Pycnogenol® Helps Asthmatic Patients

Asthma is characterised by episodes of wheezy breathlessness with intervals of relative or complete freedom from symptoms. Asthma is believed to result from inflammatory processes of the bronchi causing them to constrict and swell, aggravating the airflow. In many patients, specific hypersensitivity reactions to inhaled antigenic substances (e.g. polen, animal hair etc.) cause the episodic obstruction of the airways. Moreover, various unspecific irritants can trigger asthmatic episodes. Chemical irritants (e.g. tobacco smoke, dust, air pollution), certain medications, cold air and even exercise or psychic influences can cause a sudden over-reaction of the bronchial receptors, causing inflammation and subsequent narrowing of the air passages. Asthma is far more than a respiratory discomfort, it occasionally can even take life-threatening forms. And the occurrence is considerable, affecting about 4-5% of the population.

A clinical study was conducted with 12 women and 10 men, aged between 18 and 50 years, suffering from asthma since 1 and up to 16 years [Hosseini et al., 2001]. This was a randomized, double-blinded, placebo-controlled, crossover study design. Patients were randomly assigned to either the Pycnogenol® group, receiving 1 mg/lb/day (without exceeding 200 mg/day), or to the group receiving placebo for 4 weeks. Thereafter, subjects were crossed over to the alternate regimen.

The airway function of the patients was assessed by the "forced expiration volume in 1 second" (FEV1), by means of a spirometer. The subject fills his lungs and then exhales as fast as he can for exactly 1 second, while the spirometer measures the volume of exhaled air. The exhaled volume is expressed relative to the total lung volume, so the FEV1 value represents the percentage of a patient's lung volume he can exhale in a second. Naturally, the percentage is lower in asthmatics as their airways are constricted, and breathing is aggravated. The study showed that the percentage of their total lung volume which asthmatics could exhale within a second rose considerably after treatment with Pycnogenol®, while placebo had no effect.

Figure 4: Outcome of treatment of asthmatic patients with either Pycnogenol® or placebo. The blue curve expresses the "forced expiration volume", representative of the patient's ability to breath. It is low at baseline and in response to placebo, but improves statistical significantly after taking Pycnogenol®.

The improvement of airway function was paralleled by a reduction of leukotrienes in the blood (figure 5). The leukotrienes are inflammatory mediators which attract and activate immune cells in the bronchi. This causes the inflammatory condition and constriction of bronchi, processes which are largely responsible for the airway obstruction in asthma. Pycnogenol® significantly reduced the leukotriene values, as compared to both baseline as well as placebo medication. As expected, placebo had no significant influence on leukotriene levels in the blood.

Figure 5: The levels of inflammatory mediators, leukotrienes, were measured before and after treatment in asthmatic patients. While placebo had no effect, Pycnogenol® statistical significantly reduced leukotriene levels in asthmatics.

The severity of asthma symptoms was rated on a 4 point scale, ranging in steps from a mild intermittent form up to a severe persistent form. Before treatment and while receiving placebos the mean symptom score of all patients was considered as being a "severe persistent" form. After treatment with Pycnogenol® the symptom severity score was significantly reduced to the "moderate persistent" form (figure 6).

Figure 6: Outcome of treatment of asthmatic patients with either Pycnogenol® or placebo. The bars represent the asthma symptom score, which depicts the severity ranging from "mild intermittent asthma" up to "severe persistent asthma". The severity of asthma symptoms were significantly improved by Pycnogenol®.

Pycnogenol® was well tolerated, only one patient experienced gastrointestinal discomfort, however, this occurred only during the first 3-4 days. The patients generally noted an improvement of their breathing ability when they received Pycnogenol®.

