more likely to drink >= 2L of fluid per day (OR 2.4, p<0.001), 3.5 times more likely to drink >=6 cups coffee per day (OR 3.6, 95%CI 2.3-5.7, p<0.001), and 1.5 times more likely to drink >= 1 glass alcohol per week (OR 1.4, 95%CI 1.1-1.6, p<0.001).
1) S, +
No
2) S, +
Swithinbank39 2005
1b
Cross-over RCT (caffeine restriction with either increased
AC C
EP
TE D
M AN U
SC
2) Urgency
Daily fluid intake (more than vs. less than 2L/day), coffee, tea, and alcohol intake (amount)
RI PT
Selo-Ojeme98 2013
Women with USI or IDO, 69
1) Frequency 2) Urgency
Fluid increase to 3L daily vs. fluid decreased to 750 mL daily, both arms with caffeine
2) Similar observations for urgency except no association between urgency and fluid intake. Women with urgency 3.5 times more likely to drink >= 6 cups coffee per day (OR 3.7, 95%CI 2.5-5.8, p<0.001), and 1.5 times more likely to drink >= 1 glass alcohol per week (OR 1.5, 95%CI 1.2-1.8, p=0.002). Increasing fluid intake significantly increased frequency and urgency (both p<0.003). Decreasing fluid intake significantly decreased
1) S, + (bidirectional)
n/a
2) S, + (bidirectional)
26
ACCEPTED MANUSCRIPT
fluid vs. decreased fluid),
restriction
frequency (p<0.003) and urgency (p=0.006).
Daily fluid intake (D)
No outcomes differed by treatment group.
RCT, 10 week follow-up
Women, 307
1) 24 hour frequency (D) 2) Selfreported urgency (Q)
NS
Yes
SC
1b
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm -
AC C
EP
TE D
M AN U
Zimmern35 2009
RI PT
4 week follow-up
additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food frequency questionnaire, D = Diary, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial, USI – Urodynamic stress incontinence, IDO = Idiopathic detrusor overactivity
27
ACCEPTED MANUSCRIPT
Supplemental Table 3D - UI and Fluid Intake- Detailed Summary of Articles
2b
Study Design, Duration Follow-up
Population, N
Prospectiv e cohort,
Women, 6424
LUTSOutcome(s)
Fluid intake Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Incident SUI (Q)
Consumption of carbonated drinks associated with new SUI (OR 1.62, 95% CI 1.182.22, comparing
S, +
Yes
NS
SC
1 year follow-up
Consumption of various fluids (carbonated drinks, water, tea, coffee, wine, beer, port & spirits, fruit juices) (FFQ)
RI PT
Dallosso24 2003
Oxford Level
M AN U
Author/Year
Other fluid types NS
RCT, 5 week follow-up
Men, 3960
Women, 32
SUI, UUI, any UI, moderate to severe UI (Q)
Daily total fluid intake (structured dietary recall)
UI episodes
Daily total fluid intake
TE D
2b
Crosssectional
EP
Dowd41 1996
4b
AC C
Davis60 2013
(14 subjects randomized to increase fluid intake by 500 mL/d, 10 to reduce fluid by 300 mL/d, and 8 to maintain current fluid
No association between water intake,
NS
Yes
“Adherence to fluid intake NS protocol was poor, and consequently, quantitative results were nonsignificant”
No
any UI or moderate to severe UI.
*Poorly designed RCT, with poor adherence to fluid protocols, small no. of 28
ACCEPTED MANUSCRIPT
intake)
Crosssectional
Women, 4309
Men & Women, 128
SUI, UUI, any UI, moderate to severe UI, (Q)
Daily total fluid intake (structured dietary recall)
Water intake in upper quartile (>1.3L/d) associated with less moderate/severe UI (p<0.001), but not any UI.
S, -
Diurnal UI, nocturnal UI (gram/d) (Pad test)
1) Daily total fluid intake
1) Positive correlations for daily fluid intake and diurnal UI (0.34, p<0.02) and nocturnal UI (0.32, p<0.02) in subjects with IDO,
1) S, +
2) Evening fluid intake
RI PT
4b
Crosssectional
1b
Cross-over Men & RCT, Women, 24 4 day follow-up per each interventi on
UUI episodes (D)
AC C
Hashim40 2008
EP
TE D
M AN U
Griffiths97 1993
4b
SC
Gleason58 2013
subjects
Fluid total increased by 25% and 50% and decreased by 25% and 50%
2) No correlation for evening intake and diurnal UI but positive correlation with nocturnal UI (0.28, p<0.05)
No
NS
No
S, +
2) NS S, +
No change in urgency incontinence episodes after any of the interventions
Fluid reduction: NS
Fluid increase: NS
No Small numbers, especially in 50% fluid reduction (12) or increase (14) 29
ACCEPTED MANUSCRIPT
4b
Crosssectional
Women, 298
Presence vs. absence of UI
Daily total fluid intake
Mean daily fluid intake among UI vs. no UI was not different (p=0.62)
NS
No
Miller100 2011
4b
Crosssectional
Women, 352
UI episodes per day (3-day D)
1) Fluid intake during daytime
High fluid intake during daytime and high volume of bladder irritants consumed associated with more UI episodes in this cluster analysis, p=0.02 and p<0.001 respectively.
S, +
No
Women with UI (urgency, stress, mixed), 256
1) Urgency incontinence
1) Daily total fluid intake
Men & Women in nursing homes, 112 (~80% women)
UI episodes (observed with physical check by staff)
S, +
RCT, 3 month follow-up
2) Daily caffeinated fluid intake
TE D
1b
Crosssectional
EP
Schnelle11 2010
4b
AC C
Segal99 2011
M AN U
SC
2) Volume of bladder irritants consumed (carbonated beverages, coffee, tea, alcohol)
RI PT
Hirayama101 2011
Increased fluid intake (observed) (Multimodal intervention: toileting assistance, exercise, increased fluid and food offered between meals)
Positive correlation between UUI and daily caffeinated fluid intake, p=0.021 (but not with daily fluid intake)
S, +
Increased fluid intake associated with increase in UI episodes (coefficient not provided)
S, +
No
NS
Yes Note: complex intervention , minimal information provided
30
ACCEPTED MANUSCRIPT
1b
Cross-over Women with USI or RCT, IDO, 69 4 week follow-up
UI episodes weekly
Fluid increased to 3L daily vs. fluid decreased to 750 mL daily, both arms with caffeine restriction
Increasing fluid intake increased weekly UI (p=0.006), while decreasing fluid intake reduced weekly UI (p=0.006).
S, + (bidirectional)
n/a
Tomlinson55 1999
4a
Case series,
UI episode (daytime), grams of incontinence (pad weight)
Targeted daily fluid intake to 18002400 mL daily for those who drank <1500 mL or >4000 mL daily. Subjects also asked to reduce caffeinated fluid, reduce nighttime fluids, and do timed voiding
Among 21 women
S, + (univariate)
Yes
SC
encouraged to increase daily fluid intake, 85.7% (n = 18) did and 66.7% (n = 14) decreased UI.
NS (multivariate)
2b
Prospectiv e cohort,
Women, 65167
Incident UI: 1) any UI
2 year follow-up
AC C
Townsend42 2011
EP
TE D
M AN U
2-4 weeks follow-up
Women with UI (SUI, UUI, mixed), 41
RI PT
Swithinbank39 2005
2) frequent UI (>= 1/ week) 3) SUI 4) UUI
Daily total fluid consumption (FFQ)
Sample size possibly too small for multivariate analysis.
In multivariate analysis, increase in intake resulted in increase in volume of urine voided, without increasing UI.
No association between fluid consumption and incident UI (any UI, frequent UI, SUI, UUI, or MUI).
NS
Yes
HR 1.04 (0.98-1.09), 0.98 (0.88-1.08), 0.90 (0.761.06), 1.12 (0.88-1.42) & 1.11 (0.88-1.40) 31
ACCEPTED MANUSCRIPT
5) MUI
respectively,
RCT, 10 week follow-up
Women, 307
1) No. of incontinence episode/wk (D) 2) Selfreported pad use
No outcomes differed by treatment
NS
Yes
group.
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm -
TE D
3) Bothersome UI symptoms (Q)
Daily total fluid intake (D)
SC
1b
M AN U
Zimmern35 2009
RI PT
comparing top (1.1 L/d) vs. bottom (2.9 L/d) quintile fluid intake
AC C
EP
4) QOL (Q)
additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food frequency questionnaire, D = Diary, UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, OR = Odds ratio, RR = Relative risk, HR = Hazard ratio, RCT = Randomized controlled trial, USI = Urodynamic stress incontinence, IDO = Idiopathic detrusor overactivity
32
ACCEPTED MANUSCRIPT
Supplemental Table 4A. BPH and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
Crosssectional
Men, 1,335
LUTSOutcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
BPH (Q) vs. no BPH and no or mild LUTS
Coffee (cups/day- Q)
Never/rare- 1.0
S, +
Yes
NS, +
Age adjusted only
1-4 c – 2.20 (1.26– 3.85)
SC
Gass47 2002
Oxford Level
RI PT
Author/Year
BPH (Q) vs. no BPH and non-severe LUTS
M AN U
≥5 c - 2.74 (1.43– 5.25)
3b
Casecontrol
Men, 219 cases and 4669 controls
Surgically treated BPH
AC C
Morrison45 1978
EP
TE D
Never/rare- 1.0
Coffee (None vs. >=1/dayI)
1-4 c – 1.97 (1.16– 3.37) ≥5 c - 2.56 (1.37– 4.75) 0 c – 1.0 >=1c/day 1.3 (0.9-1.9)
33
ACCEPTED MANUSCRIPT
Morrison46 1992
3b
Casecontrol
Men, 910 cases and 2003 controls
Surgically treated BPH
Coffee (cups/day- TI)
<1 c – 1.0
NS, -
Yes
1 c – 0.88 (0.661.17)
RI PT
2 c – 0.81 (0.611.07) 3 c – 0.82 (0.591.13)
SC
≥4 c – 0.79 (0.581.08)
AC C
EP
TE D
M AN U
BPH: benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, I= interview, TI= telephone interview, Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
34
ACCEPTED MANUSCRIPT
Supplemental Table 4B. Nocturia and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
LUTSOutcome(s)
Crosssectional
Women, 3019
Nocturia (Q)
Prospective cohort,
Men, 1580
5 yr Incident Mild Nocturia (1-2; Q)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Caffeinated beverages after 6pm
Inverse association –
S, -
No
NS, +
Yes (but not for overall fluid intake)
Coffee-
Coffee- NS, +/-
Yes
0c
Tea- S, +
Coffee and tea in same model
Nocturia 2x as likely to occur in those who do not drink PM caffeine (p<0.0001)
Shiri48 2008
2b
5 year follow-up
M AN U
SC
Asplund50 2004
Oxford Level
RI PT
Author/Year
Coffee (cups/day, baseline) (Q)
0-1 1.0 2–3 1.4 (0.9–2.3) 4–5 1.1 (0.6–1.7)
TE D
≥ 6 1.1 (0.6–1.7)
5 yr Incident Mod-severe Nocturia (≥3; Q)
2-3 1.2 (0.5–2.9)
EP 4b
Crosssectional
AC C
Tettamanti53 2011
Women, 14031
Nocturia
0-1 1.0
4-5 1.3 (0.5–3.0) ≥ 6 1.9 (0.8–4.5) Coffee (cups/day; Q)
1.0
1-2 c 1.06 (0.94-1.19)
35
ACCEPTED MANUSCRIPT
3+c 0.96 (0.85-1.08)
Tea – 0c
1.0
RI PT
Tea (cups/day; Q)
1-2 c 1.02 (0.93-1.11) 3+c 1.18 (1.01-1.38)
AC C
EP
TE D
M AN U
SC
*Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
36
ACCEPTED MANUSCRIPT
Supplemental Table 4C. OAB/LUTS (non-UI) and Caffeine Intake- Detailed Summary of Articles Author/Year
Oxford Level
Study Design, Duration Followup
Population, N
LUTSOutcome(s)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted?
2b
RCT; Bladder training +/caffeine reduction,
Men & Women, 74 (90% women)
Frequency/24 hrs (D) Urgency/24 hrs (D)
Men, 1308
AUA-SI ≥8 with no prostate enlargement
TE D
Cross-sectional
AUA-SI ≥8 with prostate enlargement
EP
4b
AC C
Klein54 1999
M AN U
1 month followup
Caffeine reduction education
Frequency
S, +
35% vs. 23% reduction (p=0.037)
Caffeine (mg/day; Q)
Urgency
n/a (RCT) 78% completed outcome assessment
SC
Bryant51 2002
RI PT
Comments
S, +
61% vs. 12% reduction (p=0.002) None
1.0
1-200 1.56)
0.98 (0.61,
NS, +/-
Age only
201-400 1.21 (0.79, 1.86) 401+ 1.59)
1.00 (0.63,
None
1.0
1-200 1.75)
0.80 (0.36,
201-400 0.72 (0.33, 37
ACCEPTED MANUSCRIPT
1.55) 401+ 2.42) Women with USI, IDO, 69
Frequency (D) Urgency (D)
Cross-sectional
Women, 14,031
OAB (Q)
Coffee (cups/day; Q)
Cross-over RCT, 2 week follow-up per each
No
Women, 11
Frequency, Urgency (D) OAB symptoms
Coffee-
Coffee- NS, +/-
Yes
0c
Coffee and tea in same model
1.0
1-2 c 1.05 (0.89-1.25) 3+c 1.03 (0.86-1.23)
Tea (cups/day; Q) Tea –
EP 2b
AC C
Wells52 2014
NS, +/-
QOL- no change
TE D
4b
Frequency- no change Urgency- no change
QOL (Q)
4 week follow-up Tettamanti53 2011
Caffeine restriction
RI PT
Case series (Study is crossover RCT, but caffeine restriction done throughout in all (no controls),
SC
4a
M AN U
Swithinbank39 2005
1.04 (0.45,
0c
Tea- S, + 1.0
1-2 c 1.08 (0.95-1.24) 3+c Caffeine replacement with decaffeinated
1.34 (1.07-1.67)
Decreased voiding frequency (p<0.05) and urgency (p<0.01) on day 3 of diaries; reduced
S, +
Small sample with >20% loss to follow-up; 38
ACCEPTED MANUSCRIPT
intervention
and QOL (Q)
drinks
OAB symptoms (p<0.01)
small differences
AC C
EP
TE D
M AN U
SC
RI PT
OAB = Overactive bladder, QOL = Quality of life, AUA-SI = American Urological Association Symptom Index, USI – urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
39
ACCEPTED MANUSCRIPT
Supplemental Table 4D. UI and Caffeine Intake- Detailed Summary of Articles Author/Year Oxford Level
Study Design, Duration Followup
Population, N
LUTSOutcome(s)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted?
2b
RCT; Bladder training +/caffeine reduction,
Men & Women, 74
# UI episodes (D)
Men, 3,960
UI
Caffeine reduction
4b
Cross-sectional
M AN U
1 month follow-up
Davis60 2013
55% vs 26% reduction UI episodes (p=0.22)
+, NS
Caffeine (mg/d)
n/a (RCT) 78% completed outcome assessment, underpowered for outcome
SC
Bryant51 2002
RI PT
Comments
Any UI
Any UI - NS
≥75th% NS
Mod/severe UI
≥90th% NS
75th% +, S
Yes
th
TE D
≥75 % (≥234 mg/d) and ≥90th% (≥392 mg/d)
Cross-sectional
Women, 4,309
UI, Mod-severe UI
Mod/severe UI ≥75th% 1.69 (1.09, 2.61)
EP 4b
AC C
Gleason58 2013
90th% +, S
≥90th% 2.03 (1.09, 3.78) Caffeine, ≥75th% (≥204 mg/d) and ≥90th% (≥348 mg/d)
Any UI
Any UI
≥75th% 1.47 (1.07, 2.01)
75th% +, S
≥90th% 1.23 (0.70–2.12)
90th% +, NS
Yes
40
ACCEPTED MANUSCRIPT
Mod/severe UI
≥75th% 1.42 (0.98, 2.1)
75th% +, NS
≥90th% 0.90 (0.43–1.87)
90th% -, NS
RI PT
Mod/severe UI
SUI, UUI, MUI: all NS Cross-sectional
Women, 27,936
Any UI, Severe UI, SUI, UUI, MUI
Coffee (cups/d)
Any UI
Coffee
Yes
Coffee
Any UI NS
Tea and coffee in same model
1-2c. 1.0 (.8-1.1)
SUI +, S
SC
4b
M AN U
Hannestad59 2003
Tea (cups/d)
3+c. 1.0 (.9-1.1)
Severe MUI -, S UUI +, NS
4b
Cross-sectional
Men & Women, 683 men and 298 women
Any UI, SUI, UUI
AC C
Hirayama103 2012
EP
TE D
Tea
1-2c. 1.2 (1.1-1.2)
Tea-
3+c. 1.3 (1.2-1.5)
Any UI, SUI, MUI all +, S UUI +, NS
Caffeine (mg/d)
Men – Any UI
Any UI
0-55.8
Men +, NS
1.0
Yes
55.9-147 1.11 (0.52, 2.37) Women +/-, NS >147
1.36 (0.65, 2.88)
Men- UUI NS
UUI –Men +/-, NS
41
ACCEPTED MANUSCRIPT
SUI–Women +/-, NS Women – Any UI 0-51.2
1.0
RI PT
51.3-145 0.94 (0.48, 1.84) >145
1.12 (0.57, 2.22)
Women- SUI NS Women, 65,176
2-4 yr Incident UI:
Caffeine (mg/d; Q)
Any UI
SC
Prospective cohort,
Any UI, Frequent UI, UUI, SUI, MUI (Q)
1.0
Any UI +/-, NS
UUI +, S
300-449 1.02 (0.98–1.07)
SUI NS
0.98 (0.91–1.05)
Yes
Frequent UI +, S
150-299 0.98 (0.90–1.06)
≥450
TE D
4 year follow-up
M AN U
0-149
EP
2b
AC C
Jura56 2011
MUI NS
Frequent UI 0-149
1.0
150-299 0.98 (0.90–1.06) 300-449 1.06 (0.98–1.15) ≥450 1.19 (1.06–1.34)
UUI 0-149
1.0 42
ACCEPTED MANUSCRIPT
150-299 0.88 (0.72–1.07) 300-449 1.18 (0.97–1.44) 1.34 (1.00–1.80)
Kincade102 2007
4b
Cross-sectional
Women, 525
Urine loss (pad test)
RI PT
≥450
Caffeine (mg/d and ounces/d)
Moderate correlation between caffeine (oz/d) and UI episodes
SC
# UI episodes
Caffeine (oz/d)
No
+ correlation, S
Case series (Study is cross-over RCT, but caffeine restriction done throughout in all (no controls),
Women with USI, IDO, 69
# UI episodes
4b
Cross-sectional
AC C
4 week follow-up Tettamanti53 2011
Urine loss (24 Caffeine hr pad test) restriction
TE D
4a
Caffeine (mg/d)
Caffeine mg/d did not correlate with UI episodes or urine loss (g)
no correlation, NS
No differences in
No change, NS
No
Overall UI
Overall UI
Yes
Coffee-
Coffee - , S
0c
Tea -, NS
Coffee and tea in same model
pad weight, daily UI episodes and QOL
EP
Swithinbank 39 2005
M AN U
(r=0.53)
Women, 14,031
UI, SUI, MUI, UUI
Coffee (cups/d; Q)
Tea (cups/d; Q)
1.0
1-2 c 0.87 (0.7-1.06)
43
ACCEPTED MANUSCRIPT
3+c 0.79 (0.64-0.98)
SUI
Tea –
Coffee -, NS
0c
1.0
Tea -, S
RI PT
1-2 c 0.92 (0.79-1.07) 3+c 0.77 (0.58-1.02)
SC
SUI
UUI Coffee -, NS Tea -, NS
M AN U
Coffee-
Tomlinson55 1999
4a
Case series, 2-4 weeks followup
AC C
EP
TE D
0c
Women, 41
Urine loss (pad test) # UI episodes
1.0
MUI
1-2 c 0.86 (0.69-1.07)
Coffee -, NS
3+c 0.81 (0.64-1.01)
Tea -, NS
Tea – 0c
1.0
1-2 c 0.91 (0.77-1.08) 3+c 0.72 (0.53-0.99)
Caffeine reduction
Decrease in UI daytime episodes (p=0.07), no significant change in other outcomes
+, NS
Yes
44
ACCEPTED MANUSCRIPT
2b
Prospective cohort,
Two-year progression of UI, UUI, SUI, MUI
Caffeine intake over past year (mg/d; Q), Change in caffeine intake prior 4 years (stable, increase, decrease; Q)
Caffeine intake prior year and UI
Caffeine prior year
Yes
+/-, NS 0-149
1.0
150-299 0.99 (.83-1.18) 300-449 1.04 (.91-1.19) ≥450
0.87 (.7-1.08)
Caffeine change prior 4 years +/-, NS
SC
2 year follow-up
Women with moderate UI, 21,564
RI PT
Townsend57 2012
M AN U
UUI, SUI, MUI results – all NS
Change in caffeine intake and UI
Wells52 2014
2b
Cross-over RCT, 2 week follow-up per each intervention
AC C
EP
TE D
Stable 1.0
Women, 11
# UI episodes (D), UUI (Q)
Incr
1.08 (.95-1.22)
Decr
1.16 (1.02-1.31)
UUI, SUI, MUI: all NS Caffeine replacemen t with decaffeinate d drinks
No differences
No change, NS
Small sample with >20% loss to follow-up; small differences
45
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, USI = urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, DO= detrusor overactivity, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
46
ACCEPTED MANUSCRIPT
Supplemental Table 4E. Urodynamic parameters and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
Crosssectional
Women with UI, 131 DO and 128 SUI
DO seen on urodynamics
Women, 20
Urodynamic test parameters
LUTS-Outcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Caffeine (mg/d)(D); categorized Minimal (<100), Moderate (100-400), High (>400)
Min 1.0
2nd Urodynamics performed 30 min after 200 mg Caffeine ingested
Increase in detrusor pressure during filling (17 (0-42) vs. 11 (0-25), p<0.03)
S, + (detrusor pressure)
No difference in volume at first contraction, height of contraction or capacity
NS, +/- (others)
S, +
Yes Age, smoking
Mod 1.5 (0.1, 7.2) High 2.4 (1.1, 6.5)
Case series, 2 weeks between 1st and 2nd tests
TE D
4a
No
AC C
EP
Creighton43 1990
M AN U
SC
Arya44 2000
Oxford Level
RI PT
Author/Year
UI = Urinary incontinence, SUI, Stress urinary incontinence, DO = detrusor overactivity, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
Supplemental Table 5A. BPH and Alcohol Use- Detailed Summary of Articles 47
ACCEPTED MANUSCRIPT
Chyou17 1993
Oxford Level
2b
Study design, Duration Follow-up
Population, N
Prospective cohort,
Men, 6581
LUTSOutcome(s)
Alcohol Variable(s)
Results: OR, RR, other
Surgery for BPH
Alcohol (oz) per month,
Vs. non drinker Alcohol:
17 year (average) follow-up
Type of alcohol
<4 RR 1.02
SC
4-29 RR 0.91
TE D
M AN U
25+ RR 0.64
Analyses adjusted?
Case-control
Men, 1369 BPH and 1451 controls
Obstructive LUTS and max flow < 15 mL/sec refractory to treatment who had
Trend for Yes decrease in BPH incidence for total alcohol, Beer, Wine, Sake. Not significant for Spirits.
Beer: 361+ RR 0.66 (0.53-0.83) Wine: >4 RR 0.70 (0.52-0.94) Sake: >4 RR 0.72 (0.54-0.95)
EP 3b
AC C
Crispo104 2004
Results: Significance, Direction
Comments
RI PT
Author /Year
Spirits: 12+ OR 0.82 (0.67-1.02) Drinks/week, Duration of drinking, Age at starting
Duration drinking and Age starting drinking- NS
Drinks/week significant for trend only
No
Drink/week <3 OR 0.88 (0.62-1.24)
48
ACCEPTED MANUSCRIPT
surgery
drinking
3-4 OR 0.71(0.50-1.03) 5-6 OR 0.79(0.52-1.20) 7-8 OR 0.65 (0.41-1.02)
RI PT
>9 OR 0.65 (0.41-1.02) Chi square trend p=0.013 (for trend only)
3b
Case-control nested in a RCT
Men, 320 cases and 320 controls
Surgery for BPH
Self-reported alcohol use:
SC
Gann105 1995
M AN U
rare/never
1.0
1-3/mo
Only the group with 5+ drinks per week had significantly less surgery for BPH
Yes
0.50 (.23-1.08)
l/wk
0.76 (.38-1.52)
4b
Crosssectional
Men, 882
AC C Kang68 2004
4b
Crosssectional
Men , 17,772
1.01 (.53-1.94)
5 + /wk 0.51 (.29-.90)
Surgery for BPH or symptomatic LUTS and BPH based on selfreported prostate history and AUA-SI
Glasses alcohol per day/week :
BPH diagnosis by physician
Reference <5 g/day
EP
Gass47 2002
TE D
2-4/wk
<1 glass/wk 2-4 glasses/wk >=1 glass/d
BPH patients vs non symptomatic patients: <1 glass alcohol/week NS, but 2-4 and >=1 glass per day 0.46 (0.32– 0.66)
BPH OR:
NS for low alcohol Yes but significantly less surgery and symptoms for those who drank 2 or more drinks a day
Alcohol consumption
Yes
49
ACCEPTED MANUSCRIPT
5-15 g/day
0.8 (0.7-0.9)
15.1-30 g/day
0.8 (0.7-0.9) 0.7 (0.6-0.9)
30.1-45 g/day
0.7 (0.6-0.9) 0.6 (0.5-0.7)
45.1-60 g/day
Morrison46 1992
3b
Case-control
Men, 910 cases and 2003 controls
BPH Symptoms on AUA-SI and pathology
genetic variants & smoking, chewing tobacco & alcohol consumption
Null Genotype of GSTMI associated with increased risk of BPH with smoking, tobacco chewing or alcohol consumption
Selection bias nullifies results
No
Number of: beer/day 0≥5
Spirits: all strata NS
Yes
Spirit drinks/day 0≥5
RR Beer/day:
Significant decrease in need for surgery only for modest 2-3 beer/day and 1-3 combined alcohol per day.
M AN U
Men, 141 cases and 184 controls
TE D
Crosssectional
Surgery for BPH
AC C
EP
4b
SC
60+ g/day Mittal106 2009
significantly associated with less BPH at all levels of consumption.
