OH MAN! RESEARCH STUDY SAYS COVD-19 CAN CAUSE ERECTILE DYSFUNCTION
Posted on September 03 2021
By Steve Blechman
What's up? A research study published May 7th, 2021 in World Journal of Men’s Health reported that the coronavirus can cause erectile dysfunction (ED). This is the first study to “demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans.” The researchers from the University of Miami School of Medicine suggest that “widespread endothelial cell dysfunction from covid-19 infection can contribute to ED.” The researchers believe that COVID-19 can damage the peniIe blood vessels that supply blood to the penis, noting that “endothelial damage associated with COVID-19 is likely to affect the penile vascular flow, resulting in impaired erectile dysfunction.” This is very concerning! The virus presence in the penis is likely to worsen ED. Researchers say, “Patients should be aware of the potential complication of post-COVID-19 ED. Any changes observed in erectile function after infection should be followed up with the appropriate specialist for treatment and to help further investigation into the condition.” The researchers further acknowledged that “future studies are needed to validate the effects of this virus on sexual function.”
We know the best way to avoid hospitalization, serious illness, and death from COVID-19 is to get vaccinated. But even if you are vaccinated, it is still possible to get infected with the coronavirus and penile viral exposure. Also, people who have not gotten vaccinated and who have natural immunity after getting COVID-19 can still get re-infected with the virus.
Erectile dysfunction is the inability to obtain and maintain an erection for sexual activity as a result of hormonal, neurological and vascular factors. 30 million men worldwide have erectile dysfunction. Erectile dysfunction affects some 18 million men in the United States. As men age, the risk of erectile dysfunction increases. From the early age of 30, the number of men who have underperforming erections, or none at all, increases. The main causes of erectile dysfunction include aging, diabetes and cardiovascular disease. Today, when a man in his 30s or 40s goes to their primary care physician because of erectile dysfunction, it is often recommended that the patient see a cardiologist! Many cases of erectile dysfunction are caused by cardiovascular problems with a warning that you may be at a greater risk of a heart attack or stroke.
Do you have the major risk factors for cardiovascular disease such as: family history (mother, father, sibling, etc.), elevated blood lipids and LDL (bad) cholesterol, low HDL (good) cholesterol, hypertension, elevated triglycerides and C-reactive protein (a measure of inflammation in the body)? If you have any of these risk factors, you need to take charge and lower your risk. See your physician now! Every risk factor that you eliminate, you lower your risk of heart disease and erectile dysfunction. To improve long-term cardiovascular health and erectile function, men should eat a heart-healthy Mediterranean diet and engage in a daily resistance training and vigorous aerobic exercise program. Several studies have shown that men combining physical activity with the Mediterranean diet can provide additional and enhanced benefits to alleviate erectile function. Regular exercise and the Mediterranean diet also stimulate nitric oxide release and promote health and function of endothelial cells lining vascular walls.
Overweight men that lose weight often have improvement in their erectile function, testosterone levels, and sexual health. Research has shown that men following the Mediterranean diet, low in saturated fat and high in monounsaturated fats, omega-3 fats, nitrates and polyphenols (from extra-virgin olive oil, nuts, fatty fish, fruits, and leafy vegetables) have less erectile dysfunction. Research has also shown that men with the metabolic syndrome – a group of risk factors (i.e., hypertension, high blood lipids and insulin resistance) – were 100% more likely to have erection problems than people who exercise regularly. The incidents of heart disease were greatest in men suffering from the metabolic syndrome and erectile dysfunction. Exercise and the Mediterranean diet protects against erectile dysfunction and cardiovascular disease.
What are the best nutrients reported in the scientific literature to enhance erectile function and better sexual performance?
- L-Citrulline: L-citrulline, an amino acid that when taken orally is converted in the body to L-arginine. L-citrulline has been shown in the scientific research to increase L-arginine more efficiently in the body than L-arginine and increase nitric oxide production. Nitric oxide acts as a vasodilator (blood vessel relaxant) and controls blood flow to tissues and to the penis. It is generally accepted that nitric oxide is the principal agent responsible for relaxation of penile smooth muscle. Research has shown that 5.6 grams per day of L-citrulline for seven days reduced blood vessel stiffness in middle-aged men (International Journal of Cardiology, Nov. 8, 2010). Research has also shown that oral citrulline can improve erectile function (Sex Med, 2018). Oral citrulline supplementation of 1.5 grams (for 30 days) improves erectile hardness in men with erectile dysfunction (Urology, January 2011). A most recent study published in the July 2019 issue of the Journal of Andrology compared the erectile dysfunction drug sildenafil (50mg) alone or in combination with L-arginine (3grams) daily for eight weeks. Researchers concluded that, “adding L-arginine to sildenafil demonstrated more efficacy than sildenafil alone for treatment of erectile dysfunction patients.” Since L-citrulline is more effective than L-arginine for raising blood levels of arginine, it would be expected that citrulline would be much more effective than L-arginine.
