What Is It?

Plant sterols and plant stanols are collectively known as phytosterols. Plant sterols are plant compounds with chemical structures similar to that of cholesterol. Especially high sterol levels are found in rice bran, wheat germ, corn oils, and soybeans. In a more concentrated form, these substances are called plant stanols. However, unlike cholesterol derived from animal sources--which absorbs easily and raises the body's own cholesterol levels--phytosterols are present only at very low levels in the body because they are difficult to absorb.

Interestingly, phytosterols so closely resemble cholesterol that they can actually block food-based cholesterol from being absorbed into the bloodstream. The result is that both phytosterols and dietary cholesterol end up excreted in waste matter.

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Health Benefits

Prevent heart disease and lower total and LDL cholesterol

By lowering total and LDL cholesterol levels, plant sterols and stanols may reduce your risk of heart disease. Studies have shown that daily ingestion of phytosterols can lower these cholesterol measurements by an average of 10% to 14%. Because of these strong findings, the National Cholesterol Education Panel issued a new recommendation in 2001 that plant stanols and sterols be added to cholesterol-lowering regimens, along with the more traditional cholesterol-fighting tools, such as regular exercise, weight loss, and a low-fat diet.

Recent study results find that supplementing your diet with phytosterols may be nearly as effective as lipid lowering statin drugs. In fact the same trial demonstrated that nine out of thirty-four participants were able to achieve lower LDL levels by implementing a diet high in plant sterols, than by taking statin drugs. The mechanism behind the improvement in LDL levels is not fully understood, but study results now suggest that phytosterols may lower the LDL particle size. There is debate about whether the sterol or stanol particles are more effective at lowering cholesterol. What we do know however, is that smaller LDL particles area more easily excreted by the body resulting in lower risk of adverse cardiac events and disease.

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Numerous clinical trials have found that daily consumption of foods enriched with plant sterols or stanols in free or esterified forms lowers serum total and LDL cholesterol concentrations. A meta-analysis that combined the results of 18 controlled clinical trials found that the consumption of spreads providing an average of 2 g/d of plant sterols or stanols lowered serum LDL cholesterol concentrations by 9-14%. More recently, a meta-analysis that combined the results of 23 controlled clinical trials found that the consumption of plant foods providing an average of 3.4 g/d of plant sterols or stanols decreased LDL cholesterol concentrations by about 11%. The most extensive meta-analysis published to date analyzed the results of 23 clinical trials of plant sterol-enriched foods and 27 clinical trials of plant stanol-enriched foods separately. At doses of at least 2 g/d, both plant sterols and stanols decreased LDL cholesterol concentrations by about 10%. Doses higher than 2 g/d did not substantially improve the cholesterol-lowering effects of plant sterols or stanols.

Linus Pauling Institute

The amount of cholesterol absorbed and type that circulates in the body has implications for cardiovascular health. Cholesterol travels in the blood through "lipoproteins," distinct particles containing both lipids and protein. These include high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol - sometimes referred to as "good" and "bad" cholesterol, respectively. Excess cholesterol in the blood - particularly LDL cholesterol may increase the risk of developing coronary heart disease.   High  levels of LDL cholesterol may contribute to fatty buildup on artery walls, forming plaque deposits that narrow the arteries. Plaque restricts blood flow and can raise blood pressure. When unstable plaques rupture, they tend to form clots, which may lead to a heart attack or stroke.

Plant phytosterols may help lower LDL cholesterol levels by blocking its absorption. If enough sterols/stanols are consumed in the diet, they will compete with cholesterol in the digestive tract in the formation of "mixed micelles." This ultimately results in a reduction of the amount of cholesterol that is absorbed in the body and returned to the liver. Despite the ability of plant sterols/stanols to block cholesterol absorption, the human intestine poorly absorbs them. In addition to the "mixed micelle" mechanism, special proteins lining the small intestine called "ATP cassette transporters" also play a role in lowering cholesterol by pumping absorbed plant sterols back into the gut.

Clinical Studies

Patients on statin drug therapy may achieve further reductions in their blood cholesterol levels when consuming a plant sterol-/stanol-rich diet. A 10 to 15 percent reduction in LDL cholesterol levels has been seen in some studies for patients who combined statins with a higher intake of plant sterols.

International Food Information Council

Coronary Heart Disease Risk

The results of numerous intervention trials suggest that a 10% reduction in LDL cholesterol induced by medication or diet modification could decrease the risk of coronary heart disease by as much as 20%. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III has included the use of plant sterol or stanol esters (2 g/d) as a component of maximal dietary therapy for elevated LDL cholesterol. The addition of plant sterol or stanol-enriched foods to a heart healthy diet that is low in saturated fat and rich in fruits and vegetables, whole grains and fiber offers the potential for additive effects in coronary heart disease risk reduction. Recently, a diet that provided a portfolio of cholesterol-lowering foods, including plant sterols, soy protein, almonds and viscous fibers lowered serum LDL cholesterol concentrations by an average of 30%, a decrease that was not significantly different from that induced by statin therapy. The US Food and Drug Administration (FDA) has authorized the use of health claims on food labels indicating that regular consumption of foods enriched with plant sterol or stanol esters may reduce the risk of heart disease.

