The 35+ Benefits Of French Maritime Pine Bark (Pycnogenol, Flavangenol And Oligopin)

The 35+ Benefits Of French Maritime Pine Bark (Pycnogenol, Flavangenol And Oligopin)

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Basics Of Pine Bark

French Maritime Pine Bark (Pinus maritima or Pinus pinaster) is from pine trees off the southwest coast of France.

Pycnogenol (PYC also goes by Flavagenol or Oligopin) is a patented mix of bioflavonoid polyphenols extracted from French maritime pine bark with its main components including 60–75% oligomeric are procyanidins besides taxifolin, catechin, and phenol acids., that is well-tolerated and has a high oral bioavailability. R R

Because of the way it is metabolized in the body (more described below), pycnogenol acts like a sustained-release formulation by its combination of fast absorbed phenolic compounds and slowly metabolized procyanidins. R


Benefits Of Pine Bark

1. Combats Depression

Pycnogenol may have beneficial effects at combating depression. R

For example, in animal models with corticosterone-induced depression, pycnogenol was able to reduce behaviors from mild stress (by reducing glucocorticoid-induced increase of ROS in the brain). R

2. Reduces Allergies And Asthma

Pycnogenol can help with asthma severity (as it can inhibit expression of 5-Lipoxygenase(5-LOX) and leukotriene levels). R

For example, in a study with 76 asthma patients, pycnogenol supplementation (100mg/day; 50mg at 9 am and 9 pm) was able to reduce IgE levels, asthma scores, and the need to use inhalation corticosteroids. R

In 39 healthy male and female patients with allergic rhinitis from bee pollen, pycnogenol supplementation (50mg/day) was able to reduce eye and nasal allergy scores. R

In an animal model of allergic rhinitis, pycnogenol was able to reduce allergic markers (such as IL-4, IFN-γ, IL-10, TNF-alpha, and IL-1b) while decreasing mucus production. R

In animal models of allergic conjunctivitis, pycnogenol, similarly to the drug dexamethasone, could reduce mast cell count, TGF-β, and TNF-a levels. R

Studies have shown for seasonal allergies, the best results were found with subjects who took pycnogenol 7-8 weeks ahead of the allergy season. R

3. Improves Skin Quality


In the skin, pycnogenol (taken orally) acts to provide protection against photoaging and improve skin barrier function/extracellular matrix homeostasis. R

Pycnogenol (50mg tid orally) has shown to be similarly effective as other flavonoids (diosmin/hesperidin) at healing venous ulcers. R

Pycnogenol is a promising candidate for hyperpigmentation and photoaging/photodamaged skin from sun exposure. R

For example, in a 12 week study with 112 women that had photo-aged skin, pine bark extract supplementation (40-100mg/day) could significantly reduce pigmentation of age spots. R

In addition, pycnogenol can protect against Ultraviolet (UVB)-induced skin damage (via reduction of Ki-67/8-OHdG/VEGF, p38/MSK1/CREB/MITF, and ROS) and may act as a viable sunscreen alternative. R R R

Pycnogenol can also improve skin elasticity and hydration - in 12 week study with 20 postmenopausal women, Pycnogenol supplementation increased 2 genes related to improved skin aging - Hyaluronic Acid Synthase-1 (HAS-1) and Collagen Type I (COL1A1). R

In a 12 week study with moderate/severe plaque psoriasis patients (age range 30-45), pycnogenol (150 mg/day; 50mg tid) supplementation could improve skin moisture, reduces severity score (erythema, induration, desquamation), and lower overall oxidative stress in the skin. R

In diabetic animal models, pycnogenol can accelerate wound healing. R

4. Ameliorates Diabetes And Metabolic Syndrome

In multiple studies, pycnogenol has shown to be very effective at combating diabetes and other related metabolic syndromes. R

Pynogenol is effective in reducing diabetic-related complications in a type I model of diabetes and might be beneficial for the treatment of diabetic patients. R

In red blood cells, procynadins in pine bark are able to activate Glucose Transporter 1 (or GLUT1), a major glucose transporter. R