- Natural polyphenols from beetroot extract, grape skin extract and pine bark extract contain potent antioxidants that have many health benefits including increasing nitric oxide and vasodilation. Most erection problems are caused by poor blood flow to the penis. Cells lining the blood vessels secrete nitric oxide that controls blood flow. Blood vessel disease disturbs the function of these cells, which reduce the ability to release nitric oxide and maintain erections. Researchers from Norwich Medical School in the U.K. found that men with the greatest dietary polyphenol intake showed a 14% lower risk of erectile dysfunction. Polyphenols are chemicals found in many plants that decrease inflammation, lower blood pressure, act as antioxidants, and boost nitric oxide (American Journal of Clinical Nutrition, 2016).
- Vitamin C and N-acetylcysteine (NAC) are antioxidants that enhance the function of polyphenols in the body. Men with erectile dysfunction (ED) show higher levels of free radicals and lower levels of antioxidants than men without ED. Antioxidants such as vitamin C and N-acetylcysteine (NAC) combined with the B vitamin folic acid can improve erection capacity in aging men. Vitamin C, NAC and folic acid work synergistically together with polyphenols and the amino acid L-citrulline in the production of nitric oxide. Folic acid is a precursor of tetrahydrobiopterin (BH4), and when combined with vitamin C and NAC, plays an important role in sustaining nitric acid bioavailability and endothelial (blood vessel) nitric acid synthase and nitric oxide synthesis. BH4 increases nitric oxide bioavailability and systemic (cGMP) levels in healthy adults, which might be an attractive treatment for erectile dysfunction.
- N-acetylcysteine (NAC) is a more biologically active and more stable form of the amino acid L-cysteine. NAC increases the important antioxidant glutathione in your body. Research has shown that NAC can prevent oxidative stress and enhance nitric oxide bioavailability. NAC is also a precursor for the synthesis of hydrogen sulfide. Clinical studies are emerging that indicate hydrogen sulfide may be beneficial in the prevention of hypertension, cardiovascular disease, cancer, inflammation, neurodegenerative diseases and metabolic disorders including obesity and diabetes. Research has shown that hydrogen sulfide (H2S) is a potent vasodilator and increases healthy blood flow to the body and penis and enhances penile erection and sexual performance (Journal of Andrology, July/August 2012). “The current pharmacotherapy for erectile dysfunction (ED) relies significantly of the use of phosphodiesterase type 5 (PDE5) inhibitors, but quite a proportion of ED patients are resistant to this therapy, necessitating a search for an alternative treatment,” researchers said. “Given the mounting evidence of H2S’s role in erectile function and how it appears to achieve its pro-erectile effects through different mechanisms, H2S represents a potentially alternative treatment or adjunct to PDE5 inhibitors.” (Journal of Sexual Medicine, 2011)
Research has shown that NAC is a safer hydrogen sulfide precursor and hydrogen sulfide donor than sulfide salts such as sodium sulfide. Sulfide salts release hydrogen sulfide in an uncontrolled manner and may cause acute toxicity to organs. NAC is the preferred and safest supplement for increasing hydrogen sulfide.
Introducing Advanced Molecular Labs (AML) SEX COCKTAIL™, which is the most scientifically advanced natural sexual enhancement dietary supplement ever developed! For best result take 30-60 minutes before bedtime daily. No erectile dysfunction drugs are present. It provides the most scientifically researched nutrients (see enclosed scientific references below) for helping to support healthy vasodilation, blood flow and natural sexual enhancement. AML SEX COCKTAIL™ is not for use by persons under the age of 18. Do not use if pregnant or nursing or taking nitrate drugs. Do not exceed recommended dosage. Consult your physician prior to use if you have a medical condition before beginning any diet or supplement program.†
†These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.
© Published by Advanced Research Media, Inc. 2021
© Reprinted with permission from Advanced Research Media, Inc.