1. Blazso G, Gabor M, Sibbel R, Rohdewald P. Antiinflammatory and free radical scavenging activities of procyanidins containing extract from the bark of Pinus Pinaster and its fractions. Pharmaceutical and Pharmacological Letters 3: 217-220, 1994.
2. Blazso G, Gabor M, Rohdewald P. Antiinflammatory activities of procyanidin-containing extracts from Pinus pinaster after oral and cutaneous application. Pharmazie 52: 380-382, 1997.
3. Cho K-J, Yun C-H, Yoon D-Y, Cho Y-S, Rimbach G, Packer L, Chung A-S. Effect of bioflavonoids extracted from the bark of Pinus maritime on proinflammatory cytokine interleukin 1 production in lipopolysaccharide-stimulated raw 264.7. Toxicology and applied pharmacology 1687: 64-71, 2000.
4. Grosse Düweler K, Rohdewald P. Urinary metabolites of French maritime pine bark extract in humans. Pharmazie 55: 364-368, 2000.
5. Erben Bayeta MS, Lau BHS. Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutrition Research 20: 249-259, 2000.
6. Hosseini S, Pishnamazi S, Sadrzadeh SMH, Farid F, Farid R, Watson RR. Pycnogenol® in the management of asthma. Journal of Medicinal Food, issue 4(4): 201-209, 2001.
7. Peng Q, Wei Z, Lau BHS. Pycnogenol inhibits tumor necrosis factor-a-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothlial cells. Cellular and Molecular Liefe Sciences 57: 834-841, 2000.
8. Rohdewald P. French maritime pine bark extract (Pycnogenol®), a versatile herbal supplement. Journal of Clinical Pharmacology & Therapeutics, in print, 2002.
9. Sharma SC, Sharma S, Gulati OP. PycnogenolŇ inhibits the release of histamine from mast cells. Phytotherapy, in print 2002.

Chronic Bronchitis And Pycnogenol®

Chronic bronchitis is mainly caused by smoking. Consequently, smoking cessation is the best way to get rid of that disease, commonly known as smokers cough.

Chronic bronchitis is a continuously progressing disease, leading over a steady decline of lung function to emphysema and higher mortality (Decramer et al., 1998). In chronic bronchitis more and more cells of the lung are destroyed forever (Janoff et al., 1987) and the muscles needed to breath become weaker and weaker (Reid, 2001).

The normal therapy for those unable to quit smoking is only symptomatic and does not stop the destruction of the lung. Bronchodilators, expectorants or mucolytics helps enlarge and clear the obstructed airways, but they do not fight the fundamental processes attacking lung cells. The chronic inflammation, caused by cigarette smoke or other environmental burdens responds unfortunately only poorly to corticosteroids (Barns, 2000).

Together with the free radicals of tobacco smoke the chronic inflammation produces a great number of free radicals. These damaging radicals, insufficiently inactivated by antioxidative agents of lung cells, attack not only the cells of the lung. The oxidative stress contributes to loss of function of muscles needed to breath (Reid, 2001). Furthermore, deleterious enzymes are produced inside the inflamed tissue, attacking the proteins of lung cells. The abundant production of proteases in chronic bronchitis is a key factor for the destruction of the lung (Janoff et al., 1985).

Obviously, to slow down or to stop the loss of lung function in chronic bronchitis, the oxidative stress and the proteases must be blocked (Buhl et al., 1996).

Supplementation with Pycnogenol® offers a perspective to overcome the disappointing situation of patients with chronic bronchitis.

Pycnogenol®, French maritime pine bark extract, consists of various bioflavonoids and phenolic acids (Rohdewald, 1998). All of its constituents are potent scavengers of free radicals. Pycnogenol® is one of the most effective natural antioxidants, more powerful than vitamins C and E (Chida et al., 1999). Its radical scavenging activity is one of the reasons for the anti-inflammatory effect (Blazso et al., 1994). Pycnogenol inhibits a wide range of inflammatory substances (Packer et al., 1999). Therefore it is to expect that Pycnogenol® reduces the oxidative stress caused by smoking and inflammation.

