The stream of clinical studies continues to reveal more amazing health benefits of Pycnogenol®. The research on Pycnogenol® grows more exciting every year as its recognized versatility expands. Decades ago, we referred to Pycnogenol® as being a “Polypill” or “Poly-nutrient” because of its many health benefits in reducing the risk of cardiovascular disease. Now the health benefits in slowing the aging process are also well established.
Pycnogenol® has become the most researched nutritional supplement that is not yet recognized as being a dietary essential. That brings up the important point made by Professor Bruce Ames in our February 2019 discussion. Professor Ames pointed out that while historical emphasis in nutrition has focused primarily on the nutrients essential for short-term events such as growth and prevention of the classical diseases of malnutrition, we should focus more on “longevity vitamins.” Longevity vitamins are a class of nutrients that exist mostly to prevent degenerative diseases of aging. Pycnogenol® fits well into this category. It protects against several components of the aging process.
Professor Rohdewald discussed many of these actions in the scientific literature in 2018. His review, entitled “Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy Aging,” was published in Rejuvenation Research. Professor Rohdewald has discussed Pycnogenol® in this column several times and he is my coauthor of our 2016 book “The Pycnogenol® Phenomenon” (Basic Health Publications, 2016).
Professor Rohdewald taught pharmaceutical chemistry at the University of Münster, Germany. He is the inventor of several patents and author of more than 250 scientific publications. His fields of interest cover a broad range of pharmaceutical sciences. Although retired from teaching, today he is still involved with Pycnogenol® research directed to evaluate the full potential of Pycnogenol® for human health.
Passwater: The goal of anti-aging research has always been not merely to extend life span, but to live healthier longer. This is not only in the vital interest of the individual, but also of outstanding importance for healthcare systems. What are some of the essentials people should do to live longer in a healthier status?
Rohdewald: First of all, stopping smoking and heavy drinking is mandatory to living a life for the normal period of time. Furthermore, it is nearly a platitude to emphasize the outstanding importance of sport and healthy nutrition for human health, especially for the elderly. However, the population seems to be divided: at one side the daily runners and smoothie lovers, at the other side the couch potatoes and fast-fooders. As for nutrition, it is well documented that the Mediterranean diet contributes to healthy aging by reducing cardiovascular risk factors, disability and also cognitive decline.
Food supplements become very popular as an attempt to increase the healthy lifespan. Among the multitude of vitamins, minerals, and herbal preparations, plant extracts, rich in polyphenols, offer great potential as a kind of “longevity elixir” because of their pleiotropic actions on many organs.
Passwater: Professor Rohdewald, the word “pleiotropic” is not often used by non-scientists. What does it mean?
Rohdewald: Pleiotropic: The word is a creation, used in science, combining the Greek words pleion = more and tropic = manner, to express a multiple manner of action in different fields. In the case of Pycnogenol®, we have seen such widely differing effects as relieving asthma symptoms or diabetic retinopathy, osteoarthritis symptoms were ameliorated, but also tinnitus and atherosclerosis. One can safely say that these actions of one extract on that many organs are really pleiotropic.
Passwater: Often people choose not to exercise properly or restrict their calories or even eat a healthy diet. You mentioned dietary supplements. You have led a lot of research on the dietary supplement Pycnogenol®. Can Pycnogenol® help to counteract the aging process itself and the secondary causes due largely to the lack of proper exercise and diet?
Rohdewald: Amongst the food supplements, plant extracts provide more benefits than just vitamins because of the manifold actions attributed to their complex composition. Some of the plant extracts offer the same wide spectrum of benefits as the Mediterranean diet, but in a concentrated form. One of these plant-derived food supplements, a standardized extract from the bark of the French maritime pine, Pinus pinaster, subsp. Atlantica de Villar, marketed as Pycnogenol®, (Horphag Research), consists of a concentrate of healthy polyphenols, mainly procyanidins. Pycnogenol® demonstrated in several clinical studies a wide range of health promoting properties, leading to healthier aging (5,6,7,8,9).
