Dietary flavonoid intake and incidence of erectile dysfunction

Aedín Cassidy, Mary Franz, Eric B Rimm, Aedín Cassidy, Mary Franz, Eric B Rimm

Abstract

Background: The predominant etiology for erectile dysfunction (ED) is vascular, but limited data are available on the role of diet. A higher intake of several flavonoids reduces diabetes and cardiovascular disease risk, but no studies have examined associations between flavonoids and erectile function.

Objective: This study examined the relation between habitual flavonoid subclass intakes and incidence of ED.

Design: We conducted a prospective study among 25,096 men from the Health Professionals Follow-Up Study. Total flavonoid and subclass intakes were calculated from food-frequency questionnaires collected every 4 y. Participants rated their erectile function in 2000 (with historical reporting from 1986) and again in 2004 and 2008.

Results: During 10 y of follow-up, 35.6% reported incident ED. After multivariate adjustment, including classic cardiovascular disease risk factors, several subclasses were associated with reduced ED incidence, specifically flavones (RR = 0.91; 95% CI: 0.85, 0.97; P-trend = 0.006), flavanones (RR = 0.89; 95% CI: 0.83, 0.95; P-trend = 0.0009), and anthocyanins (RR = 0.91; 95% CI: 0.85, 0.98; P-trend = 0.002) comparing extreme intakes. The results remained statistically significant after additional adjustment for a composite dietary intake score. In analyses stratified by age, a higher intake of flavanones, anthocyanins, and flavones was significantly associated with a reduction in risk of ED only in men <70 y old and not older men (11-16% reduction in risk; P-interaction = 0.002, 0.03, and 0.007 for flavones, flavanones, and anthocyanins, respectively). In food-based analysis, higher total intake of fruit, a major source of anthocyanins and flavanones, was associated with a 14% reduction in risk of ED (RR = 0.86; 95% CI: 0.79, 0.92; P = 0.002).

Conclusions: These data suggest that a higher habitual intake of specific flavonoid-rich foods is associated with reduced ED incidence. Intervention trials are needed to further examine the impact of increasing intakes of commonly consumed flavonoid-rich foods on men's health.

Keywords: anthocyanins; erectile dysfunction; flavanones; flavones; flavonoids.

Figures

FIGURE 1
FIGURE 1
Risk of erectile dysfunction associated with total fruit intake and intake of the top 5 sources of anthocyanins, flavanones, and flavones (strawberries, blueberries, red wine, apples/pears, and citrus products) and intake of citrus and blueberries separately in the Health Professionals Follow-Up Study (n = 25,096). RRs were adjusted for the following covariates: marital status, smoking, BMI, physical activity, alcohol consumption, use of multivitamin supplements, energy intake, history of hypertension, history of myocardial infarction, history of hypercholesterolemia, and history of diabetes.

