Cardiovascular disease is the leading cause of death of both men and women world-wide. The umbrella term ‘cardiovascular disease’ includes a variety of inter-related conditions that affect the heart and blood vessels, such as atheriosclerosis, hypertension, stroke, heart failure, and coronary heart disease. The causes of cardiovascular disease are multi-factorial, but lifestyle choices (e.g., diet, exercise) appear to play a leading role in the development of cardiovascular disease.
Although there is still some controversy on the topic, most experts today believe that chronic inflammation is the primary cause of cardiovascular disease (1). Dietary choices strongly affect the degree of inflammation the body experiences. Eating colorful fruits and vegetables and avoiding processed carbohydrates and vegetable oils is one approach to reducing inflammation in the body. Certain colorful fruits, such as berries, have been shown to have particularly powerful protective effects against inflammation and cardiovascular disease (2). This effect is thought to be mediated through protective compounds called phytochemicals (such as pterostilbene).
One way that phytochemicals help protect the blood vessels from inflammation is through their antioxidant activity. Reactive oxygen species and free radicals are constantly being generated in the body, and these chemicals react with and damage the molecules and cells around them. Damage caused by free radicals triggers the body to initiate inflammatory processes, which can lead to cardiovascular disease. Antioxidants react with the free radicals before they can cause damage, therefore they prevent direct damage from free radicals and they also prevent damage by preventing inflammation.
Blueberries and their active phytochemical: Pterostilbene
In clinical studies, blueberries were found to be particularly effective in reducing the risk of cardiovascular disease (3). In the laboratory, they have been shown to have one of the highest antioxidant content of any berries tested to date. Scientists have been able to isolate the active ingredient from blueberries: pterostilbene. Pterostilbene is a stilbenoid chemical that is similar in structure to resveratrol, and has been shown to be highly bioavailable and to have a long half-life in the body after ingestion.
A recent randomized controlled trial demonstrated that pterostilbene was quite effective in treating metabolic syndrome (4). Metabolic syndrome is defined as a cluster of symptoms that have been shown to indicate an individual is at high risk of developing cardiovascular disease and/or type II diabetes in the next few years. In this recent clinical trial, individuals who took 125 mg of pterostilbene twice-daily for 8 weeks experienced a significant decrease in blood pressure and a significant increase in LDL (good cholesterol). Some individuals also lost a small amount of weight. The high-dose pterostilbene group was compared to a placebo group, a low-dose pterostilbene group, and a group given grape extract and low-dose pterostilbene. None of these comparison groups experienced the dramatic reversal of metabolic syndrome in the way that the high-dose pterostilbene group did.
Mechanism of Action
In animal models, pterostilbene has been shown to protect against cardiovascular disease through several different mechanisms (5). The primary mechanism appears to be its ability to protect the lining of the blood vessels from free radical attack. Dysfunction of the endothelial cells that line the blood vessels is thought to be one of the first steps in the development of cardiovascular disease. Inflammation induces leukocytes in the blood to release reactive oxygen species, which damage the endothelial cells unless antioxidants such as pterostilbene are available to remove them first. Studies have shown that rats fed pterostilbene-rich extracts have a 24% increase in the ability to resist the release of reactive oxygen species into the bloodstream (5). Pterostilbene has also been shown to reduce reactive oxygen production in human endothelial cells exposed to oxidative stress (6).
In addition to its direct antioxidant activity, pterostilbene is able to up-regulate the production of natural antioxidants, such as superoxide dismutase (SOD), thioredoxin, and glutathione. It also seems to be able to protect the smooth muscle cells that line the blood vessels from proliferating in response to inflammation. Excessive proliferation of the smooth muscle cells contributes to stiffening and narrowing of the blood vessels in artheriosclerosis. In animal studies, pterostilbene blocked proliferation of smooth muscle cells, apparently through down-regulation of platelet derived growth factor, Akt, and an assortment of other cell-cycle promoting kinases (7).
Pterostilbene therefore seems to have many antioxidant and anti-atherosclerotic functions that together provide potent protection against the development of cardiovascular disease, and it may be able to reverse cardiovascular disease that has already begun to develop. Although it is tempting to try to consume pterostilbene in fruit form, it is practically impossible to consume sufficient amounts of the compound from berries in order to achieve a therapeutic effect. Most studies suggest a daily dose of 25 to 50 mg is necessary to help prevent cardiovascular disease, and even higher doses are required to reverse cardiovascular disease. Clinical studies have shown that doses of up to 250 mg/day are safe for use in humans, and even very high doses exhibit no side effects (8).
(2) J Nutr. 2003 Jan;133(1):199-204.
(3) J Acad Nutr Diet. 2015 Mar;115(3):369-77. doi: 10.1016/j.jand.2014.11.001. Epub 2015 Jan 8.
(4) Evid Based Complement Alternat Med. 2014; 2014: 459165. Published online 2014 Jun 25. doi: 10.1155/2014/459165
(5) Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2013, Article ID 575482, 15 page, A Review of Pterostilbene Antioxidant Activity and Disease Modification
(6) J Nutr Biochem. 2002 May;13(5):282-288.
(7) Vascul Pharmacol. 2010 Jul-Aug;53(1-2):61-7. doi: 10.1016/j.vph.2010.04.001. Epub 2010 Apr 14.
(8) J Toxicol. 2013; 2013: 463595. Published online 2013 Feb 4. doi: 10.1155/2013/463595