Pycnogenol is a standardized pine bark extract derived specifically from French maritime pine trees (Pinus pinaster) found on the coast of France. It provides a concentrated source of <a href="/foods/flavonoids/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Flavonoids&lt;/h6&gt;&lt;p&gt;Flavonoids are a group of antioxidant plant compounds that include flavonols, isoflavones, and anthocyanins. They can be found in many colorful fruits and vegetables as well as wine, tea, and chocolate.&lt;/p&gt;&lt;/div&gt;">flavonoids</a> and phenolic acids, including procyanidin oligomers (65–75% by weight), catechin, epicatechin, taxifolin, caffeic acid, and ferulic acid. While other French maritime pine bark extracts exist (oligopin and flavangenol), their composition varies slightly due to different extraction techniques. Pycnogenol has been used in the vast majority of clinical trials to date, and will be the focus of this page unless otherwise mentioned.

What is pycnogenol?

Pycnogenol might improve some aspects of cardiometabolic health, but research has generally been mixed. 
Pycnogenol may increase <a href="/outcomes/glycemic-control/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Glycemic Control&lt;/h6&gt;&lt;p&gt;Glycemic control refers to a person's average blood sugar levels. HbA1c is the most widely used marker to monitor glycemic control. A continuous glucose monitor or fingersticks are also commonly used to help monitor and improve glycemic control.&lt;/p&gt;&lt;/div&gt;">glycemic control</a> by reducing fasting <a href="/outcomes/blood-glucose/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Blood glucose&lt;/h6&gt;&lt;p&gt;How much glucose, or blood sugar, is floating around in your blood. Fasting blood glucose is measured when your stomach is empty (usually before breakfast), whereas postprandial blood glucose is checked after a meal. Both are used as indicators of diabetes risk.&lt;/p&gt;&lt;/div&gt;">blood glucose</a> and hemoglobin A1c (<a href="/outcomes/hba1c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;HbA1c&lt;/h6&gt;&lt;p&gt;HbA1c (glycated hemoglobin) is a biomarker of glucose metabolism — it reflects glucose levels over months. Higher HbA1c is associated with more disease progression and comorbidities in states of insulin resistance or diabetes.&lt;/p&gt;&lt;/div&gt;">HbA1c</a>).<a href="#ref-25" id="ref-link-25" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Malekahmadi M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31585179" target="\_blank" rel="noopener noreferrer"&gt;Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;Pharmacol Res (2019-Dec)&lt;/div&gt;'>[25]</a> This is thought to occur primarily in the intestines by reducing the digestion and absorption of carbohydrates.<a href="#ref-26" id="ref-link-26" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Mármol I, et al. &lt;a href="https://doi.org/10.1016/j.tifs.2018.07.007" target="\_blank" rel="noopener noreferrer"&gt;A systematic review of the potential uses of pine bark in food industry and health care
&lt;/a&gt;&lt;/p&gt;Trends Food Sci Technol (2019 Jun)&lt;/div&gt;'>[26]</a> Interestingly, pycnogenol may also improve the healing of diabetic ulcers.<a href="#ref-3" id="ref-link-3" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Belcaro G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16959685" target="\_blank" rel="noopener noreferrer"&gt;Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.
&lt;/a&gt;&lt;/p&gt;Clin Appl Thromb Hemost (2006-Jul)&lt;/div&gt;'>[3]</a>
Some research suggests that pycnogenol has a blood pressure lowering effect;<a href="#ref-27" id="ref-link-27" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Pourmasoumi M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31637782" target="\_blank" rel="noopener noreferrer"&gt;Effect of pycnogenol supplementation on blood pressure: A systematic review and meta-analysis of clinical trials.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2020-Jan)&lt;/div&gt;'>[27]</a> however, when trials with a high risk of bias are excluded, this effect is generally lost.<a href="#ref-28" id="ref-link-28" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Federica Fogacci, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31763928" target="\_blank" rel="noopener noreferrer"&gt;Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies
&lt;/a&gt;&lt;/p&gt;Angiology (2020 Mar)&lt;/div&gt;'>[28]</a><a href="#ref-29" id="ref-link-29" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zhang Z, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30087862" target="\_blank" rel="noopener noreferrer"&gt;Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis.
&lt;/a&gt;&lt;/p&gt;Iran J Public Health (2018-Jun)&lt;/div&gt;'>[29]</a> Interestingly, two trials observed that taking pycnogenol along with other blood pressure-lowering medications (ramipril or nifedipine) allowed for lower overall doses of the antihypertensive medications after 12 weeks.<a href="#ref-30" id="ref-link-30" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Liu X, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/14659974" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients
&lt;/a&gt;&lt;/p&gt;Life Sci (2004 Jan 2)&lt;/div&gt;'>[30]</a><a href="#ref-31" id="ref-link-31" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zibadi S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19083426" target="\_blank" rel="noopener noreferrer"&gt;Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation
&lt;/a&gt;&lt;/p&gt;Nutr Res (2008 May)&lt;/div&gt;'>[31]</a>
The effects of pycnogenol on lipid parameters are similarly mixed. Some research suggests that pycnogenol may increase high-density lipoprotein (<a href="/outcomes/hdl/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;High-density lipoprotein (HDL)&lt;/h6&gt;&lt;p&gt;&lt;em&gt;High-density lipoprotein&lt;/em&gt; (HDL) is a particle that carries cholesterol from your blood to your liver. Low levels of &lt;em&gt;HDL cholesterol&lt;/em&gt; (HDL-C) are associated with a higher risk of &lt;em&gt;cardiovascular disease&lt;/em&gt; (CVD), which is why HDL-C is often called the “good cholesterol” (as opposed to LDL-C) — but the reality is more complex.&lt;/p&gt;&lt;/div&gt;">HDL</a>) cholesterol but likely does not affect other lipid parameters (e.g., low-density lipoprotein (<a href="/outcomes/ldl-c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Low-density lipoprotein (LDL)&lt;/h6&gt;&lt;p&gt;LDL carries cholesterol from the liver to other parts of the body. Because higher levels of LDL cholesterol (LDL-C) tend to increase the risk of cardiovascular disease (CVD), LDL-C is often called the “bad cholesterol” (as opposed to HDL-C) — but the reality is more complex.&lt;/p&gt;&lt;/div&gt;">LDL</a>) cholesterol, <a href="/outcomes/total-cholesterol/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Total cholesterol&lt;/h6&gt;&lt;p&gt;Total cholesterol refers to all the cholesterol in your blood (HDL-C and LDL-C). It is distinct from triglycerides.&lt;/p&gt;&lt;/div&gt;">total cholesterol</a>, or <a href="/outcomes/triglycerides/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Triglycerides&lt;/h6&gt;&lt;p&gt;Triglycerides refers to the fatty acids in your blood. They can be used for energy or stored into fat cells (i.e., body fat). Abnormal triglycerides raise the risk of cardiovascular disease (CVD).&lt;/p&gt;&lt;/div&gt;">triglycerides</a>.)<a href="#ref-17" id="ref-link-17" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hadi A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30456865" target="\_blank" rel="noopener noreferrer"&gt;The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2019-Feb)&lt;/div&gt;'>[17]</a>

Does pycnogenol affect cardiometabolic health?