Pine bark extract can lower fasting glucose and HbA1c levels without affecting insulin levels. R

Pycnogenol performs similarly effective as the common diabetes drug Metformin: improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, Glucose Transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of hearts; although they do not seem to have any synergistic effects. R

Pycnogenol may protect the heart of diabetic patients. R

Pynogenol helps reduce oxidative stress on the liver from high glucose levels, which may make it a useful treatment in Type 2 Diabetes (T2D). R

Pycnogenol’s effects on oxidative stress in models of diabetes may be greater when combined with astaxanthin. R

For example, in Tsumura Suzuki Obese Diabetes (TSOD) mice, a model of multi-factorial, hereditary, obese type II diabetes, pycnogenol supplementation was able to improve metabolic markers (stopped increase in visceral/subcutaneous fat, improved insulin resistance, abnormal glucose/lipid metabolism and hypertension, increased adiponectin and decreased TNF-a). R

5. Improves Cognition


Pycnogenol has shown in multiple studies to improve cognition.

In an 8 week study with 53 healthy students, Pycnogenol supplementation improved sustained attention, memory, executive functions and mood ratings. R

In 87 healthy subjects with minimal cognitive dysfunction, pycogenol (150mg/day) can significantly increase cognitive performance, due to it’s ability to reduce oxidative stress levels. R

In healthy subjects (55-70) with high oxidative stress, 12 months of pycnogenol (100mg/day) supplementation could improve all tested cognitive scores. R

In combination with Bacopa Moneri, pycnogenol (100mg/day) decreased oxidative stress, improved cognitive scores and improved test scores indicating “delayed age associated cognitive decline”. R

In a 12 week trial with 60 participants, Pycnogenol subjects showed a small but significant improvement as well as improved mood parameters (alertness, anxiety, contentedness). R

6. Protects Against TBI And Concussion-Induced Problems

Pycnogenol can significantly provide protection to the brain (specifically cortex and hippocampus) during a Traumatic Brain Injury (TBI) by quenching oxidative stress. R R

Pycnogenol can cross the Blood-Brain Barrier (BBB) as well as other cell membranes. R

In the hippocampus, pycnogenol can preserve synaptic function after Controlled Cortical Impact (CCI) injury. R R

After concussion, pycnogenol has been reported to reduced mental fatigue and sleep problems. R

7. Reduces Neuroinflammation

Pycnogenol can protect the brain against hypoxia (by reducing cell viability loss, LDH leakage, oxidative stress, inflammatory cytokines accumulation and cell apoptosis). R

Pycnogenol also protects against lipopolysaccahride (LPS)-induced neuroinflammation of microglia (by inhibiting PLIN2, TNF-α, IL-6, IL-1β, ICAM-1, NF-kB, and AP-1). R

8. May Combat Parkinson’s

Pycnogenol may combat some markers of Parkinson’s Disease (PD). R

For example, in animal models of PD, pycnogenol could protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons (by quenching free radicals). R

More specifically, in models of PD, pycnogenol reduces astrocyte and microglia from inflammation, while protecting dopaminergic neurons. R

In models of rotenone poisoning to induce PD, pycnogenol can protect against neurotoxicity by downregulation of NF-κB/iNOS signaling pathway. R

In animal models of PD, Pycnogenol (20 mg/kg) for 15 days decreased number of Dopaminergic D2 Receptors (DRD2) and increased levels of Dopamine (DA) and its metabolites. R

9. Improves Attention And Fights ADHD

Pycnogenol may be effective for reducing Attention-Deficit Disorder (ADD) and Attention-Deficit Hyperactivity Disorder (ADHD). R

For example, in a trial with 61 children with ADHD, pycnogenol (1 mg/kg/day) caused significant reduction of hyperactivity, improved attention and visual–motoric coordination and concentration, although these scores relapsed after 1 month of discontinuation. R

Pycnogenol is currently in a phase III randomized controlled trial with 144 pediatric ADHD and ADD patients to see how effective it is for attention. R

