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Oligomeric Proanthocyanidins (OPCs)
One of the bestselling herbal products of the early 1990s was an extract of the bark of French maritime pine. This substance consists of a family of chemicals known scientifically as oligomeric proanthocyanidin complexes (OPCs) or procyanidolic oligomers (PCOs). Similar (but not identical) substances are also found in grape seed. The research record is complicated by the fact that certain identically named proprietary products have consisted at different times of various proportions of these related substances.
OPCs are marketed for a wide variety of uses. As yet, however, there is no solid evidence that they are effective for any medical condition.
OPCs aren't a single chemical, but a group of closely related compounds. Several food sources contain similar chemicals: red wine, cranberries, blueberries, bilberries, tea (green and black), black currant, onions, legumes, parsley, and the herb hawthorn. However, most OPC supplements are made from either grape seed or the bark of the maritime pine. These two OPC sources lead to products that are not necessarily identical in function, although there do seem to be many similarities. In the discussion of scientific studies below, we indicate the source of the OPCs used when it is possible to do so. In some cases, however, identifying the exact product is difficult, as both grape seed and pine bark OPCs, or their combination, have at various times been sold under the same name.
Therapeutic Dosages TOP
For the treatment of specific medical conditions, studies have used doses of 150 to 300 mg daily. For use as a general antioxidant, 50 mg of OPCs daily are often recommended; however, there is no evidence that this dose provides any health benefits.
Therapeutic Uses TOP
The best-documented use of OPCs is to treat chronic venous insufficiency, a condition closely related to varicose veins. In both of these conditions, blood pools in the legs, causing aching, pain, heaviness, swelling, fatigue, and unsightly visible veins. Fairly good preliminary evidence suggests that OPCs from pine bark or grape seed can relieve the leg pain and swelling of chronic venous insufficiency.8-12,74 However, no studies have evaluated whether regular use of OPCs can make visible varicose veins disappear, or prevent new ones from developing.
One large study found some evidence that use of OPCs from pine bark might help prevent the leg blood clots that can develop on a long airplane flight.51
Some studies suggest OPCs from pine bark, alone or with arginine, may be helpful for erectile dysfunction (impotence).52,53,66 For example, in a double-blind, placebo-controlled trial, 124 men (aged 30-50) with moderate erectile dysfunction were randomized to take Prelox (a formulation of pine bark extract and arginine) or placebo for 6 months. The men who took Prelox experienced improvement in their condition over placebo.66
In a double-bind, placebo-controlled study of 61 children with attention deficit hyperactivity disorder (ADHD), use of OPCs from pine bark (at a dose of 1 g per kg per day) appeared to improve some measurements of disease severity.62
OPCs are also often recommended for allergies, but an 8-week, double-blind trial of 49 individuals found no benefit with grape seed extract.19 On a slightly more positive note, a preliminary trial involving 39 people with seasonal allergies found that those who took OPCs at least 5 weeks before the start of the season experienced more symptom relief compared to the control group. And those that took OPCs for a longer period of time (eg, 7-8 weeks before the season) seemed to have better results.65
According to several studies, OPCs might improve blood sugar control in people with diabetes.55 In addition, a small study found evidence to support the use of pine bark extract for improving the symptoms and healing time of foot ulcers, a common complication in people with diabetes.75
Some evidence suggests that OPCs protect and strengthen collagen and elastin.20-25 Theoretically, this could mean that OPCs are helpful for aging skin, and they are widely sold for this purpose, but there is as yet no direct evidence that the herbs work.
Hemorrhoids are varicose veins in and around the anus. Since OPCs are used to treat varicose veins, it is thought that this substance would also be helpful for people who have hemorrhoids. A randomized trial involving 84 people with hemorrhoids found that both the oral and topical forms of pycnogenol (pine bark extract) eased symptoms, including bleeding.68
OPCs are strong antioxidants. Vitamin E defends against fat-soluble oxidants, and vitamin C neutralizes water-soluble ones, but OPCs are active against both types.5-7 Based on the (unproven) belief that antioxidants offer many health benefits, regular use of OPCs has been proposed as a measure to prevent cancer, diabetic neuropathy and diabetic retinopathy,48 and heart disease.37-40
OPCs have been tried as a treatment for impaired night vision,35,36,45lupus (systemic lupus erythematosus),44easy bruising,16,17high blood pressure,43 and liver cirrhosis.49 However, more research needs to be performed to discover whether it actually provides any benefits in these conditions.