Linus Pauling Institute

Lower C-reactive Protein Levels

C-reactive protein (CRP) is a special type of protein whose levels are increased in the blood in response to inflammation. People who smoke, have high blood pressure, are overweight, or have sedentary lifestyles often have elevated CRP, whereas lean, active people usually have lower levels. Like high serum cholesterol, high levels of C-reactive protein carry an increased risk of cardiovascular disease. Diets high in soluble fiber can help reduce CRP and thus lower the risk of heart disease.

One review article noted a 28% reduction in CRP levels when volunteers consumed a whole-foods diet rich in soluble fiber. In another trial, 55 healthy adults were assigned one of three diets: a diet low in saturated fat; the same diet plus a cholesterol-lowering statin drug; or the same diet plus increased amounts of plant sterols, viscous fiber, soy protein, and nuts. After one month, serum C-reactive protein levels fell in all three groups. In the low-fat diet group, CRP dropped 10%, a difference not considered statistically significant. However, those who consumed a low-fat diet enriched with plant sterols and fibers achieved a statistically significant 28% reduction in CRP—nearly equaling the 33% drop seen in those taking a powerful statin drug.

Life Extension

Ease enlarged prostate

Benign prostatic hyperplasia (BPH) is the term used to describe a noncancerous enlargement of the prostate. The enlarged prostate may exert pressure on the urethra, resulting in difficulty urinating. Plant extracts that provide a mixture of phytosterols (marketed as beta-sitosterol) are often included in herbal therapies for urinary symptoms related to BPH. However, relatively few controlled studies have examined the efficacy of phytosterol supplements in men with symptomatic BPH. In a six-month study of 200 men with symptomatic BPH, 60 mg/d of a beta-sitosterol preparation improved symptom scores, increased peak urinary flow and decreased post-void residual urine volume compared to placebo. A follow-up study reported that these improvements were maintained for up to18 months in the 38 participants who continued beta-sitosterol treatment after the study ended. Similarly, in a six-month study of 177 men with symptomatic BPH, 130 mg/d of a different beta-sitosterol preparation improved urinary symptom scores, increased peak flow and decreased post-void residual volume compared to placebo. A systematic review that combined the results of those and two other controlled clinical trials found that beta-sitosterol extracts increased peak urinary flow by an average of 3.9 ml/second and decreased post-void residual volume by an average of 29 ml.

Linus Pauling Institute

Calm inflammation in rheumatoid arthritis (RA)

Most traditional treatments for RA involve drugs that suppress the body's immune response, which can often cause troubling side effects. A mixture of the phytosterols beta-sitosterol and beta-sistosterolin has shown promise in helping to decrease inflammation and calm the overactive immune response that characterizes RA and other autoimmune diseases. More research is needed, however.

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Control blood sugar in diabetes

Some phytosterols stimulate insulin secretion and may contribute to better blood sugar control, a problem in people with diabetes. Animal studies have suggested that beta-sitosterol and beta-sistosterolin might be beneficial for people with diabetic and pre-diabetic conditions. More research is necessary before these findings are recommended to people with diabetes.

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Beta-sitosterol has been shown to normalize blood sugar and insulin levels in Type II diabetics by stimulating the release of insulin in the presence of non-stimulatory glucose concentrations, and inhibiting glucose-6-phosphatase.

In the liver, the enzyme glucose-6-phosphatase is the primary pathway for conversion of dietary carbohydrates to blood sugar. Glucose-6-phosphatase dephosphorylates glucose-6-phosphate to yield free D-glucose. Free D-glucose passes into the blood, thus elevating blood sugar levels.

Reducing the blood glucose levels by down-regulation of glucose-6-phosphatase helps delay diabetes caused by old age.

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What Is It?

One of the newest and most effective cholesterol lowering alternatives to statin drugs is a recently patented proprietary formula comprising citrus and palm fruit extracts that contains polymethoxylated flavones and tocotrienols. It has been shown in human trials to significantly reduce total cholesterol, LDL cholesterol, and triglycerides. Additionally, the powerful antioxidant and anti-inflammatory properties of the extracts in this natural formulation (trademarked under the name Sytrinol™) are known to contribute to managing additional cardiovascular disease risk factors.

