Pycnogenol

Synonym(s): Scots pine, pine bark, pine bark extract, Pinus pinaster, proanthocyanidins, maritime pine, Scots pine

Nutrient group: plant extracts & active ingredients, Antioxidants

Sources and physiological effects

Dietary sources
The pine tree is native to the Atlantic coast of France and can live for up to 300 years. Pine bark was used for treatment of inflammatory diseases by Hippocrates in the 4th century BC.The patented extract of Pinus Pinaster Pycnogenol^® ,contains a consistent quantity of proanthocyanidins, bioflavonoids and organic acids with natural active properties. Horphag, the producer of Pycnogenol^®, has been dealing with the effect, safety and quality of the extract for more than 40 years. Over 130 clinical studies and more than 300 scientific publications have been made about the pine bark extract.
Physiological effects
Antioxidant	Regeneration of vitamin C, vitamin E and L-glutathione Increase in antioxidative capacity Inhibition of lipid peroxidation
Inflammation	Inhibition of proinflammatory cytokines
Pain	Inhibition of cyclooxygenase (COX) 1 and 2
Immune system	Stimulation of the immune system Reduction of histamine release
Cardiovascular	Antihrombotic effect by inhibition of platelet aggregation Vasodilative effect by increasing endothelial NO bioavailability Reduction of vasoconstrictive endothelin 1 concentration Improvement of microcirculation
Blood pressure	Antihypertensive effect by inhibition of angiotensin conversion enzyme

Detailed information

Plant-based bioactive substances are the strongest antioxidants

Free radicals are highly reactive compounds that are endogenous and increasingly also exogenous. Due to their extreme reactivity, these aggressive compounds attack almost all structures of the human organism and thereby trigger chain reactions in which new radicals are constantly being produced. The human body has developed an endogenous, antioxidative protection system for the defense against free radicals and reactive oxygen species, which is supported and strengthened by the exogenous supply of antioxidant agents. Plant components are involved in these functions as part of human nutrition.

Pycnogenol^® – natural antioxidants

Pycnogenol^® contains polyphenols from a standardized pure extract obtained from the bark of the maritime pine (Pinus pinaster) and grape seeds. It owes its strong antioxidative potential to the oligomeric proanthocyanidins (OPC) and other bioflavonoids such as catechins, epicatechins, phenolic acids and taxifolin.¹ The contained OPCs show a high antioxidative protection potential, especially against reactive oxygen and nitrogen species, and are thus a suitable instrument for the prevention and treatment of oxidative stress in various target organs.² In vitro studies show that Pycnogenol^® is many times more effective as an antioxidant than vitamin C and vitamin E. Pycnogenol^® can also recycle oxidized vitamin C and regenerate vitamin E.³

Improvement of microcirculation and stabilization of endothelia

Oligomeric proanthocyanidins (OPC) are increasingly used for the therapeutic treatment of connective tissue weaknesses due to their anti-edematous, antiphlogistic and antioxidative capabilities and are also used therapeutically in the initial phases of venous diseases. OPCs increase capillary blood flow and normalize impaired vascular permeability. They bring overstretched veins back to their normal stage and help to reduce fluid accumulations in the tissue.⁴ In addition, they can protect the fine vessel walls and the surrounding connective tissue from age-related oxidative processes. At a daily dose of 100 mg OPC, more than 80 % of patients showed significant improvements after just 10 days.⁵ In a further study in patients with chronic venous microangiopathy, a significant improvement in symptoms was observed with an 8-week administration of 150 mg Pycnogenol^® (3 x 50 mg daily). Capillary filtration was improved and edema reduced.⁶ In another study, wound healing processes were accelerated by increasing the circulation and oxygen supply.⁷

Tinnitus

Symptoms were significantly improved in patients with M. Menière, a disease characterized by the 3 symptoms of vertigo, hearing loss and tinnitus. Pycnogenol^® has been shown to improve cochlear blood flow, resulting in 87.3% of patients being symptom-free after 6 months of 150 mg Pycnogenol^®/d.⁸

Thrombosis prophylaxis

Pycnogenol^® has a patent for the regulation of platelet activity. It inhibits platelet aggregation by a nitrogen monoxide-induced reduction in the release of thromboxane from the platelets.⁹ The clinical relevance of this effect has been demonstrated in several studies. The risk of thrombosis on long-haul flights was significantly reduced if passengers received 200 mg Pycnogenol^® before departure and again after 6 hours of flight.^{10, 11}

Pain reduction

OPCs can intervene in pain perception through various mechanisms. In addition to inhibiting cyclooxygenase.¹² Pycnogenol^® can reduce the activity of proinflammatory proteins such as NF-kB¹³ and C-reactive protein¹⁴ and thus influence inflammatory processes in the body. In arthrosis patients, Pycnogenol^® led to a significant reduction in pain medication¹⁵ and to an increase in maximum walking distance and subjective well-being.¹⁶In several studies in women with endometriosis¹⁷ or dysmenorrhea,^{18, 30} taking Pycnogenol^® resulted in a significant reduction in menstrual pain.