Passwater: In addition to the primary aging process and general metabolism, the body has many systems that affect aging. Clinical studies show that Pycnogenol® is effective against many aspects of aging. How can one dietary supplement be so effective against so many aging pathways?
Rohdewald: During aging we are exposed to degenerative diseases generating oxidative stress associated with inflammation. Regulation of metabolism becomes defective and the endothelial function may become impaired. The diverse actions of Pycnogenol® are based on its promotion of endothelial health as well as on its various anti-oxidative and anti-inflammatory effects.
Passwater: An important factor for living longer as well as better are the arteries. We are as young or as old as our arteries. Would you please review some of the major ways in which Pycnogenol® keeps the arteries healthy?
Rohdewald: Improvement of endothelial health is key to the prevention of atherosclerosis and cardiovascular diseases. The endothelial function is impaired by inflammatory stimuli and oxidative stress (10,11,12) and declines gradually with aging.
Pycnogenol® demonstrated a range of positive effects on the endothelium by increasing the production of NO from endothelial cells. This could be shown in ex-vivo studies on isolated aortic rings from rats where Pycnogenol® induced relaxation, which could be inhibited by the NO-inhibitor N-methyl-L-arginine (13). In human volunteers, Pycnogenol® improved flow-mediated dilation of the artery. This relaxation was also inhibited in the presence of an inhibitor of the endothelial nitric oxide synthase (e-NOS) (14). Aside the stimulation of e-NOS, Pycnogenol® inhibits the release of the vasoconstrictor endothelin-1 (15) and enhances blood levels of vasodilating prostacyclin (15), thus
combining inhibition of vasoconstriction and promotion of vasorelaxation.
In addition to this fundamental vasomotoric regulation, Pycnogenol® protects the endothelium against oxidative stress and inflammatory agents by several mechanisms. As an anti-oxidative agent, it deactivates reactive oxygen species as well as other free radicals (16), so it increased plasma antioxidative capacity in studies with seniors, students, athletes, smokers, and women (5). The stimulation of activity of antioxidative enzymes as superoxide dismutase and catalase (17) contributes to an increase of antioxidative capacity. Furthermore, important risk factors for cardiovascular health such as C-reactive protein and fibrinogen were inhibited, too (18).
The anti-inflammatory activity of Pycnogenol® is based on several elements. The inhibition of NF-kB plays a central role (19); down-stream in the inflammatory cascade the cyclooxygenases and lipoxygenases were inhibited, too (20,21). The inhibition of adhesion factors (22) by Pycnogenol® contributes to the protection of the endothelium against inflammatory stimuli. The inhibition of NF-kB and the toll-like receptor 4 by Pycnogenol® contributes to prevention of atherosclerosis. Lipid accumulation in monocytes will be blocked as well as synthesis of the adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2).
The inhibition of oxidative stress is important for prevention of atherosclerosis, as the oxidation of cholesterol is the first step to start foam cell formation. For atherosclerosis prevention, the regulation of the lipid metabolism is mandatory to prevent deposition of a surplus of lipids in the arterial wall. Pycnogenol® helps to balance lipid metabolism by increasing HDL cholesterol concentrations and lowering of LDL-cholesterol and triglycerides (5), thus improving the atherosclerotic index. The combination of normalization of lipids together with activation of free radicals is fundamental for blocking the development of atherosclerosis.
A further risk factor for the development of atherosclerosis is hypertension. Steady hypertension damages the endothelium, thereby promoting adhesion and invasion of inflammatory cells. Pycnogenol® has antihypertensive properties, as has been shown in several clinical studies (24-28). The consumption of Pycnogenol® allows subjects to reduce the dosage of antihypertensive drugs (15,25,29). The protection of the endothelial surface by normalizing blood pressure is another contribution of Pycnogenol® to atherosclerosis prevention.
