Beta Sitosterol

Scientific Name

Βeta-sitosterol

Common Name(s)

Phytosterol; Plant sterol

Clinical Overview: Uses

Beta-sitosterol has been used to lower low-density lipoprotein (LDL) cholesterol and improve symptoms in mild to moderate benign prostatic hypertrophy (BPH). Beta-sitosterol has also been investigated for its immunomodulatory and anticancer effects.

Clinical Overview: Dosing

Beta-sitosterol is incorporated in margarine, yogurt, or other foods to provide a daily intake of 1.5 to 3 g.

Clinical Overview: Contraindications

Avoid plant sterols such as beta-sitosterol in patients with sitosterolemia, a condition in which high plasma concentrations of plant sterols can lead to tendon xanthomas, premature atherosclerosis, and hemolytic anemia.

Clinical Overview: Pregnancy/Lactation

Beta-sitosterol should be avoided in pregnant women due to demonstrated uterine stimulant effects.

Clinical Overview: Interactions

Plant sterols reduce the absorption of the fat-soluble vitamins beta-carotene, alpha-carotene, and vitamin E. No effects on vitamins A and K have been noted. Beta-sitosterol levels may decrease in patients receiving ezetimibe through its inhibition of intestinal absorption of plant sterols.

Clinical Overview: Adverse Reactions

A review of the literature suggests that beta-sitosterol may cause GI adverse effects as well as impotence. In 1 study, adverse reactions deemed related to beta-sitosterol use were flatulence, discoloration of the feces, appetite changes, dyspepsia, leg cramps, skin rash, and leukopenia. A 1-year study in healthy patients consuming 1.6 g/day of plant sterols contained in a dietary spread demonstrated cholesterol-lowering effects as well as general tolerability with long-term consumption.

Clinical Overview: Toxicology

Clinical data are lacking.

Source

Dietary consumption is the main source of plasma phytosterols, which are not synthesized endogenously. Fortified margarines used for lowering cholesterol contain 2 g of plant sterols per daily portion.Ref The sitosterols are usually obtained from soybean oil,Ref peanut oil (207 mg per 100 g of unrefined oil),Ref and avocado oil (76 mg per 100 g).Ref Preparations containing beta-sitosterol derived from the South African star grass Hypoxis rooperi or from species of Pinus and Picea are available for the treatment of BPH.Ref Saw palmetto berries also contain large quantities of beta-sitosterol and other plant sterols.

History

Plant sterols were chemically described in 1922.Ref In the 1950s, it was noted that these sterols lower serum cholesterol concentrations by reducing the absorption of cholesterol from the gut. However, by the 1980s, statins were introduced to the market, and the role of plant sterols in lipid lowering was diminished. Subsequently, it has been recognized that, as naturally occurring substances, plant sterols can be added to foods. Margarine appears to be an ideal vehicle, although cream cheese, salad dressing, and yogurt are also used.Ref Over the last 15 years, there also have been several reports in the literature indicating that phytosterols have some immunological activity.Ref

Chemistry

Sterols are essential components of cell membranes, and both animals and plants produce them. The sterol ring system is common to all sterols; the differences are in the side chain. Phytosterols are 28- or 29-carbon alcohols.Ref Beta-sitosterol is the most common plant sterol and is structurally similar to cholesterol.Ref Because of this structural similarity, beta-sitosterol can replace cholesterol in the human body.Ref Beta-sitosterol is a 4-desmethyl sterol (lacking a methyl group at carbon atom number 4).Ref It has a double bond at the C-5 position in the ring,Ref and it is usually esterified with fatty acids for incorporation into margarine.Ref

Uses and Pharmacology

Cholesterol-lowering effects and other cardiovascular effects

Plant sterols in fortified margarine reduce the absorption of cholesterol from the gut by about half. This reduced absorption lowers serum cholesterol concentrations despite the compensatory increase in cholesterol synthesis that occurs in the liver and other tissues. Plant sterols are potentially atherogenic, like cholesterol, but atherogenesis does not occur because very little of the plant sterol is absorbed (approximately 5% of beta-sitosterol).Ref

Animal/In vitro data

In tumor necrosis factor (TNF)-alpha–stimulated human aortic endothelial cells, beta-sitosterol was found to significantly inhibit vascular adhesion molecule 1 and intracellular adhesion molecule 1 expression. A potential cardioprotective effect was also suggested.Ref