- Kresch E, Achua J, Saltzman R, Khodamoradi K, Arora H, Ibrahim E, Kryvenko ON, Almeida VW, Firdaus F, Hare JM, Ramasamy R. COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the Human Penis. World J Mens Health. May 7, 2021;39:e22. https://doi.org/10.5534/wjmh.210055
- Ma M, Wu CJ, Zhang P, Li T, Wei SZ, Yu BT, Qin F, Yuan JH. N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis. Asian J Androl. 2021 Mar-Apr;23(2):215-221. doi: 10.4103/aja.aja_17_20. PMID: 32394901; PMCID: PMC7991820.
- Bourgonje AR, Offringa AK, van Eijk LE, Abdulle AE, Hillebrands JL, van der Voort PHJ, van Goor H, van Hezik EJ. N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019. Antioxid Redox Signal. 2021 Mar 25. doi: 10.1089/ars.2020.8247. Epub ahead of print. PMID: 33607929.
- Papi A, Di Stefano AFD, Radicioni M. Pharmacokinetics and Safety of Single and Multiple Doses of Oral N-Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study. Adv Ther. 2021 Jan;38(1):468-478. doi: 10.1007/s12325-020-01542-4. Epub 2020 Nov 4. PMID: 33146843; PMCID: PMC7854405.
- Hydrogen sulfide compensates nitric oxide deficiency in murine corpus cavernosum. Pharmacological research, November 2016. Yetik-Anacak, Günay; Dikmen, Aycan; Coletta et al. https://doi.org/10.1016/j.phrs.2016.08.015
- Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. March 2009. d'Emmanuele di Villa Bianca R, Sorrentino R, Maffia P, et al. Proc Natl Acad Sci USA. 2009;106(11):4513-4518. doi:10.1073/pnas.0807974105
- Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction - a pilot study. March 2006. European Journal of Pharmacology. Balasubramanian Srilatha, P. Ganesan Adaikan, Philip K. Moore. https://doi.org/10.1016/j.ejphar.2006.02.001
- Meng, J., Ganesan Adaikan, P. & Srilatha, B. Hydrogen sulfide promotes nitric oxide production in corpus cavernosum by enhancing expression of endothelial nitric oxide synthase. Int J Impot Res25, 86-90 (2013) doi:10.1038/ijir.2012.39
- Qiu X, Villalta J, Lin G, Lue TF. Role of hydrogen sulfide in the physiology of penile erection. J Androl. 2012;33(4):529-535. doi:10.2164/jandrol.111.014936
- N-acetylcysteine Ameliorates the Erectile Dysfunction Caused by Chronic Intermittent Hypoxia in Rats: Partly Involvement of Endoplasmic Reticulum Stress. Zhu, Die et al. October 2015. Journal of Urology.
- Hydrogen sulfide and erectile function: a novel therapeutic target. d'Emmanuele di Villa Bianca, R., Sorrentino, R., Mirone, V. et al.Nat Rev Urol 8, 286-289 (April 2011) doi:10.1038/nrurol.2011.45
- Hydrogen Sulfide: From Physiology to Pharmacology, Inflammation & Allergy. Fiorucci, S. Drug Targets (Discontinued) (April 2011) 10: 77. https://doi.org/10.2174/187152811794776277
- Contribution of cysteine aminotransferase and mercaptopyruvate sulfurtransferase to hydrogen sulfide production in peripheral neurons. Ryo Miyamoto et al. Neurochem.(2014) 130, 29-40. February 2014. https://doi.org/10.1111/jnc.12698
- Hydrogen sulfide: role in vascular physiology and pathology. Kim Holwerda, S. Karumanchi, and A. Lely. Current Opinion in Nephrology and Hypertension. Mar 1, 2015. doi: 10.1097/MNH.0000000000000096
- Martelli, A., Testai, L., Breschi, M. C., Blandizzi, C., Virdis, A., Taddei, S. and Calderone, V. (2012), Hydrogen sulphide: novel opportunity for drug discovery. Med. Res. Rev., 32: 1093-1130. doi:1002/med.20234
- Suzuki K, Olah G, Modis K, et al. Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function. Proc Natl Acad Sci USA. 2011;108(33):13829-13834. doi:10.1073/pnas.1105121108
- Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men. Ochiai, Masayuki et al. (March 2012) International Journal of Cardiology, Volume 155, Issue 2, 257-261 doi: 10.1016/j.ijcard.2010.10.004
- Effects of Hydrogen Sulfide on Erectile Function and Its Possible Mechanism(s) of Action. Liaw, Roeswita Leono et al. July 2011. The Journal of Sexual Medicine, Volume 8, Issue 7, 1853-1864 doi: 10.1111/j.1743-6109.2011.02279.x
- Oxidative Stress and Antioxidant Status in Patients with Erectile Dysfunction. Barassi, Alessandra et al. October 2009. The Journal of Sexual Medicine, Volume 6, Issue 10, 2820-2825. DOI: https://doi.org/10.1111/j.1743-6109.2009.01279.x
- Maiorino MI, Bellastella G, Chiodini P et al. (2016) Primary Prevention of Sexual Dysfunction With Mediterranean Diet in Type 2 Diabetes: the MÈDITA Randomized Trial. Diabetes Care 39:e143-e144. September 2016. https://care.diabetesjournals.org/content/39/9/e143.abstract