A systematic review of 15 trials evaluated the possible effectiveness of OPCs from pine bark in treating chronic disorders.76 While the pooled results did not show the benefits of OPCs, 3 trials hinted that the supplement may be useful in people with osteoarthritis.
What Is the Scientific Evidence for Oligomeric Proanthocyanidins? TOP
Venous Insufficiency (Varicose Veins)
There is fairly good preliminary evidence for the use of OPCs to treat people with symptoms of venous insufficiency.
A double-blind, placebo-controlled study of 71 subjects found that grape seed OPCs, taken at a dose of 100 mg 3 times daily, significantly improved major symptoms, including heaviness, swelling, and leg discomfort.27 Over a period of 1 month, 75% of the participants treated with OPCs improved substantially. This result doesn't seem quite so impressive when you note that significant improvement was also seen in 41% of the placebo group; nonetheless, OPCs still did significantly better than placebo.
A 2-month, double-blind, placebo-controlled trial of 40 people with chronic venous insufficiency found that 100 mg of pine bark OPCs 3 times daily significantly reduced edema, pain, and the sensation of leg heaviness.28 A similar study of 20 individuals also found OPCs from pine bark effective.29
A placebo-controlled study (blinding not stated) that enrolled 364 people with varicose veins found that treatment with grape seed OPCs produced statistically significant improvements as compared to baseline.30 There was a lesser response in the placebo group, but whether this difference was statistically significant was not stated.
In another study, 98 people with chronic venous insufficiency and edema were randomized to receive pycnogenol (150 mg/day), pycnogenol (150 mg) plus elastic stockings, or elastic stockings alone.74 After 8 weeks, the two groups that included pycenogenol had improvements in their symptoms compared with group using only elastic stockings, and the combination of pycnogenol and stockings was associated with the best results of all.
OPCs have also been compared against other natural treatments for venous insufficiency. A double-blind study of 50 people with varicose veins of the legs found that doses of 150 mg per day of grape seed OPCs were more effective in reducing symptoms and signs than the bioflavonoid diosmin.31 Similarly, a double-blind study of 39 people found pine bark OPCs more effective than the herb horse chestnut.46
Edema After Surgery or Injury
Breast cancer surgery often leads to swelling of the arm. A double-blind, placebo-controlled study of 63 post-operative breast cancer patients found that 600 mg of grape seed OPCs daily for 6 months reduced edema, pain, and peculiar sensations known as paresthesias.32 Also, in a double-blind, placebo-controlled study of 32 people who had received facial surgery, edema disappeared much faster in the group treated with grape seed OPCs.33
Blood Clots After Plane Flights TOP
It is commonly thought, though not proven, that the immobility endured during a long plane flight can lead to the development of potentially dangerous blood clots in the legs known as DVTs.57 Travelers at high risk are often recommended to take aspirin to "thin" their blood prior to flying.
One crossover study of 22 smokers found that 100 mg of OPCs had an equivalent blood thinning effect as 500 mg of aspirin.58 On the basis of this, a large double-blind study was performed to evaluate whether OPCs from pine bark could help reduce risk of blood clots on long airplane flights.59 The study followed 198 people thought to be at high risk for blood clots. Some participants were given 200 mg of OPCs 2 to 3 hours prior to the flight, 200 mg 6 hours later, and 100 mg the next day; while others received placebo at the same schedule. The average flight length was about 8 hours. The results indicated that use of OPCs significantly reduced risk of blood clots. There were five cases of DVTs or superficial thrombosis in the placebo group, as compared to none in the OPC group, a difference that was statistically significant.
Another substantial double-blind study (204 participants) found benefit with a product that contains OPCs combined with nattokinase.63 Nattokinase, also known as natto, is an extract of fermented soy thought to have some blood clot dissolving properties.