RI PT
or having had a TURP
Wine: all strata NS
1-0.80 (0.55-1.16) 2-0.66 (0.43-1.00)
Glasses wine/day 0≥5
3-0.30(0.14-0.63)
Combined alcohol
≥5 0.97(0.61-1.54)
4- 0.34(0.13-0.90)
50
ACCEPTED MANUSCRIPT
RR combined EtOH/day: 1- 0.77(0.60-0.99) 2- 0.64 (0.46-0.87)
RI PT
3- 0.49 (0.32-0.77) 4- 0.59(0.34-1.02)
≥5 0.86 (0.60-1.23)
Grams per day alcohol:
Pooled OR for BPH 12 studies :
SC
Development of BPH or worsening LUTS on AUASI
M AN U
Men, 120,091
TE D
Metaanalysis of cohort and case-control studies
EP
3a
AC C
Parsons107 2009
Up to 5g
Up to 12g
0.90 (0.80-1.01)
Up to 15g
0.86 (0.79-0.94)
Up to 24g
0.66 (0.54-0.81)
Up to 36g
0.82 (0.69-0.97)
>36g
0.78 (0.69-0.88) 0.65 (0.58-0.74)
Pooled OR for LUTS alone 4 studies: ≥12g/day OR 1.42 (0.772.64)
14/19 studies showed decreased BPH with alcohol intake. In pooled analysis all strata of consumption showed a significant decreased likelihood of BPH compared to nondrinkers. ¾ Studies on LUTS alone showed increased symptoms, but pooled analysis NS
n/a
51
ACCEPTED MANUSCRIPT
Williams108 2008
2b
Prospective cohort,
New physician diagnosis of BPH
Men, 28,612
Alochol intake BPH men 81.32 ml +/- 2.5 no BPH men 81.02 +/- 0.70 ml per week p=0.91
No. Alcohol intake did not predict new diagnosis of BPH
Yes
RI PT
7.7 year (average) follow-up
alcohol mL/week (self- report)
AC C
EP
TE D
M AN U
SC
BPH = Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, USI – urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
52
ACCEPTED MANUSCRIPT
Supplemental Table 5B. General Urinary Symptoms and Alcohol Use- Detailed Summary of Articles Oxford Level
Study Design, Duration Follow-up
Population, N
LUTSOutcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
RI PT
Author /Year
Bhojani112 2008
4b
Crosssectional
Men, 1162
Bother associated with urinary function
Joseph61 2003
4b
Crosssectional
Men, 819
Moderatesevere LUTS (AUA-SI 8+);
Never drinker (reference)
LUTS
Mod-severe obstructive sx (5+);
Former drinker
0.87 (0.68, 1.12)
Current <= 72g/day
Obstructive
OR 3.12 (1.4-6.8)
TE D
M AN U
SC
Alcoholism
AC C
EP
Mod-severe irritative sx (4+)
1.21 (0.95, 1.55)
2.35 (1.67, 3.29)
Alcoholism or alcohol-related problems associated with severe urinary function
Yes
Only heavy drinkers had significantly worse LUTS, obstructive and irritative symptoms
Yes
1.24 (0.94, 1.64) Current >72 g/day
0.74 (0.56, 0.98) 1.65 (1.13, 2.41) Irritative 1.19 (0.95, 1.48) 1.20 (0.96, 1.50) 1.92 (1.40, 2.62) 53
ACCEPTED MANUSCRIPT
4b
Crosssectional
AUA-SI score 8+ (reference <8)
Men, 1612
Reference: none
LUTS In men w/o hx of enlarged prostate:
1-42 g/wk
0.95 (0.60, 1.52)
43-98 g/wk
0.76 (0.46, 1.26)
99+ g/wk
RI PT
Klein54 1999
1.03 (0.69, 1.54)
Alcohol intake had little to no impact on LUTS in men with or without a history of enlarged prostate
Yes
The risk of developing an AUA-SI ≥15 is significantly lower on higher consumers of alcohol (0 vs. ≥2/day) hazard ratio= 0.67
Yes
Significantly lower risk of increased AUASI for all types of
Yes
SC
LUTS In men with hx of enlarged prostate:
Kristal19 2008
2b
Prospective cohort,
M AN U
0.53 (0.23, 1.25)
BPH defined as AUA-SI ≥15
Men, 4770
Lee95 1997
4b
Crosssectional
AC C
EP
TE D
7 year follow-up
Men, 496
0.33 (0.14, 0.77) 0.88 (0.39, 1.99)
Drinks per month reference <1/mo:
1-3/month
Hazard ratio
1-6/week
0.74 (0.58, 0.96)
7-13/week
0.85 (0.72, 1.01)
>=14/week
0.83 (0.68, 1.01) 0.67 (0.45, 0.84)
AUA-SI 8+
non-drinker vs drinker
Drinkers RR 0.61 (0.490.76)
beer <500ml vs. >500ml
Beer <500 RR 0.41
54
ACCEPTED MANUSCRIPT
per day
(0.25-0.66)
Soju <180 vs. >180 ml per day
Beer >500 RR 0.25 (0.09-0.73)
alcohol compared to non-drinkers
RI PT
Soju <180 RR 0.62 (0.480.81) Soju >180 RR 0.58 (0.440.77)
4b
Crosssectional
Men, 30,196
AUA-SI score
M AN U
None/mild 0-7
Calculated grams EtOH/day:
Moderate 819
Moderate or severe LUTS OR:
SC
Oh62 2012
None (ref) >0-10g
Severe 20-35
0.91(0.84-0.98)
Modest drinkers Yes have a lower risk of LUTS compared to non- drinkers but heavy consumption increases LUTS
4b
Crosssectional
Men, 2797
AC C
Rohrmann113 2005
EP
TE D
>10-20g
LUTS (at least 3 of these 4 sx: nocturia, incomplete emptying, hesitancy, and weak stream;
0.94 (0.86-1.02)
>20-30g 1.02 (0.91-1.14) >30-40g 1.12 (1.01-1.24) >40g (heavy) 1.19 (1.07-1.33)
Alcohol:
Never 1.00
Never, <1/wk, >1/wk but < 1/day, >=daily
<1/wk 0.53 (0.24, 1.18) >1/wk to < 1/d
Inverse association between alcohol and LUTS
Yes
0.99 (0.47, 2.08) >=1/d 0.59 (0.34, 1.03)
55
ACCEPTED MANUSCRIPT
I) 4b
Crosssectional
AUA-SI classified as mild 0-7, mod/severe 835
Men, 21,694
Number of alcoholic drinks per week : 0, 1-5, 6-10, >10
OR for mod/severe LUTS: 1-5 drinks per week 1.12 (1.01-1.25)
RI PT
Seim109 2005
only the 6-10 drink per week group had a greater OR of mod/sever LUTS
Yes
OR for moderate/severe LUTS showed a J shaped curve with modest consumption associated with lower symptoms but when HDL is added to model effect is attenuated
Yes
NS for either
Yes
6-10 drinks OR 1.41 (1.19-1.66)
2b
Prospective cohort,
AUA-SI classified as mild 0-7, mod/severe 835
Men, 9712
4b
Crosssectional
AC C
EP
TE D
27.9 months (average) follow-up
Tomita111 2009
Alcohol grams per day:
OR
0g
1.0 (ref)
0.1-9.9g
1.02 (0.94-1.10)
10.0-19.9g
1.10 (1.00-1.20)
20-29.9g
0.95 (0.85-1.05)
30.0-39.9g
1.16 (1.04-1.28)
≥40g
1.32(1.19-1.46)
weekly calculated grams alcohol:
OR AUA-SI>=1
none (ref)
1.1 (0.6-2.1)
M AN U
Suh110 2014
SC
>10 OR 1.23 (0.88-1.72)
Men, 1278
score of≥ 1 or ≥3 on modified AUASI
1.1 (0.8-1.5) 1.1 (0.7-1.6)
56
ACCEPTED MANUSCRIPT
1-29g
OR AUA-SI >=3
30-59 g
1.0 (0.6-1.5)
>60 g
1.0 (0.6-1.7)
RI PT
0.8 (0.3-2.0)
AC C
EP
TE D
M AN U
SC
BPH = Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
57
ACCEPTED MANUSCRIPT
Supplemental Table 5C. Nocturia and Alcohol Use- Detailed Summary of Articles Study Design, Duration Follow-up
Population, N
LUTS-Outcome(s)*
Alcohol Variable(s)*
Schneider63 2010
4b
Crosssectional
Men & Women, 3766
Nocturia improvement
No alcohol (ref), light, moderate and strong consumption (self-report)
Shiri48 2008
2b
Prospectiv e cohort,
Men, 1580
Nocturia: mild (12), moderate (3-4), severe (5 or more)
Results: Significance
Adjusted analyses?
Multiple regression model mild alcohol vs. none: nocturia: -.06, P value NS; comparing mod/severe alcohol to mild: nocturia: -.066
NS
no
Mild nocturia in modest drinkers RR 0.4 (0.2-0.8) heavy drinkers RR 1.0 (0.7-1.5)
Only for modest drinkers lower RR of moderate/severe nocturia
yes
Results: OR, RR, other
RI PT
Oxford Level
M AN U
SC
Author/Year
5 year follow-up
Alcohol (g/week): none, 1-150,
TE D
>150
OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
EP
Supplemental Table 5D. OAB and Alcohol Use- Detailed Summary of Articles Author/Year
Oxford Level
Study Design, Duration Followup
Population, N
Ikeda65 2011
4b
Crosssectional
Men & OAB: urgency with Women, 414 urination 8 times or men and more per day
AC C
LUTS-Outcome(s)*
Alcohol Variable(s)*
Results: OR, RR, other
Results: Significance
Adjusted analyses?
Never drinkers (ref), exdrinkers, current
Ex-drinker
NS for exdrinkers, current drinkers significantly
Yes
OR 0.98 (0.50-1.91)
58
ACCEPTED MANUSCRIPT
419 women
drinkers
Current drinker
more OAB
OR1.65 (1.04-2.62) Women: LUTS <1 drink OR 1.13 (0.70, 1.83)
RI PT
Reference 0 drinks <1 or 1+ drinks daily in the last 30 days
1+ OR 1.47 (0.75-2.86) Storage
SC
AUA-SI score 8+ (moderate to severe LUTS); AUA-SI score 5+ on 4 items (voiding); AUA-SI score 4+ on 3 items (storage)
<1 OR 0.95 (0.63, 1.46)
M AN U
5 years follow-up
Men & Women, 1,610 men and 2,535 women
TE D
Prospecti ve cohort,
EP
2b
AC C
Maserejian74 2012
1+ OR 0.55 (0.31-0.97)
Results for alcohol intake were inconsistent by intake level and symptom subtype with few groups achieving statistical significance
Yes
Voiding <1 OR 1.26 (0.66, 2.42) 1+ OR 3.12 (1.41-6.90) MEN: LUTS <1 OR 2.42 (1.24, 4.75) 1+ OR 1.73 (0.87-3.43) Storage <1 OR 2.19 (1.10, 4.38) 1+ OR 1.49 (0.77-2.87) Voiding <1 OR 1.08 (0.56, 2.08)
59
ACCEPTED MANUSCRIPT
1+ OR 1.07 (0.54-2.05) 4b
Crosssectional
Men & Women, 3766
Urgency episode improvement, Frequency improvement
Alcohol intake (none, light, moderate, severe; (Q))
Multiple regression model comparing mild alcohol to none: urgency episodes: parameter estimate -.18, frequency: -.10, all P values NS, comparing mod/severe alcohol to mild: urgency: -0.19, incontinence: .08, frequency: .074.
no
No
M AN U
SC
RI PT
Schneider7720 10
AC C
EP
TE D
OAB = Overactive bladder, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
60
ACCEPTED MANUSCRIPT
Author/Year Oxford Level
Study Design, Duration Followup
Population, N
LUTS-Outcome(s)*
Alcohol Variable(s)*
Results: OR, RR, other
Bhojani112 2008
4b
Crosssectional
Men, 1162
Moderate to severe leakage of urine
Alcoholism
RI PT
Supplemental Table 5E. UI and Alcohol Use- Detailed Summary of Articles
Hannestad59 2003
4b
Crosssectional
Women, 27,936
Alcoholism:
M AN U
SC
Leakage: OR 3.9(1.98.2)
glasses beer, wine, spirits per 2 weeks:
OR incontinence:
0-2 (ref)
SUI 1.1 (1.0-1.2)
TE D
UI: any, severe, stress, mixed, urgency
4b
Crosssectional
Women, 298
UI
AC C
Lee125 2012
EP
3+
Any type 1.1 (0.9-1.2)
Results: Significance
Adjusted analyses?
Alcoholism or alcohol-related problems associated with leakage
yes
None significant
yes
no
yes
UUI 1.0 (0.8-1.2) MUI 0.8 (0.7-1.1)
Reference nondrinkers
Alcohol OR 1.31 (0.74, 2.33)
Alcohol drinker
Beer OR 1.03 (0.55, 1.90)
Beer drinker Shochu drinker
Shochu OR 1.65 (0.64, 4.27)
Alcohol intake 0.1-32 g/day or >32 g/day (ref:
0.1-32 g/day OR 1.28 (0.71,2.31) 32+ g/day OR 1.69 61
ACCEPTED MANUSCRIPT
Crosssectional
Men & Women 3766
Urgency, frequency, UI, nocturia
Yoo114 2011
4b
Crosssectional
Women with UI on UDS, 86
Success defined as no further treatment for SUI, UUI, MUI
Beer intake 0.1350 mL/day or >350 mL/day (ref: none)
0.1-350 mL/day OR 1.07 (0.56,2.04)
No alcohol (ref) , light, moderate and strong consumption (self-report)
350+ mL/day OR 0.79 (0.18,3.40)
RI PT
4b
(0.42, 6.81)
Multiple regression model comparing mild alcohol to none: urgency episodes: parameter estimate .18, incontinence: .026, frequency: -.10, nocturia: -.06 all P values NS, comparing mod/severe alcohol to mild: urgency: 0.19, incontinence: .08, frequency: .074. nocturia: -.066
NS
no
Univariate analysis of predictors of success of pelvic floor muscle training estimated coefficient 2.088 p=0.057, multivariate= NS
NS
no
AC C
EP
TE D
M AN U
SC
Schneider63 2010
none);
Alcohol (≤3 or >3 drinks per week; Q)
UI = Urinary incontinence, SUI, Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI = Mixed urinary incontinence, Q = Questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
62
ACCEPTED MANUSCRIPT
Supplemental Table 6A. BPH and Tobacco Use- Detailed Summary of Articles Population, N
Prospecti ve cohort,
Men, 6581
LUTSOutcome(s)
Tobacco Variable(s)
Surgically treated obstructive uropathy
Smoking history: former, current, vs. never
BPH with surgery or prostatic enlargement detected by medical exam and indications for surgery vs. no BPH diagnosis and no or mild LUTS
Cigarette smoking:
Never 1.0
NS
No
S- for current smoking of 20+ cigarettes per day only
Yes
Former 1.04 (0.88-1.22)
BPH vs. no BPH diagnosis and non-severe LUTS or no LUTS
BPH vs. no BPH Never 1.00
Distant former (not for >10 years), Former or light (not for up to 10 years, or current 1-9 cigarettes /day), Current 1019/day, Current 20+/day, vs. never
TE D
Men, 882
EP
Crosssectional
Analyses adjusted?
Current 0.90 (0.76-1.06)
AC C
4b
Results: Significance, Direction
Comments
17 year follow-up Gass47 2002
Results: OR, RR, other
RI PT
2b
Study Design, Duration Followup
SC
Chyou17 1993
Oxford Level
M AN U
Author /Year
Distant former 0.87 (0.59, 1.29)
Former or light current 0.80 (0.52, 1.22) 10-19/day 0.91 (0.47, 1.76)
NS for other associations
20+/day 0.48 (0.24, 0.96)
BPH vs. no BPH/non-severe LUTS Never 1.00 Distant former 0.87 (0.60, 1.26) Former or light current 0.75 63
ACCEPTED MANUSCRIPT
(0.50, 1.11) 10-19/day 0.86 (0.46, 1.59) 20+/day 0.52 (0.26, 1.01) 4b
Crosssectional
Men, 599
BPH (AUA-SIBPH score 8+ and prostate volume 25mL+) vs. no BPH
Smoking history: never (reference), former, current
S- current smoker
Yes
BPH
S- Current smoker
Yes, age only
Never 1.0
NS Former smoker
Former smoker 1.0 (0.9-1.1)
NS cigar/pipe
Current smoker 0.7 (0.6-0.8)
NS trends for # cigarettes/day
BPH
RI PT
Goh67
Never 1.0
Former smoker 0.79 (0.49-1.28)
BPH diagnosis
History of TURP
M AN U
Men, 34694
Smoking history: never (reference), former, current, or only cigars/pipe
TE D
Crosssectional
Current smoking: never (reference), 1-10 cigarettes/day, 11-20, 21-30, 31+
EP
4b
AC C
Kang68 2004*
SC
Current smoker 0.44 (0.220.85)
Cigars/pipe 1.0 (0.8-1.1)
Never 1.0 1-10/day 0.7 (0.5-1.0) 11-20/day 0.7 (0.6-0.9) 21-30/day 0.7 (0.5-0.9) 31+/day 0.8 (0.6-1.1)
64
ACCEPTED MANUSCRIPT
TURP Never 1.0 Current smoker 0.6 (0.4-0.8)
RI PT
Former smoker 0.9 (0.8-1.1) Cigars/pipe 1.0 (0.7-1.3)
SC
Never 1.0
M AN U
1-10/day 0.5 (0.2-1.2) 11-20/day 0.7 (0.4-1.1) 21-30/day 0.6 (0.3-1.1) 31+/day 0.5 (0.2-1.1)
Casecontrol
Men, 4888
BPH, surgically treated
Tobacco use: cigarettes, other tobacco, exsmoker vs. never smoked (I)
TE D
3b
Morrison 46 1992
3b
Casecontrol
Men, 2913
AC C
EP
Morrison 45 1978
BPH, surgically treated
Cigarette use: former, current <1 packs/day, current 1 pack/day, current 2+
Never 1.0
S-
No
NS
Yes
Former 0.7 (0.5, 1.0) Current, cigarettes 0.5 (0.3, 0.7) Current, other 1.0 (0.6, 1.6) Never 1.0 Former 0.96 (0.78, 1.18) Current <1 pk/d 0.93 (0.59, 1.46)
65
ACCEPTED MANUSCRIPT
packs/day)
Current 1 pk/d 0.82 (0.59, 1.14) Current 2+ pk/d 0.88 (0.59, 1.39)
Crosssectional
Men, 62
BPH, clinical diagnosis
Smoking: yes vs. no; duration of smoking in years; number of cigarettes smoked per day
Percentage with BPH among:
NS
No
NS total trend, S+ for heavy smokers
Yes
RI PT
4b
Not smokers 50.0% Smokers 50.0%
SC
Naz115 2010
M AN U
MEAN (SD)
Years of smoking BPH 24.26 (3.63)
2b
Prospecti ve cohort, 6-8 year follow-up
Men, 29386
BPH, surgically treated, or modified AUA-SI score 15+ (Q)
AC C
Platz66 1999
EP
TE D
Controls 26.71 (4.57)
Cigarette smoking (20+ packs in lifetime): former, current 1-14 cigarettes/ day, current 1534 cigarettes/ day, current 35+ cigarettes/ day,
Cigarettes smoked/day BPH 13.88 (3.17) Controls 9.82 (1.90) Total BPH Never 1.00 Former 1.06 (0.97, 1.15) Current 1-14 0.90 (0.70, 1.16) Current 15-34 0.88 (0.73, 1.07)
NS trends for surgically-treated BPH, highmoderate/ severe 66
ACCEPTED MANUSCRIPT
Current 35+ 1.45 (1.07-1.97)
Crosssectional
Men, 471
Prostatic volume 40 mL+ vs. less, measured by transrectal ultrasound
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
Crosssectional
Men, 286
EP
4b
Prostatic volume 30 mL+ vs. less, measured by transrectal ultrasound
AC C
Roberts86 1997*
Never 1.00
symptoms, and enlarged prostate
S+ trends for severe symptoms, severe obstructive symptoms, and severe irritative symptoms NS
Yes, age and BMI only
NS
Yes, age and BMI only
M AN U
4b
TE D
Roberts85 1994*
SC
RI PT
vs. never (Q)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d
Former 0.89 (0.48, 1.63) Current 0.54 (0.19, 1.55)
No packs/day 1.00 0-0.9 pks/day 0.39 (0.08, 1.84) 1-1.4 pks/day 0.71 (0.15, 3.42) 1.5+ pks/day 0.75 (0.09, 6.31) Never 1.00 Former 1.10 (0.34, 3.88) Current 1.00 (0.30, 3.27)
No packs/day 1.00
67
ACCEPTED MANUSCRIPT
(Q)
0-0.9 pks/day 2.40 (0.56, 10.34) 1-1.4 pks/day 0.39 (0.04, 3.49) 1.5+ pks/day 1.61 (0.26, 10.8)
BPH, surgically treated
Acute Urinary Retention
RI PT
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d
(both chart review)
NS
Yes, age only
Never 1.00
Former 0.88 (0.59, 1.31)
Current 0.78 (0.41, 1.49)
SC
Acute urinary retention with catheterization
M AN U
8.75 year (median) follow-up
Men, 2089
0 pack-years 1.00
Additional analyses separated by symptoms at baseline (not shown here) were also NS
1-20 0.96 (0.61, 1.51) > 20 0.76 (0.49, 1.20)
TE D
Prospecti ve cohort,
EP
2b
AC C
Sarma116 2009
BPH, surgically treated Never 1.00 Former 0.96 (0.69, 1.32) Current 0.70 (0.40, 1.21)
0 pack-years 1.00 1-20 0.91 (0.62, 1.34) > 20 0.94 (0.66, 1.34) 68
ACCEPTED MANUSCRIPT
2b
Prospecti ve cohort,
Men, 929
Smoking history: ever vs. never; cigarettes smoked per day (0, 1-19, 20-29, 30+); years smoked (0, 1-19, 20-29, 30+). (I)
BPH (I)
12 year (average) follow-up
Never smoked 1.0
NS
Yes, age only
Ever smoked 1.1 (0.8, 1.6)
0 cig/day 1.0
RI PT
Seitter117 1992
1-19 1.2 (0.8, 1.8)
20-29 1.0 (0.6, 1.7)
1.2 (0.7, 1.9)
M AN U
SC
30+
0 years smoked 1.0 1-19 1.0 (0.7, 1.4)
Additional analyses by age and BMI shows that smokers age 60-79 with BMI 24.4026.75 had a relative risk of 2.8 (1.2, 6.6) compared to never smokers with the same age and BMI. All other additional analyses were NS.
TE D
20-29 1.2 (0.7, 2.1) 30+
1.3 (0.8, 2.0)
AC C
EP
BPH – Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, D = Bladder diary I= interview, Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
69
ACCEPTED MANUSCRIPT
Supplemental Table 6B. Nocturia and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 3669
LUTSOutcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Nocturia (2+ voids per night; Q)
Current smoking: 1-15 cigarettes/day, 16+ per day, vs. non-smoker
0 cig/day 1.0
Crosssectional
Women, 1071
Nocturia (not specified, Q)
Current smoking: yes vs. no
S+
Yes
S-
No
S- Current smoker
Yes, age only
1.8 (1.1-2.8)
Percent with nocturia
M AN U
4b
Analyses adjusted?
1-15 1.4 (1.1-1.8) 16+
Aydin69 2014*
Results: Significance , Direction
Comments
RI PT
Asplund50 2004
Oxford Level
SC
Author /Year
No smoking 41.2% Yes 34.2%
Men, 34694
Nocturia (2+ voids per night)
Smoking history: never (reference), former, current, or only cigars/pipe
TE D
Crosssectional
Never 1.0 Current smoker 0.8 (0.7-0.9) Former smoker 1.1 (1.0-1.2)
Current smoking: never Cigars/pipe 1.1 (1.0-1.3) (reference), 1-10 cigarettes/day, 11-20, 2130, 31+ Never 1.0
EP
4b
AC C
Kang68 2004*
1-10/day 0.9 (0.7-1.2) 11-20/day 0.7 (0.6-0.9)
NS Former smoker NS cigar/pipe NS trends for cigarettes /day
21-30/day 0.9 (0.7-1.2)
70
ACCEPTED MANUSCRIPT
31+/day 1.0 (0.8-1.3) Shiri48 2008 2b
Prospecti ve cohort,
Men, 1633
Mild nocturia (1 or 2 voids/night)
Smoking history (at least 1 year): former, current, vs. never (Q)
Mild
NS
Yes, age only
NS
Yes
Never 1.0 Former 1.0 (0.7, 1.4)
RI PT
5 year follow-up
Current 0.9 (0.6, 1.3)
Moderate or severe (3 or more voids/night) (Q)
SC
Moderate or severe
M AN U
Never 1.0 Former 0.8 (0.5, 1.4) Current 0.8 (0.4, 1.7)
4b
Crosssectional
Women, 1790
Nocturia (2+ voids per night on single item from AUA-SI) (Q)
Smoking status: former, current, vs. never.
TE D
Tähtinen71 2011*
Yoshimura7 0 2004
4b
Crosssectional
Men & Women, 6517
AC C
EP
Among current smokers, intensity: 1-10 cigarettes /day, 11-20, >20. (Q)
Nocturia (2+ voids per night, single item) (Q)
Smoking history: current 1-19 cigarettes /day, current 20+ cigarettes /day, vs. non-smoker
Never 1.0 Former 1.0 (0.6, 1.5) Current 1.1 (0.7, 1.8)
Among current smokers:
NS
1-10 cigs/d 1.0 >10
1.4 (0.6, 2.9)
Non-smoker 1.0
S-
Yes
Current 1-19 not reported Current 20+ 0.72 (0.62-0.83)
71
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Q= questionnaire, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, = Negative association
72
ACCEPTED MANUSCRIPT
Supplemental Table 6C. OAB/LUTS (non-UI) and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 1071
LUTS-Outcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted? Comments
Frequency Urgency (not specified, Q)
Current smoking: yes vs. no
RI PT
Aydin69 2014*
Oxford Level
Percent with frequency
NS
No
S+ (frequency, former only)
No
No smoking 38.0%
SC
Author /Year
Women, 1397
Frequency Urgency
Current smoking (vs. not current), former smoking (vs. not former)
TE D
Crosssectional
Any OAB (including UI)
EP
4b
Outcomes not independent of each other.
AC C
de Boer73 2011*
M AN U
Yes 39.7% Percent with urgency No smoking 34.7% Yes 39.3% Frequency Not former 1.0 Former 1.3 (1.0, 1.8) Not current 1.0
NS
Current 1.0 (0.8, 1.4) NS Urgency Not former 1.0 Former 1.2 (0.9, 1.6)
73
ACCEPTED MANUSCRIPT
Not current 1.0 Current 1.3 (1.0, 1.7)
RI PT
Any OAB
Not former 1.0
Former 1.1 (0.8, 1.4)
SC
Not current 1.0
4
Crosssectional
Women, 104
Storage symptoms and voiding symptoms reported by FLUTS (Q)
Hall119 2008
4b
Crosssectional
Women, 3167
Clusters of symptoms (Q) vs asymptomatic
Hsieh120 2010
4b
Crosssectional
Women, 1521
Lifetime history of smoking at least 100 cigarettes
Not reported
n/a
Current cigarette smoker (yes/no)
Percentage of cigarette smokers was higher in all four symptomatic clusters (25.2%, 22.1%, 23.5%, 28.0%) than in asymptomatic controls (16.1%, equality of means p = 0.016)
S+
Smoker (yes vs. no)
Percent with frequency:
S+
AC C
EP
TE D
Donovan118 2014*
M AN U
Current 1.2 (1.0, 1.6)
Daytime frequency (I; yes vs. no)
n/a
No
Non-smoker 18.2% Smoker 32.3% P = 0.005
74
ACCEPTED MANUSCRIPT
4b
Crosssectional
Men , 708
LUTS Moderate/ severe LUTS; moderate/ severe obstructive symptoms; moderate/ severe irritative symptoms on AUA-SI (I).
Cigarette smoking
LUTS
LUTS S+
Never
Never 1.00
Former
Former 1.76 (1.29, 2.39)
Obstructive S+/NS
Current <20/day Current 20+/day (I)
Current <20 2.07 (1.50, 2.85)
Irritative NS
RI PT
Joseph61 2003
Yes, LUTS and obstructiv e outcomes only
Current 20+ 1.51 (1.06, 2.15)
SC
OBSTRUCTIVE
EP
TE D
M AN U
Never 1.00
4b
Crosssectional
Men, 1612
LUTS (8+ on AUASI, Q)
Current <20 1.32 (0.90, 1.94) Current 20+ 1.73 (1.16, 2.56)
IRRITATIVE (unadjusted) Never 1.00 Former 1.13 (0.76, 1.68) Current <20 1.01 (0.65, 1.57)
AC C Klein54 1999
Former 1.87 (1.31, 2.66)
Current 20+ 1.48 (0.91, 2.40)
Cigarette smoking: former, current vs.
PX WITHOUT HX OF ENLARGED PROSTATE:
NS
Yes, age only
75
ACCEPTED MANUSCRIPT
never (Q)
Never 1.00 Former 0.99 (0.67-1.45)
Among smokers, packyears (pk-yrs)
RI PT
Current 1.16 (0.71-1.88)
None 1.00
0.5-20 pk-yrs 0.93 (0.59-1.44)
SC
21-40 pk-yrs 1.12 (0.70-1.79)
EP
TE D
M AN U
41+ pk-yrs 1.11 (0.70-1.75)
PX WITH HX OF ENLARGED PROSTATE: Never 1.00 Former 1.28 (0.68-2.38) Current 0.87 (0.32-2.35)
AC C
None 1.00 0.5-20 pk-yrs 1.25 (0.60-2.60) 21-40 pk-yrs 1.36 (0.57-3.20) 41+ pk-yrs 0.86 (0.38-1.94)
Koskimaki1
4b
Cross-
Men, 2128
LUTS (DAN-PSS-1
Cigarette smoking: former, current vs.
Smoking status was included as a “confounder” in a
Not
n/a
76
ACCEPTED MANUSCRIPT
reported
Moderate/ severe LUTS (AUA-SI score 8+; Q)
Cigarette smoking: former, current vs. never (Q); Quantity smoked (<1 pack/day, 1+ pack/day vs none); Length of smoking (<30 years, 30+ years vs none)
Never 1.00
NS
Yes, age only
Former 1.04 (0.74-1.50)
RI PT
Men, 514
multivariable model, but results were not reported.