- Yan WJ, Yu N, Yin TL, Zou YJ, Yang J. A new potential risk factor in patients with erectile dysfunction and premature ejaculation: folate deficiency. Asian J Androl 2014;16(6):902-906. doi:10.4103/1008-682X.135981
- Aldemir, M., Okulu, E., Neşelioğlu, S. et al.Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction. Int J Impot Res 23, 32-38 (2011) doi:10.1038/ijir.2010.33
- Ng, C., Lee, C., Ho, A. L. and Lee, V. W. (2011). Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia. The Journal of Sexual Medicine, 8: 2883-2893. doi:1111/j.1743-6109.2011.02414.x
- Effects of tetrahydrobiopterin on nitric oxide bioavailability and renal hemodynamics in healthy volunteers. Ferruh Artunc et al. 2008. J. Nephrology 21: 850-860.
- Aedín Cassidy, Mary Franz, Eric B Rimm, Dietary flavonoid intake and incidence of erectile dysfunction. The American Journal of Clinical Nutrition, Volume 103, Issue 2, February 2016, Pages 534-541, https://doi.org/10.3945/ajcn.115.122010
- Jon Cartledge, Suks Minhas & Ian Eardley (2001) The role of nitric oxide in penile erection, Expert Opinion on Pharmacotherapy, 2:1, 95-107, DOI: 1517/146565184.108.40.206
- Hydrogen Sulphide: A Novel Endogenous Gasotransmitter Facilitates Erectile Function. The Journal of Sexual Medicine. Balasubramanian Srilatha, P. Ganesan Adaikan, Ling Li, Philip K. Moore. Volume 4, Issue 5, 2007, Pages 1304-1311. https://doi.org/10.1111/j.1743-6109.2007.00561.x.
- Ali, M. Y., Ping, C.Y., Mok, Y., Ling, L., Whiteman, M., Bhatia, M. and Moore, P.K. (2006). Regulation of vascular nitric oxide in vitroand in vivo; a new role for endogenous hydrogen sulphide? British Journal of Pharmacology, 149: 625-634. doi:1038/sj.bjp.0706906
- Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed. Rui Wang. Physiological Reviews 2012 92:2, 791-896. April 2012 https://www.physiology.org/doi/full/10.1152/physrev.00017.2011#
- Jacqueline Barona, Juan C. Aristizabal, Christopher N. Blesso, Jeff S. Volek, Maria Luz Fernandez. Grape Polyphenols Reduce Blood Pressure and Increase Flow-Mediated Vasodilation in Men with Metabolic Syndrome. The Journal of Nutrition, Volume 142, Issue 9, September 2012, Pages 1626-1632 https://doi.org/10.3945/jn.112.162743
- Matthew Whiteman, Sophie Le Trionnaire, Mohit Chopra, Bridget Fox, Jacqueline Whatmore; Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools. Clin Sci (Lond)1 December 2011; 121 (11): 459-488. doi: https://doi.org/10.1042/CS20110267
- Meldrum, D., Gambone, J., Morris, M. et al.Lifestyle and metabolic approaches to maximizing erectile and vascular health. Int J Impot Res 24, 61-68 (March 2012) doi:10.1038/ijir.2011.51
- Shirai M, Hiramatsu I, Aoki Y, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med 2018;6(4):291-296. doi:10.1016/j.esxm.2018.07.001
- Uddin SMI, Mirbolouk M, Dardari Z, et al. Erectile Dysfunction as an Independent Predictor of Future Cardiovascular Events. Circulation. 2018;138(5):540-542. doi:10.1161/CIRCULATIONAHA.118.033990
- Long-Term N-Acetylcysteine and l-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes. Valentino Martina, Andi Masha, Anna Iannone et al. Diabetes Care May 2008, 31 (5) 940-944; DOI: 10.2337/dc07-2251
- Olga Pecháňová, Josef Zicha, Stanislava Kojšová, Zdenka Dobešová, Lýdia Jendeková, Jaroslav Kuneš. Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension. Clin Sci (Lond) 1 February 2006; 110 (2): 235-242. doi: https://doi.org/10.1042/CS20050227
- Liu, L., Zhang, T., Zhang, Y. et al.Metabolic syndrome and risk for ED: a meta-analysis. Int J Impot Res 26, 196-200 (September 2014) doi:10.1038/ijir.2014.3
- McKinley-Barnard, S., Andre, T., Morita, M. et al.Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. J Int Soc Sports Nutr 12,27 (2015) doi:10.1186/s12970-015-0086-7
- Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity. Sci Rep6, 26647 (May 2016) doi:10.1038/srep26647
- Suganya, N., Bhakkiyalakshmi, E., Sarada, D., & Ramkumar, K. (2016). Reversibility of endothelial dysfunction in diabetes: Role of polyphenols. British Journal of Nutrition,116(2), 223-246. doi:10.1017/S0007114516001884
- Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine. H Drexler, A.M Zeiher, K Meinzer, H Just. December 1991 https://doi.org/10.1016/0140-6736(91)92372-9.