A consequence of atherosclerosis is the formation of atherosclerotic plaques, starting with activation of blood platelets. Activated platelets activate monocytes to initiate local vascular inflammation (30). Pycnogenol® interferes with the process of platelet activation as could be demonstrated in studies with smokers. Smoking cigarettes activates blood platelets within 30 minutes. Intake of Pycnogenol® before smoking inhibits platelet activation to the same extent as aspirin, but with a lower dose (31), and it inhibits thromboxane formation (32). Thus Pycnogenol® intervenes in one of the first steps of atherosclerosis initiation.
The manifold actions of Pycnogenol® in promoting endothelial health and its antithrombotic effects result in anti-atherosclerotic effects. Two clinical studies compared the antisclerotic effects of Pycnogenol®, aspirin, ticlopidine and a combination of Pycnogenol® with an extract from Centella asiatica. The extract from Centella asiatica contains special triterpenes with antioxidative properties. The triterpenes stimulate collagen synthesis (33).
An ultrasound investigation of 1,191 participants with non-stenosing plaques after a 30-month study period revealed that progression of non-stenosing plaques to plaques causing more than 50% stenosis could be reduced by interventions with Pycnogenol®, aspirin and a combination of Pycnogenol® with an extract of Centella asiatica, TECA (Bayer, Basel) (34).
In untreated controls, 21.3% of individuals showed a progression of stenosis after 30 months to more than 50%. The percentage of participants with progressed stenosis was much lower following consumption of Pycnogenol®, depending on dose: 8.4% for 50mg and just 5.3% for 100mg. 100mg aspirin or ticlopedin were less effective with 16.6% of participants developing greater stenosis. The combination of aspirin 100mg with Pycnogenol® 100mg was slightly more effective than Pycnogenol® alone (4.3%). Best result with only 1.1% deterioration of stenosis was obtained with the combination of 100mg TECA and 100mg Pycnogenol®.
A further study (35), ongoing for 42 months, investigated plaque progression and frequency of cardiovascular events in 824 patients with stenosing arteriosclerotic plaques (50-60%).
Progression from asymptomatic to symptomatic plaques was observed in 48% of untreated controls. Treatment with 100mg Pycnogenol® or aspirin 100mg + 100mg Pycnogenol® reduced progression to 10%, whereas Pycnogenol® 50mg was less efficient with 35% reduction. 100mg aspirin or 250mg ticlopidine slowed down progression to 21%. The group: Pycnogenol® + triterpenic fraction of Centella asiatica extract (TTFCA) could obtain a reduction of plaque progression to just 6.5%.
The frequency of cardiovascular events corresponded with the progression of atherosclerotic plaques (35). The number of subjects experiencing cardiovascular events as hospital admission or needing specialized care was 16% in controls, 8.8% under 50mg Pycnogenol®, and 8% with 100mg Pycnogenol® and 8.5% with 100mg aspirin or 250mg ticlopidine. With TTFCA + Pycnogenol, the number of events was significantly (p< 0.05) lower compared to all other groups with just 4.4%.
The next question is whether the combination Pycnogenol® plus an extract from Centella asiatica would be able to stabilize atherosclerotic plaques against rupture, forming emboli. This was investigated in two clinical studies.
The first study (37) revealed an enhanced plaque stability relative to untreated control in 26 patients treated for 3 months with the combination of Pycnogenol® and an extract from Centella asiatica (Centellicum®, Horphag Research). Plaque height and length were reduced significantly (p< 0.05).
Results of the 3-month study were corroborated by a further 6-month study with 79 patients showing stenosing plaques (38). With the combination of 100mg Pycnogenol® plus 450mg extract from Centella asiatica (Centellicum), plaque height and length decreased significantly (p<0.05) compared to control.
A long-term study with 391 subjects with stenosing arteriosclerotic plaques (stenosis 50-60%) documented after 4 years a range of improvements under Pycnogenol® and the combination of Pycnogenol® with an extract from Centella asiatica (CA) (Bayer AG, Basel) (39).
