The Rising Stock of Sterols & Stanols
The background, science, regulatory issues and food applications surrounding these plant-based nutrients

by Susan Colebank

Cholesterol is important for the body's functions. It is used to form cell membranes and even certain hormones. Absorbable cholesterol comes from three sources: the diet, the liver and from intestinal cell turnover. Typically, Americans consume 200 mg/d to 500 mg/d of cholesterol, while bile from the liver can contribute up to 1,000 mg/d. New intestinal cells, which are created every five days, slough off old cells that contribute an additional 250 mg/d to 400 mg/d of cholesterol that can be reabsorbed.

It is when cholesterol levels become too high (greater than 240 mg/dl)--leading to hypercholesterolemia--that trouble ensues. Artery-clogging plaques may be formed from this excess, leading to future vascular issues.

Plant sterols and stanols are similar in structure to cholesterol but are not made by the human body. Because plant sterols and stanols are similar to the chemical structure of cholesterol, they block the absorption of cholesterol in the gut by mimicking cholesterol.

Phytosterols--which is the umbrella term for both plant sterols and stanols--occur naturally in food as free alcohol, esterfied with long-chain fatty acids and conjugated as glucosides. They are hydrolyzed by pancreatic carboxyl ester lipase, although absorption has been found to be low in human and animal studies. Esters that are absorbed are transported into very low-density lipoprotein (VLDL), taken up by the liver and are then excreted into the bile. Tissues with LDL receptors--such as the liver, adrenals and testes--may convert the phytosterols into steroid hormones. Interestingly, sterol absorption has been found to be slightly higher in women than men and even higher yet in children compared to adults.

According to Minneapolis-based Cargill Health & Food Technologies, phytostanols are fully saturated forms of phytosterols and are found in much lower concentrations than phytosterols.

"There are four forms of phytosterols on the market, all being promoted for their ability to lower cholesterol levels," said Clint Fairow, research and development manager at Champaign, Ill.-based Degussa Health & Nutrition, makers of Cholestatin plant sterols. "Free phytosterols, free phytostanols, esterified phytosterols and esterified phytostanols are all available to consumers. The weight of evidence at this time does not support any claim to the superiority of any of the four forms of phytosterols available."

The Science

Not only have stanols and sterols been found to help reduce high cholesterol levels, but they also provide a protective effect for children with family histories of high cholesterol. They have also been seen to enhance cholesterol-lowering therapy (i.e., statins) and have shown promise in immune and prostate health.

"The short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies," wrote researchers from the University of Kuopio, Finland.¹ However, in their study of 11 mildly to moderately hypercholesterolemic subjects given 2 g/d of stanol esters for 14 days, LDL cholesterol concentrations were reduced 10.2 percent.

In research out of Brazil, patients with primary moderate hypercholesterolemia who were given 2.8 g/d of plant sterol esters in the form of margarine exhibited reductions in total and LDL cholesterol by 10 percent and 12 percent, respectively.² According to researchers in Australia, both plant sterol esters and non-esterfied stanols can contribute to LDL decreases.³

Norwegian research has indicated that children between the ages of 7 and 12 with familial hypercholesterolemia lowered LDL plasma concentrations after taking 1.6 g/d of sterol esters over an eight-week period.⁴ Even children with no history can benefit from these plant ingredients. Researchers in Finland found that in 6-year-old children with normal cholesterol levels, plant stanol esters reduced serum cholesterol concentration when replacing 20 g of the children's usual daily fat intake.⁵

Plant sterols have shown great promise in enhancing statins' cholesterol-lowering effects. Research out of Sydney, Australia, indicated that 2 g/d of sterol esters, consumed as a spread, helped reduce LDL cholesterol even more so for those patients on cerivastatin therapy.⁶ "The addition of sterol-ester margarine to statin therapy offers LDL cholesterol reduction equivalent to doubling the dose of statin," the researcher wrote.

Research out of Dallas also indicated that stanol esters combined with statin drugs might reduce total and LDL cholesterol levels,⁷ and researchers from Finland reported terrific results from a triple treatment of simvastatin (20 mg/d) for three months, followed by eight weeks of stanol ester margarine use (2.25 g/d of stanols), and another eight weeks of cholestyramine at 8 g/d.⁸ The therapy led to a 67-percent reduction in baseline LDL cholesterol levels and increased HDL by 15 percent.

A possible side effect from consuming plant sterols and stanols may be a reduction in carotenoid plasma levels. Researchers from The Netherlands-based Unilever, makers of Take Control spread, reported there is an observed 10-percent to 20-percent decrease in plasma carotenoids when foods containing plant sterols and or stanols are consumed regularly.⁹ However, by implementing just one additional serving of carotenoid-rich food into the diet, this side effect may be avoided.¹⁰

Sterols are not just good for the heart, but also for the rest of the body. In South Africa, researchers believe that the use of sterols and sterolins (the glucoside of sterols) may improve immune health--particularly as it relates to HIV (the patented formula is currently sold by Eugene, Ore.-based EPI/Moducare).¹¹ Those with prostate problems may also find a benefit in taking sterols.¹² In Germany, researchers reported that during a six-month, placebo-controlled clinical trial with beta-sitosterol (as Germany-based Hoyer's Harzol), patients who continued beta-sitosterol treatment after the study ended had stable values for all outcome variables at the 18-month follow-up.

