Beta Sitosterol


 

Beta-Sitosterol Clinical Report Summary

 

Beta-sitosterol is a plant sterol that benefits heart and prostate health due to the fact that plant sterols and stanols reduce the absorption of cholesterol from the gut and so lower serum concentrations of cholesterol (1). A meta-analysis of 41 trials showed that plant sterols or stanols reduced low-density lipoprotein (LDL), in some cases up to 10% (using 2 g per day).  Additionally, long term studies have observed an LDL reduction of 20% due to plant sterols in combination with a low-fat diet and eating foods low in saturated fat and cholesterol.  It is for this reason that studies have noted the addition of stanols or sterols to statin medication results in greater effectiveness than simply doubling the prescription medication.  This may also affect sexual performance as fewer blocked arteries would indicate better circulation in the body.  Further health benefits of beta-sitosterol include a protective role in prostate, colon and breast health.  For instance, modern studies show that beta-sitosterol is useful in treating benign prostate hypertrophy, particularly stages 1 and 2, but these studies do not link it to the enlarged size of the gland.  In one systematic review of four double-blind trials with 519 men, beta-sitosterol also improved urinary symptom scores and flow measures when compared with a placebo (2).  The existing studies are limited by short treatment duration and variance of beta-sitosterol preparations.  Long-term benefits of beta-sitosterol supplementation require further examination; however, considering people are consuming beta-sitosterol in their diet on a regular basis, it appears to be a safe ingredient with few drawbacks.

 

Beta-Sitosterol Overview

 

Beta-sitosterol is a specific plant compound that falls under the category of phytosterols otherwise known as plant sterols. (Stanols are sterols that have been hydrogenated.)  Beta-sitosterol is one of the most prevalent of the phytosterols, with a similar molecular structure to cholesterol. The average American diet includes between 165-200 milligrams of beta-sitosterol per day, of which less than 5% is actually absorbed in the body.  This amount, which is not adequate, is why studies debate that dietary supplements of beta-sitosterol could result in a 25% reduction in the risk of heart disease (3). It has also been suggested by health expert Earl Mindell that high cholesterol can affect sexual performance due to poor circulation.  In addition to reducing overall cholesterol, plant sterols have been found to be beneficial for benign prostatic hypertrophy (BPH).  In plant foods, the highest concentration of beta-sitosterol is found in oil-based food sources while olive, avocado, flaxseed, tuna, and peanut are examples of foods containing the highest levels of phytosterols (4, 5).  Dietary supplements of beta-sitosterol can also be derived from pine trees.

 

Safe Use of Beta-Sitosterol

 

The FDA has an approved health claim for beta-sitosterol that states, "Scientific studies show that 1.3 grams per day of plant sterol esters or 3.4 grams per day of plant stanol esters in the diet are needed to show a significant cholesterol lowering effect. In order to qualify for this health claim, a food must contain at least 0.65 grams of plant sterol esters per serving or at least 1.7 grams of plant stanol esters per serving"(6). The typical dose found in supplements is 500 mg up to 6 g per day (1).

 

Clinical Studies for Beta-Sitosterol

 

1. Beta-Sitosterol and Cholesterol/LDL Reduction

 

Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells.  Field FJ, Born E, Mathur SN. (7)

CaCo-2 cells were used to address the effect of the plant sterol, beta-sitosterol, on cholesterol trafficking, cholesterol metabolism, and apoB secretion. Compared to cells incubated with micelles (5 mM taurocholate and 250 microM oleic acid) containing cholesterol, which caused an increase in the influx of plasma membrane cholesterol to the endoplasmic reticulum and increased the secretion of cholesteryl esters derived from the plasma membrane, beta-sitosterol did not alter cholesterol trafficking or cholesteryl ester secretion. Including beta-sitosterol in the micelle together with cholesterol attenuated the influx of plasma membrane cholesterol and prevented the secretion of cholesteryl esters derived from the plasma membrane. Stigmasterol and campesterol had effects similar to beta-sitosterol, although campesterol did not promote a modest influx of plasma membrane cholesterol. Including beta-sitosterol in the micelle with cholesterol decreased the uptake of cholesterol. Compared to cholesterol, 60% less beta-sitosterol was taken up by CaCo-2 cells. No observable esterification of beta-sitosterol was appreciated and the transport of the plant sterol to the basolateral medium was negligible. Cholesterol synthesis and HMG-CoA reductase activities were decreased in cells incubated with beta-sitosterol. This was associated with a decrease in reductase mass and mRNA levels. Cholesteryl ester synthesis and ACAT activities were unaltered by beta-sitosterol. Both stigmasterol and campesterol decreased reductase activity, but only campesterol increased ACAT activity. beta-sitosterol did not affect the secretion of apoB mass. The results suggest that beta-sitosterol does not promote cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. beta-sitosterol interferes with the uptake of micellar cholesterol causing less plasma membrane cholesterol to influx and less cholesteryl ester to be secreted. Despite its lack of effect on cholesterol trafficking, beta-sitosterol decreases cholesterol synthesis at the level of HMG-CoA reductase gene expression.