While pycnogenol might impact <a href="/outcomes/cognition/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Cognition&lt;/h6&gt;&lt;p&gt;Cognition broadly represents the workings of the mind. Individual pages for specific cognitive faculties (memory, attention, alertness, processing speed, etc.) will generally be more useful.&lt;/p&gt;&lt;/div&gt;">cognition</a> or <a href="/conditions/attention-deficit-hyperactivity-disorder/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Attention Deficit Hyperactivity Disorder&lt;/h6&gt;&lt;p&gt;Attention deficit/hyperactivity disorder (ADHD) is characterized by impulsivity, inattention, and hyperactivity. Although often diagnosed in children, it’s nearly as common in adults.&lt;/p&gt;&lt;/div&gt;">ADHD</a>, the existing evidence is not sufficient to draw any meaningful conclusions. 
Both pycnogenol and oligopin (a different standardized extract of French maritime pine bark) have demonstrated mixed and unconvincing results when used in ADHD. Some research has reported reductions in the symptoms of ADHD (e.g., inattentiveness, hyperactivity) in children, but the effects tend to vary based on who is assessing the symptoms and what measurement tool is used.<a href="#ref-32" id="ref-link-32" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hsu CD, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/33559134" target="\_blank" rel="noopener noreferrer"&gt;Complementary effects of pine bark extract supplementation on inattention, impulsivity, and antioxidative status in children with attention-deficit hyperactivity disorder: A double-blinded randomized placebo-controlled cross-over study.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2021-Jun)&lt;/div&gt;'>[32]</a><a href="#ref-33" id="ref-link-33" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Trebatická J, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16699814" target="\_blank" rel="noopener noreferrer"&gt;Treatment of ADHD with French maritime pine bark extract, Pycnogenol.
&lt;/a&gt;&lt;/p&gt;Eur Child Adolesc Psychiatry (2006-Sep)&lt;/div&gt;'>[33]</a><a href="#ref-34" id="ref-link-34" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dutta T, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/35592415" target="\_blank" rel="noopener noreferrer"&gt;Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis.
&lt;/a&gt;&lt;/p&gt;Front Pharmacol (2022)&lt;/div&gt;'>[34]</a> Pycnogenol does seem to improve antioxidant status in children with ADHD, but whether this is clinically meaningful still needs to be determined.<a href="#ref-35" id="ref-link-35" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dvoráková M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18019397" target="\_blank" rel="noopener noreferrer"&gt;Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol).
&lt;/a&gt;&lt;/p&gt;Nutr Neurosci (2007)&lt;/div&gt;'>[35]</a><a href="#ref-36" id="ref-link-36" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Dvoráková M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16984739" target="\_blank" rel="noopener noreferrer"&gt;The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD).
&lt;/a&gt;&lt;/p&gt;Redox Rep (2006)&lt;/div&gt;'>[36]</a> 
Several trials have assessed the effects of pycnogenol on cognition in a variety of populations, including university students,<a href="#ref-37" id="ref-link-37" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Luzzi R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22108481" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® supplementation improves cognitive function, attention and mental performance in students
&lt;/a&gt;&lt;/p&gt;Panminerva Med (2011 Sep)&lt;/div&gt;'>[37]</a> people with <a href="/conditions/mild-cognitive-impairment/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Mild Cognitive Impairment&lt;/h6&gt;&lt;p&gt;MCI is a form of cognitive decline where changes are serious enough to be noticed by the affected individual and their family members, but not severe enough to interfere with normal activities of daily living.&lt;/p&gt;&lt;/div&gt;">mild cognitive impairment</a>,<a href="#ref-38" id="ref-link-38" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hosoi M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29754480" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® supplementation in minimal cognitive dysfunction.
&lt;/a&gt;&lt;/p&gt;J Neurosurg Sci (2018-Jun)&lt;/div&gt;'>[38]</a> professionals without apparent health conditions,<a href="#ref-39" id="ref-link-39" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Belcaro G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/24675223" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55.
&lt;/a&gt;&lt;/p&gt;J Neurosurg Sci (2014-Dec)&lt;/div&gt;'>[39]</a> people with elevated levels of oxidative stress,<a href="#ref-40" id="ref-link-40" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Belcaro G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/26635191" target="\_blank" rel="noopener noreferrer"&gt;The COFU3 Study. Improvement in cognitive function, attention, mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress.
&lt;/a&gt;&lt;/p&gt;J Neurosurg Sci (2015-Dec)&lt;/div&gt;'>[40]</a> and elderly individuals.<a href="#ref-41" id="ref-link-41" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Ryan J, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18701642" target="\_blank" rel="noopener noreferrer"&gt;An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.
&lt;/a&gt;&lt;/p&gt;J Psychopharmacol (2008-Jul)&lt;/div&gt;'>[41]</a> All studies reported improvements in some aspect of cognition (e.g., alertness, memory, attention), but only one study was placebo-controlled, which undermines the validity of these results.

Does pycnogenol impact cognition or attention-deficit/hyperactivity disorder (ADHD)?

Some preliminary research suggests that pycnogenol, taken orally, might beneficially impact several aspects of skin health; however, most of these trials have been uncontrolled, which reduces our confidence in these findings. 
When used alone or in addition to standard treatment, pycnogenol may reduce the appearance of facial melasma — a type of <a href="/outcomes/hyperpigmentation/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hyperpigmentation&lt;/h6&gt;&lt;p&gt;Hyperpigmentation is the condition of excess pigmentation (melanin) in a localized region, such as an area of skin.&lt;/p&gt;&lt;/div&gt;">hyperpigmentation</a> that can appear as brown spots on sun-exposed areas of skin. <a href="#ref-42" id="ref-link-42" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Ni Z, Mu Y, Gulati O. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/12237816" target="\_blank" rel="noopener noreferrer"&gt;Treatment of melasma with Pycnogenol.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2002-Sep)&lt;/div&gt;'>[42]</a><a href="#ref-43" id="ref-link-43" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Lima PB, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/32841433" target="\_blank" rel="noopener noreferrer"&gt;French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.
&lt;/a&gt;&lt;/p&gt;J Eur Acad Dermatol Venereol (2021-Feb)&lt;/div&gt;'>[43]</a><a href="#ref-44" id="ref-link-44" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Pinto C, et al. &lt;a href="www.surgicalcosmetic.org.br/details/417/en-US/the-use-of-pycnogenol-in-the-treatment-of-melasma" target="\_blank" rel="noopener noreferrer"&gt;The use of pycnogenol in the treatment of melasma
&lt;/a&gt;&lt;/p&gt;Surg Cosmet Dermatol (2015 Sep)&lt;/div&gt;'>[44]</a> This is further supported by <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro research</a> showing that pycnogenol may inhibit the synthesis of melanin, the major pigment in skin.<a href="#ref-45" id="ref-link-45" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Kim YJ, Kang KS, Yokozawa T. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18482785" target="\_blank" rel="noopener noreferrer"&gt;The anti-melanogenic effect of pycnogenol by its anti-oxidative actions.
&lt;/a&gt;&lt;/p&gt;Food Chem Toxicol (2008-Jul)&lt;/div&gt;'>[45]</a> A single uncontrolled trial using flavangenol (a different standardized extract of French maritime pine bark) also reported beneficial effects on skin pigmentation.<a href="#ref-46" id="ref-link-46" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Furumura M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22956863" target="\_blank" rel="noopener noreferrer"&gt;Oral administration of French maritime pine bark extract (Flavangenol(®)) improves clinical symptoms in photoaged facial skin.
&lt;/a&gt;&lt;/p&gt;Clin Interv Aging (2012)&lt;/div&gt;'>[46]</a>
Further, there is some limited research to suggest that pycnogenol may reduce skin redness following ultraviolet (UV) radiation exposure in fair-skinned individuals<a href="#ref-47" id="ref-link-47" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Saliou C, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/11163532" target="\_blank" rel="noopener noreferrer"&gt;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.
&lt;/a&gt;&lt;/p&gt;Free Radic Biol Med (2001-Jan-15)&lt;/div&gt;'>[47]</a> and increase skin hydration and elasticity, which might correspond with increases in the synthesis of <a href="/supplements/type-ii-collagen/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type-II Collagen&lt;/h6&gt;&lt;p&gt;Type II collagen (CII) is a protein and component of joint cartilage. Oral ingestion of CII in its undenatured form may reduce autoimmunity to the body's own CII, resulting in less joint inflammation in instances of osteoarthritis and rheumatism.&lt;/p&gt;&lt;/div&gt;">collagen</a> and <a href="/supplements/hyaluronic-acid/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hyaluronic Acid&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Hyaluronic acid&lt;/em&gt; (HA) is a large polysaccharide that is found naturally throughout the body and in high concentrations in the skin, the joint fluid, and the eye. It plays a role in many important bodily functions, including wound healing, joint lubrication and ovulation. As a supplement, it is most frequently used for joint health, to treat dry eyes, and in anti-aging products for the skin.&lt;/p&gt;&lt;/div&gt;">hyaluronic acid</a>.<a href="#ref-48" id="ref-link-48" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Marini A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22270036" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women
&lt;/a&gt;&lt;/p&gt;Skin Pharmacol Physiol (2012)&lt;/div&gt;'>[48]</a><a href="#ref-49" id="ref-link-49" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hua Zhao, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/33789311" target="\_blank" rel="noopener noreferrer"&gt;Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study
&lt;/a&gt;&lt;/p&gt;Skin Pharmacol Physiol (2021)&lt;/div&gt;'>[49]</a>

Does pycnogenol affect skin health?

Preliminary research suggests that pycnogenol may reduce <a href="/conditions/erectile-dysfunction/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Erectile Dysfunction&lt;/h6&gt;&lt;p&gt;Erectile dysfunction is a type of male sexual dysfunction characterized by difficulty achieving or maintaining an erection. Erectile dysfunction can be caused by nerve or blood vessel damage, obesity, smoking, or stress.&lt;/p&gt;&lt;/div&gt;">erectile dysfunction</a>, particularly when combined with <a href="/supplements/arginine/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Arginine&lt;/h6&gt;&lt;p&gt;Arginine is an amino acid involved in the regulation of vascular function and blood flow. Supplementation may improve high blood pressure and erectile dysfunction.&lt;/p&gt;&lt;/div&gt;">L-arginine</a>. 
In people with mild to moderate erectile dysfunction, the combination of pycnogenol and L-arginine may improve several aspects of erectile dysfunction, including the ability to achieve and maintain an erection, intercourse satisfaction, and the ability to reach orgasm.<a href="#ref-50" id="ref-link-50" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Tian Y, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37908749" target="\_blank" rel="noopener noreferrer"&gt;Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;Front Endocrinol (Lausanne) (2023)&lt;/div&gt;'>[50]</a> While it’s less clear if pycnogenol is effective on its own, preliminary research suggests it may be.<a href="#ref-51" id="ref-link-51" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Trebaticky B, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31855055" target="\_blank" rel="noopener noreferrer"&gt;Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.
&lt;/a&gt;&lt;/p&gt;Bratisl Lek Listy (2019)&lt;/div&gt;'>[51]</a>
The combination of pycnogenol and L-arginine is unique in that L-arginine is used as a building block for the synthesis of <a href="/outcomes/nitric-oxide/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nitric Oxide&lt;/h6&gt;&lt;p&gt;Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.&lt;/p&gt;&lt;/div&gt;">nitric oxide</a>, and pycnogenol is thought to enhance the activity of nitric oxide synthase, the enzyme responsible for producing nitric oxide.<a href="#ref-50" id="ref-link-50" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Tian Y, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37908749" target="\_blank" rel="noopener noreferrer"&gt;Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;Front Endocrinol (Lausanne) (2023)&lt;/div&gt;'>[50]</a>

Does pycnogenol affect erectile dysfunction?

