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Wellness Foods + Supplements 3/2021

Wellness Foods & Supplements is the first European magazine devoted exclusively to health ingredients, nutraceutical foods and beverages. Questions about the trade magazine Wellness Foods & Supplements? Interested in subscribing or advertising? The board of editors at Wellness Foods & Supplements kindly remains at your disposal.

Venous health sclerosis

Venous health sclerosis or diabetes may negatively affect the endothelium’s ability to produce NO, and the responsiveness of blood vessels to NO may decline too (40, 41). This results in endothelial dysfunction, which in turn impairs blood flow, and increases the risk for thrombosis. Pycnogenol ® was shown to enhance endothelial NO generation from the precursor molecule L-arginine by stimulation endothelial NO synthase (eNOS), leading to an improved endothelial function (28, 29). In addition, it was observed that a certain metabolite of Pycnogenol ® is enriched endothelial cells by facilitated uptake and can thus exert its anti-inflammatory effects directly in the endothelium (30). In patients with coronary artery disease, the effect of Pycnogenol ® on endothelial function was assessed by measuring the flow-mediated dilatation of the brachial artery (the widening of the artery in response to elevations in blood flow-associated shear stress) (31). This 8-week randomized, double-blind, placebo-controlled crossover study showed that endothelial function was improved by 32 % in the Pycnogenol ® group, whereas it slightly decreased in the placebo group. In another double-blind placebo-controlled randomized 12-week study with hypertensive patients, taking the anti-hypertensive drug nifedipine (a calcium channel blocker), plasma markers of endothelial function were significantly improved in the Pycnogenol ® group (32). This is a clear indication of improved endothelial function. A third double-blind, placebo-controlled study reported similar effects in hypertensive patients with type II diabetes, taking an anti-hypertensive drug, an ACE inhibitor together with 125 mg Pycnogenol ® daily for 3 months (33). In borderline hypertensive, hyperlipidemic and hyperglycemic patients, flow-mediated dilatation significantly improved after 8 and 12 weeks of Pycnogenol ® supplementation (34). These studies confirm the beneficial effects of Pycnogenol ® on endothelial function. Pycnogenol ® French maritime pine bark extract is a safe, natural and evidencebased solution to efficiently support venous health. Pycnogenol ® helps to improve blood flow, platelet activity, microcirculation and endothelial function. For more information on how Pycnogenol ® helps support healthy veins, please visit . References 1. Youn YJ, Lee J. Chronic venous insufficiency and varicose veins of the lower extremities. The Korean journal of internal medicine. 2019;34(2):269-83. 2. Vlajinac HD, Radak ÐJ, Marinković JM, Maksimović MŽ. Risk factors for chronic venous disease. Phlebology. 2012;27(8):416-22. 3. Agrawal S, Saber W. Venous Ablation. Interv Cardiol Clin. 2020;9(2):255-63. 4. Cesarone MR, Belcaro,G., Rohdewald, P., L. Pellegrini, E. Ippolito, M. Scoccianti, A. Ricci, M. Dugall,M. Cacchio, I. Ruffini, F. Fano, G. Acerbi, M. G. Vinciguerra, P. Bavera, A. Di Renzo, B. M. Errichi, and F. Mucci. Prevention of Edema in Long Flights with Pycnogenol ® . Clin Appl Thrombosis/ Hemostasis. 2005;11(3):289-94. 5. Belcaro G, Cornelli U, Dugall M, Hosoi M, Cotellese R, Feragalli B. Long-haul flights, edema, and thrombotic events: prevention with stockings and Pycnogenol(R) supplementation (LONFLIT Registry Study). Minerva Cardioangiol. 2018;66(2):152-9. 6. Arcangeli P. Pycnogenol in chronic venous insufficiency. Fitoterapia. 2000;71:236-44. 7. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, et al. Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology. 2006;57(5):569- 76. 8. Cesarone MR, Belcaro G, Agus GB, Ippolito E, Dugall M, Hosoi M, et al. Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol(R). Minerva Cardioangiol. 2019;67(4):280-7. 9. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, et al. Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study. Phytomedicine. 2010;17(11):835-9. 10. Riccioni C, Sarcinella, R., Izzo, A., Palermo, G. and Liguori, L. Effectiveness of Troxerutin in association with Pycnogenol in the pharmacological treatment of venous insufficiency. Eur Bull Drug Res. 2004;12(1):7-12. 11. Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res. 2002;16 Suppl 1:S1-5. 12. Cesarone MR, Belcaro, G., Rohdewald, P., Pellegrini, L., Ledda, A., Vinciguerra, G., Ricci, A., Gizzi, G., Ippolito, E., Fano, F., Dugall, M., Acerbi, G., Cacchio M., Di Renzo, A., Hosoi, M., Stuard, S. and Corsi, M. Comparison of Pycnogenol and Daflon in Treating Chronic Venous Insufficiency: A prospective, Controlled study. Clin Appl Thromb Hemost. 2006;12(2):205-12. 13. Belcaro G. A Clinical Comparison of Pycnogenol, Antistax, and Stocking in Chronic Venous Insufficiency. Int J Angiol. 2015;24(4):268-74. 20 No. 3 November/December 2021

