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The Molecule

Our flagship product: annedda® white pine bark extract

What are proanthocyanidins?

Proanthocyanidins are a class of flavonol compounds found in a number of plants. They are especially abundant in the bark of the pine tree.

They bind naturally with collagen, the protein present in organic connective tissue, including skin, tendons, ligaments and cartilage as well as the inside walls of blood vessels. It is this natural substance that helps maintain the structure of connective tissues and ensure proper functioning of many organs and physiological processes.

Proanthocyanidins possess these properties because of their antioxydant as well as anti-inflammatory activity as they inhibit the synthesis of substances triggering allergic and inflammatory reactions. In fact, they modulate the immune system by either stimulating or weakening its activity depending on what the body needs.

What is an antioxidant?

Oxidation occurs when two free oxygene electrons (also called free radicals) attach themselves to molecules.

For example, in a molecule of iron, oxidation takes the form of rust.

In a living organism, it appears as an inflammatory or allergic type reaction. This is what is called oxidative stress, which is at the core of a number of illnesses and physiological disorders: cardiovascular issues, diabetes, cancers, degenerative or autoimmune disorders such as various types of arthritis, multiple sclerosis and Crohn’s disease, etc.

Antixoxidants inhibit the oxidation of various biological substances in the organism, thus neutralizing the free radicals responsible for the damage caused by oxidation. As an analogy, you can think of antioxidants as rust protection for your body.

In the human body, the main antioxidants are vitamins C and E, both of which come from the food we consume.

Why is our standardized proanthocyanidin extract the best antioxidant you can find?

  • Together with traditional First Nations healers, we identified the tree type whose extract saved the lives of Jacques Cartier’s crew in 1535. Annedda is the eastern white pine of North America (Pinus strobus).
  • Because it grows in regions removed from sources of agricultural and industrial pollution, the white pine makes for a raw material that is free of pesticide residue, chemical fertilizers and other environmental pollutants.
  • We do not use any solvents in our natural and exclusive extraction process, licensed under Agriculture and Agri-Food Canada. As a result, our extract is free of any industrial solvent.
  • The best bioactive fraction of the Annedda® white pine extract is measured at 400 PVU (Porter Value Units). The products from the two other major world producers of pine bark extract (from a different type of pine that grows in the Mediterranean) come in at 180 and 275 PVU.

Therapeutic indications

What are the therapeutic uses of the standardized proanthocyanidin pine bark extract?

Over the past two decades numerous clinical trials have proven the Native traditions right and confirmed the medicinal properties of pine bark. Modern science, and especially the results of tests conducted over the last ten years have shown, over and over again, that several diseases and health issues can be treated effectively and safely by pine bark extract with standardized proanthocyanidin content. The wide variety of medical applications for these compounds is impressive.


Arthritis is a general term applied to a number of rheumatic disorders such as osteoarthritis, rheumatoid arthritis, fibromyalgia, gout, lupus, psoriatic arthritis, Raynaud’s disease, as well as a number of degenerative disorders that attack connective tissue in joints and many other surrounding body parts. All of these rheumatic conditions result in inflammation and pain.

Pine bark extract is well proven to counter the inflammation by inhibiting the formation of substances that trigger inflammation in the body: 5-lipoxygenase, phospholipas A2, cyclooxygenase-2 (COX-2).4 The most prescribed anti-inflammatory drugs in the world focus on inhibiting COX-2. Clinical trials have shown that pine bark extract alleviates pain effectively, improves mobility and reduces the need for patients to rely on synthetic anti-inflammatory and conventional pain medication.5

Morevoer, the proanthocyanidins found in pine extract allow the body to regain its natural capacity to not only curb deterioration of the joint tissues but also to regenerate them. These substances are closely related with collagen, the essential protein in organic connective tissue, including skin, tendons, ligaments and cartilage as well as the inside walls of blood vessels. They bind with collagen and help maintain the structure of connective tissue. As such, pine extract helps curb disease growth and aids in the regeneration of damaged tissue.

Cardiovascular disorders

Cardiovascular disorders include a range of conditions affecting the heart and blood vessels: coronary diseases, atherosclerosis, venous insufficiency, capillary fragility, high blood pressure, etc. Over the past few years, scientific research has highlighted the role of oxidative stress as a major culprit in triggering an inflammatory response which leads to and fuels the development of cardiovascular disorders.

