Phytosterols supplements side effects and benefits, role in cholesterol metabolism and prostate health by Ray Sahelian, M.D.
September 20 2016

Phytosterols are plant sterols structurally similar to cholesterol that act in the intestine to lower cholesterol absorption. The term  phytosterols covers plant sterols and plant stanols. Plant sterols are naturally occurring substances present in the diet principally as minor components of vegetable oils. Plant stanols, occurring in nature at a lower level, are hydrogenation compounds of the respective plant sterols.

Plant sterols and their hydrogenated forms, stanols, have attracted much attention because of their benefits to human health in reducing serum and LDL cholesterol levels, with vegetable oil processing being their major source in several food products currently sold. The predominant forms of plant sterol end products are sitosterol, stigmasterol, campesterol and brassicasterol (in brassica).

Prostate Power Rx by Ray Sahelian, M.D. with Phytosterol complex, Saw Palmetto, Pygeum, Stinging Nettle, Quercetin, and several key ingredients for support of a healthy prostate gland. 





Beta sitosterol and phystosterol complex, Saw palmetto

Benefit of Phytosterols, review of studies

Cholesterol Reduction
Phytosterols may be beneficial in lowering cholesterol levels. Because they have very low systemic absorption and are already present in healthy diets, increasing the intake of phytosterols may be a practical way to reduce coronary heart disease with minimum risk.
Foods containing phytosterols have been shown to help cut cholesterol, and the US Food and Drug Administration has endorsed these products "as part of a dietary strategy to reduce the risk of coronary heart disease.
   Snacking on cocoa-flavored bars enriched with phytosterols can reduce cholesterol levels. To examine the effect of a food enriched with phytosterols on blood levels of cholesterol and nutrients, Dr. John A. Polarus of the University of California at Davis and colleagues randomly assigned 67 people with high cholesterol to eat two snack bars containing 1.5 grams of phytosterols each every day for six weeks or two bars that did not contain a phytosterol. The enriched bar, Cocoa Via Crunch, was made by Hackett town, New Jersey-based Master foods, which helped fund the research. Study participants who ate the phytosterol enriched bars had a 5 percent reduction in total cholesterol and a 6 percent reduction in LDL cholesterol after six weeks, and also showed an increase in the amount of HDL or "good" cholesterol in relation to total cholesterol. While the phytosterol enriched bars did not affect participants' blood levels of vitamins A or E, they did reduce beta-carotene levels. Making sure to get plenty of carotenoid-rich foods such as a carrot a day while using phytosterol containing products could be enough to offset this reduction. Journal of the American Dietetic Association, November 2006.
   Phytosterol supplements, when taken with a statin drug such as pravastatin, can help in further reducing cholesterol levels.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study. American Journal of Clinical Nutrition, January 2010
Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols / 2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols / d for 4 wk each, in random order. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly increased total fecal cholesterol excretion and biliary cholesterol excretion and reduced percentage intestinal cholesterol absorption. Serum LDL cholesterol declined significantly only with the highest phytosterol dose. Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation.

Harefuah. Dec 2013. Phytosterols: another way to reduce LDL cholesterol levels. These sterols found naturally in various oils from plants compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

Metabolic syndrome
J Endocrinol Diabetes Obes. 2015. Nutritional Supplementation with Essential Amino Acids and Phytosterols May Reduce Risk for Metabolic Syndrome and Cardiovascular Disease in Overweight Individuals with Mild Hyperlipidemia. We sought to determine whether EAA's combined with whey protein and phytosterols would facilitate improvements in plasma lipids and insulin sensitivity in adults with mild hypertriglyceridemia. Findings suggest that a dietary supplementation of EAAs and phytosterols may promote favorable reductions of blood lipids as well as insulin resistance in individuals with hypertriglyceridemia.

There are a number of phytosterols including beta sitosterol, stigmasterol, campesterol, and brassicasterol. Certain herbs have a high concentration of phytosterols, for instance, saw palmetto.

Phytosterol in the diet, foods high in phytosterols
Normal human diet contains small amounts of phytosterols, mainly sitosterol and campesterol. Intestinal absorption of these plant sterols is low, about one tenth of that of cholesterol, such that their serum concentrations are also low, about 0.1 to 1% of the cholesterol levels. Oils have a very high content of phytosterols. gdPeas, cauliflower and broccoli are vegetables with a high content of phytosterols. Oranges, tangerines and mangos are fruits with a high content of phytosterols.

