Beta Sitosterol

Scientific Name(s): β-sitosterol

Common Name(s): Plant sterol , phytosterol

Uses

Cholesterol lowering and symptom improvement in mild to moderate benign prostatic hypertrophy. Possible role in the control of chronic inflammatory conditions.

Dosing

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

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No major adverse effects at recommended dose. Reduced absorption of carotenes and vitamin E may occur.

Toxicology

No data.

Dietary consumption is the main source of plasma phytosterols. They are not synthesized endogenously. Fortified margarines used for lowering cholesterol contain 2 g of plant sterols per daily portion. 1 The sitosterols are usually obtained from soybean oil, 2 peanut oil (207 mg/100 g of unrefined oil), 3 and avocado oil (76 mg/100 g). 4 Preparations containing β-sitosterol, derived from the South African star grass Hypoxis rooperi or from species of Pinus and Picea , are available for the treatment of benign prostatic hypertrophy. 5 Saw palmetto berries also contain large quantities of beta-sitosterol and other plant sterols.

History

Plant sterols were chemically described in 1922. 6 Later 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, so 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. 1 Over the last 15 years, there also have been several reports in the literature indicating that phytosterols have some immunological activity. 6

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. They are 28- or 29-carbon alcohols. 7 β-sitosterol is the most common plant sterol and is structurally similar to cholesterol. 1 Because of this structural similarity, β-sitosterol can replace cholesterol in the human body. 2 β-sitosterol is a 4-desmethyl sterol (containing no methyl groups at carbon atom number 4). 1 , 2 It has a double bond at the C-5 position in the ring, 7 and it is usually esterified with fatty acids for incorporation into margarine. 2

Uses and Pharmacology

β-sitosterol has a limited number of pharmacological uses.

Cholesterol-lowering 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 so little of the plant sterol is absorbed (approximately 5% of β-sitosterol). 1

Animal data

Research reveals no animal data regarding the use of beta-sitosterol to reduce cholesterol.

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. Low density lipoprotein (LDL) cholesterol ranged from 116 to 174 mg/dL in the control groups in these studies. This is consistent with normal values in the general population. The margarine produced a reduction in the mean concentration of LDL cholesterol. The effect increased with age. In each age group, the dose response relation was continuous up to a dose of about 2 g of plant sterol or stanol per day. 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 is apparent. This trend was statistically significant ( P  = 0.005). 1

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. 1

Immunomodulatory effects

Initial studies have shown that β-sitosterol can increase the proliferation of peripheral blood lymphocytes and enhance 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. 6

Excessive physical stress such as that observed in marathon runners can cause subtle immunosuppression. This may be due, in part, to the fact that it disturbs the normal physiological equilibrium or homeostasis, including that of the immune system. Administration of β-sitosterol (vs placebo) can prevent the typical neutrophilia, lymphopenia, and total leukocytosis. 8

Animal data

Research reveals no animal data regarding the use of beta-sitosterol as an immunomodulatory agent.

Clinical data

A randomized controlled trial of 47 patients with pulmonary tuberculosis investigated adjuvant β-sitosterol therapy vs placebo. The β-sitosterol treatment group (average dose of 60 mg/day) demonstrated increased weight gain, higher lymphocyte and eosinophil counts, and a generally faster clinical recovery. 9

Anticancer properties

β-sitosterol has demonstrated effects on tumor cell lines in vitro. Growth is inhibited in human colon, prostate, and breast cancer cell lines. It has been postulated that cell death (apoptosis) is initiated, probably by activation of the protein phosphatase A2 pathway.

Animal data

Studies using rat and mice models have shown β-sitosterol to reduce the number of tumors. 6

Clinical data

A cohort study performed in the Netherlands was unable to demonstrate any effect of plant sterols on the risk of colon and rectal cancers. For 6.3 years, 120,852 patients 55 to 69 years of age were followed. The average amount of plant sterols consumed by the participants was 285 mg/day. 7

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 benign prostatic hypertrophy (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 they had tried phytotherapeutic agents. 5

Animal data

Research reveals no animal data regarding the use of beta-sitosterol for benign prostatic hyperplasia.

Clinical data

A Cochrane review of 4 randomized, controlled trials comparing β-sitosterol with placebo (or other BPH medications) investigated the effects of β-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. β-sitosterol improved urinary symptoms and flow measures and was generally well tolerated. The authors of this review suggested that β-sitosterol may be a useful treatment option for men with mild to moderate BPH, particularly those who would like to avoid or are at increased risk for adverse effects from alpha-adrenergic receptor blockers. 5 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.

Dosage

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

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

On the basis of extensive safety evaluation studies, the plant sterols are generally recognized as safe when consumed in margarine at the recommended doses. The most important concern about plant sterols is that they reduce the absorption of the fat-soluble vitamins β-carotene, α-carotene, and vitamin E. No effects on vitamins A and K have been noted. No other side effects were evident in the randomized trials (1 of which lasted 1 year). 1 Increased concentrations of phytosterols in erythrocyte membranes may result in increased fragility; episodes of hemolysis have been reported. However, these were in patients with sitosterolemia. 10 Despite the lack of evidence of harm with beta-sitosterol use, it should be noted that hydrogenation into transfatty acids occurs with margarine ingestion. Therefore, margarine should be used in moderation only and cannot be recommended as the sole therapeutic option in the diseases mentioned in this monograph.

Toxicology

Research reveals little or no information regarding toxicology with the use of this product.

Bibliography

1. Law MR. Plant sterol and stanol margarines and health. West J Med . 2000;173:43-47.
2. Plat J, Kerckhoffs DA, Mensink RP. Therapeutic potential of plant sterols and stanols. Curr Opin Lipidol . 2000;11:571-576.
3. Awad AB, Chan KC, Downie AC, Fink CS. Peanuts as a source of β-sitosterol, a sterol with anticancer properties. Nutr Cancer . 2000;36:238-241.
4. Duester KC. Avocado fruit is a rich source of beta-sitosterol. J Am Diet Assoc . 2001;101:404-405.
5. Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev . 2000:CD001043.
6. 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;4:471-475.
7. Normen 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;74:141-148.
8. Bouic PJ, Clark A, Lamprecht J, et al. The effects of β-sitosterol (BSS) and β-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation. Int J Sports Med . 1999;20:258-262.
9. 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;1:518-522.
10. Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med . 1999;107:588-594.

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