Preliminary research suggests that pycnogenol may have a beneficial role in allergy prevention and <a href="/conditions/asthma/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Asthma&lt;/h6&gt;&lt;p&gt;Asthma is a lung condition characterized by inflammation and narrowing of the airways, which results in episodes of wheezing and breathlessness. Asthma can be worsened by environmental exposures, such as allergens, cold air, exercise, viral/bacterial infections, and some drugs. Diet and supplementation may alleviate asthma by way of reducing inflammation.&lt;/p&gt;&lt;/div&gt;">asthma</a> control, but more research is needed.
Pycnogenol may have a beneficial effect on mild to moderate <a href="/conditions/asthma/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Asthma&lt;/h6&gt;&lt;p&gt;Asthma is a lung condition characterized by inflammation and narrowing of the airways, which results in episodes of wheezing and breathlessness. Asthma can be worsened by environmental exposures, such as allergens, cold air, exercise, viral/bacterial infections, and some drugs. Diet and supplementation may alleviate asthma by way of reducing inflammation.&lt;/p&gt;&lt;/div&gt;">asthma</a>, with research suggesting that supplementation may improve lung function in both children and adults.<a href="#ref-52" id="ref-link-52" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Lau BH, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/15641632" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol as an adjunct in the management of childhood asthma.
&lt;/a&gt;&lt;/p&gt;J Asthma (2004)&lt;/div&gt;'>[52]</a><a href="#ref-53" id="ref-link-53" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hosseini S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/12639402" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol((R)) in the Management of Asthma
&lt;/a&gt;&lt;/p&gt;J Med Food (2001 Winter)&lt;/div&gt;'>[53]</a><a href="#ref-54" id="ref-link-54" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;G Belcaro, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22108478" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® improvements in asthma management
&lt;/a&gt;&lt;/p&gt;Panminerva Med (2011 Sep)&lt;/div&gt;'>[54]</a> In adults with allergic asthma, those who were supplemented with pycnogenol were more likely to reduce their required dose of inhaled corticosteroids.<a href="#ref-54" id="ref-link-54" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;G Belcaro, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22108478" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® improvements in asthma management
&lt;/a&gt;&lt;/p&gt;Panminerva Med (2011 Sep)&lt;/div&gt;'>[54]</a> In childhood asthma, supplementation led to a reduced need for rescue inhalers compared to placebo.<a href="#ref-52" id="ref-link-52" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Lau BH, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/15641632" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol as an adjunct in the management of childhood asthma.
&lt;/a&gt;&lt;/p&gt;J Asthma (2004)&lt;/div&gt;'>[52]</a> 
In terms of allergies, one study found that pycnogenol reduced symptoms of <a href="/conditions/allergic-rhinitis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Allergic Rhinitis&lt;/h6&gt;&lt;p&gt;Allergic rhinitis is a condition mainly characterized by runny nose, sinus congestion, sneezing, and itching after being exposed to an allergen.&lt;/p&gt;&lt;/div&gt;">allergic rhinitis</a> and the use of allergy medications (antihistamines) compared to placebo when started at least 5 weeks before allergy season. This effect could be due to pycnogenol reducing the release of histamine from mast cells, which has been observed in <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> and animal studies.<a href="#ref-55" id="ref-link-55" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Choi YH, Yan GH. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19441014" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol inhibits immunoglobulin E-mediated allergic response in mast cells.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2009-Dec)&lt;/div&gt;'>[55]</a><a href="#ref-26" id="ref-link-26" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Mármol I, et al. &lt;a href="https://doi.org/10.1016/j.tifs.2018.07.007" target="\_blank" rel="noopener noreferrer"&gt;A systematic review of the potential uses of pine bark in food industry and health care
&lt;/a&gt;&lt;/p&gt;Trends Food Sci Technol (2019 Jun)&lt;/div&gt;'>[26]</a>

Does pycnogenol affect asthma or allergies?

Pycnogenol possesses anti-inflammatory, antioxidant, and vasoactive properties that may beneficially impact various health conditions. Despite some promising results, most health outcomes are supported by just a handful of small trials, and many of the existing trials have a high risk of bias.
Pycnogenol may reduce the signs and symptoms of <a href="/conditions/chronic-venous-insufficiency/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chronic Venous Insufficiency&lt;/h6&gt;&lt;p&gt;Chronic venous insufficiency is a condition in which the veins of the legs are unable to pump blood up toward the heart. Symptoms include leg swelling, itchy skin, ulcers, and varicose veins.&lt;/p&gt;&lt;/div&gt;">chronic venous insufficiency</a> (e.g., leg pain, heaviness, and <a href="/outcomes/leg-edema/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Leg Edema&lt;/h6&gt;&lt;p&gt;Leg swelling is a transient state of edema caused by prolonged sitting, and may occur even during walking in persons with poor circulation or during the later months of pregnancy. Some supplements that improve blood circulation may help with leg swelling.&lt;/p&gt;&lt;/div&gt;">edema</a>; venous ulcers; <a href="/conditions/microangiopathy/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Microangiopathy&lt;/h6&gt;&lt;p&gt;Microangiopathy is a disease of the small blood vessels in the microcirculation and is sometimes referred to as small vessel disease (SVD). Microangiopathy is one of the main complications of diabetes mellitus and can lead to a lack of blood flow to organs and organ damage.&lt;/p&gt;&lt;/div&gt;">microangiopathy</a>)<a href="#ref-4" id="ref-link-4" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cesarone MR, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31347820" target="\_blank" rel="noopener noreferrer"&gt;Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol®.
&lt;/a&gt;&lt;/p&gt;Minerva Cardioangiol (2019-Aug)&lt;/div&gt;'>[4]</a><a href="#ref-5" id="ref-link-5" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cesarone MR, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17067979" target="\_blank" rel="noopener noreferrer"&gt;Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study.
&lt;/a&gt;&lt;/p&gt;Angiology (2006)&lt;/div&gt;'>[5]</a><a href="#ref-6" id="ref-link-6" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cesarone MR, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16708123" target="\_blank" rel="noopener noreferrer"&gt;Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study
&lt;/a&gt;&lt;/p&gt;Clin Appl Thromb Hemost (2006 Apr)&lt;/div&gt;'>[6]</a><a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gulati OP. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/23775628" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® in chronic venous insufficiency and related venous disorders.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2014-Mar)&lt;/div&gt;'>[7]</a> and reduce <a href="/outcomes/leg-edema/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Leg Edema&lt;/h6&gt;&lt;p&gt;Leg swelling is a transient state of edema caused by prolonged sitting, and may occur even during walking in persons with poor circulation or during the later months of pregnancy. Some supplements that improve blood circulation may help with leg swelling.&lt;/p&gt;&lt;/div&gt;">leg edema</a> and blood clot risk during long-duration air travel (although the latter has only been observed in a single trial).<a href="#ref-8" id="ref-link-8" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Chan V, Wang L, Allman-Farinelli M. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/33809656" target="\_blank" rel="noopener noreferrer"&gt;Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis.
&lt;/a&gt;&lt;/p&gt;Nutrients (2021-Mar-16)&lt;/div&gt;'>[8]</a><a href="#ref-9" id="ref-link-9" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Belcaro G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/15497024" target="\_blank" rel="noopener noreferrer"&gt;Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.
&lt;/a&gt;&lt;/p&gt;Clin Appl Thromb Hemost (2004-Oct)&lt;/div&gt;'>[9]</a> 
Short-term (≤3 months) trials have found that pycnogenol may reduce pain, improve physical functioning, and reduce the use of non-steroidal anti-inflammatory drugs (NSAIDs) in people with <a href="/conditions/osteoarthritis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Osteoarthritis&lt;/h6&gt;&lt;p&gt;Osteoarthritis (OA) is a joint disease involving cartilage degradation. It’s not clear what exactly causes OA, but some risk factors include joint injury, overweight or obesity, aging, misaligned joints, and family history. Lots of supplements have been studied in people with OA, as have lifestyle interventions including weight loss and exercise.&lt;/p&gt;&lt;/div&gt;">osteoarthritis</a>.<a href="#ref-10" id="ref-link-10" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Xiaoqian Liu, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29018060" target="\_blank" rel="noopener noreferrer"&gt;Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis
&lt;/a&gt;&lt;/p&gt;Br J Sports Med (2018 Feb)&lt;/div&gt;'>[10]</a><a href="#ref-11" id="ref-link-11" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Belcaro G, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18386255" target="\_blank" rel="noopener noreferrer"&gt;Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects
&lt;/a&gt;&lt;/p&gt;Phytother Res (2008 Apr)&lt;/div&gt;'>[11]</a><a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cisár P, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/18570266" target="\_blank" rel="noopener noreferrer"&gt;Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis
&lt;/a&gt;&lt;/p&gt;Phytother Res (2008 Aug)&lt;/div&gt;'>[12]</a><a href="#ref-13" id="ref-link-13" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Farid R, et al. &lt;a href="https://doi.org/10.1016/j.nutres.2007.09.007" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis
&lt;/a&gt;&lt;/p&gt;Nutr Res (2007 Nov)&lt;/div&gt;'>[13]</a> Interestingly, research suggests that some compounds in pycnogenol can enter the synovial fluid in joints, where they may act locally to reduce inflammation and inhibit the breakdown of collagen.<a href="#ref-14" id="ref-link-14" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Mülek M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/28452960" target="\_blank" rel="noopener noreferrer"&gt;Distribution of Constituents and Metabolites of Maritime Pine Bark Extract (Pycnogenol) into Serum, Blood Cells, and Synovial Fluid of Patients with Severe Osteoarthritis: A Randomized Controlled Trial.
&lt;/a&gt;&lt;/p&gt;Nutrients (2017-Apr-28)&lt;/div&gt;'>[14]</a><a href="#ref-15" id="ref-link-15" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Grimm T, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16441890" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol).
&lt;/a&gt;&lt;/p&gt;J Inflamm (Lond) (2006-Jan-27)&lt;/div&gt;'>[15]</a><a href="#ref-16" id="ref-link-16" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Jessberger S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29246219" target="\_blank" rel="noopener noreferrer"&gt;Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study.
&lt;/a&gt;&lt;/p&gt;BMC Complement Altern Med (2017-Dec-16)&lt;/div&gt;'>[16]</a>

