Pine Bark Extract

Generic name: Pinus Pinaster Aiton., Pinus Radiata
Brand names: Enzogenol, Maritime Pine, Maritime Pine Extract, Monterey Pine Extract, Pycnogenol

Usage of Pine Bark Extract

The quality of many published clinical studies has been limited by small sample sizes or the use of nonrandomized or open-label designs. Many studies have been conducted by a small pool of researchers, some being industry sponsored. Insufficient evidence exists supporting the use of pine bark extracts for any chronic condition. Findings from ongoing clinical trials are anticipated.(D'Andrea 2010, Maimoona 2011, Schoonees 2012)

Antioxidant properties of pine bark extracts have been well described in laboratory studies and are considered to be responsible for the majority of clinical effects.(D'Andrea 2010, Frevel 2012, Maimoona 2011) However, clinical studies evaluating changes in antioxidant status after pine bark extract administration have produced equivocal results.(Devaraj 2002, Dvořáková 2010, Silliman 2003)

Antibacterial activity

Animal data

In a murine model of periodontitis, pine bark extract as part of the diet exerted antibacterial activity against Porphyromonas gingivalis.(Sugimoto 2015)

Antidepressant-induced sexual dysfunction

Clinical data

In a clinical study involving men and women with antidepressant-induced sexual dysfunction, the effects of pine bark extract 50 mg/day for 4 months in combination with escitalopram were compared with escitalopram alone. The combination attenuated sexual dysfunction after 1 month of treatment and continued until the last visit.(Smetanka 2019)

Anti-inflammatory/Osteoarthritic effects

Animal and in vitro data

In a murine model of ischemia/reperfusion-induced injury, rats treated with pine bark extract (Pycnogenol) demonstrated less cortex damage and edema compared to the control group. Pycnogenol also significantly reduced interleukin (IL)-1beta and tumor necrosis factor alpha levels compared with the control group (P<0.001).(Ozoner 2019)

Clinical data

In a clinical study of patients with severe osteoarthritis scheduled to undergo knee arthroplasty, effects of pine bark extract 100 mg twice daily or placebo for 3 weeks prior to the procedure were assessed. Patients receiving pine bark extract had a reduction in matrix metallopeptidase-3 (MMP-3), MMP-13, and IL-1beta levels (markers of cartilage degradation).(Jessberger 2017) Evidence also suggests that polyphenols of pine bark extract distribute into synovial fluid.(Mülek 2017)

Antiviral effects

In vitro data

In one study, pine bark extract combined with ribavirin, interferon, and telaprevir increased hepatitis C virus antiviral activity, either synergistically or additively.(Ezzikouri 2016)

Bone effects

Animal and in vitro data

In a study of ovariectomized rats, pine bark extract 40 mg/kg given for 9 weeks increased bone mineral density, decreased biomarkers of bone resorption, and restored impaired trabecular microarchitecture.(Huang 2015) In a murine model of periodontitis, pine bark extract as part of the diet inhibited osteoclast differentiation.(Sugimoto 2015)

Clinical data

Administration of 250 mg/day of French maritime pine bark extract (Oligopin) for 12 weeks significantly improved bone remodelling markers compared to placebo (P=0.006) in postmenopausal women with osteopenia in a double-blind, randomized, controlled trial (n=44). No between-group differences were observed in calcium, phosphorus, magnesium, vitamin D, or parathyroid hormone levels.(Panahande 2019)

Cardiovascular effects

Animal and in vitro data

Studies in spontaneously hypertensive rats suggest a protective effect on microvasculature by pine bark extract, thought to be due to its antioxidant effects. Small decreases in systolic blood pressure were also observed.(Rezzani 2010) In a study of diabetic rats, cardiomyopathy was reduced by pine bark extract; the reduction was considered to be due to antioxidant activity but also possibly due to improved cardiac energy metabolism via observed lowered plasma glucose.(Klimas 2010) In a murine model of atherosclerosis, 12-week administration of pine bark extract was associated with a reduction in plaque areas as well as a reduction in lipids in the plaques. Additionally, serum lipid levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) were decreased, and high-density lipoprotein (HDL) was increased with pine bark extract treatment.(Luo 2015)