- Tsuboi T, Maeda M, Hayashi T (2018) Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence. PLoS ONE 13(2): e0192252. https://doi.org/10.1371/journal.pone.0192252
- Devaraj, S., Vega‐López, S., Kaul, N., Schönlau, F., Rohdewald, P. and Jialal, I. (October 2002). Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids, 37: 931-934. doi:1007/s11745-006-0982-3
- Pycnogenol®, French maritime pine bark extract, improves endothelial function of hypertensive patients. Ximing Liu, Junping Wei, Fengsen Tan, Shengming Zhou, Gudrun Würthwein, Peter Rohdewald. January 2004. Life Sciences, https://doi.org/10.1016/j.lfs.2003.07.037
- A randomized, double-blind, placebo-controlled, prospective, 16 week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients. Saeed Hosseini, Jeongmin Lee, Ramon T. Sepulveda. Nutrition Research, Volume 21, Issue 9,2001,Pages 1251-1260. https://www.sciencedirect.com/science/article/pii/S0271531701003426
- Endothelium-Dependent Vascular Effects of Pycnogenol. Fitzpatrick, David F.; Bing, Bettye; Rohdewald, Peter. Journal of Cardiovascular Pharmacology: October 1998 https://journals.lww.com/cardiovascularpharm/Fulltext/1998/10000/Endothelium_Dependent_Vascular_Effects_of.1.aspx
- Stanislavov R, Rohdewald P. Improvement of erectile function by a combination of French maritime pine bark and roburins with aminoacids. Minerva Urol Nefrol. 2015 Mar;67(1) 27-32. PMID: 25664962.
- Stanislavov & V. Nikolova (November 2003). Treatment of Erectile Dysfunction with Pycnogenol and L-arginine, Journal of Sex & Marital Therapy, 29:3, 207-213, DOI: 10.1080/00926230390155104
- Toru Okazaki, Hajime Otani, Takayuki Shimazu, Kei Yoshioka, Masanori Fujita & Toshiji Iwasaka (2011). Ascorbic acid and N-acetyl cysteine prevent uncoupling of nitric oxide synthase and increase tolerance to ischemia/reperfusion injury in diabetic rat heart. Free Radical Research, 45:10, 1173-1183, DOI: 10.3109/10715762.2011.605361
- Luigi Cormio, Mario De Siati, Fabrizio Lorusso, Oscar Selvaggio, Lucia Mirabella, Francesca Sanguedolce, Giuseppe Carrieri. Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction. January 2011. Urology. https://www.sciencedirect.com/science/article/pii/S0090429510016614
- Zhang, R, Wang, Y, Pan, L, Tian, H. N‐Acetylcysteine potentiates the haemodynamic‐improving effect of sildenafil in a rabbit model of acute pulmonary thromboembolism via the p38 MAPK pathway. Clin Exp Pharmacol Physiol. 2019; 46: 163-172. https://doi.org/10.1111/1440-1681.13039
- Elshahid, A.R., Shahein, I.M., Mohammed, Y.F., Ismail, N.F., Zakarria, H.B. and Gamal El Din, S.F. (2019). Folic acid supplementation improves erectile function in patients with idiopathic vasculogenic erectile dysfunction by lowering peripheral and penile homocysteine plasma levels: a case‐control study. Andrology. doi:1111/andr.12672
- Low serum folic acid can be a potential independent risk factor for erectile dysfunction: a prospective case–control study. Attia, A.A.A., Amer, M.A.E.M., Hassan, M. et al. Int Urol Nephrol (Jan 2019) 51: 223. https://doi.org/10.1007/s11255-018-2055-y
- Massimiliano Sansone, Andrea Sansone, Mariagrazia Romano, Silvia Seraceno, Luigi Di Luigi & Francesco Romanelli (2018). Folate: a possible role in erectile dysfunction? The Aging Male, 21:2, 116-120, DOI: 10.1080/13685538.2017.1404022
- Karabakan, M., Erkmen, A.E., Guzel, O., Aktas, B.K., Bozkurt, A. and Akdemir, S. (2016). Association between serum folic acid level and erectile dysfunction. Andrologia, 48: 532-535. doi:1111/and.12474
