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
Introduction
Extracts from pine tree bark have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster). The extract is prepared by a standardized procedure that includes an extraction of fresh pine bark with ethanol and water. The resulting product is a mixture of flavonoids as monomers: catechin and taxifolin, and condensed polymers (85%), up to dodeoameric flavanols, designated as procyanidins. Additionally, the extract contains phenolic acids as gallic, caffeeic, and ferulic acid as minor constituents. Pycnogenol also contains glycosylation products, i.e., sugar derivatives of phenolcarbonic acids and taxifolin [21]. These molecules have antioxidant properties [21] and may act as modulators of metabolic enzymes and other cellular functions. Pycnogenol has prevented pathologic symptoms such as chronic inflammation and increased platelet aggregation, a risk factor for cardiovascular diseases [21]. Pycnogenol prolonged the ascorbate radical lifetime to the greatest extent by regenerating ascorbic acid [18]. In vitro Pycnogenol inhibits LDL peroxidation, lipid peroxidation in phospholipid liposomes [21], and lipid peroxidation caused by t-butylhydroperoxide. Pycnogenol has an efficient antioxidant activity [18]. Inhibition of vasoconstriction caused by adrenalin is produced by stimulation of nitric oxide synthesis under Pycnogenol [6].
Hypertension, or a blood pressure higher than 140/90 mm Hg, is the most common risk factor for cardiovascular and cerebrovascular morbidity and mortality [14]. In the United States, high blood pressure is responsible for 40,000 deaths annually in the U.S., while being the most modifiable risk factor for stroke. Hypertension affects about one in four adults, or almost 50 million people, in the United States [2]. The Framingham Study showed that as people aged from thirty to sixty-five years, their blood pressure increased an average 20 mm Hg systolic and 10 mm Hg in diastolic pressure with systolic blood pressure continuing to rise up to age ninety. While higher blood pressure increases the likelihood of a cardiovascular event, hypertension is not often well controlled, and too few patients are adequately treated [5]. Epidemiologic studies predict that reduction of the systemic blood pressure by the amount usually achieved in major clinical trials could reduce cerebrovascular events by 42% and cardiac events by 24% [8]. Although our understanding of the pathophysiology of elevated arterial pressure has increased, in most cases, the etiology, and thus potentially the means to be employed to prevent or cure it, are still largely unknown. In consequence, hypertension is frequently treated nonspecifically, resulting in a large number of minor side effects and a relatively high rate of non or inadequate treatment [9].
In hypertensive patients, the release of vasoconstrictor peroxides derived from the activity of cyclo-oxygenase in the endothelium and in the vascular smooth muscle is important. Excess free radicals released by the dysfunctional endothelium also stimulate the synthesis of contracting agents. The therapeutic benefit of some anti-hypertensive drugs, such as calcium antagonists and angiotensin-converting enzyme inhibitors, could be in part due to their inhibition of the production of free radicals. Pycnogenol is a strong antioxidant [21], inhibits ACE [4], and produces anti-hypertensive effects in rats [18], [21]. The inhibition of thromboxane has been shown previously [3].
Blood Pressure of 140–159/90–99 mm Hg should have blood pressure continued within 2 months, and if no more than 1 other risk factor is present, pharmacological therapy may be delayed for up to 6 months [9]. Therefore Pycnogenol’s actions on patients with mild hypertension, not routinely treated with standard drugs, were studied.
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Subjects
Eleven patients (four women and seven men) with an average age of fifty years (mean ± SD = 50.3 ± 9.3 years), systolic blood pressure of 140–159 mm Hg, and/or diastolic blood pressure of 90–99 mm Hg were investigated. The exclusion criteria included those taking antihypertensive medication; taking non-steroidal, anti-inflammatory drugs, including aspirin, use of tobacco, or taking any vitamin supplements other than a single, daily multivitamin tablet. These items were assessed using the Arizona
Results
Pycnogenol or placebo pills were given in a randomized, double-blind, cross-over fashion for eight weeks to non-smoking, mildly hypertensive patients (7 females and 4 males, all Caucasians). They had an average systolic blood pressure of 140 (mean ± SEM = 139.9 ± 3.3). Pycnogenol treatment decreased systolic blood pressure significantly (p < 0.05) to 133 (mean ± SEM = 132.7 ± 4.18) as compared to placebo supplementation in the same individuals for 8 weeks (Fig. 1A). Our data also demonstrated
Discussion
Our data show a significant decrease in systolic blood pressure and serum thromboxane B2 levels after eight weeks of Pycnogenol supplementation in non-smoking, mildly hypertensive patients who did not require standard pharmacological drug therapy.
Pycnogenol’s antioxidant effects could protect cell membranes against oxidative stress, which could ultimately promote the production and release of arachidonic acid mediators including thromboxane. By protecting cell membranes, Pycnogenol should
Acknowledgements
We greatly appreciate the assistance of Valerie Butler for study coordination and assessment, and Timothy Fagan, M.D. for clinical evaluation. This research was supported by a grant from Horphag, Inc.
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