Clinical data

A meta-analysis of 14 randomized controlled trials (N = 473) investigated the effects of plant sterols and stanols (when added to margarine) on cholesterol. LDL cholesterol ranged from 116 to 174 mg/dL in the control groups in these studies, consistent with normal values in the general population. The fortified margarine reduced the mean concentration of LDL cholesterol, and the effect increased with age. In each age group, the dose response relation was linear up to a dosage of about 2 g/day of plant sterol or stanol. At doses of 2 g or higher, the average reduction in LDL cholesterol was 21 mg/dL for participants 50 to 59 years of age, 17 mg/dL for participants 40 to 49 years of age, and 13 mg/dL for those 30 to 39 years of age. At higher doses, no further reduction in LDL cholesterol was apparent. This trend was statistically significant (P = 0.005).Ref

Data suggest that in people 50 to 59 years of age, a reduction in LDL cholesterol concentration of 20 mg/dL would reduce the risk of heart disease by approximately 25% after 2 years. The effect is calculated to be superior to that expected if people merely ate less animal fat. For a person replacing butter with a plant sterol margarine, the reduction in cholesterol would be even greater.Ref

In a parallel, double-blind study, 164 Finnish patients with hypercholesterolemia were randomized to receive plant sterols targeted at 2 g/day or placebo for 6 weeks. Treatment resulted in a 6.5% decrease in total cholesterol and a 10.4% decrease in LDL cholesterol in those receiving plant sterols (P < 0.0005, P < 0.00005, respectively). High-density lipoprotein cholesterol levels did not change.Ref In a randomized, double-blind, placebo-controlled trial, the addition of phytosterol to red yeast rice therapy and life style changes did not result in any further reductions in lipid parameters compared with placebo.Ref

As a component of medical nutrition therapy for patients with type 1 or type 2 diabetes, the American Diabetes Association Standards of Care (2014) recommends an increase in foods containing n-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; from fatty fish), viscous fiber (eg, oats, legumes, citrus), and plant-based stanols or sterols to help treat dyslipidemias in most diabetic patients (ie, those who do not have severe hypertriglyceridemia) (high quality evidence).Ref The 2017 joint position statement of the Italian Society of Diabetology (ISD) and the Italian Society for the Study of Arteriosclerosis (ISSA) on nutraceuticals for the treatment of hypercholesterolemia strongly recommends the use of phytosterols to lower LDL in patients with mild hypercholesterolemia and low to moderate cardiovascular risk; patients with multi-statin resistance; or as an adjunct to drug therapy in patients with suboptimal LDL on drug therapy alone (Level I, Strength A).Ref

Immunomodulatory effects

Beta-sitosterol increased the proliferation of peripheral blood lymphocytes and enhanced the cytotoxic effect of natural killer cells. Further investigation revealed anti-inflammatory properties and has led to suggestions of a role in the control of chronic inflammatory conditions.Ref

Excessive physical stress, such as that observed in marathon runners, can cause subtle immunosuppression. This may be due in part to the disruption of normal physiological equilibrium or homeostasis, including that of the immune system. Administration of beta-sitosterol prevented the typical neutrophilia, lymphopenia, and total leukocytosis that occurs in times of excessive physical stress.Ref

Animal/In vitro data

In a study of peripheral blood mononuclear cells from patients with multiple sclerosis, beta-sitosterol reduced TNF-alpha release by 24% and reduced interleukin (IL)-12 release by 27% to 30%, depending on concentration. Anti-inflammatory cytokine IL-10 release was increased by 47% with beta-sitosterol administration in healthy subjects.Ref

Clinical data

A randomized controlled trial of 47 patients with pulmonary tuberculosis investigated adjuvant beta-sitosterol therapy versus placebo. The beta-sitosterol treatment group (average dosage of 60 mg/day) demonstrated increased weight gain, higher lymphocyte and eosinophil counts, and a generally faster clinical recovery.Ref

Anticancer properties

Animal/In vitro data

Beta-sitosterol has demonstrated effects on tumor cell lines in vitro. Growth is inhibited in human colon, stomach, prostate, and breast cancer cell lines as well as in multiple myeloma. It has been postulated that cell death (apoptosis) is initiated, probably by activation of the protein phosphatase A2 pathway.Ref Studies using rat and mice models have shown beta-sitosterol to reduce the number of tumors.Ref