- Yan WJ, Yu N, Yin TL, Zou YJ, Yang J. A new potential risk factor in patients with erectile dysfunction and premature ejaculation: folate deficiency. Asian J Androl. 2014;16(6):902–906. doi:10.4103/1008-682X.135981
- Hamidi Madani, A, Asadolahzade, A, Mokhtari, G, Shahrokhi Damavand, R, Farzan, A, and Esmaeili, S. Assessment of the efficacy of combination therapy with folic acid and tadalafil for the management of erectile dysfunction in men with type 2 diabetes mellitus. J Sex Med. January 2013 https://doi.org/10.1111/jsm.12047
- High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. Kristen L. Jablonski, Douglas R. Seals, Iratxe Eskurza, Kevin D. Monahan, and Anthony J. Donato. Journal of Applied Physiology November 2007 103:5, 1715-1721 https://www.physiology.org/doi/full/10.1152/japplphysiol.00533.2007
- Wulf Hildebrandt, Roland Sauer, Gabriel Bonaterra, Klaus A Dugi, Lutz Edler, Ralf Kinscherf. Oral N-acetylcysteine reduces plasma homocysteine concentrations regardless of lipid or smoking status. The American Journal of Clinical Nutrition, Volume 102, Issue 5, November 2015, Pages 1014-1024, https://academic.oup.com/ajcn/article/102/5/1014/4564368
- Fitzpatrick, D.F., Bing, B., Maggi, D.A., Fleming, R.C. and O'malley, R.M. (2002). Vasodilating Procyanidins Derived from Grape Seeds. Annals of the New York Academy of Sciences, 957: 78-89. doi:10.1111/j.1749-6632.2002.tb02907.x
- Isolation and Characterization of Endothelium-Dependent Vasorelaxing Compounds from Grape Seeds. David F. Fitzpatrick,*,†, Richard C. Fleming,‡, Bettye Bing,†, David A. Maggi,† and, and Rebecca M. O'Malley‡ Journal of Agricultural and Food Chemistry 2000 48 (12), 6384-6390. DOI: 10.1021/jf0009347
- N-acetylcysteine restores nitric oxide-mediated effects in the fetoplacental circulation of preeclamptic patients. Bisseling, T.M.; Roes, E.M., Raijmakers, M., Steegers, E.A.P., Peters, W.H.M., Smits, P. 2004. American Journal of Obstetrics and Gynecology, vol. 191, iss. 1, (2004), DOI: http://dx.doi.org/10.1016/j.ajog.2003.12.033
- Hélène Girouard, Chantal Chulak, Lingyun Wu, Mireille Lejossec, Jacques de Champlain, N-acetylcysteine improves nitric oxide and α-adrenergic pathways in mesenteric beds of spontaneously hypertensive rats. American Journal of Hypertension, Volume 16, Issue 7, July 2003, Pages 577-584, https://doi.org/10.1016/S0895-7061(03)00863-X
- Judy M. Muller-Delp, Ascorbic acid and tetrahydrobiopterin: looking beyond nitric oxide bioavailability, Cardiovascular Research, Volume 84, Issue 2, 1 November 2009, Pages 178-179, https://doi.org/10.1093/cvr/cvp307
- Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]) Sivabaskari Pasupathy, BS, PhD, Rosanna Tavella, BS, PhD, Suchi Grover, MBBS, PhD, Betty Raman, MBBS, Nathan E.K. Procter, BS, PhD, Yang Timothy Du, MBBS, Gnanadevan Mahadavan, MBBS, PhD, Irene Stafford, BS, Tamila Heresztyn, BS, Andrew Holmes, BS, PhD, Christopher Zeitz, MBBS, PhD, Margaret Arstall, MBBS, PhD, Joseph Selvanayagam, MBBS, PhD, John D. Horowitz, MBBS, PhD, and John F. Beltrame, BS, BMBS, PhD. June 2017. Journal of AHA Circulation https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.117.027575
- Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine. J D Horowitz, E M Antman, B H Lorell, W H Barry, and T W Smith. December 1983. Journal of AHA Circulation https://www.ahajournals.org/doi/abs/10.1161/01.cir.68.6.1247
- Horny goat weed could be better than Viagra. By Catherine Brahic. September 26, 2008. New Scientist. https://www.newscientist.com/article/dn14825-horny-goat-weed-could-be-better-than-viagra/#ixzz64iSVGj1S