Current 1.12 (0.86-1.46)
Among former or never smokers:
SC
Crosssectional
never (Q)
M AN U
4b
score 7+; Q)
TE D
Lee95 1997
sectional
0 packs/day 1.00 <1 1.21 (0.83, 1.77) 1+ 0.63 (0.32, 1.25)
0 years 1.00 <30 0.79 (0.50, 1.25) 30+ 1.51 (1.03, 2.37)
EP
2000
AC C
21
Among current or never smokers: 0 packs/day 1.00 <1 1.05 (0.80, 1.37) 1+ 1.56 (1.04, 2.34) 77
ACCEPTED MANUSCRIPT
0 years 1.00 <30 0.97 (0.62, 1.32)
Cigarette smoking: former, current vs. never (Q)
Total LUTS
Never 1.00
storage sx (5+ on related items); voiding sx (4+ on related items)
WOMEN
SC
Moderate-severe LUTS (AUA-SI score 8+; Q);
Former 1.22 (0.71, 2.09)
M AN U
5 years follow-up
Men & Women, 4145
TE D
Prospecti ve cohort;
EP
2b
AC C
Maserejian 74 2012
RI PT
30+ 1.13 (0.86, 1.50) S+ for women who currently smoke for storage sx; NS
Yes
Current 1.62 (0.87, 3.03) Storage Never 1.00 Former 1.18 (0.72, 1.95) Current 2.15 (1.30, 3.56) Voiding Never 1.00 Former 1.18 (0.51, 2.72) Current 1.99 (0.89, 4.44) MEN Total LUTS Never 1.00 78
ACCEPTED MANUSCRIPT
Former 0.91 (0.51, 1.63) Current 1.01 (0.55, 1.84) Storage
RI PT
Never 1.00
Former 1.22 (0.66, 2.26) Current 1.12 (0.61, 2.04)
SC
Voiding
Nuotio72 2001
4b
Crosssectional
Crosssectional
Men, 617
Men, 950
Moderate-severe LUTS (AUA-SI score 8+; Q) vs. mild LUTS (< 8)
Ever smoked vs never
LUTS (AUA-SI score with unclear cutpoint; Q)
Smoker: former, current vs. never
TE D
4b
Crosssectional
EP
Ngai123 2013
4b
Men & Women, 1059
AC C
Ng122 2007
M AN U
Never 1.00
Urgency (Q, single question)
Former 1.02 (0.43, 2.45) Current 0.73 (0.36, 1.46) Never 1.00
S+
Yes, hyperurica emia only
S+
Yes
S+
Yes, age and sex
NS
Yes, age
Ever smoked 2.11 (1.24-3.57)
Never 1.000 Former 1.781 (1.128-2.814) Current 2.058 (1.358-3.201)
Smoker: former, current vs. never
Never 1.00 Former 1.63 (0.97-2.74) Current 2.76 (1.43-5.32)
Roberts85
4b
Cross-
Men, 2115
LUTS (AUA-SI score
Cigarette smoking (at
Never 1.00
79
ACCEPTED MANUSCRIPT
sectional
least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
8+) (Q)
Former 0.96 (0.79, 1.18)
only
Current 0.82 (0.61, 1.08)
No packs/day 1.00
RI PT
1994*
0-0.9 pks/day 0.53 (0.33, 0.83) 1-1.4 pks/day 0.87 (0.56, 1.36)
Crosssectional
Men, 286
LUTS (AUA-SI score 8+) (Q)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
M AN U
4b
4b
Crosssectional
Men, 2797
LUTS (at least 3 of these 4 sx: nocturia, incomplete emptying, hesitancy, and weak stream; I)
AC C
Rohrmann1 13 2005
EP
TE D
Roberts86 1997*
SC
1.5+ pks/day 1.32 (0.84, 2.07) Never 1.00
NS
Yes, age only
Former 1.00 (0.5, 1.95) Current 0.84 (0.48, 1.49)
No packs/day 1.00 0-0.9 pks/day 1.07 (0.53, 2.17) 1-1.4 pks/day 0.55 (0.27, 1.13) 1.5+ pks/day 1.10 (0.50, 2.43)
Cigarette smoking: former, current 1-34 cigarettes /day, current 35+ cigarettes /day, vs. never (I). Among current or former smokers, <21 pack years, 21-49.9 pack
Never 1.00
NS
Former 1.37 (0.79, 2.36) Current 1-34 0.78 (0.39, 1.56) Current 35+ 0.75 (0.31, 1.82)
Trends in pack-years among all men, current 80
ACCEPTED MANUSCRIPT
4b
Crosssectional
Men, 21694
LUTS (AUA-SI score 8+; Q)
Cigarette smoking: former (1-5 cigarettes /day, 6-10, 11-15, 1620, 20+), current (1-5 cigarettes /day, 6-10, 11-15, 16-20, 20+), vs. never
Never 1.00
smokers, and former smokers (not reported here) were all NS S+
Yes, age only
S+
Yes
Former 1-5 1.08 (0.89, 1.32)
TE D
M AN U
SC
Seim109 2005
RI PT
years, 50+ pack years.
Crosssectional
Women, 1790
Frequency (longest interval between urination <2 hrs on Danish Prostatic Symptom Score).
Former 11-15 1.25 (1.06, 1.49) Former 16-20 1.34 (1.13, 1.59) Former >20 1.52 (1.24, 1.87) Current 1-5 0.99 (0.79, 1.24) Current 6-10 0.94 (0.81, 1.09) Current 11-15 0.89 (0.75, 1.06) Current 16-20 1.38 (1.14, 1.68)
EP 4b
AC C
Tähtinen71 2011*
Former 6-10 1.10 (0.97, 1.25)
Current >20 1.72 (1.23, 2.39) Smoking status: former, current, vs. never.
Frequency:
Among current smokers, intensity: 110 cigarettes /day, 11-
Former 1.7 (1.0, 3.1)
Never 1.0
Current 3.0 (1.8, 5.0)
81
ACCEPTED MANUSCRIPT
20, >20. (Q)
Among current smokers: 1-10 cigs/d 1.0 >10
2.2 (1.2, 4.3)
RI PT
Urgency (often or always on Danish Prostatic Symptom Score). (Q)
Urgency:
Never 1.0
SC
Former 1.8 (1.2, 2.9)
Men, 1278
LUTS (modified AUA-SI score 1+, or score 3+; Q)
Smoking history: current 1-19 cigarettes /day, current 20+ cigarettes /day, vs. non-smoker
TE D
Crosssectional
EP
4b
AC C
Tomita111 2009
M AN U
Current 2.7 (1.7, 4.2)
Among current smokers: 1-10 cigs/d 1.0 >10
2.1 (1.1, 3.9)
Modified AUA-SI score 1+
NS
Yes
Non-smoker 1.0 Current 1-19 1.0 (0.7, 1.5) Current 20+ 0.9 (0.7, 1.2)
Modified AUA-SI score 3+
NS
Non-smoker 1.0 Current 1-19 0.9 (0.5, 1.6) Current 20+ 0.9 (0.6, 1.3) 82
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
OAB = Overactive bladder, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, Q= questionnaire, I = interview, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
83
ACCEPTED MANUSCRIPT
Supplemental Table 6D. UI and Tobacco Use- Detailed Summary of Articles
Aydin69 2014*
Oxford Level
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 1071
LUTSOutcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
UI (not specified, Q)
Current smoking: yes vs. no
RI PT
Author /Year
Percent with incontinence
NS
No
S+
Yes
SC
No smoking 37.5% Yes 34.9%
Urodynamically tested SUI and motor incontinence, vs continent
Smoking history: former, current vs. never
Genuine SUI:
M AN U
Women, 160
Never 1.00 Former 2.20 (1.18-4.11) Current 2.48 (1.60-3.84)
TE D
Cross sectional
EP
4b
AC C
Bump75 1992
0 pk/d 1.00 S-1 1
0.94 (0.43-2.04) 2.44 (1.31-4.55)
>1
4.72 (2.42-9.22)
0 pk-y 1.00 1-14
1.86 (1.01-3.42)
15-29 2.50 (1.32-4.74) 84
ACCEPTED MANUSCRIPT
30+
3.78 (2.06-6.96)
Motor Incont.:
RI PT
Never 1.00
Former 2.92 (1.58-5.39)
SC
Current 1.98 (1.19-3.02)
M AN U
0 pk/d 1.00
TE D
<1
Crosssectional
Women, 535
Genuine stress incontinence, detrusor instability, mixed (no controls)
1
2.49 (1.31-4.75)
>1
2.71 (1.29-5.69)
0 pk-y 1.00 1-14
2.71 (1.51-4.87)
15-29 2.23 (1.13-4.39)
EP 4b
AC C
Cundiff79 1997
0.97 (0.43-2.16)
30+ Smoking (not defined)
2.61 (1.34-5.06)
% smokers:
NS
No
13% genuine stress incontinence 13% SI w/ or w/o DI
85
ACCEPTED MANUSCRIPT
(p = 1.0) 22% detrusor instability 19% DI w/ or w/o SUI
Women, 83355
Self-report UI: occasional (1-3 leaks/mo), frequent (1+ leaks/wk), severe (frequent leaks enough to wet underwear)
Cigarette smoking (never, former, current)
Crosssectional
Women, 1397
UUI, not independent of other OAB
Yes
S- (current only)
Current 0.91 (0.85, 0.98)
EP 4b
Occasional incontinence
Never 1.00
Former 1.00 (0.96, 1.05)
Frequent incontinence
Frequent incontinence
Never 1.00
S+
Former 1.12 (1.08, 1.16) Current 1.20 (1.13, 1.28)
Severe incontinence S+
Severe incontinence Never 1.00
AC C de Boer73 2011*
Occasional incontinence
SC
Crosssectional
M AN U
4b
TE D
Danforth78 2006
RI PT
(p = 1.0)
Former 1.11 (1.05, 1.17) Current 1.34 (1.25, 1.45) Current smoking (vs. not current), former smoking
Not former 1.0
NS
No
Former 1.0 (0.8, 1.4) 86
ACCEPTED MANUSCRIPT
symptoms
(vs. not former)
Not current 1.0 Current 1.3 (1.0, 1.7)
Women, 104
Incontinence symptoms (Q)
Hannested59 2003
4b
Crosssectional
Women, 27936
Any UI, SUI, MUI, UUI. Each reported as all cases (vs. no UI) and severe (vs. none or mild).
Lifetime history of smoking at least 100 cigarettes
Not reported
ALL Cigarette smoking:
RI PT
Crosssectional
Any incontinence
SC
4b
n/a
n/a
ALL
Yes
Any incontinence
Never 1.0
Never
S+
Former (1-19/day) 1.1 (1.0, 1.2)
M AN U
Donovan118 2014*
Former (1-19/day)
Former (20+/day) 1.7 (1.4, 2.0)
Former (20+/day) Current (119/day)
Current (1-19/day) 0.9 (0.9, 1.0)
Stress incontinence S+/-
TE D
Current (20+/day) 1.3 (1.1, 1.6)
AC C
EP
Current (20+/day) Stress incontinence
Mixed incontinence
Never 1.0
S+
Former (1-19/day) 1.1 (1.0, 1.2) Former (20+/day) 1.3 (1.0, 1.7) Current (1-19/day) 0.8 (0.7, 0.9)
Urge incontinence NS, S+
Current (20+/day) 1.2 (1.0, 1.5)
87
ACCEPTED MANUSCRIPT
SEVERE Mixed incontinence Never 1.0
Any incontinence S+
RI PT
Former (1-19/day) 1.2 (1.0, 1.3) Former (20+/day) 2.2 (1.7, 2.8)
SC
Current (1-19/day) 1.1 (1.0, 1.3)
Stress incontinence NS, S+
M AN U
Current (20+/day) 1.6 (1.2, 2.1)
Urge incontinence
Mixed incontinence
Never 1.0
S+
AC C
EP
TE D
Former (1-19/day) 1.1 (0.9, 1.4) Former (20+/day) 1.9 (1.2, 3.2) Current (1-19/day) 1.2 (1.0, 1.5)
Urge incontinence NS
Current (20+/day) 1.3 (0.8, 1.4) SEVERE Any incontinence Never 1.0 Former (1-19/day) 1.2 (1.1, 1.5)
88
ACCEPTED MANUSCRIPT
Former (20+/day) 2.5 (1.8, 3.5) Current (1-19/day) 1.3 (1.1, 1.5)
RI PT
Current (20+/day) 2.1 (1.5, 2.8)
Stress incontinence
SC
Never 1.0
M AN U
Former (1-19/day) 1.1 (0.8, 1.4)
Former (20+/day) 1.4 (0.7, 2.6) Current (1-19/day) 1.1 (0.8, 1.4)
AC C
EP
TE D
Current (20+/day) 1.8 (1.1, 2.9)
Mixed incontinence Never 1.0 Former (1-19/day) 1.3 (1.0, 1.6) Former (20+/day) 3.3 (2.2, 4.9) Current (1-19/day) 1.4 (1.1, 1.7) Current (20+/day) 2.4 (1.6, 3.6)
89
ACCEPTED MANUSCRIPT
Urge incontinence Never 1.0 Former (1-19/day) 1.0 (0.6, 1.7)
RI PT
Former (20+/day) 2.1 (0.7, 6.0) Current (1-19/day) 1.3 (0.1, 3.6)
4b
Crosssectional
Women, 3537
UI (ever vs. never)
Smoking (yes vs. no)
Percent with UI
M AN U
Hsieh80 2008
SC
Current (20+/day) 1.3 (0.8, 2.1) NS
No
S+
Yes
NS
No
n/a
n/a
Non-smoker 18.7% Smoker 17.5% P = 0.759
Smith124 2010
4b
4b
Crosssectional
Crosssectional
Women, 650
Women, 592
Mean number UI episodes, among stressincontinent presurgical patients (D)
Current smoking: yes vs. no
UI (any type, Q)
Current smoking: yes vs. no (Q)
TE D
Crosssectional
EP
Skjeldestad81 2008
4b
AC C
Richter76 2005
Women, 572
UI (leaking Lifetime smoking more often than history (100+ cigarettes in life),
Yes 1.37 (antilog of slope coefficient, reference group is not current smoker) P = 0.01
Percentage who currently smoked: Without UI 31.4% With UI 33.0% p = 0.71 Percentage who smoked at least 100 cigarettes:
No statistical 90
ACCEPTED MANUSCRIPT
Crosssectional
Women, 1790
SUI UUI (Both measured as often or always on Danish Prostatic Symptom Score). (Q)
Smoking status: former, current, vs. never.
SUI:
Among current smokers, intensity: 1-10 cigarettes /day, 11-20, >20. (Q)
Former 1.4 (0.9, 2.1)
Among current smokers:
TE D EP Women,
SUI
NS
1-10 cigs/d 1.0 1.3 (0.6, 2.8)
NS
UUI: Never 1.0 Former 1.8 (0.8, 4.3) Current 1.5 (0.6, 3.8)
AC C Case-
Yes
Current 0.8 (0.5, 1.3)
Among current smokers:
NS
1-10 cigs/d 1.0 >10
3b
NS
Never 1.0
>10
Tampakoudis
test of association
With UI 34.4%
RI PT
4b
Without UI 37.1%
SC
Tähtinen71 2011*
measured by Behavioral Risk Factor Surveillance System Survey Questionnaire (Q)
M AN U
never; Q)
Smoking history:
1.7 (0.3, 8.5)
Percentage who were smokers:
S+ UI in
No 91
ACCEPTED MANUSCRIPT 77
1995
control
160
Without UI 25%
general
With UI 62.5% P < 0.0005
RI PT
UUI, MUI (Both urodynamically assessed)
former, current, vs. never
S+ UUI/MUI relative to SUI
Among incontinent smokers: SUI 39.6%
M AN U
SC
UUI/MUI 60.4%
Among incontinent nonsmokers: SUI 65.6%
TE D
UUI/MUI 34.4%
AC C
EP
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, Q= questionnaire, D= diary, DI= detrusor instability, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
92
ACCEPTED MANUSCRIPT
Supplemental Table 6E. Other- parameters and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 189 Urodynamic test parameters
LUTS-Outcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Active smoker vs. never smoker
Smokers had higher functional urethral length (26.4mm vs 23.6 mm, p=0.007) and maximum cough spike (114.4 cm H2O vs 96.7 cm H2O, p=0.04) relative to non-smokers. No difference in maximum closure pressure, mean pressure transmission ratio, or degree of urethral axis with stress.
S+
No
4a
Case series
Women, 319 Intravesical peak pressures generated by cough (CIPP), cough leak point pressure (CLPP)
AC C
Fuganti83 2011
EP
TE D
M AN U
SC
Bump82 1994
Oxford Level
RI PT
Author /Year
Smoking history: former, current vs. never
NS CLPP was lower in never smokers (110cmH2O) than in current or former smokers (140cmH2O, p = 0.01)
S+
CLPP – no CIPP – yes
S+
RR for CIPP
93
ACCEPTED MANUSCRIPT
Never 1.0 Smoker 14.270 (8.851, 19.689)
Prostatic tissue weight
Urinary flow rate (mL/s)
MEAN (SD), p-values compared to never
RI PT
Cigarette smoking: former, current vs. never (Q)
S+ Oestradiol
No
NS Testosterone NS DHEA
Oestradiol
NS DHEA-S
SC
Plasma levels of Oestradiol (pg/mL), Testosterone (ng/mL), DHEA (mg/mL), DHEA-S (mg/mL)
Never 26.65 (3.04)
M AN U
Men, 68
TE D
Crosssectional
Former 32.23 (2.60, p < 0.01)
NS tissue weight
Current 33.83 (6.53, p < 0.01)
Testosterone
NS Urinary flow rate
Never 3.09 (0.33) Former 3.32 (0.43, p < 0.05) Current 2.44 (0.80, p < 0.01)
EP
4b
AC C
Küpeli84 1997
DHEA Never 1.65 (0.32) Former 1.34 (0.24) Current 4.62 (0.90)
94
ACCEPTED MANUSCRIPT
DHEA-S Never 3.18 (0.32)
RI PT
Former 2.67 (0.28)
Current 3.86 (0.36)
SC
Tissue weight
Former 59.6 (5.25) Current 59.1 (7.42)
Urinary flow rate Never 5.7 Former 6.1 Current 7.2
AC C
EP
TE D
M AN U
Never 73.4 (5.41)
95
ACCEPTED MANUSCRIPT
Peak urinary flow rate less than 15 mL/sec vs. 15 or more;
Flow < 15 mL/sec Never 1.00
S-
Yes, age and voided volume only
Former 0.85 (0.69, 1.06) Current 0.48 (0.35, 0.66)
No packs/day 1.00
0-0.9 pks/day 0.46 (0.28, 0.74)
M AN U
SC
Peak urinary flow rate less than 10 mL/sec vs. 15 or more
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
RI PT
Men, 2115
TE D
Crosssectional
EP
4b
AC C
Roberts85 1994*
1-1.4 pks/day 0.49 (0.29, 0.81) 1.5+ pks/day 0.55 (0.32, 0.95)
Flow < 10 mL/sec Never 1.00 Former 0.80 (0.62, 1.09) Current 0.42 (0.25, 0.72)
No packs/day 1.00 0-0.9 pks/day 0.47 (0.21, 1.03) 1-1.4 pks/day 0.27 (0.09, 96
ACCEPTED MANUSCRIPT
0.79)
Crosssectional
Men, 286
Peak urinary flow rate less than 15 mL/sec vs. 15 or more
EP
4b
AC C
Roberts86 1997*
TE D
M AN U
SC
RI PT
1.5+ pks/day 0.65 (0.27, 1.58)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
Never 1.00 Former 0.71 (0.28, 1.76) Current 0.39 (0.18, 0.84)
S- (current smokers, and heavy smokers, have less risk)
Yes, age and voided volume only
No packs/day 1.00 0-0.9 pks/day 0.37 (0.14, 0.97) 1-1.4 pks/day 0.41 (0.14, 1.21)
97
ACCEPTED MANUSCRIPT
1.5+ pks/day 0.24 (0.08, 0.77)
AC C
EP
TE D
M AN U
SC
RI PT
Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
98
ACCEPTED MANUSCRIPT Supplemental References
57. 58. 59. 60.
61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73.
RI PT
56.
SC
55.
M AN U
54.
TE D
53.
EP
52.
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79.
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77.
TE D
76.
EP
75.
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104.
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103.
M AN U
102.
TE D
101.
EP
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Lee, A. H., Hirayama, F.: Alcohol consumption and female urinary incontinence: a community-based study in Japan. Int J Urol, 19: 143, 2012
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S0022-5347(17)59390-8 10.1016/j.juro.2017.04.097 JURO 14733
To appear in: The Journal of Urology Accepted Date: 30 April 2017 Please cite this article as: Bradley CS, Erickson BA, Messersmith EE, Cameron AP, Lai HH, Kreder KJ, Yang CC, Merion RM, Bavendam TG, Kirkali Z, for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), Evidence for the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review, The Journal of Urology® (2017), doi: 10.1016/ j.juro.2017.04.097. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
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ACCEPTED MANUSCRIPT
Evidence for the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review
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Catherine S. Bradley, MD, MSCE1, Bradley A. Erickson, MD, MS, FACS 1, Emily E. Messersmith, PhD2, Anne P. Cameron, MD3, H. Henry Lai, MD4, Karl J. Kreder, MD, MBA1, Claire C. Yang, MD5, Robert M. Merion, MD, FACS2, Tamara G. Bavendam, MD, MS6, Ziya Kirkali, MD6, for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) 1
University of Iowa Carver College of Medicine, Iowa City, IA Arbor Research Collaborative for Health, Ann Arbor, MI 3 University of Michigan, Ann Arbor, MI 4 Washington University School of Medicine, St. Louis, MO 5 University of Washington, Seattle WA 6 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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Author Emails [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected]
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2
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Running head: Lifestyle factors and lower urinary tract symptoms Key words: Lower urinary tract symptoms, systematic review
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Corresponding Author Catherine S. Bradley, MD, MSCE Professor of Ob-Gyn, Urology and Epidemiology Department of Obstetrics and Gynecology University of Iowa Hospitals & Clinics 200 Hawkins Drive Iowa City, IA 52242 [email protected]
1
ACCEPTED MANUSCRIPT
Source of Funding This is publication number 3 of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).
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This study is supported by the National Institute of Diabetes & Digestive & Kidney Diseases through cooperative agreements (grants DK097780, DK097772, DK097779, DK099932, DK100011, DK100017, DK097776, DK099879). Acknowledgement
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The following individuals were instrumental in the planning and conduct of this study at each of the participating institutions:
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Duke University, Durham, North Carolina (DK097780): PI: Cindy Amundsen, MD, Kevin Weinfurt, PhD; Co-Is: Kathryn Flynn, PhD, Matthew O. Fraser, PhD, Todd Harshbarger, PhD, Aaron Lentz, MD, Drew Peterson, MD, Nazema Siddiqui, MD, Alison Weidner, MD; Study Coordinators: Carrie Dombeck, MA, Robin Gilliam, MSW, Akira Hayes, Shantae McLean, MPH University of Iowa, Iowa City, IA (DK097772): PI: Karl Kreder, MD, MBA, Catherine S Bradley, MD, MSCE, Co-Is: Bradley A. Erickson, MD, MS, Susan K. Lutgendorf, PhD, Vince Magnotta, PhD, Michael A. O’Donnell, MD, Vivian Sung, MD; Study Coordinators: Ahmad Alzubaidi, Andrea Lopez, Linda Moss, RN, BSN, CCRC
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Northwestern University, Chicago, IL (DK097779): PI: David Cella, PhD; Co-Is: James Griffith, PhD, Kimberly Kenton, MD, MS, Christina Lewicky-Gaupp, MD, Todd Parrish, PhD, Jennie Yu Fan Chan, MD; Study Coordinators: Sarah Buono, Maria Corona, Beatriz Menendez, Alexis Siurek, Meera Tavathia, Veronica Venezuela NorthShore University Health System, Evanston, IL (DK097779): PI: Brian T. Helfand, MD, PhD; Study Coordinators: Jasmine Nero, Pooja Talaty
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University of Michigan Health System, Ann Arbor, MI (DK099932): PI: J Quentin Clemens, MD, FACS, MSCI; Co-Is: Mitch Berger, MD, PhD, John DeLancey, MD, Dee Fenner, MD, Rick Harris, MD, Steve Harte, PhD, Anne Pelletier-Cameron, MD, John Wei, MD; Study Coordinators: Morgen Barroso, Linda Drnek, Greg Mowatt, Julie Tumbarello University of Washington, Seattle Washington (DK100011): PI: Claire Yang, MD; Co-I: John L. Gore, MD, MS; Study Coordinators: Alice Liu, MPH, Brenda Vicars, RN Washington University in St. Louis, St. Louis Missouri (DK100017): PI: Gerald Andriole, MD, Henry Lai; Co-I: Joshua Shimony, MD, PhD; Study Coordinators: Susan Mueller, RN, BSN, Heather Wilson, LPN, Aleksandra Klim, RN, MHS, CCRC National Institute of Diabetes and Digestive and Kidney Diseases, Division of Kidney, Urology, and Hematology, Bethesda, MD: Project Scientist: Ziya Kirkali MD; Project Officer: John Kusek, PhD; NIH Personnel: Tamara Bavendam, MD, Robert Star, MD, Jenna Norton, MPH
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Arbor Research Collaborative for Health, Data Coordinating Center (DK097776 and DK099879): PI: Robert Merion, MD, FACS; Co-Is: Brenda Gillespie, PhD, Victor Andreev, PhD, DSc; Project Manager: Melissa Fava, MPA, PMP; Clinical Study Process Manager: Peg Hill-Callahan, BS, LSW; Clinical Monitor: Timothy Buck, BS, CCRP; Research Analysts: Margaret Helmuth, MA, Jon Wiseman, MS; Project Associate: Julieanne Lock, MLitt, BA
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Abstract Purpose: Foods, fluid intake, caffeine, alcohol, and tobacco may influence lower urinary tract symptoms (LUTS). Changes in these potentially modifiable non-urologic factors (NUF) are often suggested to improve
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LUTS. To better understand the relationship of NUFs with LUTS, we performed a systematic literature review to examine, grade, and summarize reported associations between LUTS and diet, fluid intake, caffeine,
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tobacco and alcohol use.
Materials and Methods: We performed PubMed searches for eligible articles providing evidence on
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associations between one or more NUF and LUTS. A modified Oxford system was used to grade the evidence.
Results: We reviewed 110 articles covering diet (n=28), fluid intake (n=21), caffeine (n=20), alcohol (n=26) and tobacco use (n=44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3; 59% level
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4). Fluid intake was associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with less likelihood of benign prostatic hyperplasia (BPH) diagnosis and fewer LUTS in men.
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LUTS associations with food, caffeine, and tobacco were inconsistent.
Conclusions: Evidence for associations between LUTS and diet, fluid intake, caffeine, alcohol and tobacco use
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is sparse and mostly observational. However, there is evidence of associations between increased fluid intake and urinary frequency/urgency, and between modest alcohol intake and decreased BPH diagnosis and LUTS. Given the importance of these NUF to daily life, and their perceived impact on LUTS, higher quality evidence is needed.
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Introduction
Lower urinary tract symptoms (LUTS) are common and bothersome, affecting 20-50% of men and women
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and negatively impacting health-related quality of life (QOL)1-3. Patients seeking care for LUTS are frequently instructed to modify daily behaviors to reduce symptoms. For example, providers may recommend patients change fluid intake, or use less caffeine or alcohol4. The quantity and quality of evidence to support such
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recommendations is unclear. While typically low risk, lifestyle changes may be obtrusive to patients’ lives and increase anxiety or stress. What patients eat, drink, and ingest depends on culture, region, employment,
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socioeconomic status, and other factors. These behaviors are part of the daily human experience, and as such, a better understanding of their impact on LUTS is critical.
The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-supported cooperative network with objectives to
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improve the measurement of LUTS and identify important LUTS subtypes5. In conceptualizing the scope of lower urinary tract dysfunction and its resultant symptoms, we considered multiple potential explanatory
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factors that may contribute to LUTS, including non-urologic factors (NUF), such as diet, fluid intake and
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caffeine, alcohol and tobacco use.
The objectives of this study were to identify, grade, and summarize peer-reviewed literature examining associations between diet, fluid intake, caffeine, alcohol and tobacco use and LUTS. In addition to identifying evidence-based associations between these factors and LUTS, results will help identify gaps where future efforts may be focused.
Methods
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This systematic review was designed to answer the question: “Are diet, fluid intake, and caffeine, alcohol and tobacco use associated with the prevalence and/or severity of LUTS in men and women?”. The review used findings from randomized clinical trial (RCT), cohort, case control, case series, and cross-sectional studies that
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could provide evidence related to these associations. Research focused on bladder pain and conditions such as interstitial cystitis/bladder pain syndrome were excluded. This systematic review was based on the
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Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines6.
PubMed searches were developed with assistance from a health science librarian. Five separate searches
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were performed to identify publications studying associations between LUTS and each of the five NUF. A search “string” was developed for LUTS and for each factor including MESH terms and key words for text searches and limited to English language publications (Supplemental Table 1).
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All citations and abstracts were screened using previously developed eligibility criteria (Table 1). When the initial screener was unsure whether a citation should be included, a second investigator reviewed it. If uncertainty persisted, the citation was included for additional review at the full text stage. Each article
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considered eligible after screening was reviewed (full text) by two investigators. All articles confirmed eligible were assigned a level of evidence by both reviewers, using a system based on the Oxford Centre for
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Evidence-based Medicine Level of Evidence scale (2009 version) and International Consultation on Urological Diseases, modified to include cross-sectional studies as level 4b evidence (Table 2)7, 8. If initial grades differed, investigators arrived at a grade by consensus.
Data from each article were reviewed and abstracted using a standard form. Information collated included study design, population, LUTS outcome (e.g. overactive bladder [OAB]), NUF exposure (e.g. caffeine), the
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summary measure of association and type of analysis performed. Meta-analyses were not performed given
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the heterogeneous study designs, outcomes and exposures identified.
Results
Electronic searches were performed through January 4, 2016. Results of the searches, screening and
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selection process, and reasons for exclusion are presented in Tables 1 and 3. We reviewed 110 unique articles in the areas of diet (n=28), fluid intake (n=21), caffeine (n=20), alcohol (n=26) and tobacco (n=44). Twenty-
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two articles contributed results on more than one factor. The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3, and 59% level 4). A summary of the publications reviewed and a synthesis of results related to the association of each NUF with LUTS are described below.
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Diet and LUTS
Twenty-eight publications met criteria and provided information related to the association between diet and
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LUTS (Table 4). Diet was assessed by a food-frequency questionnaire (FFQ) in almost all studies. There were five interventional RCTs9-13. Only two specifically addressed adding a particular component to improve LUTS10, 13
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. The remaining studies analyzed diet and LUTS in the setting of interventions concerning diabetes
prevention9, constipation reduction11, and weight loss12, 14. (See detailed summary of publications in Supplemental Tables 2A-D.) Diet and BPH
Overall, there appears to be a weak association for diet and surgical BPH therapy. A myriad of food types, food groups, micronutrients and macronutrients were evaluated. Consumption of a high-calorie diet, high in
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starches and red meat may be weakly associated with BPH risk, while a lower-calorie diet, high in vegetables (specifically allium vegetables, e.g. onion and garlic), high in polyunsaturated fats (including specifically eicosapentanoic and docosahexanoic acids) and low in saturated fat may be associated with decreased risk1520
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. Studies on micronutrients have implicated carotene to decrease risk while zinc may increase risk21, 22.
