Pycnogenol

• Potent antioxidant activity
• Cardiovascular health support
• Anti-inflammatory effects
• Cognitive function enhancement

• Skin health improvement
• Blood glucose regulation
• Vascular function support
• Joint health maintenance
• Immune system modulation

Pycnogenol (PYC), a standardized extract from the bark of the French maritime pine (Pinus pinaster), exerts its biological effects through multiple mechanisms. Its complex composition of procyanidins, bioflavonoids, and phenolic acids contributes to its diverse pharmacological activities. The primary mechanism underlying PYC’s effects is its potent antioxidant activity. PYC components directly neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS), including superoxide, hydroxyl, and peroxyl radicals.

This direct scavenging activity is complemented by PYC’s ability to recycle and extend the activity of other antioxidants such as vitamins C and E. Beyond direct antioxidant effects, PYC enhances endogenous antioxidant defenses by increasing the activity and expression of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. This occurs primarily through activation of the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, a master regulator of cellular antioxidant responses. PYC demonstrates significant anti-inflammatory properties through multiple pathways.

It inhibits the activity of pro-inflammatory enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX), reducing the production of inflammatory mediators like prostaglandins and leukotrienes. PYC also suppresses the activation of nuclear factor-kappa B (NF-κB), a key transcription factor that regulates the expression of numerous pro-inflammatory genes. This results in decreased production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6). Additionally, PYC inhibits the adhesion and migration of inflammatory cells by reducing the expression of adhesion molecules such as ICAM-1 and VCAM-1.

In vascular health, PYC enhances endothelial function by increasing the production of nitric oxide (NO), a potent vasodilator. This occurs through multiple mechanisms, including increased expression and activity of endothelial nitric oxide synthase (eNOS), protection of NO from degradation by free radicals, and inhibition of enzymes that break down NO. PYC also improves vascular tone and elasticity by protecting and potentially regenerating collagen and elastin in blood vessel walls. It inhibits matrix metalloproteinases (MMPs) that degrade these structural proteins and stimulates their synthesis.

PYC exhibits significant effects on platelet function, reducing platelet aggregation and adhesion through inhibition of thromboxane A2 production and modulation of platelet surface receptors. This contributes to improved microcirculation and reduced risk of thrombosis. In metabolic health, PYC enhances glucose metabolism by improving insulin sensitivity, increasing glucose uptake in tissues, and protecting pancreatic beta cells from oxidative damage. It inhibits alpha-glucosidase and alpha-amylase, enzymes involved in carbohydrate digestion, potentially reducing postprandial glucose spikes.

PYC also modulates lipid metabolism, reducing LDL oxidation, increasing HDL levels, and inhibiting lipid peroxidation. For cognitive function, PYC crosses the blood-brain barrier and exerts neuroprotective effects through multiple mechanisms. It reduces oxidative stress in neural tissues, protects neurons from excitotoxicity, and improves cerebral blood flow and microcirculation. PYC may also modulate neurotransmitter systems, particularly dopamine and glutamate, and has been shown to inhibit acetylcholinesterase, potentially enhancing cholinergic neurotransmission.

At the molecular level, PYC influences gene expression through epigenetic mechanisms, including modulation of microRNA expression and histone modifications. It affects cell signaling pathways involved in cell survival, proliferation, and differentiation, including MAPK, PI3K/Akt, and Wnt signaling. PYC also demonstrates antimicrobial properties, inhibiting the growth of various bacteria and viruses, potentially through disruption of microbial membranes and interference with viral attachment to host cells. These diverse mechanisms work synergistically to produce PYC’s wide range of health benefits, from cardiovascular and cognitive support to anti-aging and immune-modulating effects.

The optimal dosage of Pycnogenol (PYC) varies depending on the specific health condition being addressed. Based on clinical studies, the standard adult dosage range is typically 50-200 mg per day. For general health maintenance and antioxidant support, 50-100 mg daily is commonly recommended. Higher doses (150-200 mg daily) are typically used for specific therapeutic purposes.

PYC is generally well-absorbed, with peak plasma levels occurring approximately 30 minutes to 4 hours after oral administration. The biological effects of PYC are dose-dependent, with higher doses generally producing more pronounced effects. However, even lower doses (25-50 mg daily) have demonstrated measurable biological activity in some studies. For optimal absorption and effectiveness, PYC is typically taken with meals, and the daily dose is often divided into two administrations (morning and evening) when exceeding 100 mg per day.