A rather unique property of Pycnogenol® is its ability to stimulate cells to produce more antioxidative substances. In presence of Pycnogenol®, cells doubled the synthesis of the most important anti-oxidative enzymes - e. g. superoxide dismutase and catalase (Wei et al., 1997), strengthening the cellular defense system against the dangerous free radicals.

In respect to the destructive action of the proteases Pycnogenol® offers another beneficial aspect. Procyanidins, the main constituents of Pycnogenol® inhibit the most prominent proteases, collagenase (Kuttan et al., 1981) and elastase (Jonadet et al., 1983). By inhibiting these enzymes, the progressing destruction of lung cells should at least be retarded. Finally, Pycnogenol® has been shown to reduce the concentrations of bronchoconstrictors like leukotrienes (Watson et al., 2001) and thromboxane (Araghi-Nicknam et al., 1995) and it inhibits the release of histamine (Sharma, 2001) another potent constrictor of the bronchi. That inhibition of bronchoconstriction is also important for patients with chronic bronchitis, because a narrowing of the airways makes breathing difficult.

That threefold action: Antioxidant, inactivation of proteases and blocking of bronchoconstricting agents, suggest that supplementation with Pycnogenol® will help patients with chronic bronchitis to slow down the progression of destruction of their lungs.

1. Decramer M, Gosselink R, Troosters T, Schepers R, Peripheral muscle weakness is associated with reduced survival in COPD. Am J Respir Crit Care Med 157: A19, 1998.
2. Janoff A, Pryor WA and Bengali ZH. Effects of tobacco smoke components on cellular and biochemical processes in the lung. Am Rev Respir Dis 136: 1058-1064, 1987.
3. Reid MB. COPD as a muscle disease. Am J Respir Crit Care Med 764: 1101-1102, 2001.
4. Barns P. Novel approaches and targets for the treatment of COPD. Am J Respir Crit Care Med 160: S72-S79, 1999.
5. Janoff A. Elastases and emphysema. Am Rev Respir Dis 132: 417-433, 1985.
6. Buhl R, Meyer A, Vogelmeier C. Oxidant-protease interaction in the lung: prospects for antioxidant therapy. Chest 110: 2679-2725, 1996.
7. Rohdewald P. Pycnogenol. In: C. A. Rice-Evans, L. Packer (eds), Flavonoids in Health and Disease. New York: Marcel Dekker Inc. 405-419, 1998.
8. Chida M, Suzuki K, Nakanishi-Ueda T, et al. In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue. Ophthal Res 31: 407-415, 1999.
9. Blazso G, Gabor M, Sibbel R, Rohdewald P. Anti-inflammatory and superoxide radical scavenging activities of procyanidins containing extract from the bark of Pinus pinaster sol. and its fractions. Pharm Pharmacol Lett 3: 217-220, 1994.
10. Packer L, Rimbach G, Virgili F. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, Pycnogenol. Free Radical Biol & Med 27: 704-724, 1999.
11. Wei ZH, Peng QL, Lau BHS. Pycnogenol enhances endothelial cell antioxidant defences. Redox report 3: 219-224, 1997.
12. Kuttan R, Donnelly PV, Ferrante ND. Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase. Experientia 37: 221-223, 1981.
13. Jonadet M, Meunier MT, Bastide J, Bastide P. Anthocyanosides extraits de vitis vinifera, de vaccinium myrtillus et de Pinus maritimus. J Pharm Belg 38: 41-46, 1983.
14. Watson RR, Hosseini S, Pishnamazi S, Sadrzadeh S, Farid F, Farid R. Pycnogenol in the management of asthma. J Med Food 4: 201-209, 2001.
15. Araghi-Nicknam M, Hosseini S, Larson D, Rohdewald P, Watson RR. Pine bark extract reduces platelet aggregation. Integrative Med 2: 73-77, 1999.
16. Sharma SC. Pycnogenol inhibits the release of histamine from mast cells. Phytother Res 15: 1-5, 2001.