Pine bark extract, with its exceptional antioxidant power, anti-inflammatory properties and favourable action on the connective tissues that form the internal walls of blood vessels, offers many benefits: counteracting blood clot formation and thus preventing heart attack and stroke,6 helping control blood pressure,7 protecting vessels when blood cholesterol and triglyceride levels rise,8 ensuring the integrity and proper functioning of blood vessel walls,9 and contributing to the treatment of venous insufficiency.10

Diabetes and metabolic syndrome

When blood sugar levels rise, the pancreas secretes insulin in order to control the blood sugar as quickly as possible. In the presence of frequent and significant blood sugar spikes, the body can become resistant to insulin, leaving it unable to process sugars, which end up accumulating in the body. The pancreas subsequently compensates by producing more insulin, which further complicates matters.

The individual gains weight, especially in the abdominal region, and begins a vicious cycle: sugar and fat build up in the body, increasing the risk of diabetes, cardiovascular problems, heart attack, stroke and cancer. This is metabolic syndrome, also referred to as “prediabetes,” an increasingly common physiological disorder in post-industrial society.

Clinical trials have shown that the proanthocyanidins from pine bark lower blood sugar levels thus protecting the body from developing metabolic syndrome, and help reduce the negative effects if metabolic syndrome is already present.11 Even diabetics who take pine bark extract experience a significantly reduced risk of heart complications, angiopathy, retinopathy and diabetic ulcers.12


Cancer develops when cells stop working on behalf of the body and develop into a tumour, a harmful growth that feeds on the organism but functions independently.

Numerous studies show that pine bark proanthocyanidins contain properties that counteract the formation of cancerous tumours and limit their growth.14

Immune system disorders

The immune system is designed to recognize and remove toxic bacteria, viruses and other toxic substances that can harm the body. It can also trigger an inappropriate immune response by attacking harmless substances. This is referred to as intolerance or allergy, depending on the seriousness of the body’s reaction. In some cases, the immune system will attack the body’s tissues, which it is designed to protect. Such cases consitute autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis.

Studies on animals have demonstrated that pine bark extract can counter the immune system’s production of histamine, a substance that triggers an allergic type reaction.15 In fact, clinical trials have shown the extract to be effective in preventing allergic asthma.16

Cognitive disorders and alzheimer’s

Researchers relate the loss of congitive faculties to the presence of beta-amyloid peptides which are found in formations of senile plaques in individuals suffering from senile dementia or Alzheimer’s disease. Pine bark extract has been shown to inhibit this peptide or to counteract its toxic effect on neurons. 17 In a clinical trial conducted on men between 50 and 65 years of age, pine extract improved cognitive abilities.18

Attention deficit hyperactivity disorder

ADHD is a behavioural disorder affecting more and more children and adults. It is often treated with Ritalin® (methylphenidate). Pine bark extract has been shown to possess an ability to alleviate symptoms of this disorder that is comparable to that of methylphenidate but without the side effects.19

Skin disorders

Clinical trials have shown that proanthocyanidin-rich pine extract can be useful in treating inflammatory skin disorders such as psoriasis, eczema and lupus erythematosus.20


4- Canali R, Comitato R, Schonlau F, et al. The anti-inflammatory pharmacology of Pycnogenol in humans involves COX-2 and 5-LOX mRNA expression in leukocytes. Int Immunopharmacol. 2009 Sep;9(10):1145-9.

Schäfer A, Chovanová Z, Muchová J, et al. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed Pharmacother. 2006 Jan;60(1):5-9.

5- Belcaro G, Cesarone MR, Errichi S, et al. Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res. 2008 Apr;22(4):518-23.

Cisár P, Jány R, Waczulíková I, et al. Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis. Phytother Res. 2008 Aug;22(8):1087-92.

6- Araghi-Niknam M, Hosseini S, Larson D, et al. Pine bark extract reduces platelet aggregation. Integr Med. 2000 Mar 21;2(2):73-77.

Pütter M, Grotemeyer KH, Würthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res. 1999 Aug 15;95(4):155-61.

7- Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol. 1998 Oct;32(4):509-15.

Liu X, Wei J, Tan F, et al. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004 Jan 2;74(7):855-62.

8- da Silva Porto PA, Laranjinha JA, de Freitas VA. Antioxidant protection of low density lipoprotein by procyanidins: structure/activity relationships. Biochem Pharmacol. 2003 Sep 15;66(6):947-54.

Devaraj S, Vega-López S, Kaul N, et al. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids. 2002 Oct;37(10):931-4.

9- Liu F, Lau BH, Peng Q, Shah V. Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000 Jun;23(6):735-7. Peng Q, Wei Z, Lau BH. Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci. 2000 May;57(5):834-41.

Virgili F, Kim D, Packer L. Procyanidins extracted from pine bark protect alpha-tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite. FEBS Lett. 1998 Jul 24;431(3):315-8.

Belcaro G, Cesarone MR, Ricci A, et al. Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin- converting enzyme inhibitors with Pycnogenol. Clin Appl Thromb Hemost. 2006 Oct;12(4):440-4.