The onset of effects varies by condition, with some acute effects (such as improved blood flow) observable within hours, while other benefits (such as improved cognitive function or joint health) may require consistent supplementation for 4-12 weeks.

Pycnogenol (PYC) demonstrates complex absorption kinetics due to its heterogeneous composition of procyanidins, bioflavonoids, and phenolic acids. The bioavailability of PYC components varies significantly based on their molecular size and structure. Smaller monomeric catechins and phenolic acids (such as caffeic acid, ferulic acid, and taxifolin) are readily absorbed in the small intestine, with absorption rates estimated between 40-90%. These compounds can be detected in plasma within 30 minutes after oral administration, with peak plasma concentrations typically occurring between 1-2 hours post-ingestion.

Larger oligomeric and polymeric procyanidins (which constitute approximately 65-75% of PYC) have lower direct absorption rates due to their molecular size. However, these compounds undergo partial breakdown in the gastrointestinal tract, releasing smaller, more absorbable metabolites. Additionally, unabsorbed procyanidins reach the colon where they are metabolized by gut microbiota into various phenolic acids and other metabolites that can then be absorbed. This results in a biphasic absorption pattern, with a second peak of metabolites appearing in plasma 4-8 hours after ingestion.

After absorption, PYC components undergo extensive phase II metabolism in the intestinal epithelium and liver, primarily through glucuronidation, sulfation, and methylation. These conjugated forms represent the majority of circulating PYC metabolites in plasma. Despite this extensive metabolism, evidence suggests that many of these metabolites retain significant biological activity. The plasma elimination half-life of various PYC metabolites ranges from approximately 3-7 hours, with some metabolites detectable in plasma for up to 24 hours after a single dose.

This relatively long presence in circulation contributes to PYC’s sustained biological effects. Studies have demonstrated that certain PYC metabolites can cross the blood-brain barrier and accumulate in various tissues, including the brain, heart, and skin, extending their potential therapeutic effects beyond their plasma half-life. Excretion occurs primarily through the urine, with approximately 40-60% of the ingested dose recovered as metabolites within 24 hours. A smaller portion is excreted via the biliary route into feces.

Taking PYC with meals containing some fat enhances absorption by stimulating bile release and improving the solubility of certain components, Dividing the daily dose (particularly doses exceeding 100 mg) into morning and evening administrations may provide more consistent plasma levels of active metabolites, Liposomal formulations significantly improve bioavailability by enhancing membrane permeability and providing protection from digestive enzymes, Phytosome complexes (phospholipid-bound PYC) have demonstrated up to 2-3 times greater bioavailability compared to standard formulations, Micronized forms with reduced particle size increase the surface area available for absorption, Enteric-coated formulations protect PYC components from degradation in the stomach’s acidic environment, Co-administration with vitamin C may enhance the absorption and biological activity of certain PYC components through synergistic antioxidant recycling, Sustained-release formulations can provide more consistent plasma levels over time, Consuming PYC with foods rich in prebiotics may enhance colonic metabolism of larger procyanidins by beneficial gut bacteria, Avoiding simultaneous consumption of foods high in iron or calcium, which may form complexes with certain PYC components and reduce absorption

For optimal absorption and effectiveness, Pycnogenol supplementation should follow specific timing considerations. Taking PYC with meals, particularly those containing some fat, significantly enhances absorption by stimulating bile release and improving the solubility of certain components. Morning administration is often recommended to align with the body’s natural circadian rhythms and to potentially provide antioxidant protection throughout the day. However, for specific conditions like insomnia or nocturnal leg cramps, evening administration may be more beneficial.

For cardiovascular benefits, dividing the daily dose into morning and evening administrations (particularly for doses exceeding 100 mg) provides more consistent plasma levels of active metabolites throughout the 24-hour cycle. For cognitive enhancement, some studies suggest that morning administration may optimize mental performance during peak activity hours. When using PYC for blood glucose management, taking it approximately 15-30 minutes before meals may help optimize its effects on postprandial glucose levels. For individuals using PYC for skin health, consistent daily timing is more important than specific time of day, as benefits accumulate with regular use over weeks to months.