10. Helps Treat Arthritis

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Pycnogenol can help treat Mild Osteoarthritis (OA) in stage 1 and 2, as it can improve daily pain, stiffness, and physical function. R

For example, in a 3 month double-blind, placebo-controlled study with 77 patients with OA, pycnogenol supplementation (100mg/day) was able to: R

  • Reduce test (pain/stiffness) scores (56% vs 9.6% of placebo)

  • Increase physical performance scores (walking distance on the treadmill)

  • Decrease the need for NSAIDs/anti-inflammatory drugs

  • Decrease overall gastrointestinal complications (63% vs 3% of placebo)

  • Decrease foot swelling/edema (79% vs 1% of placebo)

In 35 patients with severe osteoarthritis, pycnogenol supplementation (200mg/day) could effectively get the polyphenols into the joints. R

In another study with 33 patients with severe osteoarthritis, pycnogenol supplementation (200mg/day; aka 100mg bid) could effectively downregulate the gene expression of various cartilage degradation/proinflammatory markers (MMP3, MMP13 and IL-1b) as well as reduce protein concentrations of ADAMTS-5. R

Pycnogenol may also help arthritis patients get off NSAIDs and can help with unwanted side effects of NSAIDs. R

Pycnogenol may also help with gout-related arthritis as pycnogenol (in vitro) can inhibit the up-regulation of COX-2, IL-8 and iNOS in cartilage (as well as inhibit other inflammatory pathways such as NF-κB, SAPK/JNK, ERK1/2, and p38 MAPK). R

In animal models, pycnogenol has shown to improve collagen-induced arthritis by inhibiting both acute and chronic inflammatory reactions. R

11. Improves Metabolism And Weight Loss

Pycnogenol can stimulate weight loss via lipolysis. R

For example, in a 6 month study with 66 subjects with metabolic syndrome, men’s and women’s waist circumference were able to be reduced on average by 7.9cm and 7.3cm respectively. R

Pycnogenol also helps with reducing oxidative stress on fat cells (via ↓NOX4, G6PDH, PPAR-γ, C/EBP-α, aP2 and ↑Cu/Zn-SOD, Mn-SOD, GPx, GR). R

Pycnogenol can also enhance the browning of fat (via UCP1 and PKA). R R

For example, in animal models the combination of L-Ornithine + pycnogenol was able to increase Proopiomelanocortin (POMC) levels in the hypothalamus and Uncoupling Protein 1 (UCP1) in brown adipose tissue over 9 weeks. R

12. Improves Liver Function

Pycnogenol can protect against oxidative stress on the liver by upregulating antioxidant genes (GSH, CAT, SOD, and GST) and inhibiting lipid peroxidation (via PLIN/AP-1/PPRE). R R

For example, in Apolipoprotein E (ApoE)-deficient male mice, pycnogenol protects against the occurrence and development of hepatic steatosis and may provide a new prophylactic approach for Nonalcoholic Fatty Liver Disease (NAFLD). R

In animal models, pycnogenol has shown to protect against Methionine-Choline Deficient (MCD) diet causing Non-Alcoholic Steatohepatitis (NASH). R

In animal models, chronic pycnogenol can reduce diencephalic mRNA expression of Heat-Shock Proteins (HSP)-70 and -90 and plasma Aminotransferase (AAT), thus preventing liver damage. R

Pycnogenol protects against cirrhosis on the liver from chronic Hepatitis C Virus (HCV) infection. R

13. Improves Vascular Function

Pycnogenol may also help to prevent thrombosis from sitting for long periods of time (such as on flights). R R

For example, in a 12 month study, pycnogenol supplementation was shown to be as effective as compression stockings in preventing thrombosis (pycn improved micro-circulation → increased pO2 and decreased pCO2). R

In other studies, pycnogenol (100mg/day) has shown to be similarly effective as Aspirin and Antistax at preventing thrombotic events and edema. R

Pycnogenol is also able to reduce high blood pressure (systolic/diastolic BPs were -3.22 mmHg/-3.11 mmHg respectively). R

