Pycnogenol® for diabetic retinopathy


Diabetic retinopathy represents a serious health threat to a rapidly growing numberof patients with diabetes mellitus. The retinal microangiopathy is characterised byvascular lesions with exudate deposits and haemorrhages causing vision loss.Pycnogenol®, a standardised extract of the bark of the French maritime pine (Pinus pinaster), is known to increase capillary resistance. Pycnogenol® has been tested for treatment and prevention of retinopathy in five clinical trials with atotal number of 1289 patients since the late 1960's. All but one of these studies have been reported in French and German and, today, are of limited accessibility, giving the impetus for reviewing them in detail in this article.There were two open case studies and two double blind studies (one controlledagainst calcium dobesilate and another against placebo) and, finally, one multi-centerfield study with 1169 diabetics. All of these studies unequivocally showed thatPycnogenol® retains progression of retinopathy and partly recoversvisual acuity. Treatment efficacy of Pycnogenol® was at least asgood as that of calcium dobesilate. Pycnogenol® was shown toimprove capillary resistance and reduce leakages into the retina. Tolerance wasgenerally very good and side effects were rare, mostly referring to gastric discomfort.In conclusion, treatment with Pycnogenol® had a favourable outcomein the majority of the patients with diabetic retinopathy.

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  1. 1.

    Shaw JE, Zimmet PZ, McCarty D, de Courten M. Type 2 diabetes worldwide according to the new classification and criteria. Diabetes Care 2000; 23 Suppl 2: B5–10.

    PubMed  Google Scholar 

  2. 2.

    Taylor HR, Keeffe JE. World blindness: a 21st century perspective. Br J Ophthalmol 2001; 85: 261–6.

    PubMed  Google Scholar 

  3. 3.

    Hutchinson A, McIntosh A, Peters J, O'Keefe C, Khunti K, BAker R, Booth A. Effectiveness of screening and monitoring tests for diabetic retinopathy-a systematic review. Diabetic Medicine 2000; 17: 495–506.

    PubMed  Google Scholar 

  4. 4.

    Ferris FL. How effective are treatments for diabetic retinopathy? JAMA 1993; 269: 1290–1.

    PubMed  Google Scholar 

  5. 5.

    The DCCT Research Group. The effect of intensive diabetes treatment on the development and progression of long term complications in insulin dependent diabetes mellitus: the diabetes control and complications trial. New Engl J Med 1993; 329: 977–86.

    Google Scholar 

  6. 6.

    Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type II diabetes: (UKPDS 33). Lancet 1998; 352: 837–51.

  7. 7.

    John WG, Lamb EJ. The maillard or browning reaction in diabetes. Eye 1993; 7: 230–7.

    PubMed  Google Scholar 

  8. 8.

    Singh R, Barden A, Mori T, Beilin L. Advanced glycation endproducts: a review. Diabetologia 2001; 44: 129–46.

    PubMed  Google Scholar 

  9. 9.

    McCance DR, Dyer DG, Dunn JA, Bailie KE, Thorpe SR, Baynes JW et al. Maillard reaction products and their relation to complications in insulin dependent diabetes mellitus. J Clin Invest 1993; 91: 2470–8.

    PubMed  Google Scholar 

  10. 10.

    Chappey O, Dosquet C, Wautier M-P, Wautier J-L. Advanced glycation end-products, oxidant stress and vascular lesions. Eur J Clin Invest 1997; 27: 97–108.

    PubMed  Google Scholar 

  11. 11.

    Monnier VM, Glomb M, Elgawish A, Sell DR. The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution. Diabetes 1996; 45 Suppl 3: 367–72.

    PubMed  Google Scholar 

  12. 12.

    Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol & Therapeutics 2002; 40: 158–168.

    Google Scholar 

  13. 13.

    Gábor M, Engi E, Sonkodi S. Die Kapillarwandresistenz und ihre Beeinflussung durch wasserlösliche Flavonderivate bei spontan hypertonischen Ratten. Phlebologie 1993; 22: 178–82.

    Google Scholar 

  14. 14.

    Blazsó G, Gábor M, Sibbel R, Rohdewald P. Antiinflammatory and superoxide radical scavenging activities of a procyandin containing extract from the bark of Pinus pinaster Sol. and its fractions. Pharm Pharmacol Lett 1994; 3: 217–20.

    Google Scholar 

  15. 15.

    Blazsó G, Gábor M, Rohdewald P. Antiinflammatory activities of procyanidin-containing extracts from Pinus pinaster Ait after oral and cutaneous application. Pharmazie 1997; 52: 380–2.

    PubMed  Google Scholar 

  16. 16.

    Gulati OP. Pycnogenol® in venous disorders: A review. Eur Bull Drug Res 1999; 7: 8–13.

    Google Scholar 

  17. 17.

    Bessière E: Étude clinique de flavan, deuxieme partie: Ophtalmologie. Informations Médicales Laboratoires Millot Paris; 1970.