Periodontal Disease TOP
Inflammation of the gums (gingivitis) and plaque formation lead to periodontal disease, one of the most common causes of tooth loss. A 14-day, double-blind, placebo-controlled trial of 40 people evaluated the potential benefits of a chewing gum product containing 5 mg of OPCs from pine bark.47 Use of the OPC gum resulted in significant improvements in gum health and reductions in plaque formation; no similar benefits were seen in the placebo group.
Safety Issues TOP
OPCs have been extensively tested for safety and are generally considered to be essentially nontoxic.41 Side effects are rare, but when they do occur they are limited to occasional allergic reactions and mild digestive distress.
However, one study unexpectedly found that a combination of OPCs and vitamin C might slightly increase blood pressure in people with high blood pressure.60 Neither treatment alone had this effect. These results may have been a statistical fluke, but nonetheless people with hypertension should use the combination of vitamin C and OPCs only with caution. One study, though, found that pycnogenol (pine bark extract) may help improve kidney function in people with metabolic syndrome who take high blood pressure medicine.67
Maximum safe dosages for young children, pregnant or nursing women, or those with severe liver or kidney disease have not been established.
OPCs may have some anticoagulant properties when taken in high doses, and therefore should be used only under medical supervision by individuals on blood-thinner drugs, such as warfarin (Coumadin), heparin, clopidogrel (Plavix), ticlopidine (Ticlid), pentoxifylline (Trental), or aspirin.
References[ + ]
1. Schwitters B, Masquelier J. OPC in Practice: Bioflavanols and their Applications. Rome, Italy: Alfa Omega; 1993.
2. Masquelier J, Dumon MC, Dumas J. Stabilization of collagen by procyanidolic oligomers [in French; English abstract]. Acta Ther. 1981;7:101-105.
3. Masquelier J. Procyanidolic oligomers (Leucocyanidins) [translated from French]. Parfums Cosmetiques Aromes. 1990;95:89-97.
4. Tixier JM, Godeau G, Robert AM, et al. Evidence by in vivo and in vitro studies that binding of pycnogenols to elastin affects its rate of degradation by elastases. Biochem Pharmacol. 1984;33:3933-3939.
5. Maffei Facino R, Carini M, Aldini G, et al. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung. 1994;44:592-601.
6. Kuttan R, Donnelly PV, Di Ferrante N. Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase. Experientia. 1981;37:221-223.
7. Masquelier J, Dumon MC, Dumas J. Stabilization of collagen by procyanidolic oligomers [in French; English abstract]. Acta Ther. 1981;7:101-105.
8. Thebaut JF, Thebaut P, Vin F. Study of Endotelon Ŵ in functional manifestations of peripheral venous insufficiency [translated from French]. Gaz Med. 1985;92:96-100.
9. Henriet JP. Exemplary study for a phlebotropic substance, the EIVE Study [translated from French]. Fairfield, CT: Primary Source; not dated.
10. Delacroix P. Double-blind study of Endotelon Ŵ in chronic venous insufficiency [translated from French]. La Revue de Medecine. 1981;27-28:1793-1802.
11. Arcangeli P. Pycnogenol in chronic venous insufficiency. Fitoterapia. 2000;71:236-244.
12. Petrassi C, Mastromarino A, Spartera C. Pycnogenol in chronic venous insufficiency. Phytomedicine. 2000;7:383-388.
13. Pecking A, Desprez-Curely JP, Megret G. Oligomeric grape flavanols (Endotelon) in the treatment of secondary upper limb lymphedemas [translated from French]. Study on file with manufacturer, International Nutrition Company (INC),Vaduz, Liechtenstein. 1989;69-73.
14. Baruch J. Effect of Endotelon in postoperative edema. Results of a double-blind study versus placebo in 32 female patients [translated from French]. Ann Chir Plast Esthet. 1984;29:393-395.
15. Parienti JJ, Parienti-Amsellem J. Post traumatic edemas in sports: a controlled test of Endotelon Ŵ [translated from French]. Gaz Med Fr. 1983;90:231-236.
16. Maffei Facino R, Carini M, Aldini G, et al. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung. 1994;44:592-601.