If taking multiple supplements, separate PYC from iron or calcium supplements by at least 2 hours, as these minerals may form complexes with certain PYC components and reduce absorption. For those using PYC for exercise performance or recovery, taking it approximately 60 minutes before exercise may help optimize blood flow and antioxidant protection during physical activity. When using PYC for jet lag or travel-related oxidative stress, taking it before, during, and after travel (particularly air travel) may provide optimal protection. Consistency in daily administration is generally more important than precise timing for most of PYC’s health benefits, as many effects build cumulatively with regular use over time.

• Mild gastrointestinal discomfort (occasional nausea, upset stomach) – uncommon
• Dizziness or headache – rare
• Mouth dryness – rare
• Mild skin reactions (itching, rash) – very rare
• Temporary changes in taste perception – very rare

• Known allergy or hypersensitivity to pine products or other plant extracts
• Caution advised in individuals with autoimmune disorders due to potential immune-modulating effects (theoretical concern, limited clinical evidence)
• Caution advised in individuals with bleeding disorders or those taking anticoagulant medications, due to potential mild antiplatelet effects
• Pregnancy and lactation (due to insufficient safety data, though no adverse effects have been reported)
• Scheduled surgery (discontinue at least 2 weeks before due to theoretical anticoagulant effects)

• Anticoagulant and antiplatelet medications (theoretical risk of enhanced effect due to PYC’s mild antiplatelet properties)
• Immunosuppressive medications (theoretical concern for immune modulation effects of PYC)
• Antihypertensive medications (potential additive effect, generally beneficial but may require monitoring)
• Antidiabetic medications (potential additive effect on blood glucose lowering, generally beneficial but may require monitoring)
• Medications metabolized by cytochrome P450 enzymes (limited evidence for mild inhibition of certain CYP enzymes)

Pycnogenol (PYC) has demonstrated an excellent safety profile in both preclinical toxicology studies and human clinical trials. Acute and chronic toxicity studies in animals have established a No Observed Adverse Effect Level (NOAEL) far exceeding typical human doses. The European Food Safety Authority (EFSA) has evaluated PYC and concluded that it is safe for human consumption at the doses typically used in supplements (50-450 mg per day). In human clinical trials, doses up to 450 mg daily have been used for periods of up to one year without significant adverse effects.

Most studies have used doses between 50-200 mg daily, which appear to be well-tolerated by the vast majority of participants. Based on the available evidence, a conservative upper limit for long-term daily consumption would be approximately 200-300 mg of PYC per day for most healthy adults. Higher doses (300-450 mg daily) have been used in specific clinical situations for limited periods without reported toxicity, but such doses should be used only under healthcare provider supervision. It’s worth noting that individual tolerance may vary, and some sensitive individuals may experience mild gastrointestinal discomfort at lower doses.

In such cases, starting with a lower dose (25-50 mg daily) and gradually increasing as tolerated is recommended. For children, doses have typically been calculated based on body weight (1-3 mg/kg daily), with total daily doses rarely exceeding 100 mg even in adolescents. Pregnant and lactating women should exercise caution due to limited safety data in these populations, though no specific adverse effects have been reported. Individuals with specific health conditions, particularly those with bleeding disorders or autoimmune conditions, should consult healthcare providers before using PYC, especially at higher doses.

As with any supplement, it’s advisable to start with lower doses and gradually increase if needed, monitoring for any adverse effects.

In the United States, Pycnogenol® is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. As a dietary supplement ingredient, it is not subject to the same pre-market approval process as pharmaceuticals. Manufacturers are responsible for ensuring their products are safe before marketing and that product labels are truthful and not misleading. Pycnogenol has self-affirmed Generally Recognized as Safe (GRAS) status for use in certain food applications, though this is distinct from FDA-affirmed GRAS status.

The FDA has not approved any specific health claims for Pycnogenol supplements. Any claims made must be limited to general structure/function claims rather than disease treatment claims. For example, manufacturers can claim that Pycnogenol ‘supports cardiovascular health’ but not that it ‘treats hypertension.’ The FDA has not established a specific upper limit for Pycnogenol consumption. The FDA has not issued any significant safety warnings or recalls specifically related to Pycnogenol, which reflects its generally good safety profile.

If Pycnogenol were to be developed as a pharmaceutical agent for specific therapeutic applications, it would require formal FDA approval through the standard drug approval process, including clinical trials demonstrating safety and efficacy.