This may be because pycnogenol can activate Endothelial Nitric Oxide Synthase (eNOS), while reducing overall vascular oxidative stress. R R

Pycnogenol has protective effects on lipid markers. R R

For example, in stage 1 hypertensive patients, pycnogenol supplementation (150mg/day) for 5 weeks was able to improve lipid markers as well as increase HDL-c. R

Pycnogenol has protective effects on preventing atherosclerosis (acts via ↓TLR4/NF-kB and TNF-a/IKba/p38MAPK). R R R

The combination of pycnogenol, honey, aloe vera, and papaya extract has also shown to have protective effects against atherosclerosis in human cell cultures. R

Overall, pycnogenol reduces oxidative stress on the vascular system (homocysteine and CRP levels decreased sharply by 43% and 60%, respectively @100mg/day for 8 weeks). R R

For example, in 23 patients with Coronary Artery Disease (CAD), pycnogenol supplementation (200mg/day) for 8 weeks was able to improve endothelial function by reducing oxidative stress. R

Also, in combination with Gotu Kola (Centella Asiatica), pycnogenol can help reduce factors of carotid-femoral plaques in asymptomatic subjects with increased oxidative stress and risk factors (mild hypertension, hypercholesterolemia) as well as symptoms of atherosclerosis. R R R

In cell cultures, pycnogenol can suppress Oxidized Low-Density Lipoprotein (ox-LDL)-induced lipid accumulation (induces NRF2 in LDL to prevent oxidation). R R

In combination with Melatonin, pycnogenol can normalize COX-2 and iNOS expression, and thus protect against abnormal vascular events. R R

Pycnogenol may also help protect against oxidative stress from diabetic cardiomyopathy. R

For example, in those with diabetic cardiomyopathy, pycnogenol (10-60mg/day) has shown to reduce a Long QT (not fully correct it) by reducing high blood glucose levels and cadiac edema. R

Pycnogenol (in animal models) has also shown to protect the heart in hypoxia - when deprived of oxygen or glucose (acting on TBARS, LDH, SOD, CAT, GSH, and GPX). R

The combination of CoQ10 + Pycnogenol (called PycnoQ10) has shown to reduce systolic/diastolic pressure, heart rate and respiratory rate in those with heart failure. R

Pycnogenol may also be useful for the treatment of varicose veins. R

For example, in a study of 133 women post labor, pycnogenol supplementation (100mg/day) was able to reduce spider veins as well as cramps and other minor symptoms. R

14. Combats Inflammation And Immunity

Pycnogenol is strong at combating inflammation.

For example, in a study with 78 smokers, pycnogenol supplementation (50mg/day) could significantly lowers reactive oxygen species as compared to a placebo-treated equivalent control group. R

Pycnogenol consumption can decrease the level of C-Reactive Protein (CRP), a positive acute-phase protein, whose plasma concentration increases in response to inflammation. R

Pycnogenol may also help with sepsis-induced DNA damage. R

Pycnogenol may also help improve the immune system.

Pycnogenol can reduce the size of lymph nodes. R

Pycnogenol may also be able to reduce symptoms of immune dysfunction in those who are malnourished (ameliorates premature death by restoring immune dysfunction, such as increasing lymphocyte proliferation and regulation of cytokine release from helper T cells). R

In a pilot study, pycnogenol has shown to reduce occurrence and symptoms of the common cold. R

15. May Act As A Birth Control And Menstrual Cycle Adjunct

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Pycnogenol may be an useful adjunct to birth control and menstrual symptoms (such as dysmenorrhea). R

Pycnogenol (100mg/day) can reduce effectively decrease pain and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene. R

16. Has Antioxidant Effects

Pycnogenol has potent antioxidant effects. R R R

For example, in muscle cells, pycnogenol can prevent cell death from hydrogen peroxide-induced oxidative stress. R

The antioxidant properties of pine bark extract have been compared to be similar to green tea’s Polymeric tannins and monomeric flavonoids, such as catechin and epicatechin. R

Pycnogenol’s antioxidant activities can be increased by Ginkgo Biloba (EGb 761). R