Dysmenorrhea and endometriosis

An estrogen-induced increase in prostaglandin levels is a common cause of lower abdominal pain during menstruation. In a clinical study of 116 women with dysmenorrhea, the pain-reducing effect of Pycnogenol^® was demonstrated during menstruation.¹⁷ The pain intensity and duration could be significantly reduced, which led to a reduction of up to 50% in the use of non-steroidal painkillers. Pycnogenol^® was also shown to significantly reduce pain in endometriosis patients.^{18, 30}

Skin elasticity and hyperpigmentation

Pycnogenol^® has a high affinity for collagen and elastin, the matrix proteins of the skin, and protects them from enzymatic degradation by metalloproteinases.¹⁹ After 6 weeks of oral application, the skin elasticity in women was increased by 9 %.²⁰ In addition, Pycnogenol^® reduces skin pigmentation by inhibiting tyrosine kinase in melanocytes. For example, in women with hormonal hyperpigmentation (melasma), the degree of skin pigmentation was reduced by 37 % after one month of Pycnogenol^®.³

Pycnogenol^® in Diabetes Management

Numerous studies have demonstrated positive effects of Pycnogenol^® in the therapy of patients with diabetes mellitus. The prevention of ischemia and necrosis caused by diabetic microangiopathies is a major challenge in diabetes management. Pycnogenol^® improves the microcirculation in the tissue by increasing capillary blood flow. In a study in patients with chronic venous microangiopathy, a significant improvement in symptoms was observed with an 8-week administration of 150 mg Pycnogenol^® (3 x 50 mg daily). The capillary filtration was improved and edema was reduced.²¹ In another study of more than 1000 diabetics, a 6-month intake of Pycnogenol^® prevented a worsening of the existing retinopathy.²² Diabetic ulcers heal faster by improving skin circulation²³ and the occurrence of muscle cramps and pain can also be reduced by taking Pycnogenol®.²⁴ In addition, Pycnogenol® reduces the carbohydrate intake in the intestine and thus the blood glucose levels by inhibiting duodenal alpha-glucosidase.²⁵ In diabetics with mild to moderate hypertension, 12-week administration of 125 mg Pycnogenol^® led to better diabetes management compared to the control group, reduced risk factors for cardiovascular disease, and reduced the dose of antihypertensive drugs.²⁶

Pycnogenol in Restless Legs Syndrome (RLS)

Pycnogenol impresses with its improvement of microcirculation and also shows promise in the treatment of restless legs syndrome (RLS) in a study. Twenty-one of a total of 45 subjects who received 150 mg of Pycnogenol daily in addition to standard treatment in the study showed significant improvement in their RLS-specific symptoms, including pulling, throbbing, general pain, itching, and associated sleep problems after the intervention period of 4 weeks. In addition, at the end of the study, the need for analgesics was also lower in the Pycnogenol group, with optimal tolerability and no side effects.²⁷

Further possible applications

Promising evidence exists for the use of Pycnogenol^® in asthma. Pycnogenol^® acts by inhibiting histamine release²⁸ and reducing leukotriene levels and associated bronchoconstriction.²⁹ Pycnogenol^® is also a natural preparation for the alleviation of ADHD symptoms in children and is definitely a topic of discussion.³⁰

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	To improve antioxidant status and treat oxidative stress	100 mg/d
	For prevention and treatment of venous disorders of the legs, for hemorrhoids, for connective tissue weakness and couperosis and thrombosis prevention	100 mg/d
	Therapeutic support for Diabetes mellitus	100 – 400 mg/d
	To improve capillary microcirculation in wound healing disorders and tinnitus	150 mg/d
	For pain reduction in arthrosis, pain control and endometriosis	100 – 400 mg/d
	To improve the appearance of the skin, especially with hormonal hyperpigmentation (melasma)	100 mg/d
	Preventive and concomitant therapeutic for coronary heart disease and arteriosclerosis, hypertension and increased LDL values	100 – 300 mg/d

Administration

General mode of administration
When	Pycnogenol^® should be taken with meals.
Side effects
In rare cases mild gastrointestinal complaints (nausea) or headaches and skin irritation may occur.
Contraindications
Pregnancy and lactation (due to missing safety data)

Interactions

Drug interactions
Antihypertensive drugs (nifedipine, ACE inhibitor)	Pycnogenol^® may reduce the need for antihypertensive drugs.
Anticoagulants (e.g. ASS, clopidogrel)	Simultaneous use may increase the risk of bleeding.
Nutrient interaction
Trace elements	Polyphenols inhibit the absorption of iron when taken simultaneously.
Glucosamine	Pycnogenol can be combined with glucosamine in adjuvant therapy due to its analgesic and anti-inflammatory effects.