In PC-3 cells, the combination of beta-sitosterol and resveratrol was believed to be synergistic against prostate cancer through apoptosis and by arresting cell growth at various states in the cell cycle to ultimately suppress tumor growth.Ref Another study showed that beta-sitosterol inhibited growth in DU-145 prostate cancer cells through increased p53 protein expression and decreased p21 and p27 protein expression.Ref

Beta-sitosterol inhibited cell growth of MCF-7 (estrogen receptor–positive) and MDA-MB-231 (estrogen receptor–negative) breast cancer cell lines. Additionally, a combination of beta-sitosterol and tamoxifen was found to inhibit breast cancer cell growth.Ref

Clinical data

A cohort study performed in the Netherlands found that plant sterols had no effect on the risk of colon and rectal cancers. For 6.3 years, 120,852 patients 55 to 69 years of age were followed, with an average consumption of 285 mg plant sterols per day.Ref

Benign prostatic hyperplasia

This nonmalignant enlargement of the prostate can lead to obstructive and irritative lower urinary tract symptoms. The majority of men over 60 years of age are considered to have urinary symptoms attributable to BPH. The pharmacological use of plants and herbs for the treatment of BPH symptoms has been steadily growing in most countries. Nearly a quarter of men seen with previously treated BPH at a university urology clinic for urinary symptoms indicated that they had tried phytotherapeutic agents.Ref

Beta-sitosterol may have a potential role in inhibiting 5-alpha-reductase as well as reducing steroid hormone biosynthesis, thereby reducing testosterone levels.Ref

Animal data

In gonadectomized hamster prostates, beta-sitosterol was found to inhibit the 5-alpha-reductase enzyme following subcutaneous administration.Ref

Clinical data

A Cochrane review of 4 randomized, controlled trials comparing beta-sitosterol with placebo (or other BPH medications) investigated the effects of beta-sitosterol on the outcomes of urinary symptom scores and flow measures. The treatment duration was short, with no study lasting longer than 26 weeks, and fewer than 600 men were evaluated. Beta-sitosterol improved urinary symptoms and flow measures and was generally well tolerated. The authors of this review suggested that beta-sitosterol may be a useful treatment option for men with mild to moderate BPH, particularly in those who would like to avoid or are at increased risk for adverse effects from alpha-adrenergic receptor blockers.Ref These agents (eg, prazosin) selectively block alpha-1-adrenergic receptors. The degree of smooth muscle tone in the prostate and bladder neck is mediated by the alpha-1-adrenergic receptor, which is present in high density in the prostatic stroma, prostatic capsule, and bladder neck. Blockade of the alpha-1-adrenergic receptor decreases urethral resistance and may relieve the obstruction and improve urine flow and BPH symptoms.

Androgenic alopecia

Beta-sitosterol may be useful in patients with androgenic alopecia because of its ability to reduce testosterone through inhibition of steroid hormone biosynthesis.Ref

Animal data

There are no animal data regarding the use of beta-sitosterol for androgenic alopecia.

Clinical data

In a study of 19 men between 23 and 64 years of age with mild to moderate androgenic alopecia, 60% of participants stated an "improvement" had occurred from baseline (approximately 5 months of treatment) after taking a treatment containing 50 mg of beta-sitosterol and 200 mg of saw palmetto extract compared with 11% of participants who had received placebo. This suggests a possible role for beta-sitosterol in patients with androgenic alopecia.Ref

Antimicrobial effects

Animal/In vitro data

Beta-sitosterol, along with various other compounds isolated from Ageratina pichinchensis var. bustamenta, was found to exert antimicrobial affects against Trichophyton species, which can cause tinea pedis infections.Ref Another in vivo study showed that beta-sitosterol derived from Ginkgo biloba leaves exerted antibacterial effects against Salmonella enterica and Staphylococcus aureus.Ref

Clinical data

There are no clinical data regarding the use of beta-sitosterol for its antimicrobial effects.

Dosing

Beta-sitosterol is incorporated in margarine, yogurt, or other foods to provide a daily intake of 1.5 to 3 g.