Contents of phytosterols in vegetables and fruits commonly consumed in China.
Biomed Environ Sci. 2008; Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing, China.
To quantify five specific dietary phytosterols and phytostanols in vegetables and fruits commonly consumed in China. A total of 34 different kinds of vegetables and 33 kinds of fruits were chosen according to the consuming habit of Chinese people. The contents of phytosterols (beta-sitosterol, campesterol, stigmasterol, beta-sitostanol, and campestanol) were analyzed. The total phytosterol content in vegetables ranged 1-53 mg/100 g edible portion. The highest concentration was found in pea, cauliflower, broccoli, and romaine lettuce. The phytosterol contents in fruits ranged 1.6-32 mg/100 g, the highest concentration was found in navel orange, tangerine, and mango. The phytosterol contents in vegetables and fruits are not as high as those in edible oils, but because of the large amount of consumption, they also play an important role in increasing the people's phytosterols intake.

Plant sterols in vegetables and fruits commonly consumed in Sweden.
Eur J Nutr. 1999. Department of Clinical Nutrition, Göteborg University, Sweden.
All food items of vegetable origin contain some amount of plant sterols. The aim of this study was to analyse the plant sterol content of vegetables and fruits commonly consumed in Sweden, and to compare fresh and cooked samples of the same items. Altogether 20 different vegetables and 14 fruits were analysed. The median plant sterol content of vegetables was 14 (4-50) mg/100 g edible portion. The highest concentrations were found in broccoli. Brussels sprouts, cauliflower and olives. The median plant sterol content of fruits was 16 (3-44) mg/100 gram edible portion. The highest concentrations were found in oranges and passion fruits. The plant sterol concentrations were thus low in vegetables and fruits commonly consumed in Sweden. A serum cholesterol lowering effect attributed to the plant sterols in vegetables and fruits would therefore be of limited value.

Q. On the web page it says phytosterols are found in oranges, tangerines, and mangoes. I haven't found another web site that says they're found in those food sources. Anecdotally, oranges and tangerines don't have that waxy like flavor when eating them that foods rich in phytosterols have, such as avocados, blueberries, acai, saw palmetto, and so forth. Additionally, do you know if there are phytosterols or fatty acids in red grapes?
   A. The amount in fruits appears to be small. I do not know if there are any in red grapes.

Phytosterol safety, side effects
Phytosterols are safe compounds. A multi-generational study in mice shows no significant adverse effects of phytosterol supplementation. However, long term effects are currently not fully understood.

Multigenerational exposure to phytosterols in the mouse.
Reprod Toxicol. 2005.
Due to beneficial health effects phytosterols are increasingly added to functional foods. The aim of the present study was to investigate the chronic effects of a dietary phytosterols mixture (5mg/kg/day), containing mainly beta sitosterol, on the reproduction of the mouse. General reproductive parameters, postnatal development, growth and survival of pups, weight of sex organs, the concentrations of plasma sex steroids and testicular testosterone were monitored across five generations (F(0)-F(4)). Phytosterols exposure increased the plasma levels of testosterone and decreased the relative uterine weights in the pups of F(2) and F(4) generations. Furthermore, phytosterol exposure increased the concentrations of plasma estradiol in the female pups of F(3) generation. Phytosterols supplement also increased the testicular levels of testosterone in the male pups of F(2) generation. In spite of these transitory changes, Phytosterol exposure caused no permanent deleterious effects on the reproduction of the mouse.

Q. Phytosterol supplements messed with my emotions terribly. I have suffered from depression and over time, I discovered that these exacerbated it horribly, perhaps a systemic hormonal effect? The phytosterol product I was using was Endur Products Phytosterol tablets (which I think uses Cargill's phytosterol prep).
   A. This is an interesting phytosterol supplement side effect. I will see if others have noticed mood changes with the use of phytosterol supplements.

Q. About two months ago, in Dec 2009, I started taking Centrum Cardio with the Corowise phytosterols and since that time I've noticed that I've developed some fatigue and muscle aches and pains and at times weakness. I've tried to find articles about side effects when taking phytosterols but so far I haven't found any that talk about these side effects.