 

Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Katan, M. B., Grundy, S. M., Jones, P., Law, M., Miettinen, T., and Paoletti, R.

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increas ed plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

 

2. Beta-Sitosterol and Prostate Health

 

beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. Wilt, T. J., MacDonald, R., and Ishani, A.

OBJECTIVES: To conduct a systematic review of the evidence for the efficacy of beta-sitosterol in men with symptomatic benign prostatic hyperplasia (BPH). METHODS: Studies were identified through Medlinetrade mark (1966-98), EMBASEtrade mark, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with study authors and pharmaceutical companies. Randomized trials were included if: men had symptomatic BPH; plant extract preparations contained beta-sitosterols; a control group received placebo or a pharmacological therapy; and treatment duration was >/=30 days. Study characteristics, demographic information, enrolment criteria and outcomes were extracted. RESULTS: Four trials comprising a total of 519 men met the inclusion criteria. All were double-blind and lasted 4-26 weeks. Three studies used nonglucosidic beta-sitosterols and one used a preparation that contained only beta-sitosterol-beta-d-glucoside. Compared with placebo, beta-sitosterol improved urinary symptom scores and flow measures. For the two studies reporting the International Prostate Symptom Score (IPSS), the weighted mean difference (WMD) against placebo was -4.9 IPSS points (95% confidence interval, CI,-6.3 to-3.5). The WMD for peak urinary flow rate was 3.91 mL/s (95% CI 0.91 to 6.90, four studies) and for residual volume the WMD was -28.62 mL (95% CI-41.42 to-15.83, four studies). beta-sitosterol did not reduce prostate size. The trial using pure beta-sitosterol-beta-d-glucoside (WA184) showed no improvement in urinary flow measures. Withdrawal rates for men assigned to beta-sitosterol and placebo were 7.8% and 8.0% (not significant), respectively. CONCLUSION: beta-sitosterol improves urological symptoms and flow measures. However, the existing studies are limited by short treatment duration and lack of standardized beta-sitosterol preparations. Their long-term effectiveness, safety and ability to prevent the complications of BPH are unknown.

 

Beta-Sitosterol References

 

  1. Katan, M. B., Grundy, S. M., Jones, P., Law, M., Miettinen, T., and Paoletti, R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin. Proc. 2003;78(8):965-978.
  2. Wilt, T. J., MacDonald, R., and Ishani, A. beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. BJU Int. 1999;83(9):976-983.
  3. Law, M. Education and debate: plant sterol and stanol margarines and health.  BMJ. 2000;320:861-864.
  4. Andrikopoulos, N. K., Kaliora, A. C., Assimopoulou, A. N., and Papageorgiou, V. P. Inhibitory activity of minor polyphenolic and nonpolyphenolic constituents of olive oil against in vitro low-density lipoprotein oxidation. J Med Food. 2002;5(1):1-7.
  5. Awad, A. B., Chan, K. C., Downie, A. C., and Fink, C. S. Peanuts as a source of beta-sitosterol, a sterol with anticancer properties. Nutr Cancer. 2000;36(2):238-241.
  6. Anon. FDA authorizes new coronary heart disease health claim for plant sterol and plant stanol esters. FDA. 2000. Available at: www.fda.gov/bbs/topics/ANSWERS/ANS01033.html.
  7. Field FJ, Born E, Mathur SN. Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells.  J-Lipid-Res. 1997 Feb; 38(2): 348-60.
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