Sterols: Formidable Disease Fighter

Plant sterols were proven to have cholesterol-reducing benefits back in the 1950s. But new evidence suggests there is more to this family of phytosterols than was first imagined. Chris O'Brien reports.

Everyone knows fruits and vegetables are good for you. What's not so well known is that they contain health-promoting compounds called phytosterols, specifically sterols and stanols. According to the UK's Institute of Food Science and Technology, sterols are naturally occurring substances in plants, whereas stanols are the hydrogenated compounds of sterols. The common term for both is sterols.

Since the 1950s, sterols have been researched for their cholesterol-lowering effects, more recently for their immune-improving properties, and the latest studies tout sterols as aids for benign prostatic hyperplasia and as potential cancer preventives.

When the National Institutes of Health (NIH) lowered the acceptable cholesterol-level limits in the United States, they essentially pre-prescribed statin drugs to an additional 23 million Americans. Unfortunately, one statin, Baycol, was pulled from the market in August 2000 after 52 people died from related complications—fatal rhabdomyolysis, a condition in which statins break down muscle tissue that then enters the bloodstream and causes kidney failure—and the long-term side effects of statin drugs are as yet unknown. As a result, conscientious consumers are seeking safer alternatives to lower cholesterol levels.

Sterols are viable cholesterol-lowering alternatives to drugs. In fact, they can be marketed in the US with a Food and Drug Administration (FDA) health claim stating that foods containing at least 1.3 grams of sterol esters or 3.4 grams of stanol esters in daily servings may reduce the risk of heart disease. As such, sterols have become key ingredients in a new wave of cholesterol-reducing margarines such as Raisio Group's Benecol and Unilever's Take Control (US) and pro.activ (Europe), as well as Pharmavite's Cholest-Off sterol-containing tablet. Cholest-off contains Forbes Medi-tech's branded plant-sterol-based ingredient Reducol.

Recently, the American Heart Association challenged the health claim, stating that because sterols can lower levels of beta-carotene and other fat-soluble vitamins, the FDA should issue an advisory against consumption by children and pregnant women. The revision comment period closed in November 2001, and the FDA is preparing to make a decision. In the meantime, sterols are still recognised as potent science-backed phytochemicals for cholesterol reduction.

In the 1950s, large doses (25g) of crystalline sterols were found to lower cholesterol absorption. Then in the 1980s, scientists discovered smaller doses of esterified sterols that dissolved in edible fats were more effective.

Current scientific review began with a 1982 placebo-controlled study published in the American Journal of Clinical Nutrition. Researchers found that beta-sitosterol added to the diet decreased total cholesterol absorption by 43 per cent among a sample of nine adults.1 A year later, scientists found sterols reduced the absorption of cholesterol by a factor of five, both in rats and in vitro.2

A 1999 study at McGill University in Montreal, Canada, examined the effects of Reducol-brand sitosterol-containing sterol combination vs. a low-fat diet on 32 patients. Patients taking 1.7g/day Reducol experienced LDL reduction of up to 24 per cent compared to a 9 per cent dietary-influenced drop.3 In this study and others, no significant increases in plasma sterol levels were detected, indicating the sterols were not absorbed. Rather, sterols bound to cholesterol in the intestines and passed through the body before being absorbed.

In the past 15 years, researchers also have found sterols to enhance immunity. A pivotal study by sterol researcher Patrick Bouic, Ph.D., conducted in 1996 at the University of Stellenbosch, South Africa, found a 100-to-1 ratio of beta-sitosterol to its glucoside—a patented combination marketed by Ontario-based Essential Phytosterolins—affected T cell proliferation by up to 920 per cent in vivo.4

A 2001 study, also at the University of Stellenbosch, found HIV-positive subjects taking a sterol mixture exhibited a beneficial T-helper-cell-1 response compared to control subjects.5 Another Bouic study investigated the effects of the patented 100-to-1 sterol combination on post-marathon immune response and inflammation.