What are pycnogenol’s main benefits?

Pycnogenol is generally considered safe and well tolerated. Side effects occur rarely and may include headache, dizziness, drowsiness, skin irritation, and gastrointestinal upset (e.g., nausea), the latter of which may improve if pycnogenol is taken with food.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Rohdewald P. &lt;a href="https://esmed.org/MRA/mra/article/view/183" target="\_blank" rel="noopener noreferrer"&gt;UPDATE ON THE CLINICAL PHARMACOLOGY OF PYCNOGENOL®
&lt;/a&gt;&lt;/p&gt;Medical Research Archives (2015 Jul)&lt;/div&gt;'>[1]</a> 
Most of the research on pycnogenol has been at least partially funded by the manufacturer of pycnogenol. While this doesn’t invalidate the research, it does make it more prone to bias in favor of pycnogenol.

What are pycnogenol’s main drawbacks?

The biological activity of pycnogenol is due to its diverse and rich content of polyphenols.<a href="#ref-17" id="ref-link-17" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hadi A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30456865" target="\_blank" rel="noopener noreferrer"&gt;The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2019-Feb)&lt;/div&gt;'>[17]</a> Following ingestion, some of these compounds are metabolized by bacteria in the colon into other bioactive compounds that can be absorbed. For example, bacteria can convert the procyanidins in pycnogenol into the compound M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone), which is thought to strongly contribute to its overall biological effects.<a href="#ref-18" id="ref-link-18" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Grimm T, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16887024" target="\_blank" rel="noopener noreferrer"&gt;Single and multiple dose pharmacokinetics of maritime pine bark extract (pycnogenol) after oral administration to healthy volunteers
&lt;/a&gt;&lt;/p&gt;BMC Clin Pharmacol (2006 Aug 3)&lt;/div&gt;'>[18]</a><a href="#ref-19" id="ref-link-19" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Rohdewald PJ. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/28836883" target="\_blank" rel="noopener noreferrer"&gt;Review on Sustained Relief of Osteoarthritis Symptoms with a Proprietary Extract from Pine Bark, Pycnogenol
&lt;/a&gt;&lt;/p&gt;J Med Food (2018 Jan)&lt;/div&gt;'>[19]</a> 
Pycnogenol seems to decrease pain and inflammation by reducing the activity of certain pathways in the body that lead to the production of pro-inflammatory compounds, including <a href="/outcomes/nf-kb-activity/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;NF-kB Activity&lt;/h6&gt;&lt;p&gt;Nuclear factor kappa B (NF-kB) is a protein that induces inflammation. NF-kB is crucial for preventing infection, but its dysregulation has been linked to various inflammatory and autoimmune diseases.&lt;/p&gt;&lt;/div&gt;">nuclear factor kappa B</a> (NF-κB) and cyclooxygenase (COX)-1 and COX-2 enzymes.<a href="#ref-15" id="ref-link-15" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Grimm T, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16441890" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol).
&lt;/a&gt;&lt;/p&gt;J Inflamm (Lond) (2006-Jan-27)&lt;/div&gt;'>[15]</a><a href="#ref-20" id="ref-link-20" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Schäfer A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16330178" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol).
&lt;/a&gt;&lt;/p&gt;Biomed Pharmacother (2006-Jan)&lt;/div&gt;'>[20]</a> As an antioxidant, in vitro and animal research suggests that pycnogenol may directly scavenge free radicals, regenerate other antioxidants in the body (e.g., vitamin C, vitamin E, and glutathione), and increase the activity of antioxidant enzymes.<a href="#ref-21" id="ref-link-21" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Packer L, Rimbach G, Virgili F. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/10490291" target="\_blank" rel="noopener noreferrer"&gt;Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol.
&lt;/a&gt;&lt;/p&gt;Free Radic Biol Med (1999-Sep)&lt;/div&gt;'>[21]</a><a href="#ref-22" id="ref-link-22" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Wei ZH, Peng QL, Lau BH. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/27415023" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol enhances endothelial cell antioxidant defenses.
&lt;/a&gt;&lt;/p&gt;Redox Rep (1997-Aug)&lt;/div&gt;'>[22]</a><a href="#ref-23" id="ref-link-23" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Maritim A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/12815616" target="\_blank" rel="noopener noreferrer"&gt;Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats.
&lt;/a&gt;&lt;/p&gt;J Biochem Mol Toxicol (2003)&lt;/div&gt;'>[23]</a> The above effects, as well as pycnogenol's ability to enhance <a href="/outcomes/nitric-oxide/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nitric Oxide&lt;/h6&gt;&lt;p&gt;Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.&lt;/p&gt;&lt;/div&gt;">nitric oxide</a> synthesis and increase capillary integrity, may contribute to reduced capillary permeability and increased blood flow.<a href="#ref-24" id="ref-link-24" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Fitzpatrick DF, Bing B, Rohdewald P. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/9781917" target="\_blank" rel="noopener noreferrer"&gt;Endothelium-dependent vascular effects of Pycnogenol.
&lt;/a&gt;&lt;/p&gt;J Cardiovasc Pharmacol (1998-Oct)&lt;/div&gt;'>[24]</a><a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gulati OP. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/23775628" target="\_blank" rel="noopener noreferrer"&gt;Pycnogenol® in chronic venous insufficiency and related venous disorders.
&lt;/a&gt;&lt;/p&gt;Phytother Res (2014-Mar)&lt;/div&gt;'>[7]</a>

How does pycnogenol work?

Pycnogenol

Cardiovascular Health

UPDATE ON THE CLINICAL PHARMACOLOGY OF PYCNOGENOL®

Venous ulcers: microcirculatory improvement and faster healing with local use of Pycnogenol

Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.

Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol®.

Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study.

Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study

Pycnogenol® in chronic venous insufficiency and related venous disorders.

Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis

Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects

Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis

Pycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis

Distribution of Constituents and Metabolites of Maritime Pine Bark Extract (Pycnogenol) into Serum, Blood Cells, and Synovial Fluid of Patients with Severe Osteoarthritis: A Randomized Controlled Trial.

Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol).

Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study.

The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials.

Single and multiple dose pharmacokinetics of maritime pine bark extract (pycnogenol) after oral administration to healthy volunteers

Review on Sustained Relief of Osteoarthritis Symptoms with a Proprietary Extract from Pine Bark, Pycnogenol

Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol).

Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol.

Pycnogenol enhances endothelial cell antioxidant defenses.

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats.

Endothelium-dependent vascular effects of Pycnogenol.

Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.

A systematic review of the potential uses of pine bark in food industry and health care

Effect of pycnogenol supplementation on blood pressure: A systematic review and meta-analysis of clinical trials.

Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies

Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis.

Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients

Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation

Complementary effects of pine bark extract supplementation on inattention, impulsivity, and antioxidative status in children with attention-deficit hyperactivity disorder: A double-blinded randomized placebo-controlled cross-over study.

Treatment of ADHD with French maritime pine bark extract, Pycnogenol.

Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis.

Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol).

The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD).

Pycnogenol® supplementation improves cognitive function, attention and mental performance in students

Pycnogenol® supplementation in minimal cognitive dysfunction.

Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55.

The COFU3 Study. Improvement in cognitive function, attention, mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

Treatment of melasma with Pycnogenol.

French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.

The use of pycnogenol in the treatment of melasma

The anti-melanogenic effect of pycnogenol by its anti-oxidative actions.

Oral administration of French maritime pine bark extract (Flavangenol(®)) improves clinical symptoms in photoaged facial skin.

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.

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women

Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study

Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.

Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.

Pycnogenol as an adjunct in the management of childhood asthma.

Pycnogenol((R)) in the Management of Asthma

Pycnogenol® improvements in asthma management

Pycnogenol inhibits immunoglobulin E-mediated allergic response in mast cells.

Nick Milazzo

Conni Covington

Natalka Roshak

Katie Jantz

General Cardiovascular Health

High-density lipoprotein (HDL)

Blood Flow

Blood glucose

Body Mass Index (BMI)

C-Reactive Protein (CRP)

HbA1c

Liver Enzymes

Oxidative Stress Biomarkers

Blood Pressure

Creatinine

Fibrinogen

Heart Rate

Hemoglobin

Low-density lipoprotein (LDL)

Pulse Pressure

Total cholesterol

Triglycerides

Weight

White Blood Cell Count

Joint Health

Osteoarthritis

Osteoarthritis Symptoms

Pain

Chronic Venous Insufficiency

Chronic Venous Insufficiency Signs

Leg Edema

Asthma

Asthma Symptoms

High Blood Pressure

Nitric Oxide

Diabetes & Blood Sugar

Type 2 Diabetes

Endothelin-1

Insulin

Liver Health

Healthy Aging

Metabolic Health

NF-kB Activity

Inflammation

Coronary Artery Disease

Irritable Bowel Syndrome

Irritable Bowel Syndrome Symptoms

Menopause

Menopausal Symptoms

Libido & Sexual Function

Male Sexual Dysfunction

Erections

Memory & Focus

Vegetarians & Vegans

Cognitive Improvement

Attention

Cognition

Subjective Well-Being

Dyslipidemia

Skin, Hair & Nails

Skin Health

Skin Elasticity

Skin Quality

French maritime pine bark extract Pycnogenol dose-dependently lowers glucose in type 2 diabetic patients

Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans

Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile

The Effect of Pycnogenol Supplementation on Plasma C-Reactive Protein Concentration: a Systematic Review and Meta-Analysis

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency

Treatment of erectile dysfunction with pycnogenol and L-arginine

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

Supplementation with Pycnogenol® improves signs and symptoms of menopausal transition

Inhibition of NF-κB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol)

Pycnogenol® supplementation improves the control of irritable bowel syndrome symptoms

Pycnogenol might improve some aspects of cardiometabolic health, but research has generally been mixed. 
Pycnogenol may increase <a href="/outcomes/glycemic-control/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Glycemic Control&lt;/h6&gt;&lt;p&gt;Glycemic control refers to a person's average blood sugar levels. HbA1c is the most widely used marker to monitor glycemic control. A continuous glucose monitor or fingersticks are also commonly used to help monitor and improve glycemic control.&lt;/p&gt;&lt;/div&gt;">glycemic control</a> by reducing fasting <a href="/outcomes/blood-glucose/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Blood glucose&lt;/h6&gt;&lt;p&gt;How much glucose, or blood sugar, is floating around in your blood. Fasting blood glucose is measured when your stomach is empty (usually before breakfast), whereas postprandial blood glucose is checked after a meal. Both are used as indicators of diabetes risk.&lt;/p&gt;&lt;/div&gt;">blood glucose</a> and hemoglobin A1c (<a href="/outcomes/hba1c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;HbA1c&lt;/h6&gt;&lt;p&gt;HbA1c (glycated hemoglobin) is a biomarker of glucose metabolism — it reflects glucose levels over months. Higher HbA1c is associated with more disease progression and comorbidities in states of insulin resistance or diabetes.&lt;/p&gt;&lt;/div&gt;">HbA1c</a>).[reference|url=https://pubmed.ncbi.nlm.nih.gov/31585179|title=Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.|published=2019-Dec|authors=Malekahmadi M, Moradi Moghaddam O, Firouzi S, Daryabeygi-Khotbehsara R, Shariful Islam SM, Norouzy A, Soltani S|journal=Pharmacol Res|] This is thought to occur primarily in the intestines by reducing the digestion and absorption of carbohydrates.[reference|url=https://doi.org/10.1016/j.tifs.2018.07.007|title=A systematic review of the potential uses of pine bark in food industry and health care|published=2019 Jun|authors=Mármol I, Quero J, Jiménez-Moreno N, Rodríguez-Yoldi M, Ancín-Azpilicueta C|journal=Trends Food Sci Technol] Interestingly, pycnogenol may also improve the healing of diabetic ulcers.[reference|url=https://pubmed.ncbi.nlm.nih.gov/16959685|title=Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.|published=2006-Jul|authors=Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Gizzi G, Rohdewald P, Ippolito E, Ricci A, Cacchio M, Cipollone G, Ruffini I, Fano F, Hosoi M|journal=Clin Appl Thromb Hemost|]
Some research suggests that pycnogenol has a blood pressure lowering effect;[reference|url=https://pubmed.ncbi.nlm.nih.gov/31637782|title=Effect of pycnogenol supplementation on blood pressure: A systematic review and meta-analysis of clinical trials.|published=2020-Jan|authors=Pourmasoumi M, Hadi A, Mohammadi H, Rouhani MH|journal=Phytother Res|] however, when trials with a high risk of bias are excluded, this effect is generally lost.[reference|url=https://pubmed.ncbi.nlm.nih.gov/31763928|title=Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies|published=2020 Mar|authors=Federica Fogacci, Giuliano Tocci, Amirhossein Sahebkar, Vivianne Presta, Maciej Banach, Arrigo Francesco Giuseppe Cicero|journal=Angiology|][reference|url=https://pubmed.ncbi.nlm.nih.gov/30087862|title=Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis.|published=2018-Jun|authors=Zhang Z, Tong X, Wei YL, Zhao L, Xu JY, Qin LQ|journal=Iran J Public Health|] Interestingly, two trials observed that taking pycnogenol along with other blood pressure-lowering medications (ramipril or nifedipine) allowed for lower overall doses of the antihypertensive medications after 12 weeks.[reference|url=https://pubmed.ncbi.nlm.nih.gov/14659974|title=Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients|published=2004 Jan 2|authors=Liu X, Wei J, Tan F, Zhou S, Würthwein G, Rohdewald P|journal=Life Sci|][reference|url=https://pubmed.ncbi.nlm.nih.gov/19083426|title=Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation|published=2008 May|authors=Zibadi S, Rohdewald PJ, Park D, Watson RR|journal=Nutr Res|]
The effects of pycnogenol on lipid parameters are similarly mixed. Some research suggests that pycnogenol may increase high-density lipoprotein (<a href="/outcomes/hdl/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;High-density lipoprotein (HDL)&lt;/h6&gt;&lt;p&gt;&lt;em&gt;High-density lipoprotein&lt;/em&gt; (HDL) is a particle that carries cholesterol from your blood to your liver. Low levels of &lt;em&gt;HDL cholesterol&lt;/em&gt; (HDL-C) are associated with a higher risk of &lt;em&gt;cardiovascular disease&lt;/em&gt; (CVD), which is why HDL-C is often called the “good cholesterol” (as opposed to LDL-C) — but the reality is more complex.&lt;/p&gt;&lt;/div&gt;">HDL</a>) cholesterol but likely does not affect other lipid parameters (e.g., low-density lipoprotein (<a href="/outcomes/ldl-c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Low-density lipoprotein (LDL)&lt;/h6&gt;&lt;p&gt;LDL carries cholesterol from the liver to other parts of the body. Because higher levels of LDL cholesterol (LDL-C) tend to increase the risk of cardiovascular disease (CVD), LDL-C is often called the “bad cholesterol” (as opposed to HDL-C) — but the reality is more complex.&lt;/p&gt;&lt;/div&gt;">LDL</a>) cholesterol, <a href="/outcomes/total-cholesterol/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Total cholesterol&lt;/h6&gt;&lt;p&gt;Total cholesterol refers to all the cholesterol in your blood (HDL-C and LDL-C). It is distinct from triglycerides.&lt;/p&gt;&lt;/div&gt;">total cholesterol</a>, or <a href="/outcomes/triglycerides/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Triglycerides&lt;/h6&gt;&lt;p&gt;Triglycerides refers to the fatty acids in your blood. They can be used for energy or stored into fat cells (i.e., body fat). Abnormal triglycerides raise the risk of cardiovascular disease (CVD).&lt;/p&gt;&lt;/div&gt;">triglycerides</a>.)[reference|url=https://pubmed.ncbi.nlm.nih.gov/30456865|title=The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials.|published=2019-Feb|authors=Hadi A, Pourmasoumi M, Mohammadi H, Javaheri A, Rouhani MH|journal=Phytother Res|]