Description and related substances

Description

Pycnogenol® is a special extract from the bark of the French maritime pine.

Related substances

Pycnogenol^®contains 70% specified procyanidins (e.g. oligomeric proanthocyanidins; monomeric catechins).

References

¹ MedlinePlus: http://www.nlm.nih.gov/medlineplus/druginfo/natural/patientpycnogenol.html, Stand: 22.12.09
² Packer, L. et al. 1999. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med. 27(5-6):704-24.
³ Ni, Z. et al. 2002. Treatment of melasma with Pycnogenol. Phytother Res. 16(6):567-71.
⁴ Gulati, O. P. 2013. Pycnogenol® in chronic venous insufficiency and related venous disorders. Phytotherapy Research. 28(3):348-362.
⁵ Costantini, A. et al. 1999. Clinical and capillaroscopic evaluation of chronic uncomplicated venous insufficiency with procyanidins extracted from vitis vinifera. Minerva Cardioangiol. 47(1-2):39-46.
⁶ Cesarone, M. R. et al. 2006. Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology. 57(5):569-76.
⁷ Belcaro, G. et al. 2006. Diabetic ulcers: microcirculatory improvement and faster healing with Pycnogenol®. Clin Appl Thromb Hemost. 12:318–323.
⁸ Luzzi, R. et al. 2014. Improvement in symptoms and cochlear flow with Pycnogenol® in patients with Meniere’s disease and tinnitus. Minerva Med. 104 No.3:245–254.
⁹ Pütter, M. et al. 1999. Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol®. Thromb Res. 95:155-161.
¹⁰ Cesarone, M. R. et al. 2004. Prevention of edema in long flights with Pycnogenol®. Clin Appl Thromb Hemost. 11:289-294.
¹¹ Belcaro, G. et al. 2004. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with Pycnogenol®. Clin Appl Thromb Hemost. 10:373-377.
¹² Schäfer, A. et al. 2005. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol®). Biomed Pharmacother. 60:5–9.
¹³ Grimm, T. et al. 2006. Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol®). J Inflamm. 3:1-6.
¹⁴ Belcaro, G. et al. 2008. Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol®. Redox Rep 13: 271-276.
¹⁵ Cisar, P. et al. 2008. Effect of pine bark extract (Pycnogenol®) on symptoms of knee osteoarthritis. Phytother Res 22:1087–1092.
¹⁶ Belcaro G. et al. 2008. Treatment of osteoarthritis with Pycnogenol®. The SVOS (San Valentino Osteo-Arthrosis Study). Evaluation of Signs, Symptoms, Physical Performance and Vascular Aspects. Phytother Res. 22:518-523.
¹⁷ Suzuki, N. et al. 2007. Effect of Pycnogenol®, French maritime pine bark extract, on dysmenorrhea: a multicenter, randomized, double-blind, placebo-controlled study. J Reprod Med.
¹⁸ Jr., H. M. et al. 2013. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain. International Journal of Women's Health. 35.
¹⁹ Marini, A. et al. 2012. Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women. Skin Pharmacol Physiol. 25:86-92.
²⁰ Segger, D., Schönlau, F. 2004. Supplementation with Evelle® improves smoothness and elasticity in a double blind, placebocontrolled study with 62 women. J Dermatolog Treat. 15:222–226.
²¹ Cesarone, M. R. et al. 2006. Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology. 57(5):569-76.
^₂₂ Schönlau, F., Rohdewald, P. 2002. Pycnogenol® for diabetic retinopathy. A review. Int Ophthalmol. 24:161–171.
²³ Belcaro, G. et al. 2006. Diabetic ulcers: microcirculatory improvement and faster healing with Pycnogenol®. Clin Appl Thromb Hemost. 12:318–323.
²⁴ Vinciguerra, G. et al. 2006. Cramps and muscular pain: prevention with Pycnogenol® in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathie. Angiology. 57(3):333–339.
²⁵ Schäfer, A., Högger, P. 2007. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol®) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract. 77:41–46.
²⁶ Zibadi, S. et al. 2008. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplemtation. Nutr Res. 28(5):315-20.
²⁷ Belcaro, G. et al. 2022. Restless legs syndrome: prevention with Pycnogenol® and improvement of the venoarteriolar response. Panminerva Med.64(2):253-258.
²⁸ Sharma, S. C. et al. 2003. Pycnogenol® inhibits the release of histamine from mast cells. Phytother Res. 17:66–69.
²⁹ Hosseini, S. et al. 2001. Pycnogenol® in the management of asthma. J Med Food 4:201–209.
³⁰ Trebatická, J. et al. 2006. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry. 15(6):329-35.
³¹ Maia, H. et al. 2014. The effect of Pycnogenol on patients with dysmenorrhea using low-dose oral contraceptives. International Journal of Women's Health. 1019-1022.

References Interactions

Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.