Diet and Urinary Incontinence (UI)
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Many studies that assess diet and UI are indirectly evaluating diet through weight loss. The review found two RCTs in women, the first showing intensive lifestyle therapy (including a low calorie diet) decreased UI in pre-
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diabetic women9 and the second that modest weight reduction (mean 7.8 kg) can decrease stress urinary incontinence (SUI) episodes (but not urge)12, and that weight loss (5-10% of body weight) was sufficient to significantly decrease UI episodes14. Another RCT specifically looked at urgency incontinence episodes in nursing home patients and found when combined with toileting assistance, exercise and an increase in caloric intake, UI episodes decreased significantly11. Another RCT evaluated a diet rich in soy, hypothesized to
LUTS or UI.10
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increase circulating estrogens via phytoestrogens, showed no improvement versus a control diet on overall
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Studies looking at the association of dietary components and incontinence found consumption of saturated and monounsaturated fats and carbonated beverages may increase the risk of SUI while intake of
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breads/starches and vegetables may decrease the risk23, 24. Interestingly, similar to the association seen in BPH, zinc intake was associated with SUI in women as was vitamin B12.23, 24 Consumption of phytoestrogens did not affect SUI.
Diet and General Urinary Symptoms Validated questionnaire use was a common way to test associations between diet and LUTS. Most studies were cross-sectional, and thus, determining causality becomes more difficult given researchers believe
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lifetime exposure is more important for health than current diet. Clinically significant LUTS was associated with poor overall diet and dietary variety25, increase in total caloric intake (adjusting for weight),26, 27 and sodium intake in men26. Protein intake may decrease the risk in men25 but increases the risk of storage
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symptoms in women27. In elderly men, consumption of isoflavone (a phytoestrogen) showed a strong correlation with LUTS28. However, a single RCT evaluated the effects of flaxseed extract (high in
phytoestrogens) on LUTS and noted a dose-dependent and significant decrease in LUTS in men on flaxseed13.
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In a longitudinal cohort study, higher vitamin C intake at baseline was associated with less progression of storage LUTS but vitamin C supplementation was associated with worse LUTS at five-year follow-up in
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women29. Diet and OAB
Few studies have directly assessed OAB and diet. There appears to be a weak association with potato/starch consumption30. Evaluation of micronutrients suggests higher consumption of vitamin D, protein, and
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potassium may be protective of OAB in women31. High energy/caloric intake in the setting of high glycemic
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indices and low physical activity may also be a risk factor in women32.
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Fluid intake and LUTS
Table 5 summarizes the 21 publications reviewed with more details provided in Supplemental Tables 3A-D. Fluid Intake and BPH
It is unclear from the few published articles whether there is an association between fluid intake and BPH. In one RCT, 138 men with BPH were randomized to increase fluid intake by 1.5L per day versus placebo33. There was no difference in AUA-SI total, voiding and QOL scores between the groups at six months. However, AUASI storage scores were worse in those who increased fluid intake (effect size=1.3, p<0.001). In a non9
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randomized, uncontrolled study, AUA-SI increased from 7.9 to 8.9 (p=0.028) after subjects increased fluid intake by 2L per day for eight weeks34. However, the magnitude of symptom worsening was small and likely
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clinically insignificant. Fluid Intake and Nocturia
There is not a clear association between fluid intake and nocturia. In a large RCT35, 307 women were
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randomized to receive tolterodine versus tolterodine plus behavioral therapy, which included pelvic floor muscle exercise training, bladder control techniques, and fluid management. No difference in numbers of
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voids at night was found between treatment groups at 10 weeks. However, this RCT did not specifically examine fluid management, since other behavioral therapies were included and all subjects received general information to avoid excessive fluid intake. Similarly a large cohort study in men found no association between night-time fluids and incident nocturia36. In contrast, two uncontrolled case series showed fluid
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restriction improved nocturia37, 38. Fluid Intake and OAB Symptoms
Six out of seven studies on OAB symptoms reported a positive association between fluid intake and urinary
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frequency/urgency, including two small cross-over RCTs. One randomized 69 women to caffeine restriction plus daily fluid increase to 3L, compared to caffeine restriction plus fluid decrease to 750 mL daily39. Another
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included 24 men and women randomized to increase vs. decrease their daily fluid intake by 25% compared to their baseline40. Both trials found significantly increased frequency and urgency symptoms with fluid increase, and decreased frequency and urgency with fluid reductions. Fluid Intake and UI Fourteen articles had mixed results on association between fluid intake and UI: six showed positive, one showed negative and seven no correlations. In a small RCT, increasing fluid intake worsened weekly UI 10
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episodes, while decreasing fluid intake improved weekly incontinence. In contrast, the Zimmern RCT35 did not show any correlation. One RCT did not yield any useful results, since most patients were not able to adhere to the fluid protocols41. Two cohort studies examined new-onset UI: one found consumption of carbonated
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drinks was associated with new onset SUI,24 while another did not show an association between fluid intake
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and new UI42.
Caffeine Intake and LUTS
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Twenty articles on caffeine intake and LUTS are summarized in Table 6 (detailed summary found in Supplemental Tables 4A-E). Most were observational studies, but two small RCTs were reviewed. Most assessed caffeine intake as self-reported cups of coffee or milligrams of caffeine per day, estimated using a self-reported FFQ or other non-validated questions. Two studies in women focused on urodynamic test
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findings related to caffeine. One small study found detrusor pressure during filling increased (but other parameters were unchanged) after caffeine ingestion.43Another found detrusor overactivity in women with UI was associated with higher caffeine intake.44
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Caffeine and BPH
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It is unclear if caffeine intake and BPH are associated, and evidence reviewed was limited to coffee, not caffeine, intake. Three studies on caffeine intake in men with BPH had conflicting results. Two older case control studies of men with surgically-treated BPH found non-significant associations between coffee intake and BPH45, 46. A large, population-based, cross-sectional study found increasing coffee consumption positively associated with BPH47. Caffeine and Nocturia
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Coffee consumption was not associated with nocturia in men or women, as tested in a cohort study of men and a large cross-sectional study of women48, 49. In contrast, the same cross-sectional study found tea intake was associated with increasing nocturia, although the increased risk was small (OR 1.2) and only in women
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drinking three or more cups of tea daily. Another large cross sectional study found women with nocturia were less likely to drink caffeinated beverages after 6pm50. This finding highlights the limitations of crosssectional analyses, since women who have nocturia may be likely to avoid caffeinated beverages in the
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evening.
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Caffeine and OAB/LUTS
Small, randomized interventional studies provide limited evidence that caffeine reduction may decrease OAB symptoms in women. In two RCT (mostly women), caffeine reduction was associated with reduced urinary frequency, urgency, and OAB QOL scores51, 52. Caffeine restriction was not associated with changes in frequency/urgency in a third uncontrolled study39. Coffee consumption in a large cross-sectional study was
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not associated with urgency, but women reporting tea intake (three or more cups daily) were more likely to report urgency53. Fewer studies have evaluated caffeine and OAB in men, though one large, cross-sectional
Caffeine and UI
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study found caffeine intake was not associated with increased LUTS54.
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Overall evidence may suggest a weak positive association between caffeine and UI, but there are conflicting results for UI types, and studies in men are lacking. Four interventional studies (two randomized, two uncontrolled) found no impact for caffeine reduction on UI39, 51, 52, 55. A longitudinal study in women found caffeine associated with frequent UI and urgency urinary incontinence (UUI), but only in women with the greatest caffeine intake56. Caffeine intake was not associated with UI progression when analyzed in the same longitudinal data57. Mixed results were found in several large cross-sectional studies in women, with one finding coffee and tea intake associated with SUI, and tea intake with overall UI (but not UUI), while another 12
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found no association between tea or coffee consumption and any type of UI53, 58, 59. One large cross-sectional study of men found the highest level of caffeine intake associated with moderate to severe UI (but not with
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any UI)60.
Alcohol and LUTS
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Twenty-six articles on alcohol intake and LUTS were identified, reviewed and graded (Table 7). Study details are presented in Supplemental Tables 5A-E. Most publications assessed alcohol intake as self-reported drinks
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per day, week or month, or grams of alcohol consumed based on the subject’s self-report. Four articles analyzed alcohol type (beer, wine, spirits) as well as total consumption. Alcohol and BPH and LUTS in Men
Results for BPH and BPH surgery were consistent among seven of eight articles reviewed, with a decrease in
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BPH diagnosis or surgery in men who drank alcohol compared to non-drinkers. The association between alcohol intake and the reduction in BPH diagnosis and surgery was particularly strong for modest alcohol consumption (defined as 1-3 drinks per day), with this consumption level having the greatest BPH reduction
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compared to non-drinkers.
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LUTS, UI and nocturia in men alone were assessed in 14 articles and had relatively consistent findings with modest drinking associated with fewer symptoms compared to non-drinkers in all but two articles. Heavy alcohol consumption (defined as self-reported alcoholism, >72g/day [>5.1 drinks a day] or >40g/day [>2.9 drinks a day]), however, appears to have a negative effect with an increase in incontinence, obstructive and irritative LUTS61. This “J-shaped” association of alcohol intake and LUTS was most clearly seen in a crosssectional study of 30,196 Korean men participating in a comprehensive health examination, where the odds
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of moderate or severe AUA-SI scores were lowest among modest drinkers (0-10g/day) compared to nondrinkers and highest in men who drank >40g/day62.
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Alcohol and Nocturia Only two articles assessed nocturia. In a group with both genders, no association was found between alcohol intake and nocturia63, whereas in a single article including only men, modest alcohol intake had the lowest
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risk of moderate or severe nocturia48.
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Alcohol and OAB/UI
Among three articles assessing OAB there were inconsistent results. Results from the BACH study showed inconsistent findings by intake level and symptom subtype with few groups achieving statistical significance64, whereas an interview study of 833 elderly individuals found greater odds of urgency and frequency among current drinkers compared to non-drinkers, but not ex-drinkers65. In four articles assessing UI no association
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Tobacco and LUTS
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was found between any type of UI and alcohol intake.
Forty-four articles on tobacco use and LUTS were systematically reviewed (Table 8). Most were cross-
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sectional, but some cohort and case-controls studies were reviewed. Tobacco use was almost always studied as self-reported current cigarette smoking. Tobacco and BPH
Eight of 12 articles reported no association between BPH and tobacco. Four found a negative association between heavy or current smoking and BPH, but no trend in the association with quantity of cigarettes smoked47, 66-68. 14
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Tobacco and Nocturia Evidence regarding nocturia was inconsistent. Of six studies, one showed a positive association between
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current smoking and nocturia in women50, two showed a negative association in women69 and men68, one showed a negative association with heavy current smoking (but not lighter current smoking) in a sample of men and women70. Two studies showed no association48, 71.
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Tobacco and OAB
Within the broad category of evidence for OAB or LUTS in general, there are some consistent and some
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inconsistent findings. A small amount of evidence suggests former and/or current smoking is related to frequency in women. Two studies showed a positive association between urgency and current tobacco use,71, 72
while two did not69, 73. A single study each showed no association with irritative symptoms in men61 or
voiding symptoms in men and women74, but a positive association with obstructive symptoms in men61 and
most inconsistent results. Tobacco and UI
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storage symptoms in women74. LUTS in general was the most common outcome in this category but had the
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We found no evidence to review regarding UI in men. In women, studies reported inconsistent results. Some
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studies provided evidence of a positive association between tobacco use and SUI75, 76, UUI and mixed incontinence77, motor incontinence75, and incontinence of any (unspecified) type59, 77, 78. Six studies showed no associations69, 71, 73, 79-81, and one showed a negative association between occasional UI and current smoking78. In addition, Hannested 200359 showed mixed results between current, former, and heavy smoking and various measures of incontinence. The two studies that examined severe UI showed a positive association59, 78. Tobacco and Other LUTS Measures 15
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A few studies focused on other parameters. Single studies showed positive associations between smoking and women’s maximum cough spike82, cough leak point pressure and maximal intravesical pressures generated by cough83, and men’s estradiol levels84. Two studies showed evidence that male smokers were at
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lower risk of low urinary flow rates85, 86, but another found no association84. No associations were found between tobacco use and women’s maximum closure pressure, mean pressure transmission ratio, degree of urethral axis with stress82, or men’s testosterone, dehydroepiandrosterone (DHEA), or DHEA-S levels or
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prostate weight.84
Key Point Summary
• Expert consensus of the reviewed literature suggests a balanced low-calorie/low-saturated fat diet in a physically active, non-obese person will decrease the lifetime likelihood of developing LUTS and/or BPH,
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but current evidence for associations between diet and individual dietary constituents and LUTS is mixed and suggests associations, if present, are weak.
• Fluid intake is associated with urinary frequency and urgency in men and women and the association is
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bi-directional. Evidence supports the use of fluid reduction to manage urinary urgency (as in the AUA Guideline on OAB)4. Given potential risks from dehydration, recommendations that patients reduce their
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fluid intake by 25%, providing they do not drink <1 L/day, seem reasonable87. Relationships between UI, nocturia and fluid intake are less conclusive. • We found inconsistent associations between caffeine intake and BPH and nocturia. Mixed evidence suggests caffeine reduction may reduce urinary frequency and urgency in women (small effects). Conflicting results related to caffeine and overall UI and UI types suggests any association if present is weak. The small number of studies focused on caffeine and LUTS in men (particularly OAB and UI symptoms) made it difficult to interpret these results. 16
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• Moderate/modest alcohol consumption in men is associated with a reduced risk of BPH and BPH surgery, as well as decreased LUTS compared to non-drinkers, however excessive alcohol intake above the recommended threshold of healthy consumption is associated with worse LUTS in men. These results are
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consistent with the U.S. Department of Health and Human Services’ recommendation on alcohol consumption for men (two drinks or less/day)88. In contrast, we found no evidence for women that avoidance of alcohol reduces the risk of UI or LUTS.
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• We did not find strong evidence that smoking increases UI. Indeed, we found mixed, and therefore weak, evidence for any associations between tobacco use and LUTS. There was perhaps a positive association
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between smoking and urinary frequency in women, based on limited evidence.
Discussion
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We systematically reviewed the literature studying associations between LUTS and daily behaviors, including diet, fluid intake, and caffeine, alcohol and tobacco use. We identified 110 articles meeting our eligibility criteria, graded their evidence, and summarized these findings by population and LUTS condition studied.
low.
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Overall, relatively few, largely observational studies were eligible (< 50 per factor) and evidence quality was
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Based on our review, few definitive conclusions about associations could be made. In observational studies of men, modest alcohol use (compared to non-use) was associated with less likelihood of a BPH diagnosis and fewer LUTS. As alcohol intake of this level falls within federal recommendations, this might be considered a reasonable recommendation in clinical practice. Fluid intake was positively associated with urinary frequency and urgency symptoms in men and women in two small interventional studies and in observational studies of mixed quality. These findings support the inclusion of fluid management within the behavioral strategies
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recommended as first-line treatments for OAB4. In other areas of our review, inconsistent results or lack of evidence precluded conclusions about associations between NUF and LUTS.
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Strengths of this effort include our standardized protocol used for screening citations, determining eligibility for inclusion and abstracting study results. We used an accepted and widely-used system for grading the evidence of the included studies. When possible, we attempted to synthesize results to help clarify clinical
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usefulness of the literature.
One study limitation is that most of the evidence was from observational studies, and we did not attempt
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meta-analyses due to the heterogeneous search results. Few studies in any single area included similar enough outcomes and exposures that statistical integration would be useful or valid. Given our results included lower evidence levels, caution must be taken in making clinical recommendations based on these findings89, 90. However, systematic review of observational studies may be an important alternative when RCTs cannot produce the evidence needed or would be unethical90. For example, a dietary factor may require
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an extended duration of exposure to cause LUTS, which could not be feasibly assessed in an RCT. In another example, RCTs measuring the impact of tobacco on LUTS would be unethical.
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Another weakness to much of the evidence included in this review is the use of self-report measurement to assess exposures. Most of the reviewed articles assessed exposures using self-report, often by interview or
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questionnaire. Thus, the associations between the NUF and LUTS summarized here are subject to limitations of participants’ memory and social desirability effects. Other measurement tools, such as electronic diaries or biomarkers, may provide more valid assessment of exposure in future studies. However, any research in lifestyle factors is likely to face challenges obtaining accurate and unbiased measurements of these factors. The challenges in performing research on lifestyle factors may partially explain the lack of higher quality evidence available. Despite this (or perhaps because of this), we feel a systematic review of this observational data is important to summarize the evidence available (even if lower quality) and to highlight the lack of 18
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evidence in this important topic area. We hope results from this review will spur additional research on lifestyle changes that may modify and/or prevent LUTS. On the other hand, we also acknowledge that strong evidence may never exist for some of these research questions. In these cases, LUTS providers should make a
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practical assessment of the evidence available and consider the individual situation of each patient in making clinical recommendations.
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Conclusions
Systematic literature review revealed that evidence supporting associations between LUTS and diet, fluid
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intake, and caffeine, alcohol and tobacco use is sparse. The data available are largely observational and generally lower quality. Given these factors are often modifiable and are frequently included in management recommendations by LUTS care providers, more and higher quality evidence is needed to better understand
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their impact on LUTS.
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References* 1. Kupelian V, Wei JT, O'Leary MP et al: Prevalence of lower urinary tract symptoms and effect on quality of life in a racially and ethnically diverse random sample: the Boston Area Community Health (BACH) Survey. Arch Intern Med 2006; 166: 2381. 2. Coyne KS, Sexton CC, Thompson CL et al: The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int 2009; 104: 352. 3. Coyne KS, Wein AJ, Tubaro A et al: The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS. BJU Int, suppl., 2009; 103: 4. 4. Gormley EA, Lightner DJ, Burgio KL et al: Diagnosis and treatment of overactive bladder (nonneurogenic) in adults: AUA/SUFU guideline. J Urol, suppl., 2012; 188: 2455. 5. Yang CC, Weinfurt KP, Merion RM et al: Symptoms of Lower Urinary Tract Dysfunction Research Network. J Urol ; 196: 146. 6. Moher D, Liberati 2016A, Tetzlaff J et al: Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med 2009; 6: e1000097. 7. Oxford Centre for Evidence-based Medicine: Oxford Centre for Evidence-based Medicine—Levels of Evidence (March 2009). Available at http://www.cebm.net/oxford-centre-evidence-based-medicinelevels-evidence-march-2009/. 8. Abrams P and Khoury S: International Consultation on Urological Diseases: Evidence-based medicine overview of the main steps for developing and grading guideline recommendations. Neurourol Urodyn 2010; 29: 116. 9. Brown JS, Wing R, Barrett-Connor E et al: Lifestyle intervention is associated with lower prevalence of urinary incontinence: the Diabetes Prevention Program. Diabetes Care 2006; 29: 385. 10. Manonai J, Songchitsomboon S, Chanda K et al: The effect of a soy-rich diet on urogenital atrophy: a randomized, cross-over trial. Maturitas 2006; 54: 135. 11. Schnelle JF, Leung FW, Rao SS et al: A controlled trial of an intervention to improve urinary and fecal incontinence and constipation. J Am Geriatr Soc 2010; 58: 1504. 12. Subak LL, Wing R, West DS et al: Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med 2009; 360: 481. 13. Zhang W, Wang X, Liu Y et al: Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J Med Food 2008; 11: 207. 14. Wing RR, Creasman JM, West DS et al: Improving urinary incontinence in overweight and obese women through modest weight loss. Obstet Gynecol 2010; 116: 284. 15. Araki H, Watanabe H, Mishina T et al: High-risk group for benign prostatic hypertrophy. Prostate 1983; 4: 253. 16. Bravi F, Bosetti C, Dal Maso L et al: Food groups and risk of benign prostatic hyperplasia. Urology 2006; 67: 73. 17. Chyou PH, Nomura AM, Stemmermann GN et al: A prospective study of alcohol, diet, and other lifestyle factors in relation to obstructive uropathy. Prostate 1993; 22: 253. 18. Galeone C, Pelucchi C, Talamini R et al: Onion and garlic intake and the odds of benign prostatic hyperplasia. Urology 2007; 70: 672. 19. Kristal AR, Arnold KB, Schenk JM et al: Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol 2008; 167: 925. 20. Suzuki S, Platz EA, Kawachi I et al: Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia. Am J Clin Nutr 2002; 75: 689. 20
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27. 28. 29. 30. 31. 32. 33.
34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44.
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26.
SC
25.
M AN U
24.
TE D
23.
EP
22.
Lagiou P, Wuu J, Trichopoulou A et al: Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999; 54: 284. Tavani A, Longoni E, Bosetti C et al: Intake of selected micronutrients and the risk of surgically treated benign prostatic hyperplasia: a case-control study from Italy. Eur Urol 2006; 50: 549. Dallosso H, Matthews R, McGrother C et al: Diet as a risk factor for the development of stress urinary incontinence: a longitudinal study in women. Eur J Clin Nutr 2004; 58: 920. Dallosso HM, McGrother CW, Matthews RJ et al: The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int 2003; 92: 69. Erickson BA, Vaughan-Sarrazin M, Liu X et al: Lower urinary tract symptoms and diet quality: findings from the 2000-2001 National Health and Nutrition Examination Survey. Urology 2012; 79: 1262. Maserejian NN, Giovannucci EL and McKinlay JB: Dietary macronutrients, cholesterol, and sodium and lower urinary tract symptoms in men. Eur Urol 2009; 55: 1179. Maserejian NN, McVary KT, Giovannucci EL et al: Dietary macronutrient intake and lower urinary tract symptoms in women. Ann Epidemiol 2011; 21: 421. Wong SY, Lau WW, Leung PC et al: The association between isoflavone and lower urinary tract symptoms in elderly men. Br J Nutr 2007; 98: 1237. Curto TM, Giovannucci EL, McKinlay JB et al: Associations between supplemental or dietary intake of vitamin C and severity of lower urinary tract symptoms. BJU Int 2015; 115: 134. Dallosso HM, Matthews RJ, McGrother CW et al: The association of diet and other lifestyle factors with the onset of overactive bladder: a longitudinal study in men. Public Health Nutr 2004; 7: 885. Dallosso HM, McGrother CW, Matthews RJ et al: Nutrient composition of the diet and the development of overactive bladder: a longitudinal study in women. Neurourol Urodyn 2004; 23: 204. McGrother CW, Donaldson MM, Thompson J et al: Etiology of overactive bladder: a diet and lifestyle model for diabetes and obesity in older women. Neurourol Urodyn 2012; 31: 487. Spigt M, van Schayck O, Knipschild P et al: Is it possible to improve elderly male bladder function by having them drink more water? A randomized trial of effects of increased fluid intake/urine output on male lower urinary tract function. Urology 2006; 68: 1031. Spigt MG, Knottnerus JA, van de Beek C et al: Short-term effects of increased urine output on male bladder function and lower urinary tract symptoms. Urology 2004; 64: 499. Zimmern P, Litman HJ, Mueller E et al: Effect of fluid management on fluid intake and urge incontinence in a trial for overactive bladder in women. BJU Int 2010; 105: 1680. Johnson TM 2nd, Sattin RW, Parmelee P et al: Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults. J Am Geriatr Soc 2005; 53: 1011. Soda T, Masui K, Okuno H et al: Efficacy of nondrug lifestyle measures for the treatment of nocturia. J Urol 2010; 184: 1000. Tani M, Hirayama A, Torimoto K et al: Guidance on water intake effectively improves urinary frequency in patients with nocturia. Int J Urol 2014; 21: 595. Swithinbank L, Hashim H and Abrams P: The effect of fluid intake on urinary symptoms in women. J Urol 2005; 174: 187. Hashim H and Abrams P: How should patients with an overactive bladder manipulate their fluid intake? BJU Int 2008; 102: 62. Dowd TT, Campbell JM and Jones JA: Fluid intake and urinary incontinence in older communitydwelling women. J Community Health Nurs 1996; 13: 179. Townsend MK, Jura YH, Curhan GC et al: Fluid intake and risk of stress, urgency, and mixed urinary incontinence. Am J Obstet Gynecol 2011; 205: 73. Creighton SM and Stanton SL: Caffeine: does it affect your bladder? Br J Urol 1990; 66: 613. Arya LA, Myers DL and Jackson ND: Dietary caffeine intake and the risk for detrusor instability: a casecontrol study. Obstet Gynecol 2000; 96: 85.
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48. 49. 50.
Morrison AS: Prostatic hypertrophy in greater Boston. J Chronic Dis 1978; 31: 357. Morrison AS: Risk factors for surgery for prostatic hypertrophy. Am J Epidemiol 1992; 135: 974. Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002; 90: 649. Shiri R, Hakama M, Häkkinen J et al: The effects of lifestyle factors on the incidence of nocturia. J Urol 2008; 180: 2059. Tettamanti G, Nyman-Iliadou A, Pedersen NL et al: Influence of smoking, coffee, and tea consumption on bladder pain syndrome in female twins. Urology 2011; 77: 1313. Asplund R and Aberg HE: Nocturia in relation to body mass index, smoking and some other life-style factors in women. Climacteric 2004; 7: 267.
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45. 46. 47.
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* References 51 to 125 for this article can be obtained at http://jurology.com/.
22
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Table 1. Criteria for excluding article from the systematic review Number* 158
No relevant LUTS or LUT condition (including prostate cancer)
83
LUTS studied as treatment result or adverse effect (e.g. post-prostatectomy incontinence)
24
Sample size < 25 (unless RCT design)
3
Editorial, commentary, non-systematic review
76
Non-relevant research type (e.g. qualitative studies, instrument development)
6
Pregnant population
M AN U
TE D EP
Pediatric population
9
5 1
AC C
Not human subjects research
SC
No relevant non-urologic factor studied
RI PT
Reason for Exclusion
*More than one reason for exclusion may be listed for an individual article
1
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Level
RI PT
Table 2. Levels of evidence used in grading the articles (modified from the 2009 Oxford Centre for Evidence-based Medicine Levels of Evidence and the International Consultation on Urological Diseases)7, 8 Study Design or Type Systematic review of RCTs
1b
Individual RCT (good quality)
2a
Systematic review of cohort studies
2b
Individual cohort study, low quality RCT
3a
Systematic review of case control studies
3b
Individual case control study
4a
Good quality case-series, poor quality cohort or case control study
4b
Cross-sectional study
5
Expert opinion
M AN U
TE D
EP
AC C
RCT – Randomized controlled trial
SC
1a
2
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Table 3. Numbers of publications obtained in each PubMed search and included in review Additional article identified during review
Diet
128
31
28
0
Fluid Intake
207
30
19
2
Caffeine
36
22
19
Alcohol
66
30
26
Tobacco
126
45
44
TOTAL
563
158
136
Total Publications included in Systematic Review
RI PT
Publications eligible after full text review
SC
Publications eligible after screening citation/abstract
M AN U
Citations from PubMed Search
TE D
Non-urologic Factor
28
21
1
20
0
26
0
44
3
110*
EP
*Some publications provided results for more than one non-urologic factor; specifically 15 and 7 publications contributed results for 2 and 3 factors, respectively.
Table 4. Overview of search results for diet and LUTS Number articles
Study Design
Population
Results Summary*
Comments
BPH15-22, 91, 92
9
2-Cohort
All Men
Mixed results:
Diet may indirectly affect prostate growth through influences on androgens. Low caloric intake high in polyunsaturated fats may
AC C
LUTS Condition Studied
6-Case-control 1 -Cross-
7 - S, + 7 - S, -
3
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9
be protective. Most effects from diet came indirectly through weight alteration.
4- RCT
8 – Women
Mixed results:
4 - Cohort
1– Men/Women
6 - S, +
14, 23, 24, 93, 94
1 - Crosssectional
3 - S, 5 - NS
7
1 – RCT
5 – Men
Mixed results:
1 – Cohort
1 – Women
3 - S, +
5 – Crosssectional
1– Men/Women
2 - S, -
29, 95
2 - NS
3
3 - Cohort
2 –Women
Mixed results:
1 – Men
1 - S, +
TE D
OAB30-32
2 - S, -
3 – NS
Weak associations noted, mostly indirect through weight gain/loss. Some evidence for effects on OAB through diabetes mechanism (neurovascular)
AC C
EP
Overall weak associations. Low caloric intake, high in polyunsaturated fats and high in vegetables may be protective from LUTS. Vit C may be protective when obtained from food.
M AN U
Non-Specific Urinary Symptoms13, 25-
RI PT
Incontinence 9-12,
7 – NS
SC
sectional
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association * Studies that tested more than one association may be counted more than once in this column.
4
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Table 5. Overview of search results for fluid intake and LUTS Number articles
Study Design
Population
Results Summary
Comments
BPH33, 34, 96
3
1 - RCT
3 - Men
Mixed results:
Fluid intake worsens storage symptoms with no impact on voiding symptoms.
1 - Outcome research
SC
1 - S, +
1 - Crosssectional 1 – RCT
3- Men
1- Cohort study
2 - Men & Women
2 - Outcome research
7
3 - RCT
1 - Cohort study
AC C
35, 39, 40, 97-99
1- Women
EP
2 - Crosssectional OAB/LUTS (non-UI)24,
M AN U
6
2 - NS
TE D
Nocturia35-38, 96, 97
3 - Crosssectional
RI PT
LUTS Condition Studied
5 - Women 2 - Men & Women
Mixed results: 2 - S, + 4 - NS
Positive association in most studies: 6 - S, + 1 - NS
Evidence was inconclusive whether fluid restriction reduces nocturia.
Most studies showed positive association between fluid intake and frequency and/or urgency
5
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symptoms. 14
5 - RCT
10 - Women
2 - Cohort study
1 - Men
1 – Case series
3 - Men & Women
97, 99-101
6 - Crosssectional
Mixed results: 6 - S, + 1 - S, -
Results were inconclusive for an association between fluid intake and UI.
RI PT
UI11, 24, 35, 39-42, 55, 58, 60,
M AN U
SC
7 - NS
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
Table 6. Overview of search results for caffeine intake and LUTS Study Design
BPH45-47
2- Case-control
Results Comments Summary*
3- Men
Mixed results:
EP
3
Population
TE D
LUTS Condition Studied Number articles
Nocturia48, 50, 53
3
AC C
1- Cross-sectional
2- NS, -, + 1- S, +
1- Cohort
1- Men
2- Cross-sectional
2- Women
Mixed results: 1- S, +
Unclear if caffeine or other coffee constituents might influence BPH. Tea (but not coffee) intake associated with nocturia.