While pycnogenol might impact <a href="/outcomes/cognition/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Cognition&lt;/h6&gt;&lt;p&gt;Cognition broadly represents the workings of the mind. Individual pages for specific cognitive faculties (memory, attention, alertness, processing speed, etc.) will generally be more useful.&lt;/p&gt;&lt;/div&gt;">cognition</a> or <a href="/conditions/attention-deficit-hyperactivity-disorder/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Attention Deficit Hyperactivity Disorder&lt;/h6&gt;&lt;p&gt;Attention deficit/hyperactivity disorder (ADHD) is characterized by impulsivity, inattention, and hyperactivity. Although often diagnosed in children, it’s nearly as common in adults.&lt;/p&gt;&lt;/div&gt;">ADHD</a>, the existing evidence is not sufficient to draw any meaningful conclusions. 
Both pycnogenol and oligopin (a different standardized extract of French maritime pine bark) have demonstrated mixed and unconvincing results when used in ADHD. Some research has reported reductions in the symptoms of ADHD (e.g., inattentiveness, hyperactivity) in children, but the effects tend to vary based on who is assessing the symptoms and what measurement tool is used.[reference|url=https://pubmed.ncbi.nlm.nih.gov/33559134|title=Complementary effects of pine bark extract supplementation on inattention, impulsivity, and antioxidative status in children with attention-deficit hyperactivity disorder: A double-blinded randomized placebo-controlled cross-over study.|published=2021-Jun|authors=Hsu CD, Hsieh LH, Chen YL, Lin IC, Chen YR, Chen CC, Shirakawa H, Yang SC|journal=Phytother Res|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16699814|title=Treatment of ADHD with French maritime pine bark extract, Pycnogenol.|published=2006-Sep|authors=Trebatická J, Kopasová S, Hradecná Z, Cinovský K, Skodácek I, Suba J, Muchová J, Zitnanová I, Waczulíková I, Rohdewald P, Duracková Z|journal=Eur Child Adolesc Psychiatry|][reference|url=https://pubmed.ncbi.nlm.nih.gov/35592415|title=Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis.|published=2022|authors=Dutta T, Anand U, Mitra SS, Ghorai M, Jha NK, Shaikh NK, Shekhawat MS, Pandey DK, Proćków J, Dey A|journal=Front Pharmacol|] Pycnogenol does seem to improve antioxidant status in children with ADHD, but whether this is clinically meaningful still needs to be determined.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18019397|title=Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol).|published=2007|authors=Dvoráková M, Jezová D, Blazícek P, Trebatická J, Skodácek I, Suba J, Iveta W, Rohdewald P, Duracková Z|journal=Nutr Neurosci|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16984739|title=The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD).|published=2006|authors=Dvoráková M, Sivonová M, Trebatická J, Skodácek I, Waczuliková I, Muchová J, Duracková Z|journal=Redox Rep|] 
Several trials have assessed the effects of pycnogenol on cognition in a variety of populations, including university students,[reference|url=https://pubmed.ncbi.nlm.nih.gov/22108481|title=Pycnogenol® supplementation improves cognitive function, attention and mental performance in students|published=2011 Sep|authors=Luzzi R, Belcaro G, Zulli C, Cesarone MR, Cornelli U, Dugall M, Hosoi M, Feragalli B|journal=Panminerva Med|] people with <a href="/conditions/mild-cognitive-impairment/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Mild Cognitive Impairment&lt;/h6&gt;&lt;p&gt;MCI is a form of cognitive decline where changes are serious enough to be noticed by the affected individual and their family members, but not severe enough to interfere with normal activities of daily living.&lt;/p&gt;&lt;/div&gt;">mild cognitive impairment</a>,[reference|url=https://pubmed.ncbi.nlm.nih.gov/29754480|title=Pycnogenol® supplementation in minimal cognitive dysfunction.|published=2018-Jun|authors=Hosoi M, Belcaro G, Saggino A, Luzzi R, Dugall M, Feragalli B|journal=J Neurosurg Sci|] professionals without apparent health conditions,[reference|url=https://pubmed.ncbi.nlm.nih.gov/24675223|title=Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55.|published=2014-Dec|authors=Belcaro G, Luzzi R, Dugall M, Ippolito E, Saggino A|journal=J Neurosurg Sci|] people with elevated levels of oxidative stress,[reference|url=https://pubmed.ncbi.nlm.nih.gov/26635191|title=The COFU3 Study. Improvement in cognitive function, attention, mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress.|published=2015-Dec|authors=Belcaro G, Dugall M, Ippolito E, Hu S, Saggino A, Feragalli B|journal=J Neurosurg Sci|] and elderly individuals.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18701642|title=An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.|published=2008-Jul|authors=Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L, Kure C, Lloyd J, Stough C|journal=J Psychopharmacol|] All studies reported improvements in some aspect of cognition (e.g., alertness, memory, attention), but only one study was placebo-controlled, which undermines the validity of these results.

Some preliminary research suggests that pycnogenol, taken orally, might beneficially impact several aspects of skin health; however, most of these trials have been uncontrolled, which reduces our confidence in these findings. 
When used alone or in addition to standard treatment, pycnogenol may reduce the appearance of facial melasma — a type of <a href="/outcomes/hyperpigmentation/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hyperpigmentation&lt;/h6&gt;&lt;p&gt;Hyperpigmentation is the condition of excess pigmentation (melanin) in a localized region, such as an area of skin.&lt;/p&gt;&lt;/div&gt;">hyperpigmentation</a> that can appear as brown spots on sun-exposed areas of skin. [reference|url=https://pubmed.ncbi.nlm.nih.gov/12237816|title=Treatment of melasma with Pycnogenol.|published=2002-Sep|authors=Ni Z, Mu Y, Gulati O|journal=Phytother Res|][reference|url=https://pubmed.ncbi.nlm.nih.gov/32841433|title=French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.|published=2021-Feb|authors=Lima PB, Dias JAF, Esposito ACC, Miot LDB, Miot HA|journal=J Eur Acad Dermatol Venereol|][reference|url=www.surgicalcosmetic.org.br/details/417/en-US/the-use-of-pycnogenol-in-the-treatment-of-melasma|title=The use of pycnogenol in the treatment of melasma|published=2015 Sep|authors=Pinto C, Delfes M, Montanheiro dos Reis L, Garbers L, Passos P, Skusa de Torre D|journal=Surg Cosmet Dermatol] This is further supported by <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro research</a> showing that pycnogenol may inhibit the synthesis of melanin, the major pigment in skin.[reference|url=https://pubmed.ncbi.nlm.nih.gov/18482785|title=The anti-melanogenic effect of pycnogenol by its anti-oxidative actions.|published=2008-Jul|authors=Kim YJ, Kang KS, Yokozawa T|journal=Food Chem Toxicol|] A single uncontrolled trial using flavangenol (a different standardized extract of French maritime pine bark) also reported beneficial effects on skin pigmentation.[reference|url=https://pubmed.ncbi.nlm.nih.gov/22956863|title=Oral administration of French maritime pine bark extract (Flavangenol(®)) improves clinical symptoms in photoaged facial skin.|published=2012|authors=Furumura M, Sato N, Kusaba N, Takagaki K, Nakayama J|journal=Clin Interv Aging|]
Further, there is some limited research to suggest that pycnogenol may reduce skin redness following ultraviolet (UV) radiation exposure in fair-skinned individuals[reference|url=https://pubmed.ncbi.nlm.nih.gov/11163532|title=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.|published=2001-Jan-15|authors=Saliou C, Rimbach G, Moini H, McLaughlin L, Hosseini S, Lee J, Watson RR, Packer L|journal=Free Radic Biol Med|] and increase skin hydration and elasticity, which might correspond with increases in the synthesis of <a href="/supplements/type-ii-collagen/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type-II Collagen&lt;/h6&gt;&lt;p&gt;Type II collagen (CII) is a protein and component of joint cartilage. Oral ingestion of CII in its undenatured form may reduce autoimmunity to the body's own CII, resulting in less joint inflammation in instances of osteoarthritis and rheumatism.&lt;/p&gt;&lt;/div&gt;">collagen</a> and <a href="/supplements/hyaluronic-acid/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hyaluronic Acid&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Hyaluronic acid&lt;/em&gt; (HA) is a large polysaccharide that is found naturally throughout the body and in high concentrations in the skin, the joint fluid, and the eye. It plays a role in many important bodily functions, including wound healing, joint lubrication and ovulation. As a supplement, it is most frequently used for joint health, to treat dry eyes, and in anti-aging products for the skin.&lt;/p&gt;&lt;/div&gt;">hyaluronic acid</a>.[reference|url=https://pubmed.ncbi.nlm.nih.gov/22270036|title=Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women|published=2012|authors=Marini A, Grether-Beck S, Jaenicke T, Weber M, Burki C, Formann P, Brenden H, Schönlau F, Krutmann J|journal=Skin Pharmacol Physiol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/33789311|title=Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study|published=2021|authors=Hua Zhao, Jinhao Wu, Nan Wang, Susanne Grether-Beck, Jean Krutmann, Liu Wei|journal=Skin Pharmacol Physiol|]