10- Gulati OP. Pycnogenol® in Chronic Venous Insufficiency and Related Venous Disorders. Phytother Res. 2013 Jun 15. doi: 10.1002/ ptr.5019.

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 Oct;10(4):373-7.

Petrassi C, Mastromarino A, Spartera C. PYCNOGENOL in chronic venous insufficiency. Phytomedicine. 2000 Oct;7(5):383-8.

Daróczy J, Pál A, Blaskó G. [Microcirculatory changes in patients with chronic venous and lymphatic insufficiency and heavy leg symptoms before and after therapy with procyanidol oligomers (laser-Doppler study)]. [Article in Hungarian; summary in English]. Orv Hetil. 2004 May 30;145(22):1177-81.

11- Belcaro G, Cornelli U, Luzzi R, et al. Pycnogenol® Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome. Phytother Res. 2013 Jan 28. doi: 10.1002/ptr.4883.

Zibadi S, Rohdewald PJ, Park D, et al. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res. 2008 May;28(5):315-20.

12- 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 May;28(5):315-20.

Cesarone MR, Belcaro G, Rohdewald P, et al. Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study. Angiology. 2006 Aug-Sep;57(4):431-6.

Belcaro G, Cesarone MR, Errichi BM, et al. Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol. Clin Appl Thromb Hemost. 2006 Jul;12(3):318-23.

Steigerwalt R, Belcaro G, Cesarone MR, et al. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009 Dec;25(6):537-40.

13- Hasegawa N. Inhibition of lipogenesis by pycnogenol. Phytother Res. 2000 Sep;14(6):472-3.

Mochizuki M, Hasegawa N. Pycnogenol stimulates lipolysis in 3t3-L1 cells via stimulation of beta-receptor mediated activity. Phytother Res. 2004 Dec;18(12):1029-30.

Kim YM, Jeong YK, Wang MH, et al. Inhibitory effect of pine extract on alpha-glucosidase activity and postprandial hyperglycemia. Nutrition. 2005 Jun;21(6):756-61.

14- Chen G, Perchellet EM, Gao XM, et al. Ability of m-chloroperoxybenzoic acid to induce the ornithine decarboxylase marker of skin tumor promotion and inhibition of this response by gallotannins, oligomeric proanthocyanidins, and their monomeric units in mouse epidermis in vivo. Anticancer Res. 1995 Jul-Aug;15(4):1183-9.

Kozikowski AP, Tückmantel W, Böttcher G, Romanczyk LJ Jr. Studies in polyphenol chemistry and bioactivity. 4.(1) Synthesis of trimeric, tetrameric, pentameric, and higher oligomeric epicatechin-derived procyanidins having all-4beta,8-interflavan connectivity and their inhibition of cancer cell growth through cell cycle arrest. J Org Chem. 2003 Mar 7;68(5):1641-58.

Huang WW, Yang JS, Lin CF, et al. Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells. Leuk Res. 2005 Jun;29(6):685-92. Epub 2005 Jan 19.

Kim DS, Kim MS, Kang SW, et al. Pine bark extract enzogenol attenuated tumor necrosis factor-alpha-induced endothelial cell adhesion and monocyte transmigration. J Agric Food Chem. 2010 Jun 9;58(11):7088-95.

15- Sharma SC, Sharma S, Gulati OP. Pycnogenol inhibits the release of histamine from mast cells. Phytother Res. 2003 Jan;17(1):66-9.

16- Hosseini S, Pishnamazi S, Sadrzadeh SM, et al. Pycnogenol((R)) in the Management of Asthma. J Med Food. 2001

Winter;4(4):201-209. Lau BH, Riesen SK, Truong KP, et al. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma. 2004;41(8):825-32.

17- Liu F, Lau BH, Peng Q, Shah V. Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000 Jun;23(6):735-7.

Peng QL, Buz’Zard AR, Lau BH. Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis. Brain Res Mol Brain Res. 2002 Jul 15;104(1):55-65.

18- Pipingas A, Silberstein RB, Vitetta L, et al. Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation. Phytother Res. 2008 Sep;22(9):1168-74.

19- Trebatická J, Kopasová S, Hradecná Z, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry. 2006 Sep;15(6):329-35.

20- Bito T, Roy S, Sen CK, Packer L. Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med. 2000 Jan 15;28(2):219-27.

Wu C, Feng D, Ma H, et al. Effect of Pinus massoniana bark extract on IFN-gamma-induced ICAM-1 expression in HaCaT human keratinocytes. J Ethnopharmacol. 2009 Feb 25;122(1):48-53.

Saliou C, Rimbach G, Moini H, et al. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med. 2001 Jan 15;30(2) :154-60.