RNP Pregnancy/Lactation

Beta-sitosterol should be avoided in pregnant women due to demonstrated uterine stimulant effects. In a study of rats, beta-sitosterol derived from pomegranate seeds increased spontaneous uterine contractions in a concentration-dependent fashion through effects on calcium-activated K channels. Specifically, it increased uterine contraction force and duration, but not frequency. Maximum effects were noted at 1 mg per 100 mL.Ref

Interactions

Plant sterols reduce the absorption of the fat-soluble vitamins beta-carotene, alpha-carotene, and vitamin E. No effects on vitamins A and K have been noted.Ref Beta-sitosterol levels may decrease in patients receiving ezetimibe through its inhibition of intestinal absorption of plant sterols.Ref

Adverse Reactions

On the basis of extensive safety evaluation studies, the plant sterols are generally recognized as safe (GRAS) when consumed in margarine at the recommended doses. However, a review of the literature suggests that beta-sitosterol may cause GI adverse effects as well as impotence.Ref In 1 study, adverse reactions deemed related to beta-sitosterol use were flatulence, discoloration of the feces, appetite changes, dyspepsia, leg cramps, skin rash, and leukopenia.Ref In rats, a decrease in testicular weight and sperm concentration occurred with prolonged treatment at a low dose (0.5 mg/kg) of beta-sitosterol. Antifertility effects were noted at a higher dose (5 mg/kg).Ref In a study of rats, administration of a phytosterol diet for 5 weeks resulted in increases in systolic and diastolic blood pressure values.Ref A 1-year study in healthy patients consuming 1.6 g/day of plant sterols contained in a dietary spread demonstrated cholesterol-lowering effects as well as general tolerability with long-term consumption.Ref Increased concentrations of phytosterols in erythrocyte membranes may result in increased fragility; episodes of hemolysis have been reported, but these adverse reactions occurred in patients with sitosterolemia.Ref Despite no evidence of harm with beta-sitosterol use, hydrogenation into transfatty acids does occur with margarine ingestion. Therefore, margarine cannot be recommended as the sole therapeutic option in the diseases mentioned in this monograph.

Toxicology

In a study of hamsters, diets containing oxidation products of phytosterols (ie, beta-sitosterol, stigmasterol) resulted in greater liver weights compared with controls. Additionally, hamsters receiving the oxidation products lost the capacity to lower total cholesterol, LDL, and triacylglycerols.Ref

References

Aguilar-Guadarrama B, Navarro V, León-Rivera I, Rios MY. Active compounds against tinea pedis dermatophytes from Ageratina pichinchensis var. bustamenta. Nat Prod Res. 2009;23(16):1559-1565.[PubMed 19844829]

American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(suppl 1):S14-S80.[PubMed 24357209]

Awad AB, Barta SL, Fink CS, Bradford PG. beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism. Mol Nutr Food Res. 2008;52(4):419-426.[PubMed 18338406]

Awad AB, Burr AT, Fink CS. Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot Essent Fatty Acids. 2005;72(3):219-226.[PubMed 15664307]

Awad AB, Chan KC, Downie AC, Fink CS. Peanuts as a source of beta-sitosterol, a sterol with anticancer properties. Nutr Cancer. 2000;36(2):238-241.[PubMed 10890036]

Becker DJ, French B, Morris PB, Silvent E, Gordon RY. Phytosterols, red yeast rice, and lifestyle changes instead of statins: a randomized, double-blinded, placebo-controlled trial. Am Heart J. 2013;166(1):187-196.[PubMed 23816039]

Bouic PJ. The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr Metab Care. 2001;4(6):471-475.[PubMed 11706278]

Bouic PJ, Clark A, Lamprecht J, et al. The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation. Int J Sports Med. 1999;20(4):258-262.[PubMed 10376483]

Cabeza M, Bratoeff E, Heuze I, Ramírez E, Sánchez M, Flores E. Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate. Proc West Pharmacol. 2003;46:153-155.[PubMed 14699915]

Chen Q, Gruber H, Swist E, et al. Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading. Nutr Metab (London). 2010;7:11.[PubMed 20637058]

Choudhary SP, Tran LS. Phytosterols: perspectives in human nutrition and clinical therapy. Curr Med Chem. 2011;18(29):4557-4567.[PubMed 21864283]

Davidson MH, Maki KC, Umporowicz DM, et al. Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J Am Coll Nutr. 2001;20(4):307-319.[PubMed 11506058]