6
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2- NS, + and +/OAB/LUTS (non-UI)39, 51-
5
2- RCT
3-Women
1- Case series
1- Men & Women
2- Cross-sectional
2- NS, +/-
2- RCT
9-Women
2- Cohort
2- Men & Women
1- Case series
TE D
12
3- S, +
1-Men
Mixed results: 5- S, +
2- NS, +
2
AC C
EP
7- Cross-sectional
Urodynamic parameters43, 44
Caffeine restriction associated with small improvements in frequency and urgency in women.
M AN U
1- Men
UI39, 49, 51, 52, 55-60, 102, 103
Mixed results:
SC
54
RI PT
1- S, -
1- Case series
1- Cross-sectional
2-Women
4- NS, +/1- NS, -
2- S, +
Overall evidence may suggest weak positive association between caffeine and UI, but conflicting results for UI types. Studies in men are lacking. Positive results but conflicting findings (varying endpoints)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association * Studies that tested more than one association may be counted more than once in this column. 7
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Table 7. Overview of search results for alcohol and LUTS Number articles
Study Design
Population
Results Summary
Comments
BPH17, 46, 47, 68, 104-108
9
2- Cohort
10- Men
Consistent results:
Decrease in BPH diagnosis surgery in men who drank alcohol compared to non-drinkers (all but one study)
3- Case control
1- Metaanalysis 10
2- Cohort
9- Men
AC C
EP
8- Cross sectional
Consistent results:
TE D
109-113
M AN U
1- NS
SC
8- S +
3- Cross sectional
Male LUTS19, 54, 61, 62, 95,
RI PT
LUTS Condition Studied
7- S+ (negative associations with modest alcohol, positive with heavy alcohol use) 2- NS
Modest drinking associated with fewer symptoms compared to non-drinkers (all but two articles). Alcoholism has negative effect on urinary symptoms.
1- variable results
9
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1- Cohort
1- Men
1- Crosssectional
1- Women and Men
Inconsistent results: 1- 1 subgroup S+ 1- NS
3
3- Women and Men
1- Cohort 2- Crosssectional
Inconsistent results: 2- NS
1- S only for subgroup
5
3- Crosssectional
1- Men 3-Women
2- NS, +
1- Women and Men
2- NS, +/-
No significant association noted
EP
1- Case series
1- S+
TE D
UI59, 63, 95, 112, 114
Inconsistent findings for association between alcohol and urinary symptoms
M AN U
OAB/LUTS (non-UI)63-65
Inconsistent results for alcohol and nocturia
RI PT
2
SC
Nocturia48, 63
AC C
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
10
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Table 8. Overview of search results for tobacco use and LUTS Number articles
Study Design
Population
Results Summary
BPH17, 45-47, 66-68, 85, 86, 115-117
12
4-Cohort
All Men
Mixed results: 7NS
Some evidence for negative association, more evidence for no association
SC
6-Crosssectional
Comments
RI PT
LUTS Condition Studied
1- NS, S, + 2-Casecontrol
M AN U
2- NS, S, 2- S, -
Nocturia48, 50, 68-71
6
5-Crosssectional
3-Women
Mixed results:
Inconsistent results
85, 86, 95, 109, 111, 113, 118-123
EP
19
18-Crosssectional
AC C
OAB/LUTS (non-UI)54, 61, 69, 71-74,
TE D
2-Men 1-Cohort
6-Women 11-Men
2- NS
1- NS, S, 1- S, + 2- S, Mixed results: 7NS
1-Cohort
2- Women and Men
3- NS, S, + 7- S, +
Some evidence for a positive association, other evidence shows no association
2- not 11
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reported 13
2-Casecontrol
All Women
Some evidence for a positive association, other evidence 1- NS, S, +/- shows no association 3- S, +
SC
11-Crosssectional
Mixed results: 6NS
RI PT
UI59, 69, 71, 73, 75-81, 118, 124
M AN U
1- S, +/-
2- not reported
Other- UDS parameters & plasma levels82-86
5
1-Case control
2-Women
Mixed results:
3- Men
2- NS, S, + 1- S, + 2- S, -
EP
3-Crosssectional
TE D
1-Case series
Outcomes varied, some evidence of associations
AC C
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association
12
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Abbreviation Key
AUA-SI: American Urological Association Symptom Index
DHEA: dehydroepiandrosterone FFQ: food-frequency questionnaire LURN: Symptoms of Lower Urinary Tract Dysfunction Research Network LUTS: lower urinary tract symptoms NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases
SC
NUF: non-urologic factors
RI PT
BPH: benign prostatic hyperplasia
OAB: overactive bladder
QOL: quality of life RCT: randomized clinical trial SUI: stress urinary incontinence UI: urinary incontinence
AC C
EP
TE D
UUI: urgency urinary incontinence
M AN U
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Bradley et al. Evidence for the Impact of Diet
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Supplemental Table 1. Terms used in PubMed literature search. Terms for each topic were combined into search strings, and each search performed by combining the search string for LUTS with the string for one of the non-urologic factors. Searches were further limited to human studies, adult study populations and English language publications, and to publications not labeled as case reports, editorials and letters.
MESH Terms
Complete Search String
Alcohol intake
Alcohol drinking
"Alcohol Drinking"[Mesh] OR "Alcoholic Intoxication"[Mesh] OR "Alcoholism"[Mesh] OR “Binge Drinking”[Mesh]
SC
Alcohol intoxication Alcoholism
M AN U
Binge drinking Caffeine intake
"Caffeine"[Mesh] OR "Coffee"[Mesh] OR "Coffea"[Mesh] OR "Energy Drinks"[Mesh]
Caffeine Coffee Coffea
TE D
Energy Drinks Diet
Diet
"Diet"[Mesh] OR "Eating"[Mesh:NoExp] OR "Nutritional Status"[Mesh]
EP
Nutritional status
Drinking Drinking behavior
AC C
Eating Fluid intake
RI PT
Search Topic
"Water-Electrolyte Balance"[Mesh] OR "Drinking Behavior"[Mesh:NoExp] OR "Drinking"[Mesh] OR fluid intake [title/abstract]
Water/electrolyte balance Fluid Intake*
1
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Lower Urinary Tract Symptoms Prostatic Hyperplasia
LUTS
"Lower Urinary Tract Symptoms"[Mesh] OR "Prostatic Hyperplasia"[Mesh] OR "Urination Disorders"[Mesh:NoExp] OR "Urethral Obstruction"[Mesh] OR “enuresis”[Mesh] OR “urinary retention”[Mesh] OR urinary hesitanc*[Title/Abstract] OR post void dribbl*[Title/Abstract] OR post-void dribbl*[Title/Abstract] OR postvoid dribbl*[Title/Abstract] OR underactive bladder*[Title/Abstract] OR under-active bladder*[Title/Abstract] OR under active bladder*[Title/Abstract]
Urination Disorders
RI PT
Urethral Obstruction Enuresis Urinary retention
SC
Urinary hesitancy*
Tobacco use
M AN U
Post void dribble* Underactive bladder*
"Tobacco Products"[Mesh] OR "Tobacco"[Mesh] OR "Smoking"[Mesh] OR "Nicotine"[Mesh] OR "Tobacco Use Cessation Products"[Mesh]
Smoking Nicotine Tobacco
TE D
Tobacco Products Tobacco Use Cessation Products
EP
*Terms searched as text words (limited to the title or abstract). Text words were used in search strings when MESH terms were not sufficient.
Author /Year
Araki15
Oxford Level
3b
AC C
Supplemental Table 2A. BPH and Diet- Detailed Summary of Articles Study Design, Duration Followup
Population, N
Case-
Men, 100 BPH and
LUTSOutcome(s)
BPH (diagnosis confirmed by hx,
Diet Variable
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Rice, wheat, seafood, meat, milk, green & yellow
milk OR=2.25 vegetables OR=3.91
NS rice, wheat,
No 2
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3b
Bravi16 2006
3b
100 controls
digital palpitation, transrectal ultrasonotomog raphy, x-ray, and biopsy)
vegetables, pickles (FFQ, 5point scale)
Casecontrol
Men, 1369 BPH, 1451 controls
BPH (surgically treated, dx ≤ 1yr before)
(daily g, FFQ) Proteins --Vegetable proteins --Animal proteins Sugars Starch Total fats --Vegetable fats --Animal fats Saturated fatty acids Monounsaturated fatty acids Polyunsaturated fatty acids Oleic acid Linoleic acid Linolenic acid Other polyunsat fatty acids Cholesterol (mg)
Quintiles 2-5 (ref: 1) 1.04 1.01 1.21 1.04 1.31 1.15 1.13 1.09 1.02 1.13 1.01 1.07 0.82 0.84 0.88 0.87 1.31 1.19 1.35 1.51 1.00 1.03 0.94 0.94 1.05 0.97 1.05 0.95 0.92 1.11 0.84 0.85 1.01 0.95 0.94 0.91 0.89 1.10 1.09 1.06 0.95 0.80 0.67 0.72 0.91 1.13 1.05 1.10 0.97 0.78 0.67 0.73 0.95 1.07 0.86 0.71 0.98 1.05 0.98 1.02 1.13 1.16 1.20 1.00
Casecontrol
Men, 1369 BPH, 1451 controls
(weekly servings, FFQ)
Quintiles 2-5 (ref: 1) 0.89 1.11 1.11 1.11 0.69 0.86 0.94 0.96 1.12 1.42 1.60 1.55 1.08 1.26 1.59 1.69 1.68 1.43 1.43 1.30 1.03 0.96 0.93 0.74 1.53 1.43 n/a n/a
pickles OR=1.99
AC C
EP
TE D
M AN U
SC
Bravi91, 2006
control
RI PT
1983
BPH (surgically treated, dx ≤ 1yr before)
Milk & diary Coffee & tea Cereals
seafood, meat; S+ milk, vegetables, pickles
Yes NS NS NS NS S+ NS NS NS NS NS SNS SSNS NS Yes NS NS S+ S+ NS SS+ 3
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Bread Pasta & rice
Poultry Red meat Fish
M AN U
Cheese
SC
Eggs
RI PT
Soups
1.03 1.52 1.40 1.39 0.90 0.89 0.95 0.75 1.18 1.00 1.11 1.13 1.02 0.85 0.91 0.88 0.88 0.74 n/a n/a 1.07 1.16 0.97 1.07 1.02 0.83 0.67 0.66 0.97 0.95 0.88 0.81 0.97 0.86 0.90 n/a 1.02 0.66 0.79 0.82 1.05 0.71 1.06 1.04 0.86 0.85 0.86 0.94 1.06 1.08 1.02 0.97
S+ NS NS NS SNS SNS NS SNS NS NS
Pulses
Raw vegetables
Cooked vegetables
TE D
Total vegetables Potatoes
EP
Citrus fruit
Chyou17 1993
4b
Crosssectional
Men,
AC C
Other fruit
846 BPH and 5735 no
BPH (tissueconfirmed)
Total fruit Desserts
Beef Chicken Wieners Spam/lunchmeat
Low, high (ref: none) 1.06 1.25 0.89 0.98 1.01 0.79 0.91 1.01
Yes S+ NS NS NS 4
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1.06 1.03 0.98 0.96 0.94 0.92 1.01 0.69 0.98 0.99 1.09 0.91 1.06 0.93 0.59 0.92 1.01 1.08 0.87 1.00 0.76 0.92 1.03 0.94 1.20 1.04 1.16 1.14 1.26 1.08 1.12 1.04 1.05 0.99 0.99 1.09 0.91 0.79 1.07 1.06 0.79 1.07 0.99 1.04 0.95 0.82 1.00 1.21 1.09 1.12
NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS
Onion <4/wk 0.94 (0.80 -1.11), >=4 per wk 0.41 (0.24-0.72) Garlic intermediate use 0.89 (0.75-1.06), high
Onion and garlic, both significant inverse association
Galeone 18 2007
3b
Casecontrol
AC C
EP
TE D
M AN U
SC
RI PT
Vienna/pork sausage Bacon Eggs Char siu Shrimp Raw fish Dried fish Dried cuttlefish Fish cake Tofu Rice Miso soup Saimin/udon Corn, on the cob Corn, whole kernel Tomatoes, sliced Tomato juice Lettuce Celery Salted cabbage Pickled turnip Pickled plum Tsukudani Milk Fruit drinks (g/week)
BPH
Men (age <75), 1369 cases, 1451 controls
Surgical admission BPH
FFQ - onion intake (nonusers, infrequent users [fewer than 4 portions per week], regular users [4 or more portions per week])
Yes- age, site, BMI, education, calorie intake, 5
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Incident BPHmedical or surgical treatment or repeated elevation (>14) on AUA-SI
new surgically treated BPHhistologically confirmed, dx within 1 yr
FFQ- intake assessed in quintiles
Surgery for BPH (n=1589) or AUASI score of 15-35 (n=1934)
131 item validated FFQ
Lagiou21 1999
3b
Casecontrol
Men, 184 cases, 246 controls
Suzuki20 2002
2b
Prospecti ve cohort,
Men, 3523 BPH and 24388 no BPH
8 year
M AN U
7 year follow-up
FFQ - Macronutrients, micronutrients, diet supplements, food groups
with BPH
activitylevel , smoking, EtOH
Fat intake (highest vs lowest quintile) HR 1.31 (1.05, 1.63), Polyunsat fats (high v. low quintile) HR 1.27 (1.03, 1.57), Zinc (high vs low quintile) 0.69 (0.50-0.96), Vegetables ( 4 vs <1 /day) HR 0.68 (.50-.92), Red meat daily (vs. <1/week) HR 1.38 (1.01-1.88)
Total Energy NS, Total and polyunsaturat ed fats S, Antioxidants NS, Total and dietary Zinc S, Lycopene/Zinc /Vit D S (weak), Red meat S, Vegetables S
Yes- age, race, waist/hip ratio, TEI
Fruits OR per quintile increase 0.84 (0.72– 0.97), Added lipids OR per quintile 1.28 (1.111.48), Zinc OR per daily increase 1.89 (1.03– 3.46)
Fruits S-, added lipids S+, zinc S+
Yes- age, height, BMI, education, TEI
TEI, highest vs. lowest quintile for BPH
S+
Yes
SC
Men (age > 54), 4770
TE D
Prospecti ve cohort,
EP
2b
AC C
Kristal19 2008
use 0.72 (0.57 -0.91) per week], regular users [4 or more portions per week]) and garlic use (none or low, intermediate, high)
RI PT
and garlic use (none or low, intermediate, high)
S+ OR: 1.29; 95% CI: 1.14, 1.45; and BPH
NS 6
ACCEPTED MANUSCRIPT
symptoms OR: 1.43; (95%CI 1.23, 1.66)
follow-up
S+
3b
Casecontrol
Men, 1369 cases, 1451 controls
Surgery for BPH (BPH defined as need for surgery)
AC C
Tavani22 2006
EP
TE D
M AN U
SC
RI PT
Energy-adjusted total protein intake with total BPH (OR 1.18; 1.05, 1.33) and BPH surgery (1.26; 1.06, 1.49).
FFQ - structured
Energy-adjusted total fat intake - not associated with BPH
Eicosapentaenoic, docosahexaenoic, and arachidonic acids – associated with moderate increase in BPH Carotene - OR 0.8 a-carotene - OR 0.83 b-carotene - OR 0.82 CisBCarotene - OR 0.82 Sodium - OR 1.3 Zinc
Variable
Yes
BPH: benign prostatic hyperplasia, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, FFQ = Food frequency questionnaire, OR = Odds ratio, TEI = Total energy intake, RR = Relative risk, HR = Hazard ratio 7
ACCEPTED MANUSCRIPT
Supplemental Table 2B. Incontinence and Diet - Detailed Summary of Articles Population, N
RCT,
Women (overweigh t, prediabetic), 1957
UI 1+/week,
Women, 4592
SUI at least several times/ month
2b
Prospecti ve cohort, 1 year follow-up
Diet Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted?
OR 0.76 (0.61-0.95) OR 0.80 (0.64-1.01) OR weekly urge not reported
SNS NS
Yes
SC
SUI 1+/week,
Intervention of a low-fat diet and 150 min/week of moderate-intensity physical activity
RI PT
Comments
UUI 1+/week, ; (Q)
M AN U
2.9 year mean follow-up
LUTSOutcome(s)
per day Protein (g) Total fat (g) Monounsaturated fatty acids (g) Saturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrates (g) Starch (g) Sugars (g) Cholesterol (mg) Fiber (g) Retinol (μg) Carotene (μg) Thiamin (mg) Riboflavin (mg) Niacin (mg)
TE D
Dallosso23 2004
1b
Study Design, Duration Followup
EP
Brown9 2006
Oxford Level
AC C
Author /Year
Quintiles (2-5 vs 1) 1.33 1.35 1.73 1.23 1.38 1.35 1.27 2.02
NS S+
1.10 1.52 1.55 1.57
NS
1.08 1.46 1.08 2.02
S+
1.22 1.11 1.16 0.95 0.95 0.68 0.59 0.73 0.87 0.93 0.68 0.85 1.22 0.94 0.74 0.70 1.09 1.24 1.34 2.09 1.09 0.88 1.02 0.76 1.28 1.12 1.60 1.60 0.96 1.02 0.86 1.07
NS S- (p=0.05) NS SS+ NS NS NS
Yes
8
ACCEPTED MANUSCRIPT
NS NS NS NS S+ NS NS NS NS NS NS NS S+ NS NS NS NS NS
OAB
OAB S-
SC
RI PT
0.92 0.99 1.12 0.82 0.84 1.07 0.92 0.93 1.10 1.31 1.08 0.92 1.12 0.71 1.12 0.92 1.52 1.27 1.84 1.66 0.84 0.62 0.76 0.82 0.99 1.03 1.23 1.20 1.10 1.13 1.13 0.73 0.73 0.73 0.81 0.81 0.79 0.93 1.12 0.85 0.86 0.94 0.99 0.90 0.95 0.98 0.82 0.80 1.40 1.57 1.89 0.52 0.78 1.04 1.15 1.14 1.20 1.10 0.91 1.05 1.17 1.18 0.98 0.94 1.07 0.82 0.83 0.82 0.99 0.93 1.03 1.00
Prospecti ve cohort, 1 year follow-up
Women, 5873 (OAB analyses), 5682 (SUI analyses)
OAB at least several times/ month; SUI at least several times/ month
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (daily) Dairy & eggs (5-7, 8-9, 10-12, 13+/week)
EP
2b
AC C
Dallosso24 2003
TE D
M AN U
Vitamin B6 (mg) Vitamin B12 (μg) Vitamin C (mg) Vitamin D (μg) Vitamin E (mg) Total folate (μg) Calcium (mg) Iron (mg) Potassium (mg) Zinc (mg) Sodium (mg) Selenium (μg) Iodine (μg) Magnesium (mg) Copper (mg)
No
0.61 0.71 0.64 0.88
0.98 0.92 0.96 0.88 0.86 1.07
0.94 1.02 1.05 1.00 0.89 0.85
NS NS
NS NS
NS 1.05 0.98
9
ACCEPTED MANUSCRIPT
NS
1.13 1.03 0.89 1.11
NS
1.18 1.11 1.41 0.65
NS S-
0.75 0.62 0.78 0.80
NS SUI NS
SC
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (daily) Dairy & eggs (5-7, 8-9, 10-12, 13+/week) Milk (280-424ml, 425567ml, 568+ml/day) Bread (>daily) Sweets & snacks (1, 2, 34, 5+/day)
1.00
RI PT
Milk (280-424ml, 425567ml, 568+ml/day) Bread (> daily) Sweets & snacks (1, 2, 34, 5+/day)
AC C
EP
TE D
M AN U
SUI 0.99 0.81 0.96 0.81
1.16 1.22 0.95 0.79 0.57 0.78
0.96 1.02 1.27 1.30 1.06 0.96
NS S-
NS NS
NS 0.99 0.87 NS 0.86 NS 1.10 0.86 0.88 0.93
1.21 1.09 1.36 0.73
NS S-
10
ACCEPTED MANUSCRIPT
Maserejian 93 2010
4b
Schnelle11 2010
1b
Subak12 2009
1b
Crosssectional
RCT,
Soy-free diet (control) vs. Soy-rich diet
Women, 2060
UI, modsevere (Sandvik Index)
TEI, Carbohydrate, Protein, total fat, saturated: polyunsaturated fat ratio (FFQ)
TEI - quintile 5 vs 1
UI episodes
Toileting assistance, exercise, choice of food/snack/fluid every 2 hour for 8 hours/day for 3 months
n/a
All other NS
Men & Women in nursing homes, 112
TEI S+, Carbs NS, Protein NS, total fat NS, SFA:PUFA ratio S+
Yes
Intervention - increase in fluid intake, caloric intake and weight
more fluid = more UI
No
Mean weekly number of UI episodes decreased by 47% in intervention group, compared with 28% control group (P=0.01).
S+ (UI)
n/a
OR 2.86 (1.56-5.23); SFQ:PUFA ratio (quintile 5 vs 1) OR 2.48 (1.22-5.06)
RCT
AC C
EP
3 month follow-up
UUI- S,
UUI, SUI, Urgency, Frequency
RI PT
12 week follow-up for each intervent ion
Soy-free control diet: increased UUI (22.2 vs 11.1, p< 0.05)
Women (peri/post menopausa l), 36
SC
Small crossover RCT,
NS
M AN U
2b
TE D
Manonai10 2006
0.77 0.99 1.03 1.07
Women, 226 weight loss program, 112 controls
UI, SUI, UUI after 6 months
Standard reduced calorie diet (1200 to 1500 kcal/day) - no more than 30% of calories from fat; Increase physical activity
11
ACCEPTED MANUSCRIPT
Compared with control group, intervention group had greater decrease in frequency of SUI (P=0.02), but not UUI (P=0.14).
UI
Prospecti ve, nonrandomiz ed Cohort (analysis using RCT
Baseline dietary phytoestrogen
Women, 226 weight loss program, 112 controls
Total UI, SUI and UUI episodes/wk (D)
AC C
2b
SC
Women, 1459
10 year follow-up Wing14 2010
M AN U
Prospecti ve cohort,
NS (UUI)
OR all NS
S+ (UI, SUI, UUI) NS
Yes
TE D
2b
S+ (SUI)
Higher proportion of intervention group than control group had >=70% reduction in frequency of all UI (P<0.001), SUI (P=0.009), and UUI (P=0.04).
EP
Waetjen94 2013
RI PT
(Interventio n group had mean weight loss 8.0% (7.8 kg), compared with 1.6% (1.5 kg) in control group (P<0.001)).
24h urine loss (pad
Weight loss program: Calorie and fat restricted diet of 1,200 - 1,800 kcal/day; < 30% of calories from fat
Yes
Ref: Weight gain <5% weight loss – no change
5-10% weight loss – 5-10% weight loss
53-63% fewer total UI/wk at 6/12/18 months (p<0.05)
5-10% weight loss 12
ACCEPTED MANUSCRIPT
data),
test)
>=10% weight loss
at 6/12/18 months:
43-56% fewer Urge UI/wk at 6/12/18 mo (p<=.001, .02 and .06)
S+ Total
RI PT
18 month follow-up
68-70% fewer Stress UI/wk at 6/12/18 mo (p<=0.05)
SC
50-56% less urine loss on pad test at 6/12/18 mo (p>.05)
S+ Stress S+ Urge (except NS at 18 mo) Pad test NS
M AN U
>10% weight loss – 52-66% fewer total UI/wk at 6/12/18 months (p<0.001)
AC C
EP
TE D
74-77% fewer Stress UI/wk at 6/12/18 mo (p<.02) 30-62% fewer Urge UI/wk at 6/12/18 mo (p<.01) 55-56% less urine loss on pad test at 6/12/18 mo (p=.01, .02, .10)
>10% weight loss at 6/12/18 months: S+ Total S+ Stress S+ Urge Pad test NS (borderline S+ p~0.05 at 13
ACCEPTED MANUSCRIPT
12/18 mo)
AC C
EP
TE D
M AN U
SC
RI PT
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, OAB = Overactive bladder, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial, TEI = Total energy intake
14
ACCEPTED MANUSCRIPT
Supplemental Table 2C. OAB/LUTS (non-UI) and Diet- Detailed Summary of Articles Populatio n, N
Prospecti ve cohort,
Women, 5816
LUTSOutcome(s)
Diet Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted?
PER DAY Protein (g) Total fat (g) Monounsaturated fatty acids (g) Saturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrates (g) Starch (g) Sugars (g) Cholesterol (mg) Fiber (g) Retinol (μg) Total carotene (μg) Thiamin (mg) Riboflavin (mg) Niacin (mg) Vitamin B6 (mg) Vitamin B12 (μg) Vitamin C (mg) Vitamin D (μg) Vitamin E (mg) Total folate (μg) Calcium (mg)
Quintiles (2-5 vs 1) 0.95 0.56 0.86 0.87 0.80 0.95 1.23 0.78
SC
OAB at least several times/month
RI PT
Comments
Yes NS NS
0.71 0.76 0.97 0.80 0.77 0.79 1.27 0.93
NS NS
0.82 0.85 0.86 0.72 1.19 1.31 1.01 1.22 1.18 0.88 1.11 0.82 0.94 0.89 1.31 1.33 0.87 0.96 1.05 0.85 1.22 0.96 0.88 1.24 0.63 1.13 0.83 0.94 0.89 1.05 0.97 0.95 0.68 0.74 0.65 0.72 1.02 0.74 1.08 1.22 0.66 0.67 0.65 0.70 0.72 0.93 0.62 0.98 0.75 0.91 0.75 0.98 1.25 1.15 1.05 1.33 0.99 0.73 0.51 0.75 1.09 1.09 1.11 1.01
NS NS NS NS NS NS NS NS NS NS NS NS NS NS SNS NS
M AN U
1 year follow-up
TE D
2b
Study Design, Duration Followup
EP
Dallosso30 2004
Oxford Level
AC C
Author /Year
15
ACCEPTED MANUSCRIPT
SC
Men, 4382
OAB at least several times/month
All veg. (4, 5, 6, 7+/day) Potatoes (5-7/week, > daily) Fruit (2, 3, 4, 5+/day) All meat (6-7, 8-9, 10-11, 12+/week) Fish (2, 3+/week) Cereal products (2-3, 4+/week) Breakfast cereals (>=daily) Dairy & eggs (5-7, 8-9, 1012, 13+/week) Milk (280-424ml, 425567ml, 568+ml/day) Bread (more than daily) Sweets & snacks (1, 2, 3-4, 5+/day)
1.13 1.15 0.91 1.15
M AN U
Prospecti ve cohort,
TE D
1 year follow-up
EP
2b
AC C
Dallosso31 2004
0.90 0.94 0.76 1.01 1.11 0.90 0.99 1.29 0.89 0.83 0.81 0.96 0.69 0.60 0.83 0.99 0.87 0.63 0.85 0.90 0.82 0.77 0.72 0.80 0.66 0.89 0.80 0.67 0.94 0.96 1.02 1.36 0.85 0.84 0.65 0.99 0.91 0.89 0.94 1.05
RI PT
Iron (mg) Potassium (mg) Zinc (mg) Sodium (mg) Selenium (μg) Iodine (μg) Magnesium (mg) Copper (mg)
NS NS S- (P=0.05) NS NS NS NS NS NS
NS
1.05 1.40 0.77 1.08 0.99 0.94
S+ (p=0.05) NS
0.84 0.95 1.17 1.38 1.03 0.91
NS NS
1.19 1.08 0.86
NS
1.04
NS
1.19 0.93 0.93 1.04
NS
1.09 1.12 0.96 1.06
NS NS
No
16
ACCEPTED MANUSCRIPT
McGrother 32 2012
2b
Prospecti ve cohort,
Women age >39), 3411
Incident OAB (Q)
Dietary GI, TEI (FFQ)
NS
No direct relationship between total energy index or GI with new OAB (no numbers)
NS; NS
RI PT
1 year follow-up
0.82 0.80 1.02 0.99
2b
Study Design, Duration Followup
Population, N
Prospecti ve cohort,
Men and Women, 2825
4b
Crosssectional
AC C
Erickson25 2012
AUA-SI scores
Diet Variable(s)
Men, 1385
"LUTS" - difficulty voiding and/or bladder does not feel empty
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Baseline Vit C intake and Followup Vit C intake (FFQ)
Q4 v Q1 - 0.63 (progression of disease); Men: Recent Vit C intake = improved symptoms. Women: recent Vit C intake = worse storage symptoms (OR 1.66 (1.18 2.35)
Baseline Vit C = decreased progression; Current Vit C = decreased symptoms in men, increased in women
Yes
Overall dietary quality - 3 tertiles from HEI score; Poor diet (lowest vs. highest tertile) . Source: USDA Healthy Eating Index (HEI)-
Poor diet- OR 1.7 (95% CI 1.05-2.90)
LUTS- poor diet quality, S+
Yes
EP
5 year follow-up
LUTSOutcome(s)
M AN U
Curto29 2015
Oxford Level
TE D
Author /Year
SC
OAB = Overactive bladder, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, GI = Glycemic index, TEI = Total energy intakeSupplemental Table 2D. General Urinary Symptoms and Diet - Detailed Summary of Articles
17
ACCEPTED MANUSCRIPT
derived from 24 hr diet recall
Crosssectional
Men, 1545
"Moderate to severe Prostatism" = AUA-SI >=8)
Questionnaire/int erview - 24 hr recall - daily consumption calories, fat, protein, carbohydrate
Moderate to severe LUTS (>=8 AUA-SI), voiding symptoms (>=5), storage symptoms (>=4)
TEI, Carbohydrate, Protein, total fat, fat types, sodium (FFQ)
Crosssectional
Women, 2060
EP
4b
Moderate to severe LUTS (>=8 AUA-SI), voiding symptoms (>=5), storage symptoms (>=4)
AC C
Maserejian27 2011
No numbers given
Calories NS,
No
Fat NS,
RI PT
Men (age >49), 514
SC
4b
Crosssectional
Greater TEI assoc with higher LUTS score (continuous) and storage symptoms (p trend <0.01);
Protein NS, Carbohydrate NS
Carbohydrate NS,
Yes
Total fat NS, Protein intake S - (voiding sx)
Protein (quintile 5 vs 1) OR 0.35 (0.17-74);
TE D
Maserejian26 2009
4b
M AN U
Lee95 1997
TEI, Carbohydrate, Protein, total fat, fat types, sodium (FFQ)
weak association polyunsaturated fat with storage symptoms. Sodium (quintile 5 vs 1) OR 2.25 (1.26-4.03) LUTS: TEI- quintile 5 vs 1 OR 1.77 (1.01-3.09); Post micturition sx: Saturated fats (quintle 5 vs 1) 3.94 (1.57-9.89)
TEI S+
Yes
Monounsat fat NS Carbohydrates NS Sodium NS Protein S + (nocturia)
18
ACCEPTED MANUSCRIPT
Wong28 2007 4b
Crosssectional
Men, 2000
Chinese AUA-SI
Dietary total isoflavone (mg) (FFQ)
Ref: <5.1mg
S-
5.1 to 9.5 mg: OR 0.59 (95 % CI 0.44, 0.80)
(subjects with dietary total isoflavone of more than 5.1 mg were significantly less likely to suffer from more severe LUTS)
RI PT
9.6 to 14.3 mg: OR 0.81 (95% CI 0.61, 1.09) 14.4 to 21.7 mg: OR 0.68 (95% CI 0.51, 0.92)
Yes - TEI
AUA-SI Uroflowmetry
Randomized to placebo vs. 300 or 600 mg/day secoisolariciresino l diglucoside (SDG)
AUA-SI score changed: -3.67 +/- 1.56, -7.33 +/- 1.18, and 6.88 +/- 1.43 (mean +/- SE; P = .10, < .001, and < .001 compared to baseline)
M AN U
4 month follow-up
Men, 78
TE D
RCT,
EP
1b
AC C
Zhang13 2008
SC
>=21.8 mg: OR 0.73 (95% CI 0.54, 0.98) S(secoisolariciresinol diglucoside use associated with fewer LUTS)
No
Quality of Life score improved by -0.71 +/- 0.23, 1.48 +/- 0.24, and -1.75 +/0.25 (mean +/- SE; P = .16 and .012 compared to placebo and P = .10, < .001, and < .001 compared to baseline)
Number of subjects with LUTS change from "moderate/severe" to 19
ACCEPTED MANUSCRIPT
"mild" increased by 3, 6, and 10 (P = .19, .03, and .01 compared to baseline)
RI PT
Maximum urinary flows and postvoid volumes NS
Population, N
4b
Crosssectional
Men, 23 BPH, 11 controls
Spigt34 2004
4a
Case series,
Men, 44
2 month follow-up
Spigt33 2006
1b
RCT,
LUTS vs. no LUTS
AUA-SI total score, QOL
AC C
Matthiesen96 1999
LUTSOutcome(s)
Men, 138
Fluid intake Variable(s)
AUA-SI total score, AUA-SI
Results: OR, RR, other
M AN U
Study Design, Duration Follow-up
Results: Significance, Direction
Analyses adjusted? Comments
24-hour fluid intake (exclude fluid in food) (D)
No difference in 24hour fluid intake between patients with LUTS vs. controls without LUTS.