17. Dartenuc JY, Marache P, Choussat H. Capillary resistance in geriatry: a study of microangioprotector = Endotelon [translated from French]. Bord Med. 1980;13:903-907.
18. Preuss HG, Wallerstedt D, Talpur N, et al. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med. 2000;31:227-246.
19. Bernstein CK, Deng C, Shuklah R, et al. Double blind, placebo controlled (DBPC) study of grapeseed extract in the treatment of seasonal allergic rhinitis (SAR) [abstract]. J Allergy Clin Immunol. 2001;107:1018.
20. Maffei Facino R, Carini M, Aldini G, et al. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung. 1994;44:592-601.
21. Kuttan R, Donnelly PV, Di Ferrante N. Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase. Experientia. 1981;37:221-223.
22. Masquelier J. Procyanidolic oligomers. Parfums Cosmetiques Aromes. 1990;95:89-97.
23. Masquelier J, Dumon MC, Dumas J. Stabilization of collagen by procyanidolic oligomers [in French; English abstract]. Acta Ther. 1981;7:101-105.
24. Schwitters B, Masquelier J. OPC in Practice: Bioflavanols and their Applications. Rome, Italy: Alfa Omega; 1993.
25. Tixier JM, Godeau G, Robert AM, et al. Evidence by in vivo and in vitro studies that binding of pycnogenols to elastin affects its rate of degradation by elastases. Biochem Pharmacol. 1984;33:3933-3939.
26. Bagchi D, Garg A, Krohn RL, et al. Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol. 1997;95:179-189.
27. Thebaut JF, Thebaut P, Vin F. Study of Endotelon in functional manifestations of peripheral venous insufficiency [translated from French]. Gaz Med. 1985;92:96-100.
28. Arcangeli P. Pycnogenol in chronic venous insufficiency. Fitoterapia. 2000;71:236-244.
29. Petrassi C, Mastromarino A, Spartera C. Pycnogenol in chronic venous insufficiency. Phytomedicine. 2000;7:383-388.
30. Henriet JP. Exemplary study for a phlebotropic substance, the EIVE Study [translated from French]. Fairfield, CT: Primary Source; not dated.
31. Delacroix P. Double-blind study of Endotelon Ŵ in chronic venous insufficiency [translated from French]. La Revue de Medecine. 1981;27-28:1793-1802.
32. Pecking A, Desprez-Curely JP, Megret G. Oligomeric grape flavanols (Endotelon) in the treatment of secondary upper limb lymphedemas [translated from French]. Study on file with manufacturer, International Nutrition Company (INC),Vaduz, Liechtenstein. 1989;69-73.
33. Baruch J. Effect of Endotelon in postoperative edema. Results of a double-blind study versus placebo in 32 female patients [translated from French]. Ann Chir Plast Esthet. 1984;29:393-395.
34. Parienti JJ, Parienti-Amsellem J. Post traumatic edemas in sports: a controlled test of Endotelon [translated from French]. Gaz Med Fr. 1983;90:231-236.
35. Corbe C, Boissin JP, Siou A. Light vision and chorioretinal circulation. Study of the effect of procyanidolic oligomers [translated from French]. J Fr Ophtalmol. 1988;11:453-460.
36. Boissin JP, Corbe C, Siou A. Chorioretinal circulation and dazzling: use of procyanidol oligomers [in French; English abstract]. Bull Soc Ophtamol Fr. 1988;88:173-174,177-179.
37. Schwitters B, Masquelier J. OPC in Practice: Bioflavanols and their Applications. Rome, Italy: Alfa Omega; 1993.
38. Wegrowski J, Robert AM, Moczar M. The effect of procyanidolic oligomers on the composition of normal and hypercholesterolemic rabbit aortas. Biochem Pharmacol. 1984;33:3491-3497.
39. Uchida S, Edamatsu R, Hiramatsu M. Condensed tannins scavenge active oxygen free radicals. Med Sci Res. 1987;15:831-832.
40. Gendre PM, Laparra J, Barraud E. Protective effect of procyanidolic oligomers on experimental lathyrism in rats [in French; English abstract]. Ann Pharm Fr. 1985;43:61-71.
41. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer Verlag; 1998:283.
42. Hosseini S, et al. Pycnogenol in the management of asthma. J Med Food. 2001;4:201-210
43. Hosseini S, et al. 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. Nutr Res. 2001; 21:1251-1260.
44. Stefanescu M, et al. Pycnogenol efficacy in the treatment of systemic lupus Erythematosus Patients. Phytother Res. 2001;15:698-704.
45. Spadea L, Balestrazzi E., Treatment of vascular retinopathies with pycnogenol. Phytother Res. 2001;15:219-223.
46. Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res. 2002;16(suppl):S1-S5.
47. Kimbrough C, Chun M, dela Roca G, et al. Pycnogenol chewing gum minimizes gingival bleeding and plaque formation. Phytomedicine. 2002;9:410-413.
48. Schonlau F, Rohdewald P. Pycnogenol for diabetic retinopathy. A review. Int Ophthalmol. 2001;24:161-171.
49. Lesbre FX. Effect of endotelon on the capillary fragility index in a specific group: cirrhotic subjects. Gaz Med Fr. 1983;90:332-337.
50. Christie S, Walker AF, Hicks SM, et al. Flavonoid supplement improves leg health and reduces fluid retention in pre-menopausal women in a double-blind, placebo-controlled study. Phytomedicine. 2004;11:11-17.
51. Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with Pycnogenol®. Clin Appl Thromb Hemost. 2004;10:373-377.
52. Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003;29:207-213.
53. Durackova Z, Trebaticky B, Novotny V, et al. Lipid metabolism and erectile function improvement by pycnogenol extract from the bark of Pinus pinaster in patients suffering from erectile dysfunction—a pilot study. Nutr Res. 2003;23:1189-1198.
54. Lau BH, Riesen SK, Truong KP, et al. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma. 2005;41:825-832.
55. Liu X, Wei J, Tan F, et al. Antidiabetic effect of Pycnogenol® French maritime pine bark extract in patients with diabetes type II. Life Sci. 2004;75:2505-2513.
56. Vogels N, Nijs IM, Westerterp-Plantenga MS. The effect of grape-seed extract on 24 h energy intake in humans. Eur J Clin Nutr. 2004;58:667-673.
57. ten Wolde M, Kraaijenhagen RA, et al. Travel and the risk of symptomatic venous thromboembolism. Thromb Haemost. 2003;89:499-505.
58. Putter M, Grotemeyer KH, Wurthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res. 1999;95:155-161.
59. Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with Pycnogenol®. Clin Appl Thromb Hemost. 2004;10:373-377.
60. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens. 2005;23:427-34.
61. Brooker S, Martin S, Pearson A, et al. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiother Oncol. 2006 Mar 16. [Epub ahead of print]
62. Trebaticka J, Kopasova S, Hradecna Z, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol®. Eur Child Adolesc Psychiatry. 2006 May 13. [Epub ahead of print]
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64. Yang HM, Liao MF, Zhu SY, et al. A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol® on the climacteric syndrome in peri-menopausal women. Acta Obstet Gynecol Scand. 2007;86:978-985.
65. Wilson D, Evans M, Guthrie N, Sharma P, Baisley J, Schonlau F, Burki C. A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol for improving allergic rhinitis symptoms. Phytother Res. 2010;24(8):1115-1119.
66. Ledda A, Belcaro G, Cesarone MR, Dugall M, Schönlau F. Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study. BJU Int. 2010;106(7):1030-1033.
67. Stuard S, Belcaro G, Cesarone MR, et al. Kidney function in metabolic syndrome may be improved with Pycnogenol. Panminerva Med. 2010;52(2 Suppl 1):27-32.
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73. Cisár P, Jány R, Waczulíková I, et al. Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis. Phytother Res. 2008;22(8):1087-1092.
74. Cesarone MR, Belcaro G, Rohdewald P, et al. Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study. Phytomedicine. 2010;17(11):835-839.
75. Belcaro G, Cesarone MR, Errichi BM, et al. Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol. Clin Appl Thromb Hemost. 2006;12(3):318-323.
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Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015
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