Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68. Related Articles, Links

A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology.

Rohdewald P.

Institute Pharmaceutical Chemistry, Westfalische Wilhelms-Universitat Munster, Germany. rohdewa@uni-muenster.de

OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC), a standardized extract of French maritime pine bark, has favorable pharmacological properties. This is a review of studies with both PYC and components of the preparation, that have helped to elucidate target sites and possible mechanisms for activity in men. METHODS: Studies appearing in peer reviewed literature, as well as results presented at international meetings not yet available as published papers, are included in this review. Additional data from published sources in German and French languages that are not widely available are also included. RESULTS: Chemical identification studies showed that PYC is primarily composed of procyanidins and phenolic acids. Procyanidins are biopolymers of catechin and epicatechin subunits which are recognized as important constituents in human nutrition. PYC contains a wide variety of procyanidins that range from the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The ferulic acid and taxifolin components are rapidly absorbed and excreted as glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and metabolized to valerolactones which are excreted as glucuronides. PYC has low acute and chronic toxicity with mild unwanted effects occurring in a small percentage of patients following oral administration. Clinical studies indicate that PYC is effective in the treatment of chronic venous insufficiency and retinal micro-hemorrhages. PYC protects against oxidative stress in several cell systems by doubling the intracellular synthesis of anti-oxidative enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant effects involve a role in the regeneration and protection of vitamin C and E. Anti-inflammatory activity has been demonstrated in vitro and in vivo in animals. Protection against UV-radiation-induced erythema was found in a clinical study following oral intake of PYC. In asthma patients symptom scores and circulating leukotrienes are reduced and lung function is improved. Immunomodulation has been observed in both animal models as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase. Dilation of the small blood vessels has been observed in patients with cardiovascular disease, whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces the concentration of thromboxane. The ability to inhibit angiotensin-converting enzyme is associated with a mild antihypertensive effect. PYC relieves premenstrual symptoms, including abdominal pain and this action may be associated with the spasmolytic action of some phenolic acids. An improvement in cognitive function has been observed in controlled animal experiments and these findings support anecdotal reports of improvement in ADHD patients taking PYC supplements. CONCLUSIONS: There is much evidence showing that PYC has beneficial effects on physiological functions. Results from ongoing clinical research are required to confirm and extend previous observations.

Publication Types:
Review
Review, Tutorial

PMID: 11996210 [PubMed - indexed for MEDLINE]

We have had several discussions on ADHD about them, and Tourette's has had many also.
 http://neuro-mancer.mgh.harvard.edu/ubb/Forum99/HTML/001263.html studies supporting grapeseed extract

http://neuro-mancer.mgh.harvard.edu/ubb/Forum7/HTML/001142.html

If you type into the search function
grape seed extract, or pycnogenols on both forums you can find more.

Here are two overviews that explain what these natural substances are chemically and their safety issues, and uses:
http://www.mcp.edu/herbal/opcs/opcs.pdf

http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/GrapeSeeds_PineBark.pdf

This is another:
http://www.antioxidants-online.com/opc_mfine.htm

quote:

Oligomeric proanthocyanidin complexes are primarily known for their free radical scavenging and antioxidant activity. However, these compounds have also been reported to demonstrate antibacterial, antiviral, anticarcinogenic, anti-inflammatory, anti-allergic and vasodilatory actions. In addition, OPCs have been reported to inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and to affect enzyme systems including phospholipase A2, cyclooxygenase, and lipoxygenase. These varied biological activities have resulted in the phytopharmaceutical application of OPCs in reduction of edema, increased peripheral circulation, improvement in vision, treatment of diabetic retinopathy, prevention of cardiovascular disease, treatment of hypercholesterolemia, stabilization of connective tissue tone, reduced adverse allergic and inflammatory responses, and enhanced immune function and wound healing. Additional clinical research is warranted.

There are several ADHD websites with various testamonials about OPCs/grapeseed extract-- this one is typical-- http://www.add-adhd-infoplus.com/oligomeric-proanthocyanidins.html
mostly testamonial in content

There are many products out there.. some expensive (like Flavay), some reasonable.
http://neuro-mancer.mgh.harvard.edu/ubb/Forum7/HTML/001166.html in general grapeseed extract is considered by many to be comparable to the more expensive OPCs from France and elsewhere.

I think the "heart" of the issue is that OPCs work to reduce allergic expression, reduce oxidative load and in those people/children with ADHD and the autism spectrum, they can be useful. This paper shows a reduction of histamine release:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12557250&dopt=Abstract
I also found this interesting quote from
http://www.healthresearch.com/add.htmResearch Article

^*Correspondence to S. C. Sharma, Department of Pharmacology and Therapeutics, Trinity College, Dublin-2, Irish Republic

Received: 12 October 2001; Accepted: 14 February 2002

Pycnogenol prevents haemolytic injury in G6PD deficient human erythrocytes.