Subjects were asked to increase fluid intake by 2L per day for 8 weeks
Score increased from S, + 7.9 to 8.9 (p = 0.028) after increase in fluid intake. QOL decreased by 0.2 (p=0.30). No comparison group.
No
Subjects randomized
No difference in total score, voiding
No
TE D
Oxford Level
EP
Author/Year
SC
American Urological Association Symptom Index = (AUA-SI), LUTS = Lower urinary tract symptoms, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, FFQ = Food Frequency Questionnaire, OR = Odds ratio, RR = Relative risk, TEI = Total energy intakeSupplemental Table 3A. BPH and Fluid Intake- Detailed Summary of Articles
NS
NS (total scores)
No
20
ACCEPTED MANUSCRIPT
QOL, AUA-SI storage symptoms, and voiding symptoms
to increase fluid intake by 1.5L per day for 6 months, versus placebo
score, and QOL between groups. AUA-SI storage scores worse in subjects who increased fluid intake (effect size=1.3, p<0.001).
S, + (storage scores)
RI PT
6 month follow-up
4b
Study Design, Duration Follow-up
Population ,N
Crosssectional
Men & Women, 128
LUTSOutcome(s)
Nocturnal micturition (nocturia)
Fluid intake Variable(s)
1) Daily fluid intake 2) Evening fluid intake
Johnson36 2005
2b
Prospectiv e cohort, 2 year follow-up
AC C
EP
Griffiths97 1993
Oxford Level
TE D
Author/Year
M AN U
Supplemental Table 3B. Nocturia and Fluid Intake- Detailed Summary of Articles
Men, 1289
2-year Incident nocturia
SC
BPH: benign prostatic hyperplasia, S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, D = Diary, American Urological Association Symptom Index = (AUA-SI), OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial
Nighttime fluid intake (y/n), amount of nighttime
Results: OR, RR, other
1) Positive correlation between daily fluid intake and nocturia (0.21, p<0.02),
Results: Significance, Direction
Analyses adjusted? Comments
1) S, +
No
2) NS
2) No correlation between evening fluid intake and nocturia (0.17, p>0.05). Fluids at bedtime
NS
0.97 (0.76-1.25)
NS
Yes
21
ACCEPTED MANUSCRIPT
intake
Amount bedtime fluids 1.05 (0.96, 1.15)
Men with BPH, 23; Controls 11
Soda37 2010
4a
Case series,
24-hour fluid intake (exclude fluid in food) (D)
No statistical difference (but positive trend) in 24hour fluid intake and nocturnal polyuria
NS
No
Nocturia indices (nocturnal frequency, nocturnal urine volume, nocturia index, nocturnal polyuria index, nocturnal bladder capacity index), Urinary frequency
Fluid intervention (restriction of fluid intake) and subjects asked to refrain from excessive hours in bed keep bed warm, and perform moderate exercise
Fluid restriction (plus other interventions) associated with reduction of nocturnal frequency (p<0.001), nocturnal urine volume (p<0.001), nocturia index (p<0.001), nocturnal polyuria index (p=0.004), nocturnal bladder capacity index (p=0.002), and urinary frequency (p=0.007). No comparison group. The effect of fluid restriction could not be isolated from other interventions.
S, +
No
Subjects asked to reduce water and food intake so urine output
Nocturia decreased from mean 4.1 to 3.1/night, p<0.0001.
S, +
No
Tani38 2014
4a
Case series, 1 month follow-up
AC C
EP
TE D
4 week follow-up
Men & Women, 47 men and 9 women
Presence vs. absence of nocturnal polyuria
Men, 65
Numbers of nocturnal voids (nocturia)
RI PT
Crosssectional
SC
4b
M AN U
Matthiesen96 1999
22
ACCEPTED MANUSCRIPT
reduced to 30 mL/kg. 1b
RCT, 10 week follow-up
Women, 307
Nocturnal voids (nocturia)
Daily fluid intake (D)
None of the changes in the variable outcomes differed by treatment
NS
Yes
RI PT
Zimmern35 2009
group at 10 weeks.
AC C
EP
TE D
M AN U
SC
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, D = Diary, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial
23
ACCEPTED MANUSCRIPT
Supplemental Table 3C- OAB/LUTS (non-UI) and Fluid Intake- Detailed Summary of Articles Population, N
Prospective cohort,
Women, 6424
LUTSOutcome(s)
Incident OAB (Q)
1 year follow-up
Crosssectional
Results: OR, RR, other
Men & Women, 128
Diurnal micturition (daytime frequency)
S, +
1) Daily fluid intake
1) Positive correlation for daily fluid intake and diurnal micturition (0.33, p<0.002),
S, +
2) Evening fluid intake
Cross-over RCT, 4 day follow-up per each interventio
Men & Women, 24
Frequency, Urgency, Nocturia (D)
Fluid total increased by 25% and 50% and decreased by 25% and 50%
Analyses adjusted? Comments
Carbonated drinks associated with new OAB (OR 1.41, 95% CI 1.021.95), comparing
EP 1b
AC C
Hashim40 2008
Results: Significance, Direction
Consumption of various fluid (carbonated drinks, water, tea, coffee, wine, beer, port & spirits, fruit juices) (FFQ)
TE D
Griffiths97 1993 4b
Fluid intake Variable(s)
RI PT
2b
Study Design, Duration Follow-up
SC
Dallosso24 2003
Oxford Level
M AN U
Author/Year
Yes
NS
No
S, +
2) Positive correlation for evening fluid intake and diurnal micturition (0.29, p<0.002). Frequency, urgency and nocturia all decreased with 25% (all p<.001) and 50% reduction (all p<0.05) in fluid intake Frequency increased with
Fluid reduction: S, + (frequency, urgency,
No; Small numbers, especially in 50% fluid reduction 24
ACCEPTED MANUSCRIPT
25% (p=0.03) and 50% (p=0.002) increase in fluid intake
n
nocturia)
(12) or increase (14)
1) Daily total fluid intake
Positive correlation for urinary frequency and daily total fluid intake, p=0.04 (but not for daily caffeinated fluid intake)
S, +
No
SC
Urinary frequency
2) Daily caffeinated fluid intake
M AN U
Women with UI (urgency, stress, mixed), 256
TE D
Crosssectional
(frequency)
EP
4b
S, +
AC C
Segal99 2011
RI PT
Fluid increase:
25
ACCEPTED MANUSCRIPT
4b
Crosssectional
Women, 2244
1) Urinary frequency
1) Women with frequency 2.5 times more likely to drink >= 2L of fluid per day (OR 2.4, p<0.001), 3.5 times more likely to drink >=6 cups coffee per day (OR 3.6, 95%CI 2.3-5.7, p<0.001), and 1.5 times more likely to drink >= 1 glass alcohol per week (OR 1.4, 95%CI 1.1-1.6, p<0.001).
1) S, +
No
2) S, +
Swithinbank39 2005
1b
Cross-over RCT (caffeine restriction with either increased
AC C
EP
TE D
M AN U
SC
2) Urgency
Daily fluid intake (more than vs. less than 2L/day), coffee, tea, and alcohol intake (amount)
RI PT
Selo-Ojeme98 2013
Women with USI or IDO, 69
1) Frequency 2) Urgency
Fluid increase to 3L daily vs. fluid decreased to 750 mL daily, both arms with caffeine
2) Similar observations for urgency except no association between urgency and fluid intake. Women with urgency 3.5 times more likely to drink >= 6 cups coffee per day (OR 3.7, 95%CI 2.5-5.8, p<0.001), and 1.5 times more likely to drink >= 1 glass alcohol per week (OR 1.5, 95%CI 1.2-1.8, p=0.002). Increasing fluid intake significantly increased frequency and urgency (both p<0.003). Decreasing fluid intake significantly decreased
1) S, + (bidirectional)
n/a
2) S, + (bidirectional)
26
ACCEPTED MANUSCRIPT
fluid vs. decreased fluid),
restriction
frequency (p<0.003) and urgency (p=0.006).
Daily fluid intake (D)
No outcomes differed by treatment group.
RCT, 10 week follow-up
Women, 307
1) 24 hour frequency (D) 2) Selfreported urgency (Q)
NS
Yes
SC
1b
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm -
AC C
EP
TE D
M AN U
Zimmern35 2009
RI PT
4 week follow-up
additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food frequency questionnaire, D = Diary, OR = Odds ratio, RR = Relative risk, RCT = Randomized controlled trial, USI – Urodynamic stress incontinence, IDO = Idiopathic detrusor overactivity
27
ACCEPTED MANUSCRIPT
Supplemental Table 3D - UI and Fluid Intake- Detailed Summary of Articles
2b
Study Design, Duration Follow-up
Population, N
Prospectiv e cohort,
Women, 6424
LUTSOutcome(s)
Fluid intake Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Incident SUI (Q)
Consumption of carbonated drinks associated with new SUI (OR 1.62, 95% CI 1.182.22, comparing
S, +
Yes
NS
SC
1 year follow-up
Consumption of various fluids (carbonated drinks, water, tea, coffee, wine, beer, port & spirits, fruit juices) (FFQ)
RI PT
Dallosso24 2003
Oxford Level
M AN U
Author/Year
Other fluid types NS
RCT, 5 week follow-up
Men, 3960
Women, 32
SUI, UUI, any UI, moderate to severe UI (Q)
Daily total fluid intake (structured dietary recall)
UI episodes
Daily total fluid intake
TE D
2b
Crosssectional
EP
Dowd41 1996
4b
AC C
Davis60 2013
(14 subjects randomized to increase fluid intake by 500 mL/d, 10 to reduce fluid by 300 mL/d, and 8 to maintain current fluid
No association between water intake,
NS
Yes
“Adherence to fluid intake NS protocol was poor, and consequently, quantitative results were nonsignificant”
No
any UI or moderate to severe UI.
*Poorly designed RCT, with poor adherence to fluid protocols, small no. of 28
ACCEPTED MANUSCRIPT
intake)
Crosssectional
Women, 4309
Men & Women, 128
SUI, UUI, any UI, moderate to severe UI, (Q)
Daily total fluid intake (structured dietary recall)
Water intake in upper quartile (>1.3L/d) associated with less moderate/severe UI (p<0.001), but not any UI.
S, -
Diurnal UI, nocturnal UI (gram/d) (Pad test)
1) Daily total fluid intake
1) Positive correlations for daily fluid intake and diurnal UI (0.34, p<0.02) and nocturnal UI (0.32, p<0.02) in subjects with IDO,
1) S, +
2) Evening fluid intake
RI PT
4b
Crosssectional
1b
Cross-over Men & RCT, Women, 24 4 day follow-up per each interventi on
UUI episodes (D)
AC C
Hashim40 2008
EP
TE D
M AN U
Griffiths97 1993
4b
SC
Gleason58 2013
subjects
Fluid total increased by 25% and 50% and decreased by 25% and 50%
2) No correlation for evening intake and diurnal UI but positive correlation with nocturnal UI (0.28, p<0.05)
No
NS
No
S, +
2) NS S, +
No change in urgency incontinence episodes after any of the interventions
Fluid reduction: NS
Fluid increase: NS
No Small numbers, especially in 50% fluid reduction (12) or increase (14) 29
ACCEPTED MANUSCRIPT
4b
Crosssectional
Women, 298
Presence vs. absence of UI
Daily total fluid intake
Mean daily fluid intake among UI vs. no UI was not different (p=0.62)
NS
No
Miller100 2011
4b
Crosssectional
Women, 352
UI episodes per day (3-day D)
1) Fluid intake during daytime
High fluid intake during daytime and high volume of bladder irritants consumed associated with more UI episodes in this cluster analysis, p=0.02 and p<0.001 respectively.
S, +
No
Women with UI (urgency, stress, mixed), 256
1) Urgency incontinence
1) Daily total fluid intake
Men & Women in nursing homes, 112 (~80% women)
UI episodes (observed with physical check by staff)
S, +
RCT, 3 month follow-up
2) Daily caffeinated fluid intake
TE D
1b
Crosssectional
EP
Schnelle11 2010
4b
AC C
Segal99 2011
M AN U
SC
2) Volume of bladder irritants consumed (carbonated beverages, coffee, tea, alcohol)
RI PT
Hirayama101 2011
Increased fluid intake (observed) (Multimodal intervention: toileting assistance, exercise, increased fluid and food offered between meals)
Positive correlation between UUI and daily caffeinated fluid intake, p=0.021 (but not with daily fluid intake)
S, +
Increased fluid intake associated with increase in UI episodes (coefficient not provided)
S, +
No
NS
Yes Note: complex intervention , minimal information provided
30
ACCEPTED MANUSCRIPT
1b
Cross-over Women with USI or RCT, IDO, 69 4 week follow-up
UI episodes weekly
Fluid increased to 3L daily vs. fluid decreased to 750 mL daily, both arms with caffeine restriction
Increasing fluid intake increased weekly UI (p=0.006), while decreasing fluid intake reduced weekly UI (p=0.006).
S, + (bidirectional)
n/a
Tomlinson55 1999
4a
Case series,
UI episode (daytime), grams of incontinence (pad weight)
Targeted daily fluid intake to 18002400 mL daily for those who drank <1500 mL or >4000 mL daily. Subjects also asked to reduce caffeinated fluid, reduce nighttime fluids, and do timed voiding
Among 21 women
S, + (univariate)
Yes
SC
encouraged to increase daily fluid intake, 85.7% (n = 18) did and 66.7% (n = 14) decreased UI.
NS (multivariate)
2b
Prospectiv e cohort,
Women, 65167
Incident UI: 1) any UI
2 year follow-up
AC C
Townsend42 2011
EP
TE D
M AN U
2-4 weeks follow-up
Women with UI (SUI, UUI, mixed), 41
RI PT
Swithinbank39 2005
2) frequent UI (>= 1/ week) 3) SUI 4) UUI
Daily total fluid consumption (FFQ)
Sample size possibly too small for multivariate analysis.
In multivariate analysis, increase in intake resulted in increase in volume of urine voided, without increasing UI.
No association between fluid consumption and incident UI (any UI, frequent UI, SUI, UUI, or MUI).
NS
Yes
HR 1.04 (0.98-1.09), 0.98 (0.88-1.08), 0.90 (0.761.06), 1.12 (0.88-1.42) & 1.11 (0.88-1.40) 31
ACCEPTED MANUSCRIPT
5) MUI
respectively,
RCT, 10 week follow-up
Women, 307
1) No. of incontinence episode/wk (D) 2) Selfreported pad use
No outcomes differed by treatment
NS
Yes
group.
(Tolterodine vs. tolterodine + behavioral therapy; general information to avoid excessive fluid intake in all; if excessive urine output (>2.1 L/d) in behavioral + drug arm -
TE D
3) Bothersome UI symptoms (Q)
Daily total fluid intake (D)
SC
1b
M AN U
Zimmern35 2009
RI PT
comparing top (1.1 L/d) vs. bottom (2.9 L/d) quintile fluid intake
AC C
EP
4) QOL (Q)
additional instruction on fluid reduction.)
S = Statistically significant association, NS = Not statistically significant association, + = Positive association, - = Negative association, Q = Questionnaire, FFQ = Food frequency questionnaire, D = Diary, UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, OR = Odds ratio, RR = Relative risk, HR = Hazard ratio, RCT = Randomized controlled trial, USI = Urodynamic stress incontinence, IDO = Idiopathic detrusor overactivity
32
ACCEPTED MANUSCRIPT
Supplemental Table 4A. BPH and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
Crosssectional
Men, 1,335
LUTSOutcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
BPH (Q) vs. no BPH and no or mild LUTS
Coffee (cups/day- Q)
Never/rare- 1.0
S, +
Yes
NS, +
Age adjusted only
1-4 c – 2.20 (1.26– 3.85)
SC
Gass47 2002
Oxford Level
RI PT
Author/Year
BPH (Q) vs. no BPH and non-severe LUTS
M AN U
≥5 c - 2.74 (1.43– 5.25)
3b
Casecontrol
Men, 219 cases and 4669 controls
Surgically treated BPH
AC C
Morrison45 1978
EP
TE D
Never/rare- 1.0
Coffee (None vs. >=1/dayI)
1-4 c – 1.97 (1.16– 3.37) ≥5 c - 2.56 (1.37– 4.75) 0 c – 1.0 >=1c/day 1.3 (0.9-1.9)
33
ACCEPTED MANUSCRIPT
Morrison46 1992
3b
Casecontrol
Men, 910 cases and 2003 controls
Surgically treated BPH
Coffee (cups/day- TI)
<1 c – 1.0
NS, -
Yes
1 c – 0.88 (0.661.17)
RI PT
2 c – 0.81 (0.611.07) 3 c – 0.82 (0.591.13)
SC
≥4 c – 0.79 (0.581.08)
AC C
EP
TE D
M AN U
BPH: benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, I= interview, TI= telephone interview, Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
34
ACCEPTED MANUSCRIPT
Supplemental Table 4B. Nocturia and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
LUTSOutcome(s)
Crosssectional
Women, 3019
Nocturia (Q)
Prospective cohort,
Men, 1580
5 yr Incident Mild Nocturia (1-2; Q)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Caffeinated beverages after 6pm
Inverse association –
S, -
No
NS, +
Yes (but not for overall fluid intake)
Coffee-
Coffee- NS, +/-
Yes
0c
Tea- S, +
Coffee and tea in same model
Nocturia 2x as likely to occur in those who do not drink PM caffeine (p<0.0001)
Shiri48 2008
2b
5 year follow-up
M AN U
SC
Asplund50 2004
Oxford Level
RI PT
Author/Year
Coffee (cups/day, baseline) (Q)
0-1 1.0 2–3 1.4 (0.9–2.3) 4–5 1.1 (0.6–1.7)
TE D
≥ 6 1.1 (0.6–1.7)
5 yr Incident Mod-severe Nocturia (≥3; Q)
2-3 1.2 (0.5–2.9)
EP 4b
Crosssectional
AC C
Tettamanti53 2011
Women, 14031
Nocturia
0-1 1.0
4-5 1.3 (0.5–3.0) ≥ 6 1.9 (0.8–4.5) Coffee (cups/day; Q)
1.0
1-2 c 1.06 (0.94-1.19)
35
ACCEPTED MANUSCRIPT
3+c 0.96 (0.85-1.08)
Tea – 0c
1.0
RI PT
Tea (cups/day; Q)
1-2 c 1.02 (0.93-1.11) 3+c 1.18 (1.01-1.38)
AC C
EP
TE D
M AN U
SC
*Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
36
ACCEPTED MANUSCRIPT
Supplemental Table 4C. OAB/LUTS (non-UI) and Caffeine Intake- Detailed Summary of Articles Author/Year
Oxford Level
Study Design, Duration Followup
Population, N
LUTSOutcome(s)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted?
2b
RCT; Bladder training +/caffeine reduction,
Men & Women, 74 (90% women)
Frequency/24 hrs (D) Urgency/24 hrs (D)
Men, 1308
AUA-SI ≥8 with no prostate enlargement
TE D
Cross-sectional
AUA-SI ≥8 with prostate enlargement
EP
4b
AC C
Klein54 1999
M AN U
1 month followup
Caffeine reduction education
Frequency
S, +
35% vs. 23% reduction (p=0.037)
Caffeine (mg/day; Q)
Urgency
n/a (RCT) 78% completed outcome assessment
SC
Bryant51 2002
RI PT
Comments
S, +
61% vs. 12% reduction (p=0.002) None
1.0
1-200 1.56)
0.98 (0.61,
NS, +/-
Age only
201-400 1.21 (0.79, 1.86) 401+ 1.59)
1.00 (0.63,
None
1.0
1-200 1.75)
0.80 (0.36,
201-400 0.72 (0.33, 37
ACCEPTED MANUSCRIPT
1.55) 401+ 2.42) Women with USI, IDO, 69
Frequency (D) Urgency (D)
Cross-sectional
Women, 14,031
OAB (Q)
Coffee (cups/day; Q)
Cross-over RCT, 2 week follow-up per each
No
Women, 11
Frequency, Urgency (D) OAB symptoms
Coffee-
Coffee- NS, +/-
Yes
0c
Coffee and tea in same model
1.0
1-2 c 1.05 (0.89-1.25) 3+c 1.03 (0.86-1.23)
Tea (cups/day; Q) Tea –
EP 2b
AC C
Wells52 2014
NS, +/-
QOL- no change
TE D
4b
Frequency- no change Urgency- no change
QOL (Q)
4 week follow-up Tettamanti53 2011
Caffeine restriction
RI PT
Case series (Study is crossover RCT, but caffeine restriction done throughout in all (no controls),
SC
4a
M AN U
Swithinbank39 2005
1.04 (0.45,
0c
Tea- S, + 1.0
1-2 c 1.08 (0.95-1.24) 3+c Caffeine replacement with decaffeinated
1.34 (1.07-1.67)
Decreased voiding frequency (p<0.05) and urgency (p<0.01) on day 3 of diaries; reduced
S, +
Small sample with >20% loss to follow-up; 38
ACCEPTED MANUSCRIPT
intervention
and QOL (Q)
drinks
OAB symptoms (p<0.01)
small differences
AC C
EP
TE D
M AN U
SC
RI PT
OAB = Overactive bladder, QOL = Quality of life, AUA-SI = American Urological Association Symptom Index, USI – urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
39
ACCEPTED MANUSCRIPT
Supplemental Table 4D. UI and Caffeine Intake- Detailed Summary of Articles Author/Year Oxford Level
Study Design, Duration Followup
Population, N
LUTSOutcome(s)
Caffeine Variable(s)
Selected Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted?
2b
RCT; Bladder training +/caffeine reduction,
Men & Women, 74
# UI episodes (D)
Men, 3,960
UI
Caffeine reduction
4b
Cross-sectional
M AN U
1 month follow-up
Davis60 2013
55% vs 26% reduction UI episodes (p=0.22)
+, NS
Caffeine (mg/d)
n/a (RCT) 78% completed outcome assessment, underpowered for outcome
SC
Bryant51 2002
RI PT
Comments
Any UI
Any UI - NS
≥75th% NS
Mod/severe UI
≥90th% NS
75th% +, S
Yes
th
TE D
≥75 % (≥234 mg/d) and ≥90th% (≥392 mg/d)
Cross-sectional
Women, 4,309
UI, Mod-severe UI
Mod/severe UI ≥75th% 1.69 (1.09, 2.61)
EP 4b
AC C
Gleason58 2013
90th% +, S
≥90th% 2.03 (1.09, 3.78) Caffeine, ≥75th% (≥204 mg/d) and ≥90th% (≥348 mg/d)
Any UI
Any UI
≥75th% 1.47 (1.07, 2.01)
75th% +, S
≥90th% 1.23 (0.70–2.12)
90th% +, NS
Yes
40
ACCEPTED MANUSCRIPT
Mod/severe UI
≥75th% 1.42 (0.98, 2.1)
75th% +, NS
≥90th% 0.90 (0.43–1.87)
90th% -, NS
RI PT
Mod/severe UI
SUI, UUI, MUI: all NS Cross-sectional
Women, 27,936
Any UI, Severe UI, SUI, UUI, MUI
Coffee (cups/d)
Any UI
Coffee
Yes
Coffee
Any UI NS
Tea and coffee in same model
1-2c. 1.0 (.8-1.1)
SUI +, S
SC
4b
M AN U
Hannestad59 2003
Tea (cups/d)
3+c. 1.0 (.9-1.1)
Severe MUI -, S UUI +, NS
4b
Cross-sectional
Men & Women, 683 men and 298 women
Any UI, SUI, UUI
AC C
Hirayama103 2012
EP
TE D
Tea
1-2c. 1.2 (1.1-1.2)
Tea-
3+c. 1.3 (1.2-1.5)
Any UI, SUI, MUI all +, S UUI +, NS
Caffeine (mg/d)
Men – Any UI
Any UI
0-55.8
Men +, NS
1.0
Yes
55.9-147 1.11 (0.52, 2.37) Women +/-, NS >147
1.36 (0.65, 2.88)
Men- UUI NS
UUI –Men +/-, NS
41
ACCEPTED MANUSCRIPT
SUI–Women +/-, NS Women – Any UI 0-51.2
1.0
RI PT
51.3-145 0.94 (0.48, 1.84) >145
1.12 (0.57, 2.22)
Women- SUI NS Women, 65,176
2-4 yr Incident UI:
Caffeine (mg/d; Q)
Any UI
SC
Prospective cohort,
Any UI, Frequent UI, UUI, SUI, MUI (Q)
1.0
Any UI +/-, NS
UUI +, S
300-449 1.02 (0.98–1.07)
SUI NS
0.98 (0.91–1.05)
Yes
Frequent UI +, S
150-299 0.98 (0.90–1.06)
≥450
TE D
4 year follow-up
M AN U
0-149
EP
2b
AC C
Jura56 2011
MUI NS
Frequent UI 0-149
1.0
150-299 0.98 (0.90–1.06) 300-449 1.06 (0.98–1.15) ≥450 1.19 (1.06–1.34)
UUI 0-149
1.0 42
ACCEPTED MANUSCRIPT
150-299 0.88 (0.72–1.07) 300-449 1.18 (0.97–1.44) 1.34 (1.00–1.80)
Kincade102 2007
4b
Cross-sectional
Women, 525
Urine loss (pad test)
RI PT
≥450
Caffeine (mg/d and ounces/d)
Moderate correlation between caffeine (oz/d) and UI episodes
SC
# UI episodes
Caffeine (oz/d)
No
+ correlation, S
Case series (Study is cross-over RCT, but caffeine restriction done throughout in all (no controls),
Women with USI, IDO, 69
# UI episodes
4b
Cross-sectional
AC C
4 week follow-up Tettamanti53 2011
Urine loss (24 Caffeine hr pad test) restriction
TE D
4a
Caffeine (mg/d)
Caffeine mg/d did not correlate with UI episodes or urine loss (g)
no correlation, NS
No differences in
No change, NS
No
Overall UI
Overall UI
Yes
Coffee-
Coffee - , S
0c
Tea -, NS
Coffee and tea in same model
pad weight, daily UI episodes and QOL
EP
Swithinbank 39 2005
M AN U
(r=0.53)
Women, 14,031
UI, SUI, MUI, UUI
Coffee (cups/d; Q)
Tea (cups/d; Q)
1.0
1-2 c 0.87 (0.7-1.06)
43
ACCEPTED MANUSCRIPT
3+c 0.79 (0.64-0.98)
SUI
Tea –
Coffee -, NS
0c
1.0
Tea -, S
RI PT
1-2 c 0.92 (0.79-1.07) 3+c 0.77 (0.58-1.02)
SC
SUI
UUI Coffee -, NS Tea -, NS
M AN U
Coffee-
Tomlinson55 1999
4a
Case series, 2-4 weeks followup
AC C
EP
TE D
0c
Women, 41
Urine loss (pad test) # UI episodes
1.0
MUI
1-2 c 0.86 (0.69-1.07)
Coffee -, NS
3+c 0.81 (0.64-1.01)
Tea -, NS
Tea – 0c
1.0
1-2 c 0.91 (0.77-1.08) 3+c 0.72 (0.53-0.99)
Caffeine reduction
Decrease in UI daytime episodes (p=0.07), no significant change in other outcomes
+, NS
Yes
44
ACCEPTED MANUSCRIPT
2b
Prospective cohort,
Two-year progression of UI, UUI, SUI, MUI
Caffeine intake over past year (mg/d; Q), Change in caffeine intake prior 4 years (stable, increase, decrease; Q)
Caffeine intake prior year and UI
Caffeine prior year
Yes
+/-, NS 0-149
1.0
150-299 0.99 (.83-1.18) 300-449 1.04 (.91-1.19) ≥450
0.87 (.7-1.08)
Caffeine change prior 4 years +/-, NS
SC
2 year follow-up
Women with moderate UI, 21,564
RI PT
Townsend57 2012
M AN U
UUI, SUI, MUI results – all NS
Change in caffeine intake and UI
Wells52 2014
2b
Cross-over RCT, 2 week follow-up per each intervention
AC C
EP
TE D
Stable 1.0
Women, 11
# UI episodes (D), UUI (Q)
Incr
1.08 (.95-1.22)
Decr
1.16 (1.02-1.31)
UUI, SUI, MUI: all NS Caffeine replacemen t with decaffeinate d drinks
No differences
No change, NS
Small sample with >20% loss to follow-up; small differences
45
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, USI = urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, DO= detrusor overactivity, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
46
ACCEPTED MANUSCRIPT
Supplemental Table 4E. Urodynamic parameters and Caffeine Intake- Detailed Summary of Articles
4b
Study Design, Duration Follow-up
Population, N
Crosssectional
Women with UI, 131 DO and 128 SUI
DO seen on urodynamics
Women, 20
Urodynamic test parameters
LUTS-Outcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Caffeine (mg/d)(D); categorized Minimal (<100), Moderate (100-400), High (>400)
Min 1.0
2nd Urodynamics performed 30 min after 200 mg Caffeine ingested
Increase in detrusor pressure during filling (17 (0-42) vs. 11 (0-25), p<0.03)
S, + (detrusor pressure)
No difference in volume at first contraction, height of contraction or capacity
NS, +/- (others)
S, +
Yes Age, smoking
Mod 1.5 (0.1, 7.2) High 2.4 (1.1, 6.5)
Case series, 2 weeks between 1st and 2nd tests
TE D
4a
No
AC C
EP
Creighton43 1990
M AN U
SC
Arya44 2000
Oxford Level
RI PT
Author/Year
UI = Urinary incontinence, SUI, Stress urinary incontinence, DO = detrusor overactivity, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
Supplemental Table 5A. BPH and Alcohol Use- Detailed Summary of Articles 47
ACCEPTED MANUSCRIPT
Chyou17 1993
Oxford Level
2b
Study design, Duration Follow-up
Population, N
Prospective cohort,
Men, 6581
LUTSOutcome(s)
Alcohol Variable(s)
Results: OR, RR, other
Surgery for BPH
Alcohol (oz) per month,
Vs. non drinker Alcohol:
17 year (average) follow-up
Type of alcohol
<4 RR 1.02
SC
4-29 RR 0.91
TE D
M AN U
25+ RR 0.64
Analyses adjusted?