Clinical data

Changes in markers of oxidative stress in cardiovascular disease have been demonstrated in small clinical trials of pine bark extract.(Enseleit 2012, Nishioka 2007, Schoonees 2012, Young 2006)

A meta-analysis of 5 controlled studies (N=442) published between 2003 and 2012 included healthy volunteers as well as patients with hypertension, stable coronary artery disease, type 2 diabetes and hypertension, erectile dysfunction, elderly age, and perimenopausal status receiving the standardized maritime pine bark extract Pycnogenol (dosed at 120 to 200 mg/day for durations of 2 to 24 weeks). Lipid parameters (ie, total cholesterol, HDL, triglycerides), excluding LDL, were not affected by supplementation with Pycnogenol. A significant dose-effect association was found for effects on LDL (slope, −0.007; P=0.01). Limitations of the analysis included observed effect sizes too small to be clinically relevant, lack of data on concomitant lipid-lowering drugs, and uncontrolled dietary measures.(Sahebkar 2014)

In another systematic review and meta-analysis including 14 trials of 1,065 patients, pine bark extract (dosage range, 60 to 340 mg daily) significantly increased HDL (3.27 mg/dL; 95% CI, 0.19 to 6.36; P=0.038). However, there were no effects on other cholesterol parameters (total cholesterol, triacylglycerol, and LDL).(Hadi 2019)

Pine bark extract supplementation significantly impacted C-reactive protein levels (−1.22 mg/dL; 95% CI, −2.43 to −0.003; I2=99%; P<0.001) in another systematic review and meta-analysis.(Nikpayam 2018)

Cancer

Animal and in vitro data

Pine bark extract reduced apoptosis in human oral squamous cell carcinoma HSC-3 cells, MC-3 human mucoepidermoid carcinoma (MEC) cells, and HT 1080 fibrosarcoma cells.(Harati 2015, Yang 2014, Yang 2016) Additionally, pine bark extract suppressed neoplastic transformation in HSC-3 cells and decreased cell viability in MEC cells.(Yang 2014, Yang 2016)

CNS/Cognitive effects

Animal and in vitro data

In a murine model of Alzheimer disease, pine bark extract improved spatial memory in the pre-onset (ie, just before the development of plaques) treatment paradigm group. In both the pre-onset and post-onset (ie, after the appearance of beta-amyloid plaques) paradigm treatment groups, pine bark extract reduced plaque number (ie, decreased the number of small plaques in the pre-onset group, and reduced the number of large plaques in the post-onset group) but did not change the average plaque size.(Paarmann 2019) In a murine model of pentylenetetrazole-induced epilepsy, pine bark extract increased latency, decreased duration, and reduced frequency of seizures in a dose-dependent manner compared with the control group.(Goel 2019)

Clinical data

Pine bark extract resulted in enhanced concentration and reduced hyperactivity after 1 month of therapy in a study of children with ADHD. Visual-motor coordination was also improved. Effects might be attributed to reductions in catecholamine levels, such as dopamine, epinephrine, and norepinephrine, as well as stimulation of endothelial nitric oxide synthase.(Verlaet 2018)

In a registry study of 87 patients with mild cognitive impairment (Mini-Mental State Examination [MMSE] score of 18 to 23), pine bark extract 150 mg/day for 8 weeks significantly improved MMSE scores from baseline (21.64±1.5) to 8 weeks (25.64±1.4; P<0.05). This effect was not seen in those receiving standard care. The median increase associated with pine bark extract was 18% compared with 2.48% in the standard care group (P<0.05).(Hosoi 2018)

Dermatological effects

Clinical data

A review article describes several small studies regarding pine bark extract's potential beneficial dermatological effects. It is believed to provide ultraviolet (UV) protection, decrease skin hyperpigmentation, and improve the skin barrier. In one study, pine bark extract (1.1 mg/kg or 1.66 mg/kg) given orally for 4 to 8 weeks reduced UV-induced erythema in fair-skinned individuals. Additionally, pine bark extract 75 mg/day given orally for 1 month improved parameters measuring melasma in a study of 30 Chinese females. Lastly, when combined with vitamins and minerals, pine bark extract improved elasticity of the skin in women.(Grether-Beck 2016)