Sharma SC, Sharma S, Gulati OP.

Department of Pharmacology and Therapeutics, Trinity College, Dublin-2 Ireland. ssharma@tcd.ie

Glucose6 phosphate dehydrogenase (G6PD) deficiency is the most common X-linked disorder of human erythrocytes where cells have inadequate capacity to destroy peroxides and high susceptibility towards haemolytic changes. Pycnogenol is a proprietary dry extract of the French Maritime pine (Pinus pinaster) bark with high ability to scavenge free radicals. In the present study we have investigated if Pycnogenol can protect G6PD deficient erythrocytes against haemolytic cell damage. Venous blood samples were obtained from six subject of Mediterranean origin with known G6PD deficiency which was also confirmed with standard techniques. Erythrocyte haemolysis in the presence and absence of Pycnogenol was induced either with tert-butylhydroperoxide (t-BHP) or quinine and the haemoglobin release in the supernatant was determined by recording the optical density at 540 nm in a Shimadzu spectrophotometer. Our results have shown that Pycnogenol has protective action against a Xenobiotic chemical induced haemolysis in G6PD deficient human erythrocytes. Copyright 2003 John Wiley & Sons, Ltd.

PMID: 12820238 [PubMed - indexed for MEDLINE]

 The effects of Pycnogenol on DNA damage in vitro and expression of superoxide dismutase and HP1 in Escherichia coli SOD and catalase deficient mutant cells.

Kim YG, Park HY.

Biological Science, College of Natural sciences, Chosun University, Kwangju, Korea. ygnkim@mail.chosun.ac.kr

The procyanidin-rich French maritime pine bark extract Pycnogenol (PYC) is believed to be an antioxidant. To access whether PYC protects DNA against Fenton reaction radicals, pUC 19 plasmid DNA was damaged by OH- radicals generated from Fe(II) plus H2O2 in the presence and absence of PYC. DNA damage was quantified by measuring decreases in supercoiled DNA (SC-DNA) using agarose gel electrophoresis. The results showed that PYC (50 microg/mL) did not inhibit DNA damage from Fenton reaction-generated oxyradicals, when the Fenton reaction was allowed to proceed. However, PYC did protect against DNA damage when added prior to the initiation of the Fenton reaction, suggesting that protection resulted from chelation of Fe rather than from the scavenging of radicals. Moreover, we unexpectedly observed PYC-associated DNA breakage, which was dose- and time- dependent. Other antioxidants such as desferrioxamine (DFO) including butylated hydroxyltoluene (BHT), curcumin and alpha-tocopherol exhibited protective effects against DNA damage caused by the Fenton reaction. Subsequently, we assessed the possible pro-oxidant function of PYC on DNA damage in E. coli SOD deficient mutants under oxidative stress, after observing that PYC can induce SOD under oxidative stress. Although, PYC did not enhance DNA damage, it likewise did not protect against oxidative stress-mediated DNA damage. All together, our data indicate that PYC under some circumstances can enhance oxidative stress-mediated DNA damage in vitro and in vivo. Copyright 2004 John Wiley & Sons, Ltd.

PMID: 15597332 [PubMed - indexed for MEDLINE]

 Treatment of melasma with Pycnogenol.

Ni Z, Mu Y, Gulati O.

Beijing PHT Nutriment Science Technology Development Co. Ltd, Xiyuan Hospital of China Academy of Traditional Chinese Medicine, Institute of Food Safety Control and Inspection, Ministry of Public Health, Beijing, P R China.

Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women. The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects.Pycnogenol is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant. Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Pycnogenol protects against ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma was investigated.Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily, i.e. 75 mg Pycnogenol per day. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index and by routine blood and urine tests.After a 30-day treatment, the average melasma area of the patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the average pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001). The general effective rate was 80%. No side effect was observed. The results of the blood and urine test parameters at baseline and at day 30 were within the normal range. Moreover, several other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved.To conclude, Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:

·         Clinical Trial

PMID: 12237816 [PubMed - indexed for MEDLINE]

Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency.

Koch R.

Wolfsschlucht 6a, 34117 Kassel, Germany.

The aim of this study was to compare the efficacy of Venostasin (horse chestnut seed extract) and Pycnogenol (French maritime pine bark extract) in the treatment of chronic venous insufficiency (CVI). In an open, controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks. The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment: circumference of the lower legs and rating of subjective symptoms (scores) of pain, cramps, night-time swelling, feeling of "heaviness", and reddening of the skin. In addition, blood levels of cholesterol LDL and HDL were determined before and at the end of treatment. Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms. Furthermore, Pycnogenol significantly decreased cholesterol and LDL values in the blood, whereas HDL remained unaffected. Venostasin only moderately but not significantly, reduced the circumference of the lower limbs and marginally improved symptoms. Venostasin had no influence on the determined lipid values. Both medications were equally well tolerated. In conclusion, Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:

·         Clinical Trial

·         Randomized Controlled Trial

PMID: 11933130 [PubMed - indexed for MEDLINE]

Rohdewald P.