Case-control
Men, 1369 BPH and 1451 controls
Obstructive LUTS and max flow < 15 mL/sec refractory to treatment who had
Trend for Yes decrease in BPH incidence for total alcohol, Beer, Wine, Sake. Not significant for Spirits.
Beer: 361+ RR 0.66 (0.53-0.83) Wine: >4 RR 0.70 (0.52-0.94) Sake: >4 RR 0.72 (0.54-0.95)
EP 3b
AC C
Crispo104 2004
Results: Significance, Direction
Comments
RI PT
Author /Year
Spirits: 12+ OR 0.82 (0.67-1.02) Drinks/week, Duration of drinking, Age at starting
Duration drinking and Age starting drinking- NS
Drinks/week significant for trend only
No
Drink/week <3 OR 0.88 (0.62-1.24)
48
ACCEPTED MANUSCRIPT
surgery
drinking
3-4 OR 0.71(0.50-1.03) 5-6 OR 0.79(0.52-1.20) 7-8 OR 0.65 (0.41-1.02)
RI PT
>9 OR 0.65 (0.41-1.02) Chi square trend p=0.013 (for trend only)
3b
Case-control nested in a RCT
Men, 320 cases and 320 controls
Surgery for BPH
Self-reported alcohol use:
SC
Gann105 1995
M AN U
rare/never
1.0
1-3/mo
Only the group with 5+ drinks per week had significantly less surgery for BPH
Yes
0.50 (.23-1.08)
l/wk
0.76 (.38-1.52)
4b
Crosssectional
Men, 882
AC C Kang68 2004
4b
Crosssectional
Men , 17,772
1.01 (.53-1.94)
5 + /wk 0.51 (.29-.90)
Surgery for BPH or symptomatic LUTS and BPH based on selfreported prostate history and AUA-SI
Glasses alcohol per day/week :
BPH diagnosis by physician
Reference <5 g/day
EP
Gass47 2002
TE D
2-4/wk
<1 glass/wk 2-4 glasses/wk >=1 glass/d
BPH patients vs non symptomatic patients: <1 glass alcohol/week NS, but 2-4 and >=1 glass per day 0.46 (0.32– 0.66)
BPH OR:
NS for low alcohol Yes but significantly less surgery and symptoms for those who drank 2 or more drinks a day
Alcohol consumption
Yes
49
ACCEPTED MANUSCRIPT
5-15 g/day
0.8 (0.7-0.9)
15.1-30 g/day
0.8 (0.7-0.9) 0.7 (0.6-0.9)
30.1-45 g/day
0.7 (0.6-0.9) 0.6 (0.5-0.7)
45.1-60 g/day
Morrison46 1992
3b
Case-control
Men, 910 cases and 2003 controls
BPH Symptoms on AUA-SI and pathology
genetic variants & smoking, chewing tobacco & alcohol consumption
Null Genotype of GSTMI associated with increased risk of BPH with smoking, tobacco chewing or alcohol consumption
Selection bias nullifies results
No
Number of: beer/day 0≥5
Spirits: all strata NS
Yes
Spirit drinks/day 0≥5
RR Beer/day:
Significant decrease in need for surgery only for modest 2-3 beer/day and 1-3 combined alcohol per day.
M AN U
Men, 141 cases and 184 controls
TE D
Crosssectional
Surgery for BPH
AC C
EP
4b
SC
60+ g/day Mittal106 2009
significantly associated with less BPH at all levels of consumption.
RI PT
or having had a TURP
Wine: all strata NS
1-0.80 (0.55-1.16) 2-0.66 (0.43-1.00)
Glasses wine/day 0≥5
3-0.30(0.14-0.63)
Combined alcohol
≥5 0.97(0.61-1.54)
4- 0.34(0.13-0.90)
50
ACCEPTED MANUSCRIPT
RR combined EtOH/day: 1- 0.77(0.60-0.99) 2- 0.64 (0.46-0.87)
RI PT
3- 0.49 (0.32-0.77) 4- 0.59(0.34-1.02)
≥5 0.86 (0.60-1.23)
Grams per day alcohol:
Pooled OR for BPH 12 studies :
SC
Development of BPH or worsening LUTS on AUASI
M AN U
Men, 120,091
TE D
Metaanalysis of cohort and case-control studies
EP
3a
AC C
Parsons107 2009
Up to 5g
Up to 12g
0.90 (0.80-1.01)
Up to 15g
0.86 (0.79-0.94)
Up to 24g
0.66 (0.54-0.81)
Up to 36g
0.82 (0.69-0.97)
>36g
0.78 (0.69-0.88) 0.65 (0.58-0.74)
Pooled OR for LUTS alone 4 studies: ≥12g/day OR 1.42 (0.772.64)
14/19 studies showed decreased BPH with alcohol intake. In pooled analysis all strata of consumption showed a significant decreased likelihood of BPH compared to nondrinkers. ¾ Studies on LUTS alone showed increased symptoms, but pooled analysis NS
n/a
51
ACCEPTED MANUSCRIPT
Williams108 2008
2b
Prospective cohort,
New physician diagnosis of BPH
Men, 28,612
Alochol intake BPH men 81.32 ml +/- 2.5 no BPH men 81.02 +/- 0.70 ml per week p=0.91
No. Alcohol intake did not predict new diagnosis of BPH
Yes
RI PT
7.7 year (average) follow-up
alcohol mL/week (self- report)
AC C
EP
TE D
M AN U
SC
BPH = Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, USI – urodynamic stress incontinence, IDO = idiopathic detrusor overactivity, Q= questionnaire, D= diary, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
52
ACCEPTED MANUSCRIPT
Supplemental Table 5B. General Urinary Symptoms and Alcohol Use- Detailed Summary of Articles Oxford Level
Study Design, Duration Follow-up
Population, N
LUTSOutcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
RI PT
Author /Year
Bhojani112 2008
4b
Crosssectional
Men, 1162
Bother associated with urinary function
Joseph61 2003
4b
Crosssectional
Men, 819
Moderatesevere LUTS (AUA-SI 8+);
Never drinker (reference)
LUTS
Mod-severe obstructive sx (5+);
Former drinker
0.87 (0.68, 1.12)
Current <= 72g/day
Obstructive
OR 3.12 (1.4-6.8)
TE D
M AN U
SC
Alcoholism
AC C
EP
Mod-severe irritative sx (4+)
1.21 (0.95, 1.55)
2.35 (1.67, 3.29)
Alcoholism or alcohol-related problems associated with severe urinary function
Yes
Only heavy drinkers had significantly worse LUTS, obstructive and irritative symptoms
Yes
1.24 (0.94, 1.64) Current >72 g/day
0.74 (0.56, 0.98) 1.65 (1.13, 2.41) Irritative 1.19 (0.95, 1.48) 1.20 (0.96, 1.50) 1.92 (1.40, 2.62) 53
ACCEPTED MANUSCRIPT
4b
Crosssectional
AUA-SI score 8+ (reference <8)
Men, 1612
Reference: none
LUTS In men w/o hx of enlarged prostate:
1-42 g/wk
0.95 (0.60, 1.52)
43-98 g/wk
0.76 (0.46, 1.26)
99+ g/wk
RI PT
Klein54 1999
1.03 (0.69, 1.54)
Alcohol intake had little to no impact on LUTS in men with or without a history of enlarged prostate
Yes
The risk of developing an AUA-SI ≥15 is significantly lower on higher consumers of alcohol (0 vs. ≥2/day) hazard ratio= 0.67
Yes
Significantly lower risk of increased AUASI for all types of
Yes
SC
LUTS In men with hx of enlarged prostate:
Kristal19 2008
2b
Prospective cohort,
M AN U
0.53 (0.23, 1.25)
BPH defined as AUA-SI ≥15
Men, 4770
Lee95 1997
4b
Crosssectional
AC C
EP
TE D
7 year follow-up
Men, 496
0.33 (0.14, 0.77) 0.88 (0.39, 1.99)
Drinks per month reference <1/mo:
1-3/month
Hazard ratio
1-6/week
0.74 (0.58, 0.96)
7-13/week
0.85 (0.72, 1.01)
>=14/week
0.83 (0.68, 1.01) 0.67 (0.45, 0.84)
AUA-SI 8+
non-drinker vs drinker
Drinkers RR 0.61 (0.490.76)
beer <500ml vs. >500ml
Beer <500 RR 0.41
54
ACCEPTED MANUSCRIPT
per day
(0.25-0.66)
Soju <180 vs. >180 ml per day
Beer >500 RR 0.25 (0.09-0.73)
alcohol compared to non-drinkers
RI PT
Soju <180 RR 0.62 (0.480.81) Soju >180 RR 0.58 (0.440.77)
4b
Crosssectional
Men, 30,196
AUA-SI score
M AN U
None/mild 0-7
Calculated grams EtOH/day:
Moderate 819
Moderate or severe LUTS OR:
SC
Oh62 2012
None (ref) >0-10g
Severe 20-35
0.91(0.84-0.98)
Modest drinkers Yes have a lower risk of LUTS compared to non- drinkers but heavy consumption increases LUTS
4b
Crosssectional
Men, 2797
AC C
Rohrmann113 2005
EP
TE D
>10-20g
LUTS (at least 3 of these 4 sx: nocturia, incomplete emptying, hesitancy, and weak stream;
0.94 (0.86-1.02)
>20-30g 1.02 (0.91-1.14) >30-40g 1.12 (1.01-1.24) >40g (heavy) 1.19 (1.07-1.33)
Alcohol:
Never 1.00
Never, <1/wk, >1/wk but < 1/day, >=daily
<1/wk 0.53 (0.24, 1.18) >1/wk to < 1/d
Inverse association between alcohol and LUTS
Yes
0.99 (0.47, 2.08) >=1/d 0.59 (0.34, 1.03)
55
ACCEPTED MANUSCRIPT
I) 4b
Crosssectional
AUA-SI classified as mild 0-7, mod/severe 835
Men, 21,694
Number of alcoholic drinks per week : 0, 1-5, 6-10, >10
OR for mod/severe LUTS: 1-5 drinks per week 1.12 (1.01-1.25)
RI PT
Seim109 2005
only the 6-10 drink per week group had a greater OR of mod/sever LUTS
Yes
OR for moderate/severe LUTS showed a J shaped curve with modest consumption associated with lower symptoms but when HDL is added to model effect is attenuated
Yes
NS for either
Yes
6-10 drinks OR 1.41 (1.19-1.66)
2b
Prospective cohort,
AUA-SI classified as mild 0-7, mod/severe 835
Men, 9712
4b
Crosssectional
AC C
EP
TE D
27.9 months (average) follow-up
Tomita111 2009
Alcohol grams per day:
OR
0g
1.0 (ref)
0.1-9.9g
1.02 (0.94-1.10)
10.0-19.9g
1.10 (1.00-1.20)
20-29.9g
0.95 (0.85-1.05)
30.0-39.9g
1.16 (1.04-1.28)
≥40g
1.32(1.19-1.46)
weekly calculated grams alcohol:
OR AUA-SI>=1
none (ref)
1.1 (0.6-2.1)
M AN U
Suh110 2014
SC
>10 OR 1.23 (0.88-1.72)
Men, 1278
score of≥ 1 or ≥3 on modified AUASI
1.1 (0.8-1.5) 1.1 (0.7-1.6)
56
ACCEPTED MANUSCRIPT
1-29g
OR AUA-SI >=3
30-59 g
1.0 (0.6-1.5)
>60 g
1.0 (0.6-1.7)
RI PT
0.8 (0.3-2.0)
AC C
EP
TE D
M AN U
SC
BPH = Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
57
ACCEPTED MANUSCRIPT
Supplemental Table 5C. Nocturia and Alcohol Use- Detailed Summary of Articles Study Design, Duration Follow-up
Population, N
LUTS-Outcome(s)*
Alcohol Variable(s)*
Schneider63 2010
4b
Crosssectional
Men & Women, 3766
Nocturia improvement
No alcohol (ref), light, moderate and strong consumption (self-report)
Shiri48 2008
2b
Prospectiv e cohort,
Men, 1580
Nocturia: mild (12), moderate (3-4), severe (5 or more)
Results: Significance
Adjusted analyses?
Multiple regression model mild alcohol vs. none: nocturia: -.06, P value NS; comparing mod/severe alcohol to mild: nocturia: -.066
NS
no
Mild nocturia in modest drinkers RR 0.4 (0.2-0.8) heavy drinkers RR 1.0 (0.7-1.5)
Only for modest drinkers lower RR of moderate/severe nocturia
yes
Results: OR, RR, other
RI PT
Oxford Level
M AN U
SC
Author/Year
5 year follow-up
Alcohol (g/week): none, 1-150,
TE D
>150
OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
EP
Supplemental Table 5D. OAB and Alcohol Use- Detailed Summary of Articles Author/Year
Oxford Level
Study Design, Duration Followup
Population, N
Ikeda65 2011
4b
Crosssectional
Men & OAB: urgency with Women, 414 urination 8 times or men and more per day
AC C
LUTS-Outcome(s)*
Alcohol Variable(s)*
Results: OR, RR, other
Results: Significance
Adjusted analyses?
Never drinkers (ref), exdrinkers, current
Ex-drinker
NS for exdrinkers, current drinkers significantly
Yes
OR 0.98 (0.50-1.91)
58
ACCEPTED MANUSCRIPT
419 women
drinkers
Current drinker
more OAB
OR1.65 (1.04-2.62) Women: LUTS <1 drink OR 1.13 (0.70, 1.83)
RI PT
Reference 0 drinks <1 or 1+ drinks daily in the last 30 days
1+ OR 1.47 (0.75-2.86) Storage
SC
AUA-SI score 8+ (moderate to severe LUTS); AUA-SI score 5+ on 4 items (voiding); AUA-SI score 4+ on 3 items (storage)
<1 OR 0.95 (0.63, 1.46)
M AN U
5 years follow-up
Men & Women, 1,610 men and 2,535 women
TE D
Prospecti ve cohort,
EP
2b
AC C
Maserejian74 2012
1+ OR 0.55 (0.31-0.97)
Results for alcohol intake were inconsistent by intake level and symptom subtype with few groups achieving statistical significance
Yes
Voiding <1 OR 1.26 (0.66, 2.42) 1+ OR 3.12 (1.41-6.90) MEN: LUTS <1 OR 2.42 (1.24, 4.75) 1+ OR 1.73 (0.87-3.43) Storage <1 OR 2.19 (1.10, 4.38) 1+ OR 1.49 (0.77-2.87) Voiding <1 OR 1.08 (0.56, 2.08)
59
ACCEPTED MANUSCRIPT
1+ OR 1.07 (0.54-2.05) 4b
Crosssectional
Men & Women, 3766
Urgency episode improvement, Frequency improvement
Alcohol intake (none, light, moderate, severe; (Q))
Multiple regression model comparing mild alcohol to none: urgency episodes: parameter estimate -.18, frequency: -.10, all P values NS, comparing mod/severe alcohol to mild: urgency: -0.19, incontinence: .08, frequency: .074.
no
No
M AN U
SC
RI PT
Schneider7720 10
AC C
EP
TE D
OAB = Overactive bladder, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
60
ACCEPTED MANUSCRIPT
Author/Year Oxford Level
Study Design, Duration Followup
Population, N
LUTS-Outcome(s)*
Alcohol Variable(s)*
Results: OR, RR, other
Bhojani112 2008
4b
Crosssectional
Men, 1162
Moderate to severe leakage of urine
Alcoholism
RI PT
Supplemental Table 5E. UI and Alcohol Use- Detailed Summary of Articles
Hannestad59 2003
4b
Crosssectional
Women, 27,936
Alcoholism:
M AN U
SC
Leakage: OR 3.9(1.98.2)
glasses beer, wine, spirits per 2 weeks:
OR incontinence:
0-2 (ref)
SUI 1.1 (1.0-1.2)
TE D
UI: any, severe, stress, mixed, urgency
4b
Crosssectional
Women, 298
UI
AC C
Lee125 2012
EP
3+
Any type 1.1 (0.9-1.2)
Results: Significance
Adjusted analyses?
Alcoholism or alcohol-related problems associated with leakage
yes
None significant
yes
no
yes
UUI 1.0 (0.8-1.2) MUI 0.8 (0.7-1.1)
Reference nondrinkers
Alcohol OR 1.31 (0.74, 2.33)
Alcohol drinker
Beer OR 1.03 (0.55, 1.90)
Beer drinker Shochu drinker
Shochu OR 1.65 (0.64, 4.27)
Alcohol intake 0.1-32 g/day or >32 g/day (ref:
0.1-32 g/day OR 1.28 (0.71,2.31) 32+ g/day OR 1.69 61
ACCEPTED MANUSCRIPT
Crosssectional
Men & Women 3766
Urgency, frequency, UI, nocturia
Yoo114 2011
4b
Crosssectional
Women with UI on UDS, 86
Success defined as no further treatment for SUI, UUI, MUI
Beer intake 0.1350 mL/day or >350 mL/day (ref: none)
0.1-350 mL/day OR 1.07 (0.56,2.04)
No alcohol (ref) , light, moderate and strong consumption (self-report)
350+ mL/day OR 0.79 (0.18,3.40)
RI PT
4b
(0.42, 6.81)
Multiple regression model comparing mild alcohol to none: urgency episodes: parameter estimate .18, incontinence: .026, frequency: -.10, nocturia: -.06 all P values NS, comparing mod/severe alcohol to mild: urgency: 0.19, incontinence: .08, frequency: .074. nocturia: -.066
NS
no
Univariate analysis of predictors of success of pelvic floor muscle training estimated coefficient 2.088 p=0.057, multivariate= NS
NS
no
AC C
EP
TE D
M AN U
SC
Schneider63 2010
none);
Alcohol (≤3 or >3 drinks per week; Q)
UI = Urinary incontinence, SUI, Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI = Mixed urinary incontinence, Q = Questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
62
ACCEPTED MANUSCRIPT
Supplemental Table 6A. BPH and Tobacco Use- Detailed Summary of Articles Population, N
Prospecti ve cohort,
Men, 6581
LUTSOutcome(s)
Tobacco Variable(s)
Surgically treated obstructive uropathy
Smoking history: former, current, vs. never
BPH with surgery or prostatic enlargement detected by medical exam and indications for surgery vs. no BPH diagnosis and no or mild LUTS
Cigarette smoking:
Never 1.0
NS
No
S- for current smoking of 20+ cigarettes per day only
Yes
Former 1.04 (0.88-1.22)
BPH vs. no BPH diagnosis and non-severe LUTS or no LUTS
BPH vs. no BPH Never 1.00
Distant former (not for >10 years), Former or light (not for up to 10 years, or current 1-9 cigarettes /day), Current 1019/day, Current 20+/day, vs. never
TE D
Men, 882
EP
Crosssectional
Analyses adjusted?
Current 0.90 (0.76-1.06)
AC C
4b
Results: Significance, Direction
Comments
17 year follow-up Gass47 2002
Results: OR, RR, other
RI PT
2b
Study Design, Duration Followup
SC
Chyou17 1993
Oxford Level
M AN U
Author /Year
Distant former 0.87 (0.59, 1.29)
Former or light current 0.80 (0.52, 1.22) 10-19/day 0.91 (0.47, 1.76)
NS for other associations
20+/day 0.48 (0.24, 0.96)
BPH vs. no BPH/non-severe LUTS Never 1.00 Distant former 0.87 (0.60, 1.26) Former or light current 0.75 63
ACCEPTED MANUSCRIPT
(0.50, 1.11) 10-19/day 0.86 (0.46, 1.59) 20+/day 0.52 (0.26, 1.01) 4b
Crosssectional
Men, 599
BPH (AUA-SIBPH score 8+ and prostate volume 25mL+) vs. no BPH
Smoking history: never (reference), former, current
S- current smoker
Yes
BPH
S- Current smoker
Yes, age only
Never 1.0
NS Former smoker
Former smoker 1.0 (0.9-1.1)
NS cigar/pipe
Current smoker 0.7 (0.6-0.8)
NS trends for # cigarettes/day
BPH
RI PT
Goh67
Never 1.0
Former smoker 0.79 (0.49-1.28)
BPH diagnosis
History of TURP
M AN U
Men, 34694
Smoking history: never (reference), former, current, or only cigars/pipe
TE D
Crosssectional
Current smoking: never (reference), 1-10 cigarettes/day, 11-20, 21-30, 31+
EP
4b
AC C
Kang68 2004*
SC
Current smoker 0.44 (0.220.85)
Cigars/pipe 1.0 (0.8-1.1)
Never 1.0 1-10/day 0.7 (0.5-1.0) 11-20/day 0.7 (0.6-0.9) 21-30/day 0.7 (0.5-0.9) 31+/day 0.8 (0.6-1.1)
64
ACCEPTED MANUSCRIPT
TURP Never 1.0 Current smoker 0.6 (0.4-0.8)
RI PT
Former smoker 0.9 (0.8-1.1) Cigars/pipe 1.0 (0.7-1.3)
SC
Never 1.0
M AN U
1-10/day 0.5 (0.2-1.2) 11-20/day 0.7 (0.4-1.1) 21-30/day 0.6 (0.3-1.1) 31+/day 0.5 (0.2-1.1)
Casecontrol
Men, 4888
BPH, surgically treated
Tobacco use: cigarettes, other tobacco, exsmoker vs. never smoked (I)
TE D
3b
Morrison 46 1992
3b
Casecontrol
Men, 2913
AC C
EP
Morrison 45 1978
BPH, surgically treated
Cigarette use: former, current <1 packs/day, current 1 pack/day, current 2+
Never 1.0
S-
No
NS
Yes
Former 0.7 (0.5, 1.0) Current, cigarettes 0.5 (0.3, 0.7) Current, other 1.0 (0.6, 1.6) Never 1.0 Former 0.96 (0.78, 1.18) Current <1 pk/d 0.93 (0.59, 1.46)
65
ACCEPTED MANUSCRIPT
packs/day)
Current 1 pk/d 0.82 (0.59, 1.14) Current 2+ pk/d 0.88 (0.59, 1.39)
Crosssectional
Men, 62
BPH, clinical diagnosis
Smoking: yes vs. no; duration of smoking in years; number of cigarettes smoked per day
Percentage with BPH among:
NS
No
NS total trend, S+ for heavy smokers
Yes
RI PT
4b
Not smokers 50.0% Smokers 50.0%
SC
Naz115 2010
M AN U
MEAN (SD)
Years of smoking BPH 24.26 (3.63)
2b
Prospecti ve cohort, 6-8 year follow-up
Men, 29386
BPH, surgically treated, or modified AUA-SI score 15+ (Q)
AC C
Platz66 1999
EP
TE D
Controls 26.71 (4.57)
Cigarette smoking (20+ packs in lifetime): former, current 1-14 cigarettes/ day, current 1534 cigarettes/ day, current 35+ cigarettes/ day,
Cigarettes smoked/day BPH 13.88 (3.17) Controls 9.82 (1.90) Total BPH Never 1.00 Former 1.06 (0.97, 1.15) Current 1-14 0.90 (0.70, 1.16) Current 15-34 0.88 (0.73, 1.07)
NS trends for surgically-treated BPH, highmoderate/ severe 66
ACCEPTED MANUSCRIPT
Current 35+ 1.45 (1.07-1.97)
Crosssectional
Men, 471
Prostatic volume 40 mL+ vs. less, measured by transrectal ultrasound
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
Crosssectional
Men, 286
EP
4b
Prostatic volume 30 mL+ vs. less, measured by transrectal ultrasound
AC C
Roberts86 1997*
Never 1.00
symptoms, and enlarged prostate
S+ trends for severe symptoms, severe obstructive symptoms, and severe irritative symptoms NS
Yes, age and BMI only
NS
Yes, age and BMI only
M AN U
4b
TE D
Roberts85 1994*
SC
RI PT
vs. never (Q)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d
Former 0.89 (0.48, 1.63) Current 0.54 (0.19, 1.55)
No packs/day 1.00 0-0.9 pks/day 0.39 (0.08, 1.84) 1-1.4 pks/day 0.71 (0.15, 3.42) 1.5+ pks/day 0.75 (0.09, 6.31) Never 1.00 Former 1.10 (0.34, 3.88) Current 1.00 (0.30, 3.27)
No packs/day 1.00
67
ACCEPTED MANUSCRIPT
(Q)
0-0.9 pks/day 2.40 (0.56, 10.34) 1-1.4 pks/day 0.39 (0.04, 3.49) 1.5+ pks/day 1.61 (0.26, 10.8)
BPH, surgically treated
Acute Urinary Retention
RI PT
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d
(both chart review)
NS
Yes, age only
Never 1.00
Former 0.88 (0.59, 1.31)
Current 0.78 (0.41, 1.49)
SC
Acute urinary retention with catheterization
M AN U
8.75 year (median) follow-up
Men, 2089
0 pack-years 1.00
Additional analyses separated by symptoms at baseline (not shown here) were also NS
1-20 0.96 (0.61, 1.51) > 20 0.76 (0.49, 1.20)
TE D
Prospecti ve cohort,
EP
2b
AC C
Sarma116 2009
BPH, surgically treated Never 1.00 Former 0.96 (0.69, 1.32) Current 0.70 (0.40, 1.21)
0 pack-years 1.00 1-20 0.91 (0.62, 1.34) > 20 0.94 (0.66, 1.34) 68
ACCEPTED MANUSCRIPT
2b
Prospecti ve cohort,
Men, 929
Smoking history: ever vs. never; cigarettes smoked per day (0, 1-19, 20-29, 30+); years smoked (0, 1-19, 20-29, 30+). (I)
BPH (I)
12 year (average) follow-up
Never smoked 1.0
NS
Yes, age only
Ever smoked 1.1 (0.8, 1.6)
0 cig/day 1.0
RI PT
Seitter117 1992
1-19 1.2 (0.8, 1.8)
20-29 1.0 (0.6, 1.7)
1.2 (0.7, 1.9)
M AN U
SC
30+
0 years smoked 1.0 1-19 1.0 (0.7, 1.4)
Additional analyses by age and BMI shows that smokers age 60-79 with BMI 24.4026.75 had a relative risk of 2.8 (1.2, 6.6) compared to never smokers with the same age and BMI. All other additional analyses were NS.