Q. I would like to add my experience with phytosterols. On recommendation from my physician, I began taking phytosterols, starting at one daily and then adding a second tablet. After about a week, I began to notice increased depression and disturbing vivid dreams, so I completely discontinued taking the tablets two days ago. The depression seems to be lifting, but the dreams are still there. I think I will get my phytosterols only from food from here on.

A few weeks ago I suffered what I perceived to be a serious and unespected heart stroke which landed me straight in our local hospital. The doctor there told me that what I had was a condition called angina. He explained that this illness was due to a high bad cholesterol accumulation in my coronary arteries. He recomended "baby aspirins" to keep me safe and to also watch my diet. Later on, while on a supermarket, a friend of mine saw a jar of "GNC Heart Health" and highly recomend that i take it for my cholesterol condition. Strange enough, a few days after using it I began feeling highly depressed and very anxious at all times. I couldn't think straight and also felt sort of confused when trying to solve simple everyday problems, also my language began to break down (I would switch one word for another and even found it very hard to come up with any when trying to properly express myself). I had no idea of what was going on with me until for some unexplained reason I thought of lookin up the word Phytosterois in the Internet and found the side effects article on your website where some people commented that they also fell into depression. And, to top it off, I even lost some of the urge to even go out to do anything at all, I felt fear that if I did things might just go awfully wrong. I also felt kind of low in energy for no apparent reason.

Phytosterol Research studies
Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice.
J Nutr Biochem. 2005.
Patients with mixed dyslipidemias (increased LDL cholesterol and triglyceride as well as low HDL cholesterol levels) benefit from a combination of lipid-modifying drugs such as statins, niacin, fibrates and ezetemibe. However, safety, tolerability and cost are a concern in drug combination therapy. Dietary phytosterols reduce LDL cholesterol, and niacin or fenofibrate primarily reduces triglyceride and increases HDL-cholesterol levels. Thus, we hypothesized that a combination of phytosterols with niacin or fenofibrate will synergistically impact lipoprotein profile and atherogenesis in apo E-KO mice. Phytosterols alone significantly reduced plasma total cholesterol levels (14 vs. 16 mmol/L) and the extent of atherosclerosis. The addition of fenofibrate to phytosterols increased plasma total cholesterol levels by >50% and decreased HDL-cholesterol concentrations by 50%. These changes were accompanied by slight reductions in the extent of atherosclerosis as compared to controls, suggesting other potential anti-atherogenic effects of fenofibrate. Unlike fenofibrate, niacin caused an increase of 150% in HDL-cholesterol concentrations and a decrease of 22% in total cholesterol levels which were associated with significant reductions in atherosclerotic lesion size as compared to controls. Neither the addition of niacin nor of fenofibrate reduced plasma triglyceride levels. In conclusion, the addition of niacin to phytosterols synergistically increases HDL-cholesterol levels, while a combination of phytosterols and fenofibrate results in no synergistic effects in apo E-KO mice. Further studies in other animal models are needed to establish synergetic effects between these lipid-modifying dietary and pharmacological agents.

[Therapeutic effects of phytosterols and phytostanols in cholesterolemia]
Arch Latinoam Nutr. 2004.
Plant sterol and stanol esters are called "functional" compounds due to their hypocholesterolemic properties. The objective of this review is to update recent findings concerning the effect of phytosterols in the blood cholesterol, emphasizing the results from experimental and human studies. The hypocholesterolemic effect is observed with the intake of 2.5g/day of phytosterols or phytostanols. Daily intake, usually of stanols, for 4 weeks has shown to to be effective in lowering blood total- as well as LDL-cholesterol by about 10%. The mechanism of action in lowering blood cholesterol comes from their structural similarity to cholesterol, hence they act by competing with cholesterol at the luminal absorption site. The adverse effects of a high intake of phytosterols and phytostanols are the lower absorption of some liposoluble vitamins and antioxidants.