Institute Pharmaceutical Chemistry, Westfalische Wilhelms-Universitat Munster, Germany. rohdewa@uni-muenster.de

OBJECTIVES: An increasing body of evidence indicates that Pycnogenol (PYC), a standardized extract of French maritime pine bark, has favorable pharmacological properties. This is a review of studies with both PYC and components of the preparation, that have helped to elucidate target sites and possible mechanisms for activity in men. METHODS: Studies appearing in peer reviewed literature, as well as results presented at international meetings not yet available as published papers, are included in this review. Additional data from published sources in German and French languages that are not widely available are also included. RESULTS: Chemical identification studies showed that PYC is primarily composed of procyanidins and phenolic acids. Procyanidins are biopolymers of catechin and epicatechin subunits which are recognized as important constituents in human nutrition. PYC contains a wide variety of procyanidins that range from the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The ferulic acid and taxifolin components are rapidly absorbed and excreted as glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and metabolized to valerolactones which are excreted as glucuronides. PYC has low acute and chronic toxicity with mild unwanted effects occurring in a small percentage of patients following oral administration. Clinical studies indicate that PYC is effective in the treatment of chronic venous insufficiency and retinal micro-hemorrhages. PYC protects against oxidative stress in several cell systems by doubling the intracellular synthesis of anti-oxidative enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant effects involve a role in the regeneration and protection of vitamin C and E. Anti-inflammatory activity has been demonstrated in vitro and in vivo in animals. Protection against UV-radiation-induced erythema was found in a clinical study following oral intake of PYC. In asthma patients symptom scores and circulating leukotrienes are reduced and lung function is improved. Immunomodulation has been observed in both animal models as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase. Dilation of the small blood vessels has been observed in patients with cardiovascular disease, whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces the concentration of thromboxane. The ability to inhibit angiotensin-converting enzyme is associated with a mild antihypertensive effect. PYC relieves premenstrual symptoms, including abdominal pain and this action may be associated with the spasmolytic action of some phenolic acids. An improvement in cognitive function has been observed in controlled animal experiments and these findings support anecdotal reports of improvement in ADHD patients taking PYC supplements. CONCLUSIONS: There is much evidence showing that PYC has beneficial effects on physiological functions. Results from ongoing clinical research are required to confirm and extend previous observations.

Publication Types:

·         Review

·         Review, Tutorial

PMID: 11996210 [PubMed - indexed for MEDLINE]

 
Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II.

Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P.

Guang An Men Hospital of Chinese Medical Science Research Institute, Beijing, PR China.

A double-blind, placebo-controlled, randomized, multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract, Pynogenol. Supplementation with 100 mg Pycnogenol for 12 weeks, during which a standard anti-diabetic treatment was continued, significantly lowered plasma glucose levels as compared to placebo. HbA1(c) was also lowered; however, the difference as compared to placebo was statistically significant only for the first month. In the Pycnogenol-group endothelin-1 was significantly decreased, while 6-ketoprostaglandin F(1a) in plasma was elevated compared to placebo. Nitric oxide levels in plasma increased during treatment in both groups, but, differences did not reach statistical significance. Pycnogenol was well-tolerated with ECG, electrolytes, creatinine and blood urea nitrogen remaining unchanged in both groups. Mild and transient unwanted effects were reported for both groups without significant differences. Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function.

Publication Types:

·         Clinical Trial

·         Multicenter Study

·         Randomized Controlled Trial

PMID: 15363656 [PubMed - indexed for MEDLINE]

 
Pycnogenol accelerates wound healing and reduces scar formation.

Blazso G, Gabor M, Schonlau F, Rohdewald P.

Department of Pharmacodynamics and Biopharmacy, Szent-Gyorgyi Albert Medical and Pharmaceutical Center, University of Szeged, Hungary. blazso@pharma.szote.uszeged.hu

Pycnogenol was applied topically to experimental wounds inflicted on healthy rats by means of a branding iron. The wound-healing time was taken as the number of days required for 50% of the scabs to separate spontaneously from the animals. Application of a gel formulation containing 1% Pycnogenol significantly shortened the wound healing time, by 1.6 days compared with the group treated with gel only (15.4 days). The application of 2% Pycnogenol decreased the healing time by almost 3 days, while 5% Pycnogenol further accelerated the wound-healing process. In parallel, Pycnogenol gels reduced the diameter of the scars remaining following complete scab loss in a concentration-dependent manner. In conclusion, Pycnogenol is a potent active ingredient for the treatment of minor injuries.