Nutrition Review

Polymethoxylated flavones (PMFs) are found in a variety of citrus fruits. The most common citrus PMFs, tangeretin and nobiletin, are found in the peels of tangerines and oranges. They are also found in smaller amounts in the juices of these fruits.

The researchers are currently exploring the compound's mechanism of action on cholesterol metabolism. They now suspect, based on early results in cell and animal studies, that it works by inhibiting the synthesis of cholesterol and triglycerides inside the liver.

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Health Benefits

Lower Total and LDL "bad cholesterol"

The cardio-protective and cholesterol-lowering claims for Sytrinol™ are supported by human trials. Two early trials, consisting of ten subjects each, measured the effects of Sytrinol in men and women diagnosed with hypercholesterolemia (elevated cholesterol) and screened to eliminate thyroid disorders, kidney disorders and diabetes. Subjects were instructed to maintain normal dietary habits and discontinue using vitamins, supplements and cholesterol-lowering medications for at least 6 weeks prior to, and during the study. Fasting blood samples were drawn at the onset and end of each 4-week trial, and plasma lipids profiles and other metabolic parameters were analyzed using standard methods.

The results from the first trial show that four weeks of treatment with Sytrinol (300 mg/day) caused significant reductions in: total cholesterol (-24%); LDL cholesterol (-19%); and triglycerides (-23%). There were no changes in HDL cholesterol levels, and body mass remained relatively stable.

In the second trial, subjects with elevated cholesterol again benefited from only four weeks of treatment with Sytrinol (300 mg/day). Treatment with Sytrinol caused significant reductions in: plasma total cholesterol (19.7%); LDL cholesterol (22.01%); apo B (20.9%); and triglycerides (28.4%). Additionally, subjects in the second trial benefited from a significant 5% increase in apo-A1, an important structural protein of HDL

Compared to placebo, total cholesterol was reduced 30%, LDL cholesterol was reduced 27% and total triglycerides dropped 33%. Additionally, HDL cholesterol levels increased by 4%, resulting in a significant reduction in the LDL/HDL ratio of 30%.

Nutrition Review

Special compounds in orange peel, called polymethoxylated flavones, have been shown in a series of studies to lower blood serum cholesterol and triglycerides. An experiment with hamsters showed that these compounds were effective in lowering the bad low-density lipoprotein (LDL)-cholesterol, and triglycerides. Other experiments showed that these actions were due to at least three mechanisms. These mechanisms involved the inhibition and transport of key parts of the LDL molecule. Another mechanism involved the activation of an important cell signaling molecule in liver cells which control lipid formation. Additional mechanisms by which the polymethoxylated flavones act to prevent cardiovascular disease are discussed.

United States Department of Agriculture (USDA)

Chemicals in citrus peel have strong cholesterol-lowering actions in animals. The biological mechanisms of these chemicals have been investigated, and have been shown to block the production of lipids (fats) and cholesterol by liver cells. An additional mechanism has been found to occur for one of these compounds, nobiletin. This study shows that nobiletin prevents atherosclerosis at the level of the vascular wall by inhibiting macrophage foam cell formation.

United States Department of Agriculture (USDA)

* A study published in the May 12, 2005 issue of the Journal of Agricultural and Food Chemistry showed that PMFs reduced cholesterol by 24.7 per cent.

* They can lower triglycerides by as much as 28 per cent by decreasing levels of diacylglycerol acetyl transferase, the liver enzyme needed to produce them. High triglycerides are directly linked to heart attacks and heart disease because they contribute to the formation of plaque in the arteries.

* Studies also show that PMFs can decrease apolipoprotein B, the specific protein your liver needs to create LDL cholesterol. This has resulted in a 23-per cent drop in LDL cholesterol.

* The anti-inflammatory action of PMFs has been documented for over 38 years – well before doctors even realized that inflammation is a key cause of heart disease. Recent research shows that they can lower an inflammatory marker known as C-reactive protein (CRP). High levels of CRP can put you in the danger zone, since this protein substance is tied more directly to heart-attack risk than any other factor.

As powerful as PMFs are on their own, they're even more effective at lowering bad cholesterol when they're used in combination with tocotrienols. Tocotrienols are a form of vitamin E found in palms, rice bran, and barley that have been shown to reduce LDL cholesterol by lowering the activity of HMGR.

So scientists combined these two powerful ingredients, PMFs and tocotrienols, into the patented formula called Sytrinol. The researchers who developed Sytrinol also tested it in vitro, in vivo, and most importantly on hundreds of human subjects, using the same scientific protocols used by drug companies.

The Healthier LIfe

Tocotrienols and cardiovascular disease

One of the most striking discoveries in tocotrienol research is their ability to clear atherosclerotic blockage (stenosis) in the carotid artery, giving them the potential to significantly reduce the risk of stroke. Stroke often occurs when atherosclerotic deposits travel upstream and cut off the blood supply to part of the brain.