Size of plaques increased over the study period considerably in controls: Lengths of plaques +16%, thickness + 14.5%. Following intake of Pycnogenol®, the increase was significantly smaller, the combination of Pycnogenol® with CA reduced the size of the plaques significantly, thus reversing the trend of atherosclerosis progression.
The stability of plaques increased in the sequence: control—Pycnogenol®—Pycnogenol® + CA, the combination resulted in a nearly twofold increase of plaque stability.
The improvement of the status of atherosclerosis is reflected in the frequency of cardiovascular events. With just 5 events in 151 participants over 4 years, the combination of Pycnogenol® + Centella asiatica was far more effective than Pycnogenol® (10 events) and highly significantly different from control (21 events).
Oxidative stress, objectivated by quantification of free radicals in plasma (40), was reduced in plasma of participants in every study concerning atherosclerosis progression following supplementation with Pycnogenol®. Aspirin or ticlopidin had no significant influence on free radical formation. The combination was more effective than Pycnogenol® alone (34,35,37,38,41,42).
The stabilization of atherosclerotic plaques to prevent emboli together with the slow-down or even halve of atherosclerosis progression is doubtless an important contribution of Pycnogenol® to healthy aging.
Passwater: Diabetes accelerates aging. What do clinical studies show about Pycnogenol® and diabetes?
Rohdewald: In a dose-finding study (51) with diabetic patients, 200 mg Pycnogenol® produced the maximum effect, reducing fasting glucose from 12. 47 to 10.07 mmol/L and HbA1c from 8.02 to 7.37 (p<0.05). Insulin levels remained unchanged. In 77 diabetic patients, treated with antidiabetic drugs, the addition of 100 mg Pycnogenol® to treatment for 12 weeks decreased plasma glucose significantly (p<0.001) versus baseline. In a double-blind, placebo-controlled, randomized study (25), fasting glucose declined by 23.7 mg/dl under Pycnogenol® 12.5 mg/d, decrease under placebo was significantly (p<0.0001) lower with 5.7 mg/dl. In 64 patients with metabolic syndrome, fasting glucose dropped down from 123 mg/dl to 106 mg/dl during treatment with 150 mg Pycnogenol® for 3 months; glucose levels remained unchanged in controls (27).
According to anecdotal reports (5) patients could spare the use of insulin while taking Pycnogenol®. The clinical reports seem to suggest that Pycnogenol® could help to reduce the use of antidiabetic drugs and to ameliorate symptoms of diabetes type 2.
Passwater: Inflammation is a component of several diseases associated with aging. How does Pycnogenol® reduce the harmful effects of inflammation?
Rohdewald: Chronic inflammation of joints, osteoarthritis, is a widespread disease of the elderly; most prevalent is the osteoarthritis of the knee. The painful inflammation of the joints leads to permanent use of pain killers and loss of mobility.
Mobility is one key to healthy aging—maintaining a person’s ability to move independently from one place to another. Mobility limitations increase with advancing age, hindering the management of tasks of daily life. Mobility difficulties lead to sedentary behavior, subsequently to less social contacts and fewer nutritional options. Further functional decline prompts the need for help from others, so the risk of disability increases. The loss of independence initiates depression. Finally, the lack of mobility increases the overall-morbidity from several diseases and malfunctions. Therefore, it is mandatory to keep mobility as long as possible at a normal level during aging.
The most common cause of chronic immobility in persons over 65 is osteoarthritis, affecting about 50% of the population in that age. The restricted mobility is caused by progressing, painful destruction of joints, initiated by inflammatory reactions. Constituents and metabolites of Pycnogenol® are able to inhibit the activity of inflammatory mediators right within the joint (53,54).
Three double-blind, placebo-controlled studies with 293 patients demonstrated a better physical function, less joint stiffness and less pain; a mean improvement of 40% of these symptoms was observed in all studies (55-57). In the treadmill test, patients could triple their walking distance following intake of 100mg Pycnogenol® daily for 3 months. At the same point in time, patients in the placebo group could increase their walking distance just by one third (57).