PMID: 15305320 [PubMed - indexed for MEDLINE]

Pycnogenol for diabetic retinopathy. A review.

Schonlau F, Rohdewald P.

Institute of Pharmaceutical Chemistry, Westfalische Wilhelms Universitat Munster, Germany.

Diabetic retinopathy represents a serious health threat to a rapidly growing number of patients with diabetes mellitus. The retinal microangiopathy is characterised by vascular lesions with exudate deposits and haemorrhages causing vision loss. Pycnogenol, a standardised extract of the bark of the French maritime pine (Pinus pinaster), is known to increase capillary resistance. Pycnogenol has been tested for treatment and prevention of retinopathy in five clinical trials with a total number of 1289 patients since the late 1960's. All but one of these studies have been reported in French and German and, today, are of limited accessibility, giving the impetus for reviewing them in detail in this article. There were two open case studies and two double blind studies (one controlled against calcium dobesilate and another against placebo) and, finally, one multi-center field study with 1169 diabetics. All of these studies unequivocally showed that Pycnogenol retains progression of retinopathy and partly recovers visual acuity. Treatment efficacy of Pycnogenol was at least as good as that of calcium dobesilate. Pycnogenol was shown to improve capillary resistance and reduce leakages into the retina. Tolerance was generally very good and side effects were rare, mostly referring to gastric discomfort. In conclusion, treatment with Pycnogenol had a favourable outcome in the majority of the patients with diabetic retinopathy.

Publication Types:

·         Meta-Analysis

PMID: 12498513 [PubMed - indexed for MEDLINE]

Therapeutic efficacy of pycnogenol in experimental inflammatory bowel diseases.

Mochizuki M, Hasegawa N.

Department of Health and Nutrition, School of Health and Human Life, Nagoya Bunri University, Inazawa, Japan.

Pycnogenol was administered for 10 days by gavage to Sprague-Dawley rats fed an elemental diet, then inflammatory bowel disease (IBD) was induced by intrarectal administration of ethanol 2,4,6-trinitrobenzene sulfonic acid (TNBS). Twelve hours after TNBS treatment, the rats were killed, the colon was assessed by a macroscopic damage score and mucosa homogenate was assayed for myeloperoxidase (MPO) activity. The supplementation of pycnogenol significantly inhibited the macroscopic damage score and MPO activity in a dose-dependent manner. These results suggested that pycnogenol ameliorates TNBS-induced inflammation by radical scavenging activity, and may have beneficial effects as a supplement in enteral nutrition for IBD. 2004 John Wiley & Sons, Ltd.

PMID: 15742344 [PubMed - indexed for MEDLINE]

Kim HC, Healey JM.

Utah State University, Logan 84322, USA.

The treatment of cryptosporidiosis using pine bark extract (Pycnogenol) in immunosuppressed adult C57BL/6N mice infected with Cryptosporidium parvum was investigated. Five groups of 10 mice/group were used. Groups 1, 2, 3, and 5 served as normal, toxicity, placebo, and positive controls, respectively. Mice in groups 2-5 were immunosuppressed with dexamethasone phosphate administered ad libitum in drinking water at a dosage level of 12 microg/ml. Mice in groups 3-5 were inoculated per os with 10(6) C. parvum oocysts on the day immunosuppression was started. Mice in groups 2 and 4 were treated by administering Pycnogenol orally at 30 mg/kg/day. In group 4, Pycnogenol was first administered on day 3 postinoculation. Of the four groups of mice immunosuppressed with DEXp (groups 2-5), the two groups treated with Pycnogenol (groups 2 and 4) had no premature deaths. The other two groups (groups 3 and 5) had 3 and 4 mice die, respectively, before the experiment ended. Consequently, Pycnogenol was judged to be non-toxic at the dosage level used and even afforded mice some positive health benefits. Fecal oocyst shedding in groups 3-5 was initially detected on day 3 postinoculation. These mice continued to shed oocysts throughout the duration of the 28-day experiment. Oocyst shedding intensities were greater in group 3 and 5 than in group 4. However, histological examination of infected intestinal tissues in groups 3-5 revealed no significant difference with regard to parasite colonization and villus/crypt (V/C) length ratios. As a result, Pycnogenol was determined to be therapeutically effective against C. parvum at 30 mg/kg/day only when measured by fecal oocyst shedding intensity. There was no effect on parasite tissue colonization and V/C ratios in infected mice. We conclude that Pycnogenol is a useful dietary supplement for C. parvum-infected patients by affording some positive health benefits, significantly reduces fecal oocyst shedding, but does not decrease parasite colonization of intestinal tissue.

PMID: 11789589 [PubMed - indexed for MEDLINE]