17. Helps Lung Disease

Pine bark may help combat progression of Chronic Obstructive Pulmonary Disorder (COPD). R

For example, pine bark is able to protect the lungs from cigarette smoke-induced fibrosis (reduces TGFb1/SMAD2/3). R

Pine bark is also effective in treating COPD by inhibiting the expression of Myeloperoxidase (MPO) and Matrix Metalloproteinases-9 (MMP9) in the lungs. R

Overall, pycnogenol can reduce inflammation of the lungs by inhibiting NF-kB-mediated inflammatory responses (thus reducing TNF-α, IL-6, IL-1β and MIP-2). R

18. Improves Bone Density

Pycnogenol has a protective effect on bones. R R

For example, in animal models with ovariectomies, pycnogenol can prevent Bone Mineral Density (BMD) loss (after 9 weeks). R R

Pycnogenol may also be useful for treating periodontitis, through its ability to fight Porphyromonas gingivalis (P. gingivalis) and suppress osteoclastogenesis. R

19. May Improve Sleep

Pine bark may make barbiturates stronger for sleep. R

For example, by acting on the GABAergic system, pine bark can decreased the latency of sleep (p<0.05) and significantly increased duration of sleep (p<0.05) induced by pentobarbital, without being neurotoxic. R

This effect may be explained as quercetin (found in pine bark), increases GABAA activity. R

20. Helps With Sexual Dysfunction And Sperm Production

Supplementation of pycnogenol with amino acids for 1 month has shown to improve Erectile Dysfunction (ED). R

For example, in comparison to the herb Saw Palmetto, pycnogenol + L-Arginine supplementation was able to improve Sexual Dysfunction (SDys) in elderly patients (by increasing Nitric Oxide vis eNOS). R

This combination (Arginine + pycnogenol) has also shown to improve men’s virility and fertility. R R

Pycnogenol has multiple beneficial effects on sperm. R

In men, supplementation with Pycnogenol for 1 month has shown to improve sperm quality (increases volume and concentration, motility, vitality and morphology) when combined with L-Arginine, L-Citruline and roburins. R

Pycnogenol can also protect against oxidative stress on sperm. R R

21. Acts On Bladder-Related Diseases

Pycnogenol may help with Benign Prostatic Hyperthrophy (BPH), as BPH symptoms like emptying, frequency, intermittency, urgency, weak flow, straining, nocturia, were all significantly improved with Pycnogenol (150 mg/day) after 60 days. R

In combination with L-Arginine, pycnogenol may help elderly patients with Lower Urinary Tract Symptoms (LUTS). R

22. Improves Kidney Function

Pycnogenol may improve kidney function in those with metabolic syndromes, by reducing blood pressure, fighting inflammation (significantly lowers CRP) and increasing blood flow. R R R

Pycnogenol can also protect the kidneys against oxidative stress. R

For example, pycnogenol has shown to protect kidney tubules from high-glucose induced death (via Bcl2/Bax and NO/COX2), thus preventing diabetic nephropathy. R

Pycnogenol may also be useful for reducing the occurrence of Acute Kidney Injuries (AKI). R

In combination with Spirulina, pycnogenol supplementation can significantly increase antioxidant levels in the kidneys. R

23. May Help With Some Post Surgery Complications

Pycnogenol may help with some post-surgery complications. R R

For example, pycnogenol can blunt some of the damaging effects of ionizing radiation used for colon anastomotic healing. R

In animal models, pycnogenol can prevent surgery-related adhesions. R

24. Has Antimicrobial Effects


Pycnogenol has antiviral effects against Hepatitis C Virus (HCV) infection replication. R R

Pine Bark has insecticidal effects against Teladorsagia circumcincta and Trichostrongylus colubriformis. R

25. Combats Cancer Mechanisms

Pine bark and pycnogenol act on multiple mechanisms of cancers:

  • Brain Cancer R

  • Breast Cancer R R R

  • Colon Cancer R

  • Fibrosarcoma R R

  • Mucoepidermoid carcinoma R

  • Oral Cancer R

  • Skin Cancer R

Some molds, such as Aspergillus carbonariusAspergillus niger and Mucor wutungkiao are able to metabolize the polyphenols from pinebark extract to make/enhance the antioxidant and antitumor activities of those polyphenols. R

26. Improves Vision

Pycnogenol can protect the eye against oxidative stress-induced optic nerve damage. R

Pycnogenol also reduces glycation of proteins and may help prevent cataract buildup. R R

Pycnogenol can reduce the recurrence Retinal Vein Thrombosis (RVT). R

27. Protects The Gut

Pycnogenol seems to have protective effects on the gut.

For example, 77 healthy individuals with symptoms of Irritable Bowel Syndrome (IBS), pycnogenol (150mg/day) had a significant, protective and preventive activity on IBS symptoms, in comparison to IBS drugs such as Papaverine and Buscopan. R

In children with Crohn’s Disease (CD), pycnogenol (2 mg/kg) was able to reduce inflammatory scores of Calprotectin, CRP, TAC, SOD, and GPX. R

When combined with fruit juices (such as pineapple juice), pycnogenol may help with digestion and improve inflammatory markers such as IL-8. R R R

28. May Help Menopause Transition

Pycnogenol (30-200mg/day) can decrease climacteric symptoms (usually around 4 and 12 weeks) when transitioning into menopause, such as vasomotoric problems, insomnia, and quality of life. R R R

29. May Help With Behçet Syndrome

Pycnogenol may help with Behçet Syndrome (BS). R

For example, in a 4 week trial subjects receiving Pycnogenol (150mg/day as 50mg/tid) reported a significant decrease in symptoms, such as burning/pain due to dryness and ulcerations (P<0.05). as well as decreased Erythrocyte Sedimentation Rate (ESR) and leucocytosis. R

30. Reduces Hearing Loss And Tinnitus

Pycnogenol can protect the auditory system from oxidative stress (cisplatin ototoxicity) and may reduce hearing loss. R

Pycnogenol (150 mg/day) can also relieve tinnitus symptoms by improving cochlear blood. R

31. Protects The Pancreas

Pycnogenol (40-100 μg/mL) can protect pancreatic beta cells from cell death by regulating calcium homeostasis. R

Pycnogenol can also help improve impairment on insulin secretion from pancreatic cells. R

32. Reduces Muscle Wasting

By helping the body produce Heat-Shock Protein Beta-1 (HSPB1, a protector of muscle necrosis), pycnogenol may help repair injured structures in muscles, thus making it a promising candidate for sarcopenia. R

33. Acts On The Oral Microbiome

Pine bark extract may be useful as an alternative to sodium ascorbate for metal brackets bonded with composite resin to human enamel after bleaching with hydrogen peroxide (very little difference between the two). R

In combination with Vitamin E, pycnogenol may be effective for treating oral mucositis. R

As a chewing gum, pine bark can change the oral microbiome, thus reducing tongue coating and exhaled hydrogen sulfide. R

34. Reduces Hemmorhoid Occurance

Pycnogenol, both in oral and in topical form, is effective for controlling acute hemorrhoidal attacks and helps avoid bleedings. R

For example, pycnogenol (150 mg/day for 6 months) can help reduce postpartum hemmorhoids and symptoms in the months after pregnancy. R

35. Improves Exercise Performance


Pycnogenol can significantly increase exercise performance. R

For example, in a 2 part study:

  1. Part 1: over 8 weeks with 74 subjects (males and females), pycnogenol (100mg/day) could improve running time, number of sit-ups and push-ups, and reduce oxidative stress R

  2. Part 2: athletes training for a 100-minute triathlon supplementation of pycnogenol (150mg/day) could reduce total triathlon time by an average of 10.8 minutes, with a significant decrease in cramps and running and post-running pain, thus increasing metabolic recovery R

My Experience With Pine Bark

Within the first 30 minutes of taking pycnogenol I usually get an extreme nootropic boost - ability to focus, vision, etc. as well as my ability/capacity to exercise is A LOT higher, although it seems to lower my blood pressure significantly later on in the day, so I don’t take it very often anymore or I’ll take it after lunch.