Eu: In the European Union, Pycnogenol is regulated primarily as a food supplement under the Food Supplements Directive (2002/46/EC). The European Food Safety Authority (EFSA) has evaluated several health claims for Pycnogenol but has generally not approved specific claims due to their stringent evidence requirements. However, Pycnogenol is widely available throughout the EU as a food supplement. In some EU countries, Pycnogenol is also used in registered medical devices for specific applications, such as topical formulations for wound healing or vascular support. These applications undergo a different regulatory pathway than food supplements. The EU has not established a specific upper limit for Pycnogenol consumption. Some EU member states have implemented additional national regulations or recommendations regarding pine bark extracts, which would include Pycnogenol.

Canada: Health Canada regulates Pycnogenol as a Natural Health Product (NHP). It has been issued a Natural Product Number (NPN), indicating it has been assessed for safety, efficacy, and quality. Health Canada has approved certain claims for Pycnogenol, primarily related to its antioxidant properties and support for vascular health. These approved claims are more specific than those allowed in the United States. Health Canada has not established a specific upper limit for Pycnogenol consumption but generally recommends doses consistent with those used in approved clinical studies.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates Pycnogenol as a listed complementary medicine. Several Pycnogenol products are listed on the Australian Register of Therapeutic Goods (ARTG) as AUST L products, which are assessed for safety and quality but not efficacy. The TGA has not approved specific health claims for Pycnogenol beyond general health maintenance claims. The TGA has not established a specific upper limit for Pycnogenol consumption.

Japan: In Japan, Pycnogenol may be regulated as a Food with Function Claims (FFC) if scientific evidence supports its benefits. Manufacturers must notify the Consumer Affairs Agency before marketing such products. Some Pycnogenol products have received approval as FFCs for specific health functions. The Japanese Ministry of Health, Labour and Welfare has not established a specific upper limit for Pycnogenol consumption.

China: In China, Pycnogenol has been approved as a ‘blue hat’ health food ingredient by the National Medical Products Administration (formerly CFDA). This designation allows for specific health claims related to antioxidant activity and immune support. The registration process for health foods in China is rigorous and requires substantial safety and efficacy data.

High

Pycnogenol is relatively expensive compared to many other dietary supplements. The cost of authentic Pycnogenol® supplements varies significantly based on several factors, including brand reputation, dosage, and formulation. Typical retail prices for Pycnogenol range from $0.80 to $2.00 per day for an effective dose (50-100 mg). For higher therapeutic doses (150-200 mg daily), the cost increases proportionally to approximately $1.20-$4.00 per day.

Generic ‘pine bark extract’ products that do not contain authentic Pycnogenol® are available at lower prices (typically $0.30-$0.70 per day), but these may have different compositions and potencies, and lack the extensive research backing of the branded extract. The high cost of authentic Pycnogenol® is primarily due to several factors: the proprietary extraction and standardization process, the specific sourcing from French maritime pine trees grown in Les Landes de Gascogne forest, extensive quality control measures, and the substantial research investment by the patent holder (Horphag Research). Additionally, the relatively low yield of extract per tree contributes to the higher cost compared to many other botanical extracts.

The value proposition of Pycnogenol varies depending on the specific health application and individual factors. For cardiovascular health, Pycnogenol offers good value despite its higher cost, with multiple clinical studies demonstrating significant benefits for endothelial function, blood pressure, and circulation at doses of 100-200 mg daily. These effects are comparable or superior to some pharmaceutical interventions but with fewer side effects. For cognitive function, the value assessment is also favorable, with studies showing meaningful improvements in attention, memory, and mental performance at doses of 100-150 mg daily.

These cognitive benefits may be particularly valuable for aging individuals, students, and professionals with high cognitive demands. For joint health and osteoarthritis, Pycnogenol (100-150 mg daily) has demonstrated efficacy comparable to some conventional treatments but with better tolerability and fewer side effects. The reduced need for analgesic medications reported in some studies may offset part of Pycnogenol’s cost. For skin health, the combination of oral supplementation (50-100 mg daily) and topical application may provide unique benefits for skin elasticity, hydration, and photoprotection that are difficult to achieve with other interventions.

When comparing Pycnogenol to generic pine bark extracts, the higher cost of authentic Pycnogenol® may be justified by its standardized composition, extensive safety testing, and substantial clinical research backing. Generic extracts may contain similar compounds but in different proportions and without the same quality assurance. The long-term value of Pycnogenol supplementation may be enhanced by its preventive effects on age-related conditions, potentially reducing future healthcare costs. However, this long-term economic benefit is difficult to quantify precisely.