- Potent Inhibition of Human Phosphodiesterase-5 by Icariin Derivatives. Mario Dell’Agli, Germana V. Galli, Esther Dal Cero, Federica Belluti, Riccardo Matera, Elisa Zironi, Giampiero Pagliuca, and Enrica Bosisio. Journal of Natural Products September 2008 71 (9), 1513-1517. DOI: 10.1021/np800049y
- American Chemical Society. Natural Viagra? 'Horny Goat Weed' Shows Promise. ScienceDaily. ScienceDaily, 30 September 2008. sciencedaily.com/releases/2008/09/080929084954.htm
- Chau Y, Li FS, Levsh O, Weng JK. Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5. PLoS One. 2019;14(9):e0222803. Published 2019 Sep 20. doi:10.1371/journal.pone.0222803
- Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum. Jiang, Z., Hu, B., Wang, J. et al. J. Huazhong Univ. Sc. Technol. (September 2006) 26: 460. https://doi.org/10.1007/s11596-006-0421-y
- El‐Wakeel, L.M., Fouad, F.A., Saleem, M.D. and Saber‐Khalaf, M. (2019). Efficacy and tolerability of sildenafil/l‐arginine combination relative to sildenafil alone in patients with organic erectile dysfunction. Andrologia. doi:10.1111/andr.12671
- Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial. The Journal of Sexual Medicine, September 2019 https://doi.org/10.1016/j.jsxm.2019.06.009
- The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. Hye Chang Rhim, Min Seo Kim, Young-Jin Park, Woo Suk Choi, Hyoung Keun Park, Hyeong Gon Kim, Aram Kim, Sung Hyun Paick. The Journal of Sexual Medicine, February 2019 https://doi.org/10.1016/j.jsxm.2018.12.002
- Barassi, A., Corsi Romanelli, M.M., Pezzilli, R., Damele, C.A., Vaccalluzzo, L., Goi, G., Papini, N., Colpi, G.M., Massaccesi, L. and Melzi d'Eril, G. V. (2017), Levels of l‐arginine and l‐citrulline in patients with erectile dysfunction of different etiology. Andrology, 5: 256-261. doi:10.1111/andr.12293
- Hotta, Y., Shiota, A., Kataoka, T., Motonari, M., Maeda, Y., Morita, M. and Kimura, K. (June 2014). Oral l‐citrulline supplementation improves erectile function and penile structure in castrated rats. Int J Urol, 21: 608-612. doi:10.1111/iju.12362
- Ozge Un, Didem Yilmaz, Nur Bayatli, Ecem Kaya & Serap Gur (2014). L-Arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats. The Aging Male, 17:4, 248-255, DOI: 10.3109/13685538.2014.921150
- Oral L‐Citrulline Supplementation Improves Erectile Function in Rats with Acute Arteriogenic Erectile Dysfunction. Arufumi Shiota, Yuji Hotta, Tomoya Kataoka, Masahiko Morita, Yasuhiro Maeda, Kazunori Kimura. The Journal of Sexual Medicine. 2013 https://doi.org/10.1111/jsm.12260
- Tagliabue, M., Pinach, S., Di Bisceglie, C., Brocato, L., Cassader, M., Bertagna, A., Manieri, C. and Pescarmona, G. (2005). Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus. International Journal of Andrology, 28: 156-162. doi:10.1111/j.1365-2605.2005.00528.x
- Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. (1999). Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. Br J Urol Int 83:269-273
- Hongxiu Ning, Zhong-Cheng Xin, Guiting Lin, Lia Banie, Tom F. Lue, Ching-Shwun Lin. Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006. https://doi.org/10.1016/j.urology.2006.09.031
- Shindel, A.W., Xin, Z., Lin, G., Fandel, T.M., Huang, Y., Banie, L., Breyer, B.N., Garcia, M.M., Lin, C. and Lue, T. F. (2010). Erectogenic and Neurotrophic Effects of Icariin, a Purified Extract of Horny Goat Weed (Epimedium spp.) In Vitro and In Vivo. The Journal of Sexual Medicine, 7: 1518-1528. doi:10.1111/j.1743-6109.2009.01699.x
- Xin, Zhongcheng & Kim, E.K. & Lin, C.S. & Liu, W.J. & Tian, L & Yuan, Y.M. & Fu, J. (2003). Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian journal of andrology. 5. 15-8.