Diabetes

Animal and in vitro data

In vitro studies suggest pine bark extract exhibits a number of beneficial effects, including inhibition of lipid accumulation in adipocytes, stimulation of lipolysis, and increased glucose uptake.(Hasegawa 2000, Lee 2010, Lee 2012) Pine bark extract may inhibit alpha-glucosidase.(Gulati 2015)

In rodent studies, pine bark extract showed antioxidant effects and improved insulin resistance and hyperglycemia.(Aydin 2019, Bang 2014, Berryman 2004) Additionally, pine bark extract improved oxidative stress, lipid profiles, liver function markers, and DNA damage in hyperglycemic rats.(Aydin 2019)

Clinical data

Limited, methodologically weak clinical trials have been conducted in patients with type 2 diabetes.(Schoonees 2012) Doses of pine bark extract 150 mg daily have been used in these studies with no apparent serious adverse effects; more robust clinical studies are needed. A double-blind, randomized, placebo-controlled study conducted in 46 adults with type 2 diabetes and evidence of microalbuminuria reported significant decreases in mean adjusted glycated hemoglobin (HbA1c) (−1.17%; P<0.001), total cholesterol (−20.5 mg/dL; P=0.03), vascular cell adhesion molecule 1 (−9.16; P<0.001), and urinary albumin:creatinine ratio (−16.35; P<0.001) with supplementation of 100 mg pine bark extract daily for 8 weeks compared to placebo. However, no difference between groups was observed in fasting blood glucose, insulin, insulin resistance, triglycerides, LDL, or HDL. The supplement was well tolerated with no adverse events observed.(Navval-Esfahlan 2021)

Drug-induced toxicity

Animal and in vitro data

Rat models have demonstrated pine bark extract's ability to protect against cisplatin-induced ototoxicity and acute kidney injury.(Eryilmaz 2016, Lee 2017) Additionally, pine bark extract exerted antioxidant and hepatoprotective effects in a study of rats with acetaminophen-induced hepatotoxicity.(Rašković 2019)

Female reproductive disorders

Clinical data

In a clinical study of 58 women with endometriosis, pine bark extract 60 mg/day for 48 weeks improved symptoms of pelvic pain, pelvic tenderness, menstrual pain, and induration without impacting estrogen levels or menstrual cycles. However, CA-125 levels decreased.(Kohama 2007) In another study, women receiving pine bark extract with a low-dose oral contraceptive had lower pain scores for dysmenorrhea compared to women receiving only the low-dose oral contraceptive.(Maia 2014)

Male reproductive disorders

The beneficial effects of pine bark extract in erectile dysfunction are believed to be attributed to the activation of endothelial nitric oxide synthase, which leads to enhanced nitric oxide production and vasodilation.(Chang 2019)

Animal and in vitro data

In a murine study, pine bark extract 40 mg/kg decreased serum and prostate dihydrotestosterone concentrations and reduced the weight of the prostate. Pine bark extract also resulted in thinner epithelial cells in the prostate gland.(Ko 2018)

Clinical data

In a clinical study of 75 men with signs and symptoms of benign prostatic hyperplasia, Pycnogenol 50 mg 3 times daily for 60 days significantly improved emptying, frequency, intermittency, urgency, weak flow, straining, and nocturia compared with a standard management group and a group receiving 5-alpha reductase inhibitor therapy (P<0.05 for both comparisons).(Ledda 2018)

A meta-analysis showed that the combination of pine bark extract and arginine improved erectile dysfunction.(Chang Rhim 2019)

Respiratory effects

Animal and in vitro data

In an in vitro study of ovalbumin-induced allergic asthma, pine bark extract decreased nitric oxide production and IL-1beta and IL-6 levels. In the in vivo arm of the study, ovalbumin-sensitized mice showed a decrease in the number of inflammatory cells and in airway hyperreactivity.(Shin 2013) In a murine model of chronic obstructive pulmonary disease, pine bark extract decreased the inflammatory cells caused by cigarette smoke and lipopolysaccharide exposure in bronchoalveolar lavage fluid, and inhibited collagen deposition in the lungs.(Ko 2017, Shin 2016)