In the randomised, controlled trial, runners taking the sterol mixture had a positive immune response and reduced inflammation indicators vs. controls.6 Sterols also have been successfully tested as remedies and/or adjunct treatments in other immune-related disorders such as pulmonary tuberculosis7 and rheumatoid arthritis.8

Most recently, sterols have been studied as a remedy for benign prostatic hypertrophy (BPH). A 1995 trial at Ruhr University in Germany tested a 20mg beta-sitosterol mixture vs. placebo three times daily on 200 patients with BPH. The test group experienced significant reduction of symptoms and improved urinary flow.9 An 18-month follow-up indicated that symptoms in sterol-taking patients stabilised or improved, while those who discontinued the sterol regimen showed slightly worse symptoms.10

Another randomised, placebo-controlled trial, conducted at Academic Hospital in Germany, found that taking 130mg/day beta-sitosterol for six months improved urinary flow rate and quality of life and resulted in a statistically significant improvement in international prostate symptom score (IPSS).11 A German in vitro study, also conducted at Ruhr University, suggested that sterols induce an anti-inflammatory action in prostate tissue.12

Sterols are also being studied for their role in preventing prostate and other cancers. A 1998 in vitro study at the State University of New York at Buffalo found that human prostate cancer cells treated with beta-sitosterol decreased cell growth by 24 per cent and increased cell death—apoptosis—by 400 per cent.13

A 2000 review by some of the same researchers at SUNY-Buffalo indicated that sterols may offer protection from colon, prostate and breast cancer.14 Researchers cite both an animal study in which sterols reduced the number of colon-cancer tumors by 60 per cent as well as an in vitro study describing the inhibitory effect of sterols on human colon-cancer cells. Similar results were found in vitro with human prostate-cancer cells. Other in vitro studies found sterols to inhibit breast cancer cell growth by up to 80 per cent. The researchers suggest that sterols may have a cancer-protective role, but more human research needs to be done.

The bottom line is sterols have huge potential in nutraceuticals and particularly in functional foods. With no side effects and one minor handicap—potential fat-soluble vitamin depletion—the seeds of scientific research have already been planted for a harvest of powerful plant-derived remedies to some of the world's most challenging diseases.

Chris O'Brien is a freelance writer specialising in natural products and natural products marketplace issues.


1. Mattson FH, et al. Optimizing the effect of plant sterols on cholesterol absorption in man. Am J Clin Nutr 1982;35:697-700.

2. Ikeda I, et al. Some aspects of mechanism of inhibition of cholesterol absorption by beta-sitosterol. Biochim Biophys Acta 1983;732(3):651-8.

3. Jones et al. Cholesterol-lowering efficacy of sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Med 1999;69:1144-50.

4. Bouic PJ. beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination. Int J Immunopharmacol 1996;18(12):693-700.

5. Breytenbach U. Flow cytometric analysis of the Th1-Th2 balance in healthy individuals and patients infected with the human immunodeficiency virus (HIV) receiving a plant sterol/sterolin mixture. Cell Biol Int 2001;25(1):43-9.

6. Bouic PJ. 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):258-62.

7. Donald PR, 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(5):518-22.

8. Bouic PJ. Sterols/sterolins, the natural, non-toxic immunomodulators and their role in the control of rheumatoid arthritis. Newsletter of the Arthritis Trust of America, Summer 1998.

9. Berges RR, et al. Randomized, placebo-controlled, double-blind clinical trial of ß-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.

10. Berges RR, et al. Treatment of symptomatic benign prostatic hyperplasia with ß-sitosterol: an 18-month follow-up. Br J Urol 2000;85(7):842-6.

11. Klippel KF, et al. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. Br J Urol 1997;80(3):427-32.

12. Kassen A, et al. Effect of beta-sitosterol on transforming growth factor-beta-1 expression and translocation protein kinase C alpha in human prostate stromal cells in vitro. Eur Urol 2000;37(6):735-41.

13. von Holtz RL, et al. ß-sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr Cancer 1998;32:8-12.

14. Awad AB and Fink CS. "Phytosterols as anticancer dietary components: evidence and mechanism of action. J Nutr 2000;130(9):2127-30.

Spreading The News

A health claim-carrying ingredient and a delicious delivery method—sounds like a no-brainer for a functional food. That's what the Raisio Group thought when they introduced Benecol in 1995, tempting investors with a projected $1 billion in sales. But their fortified-margarine dream seemed to melt overnight. First, the world launch was thwarted when the FDA blocked the US introduction of Benecol as a dietary supplement in 1999. They finally received GRAS approval, but faltering sales and the introduction of a competitor, Unilever's pro.activ (Take Control in the US), sent the stock tumbling. In 2000, a new marketing partnership with McNeil promised tasty sales, but 2001 yielded a paltry $30 million in sales despite a marketing outlay of $100 million.

What happened? McNeil spokesperson Mark Gutsche stated "It's not everything that we thought it would be, but the brand is doing quite well in Europe and growing in double digits in the US."

Perhaps it's the counter-intuitive nature of the product—a margarine that's good for your heart? Yet, since its launch in the UK, pro.activ has outsold Benecol by more than two-to-one. For its part, Benecol is posting positive gains for 2001, while part of McNeil's plan includes a whole line of sterol/stanol-enriched products.

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