Tocotrienols show promise as a natural and safe alternative to risky surgery for this condition because of their ability to reverse carotid stenosis, not merely stop its progression. This was demonstrated in a clinical trial testing the effect of tocotrienols on carotid atherosclerosis. The results of this 18-month trial were remarkable.

Fifty patients with carotid stenosis were randomly assigned to receive either 160 mg daily of palm tocotrienols (gamma and alpha forms) with 64 mg of alpha-tocopherol in palm oil, or palm oil only as a placebo. After 6 months the dosage in the treatment group was increased to 240 mg of tocotrienols with 96 mg of alpha-tocopherol.

At the end of the study, ultrasound scans of the carotid artery demonstrated that none of the patients in the control group had improved during the trial, while ten showed a worsening of their condition (increased stenosis). In the tocotrienol group, however, atherosclerosis was reduced and blood flow to the brain improved in 7 of 25 patients, while the condition had worsened in only two patients. No adverse side effects were reported in either group.

Tocotrienols and statin drugs such as lovastatin both lower cholesterol by suppressing the activity of the enzyme HMG-CoA reductase, although through different mechanisms. The statins are thought to affect the enzyme through competitive inhibition, while the tocotrienols accelerate enzyme degradation and decrease the efficiency of mRNA translation of the enzyme. This difference in mechanism is believed to be a reason for the absence of adverse side effects with tocotrienols, contrary to the common side effects of the statin drugs.

Some studies have demonstrated a significant reduction of both total and LDL cholesterol with tocotrienols administered to patients with high serum lipids. In a double blind, crossover study on 25 patients with high cholesterol levels, the patients in the treatment group were given 4 capsules daily of 50 mg tocotrienols mixed with palm oil, while the control group received only corn oil. At the end of the 8-week trial period, total cholesterol and LDL cholesterol had decreased significantly (15% and 8%) in the 15 subjects given the palm tocotrienols. There was no change in the control group.

Total cholesterol and LDL-cholesterol were reduced even more (17 % and 24 % respectively) when tocotrienols were added to a low fat, low cholesterol diet and alcohol-free regimen in another double-blind, longer-lasting trial (12 weeks).

Other important cardiovascular risk factors were reduced by tocotrienols. Apoli-poprotein B and lipoprotein(a), strong predictors of cardiovascular disease, as well as thromboxane B2 and platelet factor 4 were all significantly lowered in the tocotrienol-treated group (15%, 17%, 31% and 14% respectively).

Tocotrienols were studied in combination with the statin drug lovastatin in another study. The 28 patients with elevated cholesterol levels in this double blind, cross-over clinical trial were placed on the American Heart Association Step-1 diet before beginning the treatment. After 35 days on the diet, they were given low doses of lovastatin, tocotrienols and alpha-tocopherol (and combinations of these agents) in stages of 35 days each, while staying on the diet. The combination of lovastatin (10mg) and palm tocotrienols (50mg) had a lipid-lowering effect of 20-25%, while tocotrienols or lovastatin alone in the same dosages reduced LDL-cholesterol 18% and 15% respectively. No side effects were reported during the study. It is important to note that dosages of cholesterol-lowering drugs should not be reduced on the basis of this preliminary study.

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Help support healthy insulin sensitivity

Citrus peel compounds that are known as polymethoxylated flavones may help support healthy insulin sensitivity, according to a recent study.

While citrus peel extract has been reported to improve cholesterol levels, this study was the first to examine its effects on insulin sensitivity. Scientists fed hamsters a sugar-rich diet for two weeks to induce insulin resistance and elevated triglycerides. The insulin-resistant animals then received either a low or high dose of the citrus flavones tangeretin and nobiletin. Supplementing with citrus flavones for four weeks helped reverse impaired insulin sensitivity.

Since insulin resistance, diabetes, and obesity are considered inflammatory disorders, the researchers also measured levels of two biomarkers of inflammation, tumor necrosis factor-alpha and interleukin-6. Levels of these biomarkers decreased in both groups receiving citrus flavones, as did serum levels of triglycerides and cholesterol .

These results indicate that citrus peel extracts may help fight insulin resistance and diabetes, as well as support healthy blood lipid levels.

Life Extension

Anti-inflammatory agent for rheumatoid and osteo arthritis

In particular, the flavonoid nobiletin has been identified as a novel anti-inflammatory agent that has the potential to inhibit the degradation of articular cartilage in osteoarthritis and rheumatoid arthritis. Nobiletin has also been found to interfere with numerous inflammatory cytokines, including interleukin-1 beta and interleukin-6. These anti-inflammatory effects are comparable to those seen with powerful anti-inflammatory steroids such as dexamethasone. Tangeretin , another citrus flavonoid, has been found to offer complementary effects against inflammation.

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