Preliminary research suggests that pycnogenol may reduce <a href="/conditions/erectile-dysfunction/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Erectile Dysfunction&lt;/h6&gt;&lt;p&gt;Erectile dysfunction is a type of male sexual dysfunction characterized by difficulty achieving or maintaining an erection. Erectile dysfunction can be caused by nerve or blood vessel damage, obesity, smoking, or stress.&lt;/p&gt;&lt;/div&gt;">erectile dysfunction</a>, particularly when combined with <a href="/supplements/arginine/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Arginine&lt;/h6&gt;&lt;p&gt;Arginine is an amino acid involved in the regulation of vascular function and blood flow. Supplementation may improve high blood pressure and erectile dysfunction.&lt;/p&gt;&lt;/div&gt;">L-arginine</a>. 
In people with mild to moderate erectile dysfunction, the combination of pycnogenol and L-arginine may improve several aspects of erectile dysfunction, including the ability to achieve and maintain an erection, intercourse satisfaction, and the ability to reach orgasm.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37908749|title=Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.|published=2023|authors=Tian Y, Zhou Q, Li W, Liu M, Li Q, Chen Q|journal=Front Endocrinol (Lausanne)|] While it’s less clear if pycnogenol is effective on its own, preliminary research suggests it may be.[reference|url=https://pubmed.ncbi.nlm.nih.gov/31855055|title=Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.|published=2019|authors=Trebaticky B, Muchova J, Ziaran S, Bujdak P, Breza J, Durackova Z|journal=Bratisl Lek Listy|]
The combination of pycnogenol and L-arginine is unique in that L-arginine is used as a building block for the synthesis of <a href="/outcomes/nitric-oxide/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nitric Oxide&lt;/h6&gt;&lt;p&gt;Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.&lt;/p&gt;&lt;/div&gt;">nitric oxide</a>, and pycnogenol is thought to enhance the activity of nitric oxide synthase, the enzyme responsible for producing nitric oxide.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37908749|title=Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.|published=2023|authors=Tian Y, Zhou Q, Li W, Liu M, Li Q, Chen Q|journal=Front Endocrinol (Lausanne)|]

Preliminary research suggests that pycnogenol may have a beneficial role in allergy prevention and <a href="/conditions/asthma/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Asthma&lt;/h6&gt;&lt;p&gt;Asthma is a lung condition characterized by inflammation and narrowing of the airways, which results in episodes of wheezing and breathlessness. Asthma can be worsened by environmental exposures, such as allergens, cold air, exercise, viral/bacterial infections, and some drugs. Diet and supplementation may alleviate asthma by way of reducing inflammation.&lt;/p&gt;&lt;/div&gt;">asthma</a> control, but more research is needed.
Pycnogenol may have a beneficial effect on mild to moderate <a href="/conditions/asthma/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Asthma&lt;/h6&gt;&lt;p&gt;Asthma is a lung condition characterized by inflammation and narrowing of the airways, which results in episodes of wheezing and breathlessness. Asthma can be worsened by environmental exposures, such as allergens, cold air, exercise, viral/bacterial infections, and some drugs. Diet and supplementation may alleviate asthma by way of reducing inflammation.&lt;/p&gt;&lt;/div&gt;">asthma</a>, with research suggesting that supplementation may improve lung function in both children and adults.[reference|url=https://pubmed.ncbi.nlm.nih.gov/15641632|title=Pycnogenol as an adjunct in the management of childhood asthma.|published=2004|authors=Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA|journal=J Asthma|][reference|url=https://pubmed.ncbi.nlm.nih.gov/12639402|title=Pycnogenol((R)) in the Management of Asthma|published=2001 Winter|authors=Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR|journal=J Med Food|][reference|url=https://pubmed.ncbi.nlm.nih.gov/22108478|title=Pycnogenol® improvements in asthma management|published=2011 Sep|authors=G Belcaro, R Luzzi, P Cesinaro Di Rocco, M R Cesarone, M Dugall, B Feragalli, B M Errichi, E Ippolito, M G Grossi, M Hosoi, S Errichi, U Cornelli, A Ledda, G Gizzi|journal=Panminerva Med|] In adults with allergic asthma, those who were supplemented with pycnogenol were more likely to reduce their required dose of inhaled corticosteroids.[reference|url=https://pubmed.ncbi.nlm.nih.gov/22108478|title=Pycnogenol® improvements in asthma management|published=2011 Sep|authors=G Belcaro, R Luzzi, P Cesinaro Di Rocco, M R Cesarone, M Dugall, B Feragalli, B M Errichi, E Ippolito, M G Grossi, M Hosoi, S Errichi, U Cornelli, A Ledda, G Gizzi|journal=Panminerva Med|] In childhood asthma, supplementation led to a reduced need for rescue inhalers compared to placebo.[reference|url=https://pubmed.ncbi.nlm.nih.gov/15641632|title=Pycnogenol as an adjunct in the management of childhood asthma.|published=2004|authors=Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA|journal=J Asthma|] 
In terms of allergies, one study found that pycnogenol reduced symptoms of <a href="/conditions/allergic-rhinitis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Allergic Rhinitis&lt;/h6&gt;&lt;p&gt;Allergic rhinitis is a condition mainly characterized by runny nose, sinus congestion, sneezing, and itching after being exposed to an allergen.&lt;/p&gt;&lt;/div&gt;">allergic rhinitis</a> and the use of allergy medications (antihistamines) compared to placebo when started at least 5 weeks before allergy season. This effect could be due to pycnogenol reducing the release of histamine from mast cells, which has been observed in <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> and animal studies.[reference|url=https://pubmed.ncbi.nlm.nih.gov/19441014|title=Pycnogenol inhibits immunoglobulin E-mediated allergic response in mast cells.|published=2009-Dec|authors=Choi YH, Yan GH|journal=Phytother Res|][reference|url=https://doi.org/10.1016/j.tifs.2018.07.007|title=A systematic review of the potential uses of pine bark in food industry and health care|published=2019 Jun|authors=Mármol I, Quero J, Jiménez-Moreno N, Rodríguez-Yoldi M, Ancín-Azpilicueta C|journal=Trends Food Sci Technol]

