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Emerging New Ingredients for Cardiovascular Health: Polymethoxylated Flavones, Plant Sterols, and Pomegranate
Submitted By Douglas Labs

According to the most recent statistics from the American Heart Association, 105 million Americans have an average total blood cholesterol of 200 mg/dL or less, a classification considered desirable until recently. In July 2004, new recommendations for intensive lipid (or fat) modifying treatment for highrisk patients were endorsed by the National Heart, Lung, and Blood Institute, the American College of Cardiology, and the American Heart Association. These recommendations update the 2001 National Cholesterol Education Program's (NCEP) Adult Treatment Panel III (ATP III) report, setting lower treatment goals for LDL cholesterol, as well as supporting the use of lipid-lowering treatment and lifestyle modifications including nutrition, physical activity, and weight control. Although an LDL cholesterol of less than 100 mg/dL is still considered an optimal goal, these updated recommendations advocate 70 mg/dL for individuals considered to be at very high risk.

Since dietary and exercise modifications are often unable to achieve these reductions, many patients increasingly turn to drug therapy. The use of statins (a class of fat-lowering drugs that inhibit HMGCoA, a key enzyme in cholesterol synthesis) has risen dramatically. While statins can be effective in significantly reducing cholesterol, concern over potential side effects, such as exercise intolerance, muscle weakness, and pain, has been growing. As a result, finding natural, scientifically supported products that are effective, and without significant side effects, is always welcome.

The natural products receiving increased attention in the dietary supplement marketplace for effectively targeting heart health are plant sterols, polymethoxylated flavones, tocotrienols, and pomegranate.


For over 50 years, plant sterols (or phytosterols) and their esters have been studied for their effects on blood cholesterol in humans. Extensive clinical data on animals and humans indicate that these naturally occurring, fat-soluble compounds can play important roles in maintaining healthy cholesterol levels. Chemically similar to cholesterol in structure, plant sterols cannot be manufactured in the body and must be obtained from diet. And the typical Western diet does not supply enough sterols or stanols, which are found in vegetables, fruits, legumes, grains, and oils, to result in significant alterations in blood lipids.

Cholesterol, however, can be derived from the diet or synthesized in the liver itself, playing numerous critical roles in the body, from hormone synthesis to maintaining proper cell function. Plant sterols appear to block cholesterol from reaching the blood steam. Due to the aforementioned similarity in molecular structure to cholesterol, phytosterols coat the gastrointestinal tract, preventing cholesterol from being absorbed into the blood. Plant sterols may also lower cholesterol by interfering with the liver's ability to synthesize cholesterol.


Clinical studies have demonstrated that supplemental phytosterols can lower total cholesterol an average of 6 to 10 percent, and LDL cholesterol 8 to 15 percent. Studies also show that using supplemental phytosterols, in combination with statins, may further reduce blood cholesterol. For example, the combined use of statins and phytosterols lowered blood cholesterol by 39 percent, with sterols contributing 7 percent of the overall reduction. Importantly, phytosterols do not appear to significantly decrease HDL cholesterol.

Phytosterols achieved GRAS (Generally Recognized as Safe, an FDA approval rating applied to food and nutrients) status in the late 1990s, thus confirming their safety. In 2000, the FDA approved the use of claims that foods containing plant sterols and stanols reduce risk of cardiovascular disease. Recently, the FDA has extended these health claims to include a wider variety of foods including dietary supplements. The result: an increase in the number of dietary supplements that now contain phytosterols.


Flavonoids are a large class of plant chemicals that have powerful antioxidant properties and play important roles supporting both circulatory and immune health. While the benefits of flavonoids have been known for years, a specific class called polymethoxylated flavones (PMFs) are receiving attention for their cholesterol-lowering abilities in both animal and human studies. Typical PMFs are compounds found in concentrated amounts in the peel of citrus fruits, including oranges and tangerines. These studies demonstrated that PMFs possess potent cholesterol-lowering properties. In a recent study, hamsters fed a high-cholesterol diet, adding one percent of PMFs, significantly reduced total cholesterol levels 27 percent, LDL cholesterol by 40 percent, and triglycerides by 44 percent. There appears to be at least two actions by which PMFs can function to lower cholesterol: by reducing liver production of LDL and triglycerides.


Tocotrienols comprise one-half of the vitamin E family, which include the better-known tocopherols, found in foods like rice or palm oil. Like tocopherols, tocotrienols function as antioxidants, but are thought to be more potent than tocopherols. In addition, tocotrienols have demonstrated an ability to inhibit an enzyme required for cholesterol production in the liver, thus reducing cholesterol levels. Studies showed that subjects with carotid atherosclerosis who consumed tocotrienols for two years had a reduction in the amount of cholesterol-laden atherosclerotic plaque compared with those who received a placebo.


Three human clinical studies investigating the effect of a new patented blend of PMFs and tocotrienols called Sytrinol™ on cholesterol levels have yielded impressive results. In the first study, 10 people having an average total cholesterol greater than 230 mg/dl, LDL cholesterol greater than 155 mg/dl, and total triglycerides of between 100 and 307 mg/dl received 300 mg of Sytrinol for four weeks. Total cholesterol decreased by 24 percent, LDL cholesterol decreased by 19 percent, and triglycerides dropped by 24 percent. These results were confirmed in a second study also involving 10 high-cholesterol people in whom similar reductions in cholesterol levels were observed. Given the success of the first two studies, a larger, more controlled study involving 120 high-cholesterol people was initiated. In the first 12 weeks, people received either 300 mg/day of Sytrinol or a placebo for 12 weeks. In the next four weeks, everyone stopped taking Sytrinol or placebo. Then people switched groups, so that those that received the placebo in the beginning then received the Sytrinol. After 12 weeks, those receiving Sytrinol experienced 27 percent reductions in total cholesterol, 25 percent reductions in LDL cholesterol, and 30 percent reductions in triglycerides. No significant changes were reported in the placebo group. HDL cholesterol did not increase or decrease. Sytrinol did not cause any side effects or toxicity. These results may be attributable to the unique combination of Sytrinol's mechanisms to inhibit triglyceride synthesis, and cholesterol production in the liver.


Aside from its delicious taste, pomegranates contain a wide array of beneficial polyphenolic compounds. Supplementation with pomegranate juice in animal studies showed a reduction of cholesterol and atherosclerosis. A 2004 human study out of Israel showed that after one year of pomegranate juice consumption, subjects with severe atherosclerosis experienced up to a 30 percent reduction in blood-vessel thickness indicating a reduction in atherosclerosis, compared with a nine percent increase in blood vessel thickness in the placebo group, indicating an increase in atherosclerosis. There was also an increase in the beneficial enzyme shown to be connected with lower risk of cardiovascular disease and diabetes. While the mechanisms of action and specific compounds responsible for them are not well understood, the combination of potent antioxidants present in pomegranates may in part be responsible for health benefits.

For those looking for alternatives to statin drugs, natural products that help to lower cholesterol and help maintain cardiovascular health are quickly becoming a reality. Coupled with other nutrients well-known for their cardioprotective properties, such as CoQ10, B vitamins, and omega-3 fatty acids; pomegranate, polymethoxylated flavones, and plant sterols offer strong new weapons to help maintain optimal heart health.

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