TE D
20-29 1.2 (0.7, 2.1) 30+
1.3 (0.8, 2.0)
AC C
EP
BPH – Benign prostatic hyperplasia, LUTS = Lower urinary tract symptoms, D = Bladder diary I= interview, Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
69
ACCEPTED MANUSCRIPT
Supplemental Table 6B. Nocturia and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 3669
LUTSOutcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Nocturia (2+ voids per night; Q)
Current smoking: 1-15 cigarettes/day, 16+ per day, vs. non-smoker
0 cig/day 1.0
Crosssectional
Women, 1071
Nocturia (not specified, Q)
Current smoking: yes vs. no
S+
Yes
S-
No
S- Current smoker
Yes, age only
1.8 (1.1-2.8)
Percent with nocturia
M AN U
4b
Analyses adjusted?
1-15 1.4 (1.1-1.8) 16+
Aydin69 2014*
Results: Significance , Direction
Comments
RI PT
Asplund50 2004
Oxford Level
SC
Author /Year
No smoking 41.2% Yes 34.2%
Men, 34694
Nocturia (2+ voids per night)
Smoking history: never (reference), former, current, or only cigars/pipe
TE D
Crosssectional
Never 1.0 Current smoker 0.8 (0.7-0.9) Former smoker 1.1 (1.0-1.2)
Current smoking: never Cigars/pipe 1.1 (1.0-1.3) (reference), 1-10 cigarettes/day, 11-20, 2130, 31+ Never 1.0
EP
4b
AC C
Kang68 2004*
1-10/day 0.9 (0.7-1.2) 11-20/day 0.7 (0.6-0.9)
NS Former smoker NS cigar/pipe NS trends for cigarettes /day
21-30/day 0.9 (0.7-1.2)
70
ACCEPTED MANUSCRIPT
31+/day 1.0 (0.8-1.3) Shiri48 2008 2b
Prospecti ve cohort,
Men, 1633
Mild nocturia (1 or 2 voids/night)
Smoking history (at least 1 year): former, current, vs. never (Q)
Mild
NS
Yes, age only
NS
Yes
Never 1.0 Former 1.0 (0.7, 1.4)
RI PT
5 year follow-up
Current 0.9 (0.6, 1.3)
Moderate or severe (3 or more voids/night) (Q)
SC
Moderate or severe
M AN U
Never 1.0 Former 0.8 (0.5, 1.4) Current 0.8 (0.4, 1.7)
4b
Crosssectional
Women, 1790
Nocturia (2+ voids per night on single item from AUA-SI) (Q)
Smoking status: former, current, vs. never.
TE D
Tähtinen71 2011*
Yoshimura7 0 2004
4b
Crosssectional
Men & Women, 6517
AC C
EP
Among current smokers, intensity: 1-10 cigarettes /day, 11-20, >20. (Q)
Nocturia (2+ voids per night, single item) (Q)
Smoking history: current 1-19 cigarettes /day, current 20+ cigarettes /day, vs. non-smoker
Never 1.0 Former 1.0 (0.6, 1.5) Current 1.1 (0.7, 1.8)
Among current smokers:
NS
1-10 cigs/d 1.0 >10
1.4 (0.6, 2.9)
Non-smoker 1.0
S-
Yes
Current 1-19 not reported Current 20+ 0.72 (0.62-0.83)
71
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Q= questionnaire, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, = Negative association
72
ACCEPTED MANUSCRIPT
Supplemental Table 6C. OAB/LUTS (non-UI) and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 1071
LUTS-Outcome(s)
Caffeine Variable(s)
Results: OR, RR, other
Results: Significance , Direction
Analyses adjusted? Comments
Frequency Urgency (not specified, Q)
Current smoking: yes vs. no
RI PT
Aydin69 2014*
Oxford Level
Percent with frequency
NS
No
S+ (frequency, former only)
No
No smoking 38.0%
SC
Author /Year
Women, 1397
Frequency Urgency
Current smoking (vs. not current), former smoking (vs. not former)
TE D
Crosssectional
Any OAB (including UI)
EP
4b
Outcomes not independent of each other.
AC C
de Boer73 2011*
M AN U
Yes 39.7% Percent with urgency No smoking 34.7% Yes 39.3% Frequency Not former 1.0 Former 1.3 (1.0, 1.8) Not current 1.0
NS
Current 1.0 (0.8, 1.4) NS Urgency Not former 1.0 Former 1.2 (0.9, 1.6)
73
ACCEPTED MANUSCRIPT
Not current 1.0 Current 1.3 (1.0, 1.7)
RI PT
Any OAB
Not former 1.0
Former 1.1 (0.8, 1.4)
SC
Not current 1.0
4
Crosssectional
Women, 104
Storage symptoms and voiding symptoms reported by FLUTS (Q)
Hall119 2008
4b
Crosssectional
Women, 3167
Clusters of symptoms (Q) vs asymptomatic
Hsieh120 2010
4b
Crosssectional
Women, 1521
Lifetime history of smoking at least 100 cigarettes
Not reported
n/a
Current cigarette smoker (yes/no)
Percentage of cigarette smokers was higher in all four symptomatic clusters (25.2%, 22.1%, 23.5%, 28.0%) than in asymptomatic controls (16.1%, equality of means p = 0.016)
S+
Smoker (yes vs. no)
Percent with frequency:
S+
AC C
EP
TE D
Donovan118 2014*
M AN U
Current 1.2 (1.0, 1.6)
Daytime frequency (I; yes vs. no)
n/a
No
Non-smoker 18.2% Smoker 32.3% P = 0.005
74
ACCEPTED MANUSCRIPT
4b
Crosssectional
Men , 708
LUTS Moderate/ severe LUTS; moderate/ severe obstructive symptoms; moderate/ severe irritative symptoms on AUA-SI (I).
Cigarette smoking
LUTS
LUTS S+
Never
Never 1.00
Former
Former 1.76 (1.29, 2.39)
Obstructive S+/NS
Current <20/day Current 20+/day (I)
Current <20 2.07 (1.50, 2.85)
Irritative NS
RI PT
Joseph61 2003
Yes, LUTS and obstructiv e outcomes only
Current 20+ 1.51 (1.06, 2.15)
SC
OBSTRUCTIVE
EP
TE D
M AN U
Never 1.00
4b
Crosssectional
Men, 1612
LUTS (8+ on AUASI, Q)
Current <20 1.32 (0.90, 1.94) Current 20+ 1.73 (1.16, 2.56)
IRRITATIVE (unadjusted) Never 1.00 Former 1.13 (0.76, 1.68) Current <20 1.01 (0.65, 1.57)
AC C Klein54 1999
Former 1.87 (1.31, 2.66)
Current 20+ 1.48 (0.91, 2.40)
Cigarette smoking: former, current vs.
PX WITHOUT HX OF ENLARGED PROSTATE:
NS
Yes, age only
75
ACCEPTED MANUSCRIPT
never (Q)
Never 1.00 Former 0.99 (0.67-1.45)
Among smokers, packyears (pk-yrs)
RI PT
Current 1.16 (0.71-1.88)
None 1.00
0.5-20 pk-yrs 0.93 (0.59-1.44)
SC
21-40 pk-yrs 1.12 (0.70-1.79)
EP
TE D
M AN U
41+ pk-yrs 1.11 (0.70-1.75)
PX WITH HX OF ENLARGED PROSTATE: Never 1.00 Former 1.28 (0.68-2.38) Current 0.87 (0.32-2.35)
AC C
None 1.00 0.5-20 pk-yrs 1.25 (0.60-2.60) 21-40 pk-yrs 1.36 (0.57-3.20) 41+ pk-yrs 0.86 (0.38-1.94)
Koskimaki1
4b
Cross-
Men, 2128
LUTS (DAN-PSS-1
Cigarette smoking: former, current vs.
Smoking status was included as a “confounder” in a
Not
n/a
76
ACCEPTED MANUSCRIPT
reported
Moderate/ severe LUTS (AUA-SI score 8+; Q)
Cigarette smoking: former, current vs. never (Q); Quantity smoked (<1 pack/day, 1+ pack/day vs none); Length of smoking (<30 years, 30+ years vs none)
Never 1.00
NS
Yes, age only
Former 1.04 (0.74-1.50)
RI PT
Men, 514
multivariable model, but results were not reported.
Current 1.12 (0.86-1.46)
Among former or never smokers:
SC
Crosssectional
never (Q)
M AN U
4b
score 7+; Q)
TE D
Lee95 1997
sectional
0 packs/day 1.00 <1 1.21 (0.83, 1.77) 1+ 0.63 (0.32, 1.25)
0 years 1.00 <30 0.79 (0.50, 1.25) 30+ 1.51 (1.03, 2.37)
EP
2000
AC C
21
Among current or never smokers: 0 packs/day 1.00 <1 1.05 (0.80, 1.37) 1+ 1.56 (1.04, 2.34) 77
ACCEPTED MANUSCRIPT
0 years 1.00 <30 0.97 (0.62, 1.32)
Cigarette smoking: former, current vs. never (Q)
Total LUTS
Never 1.00
storage sx (5+ on related items); voiding sx (4+ on related items)
WOMEN
SC
Moderate-severe LUTS (AUA-SI score 8+; Q);
Former 1.22 (0.71, 2.09)
M AN U
5 years follow-up
Men & Women, 4145
TE D
Prospecti ve cohort;
EP
2b
AC C
Maserejian 74 2012
RI PT
30+ 1.13 (0.86, 1.50) S+ for women who currently smoke for storage sx; NS
Yes
Current 1.62 (0.87, 3.03) Storage Never 1.00 Former 1.18 (0.72, 1.95) Current 2.15 (1.30, 3.56) Voiding Never 1.00 Former 1.18 (0.51, 2.72) Current 1.99 (0.89, 4.44) MEN Total LUTS Never 1.00 78
ACCEPTED MANUSCRIPT
Former 0.91 (0.51, 1.63) Current 1.01 (0.55, 1.84) Storage
RI PT
Never 1.00
Former 1.22 (0.66, 2.26) Current 1.12 (0.61, 2.04)
SC
Voiding
Nuotio72 2001
4b
Crosssectional
Crosssectional
Men, 617
Men, 950
Moderate-severe LUTS (AUA-SI score 8+; Q) vs. mild LUTS (< 8)
Ever smoked vs never
LUTS (AUA-SI score with unclear cutpoint; Q)
Smoker: former, current vs. never
TE D
4b
Crosssectional
EP
Ngai123 2013
4b
Men & Women, 1059
AC C
Ng122 2007
M AN U
Never 1.00
Urgency (Q, single question)
Former 1.02 (0.43, 2.45) Current 0.73 (0.36, 1.46) Never 1.00
S+
Yes, hyperurica emia only
S+
Yes
S+
Yes, age and sex
NS
Yes, age
Ever smoked 2.11 (1.24-3.57)
Never 1.000 Former 1.781 (1.128-2.814) Current 2.058 (1.358-3.201)
Smoker: former, current vs. never
Never 1.00 Former 1.63 (0.97-2.74) Current 2.76 (1.43-5.32)
Roberts85
4b
Cross-
Men, 2115
LUTS (AUA-SI score
Cigarette smoking (at
Never 1.00
79
ACCEPTED MANUSCRIPT
sectional
least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
8+) (Q)
Former 0.96 (0.79, 1.18)
only
Current 0.82 (0.61, 1.08)
No packs/day 1.00
RI PT
1994*
0-0.9 pks/day 0.53 (0.33, 0.83) 1-1.4 pks/day 0.87 (0.56, 1.36)
Crosssectional
Men, 286
LUTS (AUA-SI score 8+) (Q)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
M AN U
4b
4b
Crosssectional
Men, 2797
LUTS (at least 3 of these 4 sx: nocturia, incomplete emptying, hesitancy, and weak stream; I)
AC C
Rohrmann1 13 2005
EP
TE D
Roberts86 1997*
SC
1.5+ pks/day 1.32 (0.84, 2.07) Never 1.00
NS
Yes, age only
Former 1.00 (0.5, 1.95) Current 0.84 (0.48, 1.49)
No packs/day 1.00 0-0.9 pks/day 1.07 (0.53, 2.17) 1-1.4 pks/day 0.55 (0.27, 1.13) 1.5+ pks/day 1.10 (0.50, 2.43)
Cigarette smoking: former, current 1-34 cigarettes /day, current 35+ cigarettes /day, vs. never (I). Among current or former smokers, <21 pack years, 21-49.9 pack
Never 1.00
NS
Former 1.37 (0.79, 2.36) Current 1-34 0.78 (0.39, 1.56) Current 35+ 0.75 (0.31, 1.82)
Trends in pack-years among all men, current 80
ACCEPTED MANUSCRIPT
4b
Crosssectional
Men, 21694
LUTS (AUA-SI score 8+; Q)
Cigarette smoking: former (1-5 cigarettes /day, 6-10, 11-15, 1620, 20+), current (1-5 cigarettes /day, 6-10, 11-15, 16-20, 20+), vs. never
Never 1.00
smokers, and former smokers (not reported here) were all NS S+
Yes, age only
S+
Yes
Former 1-5 1.08 (0.89, 1.32)
TE D
M AN U
SC
Seim109 2005
RI PT
years, 50+ pack years.
Crosssectional
Women, 1790
Frequency (longest interval between urination <2 hrs on Danish Prostatic Symptom Score).
Former 11-15 1.25 (1.06, 1.49) Former 16-20 1.34 (1.13, 1.59) Former >20 1.52 (1.24, 1.87) Current 1-5 0.99 (0.79, 1.24) Current 6-10 0.94 (0.81, 1.09) Current 11-15 0.89 (0.75, 1.06) Current 16-20 1.38 (1.14, 1.68)
EP 4b
AC C
Tähtinen71 2011*
Former 6-10 1.10 (0.97, 1.25)
Current >20 1.72 (1.23, 2.39) Smoking status: former, current, vs. never.
Frequency:
Among current smokers, intensity: 110 cigarettes /day, 11-
Former 1.7 (1.0, 3.1)
Never 1.0
Current 3.0 (1.8, 5.0)
81
ACCEPTED MANUSCRIPT
20, >20. (Q)
Among current smokers: 1-10 cigs/d 1.0 >10
2.2 (1.2, 4.3)
RI PT
Urgency (often or always on Danish Prostatic Symptom Score). (Q)
Urgency:
Never 1.0
SC
Former 1.8 (1.2, 2.9)
Men, 1278
LUTS (modified AUA-SI score 1+, or score 3+; Q)
Smoking history: current 1-19 cigarettes /day, current 20+ cigarettes /day, vs. non-smoker
TE D
Crosssectional
EP
4b
AC C
Tomita111 2009
M AN U
Current 2.7 (1.7, 4.2)
Among current smokers: 1-10 cigs/d 1.0 >10
2.1 (1.1, 3.9)
Modified AUA-SI score 1+
NS
Yes
Non-smoker 1.0 Current 1-19 1.0 (0.7, 1.5) Current 20+ 0.9 (0.7, 1.2)
Modified AUA-SI score 3+
NS
Non-smoker 1.0 Current 1-19 0.9 (0.5, 1.6) Current 20+ 0.9 (0.6, 1.3) 82
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
OAB = Overactive bladder, LUTS = Lower urinary tract symptoms, AUA-SI = American Urological Association Symptom Index, Q= questionnaire, I = interview, OR = Odds ratio, RR = Relative risk, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
83
ACCEPTED MANUSCRIPT
Supplemental Table 6D. UI and Tobacco Use- Detailed Summary of Articles
Aydin69 2014*
Oxford Level
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 1071
LUTSOutcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
UI (not specified, Q)
Current smoking: yes vs. no
RI PT
Author /Year
Percent with incontinence
NS
No
S+
Yes
SC
No smoking 37.5% Yes 34.9%
Urodynamically tested SUI and motor incontinence, vs continent
Smoking history: former, current vs. never
Genuine SUI:
M AN U
Women, 160
Never 1.00 Former 2.20 (1.18-4.11) Current 2.48 (1.60-3.84)
TE D
Cross sectional
EP
4b
AC C
Bump75 1992
0 pk/d 1.00 S-1 1
0.94 (0.43-2.04) 2.44 (1.31-4.55)
>1
4.72 (2.42-9.22)
0 pk-y 1.00 1-14
1.86 (1.01-3.42)
15-29 2.50 (1.32-4.74) 84
ACCEPTED MANUSCRIPT
30+
3.78 (2.06-6.96)
Motor Incont.:
RI PT
Never 1.00
Former 2.92 (1.58-5.39)
SC
Current 1.98 (1.19-3.02)
M AN U
0 pk/d 1.00
TE D
<1
Crosssectional
Women, 535
Genuine stress incontinence, detrusor instability, mixed (no controls)
1
2.49 (1.31-4.75)
>1
2.71 (1.29-5.69)
0 pk-y 1.00 1-14
2.71 (1.51-4.87)
15-29 2.23 (1.13-4.39)
EP 4b
AC C
Cundiff79 1997
0.97 (0.43-2.16)
30+ Smoking (not defined)
2.61 (1.34-5.06)
% smokers:
NS
No
13% genuine stress incontinence 13% SI w/ or w/o DI
85
ACCEPTED MANUSCRIPT
(p = 1.0) 22% detrusor instability 19% DI w/ or w/o SUI
Women, 83355
Self-report UI: occasional (1-3 leaks/mo), frequent (1+ leaks/wk), severe (frequent leaks enough to wet underwear)
Cigarette smoking (never, former, current)
Crosssectional
Women, 1397
UUI, not independent of other OAB
Yes
S- (current only)
Current 0.91 (0.85, 0.98)
EP 4b
Occasional incontinence
Never 1.00
Former 1.00 (0.96, 1.05)
Frequent incontinence
Frequent incontinence
Never 1.00
S+
Former 1.12 (1.08, 1.16) Current 1.20 (1.13, 1.28)
Severe incontinence S+
Severe incontinence Never 1.00
AC C de Boer73 2011*
Occasional incontinence
SC
Crosssectional
M AN U
4b
TE D
Danforth78 2006
RI PT
(p = 1.0)
Former 1.11 (1.05, 1.17) Current 1.34 (1.25, 1.45) Current smoking (vs. not current), former smoking
Not former 1.0
NS
No
Former 1.0 (0.8, 1.4) 86
ACCEPTED MANUSCRIPT
symptoms
(vs. not former)
Not current 1.0 Current 1.3 (1.0, 1.7)
Women, 104
Incontinence symptoms (Q)
Hannested59 2003
4b
Crosssectional
Women, 27936
Any UI, SUI, MUI, UUI. Each reported as all cases (vs. no UI) and severe (vs. none or mild).
Lifetime history of smoking at least 100 cigarettes
Not reported
ALL Cigarette smoking:
RI PT
Crosssectional
Any incontinence
SC
4b
n/a
n/a
ALL
Yes
Any incontinence
Never 1.0
Never
S+
Former (1-19/day) 1.1 (1.0, 1.2)
M AN U
Donovan118 2014*
Former (1-19/day)
Former (20+/day) 1.7 (1.4, 2.0)
Former (20+/day) Current (119/day)
Current (1-19/day) 0.9 (0.9, 1.0)
Stress incontinence S+/-
TE D
Current (20+/day) 1.3 (1.1, 1.6)
AC C
EP
Current (20+/day) Stress incontinence
Mixed incontinence
Never 1.0
S+
Former (1-19/day) 1.1 (1.0, 1.2) Former (20+/day) 1.3 (1.0, 1.7) Current (1-19/day) 0.8 (0.7, 0.9)
Urge incontinence NS, S+
Current (20+/day) 1.2 (1.0, 1.5)
87
ACCEPTED MANUSCRIPT
SEVERE Mixed incontinence Never 1.0
Any incontinence S+
RI PT
Former (1-19/day) 1.2 (1.0, 1.3) Former (20+/day) 2.2 (1.7, 2.8)
SC
Current (1-19/day) 1.1 (1.0, 1.3)
Stress incontinence NS, S+
M AN U
Current (20+/day) 1.6 (1.2, 2.1)
Urge incontinence
Mixed incontinence
Never 1.0
S+
AC C
EP
TE D
Former (1-19/day) 1.1 (0.9, 1.4) Former (20+/day) 1.9 (1.2, 3.2) Current (1-19/day) 1.2 (1.0, 1.5)
Urge incontinence NS
Current (20+/day) 1.3 (0.8, 1.4) SEVERE Any incontinence Never 1.0 Former (1-19/day) 1.2 (1.1, 1.5)
88
ACCEPTED MANUSCRIPT
Former (20+/day) 2.5 (1.8, 3.5) Current (1-19/day) 1.3 (1.1, 1.5)
RI PT
Current (20+/day) 2.1 (1.5, 2.8)
Stress incontinence
SC
Never 1.0
M AN U
Former (1-19/day) 1.1 (0.8, 1.4)
Former (20+/day) 1.4 (0.7, 2.6) Current (1-19/day) 1.1 (0.8, 1.4)
AC C
EP
TE D
Current (20+/day) 1.8 (1.1, 2.9)
Mixed incontinence Never 1.0 Former (1-19/day) 1.3 (1.0, 1.6) Former (20+/day) 3.3 (2.2, 4.9) Current (1-19/day) 1.4 (1.1, 1.7) Current (20+/day) 2.4 (1.6, 3.6)
89
ACCEPTED MANUSCRIPT
Urge incontinence Never 1.0 Former (1-19/day) 1.0 (0.6, 1.7)
RI PT
Former (20+/day) 2.1 (0.7, 6.0) Current (1-19/day) 1.3 (0.1, 3.6)
4b
Crosssectional
Women, 3537
UI (ever vs. never)
Smoking (yes vs. no)
Percent with UI
M AN U
Hsieh80 2008
SC
Current (20+/day) 1.3 (0.8, 2.1) NS
No
S+
Yes
NS
No
n/a
n/a
Non-smoker 18.7% Smoker 17.5% P = 0.759
Smith124 2010
4b
4b
Crosssectional
Crosssectional
Women, 650
Women, 592
Mean number UI episodes, among stressincontinent presurgical patients (D)
Current smoking: yes vs. no
UI (any type, Q)
Current smoking: yes vs. no (Q)
TE D
Crosssectional
EP
Skjeldestad81 2008
4b
AC C
Richter76 2005
Women, 572
UI (leaking Lifetime smoking more often than history (100+ cigarettes in life),
Yes 1.37 (antilog of slope coefficient, reference group is not current smoker) P = 0.01
Percentage who currently smoked: Without UI 31.4% With UI 33.0% p = 0.71 Percentage who smoked at least 100 cigarettes:
No statistical 90
ACCEPTED MANUSCRIPT
Crosssectional
Women, 1790
SUI UUI (Both measured as often or always on Danish Prostatic Symptom Score). (Q)
Smoking status: former, current, vs. never.
SUI:
Among current smokers, intensity: 1-10 cigarettes /day, 11-20, >20. (Q)
Former 1.4 (0.9, 2.1)
Among current smokers:
TE D EP Women,
SUI
NS
1-10 cigs/d 1.0 1.3 (0.6, 2.8)
NS
UUI: Never 1.0 Former 1.8 (0.8, 4.3) Current 1.5 (0.6, 3.8)
AC C Case-
Yes
Current 0.8 (0.5, 1.3)
Among current smokers:
NS
1-10 cigs/d 1.0 >10
3b
NS
Never 1.0
>10
Tampakoudis
test of association
With UI 34.4%
RI PT
4b
Without UI 37.1%
SC
Tähtinen71 2011*
measured by Behavioral Risk Factor Surveillance System Survey Questionnaire (Q)
M AN U
never; Q)
Smoking history:
1.7 (0.3, 8.5)
Percentage who were smokers:
S+ UI in
No 91
ACCEPTED MANUSCRIPT 77
1995
control
160
Without UI 25%
general
With UI 62.5% P < 0.0005
RI PT
UUI, MUI (Both urodynamically assessed)
former, current, vs. never
S+ UUI/MUI relative to SUI
Among incontinent smokers: SUI 39.6%
M AN U
SC
UUI/MUI 60.4%
Among incontinent nonsmokers: SUI 65.6%
TE D
UUI/MUI 34.4%
AC C
EP
UI = Urinary incontinence, SUI = Stress urinary incontinence, UUI = Urgency urinary incontinence, MUI, Mixed urinary incontinence, OAB = Overactive bladder, Q= questionnaire, D= diary, DI= detrusor instability, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
92
ACCEPTED MANUSCRIPT
Supplemental Table 6E. Other- parameters and Tobacco Use- Detailed Summary of Articles
4b
Study Design, Duration Followup
Population, N
Crosssectional
Women, 189 Urodynamic test parameters
LUTS-Outcome(s)
Tobacco Variable(s)
Results: OR, RR, other
Results: Significance, Direction
Analyses adjusted? Comments
Active smoker vs. never smoker
Smokers had higher functional urethral length (26.4mm vs 23.6 mm, p=0.007) and maximum cough spike (114.4 cm H2O vs 96.7 cm H2O, p=0.04) relative to non-smokers. No difference in maximum closure pressure, mean pressure transmission ratio, or degree of urethral axis with stress.
S+
No
4a
Case series
Women, 319 Intravesical peak pressures generated by cough (CIPP), cough leak point pressure (CLPP)
AC C
Fuganti83 2011
EP
TE D
M AN U
SC
Bump82 1994
Oxford Level
RI PT
Author /Year
Smoking history: former, current vs. never
NS CLPP was lower in never smokers (110cmH2O) than in current or former smokers (140cmH2O, p = 0.01)
S+
CLPP – no CIPP – yes
S+
RR for CIPP
93
ACCEPTED MANUSCRIPT
Never 1.0 Smoker 14.270 (8.851, 19.689)
Prostatic tissue weight
Urinary flow rate (mL/s)
MEAN (SD), p-values compared to never
RI PT
Cigarette smoking: former, current vs. never (Q)
S+ Oestradiol
No
NS Testosterone NS DHEA
Oestradiol
NS DHEA-S
SC
Plasma levels of Oestradiol (pg/mL), Testosterone (ng/mL), DHEA (mg/mL), DHEA-S (mg/mL)
Never 26.65 (3.04)
M AN U
Men, 68
TE D
Crosssectional
Former 32.23 (2.60, p < 0.01)
NS tissue weight
Current 33.83 (6.53, p < 0.01)
Testosterone
NS Urinary flow rate
Never 3.09 (0.33) Former 3.32 (0.43, p < 0.05) Current 2.44 (0.80, p < 0.01)
EP
4b
AC C
Küpeli84 1997
DHEA Never 1.65 (0.32) Former 1.34 (0.24) Current 4.62 (0.90)
94
ACCEPTED MANUSCRIPT
DHEA-S Never 3.18 (0.32)
RI PT
Former 2.67 (0.28)
Current 3.86 (0.36)
SC
Tissue weight
Former 59.6 (5.25) Current 59.1 (7.42)
Urinary flow rate Never 5.7 Former 6.1 Current 7.2
AC C
EP
TE D
M AN U
Never 73.4 (5.41)
95
ACCEPTED MANUSCRIPT
Peak urinary flow rate less than 15 mL/sec vs. 15 or more;
Flow < 15 mL/sec Never 1.00
S-
Yes, age and voided volume only
Former 0.85 (0.69, 1.06) Current 0.48 (0.35, 0.66)
No packs/day 1.00
0-0.9 pks/day 0.46 (0.28, 0.74)
M AN U
SC
Peak urinary flow rate less than 10 mL/sec vs. 15 or more
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
RI PT
Men, 2115
TE D
Crosssectional
EP
4b
AC C
Roberts85 1994*
1-1.4 pks/day 0.49 (0.29, 0.81) 1.5+ pks/day 0.55 (0.32, 0.95)
Flow < 10 mL/sec Never 1.00 Former 0.80 (0.62, 1.09) Current 0.42 (0.25, 0.72)
No packs/day 1.00 0-0.9 pks/day 0.47 (0.21, 1.03) 1-1.4 pks/day 0.27 (0.09, 96
ACCEPTED MANUSCRIPT
0.79)
Crosssectional
Men, 286
Peak urinary flow rate less than 15 mL/sec vs. 15 or more
EP
4b
AC C
Roberts86 1997*
TE D
M AN U
SC
RI PT
1.5+ pks/day 0.65 (0.27, 1.58)
Cigarette smoking (at least 100 cigarettes in life): former, current vs. never. Among current smokers, 0-0.9 pks/d, 1-1.4 pks/d, 1.5+ pks/d (Q)
Never 1.00 Former 0.71 (0.28, 1.76) Current 0.39 (0.18, 0.84)
S- (current smokers, and heavy smokers, have less risk)
Yes, age and voided volume only
No packs/day 1.00 0-0.9 pks/day 0.37 (0.14, 0.97) 1-1.4 pks/day 0.41 (0.14, 1.21)
97
ACCEPTED MANUSCRIPT
1.5+ pks/day 0.24 (0.08, 0.77)
AC C
EP
TE D
M AN U
SC
RI PT
Q= questionnaire, S=Statistically significant association, NS= Not statistically significant association, + = Positive association, - = Negative association
98
ACCEPTED MANUSCRIPT Supplemental References
57. 58. 59. 60.
61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73.
RI PT
56.
SC
55.
M AN U
54.
TE D
53.
EP
52.
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114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124.
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104.
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102.
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Lee, A. H., Hirayama, F.: Alcohol consumption and female urinary incontinence: a community-based study in Japan. Int J Urol, 19: 143, 2012
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125.