For cost-conscious consumers, starting with lower effective doses (50-75 mg daily) and gradually increasing if needed may optimize the cost-benefit ratio. Additionally, some of Pycnogenol’s benefits may be maintained with lower maintenance doses after an initial higher-dose period. Overall, while Pycnogenol is relatively expensive, its unique composition, extensive research backing, and demonstrated efficacy for multiple health conditions provide reasonable value for those specifically seeking its benefits, particularly when conventional approaches have been unsatisfactory or poorly tolerated.

Pycnogenol demonstrates good stability compared to many other polyphenol-rich extracts, with a typical shelf life of 3-5 years when stored properly in its original, sealed container. This relatively long shelf life is attributed to the natural stability of procyanidins and the standardized extraction process that preserves the integrity of the bioactive compounds. In standard supplement formulations (capsules, tablets), Pycnogenol typically maintains at least 90% of its procyanidin content for 36 months under recommended storage conditions. The stability may be further enhanced in products that include antioxidant stabilizers or specialized packaging.

Liquid formulations generally have shorter shelf lives (18-24 months) compared to solid formulations due to increased exposure to oxygen and potential microbial growth. Topical formulations containing Pycnogenol typically have shelf lives of 24-36 months, depending on the specific formulation and preservative system. Stability studies have shown that Pycnogenol’s procyanidin profile remains relatively consistent throughout its shelf life, with minimal changes in the distribution of monomers, dimers, and oligomers. This structural stability contributes to consistent biological activity over time.

Most commercial Pycnogenol products include a buffer period in their expiration dating, meaning they typically contain slightly more than the labeled amount at manufacture to ensure they meet potency specifications throughout the labeled shelf life.

Store Pycnogenol supplements in their original container with the lid tightly closed to protect from moisture and oxygen exposure. Keep in a cool, dry place away from direct sunlight and heat sources. Optimal temperature range is 59-77°F (15-25°C). Avoid storing in bathrooms or kitchen cabinets near sinks or appliances that generate heat and moisture.

Refrigeration is not necessary and may actually introduce moisture through condensation when the container is opened. However, refrigeration may extend shelf life in very hot or humid climates if the container remains sealed until it returns to room temperature before opening. Protect from light by keeping in the original opaque container, as extended exposure to light can accelerate degradation of some procyanidins. Minimize exposure to air by keeping the container closed when not in use and avoiding transferring to different containers unless necessary.

If transferring is required, use an airtight, opaque container. For blister-packed tablets or capsules, keep unused units in their original packaging until needed. For bulk powder formulations, use a clean, dry utensil to remove the product and reseal the container immediately after use. If the product changes color significantly (becoming much darker), develops an unusual odor, or shows visible signs of degradation, it may have lost potency and should be replaced.

For topical formulations containing Pycnogenol, ensure the container is properly closed after each use and avoid contamination by always using clean applicators.

Exposure to oxygen (oxidation is a primary degradation pathway for procyanidins), Exposure to light, particularly UV light, which accelerates oxidation reactions, High temperatures (above 86°F/30°C) significantly accelerate degradation, Alkaline conditions cause rapid degradation through oxidation and structural changes, High humidity, which can promote hydrolysis and microbial growth in some formulations, Presence of metal ions, particularly iron and copper, which catalyze oxidation reactions, Enzymatic degradation in some formulations due to polyphenol oxidase activity, Prolonged exposure to air after opening the container, Microbial contamination, particularly in liquid formulations or products with high moisture content, Chemical interactions with certain other compounds in complex formulations, Extreme pH conditions (either highly acidic or alkaline), Repeated freeze-thaw cycles, which can affect the physical stability of some formulations

Synthesis Methods

Natural Sources

Quality Considerations

The history of Pycnogenol® as a specific branded extract is relatively recent, dating back to the 1960s, but the medicinal use of pine bark has ancient roots spanning several cultures and civilizations. Indigenous peoples across Europe, Asia, and North America have long recognized the therapeutic properties of pine bark. Native American tribes, including the Iroquois and Algonquin, used pine bark decoctions to treat scurvy, wounds, and respiratory conditions. In traditional European folk medicine, pine bark was used for inflammatory conditions, wound healing, and as a remedy for scurvy.