The improved mobility results in sustained social contacts (57), thus contributing to an enhanced quality of life. Having less difficulties in putting on socks, rising from sitting, going shopping, doing domestic duties…all such daily routines were greatly improved by Pycnogenol®, but not by placebo (57).
The local treatment of pain with Pycnogenol® patches (58, 59), also free from unwanted effects, helps also to improve quality of life without the use of opioids, antidepressants or NSAIDs. One may conclude from these studies that it would be worthwhile to start supplementation with Pycnogenol® at the earliest signs for mobility restrictions, keeping mobility and quality of life as long as possible at a normal level.
The reduction of pain with Pycnogenol® allowed subjects to spare the use of NSAIDs (56,57), thereby decreasing gastric problems caused by the NSAIDs.
The sparing of painkillers with Pycnogenol® is an example for reducing dose-related side effects of drugs. Another example is the replacement of antihypertensive drugs like CA-antagonists with Pycnogenol® (15,25,29).
Passwater: Cognitive function and mental fitness are problems facing many people as they grow older. What do we know about Pycnogenol® and cognitive function?
Rohdewald: There is indeed a great concern regarding how the elderly can deal with the age-related decline of memory and cognitive abilities. Cognitive aging affects mental functions such as executive functions, processing speed, or multitasking abilities, which are mandatory for engagement in daily activities. Many programs for mental or physical exercise are offered with the attempt to slow down cognitive aging. Living independently in good mental health for as long as possible is of outstanding importance for the senior citizen.
First hints for a positive effect of Pycnogenol® on mental skills were obtained from experiments with senescence-accelerated mice (60). Pycnogenol® improved learning and memory of the mice significantly (p<0.01) and dose-related.
To verify the effect of Pycnogenol® to influence cognitive aging, a series of computer-assisted memory tests are used. An investigation of 101 Australian elder citizens with moderate cognitive function decline (61) revealed a significant (p<0.05) improvement of spatial memory following intake of 150mg Pycnogenol® for 3 months.
A clinical trial with 77 elderly individuals aged 55 to 70 years used—in addition to conventional cognition tests—another approach, resembling challenges of daily life. Half of the volunteers received 100mg Pycnogenol® daily for 12 months, the other half served as an untreated group (62). Both groups were instructed to follow a personal improvement plan for better lifestyle. The participants were investigated using questionnaires for decrease in cognitive function and evaluated for the ability to handle daily tasks.
According to the Informant Questionnaire on Cognitive Decline in the Elderly, the elderly in the Pycnogenol® group could much better remember what happened recently, where things are and were better in learning new things. Furthermore, they were significantly better in handling complex situations.
The evaluation of daily tasks in the control group revealed the expected signs of cognitive aging—the ability to perform daily tasks decreased, there was no improvement in any of the tested items. In contrast, the participants in the Pycnogenol® group improved their tasks, especially the more complex challenges as decision making and dealing with problems. Furthermore, physical status and sleep quality changed to significantly better scores. The Pycnogenol® group outperformed the controls also in the Short Blessed Test for evaluation of cognitive function deterioration.
The results obtained with the elderly are in complete agreement with the improvement of cognitive function by Pycnogenol® observed in a group of students (63) and healthy professionals (64). Thus, the daily intake of Pycnogenol® appears to generally improve memory and learning, compensating for the process of cognitive aging.
The slowdown of cognitive aging by Pycnogenol® is in line with results from studies reporting that polyphenols—as contained in Pycnogenol®—act against cognitive decline.
Passwater: You have presented many health benefits of Pycnogenol® that help to extend the healthy lifespan of seniors. There are more, including reduction of menopausal symptoms, improvement of quality of sperm and erectile function and benign prostatic hyperplasia. Thank you for sharing this information with our readers.
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