Combination of phytosterols and omega-3 fatty acids: a potential strategy to promote cardiovascular health.
Curr Med Chem Cardiovasc Hematol Agents. 2004.
Phytosterols and omega-3 fatty acids (n-3) are natural food ingredients with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total cholesterol (TC) and LDL-cholesterol levels. Numerous clinical studies have shown that a daily intake of 1.5-2.0 gram of phytosterols can result in a 10-15 % reduction in LDL levels, while consumption of n-3 is associated with a significant reduction in plasma triglyceride (TG) concentrations. Furthermore, n-3 may also beneficially modify a number of other risk factors of coronary heart disease (CHD). Thus, it is reasonable to suggest that combination of phytosterols and n-3 may further reduce cardiovascular risk factors. Esterification of phytosterols with non-n-3 fatty acids has substantially improved their incorporation into a variety of foods without affecting the efficacy of phytosterols. Therefore, it is assumed that esterification of phytosterols with n-3 may have advantages for both food industry and health. Evidence suggests that this combination is effective in reducing the levels of several cardiovascular risk factors including TC and TG concentrations, pro-aggregatory factors, arrhythmic eicosanoid and thromboxane A2 levels. In this mini-review, we have critically reviewed and summarized data from clinical and animal studies in which phytosterols and n-3, alone or in combination, were used. We have also provided information on structure-function relationship for these two natural compounds. Biological properties of several phytosterol derivatives including phytosterol-glucoside have been also discussed. Although the animal studies are supportive of this combination therapy, human studies are needed to address its long term effects.

Phytosterols and cholesterol metabolism.
Curr Opin Lipidol. 2004. Department of Internal Medicine, Washington University, St Louis, Missouri
Phytosterols displace cholesterol from intestinal micelles, reducing the pool of absorbable cholesterol, but they are also rapidly taken up by enterocytes and increase expression of the adenosine triphosphate-binding cassette A1 sterol transporter. Phytosterol esters dissolved in food fat reduce LDL-cholesterol by 10% at a maximum effective dose of 2 g/day. However, this work probably understates the true effectiveness of phytosterols because it does not account for those naturally present in baseline diets. Single meal studies show that phytosterols in intact foods are bioactive at doses as low as 150 mg. The potential effectiveness of phytosterols has been improved in several ways. Individuals most likely to respond have been identified as having high cholesterol absorption and low cholesterol biosynthesis. Phytosterols can be emulsified with lecithin and delivered in non-fat or low-fat foods and beverages, and the amount of fat in fat-based preparations can be reduced substantially with the retention of bioactivity. Phytosterols effectively reduce LDL-cholesterol when given as supplements, and the smaller amounts in natural foods also appear to be important.

Potential uses and benefits of phytosterols in diet: present situation and future directions.
Clin Nutr. 2003.
Over the past decade, the possibility of using phytosterols as ingredients in functional foods has led to numerous research studies in relation to their ability to reduce blood cholesterol. Many different types of carriers have been tested, with good results. The main conclusion is that the effective doses were between 1.5 and 3g/day, leading to reductions between 8% and 15% in LDL-cholesterol. The principal mechanism of action is based on interference with the solubilisation of the cholesterol in the intestinal micelles and, thus, absorption is reduced. Work has also been done on the optimal pattern of administration, and it has been found that ingesting phytosterols in a single dose per day or between meals are equally effective methods. The only side effect is that they can interfere with the absorption of carotenoids, but this can be compensated for in the diet or by adding these compounds in appropriate carriers. It has also been reported that phytosterols have anticancer properties and act as immune system modulators.There are several possible future lines of research: alternative sources with a high phytosterol content must be found, industrial processes must be implemented which minimise their loss, phytosterols must be included in food composition tables, the potential of the different types of phytosterols must be discerned, the genetic bases of their action must be elucidated, synergic effects with other compounds must be studied, side effects must be minimised, and the effects of long-term treatment must be defined precisely.

Phytosterols and human lipid metabolism: efficacy, safety, and novel foods.
Lipids. 2003.
Plant sterols have been known for several decades to cause reductions in plasma cholesterol concentrations. These plant materials have been granted a conditional health claim in the United States regarding their effects in the prevention of cardiovascular disease and are being sold in functional foods in several countries in Europe as well as in the United States and Australia. It is generally suggested that daily consumption of approximately 2 g of plant sterols can lower cholesterol concentrations as part of a dietary prevention strategy. However, phytosterols have been added and tested for their cholesterol-lowering effects mainly in spreads. Consumption of these high-fat foods seemingly flies in the face of current recommendations for the promotion of heart health, which suggest lowering total fat and energy intake to maintain weight. Hence, new food formulations are being evaluated using phytosterols incorporated into low-fat and reduced-fat food items. The purpose of this review is to examine the cholesterol-lowering efficacy of plant sterols, focusing on novel food applications, their mechanism of action, and safety. These novel food formulations include new solubilization processes that lead to improved uses for plant sterols, as well as new foods into which phytosterols have been incorporated, such as breads, cereals, and beef. Such new foods and formulations should pave the way for greater use of phytosterols in heart health promotion, increasing the longer-term potential for the creation of innovative functional foods containing plant sterols and their derivatives.