Venous health 14. Belcaro G, Dugall M, Luzzi R, Corsi M, Ledda A, Ricci A, et al. Management of Varicose Veins and Chronic Venous Insufficiency in a Comparative Registry with Nine Venoactive Products in Comparison with Stockings. Int J Angiol. 2017;26(3):170-8. 15. Gulati OP. Pycnogenol(R) in chronic venous insufficiency and related venous disorders. Phytother Res. 2014;28(3):348-62. 16. Belcaro G, Dugall M, Luzzi R, Ippolito E, Cesarone MR. Postpartum Varicose Veins: Supplementation with Pycnogenol or Elastic Compression-A 12-Month Follow-Up. Int J Angiol. 2017;26(1):12-9. 17. Belcaro G, Dugall M, Hu S, Feragalli B, Cotellese R, Ledda A, et al. Prevention of recurrent venous thrombosis and post-thrombotic syndrome. Minerva Cardioangiol. 2018;66(3):238-45. 18. Ericchi B, Belcaro, G., Hosoi, M., Cesarone, M.R., Dugall, M., Feragalli, B., Grossi, M-G., Bavera, P., Hosoi, M., Zulli, C., Corsi, M., Ledda, A., Luzzi, R. and Ricci, A. Prevention of post-thrombotic syndrome with Pycnogenol ® : A twelve month study. Panminerva Med. 2011;53(3):21-7. 19. Rodriguez P BG, Dugall M, Hu S, Luzzi R, Ledda A, Ippolito E, Corsi M, Ricci A, Feragalli B, Cornelli U, Gizzi C, Hosoi M Recurrence of retinal vein thrombosis with Pycnogenol ® or Aspirin ® supplementation: a registry study. Panminerva Med. 2015;57:121-5. 20. Araghi-Niknam M, Hosseini, S, Larson, D, Rohdewald, P and watson, RR. Pine bark extract reduces platelet aggregation. Integrative Medicine. 1999;2(2/3). 21. Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012;33(13):1589-97. 22. Pütter M GK, Würthwein G, Araghi-Niknam M, Watson RR, Hosseini S, Rohdewald P. . Inhibition of smokinginduced platelet aggregation by Aspirin and Pycnogenol. Thrombosis Research 1999;55:155–61. 23. Wang S, Tan D, Zhao Y, Gao G, Gao X, Hu L. The effect of Pycnogenol ® on the microcirculation, platelet function and ischaemic myocardium in patients with coronary artery diseases. European Bulletin of Drug Research. 1999;7(2):19-25. 24. Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, et al. Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol. Clin Appl Thromb Hemost. 2006;12(3):318-23. 25. Belcaro G. LR, Dugall M., Ippolito E., Saggino A. Venous ulcers: Microcirculatory improvement and faster healing with local use of Pycnogenol ® . Angiology. 2005;56(6):699- 705. 26. Steigerwalt R, Belcaro G, Cesarone MR, Di Renzo A, Grossi MG, Ricci A, et al. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009;25(6):537-40. 27. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, et al. Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study. Angiology. 2006;57(4):431-6. 28. Nishioka K, Hidaka T, Nakamura S, Umemura T, Jitsuiki D, Soga J, et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007;30(9):775-80. 29. Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol. 1998;32(4):509-15. 30. Uhlenhut K, Högger P. Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol). Free Radic Biol Med. 2012;53(2):305-13. 31. Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012;33(13):1589-97. 32. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004;74(7):855-62. 33. Zibadi S, Rohdewald PJ, Park D, Watson RR. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res. 2008;28(5):315- 20. 34. Hu S BG, Cornelli U, et al Effects of Pycnogenol ® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study. Int Angiol 2015;34(1):43-52. 35. Kahn SR. The post-thrombotic syndrome. Hematology Am Soc Hematol Educ Program. 2016;2016(1):413-8. 36. Jünger M, Steins A, Hahn M, Häfner HM. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000;7(6 Pt 2):S3-12. 37. Gschwandtner ME, Ehringer H. Microcirculation in chronic venous insufficiency. Vasc Med. 2001;6(3):169-79. 38. Chwała M, Szczeklik W, Szczeklik M, Aleksiejew-Kleszczyński T, Jagielska-Chwała M. Varicose veins of lower extremities, hemodynamics and treatment methods. Adv Clin Exp Med. 2015;24(1):5-14. 39. Strijdom H, Chamane N, Lochner A. Nitric oxide in the cardiovascular system: a simple molecule with complex actions. Cardiovasc J Afr. 2009;20(5):303-10. 40. Sowers JR, Epstein M. Diabetes Mellitus and Associated Hypertension, Vascular Disease, and Nephropathy. Hypertension. 1995;26(6):869-79. 41. Mudau M, Genis A, Lochner A, Strijdom H. Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr. 2012;23(4):222-31. For more information, please visit Author: Dr. Franziska Weichmann, Manager of Scientific Communications and Product Development at Horphag Research. No. 3 November/December 2021 21

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