The specific connection between pine bark and scurvy prevention became more formalized in 1535 when Jacques Cartier and his crew, exploring what is now Quebec, Canada, were saved from scurvy by a tea made from pine bark and needles provided by local Iroquois people. This tea, rich in vitamin C and polyphenols, effectively reversed the sailors’ symptoms. This historical incident represents one of the first documented cases of pine bark’s medicinal use by Europeans. In traditional Chinese medicine, various pine species, including Pinus massoniana, have been used for centuries to treat inflammatory conditions, improve circulation, and address skin disorders.

The modern chapter of Pycnogenol’s history began in the 1950s when French researcher Dr. Jacques Masquelier became interested in the compounds that had saved Cartier’s crew. Building on earlier research by Professor Jack Masquelier, who had identified procyanidins in peanut skins in 1948, Dr. Masquelier developed a method to extract similar compounds from pine bark.

In 1965, he patented a process for extracting procyanidolic oligomers (PCOs) from the bark of the French maritime pine (Pinus pinaster). This extract would later become known as Pycnogenol®. The name ‘Pycnogenol’ was trademarked in the 1970s by Horphag Research Ltd., which continues to hold the exclusive rights to this specific pine bark extract. The company standardized the extraction process to ensure consistent composition and potency, focusing specifically on pine trees grown in Les Landes de Gascogne forest in southwest France.

Scientific research on Pycnogenol began in earnest in the 1970s, with early studies focusing on its antioxidant properties and vascular effects. By the 1980s, Pycnogenol had gained popularity in Europe as a supplement for various health conditions, particularly those related to vascular health. The 1990s saw increased research interest in Pycnogenol, with studies expanding to investigate its effects on conditions ranging from cardiovascular health to cognitive function. This period also marked Pycnogenol’s introduction to the North American market, where it gradually gained recognition among health practitioners and consumers.

In the early 2000s, research on Pycnogenol accelerated significantly, with numerous clinical trials investigating its efficacy for specific health conditions. This growing body of evidence helped establish Pycnogenol as one of the most well-researched natural supplements, with over 450 published scientific articles and more than 160 clinical studies to date. Today, Pycnogenol is used worldwide for a variety of health purposes, including cardiovascular support, cognitive enhancement, joint health, and skin protection. It has been incorporated into numerous dietary supplements, cosmetic products, and even some medical formulations.

The extract has received various patents for specific applications and has been recognized by regulatory bodies in several countries for its safety and efficacy for certain health claims. Throughout its modern history, Pycnogenol has maintained its connection to the traditional uses of pine bark while establishing itself as a scientifically validated natural extract with diverse health applications.

Malekahmadi M, et al. The effect of Pycnogenol supplementation on plasma C-reactive protein concentration: a systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition. 2020;39(4):1118-1125. This meta-analysis of 9 randomized controlled trials (RCTs) with 486 participants found that Pycnogenol supplementation significantly reduced plasma C-reactive protein (CRP) levels, a marker of systemic inflammation, compared to placebo. The effect was more pronounced in trials using higher doses (≥150 mg/day) and longer durations (≥12 weeks)., Gulati OP. Pycnogenol® in chronic venous insufficiency and related venous disorders. Phytotherapy Research. 2014;28(3):348-362. This systematic review and meta-analysis examined 15 clinical trials investigating Pycnogenol for chronic venous insufficiency (CVI). The analysis found consistent evidence for Pycnogenol’s efficacy in reducing leg swelling, pain, and other symptoms of CVI, with effects comparable or superior to conventional treatments like compression stockings and horse chestnut seed extract., Schoonees A, et al. Pycnogenol® (extract of French maritime pine bark) for the treatment of chronic disorders. Cochrane Database of Systematic Reviews. 2012;(4):CD008294. This Cochrane review evaluated 15 RCTs examining Pycnogenol for various chronic conditions. The authors concluded that there was promising evidence for Pycnogenol’s benefits in asthma, ADHD, CVI, diabetes, erectile dysfunction, and osteoarthritis, but noted that many studies had methodological limitations and called for larger, more rigorous trials.

Effects of Pycnogenol on Cognitive Function and Oxidative Stress in Older Adults (NCT04831866), Pycnogenol for Mild Cognitive Impairment: A Randomized Controlled Trial (NCT03779789), Pycnogenol Supplementation for Endothelial Function in Patients with Metabolic Syndrome (NCT04523389), Effects of Pycnogenol on Exercise Performance and Recovery in Athletes (NCT04612153), Pycnogenol for Prevention of Diabetic Retinopathy Progression (NCT04735536)