Q. I am doing personal research on phytosterol supplements and their interaction and affect on testosterone. I know that Phytosterols 'mimic' Testosterone. What I am trying to find out is...Does this mean that an increase of phytosterols WILL have an effect on the "levels of Testosterone"?
   A. We are not aware of human studies regarding the role of phytosterol ingestion in testosterone release or production.

Q. On your cholesterol page you state: ”There's still much research that needs to be done before we can make any firm recommendations regarding the use of supplements to lower cholesterol levels.” Yet many companies offer phytosterol products claiming cholesterol-lowering benefits. (At least one highly-respected company offers a phytosterol product with ingredients derived from soybean oil and corn oil.) Is it your position that evidence supporting the efficacy of such products remains inconclusive?
   A. We'll need a few more studies to have a better understanding on the long term cholesterol lowering influence of supplementation with these phytosterols. It may turn out that phytosterols could be of benefit, but it takes lots of time to find out and research studies need to be confirmed by several independent institutions.

Q. Are you familiar with Phytosterol N used in Germany to treat menopausal hot flashes? Phytosterol N has been the subject of recent small clinical studies that have shown positive effect. I have purchased the product from the Nutricentre in London  and my wife has seen a dramatic effect. It is manufactured by Carl Muller in Germany. It is quite expensive from the Nutricentre (equiv of $1 per tablet per day).
   A.  We looked at the Nutricentre website and cold only find Phytosterol Complex (Natural Source Of Plant Sterols). This product contains Hops 100mg, Alfalfa 50mg, Liquorice Root 50mg, Celery Seed 10:1 Extract 5mg (equivalent to 50mg celery seed), Rhubarb 5mg, We are not familiar with this product.

Q. I have recently started taking Centrum cardio with phytosterols and have realized that I develop a low-grade headache within an hour which is easily controlled with Advil. I have taken Centrum products in the past (Centrum silver) with no adverse effects. So, I wonder if this is a normal side effect of early therapy with phytosterols or something dangerous telling me to stop.
   A. We are not aware of research with a phytosterol supplement that have evaluated its role in headache induction. The Centrum cardio has many other vitamins and nutrients besides phytosterols so it is difficult to say that the phytosterols are the causative agents for the headache.

Q. Will taking a phytosterol supplement interfere or cause a problem with the 20mg pravachol I'm taking now?
   A. This is very difficult to predict since each person may respond differently. We don't suspect any major untoward reactions with the combination, but we have not seen any studies combining phytosterol supplements and pravachol or other stating drugs.

Solgar has announced the introduction of Phytosterol Complex 1000 mg Softgels, providing Heart Choice all-natural, scientifically researched plant sterols derived from soybean and sunflower oils.

Phytosterol supplier
Blue California, an ingredient manufacturer in Southern California, announced its introduction of micro-encapsulated phytosterols 40%, in powder form, for water-soluble applications. Phytosterols (also called plant sterols) are a group of steroid alcohol phytochemicals naturally occurring in plants. They are white powders with mild, characteristic odor, normally insoluble in water and soluble in alcohols. They have many applications as food additives, and in medicine and cosmetics. Blue California’s micro-encapsulation technology was used in the development of this new water-soluble form of phytosterols creating a wide array of opportunities for its customers in the beverage, dietary supplement and food industries. Phytosterols are widely found in the plant kingdom and studies have consistently shown that plant sterols can help reduce cholesterol levels. A 2004 study from Washington University in St. Louis found phytosterols effectively reduce LDL-cholesterol when given as supplements, and the smaller amounts in natural foods also appear to be important. The study also found that since phytosterols have very low systemic absorption and are already present in healthy diets, increasing the intake of phytosterols may be a practical way to reduce coronary heart disease with minimum risk. Contraindications for phytosterol supplementation include those with the rare genetic disorders sitosterolemia and cerebrotendinotic xanthomatosis and pregnant and nursing women.