I find it nice to combine with French Oak Wood for increased overall energy levels (see more synergies below).

Where To Get Pine Bark


This is the brand I’ve been using with great results (see My Experience).


Multiple studies have shown efficacy of pycnogenol from 50-300mg/day. R

The upper limit of French Maritime Pine Bark extract is suggested to be 100 mg/kg/day. R

Possible Synergies:

Caveats Of Pine Bark

Pycnogenol is generally well tolerated with minimal side effects (mild and transient gastrointestinal troubles, dizziness, nausea, headache, and skin sensation) in human studies. R

Why Does Pycnogenol Have A Sustained Effect?

Essentially pycnogenol (and metabolites) stays the the body for a while and some of it is broken down by the gut biome as well: R

  • Components of Pycnogenol such as catechin, ferulic acid, and caffeic acid are found rapidly in plasma after 30 min, with peak concentrations between 1 and 4 h, taxifolin appears later in plasma with a maximum at 8 h. R

  • Catechin, taxifolin, and ferulic acid are present in plasma (even after 14 h) while ferulic acid is found in urine up to 25 h after ingestion. R

  • The active metabolite M1, a valerolactone, appears in plasma not before 6 h with peak concentrations at 10 h. M1 concentrations are still present after 14 h. R

  • In the first step of metabolization, the monomers catechin or epicatechin are split from the oligomers, and subsequently, bacterial activity transforms the monomers into derivatives of δ-valerolactone, the metabolites M1 and M2. R

  • As all of these constituents of Pycnogenol and its metabolites exhibit anti-inflammatory actions, the progressing appearance of the diverse active substances provides a long-lasting pain relief, so that patients feel less pain, also during the night. R