References

    1. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999;84:50–6.
    1. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the Health Professionals Follow-up Study. Ann Intern Med 2003;139:161–8.
    1. Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, DeCarolis E. The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006;166:213–9.
    1. Kloner RA. Erectile dysfunction as a predictor of cardiovascular disease. Int J Impot Res 2008;20:460–5.
    1. Fung MM, Bettencourt R, Barrett-Connor E. Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll Cardiol 2004;43:1405–11.
    1. Chew KK, Bremner A, Jamrozik K, Earle C, Stuckey B. Male erectile dysfunction and cardiovascular disease: is there an intimate nexus? J Sex Med 2008;5:928–34.
    1. Batty GD, Li Q, Czernichow S, Neal B, Zoungas S, Huxley R. Erectile dysfunction and later cardiovascular disease in men with type 2 diabetes: prospective cohort study based on the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) trial. J Am Coll Cardiol 2010;56:1908–13.
    1. Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 2000;30:328–38.
    1. Kupelian V, Link CL, McKinlay JB. Association between smoking, passive smoking, and erectile dysfunction: results from the Boston Area Community Health (BACH) Survey. Eur Urol 2007;52:416–22.
    1. Riedner CE, Rhoden EL, Ribeiro EP, Fuchs SC. Central obesity is an independent predictor of erectile dysfunction in older men. J Urol 2006;176:1519–23.
    1. Gazzaruso C, Solerte SB, Pujia A, Coppola A, Vezzoli M, Salvucci F. Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors. J Am Coll Cardiol 2008;51:2040–4.
    1. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA 2005;294:2996–3002.
    1. Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 2011;171:1797–803.
    1. Esposito K, Ciotola M, Giugliano F, De Sio M, Giugliano G, D’Armiento M. Mediterranean diet improves erectile function in subjects with the metabolic syndrome. Int J Impot Res 2006;18:405–10.
    1. Averbeck MA, Colares C, de Lira GH, Selbach T, Rhoden EL. Evaluation of endothelial function with brachial artery ultrasound in men with or without erectile dysfunction and classified as intermediate risk according to the Framingham Score. J Sex Med 2012;9:849–56.
    1. Esposito K, Giugliano F, Maiorino MI, Giugliano D. Dietary factors, Mediterranean diet and erectile dysfunction. J Sex Med 2010;7:2338–45.
    1. Schewe T, Steffen Y, Sies H. How do dietary flavanols improve vascular function? A position paper. Arch Biochem Biophys 2008;476:102–6.
    1. de Pascual-Teresa S, Moreno DA, Garcia-Viguera C. Flavanols and anthocyanins in cardiovascular health: a review of current evidence. Int J Mol Sci 2010;11:1679–703.
    1. Cassidy A, O’Reilly EJ, Kay C, Sampson L, Franz M, Forman JP. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am J Clin Nutr 2011;93:338–47.
    1. Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008;88:38–50.
    1. Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 2012;95:740–51.
    1. Buscemi S, Rosafio G, Arcoleo G, Mattina A, Canino B, Montana M. Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk. Am J Clin Nutr 2012;95:1089–95.
    1. Jennings A, Welch AA, Fairweather-Tait SJ, Kay C, Minihane AM, Chowienczyk P. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am J Clin Nutr 2012;96:781–8.
    1. Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD. Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 2008;88:1018–25.
    1. Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radic Biol Med 2012;52:95–102.
    1. Morand C, Dubray C, Milenkovic D, Lioger D, Martin JF, Scalbert A. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93:73–80.
    1. Rimm EB, Giovannucci EL, Willett WC, Colditz GA, Ascherio A, Rosner B. Prospective study of alcohol consumption and risk of coronary disease in men. Lancet 1991;338:464–8.
    1. Bai W, Wang C, Ren C. Intakes of total and individual flavonoids by US adults. Int J Food Sci Nutr 2014;65:9–20.
    1. Liu XX, Li SH, Chen JZ, Sun K, Wang XJ, Wang XG. Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2012;22:463–70.
    1. Li SH, Liu XX, Bai YY, Wang XJ, Sun K, Chen JZ. Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am J Clin Nutr 2010;91:480–6.
    1. Salvini S, Hunter DJ, Sampson L, Stampfer MJ, Colditz GA, Rosner B. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 1989;18:858–67.
    1. Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ, Litin LB. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc 1993;93:790–6.
    1. Krogholm KS, Bysted A, Brantsaeter AL, Jakobsen J, Rasmussen SE, Kristoffersen L. Evaluation of flavonoids and enterolactone in overnight urine as intake biomarkers of fruits, vegetables and beverages in the Inter99 cohort study using the method of triads. Br J Nutr 2012;108:1904–12.
    1. Hu FB, Stampfer MJ, Rimm E, Ascherio A, Rosner BA, Spiegelman D. Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. Am J Epidemiol 1999;149:531–40.
    1. Therneau TM, Grambach PM. The counting process form of a Cox model: modeling survival data. New York: Springer; 2000. p. 68–77.
    1. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496–509.
    1. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. A prospective study of risk factors for erectile dysfunction. J Urol 2006;176:217–21.
    1. Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004;291:2978–84.
    1. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007;120:151–7.
    1. Jackson G. Erectile dysfunction: a marker of silent coronary artery disease. Eur Heart J 2006;27:2613–4.
    1. Hodges LD, Kirby M, Solanki J, O’Donnell J, Brodie DA. The temporal relationship between erectile dysfunction and cardiovascular disease. Int J Clin Pract 2007;61:2019–25.
    1. Gazzaruso C, Giordanetti S, De Amici E, Bertone G, Falcone C, Geroldi D. Relationship between erectile dysfunction and silent myocardial ischemia in apparently uncomplicated type 2 diabetic patients. Circulation 2004;110:22–6.
    1. Inman BA, Sauver JL, Jacobson DJ, McGree ME, Nehra A, Lieber MM. A population-based, longitudinal study of erectile dysfunction and future coronary artery disease. Mayo Clin Proc 2009;84:108–13.
    1. Böhm M, Baumhakel M, Teo K, Sleight P, Probstfield J, Gao P. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation 2010;121:1439–46.
    1. Lopez DS, Wang R, Tsilidis KK, Zhu H, Daniel CR, Sinha A. Role of caffeine intake on erectile dysfunction in US men: results from NHANES 2001–2004. PLoS One 2014;10:e0123547.
    1. Giugliano F, Maiorino M, Bellastella G, Gicchino M, Giugliano D, Esposito K. Determinants of erectile dysfunction in type 2 diabetes. Int J Impot Res 2010;22:204–9.
    1. Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol 2011;60:1010–6.
    1. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: a physiologic mediator of penile erection. Science 1992;257:401–3.
    1. Seok YM, Baek I, Kim YH, Jeong YS, Lee IJ, Shin DH. Isoflavone attenuates vascular contraction through inhibition of the RhoA/Rho-kinase signaling pathway. J Pharmacol Exp Ther 2008;326:991–8.
    1. Song MJ, Baek I, Seo M, Kim SH, Suk K, Woodman OL. Effects of 3′,4′-dihydroxyflavonol on vascular contractions of rat aortic rings. Clin Exp Pharmacol Physiol 2010;37:803–10.
    1. d’Emmanuele di Villa Bianca R, Sorrentino R, Mirone V, Cirino G. Hydrogen sulfide and erectile function: a novel therapeutic target. Nat Rev Urol 2011;8:286–9.
    1. Horrigan LA, Holohan CA, Lawless GA, Murtagh MA, Williams CT, Webster CM. Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H2S pathway. Food Funct 2013;4:392–400.
    1. Zhang W, Wang Y, Yang Z, Qiu J, Ma J, Zhao Z. Antioxidant treatment with quercetin ameliorates erectile dysfunction in streptozotocin-induced diabetic rats. J Biosci Bioeng 2011;112:215–8.
    1. Jin BH, Qian LB, Chen S, Li J, Wang HP, Bruce IC. Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress. Eur J Pharmacol 2009;616:200–5.
    1. Miller KB, Hurst WJ, Payne MJ, Stuart DA, Apgar J, Sweigart DS. Impact of alkalization on the antioxidant and flavanol content of commercial cocoa powders. J Agric Food Chem 2008;56:8527–33.

Source: PubMed

3
Subskrybuj