More is not necessarily better in terms of phytostanols, either. Researchers from the University of Kuopio in Finland reported that 1.6 g/d of stanol esters offered the same benefits as higher doses.¹³ It also appears that it does not matter when stanols are taken. In a study of 39 subjects with normal or mildly elevated cholesterol levels, 2.5 g of plant stanols given at lunch or 2.5 g of stanols given over the course of the day led to similar LDL-lowering benefits.¹⁴

Regulatory Issues & Food Applications

Countries around the world have gotten onboard the phytosterol and phytostanol health wagon. The U.S. Food and Drug Administration (FDA) has given them GRAS (generally recognized as safe) status for a range of food applications and allowed an interim health claim for these ingredients. Europe, Australia, New Zealand and Brazil have approved the use of these compounds in spreads.

Many Americans may be staying away from the high-fat foods that are high in plant sterols, such as sesame seeds, olive oil and peanuts, according to La Grange, Ill-based Cognis Nutrition & Health, makers of Vegapure sterol esters that come in forms suitable for softgel encapsulation, tablet-grade powder and water-dispersible powder ideal for drink mixes and energy bars.

In September 2000, FDA authorized the use of health claims for products containing plant sterol or plant stanol esters and their roles in reducing the risk of coronary heart disease. Released as an interim final rule, those foods that are allowed the claim based on sterol ester content included spreads and salad dressings; for claims in terms of stanol esters, qualifying foods included spreads, salad dressings, snack bars and dietary supplements in softgel form.

Foods carrying the claim, and containing plant sterols or stanols, must also be low in saturated fat and cholesterol--minus spreads and salad dressings as long as they bear a disclosure statement referring customers to the Nutrition Facts section in regard to fat content. They must also meet the "jelly bean rule," according to Barbara Bentson, director of regulatory affairs at Cargill. "That is, [foods] that have at least 10 percent of the daily value or RDI [recommended daily intake] for protein, fiber, vitamin A, vitamin C, calcium and iron."

In FDA's Talk Paper discussing the claims, the agency wrote, "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 .65 grams of plant sterol esters per serving or at least 1.7 grams of plant stanol esters per serving. The claim must specify that the daily dietary intake of plant sterol esters or plant stanol esters should be consumed in two servings eaten at different times of the day with other foods."

Manufacturers were allowed to use these claims as soon as they were published in the Federal Register. In early 2003, FDA expanded the enforcement discretion regarding the use of the interim health claim rule with respect to sterols, stanols and heart disease. In a letter to Cargill, which inquired about exercising the claims, the agency wrote that it intends to provide--pending publication of the final rule--enforcement discretion that goes beyond sterol and stanol esters. FDA would also be looking at foods containing 1) at least 400 mg per reference amount customarily consumed of phytosterols and 2) mixtures of sterols and stanols containing at least 80-percent beta-sitosterol, campesterol, stigmasterol, sitostanol and campestanol.

Based on this letter, Cargill reported the agency will allow a broader range of foods and dietary supplements to bear the heart health claim when products are formulated with .65 g of phytosterol esters or .4 g of free phytosterols per serving. "The best food and beverage applications for phytosterols are products that consumers naturally associate with being healthy and that are easy for them to incorporate into their diets," said Steve Snyder, director of sales and marketing at Cargill, makers of CoroWise phytosterols, with a make-up that contains more than 88 percent of a combination of sitosterol, campesterol and stigmasterol.

As of mid-March, FDA had publication of the final rule as an "A List" priority for its fiscal year 2003 Program Priorities. The agency, in its letter to Cargill, cautioned manufacturers at large that the guidelines in the final rule may differ from the interim rule.

"The health benefit is the main reason these ingredients are added to foods," said Cindy Schweitzer, Ph.D., senior scientist and head of the U.S. sterol research program at Cognis. "In some foods, like margarine-type spreads, they may replace some of the fat."

Currently, the heart-health benefits of phytosterols and stanols have been seen in spreads, mayonnaise, lozenges, low-fat yogurt, cheese, cereal and bread. This does not mean that they do not hold promise in a host of other applications, such as granola and nutritional bars, juice-based beverages, and smoothies. In fact, yogurt is one food application--besides spreads--in which plant stanol esters have shown promise. Researchers from Maastricht University, The Netherlands, reported that 60 volunteers consuming yogurt with 1 g of plant stanol esters experienced a greater drop in LDL cholesterol levels than the placebo-yogurt group.¹⁵ Researchers concluded yogurt with plant stanol esters had the same effect as stanols in oil-based products. Schweitzer added that in research using Cognis' phytosterol esters in beef products, findings indicated a decrease in total and LDL cholesterol in mildly hypercholesterolemic men.¹⁶

"The key to incorporating free phytosterols into foods or beverages will be finding a suitable matrix that is thick enough to keep the phytosterol particles suspended," Fairow said. "The use of phytosterols in a thin, watery beverage is impossible at this time. But watery beverages aside, the only limitation to incorporating phytosterols into products is the lack of innovation."

According to Snyder, "We anticipate that demand will increase as consumers and health care professionals become more aware of the cholesterol-lowering and heart-health benefits of phytosterols. One of the ways we think this awareness will increase is the expansion of the health claim to a broader range of food products, especially those that are more compatible with a heart-healthy diet."

Editor's Note:For a full list of references to this story, click here.