Mechanism Of Action



  • Increases Adiponectin R

  • Increases ADP-ribose R

  • Increases APOA-1 R

  • Increases ATGL R

  • Increases BAK R

  • Increases BCLAF R

  • Increases BCL2 R

  • Increases Calprotectin R

  • Increases CAMP R

  • Increases Caspase-3 R R

  • Increases COL1A1 R

  • Increases COX3 R

  • Increases DA R

  • Increases Drebrin R

  • Increases DUSP1 R

  • Increases eNOS R

  • Increases ER-beta R

  • Increases GLUT-4 R R

  • Increases GPX R R

  • Increases GR R

  • Increases HAS-1 R

  • Increases HDL-C R

  • Increases HSL R R

  • Increases HSPB1 R

  • Increases LDH R

  • Increases MAPK8 R

  • Increases NRF2 R

  • Increases NO R

  • Increases PKA R

  • Increases POMC R

  • Increases PSD-95 R

  • Increases SAP-97 R

  • Increases SOD R R

  • Increases Synaptophysin R

  • Increases Synapsin-I R

  • Increases TAC R

  • Increases UCP1 R R

  • Reduces ACH R

  • Reduces ADAMTS-5 R

  • Reduces AKT3 R

  • Reduces AP-1 R

  • Reduces AP-2 R R

  • Reduces APOB-100 R

  • Reduces Bax R

  • Reduces COX-2 R R R R

  • Reduces CREB R

  • Reduces CRP R R R

  • Reduces CTNNA1 R

  • Reduces C/EBP-alpha R

  • Reduces DPYD/Cr R

  • Reduces Endothelin-1 R

  • Reduces ERK1/2 R

  • Reduces ESR R

  • Reduces FAS R

  • Reduces FN1 R

  • Reduces FOXA3 R

  • Reduces Glucose R

  • Reduces G6PDH R

  • Reduces HBA1C R

  • Reduces Homocysteine R

  • Reduces ICAM-1 R

  • Reduces IFN-gamma R

  • Reduces IgE R

  • Reduces IL-1b R R R R

  • Reduces IL-4 R R

  • Reduces IL-5 R

  • Reduces IL-6 R R

  • Reduces IL-8 R R

  • Reduces IL-9 R

  • Reduces IL-10 (TH2 response) R

  • Reduces IL-13 R

  • Reduces iNOS R R R

  • Reduces ITGB1 R

  • Reduces JAK1 R

  • Reduces JNK R

  • Reduces Ki-67 R

  • Reduces KRAS R

  • Reduces LAMC1 R

  • Reduces LDH R

  • Reduces LDL-C R

  • Reduces Leukocytes R

  • Reduces MAPK R

  • Reduces MIP-2 R

  • Reduces MMP-1 R

  • Reduces MMP-2 R

  • Reduces MMP-3 R

  • Reduces MMP-9 R R R

  • Reduces MMP-13 R

  • Reduces MPO R R

  • Reduces MSK1 R

  • Reduces MITF R

  • Reduces MUC5AC R

  • Reduces NF-kB R R R R R

  • Reduces NOX4 R

  • Reduces NTX/Cr R

  • Reduces ONOO R

  • Reduces OX-LDL R

  • Reduces PDE3B R

  • Reduces Perilipin A R

  • Reduces PINP R

  • Reduces PIK3CB R

  • Reduces PIK3RI R

  • Reduces PLA2 R

  • Reduces PLIN-1 R R

  • Reduces PLIN-2 R

  • Reduces PPAR-gamma R

  • Reduces p38 R R

  • Reduces RHOA R

  • Reduces ROS R R R

  • Reduces SAPK R

  • Reduces SERCA1 R

  • Reduces SOCS7 R

  • Reduces SMAD2 R

  • Reduces SMAD3 R

  • Reduces SPDEF R

  • Reduces STAT6 R

  • Reduces TLR4 R R

  • Reduces TGF-b1 R R

  • Reduces TNF-alpha R R R R

  • Reduces VEGF R

  • Reduces 5-LOX R

  • Reduces 8-oxy-DG R R


  • Pyc can reduce oxidative stress in the striatum and thus protect dopaminergic neurons (D2) and dopamine release. R

  • Pycnogenol increases the expression of estrogen receptor β (ERβ) about 2.8-fold for 28 days in vitro bone cultures. R

  • Pyc can reduce oxidative stress and inflammatory markers in the gut, such as overproduction of IL-8, nitric oxide (NO) and reactive oxygen species (ROS). R

  • PYC inhibited the up-regulation of COX-2, and IL-8 in both articular chondrocytes and synovial fibroblasts. PYC attenuated MSU crystal induced iNOS gene expression and NO production in chondrocytes. Activation of NF-κB and SAPK/JNK, ERK1/2 and p38 MAP kinases by MSU crystals in articular chondrocytes and synovial fibroblasts in vitro was attenuated by treatment with PYC. R

  • In vitro, pycnogenol has shown to reduce the number of total inflammatory cells and levels of IL-4, IL-5, IL-9, and IL-13 in lung cells, as well as inhibited IL-13 (and IL-13 induced Acetylcholine) secretion from the Th2 cells, thereby causing a reduction in expression of the signaling molecules in JAK/STAT6 pathway in airway epithelial cells…PYC suppressed OVA-induced expression of FOXA3, SPDEF, and Muc5ac in lung. R

  • Pyc supplementation led to increased T and B cell response against mitogens and recovery of an abnormal shift of cytokine pattern designated by the decreased secretion of Th1 cytokine and increased secretion of Th2 cytokine. R

  • PYC was shown to enhance GLUT4-mediated glucose uptake via phosphoinositide 3-kinase-dependent tyrosine kinase pathways involving PKB. PYC also inhibits NF-κB and activator protein-1 (AP-1), and prevents the degradation of IκBα. More specifically, Choi and colleagues found that PYC inhibits the expression and secretion of TNF-α and IL-6, thereby reducing calcium uptake and suppressing NF-κB activation. Thus, PYC may improve T2DM therapy by enhancing GLUT4-mediated glucose uptake, inhibiting inflammatory genes such as IL6 and TNF-α, and also by inhibiting the SOCS pathways. R

  • Pycnogenol inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). R