Clinical data

Limited small studies evaluating Pycnogenol use in children and adults with asthma have indicated benefit.(Clark 2010, Schoonees 2012)

Based on data from 4,521 healthy participants enrolled in 20 randomized controlled trials (including 1 study with pycnogenol), meta-analyses demonstrated that flavonoid-containing supplements were safe and effective in preventing acute respiratory tract infections (ARTIs) compared to controls with a relative risk (RR) of 0.81 (95% confidence interval [CI] 0.74 to 0.89; P<0.001) and low heterogeneity. A reduction in mean ARTI sick days was also observed with the supplements; however, heterogeneity was significant (weighted mean difference [WMD], −0.56; 95% CI, −1.04 to −0.08; P=0.021). In subgroup analysis, significance in mean ARTI sick days was retained with flavonoid mixtures (as seen with pycnogenol products) but not with use of single flavonoids (ie, quercetin, catechin). Additionally, the pycnogenol study reported faster regression of all symptoms compared to controls (P<0.05). Pooled results from 16 of the trials indicated that adverse reactions were not increased in the flavonoid supplement groups compared to controls.(Yao 2022)

Venous insufficiency/Varicose veins

In a review of natural products used in the treatment of chronic venous insufficiency, pine bark extract exerted antioxidant, anti-inflammatory, and vasoactive effects. It reduced passive dilatation and stretching, giving the venous wall enhanced elasticity and promoting the ability of the vein to recover following stress.(Lichota 2019)

Clinical data

In healthy women after their second pregnancy, the effects of pine bark extract (100 mg/day for 12 months) on varicose veins were assessed. At 3 and 6 months, the number of varicose veins was lower. At 6 months, fewer patients in the group receiving pine bark extract (3.2%) experienced edema compared to the control group (13.3%). Cramps and the presence of spider veins were reduced in those receiving pine bark extract, and there was less of a need for interventions for varicose veins. Reevaluation at 12 months showed that variations in varicose veins, spider veins, and symptoms had not changed from the 6-month follow-up.(Belcaro 2017)

Pine Bark Extract side effects

Pine bark extract is generally well tolerated, with occasional minor GI discomfort, dizziness, nausea, and headache reported. GI discomfort may be minimized by taking the product with or after meals. In women using Pycnogenol for dysmenorrhea or endometriosis, acne and dysfunctional uterine bleeding have been reported; additionally, diarrhea has been reported in those with dysmenorrhea and epigastric pain in those with endometriosis.ABC 2019

Before taking Pine Bark Extract

Information regarding safety and efficacy during pregnancy and lactation is lacking. Pine bark extract at a dose of 30 mg/day has been studied in a small clinical trial for pain in the third trimester of pregnancy and did not result in any adverse effects; however, this should not be regarded as evidence of safety in pregnancy.Kohama 2006

How to use Pine Bark Extract

In clinical trials, Pycnogenol dosages ranged from 20 to 360 mg (or were weight based). The American Botanical Council states the most common duration of use in clinical trials was 2 to 3 weeksABC 2019; however, longer-term use has been described.

  • ADHD: 1 mg/kg/day.
  • Asthma: 100 mg/day.
  • Chronic venous insufficiency: 150 to 360 mg/day.
  • Diabetes: 50 to 200 mg/day.
  • Dyslipidemia: 120 to 150 mg/day.
  • Dysmenorrhea: 30 to 60 mg/day.
  • Endometriosis: 60 mg/day.
  • Erectile dysfunction: 120 mg/day.
  • Hypertension: 100 to 200 mg/day.
  • Osteoarthritis: 100 to 150 mg/day.
  • Retinopathy: 20 to 160 mg/day.

    • Warnings

    Pine bark extract is GRAS based on data from animal studies and clinical trials; however, few studies have evaluated safety as a primary outcome.D'Andrea 2010, Dvořáková 2010, Maimoona 2011, USDA 2019 P. radiata extract was nonmutagenic in the Ames test.Frevel 2012 Pine bark is a member of the Pinaceae (Pine) family; consumption of pine needles has been associated with abortion in cattle.Pütter 1999

    What other drugs will affect Pine Bark Extract

    None well documented.

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