Understanding Pine Bark Extract as an Alternative Treatment (UPBEAT) Research Study / Stanford
Antioxidant Natural Supplement Study
Principal Investigator: Randall S. Stafford
Funding Agency: Toyo Shinyaku Co., Ltd.
Duration: 10/1/2006 - 08/31/2008
The UPBEAT study is a randomized, placebo-controlled, double-blind, parallel trial that will investigate the efficacy and safety of Flavangenol® (Toyo Shinyaku, Japan)*, a pine bark extract. We are currently recruiting for this study. We will randomize a total of 130 individuals to take 200 mg of Flavangenol or a placebo once per day for 12 weeks. These participants will be individuals at mildly or moderately elevated risk of cardiovascular disease (CVD) because of having prehypertension and excess body weight. Results from this trial will contribute to the growing evidence that is much needed for millions of current and future consumers of pine bark extracts and other OPC products as well as for health care professionals.
Pine bark has been used as a foodstuff for thousands of years in human history. Today, pine bark extracts and other OPCs products (especially grape seed extracts) are widely consumed as a food ingredient or dietary supplement. Extensive research conducted with several formulations of pine bark extracts has established its safety and tolerability for human consumption. More recent research has focused primarily on clinical efficacy and growing data suggest an array of cardiovascular benefits. However, the studies published to date on the clinical efficacy of pine bark extracts all have outstanding methodological limitations, for example, lack of a control group, lack of randomization, lack of or inadequate blinding, insufficient statistical power, and incorrect statistical analyses.
We aim to determine (in order of priority):
1) The efficacy of Flavangenol in lowering blood pressure.
2) The efficacy of Flavangenol in improving glycemic control and plasma lipoprotein profile.
3) Changes in body weight, antioxidative capacity, anti-inflammatory markers, and liver function tests in response to Flavangenol.
4) The safety of Flavangenol, as confirmation of past studies.
* Flavangenol is a registered trade mark in Japan, and trade names of Flavangenol and TOYO-FVG have been applied in the US.
Availability of Pine Bark Extracts in Food and Supplements
Flavangenol is one of several pine bark extract formulations currently sold to consumers. Flavangenol is extracted from Pinus pinaster (= P. maritime = P. maritimus), or P. sylvestris. Human consumption of pine bark dates back to thousands of years ago, and the first commercial pine bark extract was patented in 1948 by Dr. Jacques Masquelier from France. The extraction method used for Flavangenol maximizes the content of naturally polyphenolic compounds found in the bark of the above species of the genus Pinus. These compounds are known as oligomeric proanthocyanidin complexes (OPCs) or procyanidolic oligomers (PCOs). OPCs are widely distributed in the plant kingdom, including foods such as cranberries, blueberries, apples, tea, and red wine, which are common in the American diet.(Fine 2000) As a food ingredient, pine bark extract has been incorporated into a wide variety of foods in which the astringent flavor properties of OPCs are desired. Furthermore, with sales reaching 2.4 million units in 2002, OPC supplements rank the fourth highest among popular herbal supplements in the U.S. Studies of pine bark extracts have tested tablets or capsules in amounts ranging from 80 mg to 480 mg per day in middle-aged and elderly individuals. Pharmacokinetics studies indicate pine bark extracts are readily absorbed, metabolized and eliminated by humans. The studies published to date are from different formulations of pine bark extract than the specific product we are testing.
Safety of Pine Bark Extract
The general safety of pine bark extracts have been established through extensive research conducted in both animals and humans. Based on available safety data, a panel of experts has determined Flavangenol to have “generally recognized as safe” (GRAS) status. In addition, several published studies of pine bark extracts have a favorable safety and tolerability profile for doses ranging from 50 mg per day to 480 mg per day in healthy individuals as well as in patients having hypertension or diabetes mellitus. Common side effects may include gastrointestinal discomfort, nausea, dizziness, headache, sleepiness, urinary retention, urinary frequency, constipation, and increased perspiration. All of these symptoms are mild and transient in nature and similar to the common side effects reported for many other herbal products and drugs. Please note that published studies to date have used of pine bark extract formulations other than the specific pine bark extract that we are studying in this study. The GRAS report for Flavangenol included data specifically about the pine bark extract formulation being used in the UPBEAT Research Study.
Clinical Efficacy of Pine Bark Extract
As a member of the flavonoid family, OPCs have established free radical scavenging and antioxidant activity. Pine bark extracts have been used in France since 1950 to prevent cardiovascular disease primarily on the basis of its antioxidant functionality. More recently, pine bark extracts have garnered growing research attention because of accumulating evidence regarding its diverse clinical pharmacology. Recent studies suggest that in addition to its well-known antioxidant properties, pine bark extracts may also have lowering effects on blood pressure. The blood pressure lowering effect of pine bark extracts have physiological plausibility because of its ability to antagonize the vasoconstriction caused by epinephrine and norepinephrine through increased activity of endothelial nitric oxide synthase. Pine bark extracts have also been found to reduce blood concentrations of endothelin – the most potent endothelial-derived vasoconstrictor.
Furthermore, published preliminary data of pine bark extracts suggest a myriad of additional cardiovascular benefits, including improved glycemic control, reduced body weight, improved lipid profile, improved peripheral circulation, and blunted platelet aggregation. While these studies provide promising information, relative few were as large or as rigorous as optimal for such a widely used herbal therapy. Again, please note that the published studies to date used a variety of pine bark extracts other than the specific formulation we are researching in the UPBEAT Research Study.
Click here to view the presentation presented at study orientation.