THE SCIENCE

We stand behind the ingredients in each Mr. Happy supplement because the ingredients are backed by decades of rigorous research.

The Science

  • Ning H, Xin ZC, Lin G, Banie L, Lue TF, Lin CS. Effects of icariin on phosphodiesterase-­‐5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006;68:1350–4. 3
  • Dell'Agli M, Galli GV, Dal Cero E, Belluti F, Matera R, Zironi E, Pagliuca G, Bosisio E. Potent inhibition of human phosphodiesterase-­‐5 by icariin derivatives. J Nat Prod 2008;71:1513–7.
  • Shindel, A. W., Xin, Z.-­‐C., Lin, G., Fandel, T. M., Huang, Y.-­‐C., Banie, L., Breyer, B. N., Garcia, M. M., Lin, C.-­‐S. 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
  • Oral L-­‐citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Source: Urology [0090-­‐4295] Cormio yr:2011 vol:77 iss:1 pg:119 -­‐22
  • Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue—a double blind cross-­‐over study of a standardized extract SHR-­‐5 with a repeated low-­‐dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000;7:365-­‐371.
  • Spasov AA, Wikman GK, Mandrikov VB, et al. A double-­‐blind, placebo-­‐controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-­‐5 extract on the fatigue of students caused by stress during an examination period with a repeated low-­‐dose regimen. Phytomedicine. 2000;7:85-­‐89.
  • Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-­‐5 rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003;10:95-­‐105.
  • Olsson EM, von Schéele B, Panossian AG.A randomised, double-­‐blind, placebo-­‐controlled, parallel-­‐group study of the standardised extract shr-­‐5 of the roots of Rhodiola rosea in the treatment of subjects with stress-­‐related fatigue. Planta Med. 2009 Feb;75(2):105-­‐12. Epub 2008 Nov 18.
  • Soner, et al. Evaluation of vascular smooth muscle and corpus cavernosum on hypercholesterolemia. Is resveratrol promising on erectile dysfunction? Int. J Imp Res, Volume: 22 Issue: 4 Pages: 227-­‐233 DOI: 10.1038/ijir.2010.8 Published: JUL-­‐AUG 2010
  • Fukuhara S, Tsujimura A, Okuda H, Yamamoto K, Takao T, Miyagawa Y, Nonomura N, Okuyama A. Vardenafil and resveratrol synergistically enhance the nitric oxide/cyclic guanosine monophosphate pathway in corpus cavernosal smooth muscle cells and its therapeutic potential for erectile dysfunction in the streptozotocin-­‐induced diabetic rat: preliminary findings. J Sex Med. 2011 Apr;8(4):1061-­‐71. doi: 10.1111/j.1743-­‐6109.2010.02193.x. Epub 2011 Jan 26.
  • Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB. Trans-­‐Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo. Arch Pharm Res. 2008 Jan;31(1):83-­‐7.
  • Forest CP, Padma-­‐Nathan H, Liker HR.; Efficacy and safety of pomegranate juice on improvement of erectile function in male patients with mild to moderate erectile dysfunction: a randomized, placebo-­‐controlled, double-­‐blind, crossover study. Int J Impot Res. 2007 Nov-­‐Dec;19(6):564-­‐7. Epub 2007 Jun 14.
  • Shiota A, Hotta Y, Kataoka T, Morita M, Maeda Y, Kimura K.Oral l-­‐Citrulline Supplementation Improves Erectile Function in Rats with Acute Arteriogenic Erectile Dysfunction. J Sex Med. 2013 Jul 11
  • Moinard C, Cynober L. Citrulline: a new player in the control of nitrogen homeostasis. J Nutr. 2007 Jun;137(6 Suppl 2):1621S-­‐1625S.
  • Cynober L, Moinard C, De Bandt JP.The 2009 ESPEN Sir David Cuthbertson. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game? Clin Nutr. 2010 Oct;29(5):545-­‐51.
  • Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006 Fall-­‐Winter;24(3-­‐4):275-­‐90.
  • Hecker M, Sessa WC, Harris HJ, Anggård EE, Vane JR. The metabolism of L-­‐arginine and its significance for the biosynthesis of endothelium-­‐derived relaxing factor: cultured endothelial cells recycle L-­‐citrulline to L-­‐arginine. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8612-­‐6.
  • Al-­‐Jarallah A, Igdoura F, Zhang Y, Tenedero CB, White EJ, MacDonald ME, Igdoura SA, Trigatti BL. The effect of pomegranate extract on coronary artery atherosclerosis in SR-­‐BI/APOE double knockout mice. Atherosclerosis. 2013 May;228(1):80-­‐9.
  • C. P. Forest, H. Padma-­‐Nathan, and H. R. Liker, “Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-­‐controlled, double-­‐blind, crossover study,” International Journal of Impotence Research, vol. 19, no. 6, pp. 564–567, 2007.
  • C. B. Stowe, “The effects of pomegranate juice consumption on blood pressure and cardiovascular health,” Complementary Therapies in Clinical Practice, vol. 17, no. 2, pp. 113–115, 2011.
  • Aviram M, Dornfeld L. 2001. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 158:195
  • Davidson MH, Maki KC, Dicklin MR, Feinstein SB, Witchger M, et al. 2009. Effects of consumption of pomegranate juice on carotid intima-­‐media thickness in men and women at moderate risk for coronary heart disease. Am. J. Cardiol. 104:936–42
  • Rock W, Rosenblat M, Miller-­‐Lotan R, Levy AP, Elias M, Aviram M. 2008. Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-­‐density lipoprotein and stimulates its catalytic activities. J. Agric. Food Chem. 56:8704–13
  • Sahebkar A.Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-­‐analysis of randomized controlled trials. Nutr Rev. 2013 Oct 1.
  • Frankel EN, Waterhouse AL, Kinsella JE. Inhibition of human LDL oxidation by resveratrol. Lancet. 1993;341:1103–1104.
    Xia N, Daiber A, Habermeier A, et al. Resveratrol reverses endothelial nitric-­‐oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther. 2010;335:149–154.
  • Cherniack EP, Troen BR. Resveratrol: effects on lipids and cardiovascular risk. Curr Cardiovasc Risk Rep. 2013;7:9–16.
  • Zhang H, Zhang J, Ungvari Z, et al. Resveratrol improves endothelial function: role of TNFα and vascular oxidative stress. Arterioscler Thromb Vasc Biol. 2009;29:1164–1171.
  • Chen, X.J.; Ji, H.; Zhang, Q.W.; Tu, P.F.; Wang, Y.T.; Guo, B.L.; Li, S.P. A rapid method for simultaneous determination of 15 flavonoids in Epimedium using pressurized liquid extraction and ultra-­‐performance liquid chromatography. J. Pharm. Biomed. Anal. 2008, 46, 226-­‐235.
  • Zhao, F.; Tang, Y.Z.; Liu, Z.Q. Protective effect of icariin on DNA against radical-­‐induced oxidative damage. J. Pharm. Pharmacol. 2007, 59, 1729-­‐1732.
  • Liu, Z.Q.; Luo, X.Y.; Sun, Y.X.; Wu, W.; Liu, C.M.; Liu, S.Y. The antioxidative effect of icariin in human erythrocytes against free-­‐radical-­‐induced haemolysis. J. Pharm. Pharmacol. 2004, 56, 1557-­‐1562.
    Pratico, D. Evidence of oxidative stress in Alzheimer's disease brain and antioxidant therapy: lights and shadows. Ann. N. Y. Acad. Sci. 2008, 1147, 70-­‐78.
  • Nie, J.; Luo, Y.; Huang, X.N.; Gong, Q.H.; Wu, Q.; Shi, J.S. Icariin inhibits beta-­‐amyloid peptidesegment 25-­‐35 induced expression of beta-­‐secretase in rat hippocampus. Eur. J. Pharmacol. 2010, 626, 213-­‐218.