- Taylor J. Mediterranean diet linked to improved cardiovascular function in erectile dysfunction patients. Eur Heart J. 2015 Apr;36(14) 836. PMID: 26034790.
- Di Francesco S, Tenaglia RL. Mediterranean diet and erectile dysfunction: a current perspective. Cent European J Urol. 2017;70(2):185-187. doi:10.5173/ceju.2017.1356
- Erectile dysfunction and cardiovascular risk factors in a Mediterranean diet cohort. R. Ramírez J. Pedro‐Botet M. García E. Corbella J. Merino D. Zambón X. Corbella X. Pintó the Xarxa de Unitats de Lípids i Arteriosclerosi (XULA) Investigators Group. 20 October 2015 https://doi.org/10.1111/imj.12937
- Adherence to Mediterranean Diet and Erectile Dysfunction in Men with Type 2 Diabetes Li, HaiZhang, Hong‐LiangWu, Jiang et al. The Journal of Sexual Medicine, Volume 8, Issue 2, 631
- Giugliano, D., Giugliano, F., & Esposito, K. (2006). Sexual dysfunction and the Mediterranean diet. Public Health Nutrition, 9(8A), 1118-1120. doi:10.1017/S1368980007668542
- Esposito, K., Ciotola, M., Giugliano, F. et al. Mediterranean diet improves erectile function in subjects with the metabolic syndrome. Int J Impot Res 18, 405-410 (2006) doi:10.1038/sj.ijir.3901447
- La, Vignera, S., Condorelli, R., Vicari, E., D'Agata, R. and Calogero, A.E. (2012). Physical Activity and Erectile Dysfunction in Middle‐Aged Men. Journal of Andrology, 33: 154-161. doi:10.2164/jandrol.111.013649
- Beneficial Impact of Exercise and Obesity Interventions on Erectile Function and Its Risk Factors. The Journal of Sexual Medicine. Johanna L. Hannan, M. Tina Maio, Marina Komolova, Michael A. Adams. 2009 https://doi.org/10.1111/j.1743-6109.2008.01143.x. http://www.sciencedirect.com/science/article/pii/S1743609515326965
- Esposito, K., Giugliano, F., Ciotola, M. et al. Obesity and sexual dysfunction, male and female. Int J Impot Res 20, 358-365 (April 2008) doi:10.1038/ijir.2008.9
- Metabolic syndrome and endothelial dyfunction and associated high proportions of erectile dysfunction in men: Innocent bystanders or accessories to the crime? Ahmed, M.H. Diabetes Research and Clinical Practice, Volume 75, Issue 3, 370-371
- Zahra Bahadoran et al. Endogenous flux of nitric oxide: Citrulline is preferred to Arginine. Acta Physiol (Oxf); 2021 Mar;231(3):e13572. doi: 10.1111/apha.13572.
- Wu G et al. Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans. Adv Exp Med Biol 2021; PMID: 34251644. doi: 10.1007/978-3-030-74180-8_10.
- Zhunan Xu et al. Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials. Andrologia 2021; May;53(4):e14007. doi: 10.1111/and.14007.
- Wade Muncey et al. Alternative Treatment for Erectile Dysfunction: a Growing Arsenal in Men's Health. Curr Urol Rep 2021; Jan 9;22(2):11. doi: 10.1007/s11934-020-01023-9.
- Arno R Bourgonje et al. N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019. 2021 Mar 25. doi: 10.1089/ars.2020.8247. Online ahead of print.
- Brandán Pedre et al. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H 2 S and sulfane sulfur species. Pharmacol Ther 2021; Jun 23;228:107916. doi: 10.1016/j.pharmthera.2021.107916. Online ahead of print.
- Jose Jimenez-Torres et al. Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial. Stroke 2021 Aug 10;STROKEAHA120033214. doi: 10.1161/STROKEAHA.120.033214. Online ahead of print.