Desai F, Ramanathan M, Fink CS, Wilding GE, Weinstock-Guttman B, Awad AB. Comparison of the immunomodulatory effects of the plant sterol beta-sitosterol to simvastatin in peripheral blood cells from multiple sclerosis patients. Int Immunopharmacol. 2009;9(1):153-157.[PubMed 19022404]

Donald PR, Lamprecht JH, Freestone M, et al. A randomized placebo-controlled trial of the efficacy of beta-sitosterol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis. 1997;1(6):518-522.[PubMed 9487449]

Duester KC. Avocado fruit is a rich source of beta-sitosterol. J Am Diet Assoc. 2001;101(4):404-405.[PubMed 11320941]

Hendriks HF, Brink EJ, Meijer GW, Princen HM, Ntanios FY. Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr. 2003;57(5):681-692.[PubMed 12771969]

Jayaprakasha GK, Jadegoud Y, Nagana Gowda GA, Patil BS. Bioactive compounds from sour orange inhibit colon cancer cell proliferation and induce cell cycle arrest. J Agric Food Chem. 2010;58(1):180-186.[PubMed 20000570]

Korpela R, Tuomilehto J, Högström P, et al. Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur J Clin Nutr. 2006;60(5):633-642.[PubMed 16404415]

Law MR. Plant sterol and stanol margarines and health. West J Med. 2000;173(1):43-47.[PubMed 10903294]

Liang YT, Wong WT, Guan L, et al. Effect of phytosterols and their oxidation products on lipoprotein profiles and vascular function in hamster fed a high cholesterol diet. Atherosclerosis. 2011;219(1):124-133.[PubMed 21719014]

Loizou S, Lekakis I, Chrousos GP, Moutsatsou P. Beta-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res. 2010;54(4):551-558.[PubMed 19937850]

McNicholas T, Kirby R. Benign prostatic hyperplasia and male lower urinary tract symptoms (LUTS). Clin Evid (Online). 2011 Aug 26;2011. pii: 1801.[PubMed 22963025]

Merkens LS, Myrie SB, Steiner RD, Mymin D. Sitosterolemia. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle;1993-2013.

Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med. 1999;107(6):588-594.[PubMed 10625028]

Normén AL, Brants HA, Voorrips LE, Andersson HA, van den Brandt PA, Goldbohm RA. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr. 2001;74(1):141-148.[PubMed 11451730]

Park C, Moon DO, Ryu CH, et al. Beta-sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis. Acta Pharmacol Sin. 2008;29(3):341-348.[PubMed 18298899]

Pirro M, Vetrani C, Bianchi C, Mannarino MR, Bernini F, Rivellese AA. Joint position statement on "Nutraceuticals for the treatment of hypercholesterolemia" of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutr Metab Cardiovasc Dis. 2017;27(1):2-17.[PubMed 27956024]

Plat J, Kerckhoffs DA, Mensink RP. Therapeutic potential of plant sterols and stanols. Curr Opin Lipidol. 2000;11(6):571-576.[PubMed 11086329]

Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med. 2002;8(2):143-152.[PubMed 12006122]

Salen G, von Bergmann K, Lütjohann D, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. 2004;109(8):966-971.[PubMed 14769702]

Scholtysek C, Krukiewicz AA, Alonso JL, Sharma KP, Sharma PC, Goldmann WH. Characterizing components of the saw palmetto berry extract (SPBE) on prostate cancer cell growth and traction. Biochem Biophys Res Commun. 2009;379(3):795-798.[PubMed 19059205]

Sook SH, Lee HJ, Kim JH, et al. Reactive oxygen species-mediated activation of AMP-activated protein kinase and c-jun N-terminal kinase plays a critical role in beta-sitosterol-induced apoptosis in multiple myeloma U266 cells [published online ahead of print May 3, 2013]. Phytother Res.[PubMed 23640957]10.1002/ptr.4999

Tao R, Wang CZ, Kong ZW. Antibacterial/antifungal activity and synergistic interactions between polyprenols and other lipids isolated from Ginkgo biloba L. leaves. Molecules. 2013;18(2):2166-2182.[PubMed 23434869]

Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2000;(2):CD001043.[PubMed 10796740]

Zhao Y, Chang SK, Qu G, Li T, Cui H. Beta-sitosterol inhibits cell growth and induces apoptosis in SGC-7901 human stomach cancer cells. J Agric Food Chem. 2009;57(12):5211-5218.[PubMed 19456133]

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Last Updated 5/30/19