  18. 18.

    Magnard G, Franck JP, Dorne PA. Intéret du tetrahydroxy flavane diol en ophtalmologie en particulier dans le rétinopathie diabétique. Lyon Med 1970; 4: 1–18.

    Google Scholar 

  19. 19.

    Leydhecker W. Zur medicamentösen Behandlung der diabetischen Retinopathie. The Ophthalmology Department of the University Clinic of Würzburg, Germany. Study report, 1986.

    Google Scholar 

  20. 20.

    Spadea L, Balestrazzi E. Treatment of vascular retinopathy with Pycnogenol®. Phytother Res 2001; 15: 219–23.

    PubMed  Google Scholar 

  21. 21.

    Plantorgan Arzneimittel. Pygnoforton bei diabetischer Retinopathie. Plantorgan study report, 1988.

  22. 22.

    Ceriello A. Hyperglycaemia: the bridge between nonenzymatic glycation and and oxidative stress in the pathogenesis of diabetic complications. Diabetes Nutr Metab 1999; 12: 42–6.

    PubMed  Google Scholar 

  23. 23.

    Droy-Lefaix MT, Cluzel J, Menerath JM, Bonhomme B, Doly M. Antioxidant effect of a Gingko biloba extract (EGb 761) on the retina. Int J Tissue React 1995; 17: 93–100.

    PubMed  Google Scholar 

  24. 24.

    Cossins E, Lee R, Packer L. ESR studies of vitamin C regeneration, order of reactivity of natural source phytochemical preparations. Biochem Mol Biol Int 1998; 45: 583–98.

    PubMed  Google Scholar 

  25. 25.

    Chida M, Suzuki K, Nakanishi-Ueda T, Ueda T, Yasuhara H, Koide R et al. In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue. Ophthalmic Res 1999; 31: 407–15.

    PubMed  Google Scholar 

  26. 26.

    Trevithick JR, Hirst M, Cukiernik V, Wahlman J, Chartrand M, Dzialoszynski T et al. Pycnogenol antioxidant, and cataract risk reduction experiments. Invest Ophthalmol Vis Sci 2000; 41: 476.

    Google Scholar 

  27. 27.

    Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol 1998; 32: 509–15.

    PubMed  Google Scholar 

  28. 28.

    Schmetterer L, Findl O, Fasching P, Ferber W, Strenn K, Breiteneder H et al. Nitric oxide and ocular blood flow in patients with IDDM. Diabetes 1997; 46: 653–8.

    PubMed  Google Scholar 

  29. 29.

    Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol 2001; 158: 147–52.

    PubMed  Google Scholar 

  30. 30.

    Peng Q, Wei Z, Lau BHS. Pycnogenol inhibits tumor necrosis factor-α-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci 2000; 57: 834–41.

    PubMed  Google Scholar 

  31. 31.

    Cho K-J, Yun C-H, Yoo D-Y, Cho Y-S, Rimbach G, Packer L et al. Effect of bioflavonoid extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7. Toxicol Appl Pharmacol 2000; 168: 64–71.

    PubMed  Google Scholar 

  32. 32.

    Bayetta E, Lau BHS. Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutrition Res 2000; 20: 249–59.

    Google Scholar 

  33. 33.

    Miyamoto K, Khosrof S, Bursell S-E, Rohan R, Murata T, Clermont A et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acd Sci USA 1999; 96: 10836–41.

    Google Scholar 

  34. 34.

    Pütter M, Grotemeyer KHM, Würthwein G, Araghi-Niknam M, Watson RR, Hosseini S et al. Inhibition of smokinginduced platelet aggregation by Aspirin and Pycnogenol. Thromb Res 1999; 95: 155–61.

    PubMed  Google Scholar 

  35. 35.

    Carr ME. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications 2001; 15: 44–54.

    PubMed  Google Scholar 

  36. 36.

    Boeri D, Maiello M, Lorenzi M. Increased prevalence of microthromboses in retinal capillaries of diabetic individuals. Diabetes 2001; 50: 1432–9.

    PubMed  Google Scholar 

  37. 37.

    Berthet P, Farine JC, Barras JP. Calcium dobesilate: pharmacological profile related to its use in diabetic retinopathy. Int J Clin Pract 1999; 53: 631–6.

    PubMed  Google Scholar 

  38. 38.

    Carlsson K, Patwardhan A, Poullain JC, Gerentes I. Localization of troxerutin in the venous wall measured using laser scanning microscope. J Mal Vascul 1996; 21 (suppl. C): 270–4.

    Google Scholar 

  39. 39.

    Gábor M. The pharmacology of benzopyrone derivatives and related compounds. Akadémia Kiadó, Budapest 1986.

    Google Scholar 

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Schönlau, F., Rohdewald, P. Pycnogenol® for diabetic retinopathy. Int Ophthalmol 24, 161–171 (2001).

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  • diabetes
  • diabetic retinopathy
  • Pycnogenol