Pycnogenol possesses anti-inflammatory, antioxidant, and vasoactive properties that may beneficially impact various health conditions. Despite some promising results, most health outcomes are supported by just a handful of small trials, and many of the existing trials have a high risk of bias.
Pycnogenol may reduce the signs and symptoms of <a href="/conditions/chronic-venous-insufficiency/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chronic Venous Insufficiency&lt;/h6&gt;&lt;p&gt;Chronic venous insufficiency is a condition in which the veins of the legs are unable to pump blood up toward the heart. Symptoms include leg swelling, itchy skin, ulcers, and varicose veins.&lt;/p&gt;&lt;/div&gt;">chronic venous insufficiency</a> (e.g., leg pain, heaviness, and <a href="/outcomes/leg-edema/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Leg Edema&lt;/h6&gt;&lt;p&gt;Leg swelling is a transient state of edema caused by prolonged sitting, and may occur even during walking in persons with poor circulation or during the later months of pregnancy. Some supplements that improve blood circulation may help with leg swelling.&lt;/p&gt;&lt;/div&gt;">edema</a>; venous ulcers; <a href="/conditions/microangiopathy/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Microangiopathy&lt;/h6&gt;&lt;p&gt;Microangiopathy is a disease of the small blood vessels in the microcirculation and is sometimes referred to as small vessel disease (SVD). Microangiopathy is one of the main complications of diabetes mellitus and can lead to a lack of blood flow to organs and organ damage.&lt;/p&gt;&lt;/div&gt;">microangiopathy</a>)[reference|url=https://pubmed.ncbi.nlm.nih.gov/31347820|title=Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol®.|published=2019-Aug|authors=Cesarone MR, Belcaro G, Agus GB, Ippolito E, Dugall M, Hosoi M, Corsi M, Cotellese R, Feragalli B, Scipione C, Scipione V, Maione C|journal=Minerva Cardioangiol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/17067979|title=Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study.|published=2006|authors=Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, Ricci A, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cacchio M, Di Renzo A, Hosoi M, Stuard S, Corsi M|journal=Angiology|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16708123|title=Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study|published=2006 Apr|authors=Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, Ricci A, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cacchio M, Di Renzo A, Hosoi M, Stuard S, Corsi M|journal=Clin Appl Thromb Hemost|][reference|url=https://pubmed.ncbi.nlm.nih.gov/23775628|title=Pycnogenol® in chronic venous insufficiency and related venous disorders.|published=2014-Mar|authors=Gulati OP|journal=Phytother Res|] and reduce <a href="/outcomes/leg-edema/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Leg Edema&lt;/h6&gt;&lt;p&gt;Leg swelling is a transient state of edema caused by prolonged sitting, and may occur even during walking in persons with poor circulation or during the later months of pregnancy. Some supplements that improve blood circulation may help with leg swelling.&lt;/p&gt;&lt;/div&gt;">leg edema</a> and blood clot risk during long-duration air travel (although the latter has only been observed in a single trial).[reference|url=https://pubmed.ncbi.nlm.nih.gov/33809656|title=Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis.|published=2021-Mar-16|authors=Chan V, Wang L, Allman-Farinelli M|journal=Nutrients|][reference|url=https://pubmed.ncbi.nlm.nih.gov/15497024|title=Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.|published=2004-Oct|authors=Belcaro G, Cesarone MR, Rohdewald P, Ricci A, Ippolito E, Dugall M, Griffin M, Ruffini I, Acerbi G, Vinciguerra MG, Bavera P, Di Renzo A, Errichi BM, Cerritelli F|journal=Clin Appl Thromb Hemost|] 
Short-term (≤3 months) trials have found that pycnogenol may reduce pain, improve physical functioning, and reduce the use of non-steroidal anti-inflammatory drugs (NSAIDs) in people with <a href="/conditions/osteoarthritis/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Osteoarthritis&lt;/h6&gt;&lt;p&gt;Osteoarthritis (OA) is a joint disease involving cartilage degradation. It’s not clear what exactly causes OA, but some risk factors include joint injury, overweight or obesity, aging, misaligned joints, and family history. Lots of supplements have been studied in people with OA, as have lifestyle interventions including weight loss and exercise.&lt;/p&gt;&lt;/div&gt;">osteoarthritis</a>.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29018060|title=Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis|published=2018 Feb|authors=Xiaoqian Liu, Gustavo C Machado, Jillian P Eyles, Varshini Ravi, David J Hunter|journal=Br J Sports Med|][reference|url=https://pubmed.ncbi.nlm.nih.gov/18386255|title=Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects|published=2008 Apr|authors=Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Errichi S, Gizzi G, Ippolito E, Ricci A, Cacchio M, Cipollone G, Ruffini I, Fano F, Hosoi M, Rohdewald P|journal=Phytother Res|][reference|url=https://pubmed.ncbi.nlm.nih.gov/18570266|title=Effect of pine bark extract (Pycnogenol) on symptoms of knee osteoarthritis|published=2008 Aug|authors=Cisár P, Jány R, Waczulíková I, Sumegová K, Muchová J, Vojtassák J, Duraćková Z, Lisý M, Rohdewald P|journal=Phytother Res|][reference|url=https://doi.org/10.1016/j.nutres.2007.09.007|title=Pycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis|published=2007 Nov|authors=Farid R, Mirfeizi Z, Mirheidari M, Rezaieyazdi Z, Mansouri H, Esmaelli H, Zibadi S, Rohdewald P, Watson R|journal=Nutr Res] Interestingly, research suggests that some compounds in pycnogenol can enter the synovial fluid in joints, where they may act locally to reduce inflammation and inhibit the breakdown of collagen.[reference|url=https://pubmed.ncbi.nlm.nih.gov/28452960|title=Distribution of Constituents and Metabolites of Maritime Pine Bark Extract (Pycnogenol) into Serum, Blood Cells, and Synovial Fluid of Patients with Severe Osteoarthritis: A Randomized Controlled Trial.|published=2017-Apr-28|authors=Mülek M, Seefried L, Genest F, Högger P|journal=Nutrients|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16441890|title=Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol).|published=2006-Jan-27|authors=Grimm T, Chovanová Z, Muchová J, Sumegová K, Liptáková A, Duracková Z, Högger P|journal=J Inflamm (Lond)|][reference|url=https://pubmed.ncbi.nlm.nih.gov/29246219|title=Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study.|published=2017-Dec-16|authors=Jessberger S, Högger P, Genest F, Salter DM, Seefried L|journal=BMC Complement Altern Med|]

Pycnogenol is generally considered safe and well tolerated. Side effects occur rarely and may include headache, dizziness, drowsiness, skin irritation, and gastrointestinal upset (e.g., nausea), the latter of which may improve if pycnogenol is taken with food.[reference|url=https://esmed.org/MRA/mra/article/view/183|title=UPDATE ON THE CLINICAL PHARMACOLOGY OF PYCNOGENOL®|published=2015 Jul|authors=Rohdewald P|journal=Medical Research Archives] 
Most of the research on pycnogenol has been at least partially funded by the manufacturer of pycnogenol. While this doesn’t invalidate the research, it does make it more prone to bias in favor of pycnogenol.

The biological activity of pycnogenol is due to its diverse and rich content of polyphenols.[reference|url=https://pubmed.ncbi.nlm.nih.gov/30456865|title=The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials.|published=2019-Feb|authors=Hadi A, Pourmasoumi M, Mohammadi H, Javaheri A, Rouhani MH|journal=Phytother Res|] Following ingestion, some of these compounds are metabolized by bacteria in the colon into other bioactive compounds that can be absorbed. For example, bacteria can convert the procyanidins in pycnogenol into the compound M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone), which is thought to strongly contribute to its overall biological effects.[reference|url=https://pubmed.ncbi.nlm.nih.gov/16887024|title=Single and multiple dose pharmacokinetics of maritime pine bark extract (pycnogenol) after oral administration to healthy volunteers|published=2006 Aug 3|authors=Grimm T, Skrabala R, Chovanová Z, Muchová J, Sumegová K, Liptáková A, Duracková Z, Högger P|journal=BMC Clin Pharmacol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/28836883|title=Review on Sustained Relief of Osteoarthritis Symptoms with a Proprietary Extract from Pine Bark, Pycnogenol|published=2018 Jan|authors=Rohdewald PJ|journal=J Med Food|] 
Pycnogenol seems to decrease pain and inflammation by reducing the activity of certain pathways in the body that lead to the production of pro-inflammatory compounds, including <a href="/outcomes/nf-kb-activity/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;NF-kB Activity&lt;/h6&gt;&lt;p&gt;Nuclear factor kappa B (NF-kB) is a protein that induces inflammation. NF-kB is crucial for preventing infection, but its dysregulation has been linked to various inflammatory and autoimmune diseases.&lt;/p&gt;&lt;/div&gt;">nuclear factor kappa B</a> (NF-κB) and cyclooxygenase (COX)-1 and COX-2 enzymes.[reference|url=https://pubmed.ncbi.nlm.nih.gov/16441890|title=Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol).|published=2006-Jan-27|authors=Grimm T, Chovanová Z, Muchová J, Sumegová K, Liptáková A, Duracková Z, Högger P|journal=J Inflamm (Lond)|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16330178|title=Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol).|published=2006-Jan|authors=Schäfer A, Chovanová Z, Muchová J, Sumegová K, Liptáková A, Duracková Z, Högger P|journal=Biomed Pharmacother|] As an antioxidant, in vitro and animal research suggests that pycnogenol may directly scavenge free radicals, regenerate other antioxidants in the body (e.g., vitamin C, vitamin E, and glutathione), and increase the activity of antioxidant enzymes.[reference|url=https://pubmed.ncbi.nlm.nih.gov/10490291|title=Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol.|published=1999-Sep|authors=Packer L, Rimbach G, Virgili F|journal=Free Radic Biol Med|][reference|url=https://pubmed.ncbi.nlm.nih.gov/27415023|title=Pycnogenol enhances endothelial cell antioxidant defenses.|published=1997-Aug|authors=Wei ZH, Peng QL, Lau BH|journal=Redox Rep|][reference|url=https://pubmed.ncbi.nlm.nih.gov/12815616|title=Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats.|published=2003|authors=Maritim A, Dene BA, Sanders RA, Watkins JB|journal=J Biochem Mol Toxicol|] The above effects, as well as pycnogenol's ability to enhance <a href="/outcomes/nitric-oxide/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nitric Oxide&lt;/h6&gt;&lt;p&gt;Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.&lt;/p&gt;&lt;/div&gt;">nitric oxide</a> synthesis and increase capillary integrity, may contribute to reduced capillary permeability and increased blood flow.[reference|url=https://pubmed.ncbi.nlm.nih.gov/9781917|title=Endothelium-dependent vascular effects of Pycnogenol.|published=1998-Oct|authors=Fitzpatrick DF, Bing B, Rohdewald P|journal=J Cardiovasc Pharmacol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/23775628|title=Pycnogenol® in chronic venous insufficiency and related venous disorders.|published=2014-Mar|authors=Gulati OP|journal=Phytother Res|]

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