Plant Sterols and Stanols as an Adjunct To Statin Therapy
The primary drugs used for lowering LDL cholesterol are statins. It has been well established that the lowering of LDL cholesterol by sterols/stanols is additive to that of statins. Scholle et al 2009 performed a meta-analysis on the results of 8 clinical trials where sterols or stanols were added to statin therapy. The authors concluded that the addition of sterols and stanols to statin therapy may provide the additional cholesterol lowering needed to reach LDL cholesterol goals.
As shown above, an intake of plant sterols and stanols can be an important part of Therapeutic Lifestyle changes in bringing cholesterol to target levels. Additionally, intake of plant sterols and stanols may help in reaching target levels during statin therapy.
What are Phytosterols/Plant Sterols and Stanols?
Phytosterols (plant sterols and stanols) are the plant equivalent to animal cholesterol. In both animals and plants, sterols and stanols are essential components of the cell membrane. Phytosterols are present in all foods of plant origin. The human diet includes about 167-437 mg of
phytosterols per day (Ostlund 2002). Phytosterols, because of their similar structure to cholesterol, compete with cholesterol absorption mechanisms in the intestine. The amounts of phytosterols present in the diet, however, are not usually sufficient to affect blood levels of
cholesterol. Dietary intakes of phytosterols of 800 mg per day or higher are needed to cause a measureable reduction in blood LDL cholesterol absorption (Hendriks et al 1999).
The structures of 4 major phytosterols found in plant sources are compared to that of cholesterol in Figure 1. Phytosterols are divided into two main types: Sterols and stanols. In the sterol form, the 5-6 bond is unsaturated (shown as a double line). In the stanol form, the 5-6 bond is saturated (shown as a single line).
Figure 1: Molecular structure of cholesterol compared to sterols, stanols and a fatty acid ester
Also shown is a fatty acid ester of sitostanol. In this example, oleic acid is linked to the 3 position on the sterol ring replacing the hydroxyl group. Fatty acids can form ester linkages on all of the phytosterols at this position. Fatty acid esters are created by linking free sterols and stanols to free fatty acids in the presence of a food grade catalyst. When ingested, fatty acid esters are split by digestive enzymes in the intestine to release the active free sterols and stanols.
Fatty acid esters of phytosterols were developed to increase the solubility of phytosterols in vegetable oils. The primary use of esters is in manufacturing margarines. The non-esterified phytosterol forms are better for water based food products such as yogurts and juices. Most of the phytosterols used in foods are sold in margarines. Three types of esters are in use:
(1) Stanol esters, which contain sitostanol and campestanol esters
(2) Sterol esters, which contain sitosterol, campesterol, and usually, stigmasterol (structure not shown)
(3) Reducol® ester, which contains a blend of sitostanol, campestanol, sitosterol, and campesterol esters
The Reducol® Difference
Plant sterols and stanols have different effects on blood levels of plant sterols. The sterols in the blood come from plant sources in the diet. The amounts of these sterols in the blood are quite low compared to cholesterol (about 700 times lower in normal individuals). Absorption of plant sterols from the intestine is 0.5 to 1.9% compared to 40-60% for cholesterol. The absorption of plant stanols is much lower, 0.04 to 0.16% (Ostlund 2002). Plant stanols in the diet lower plant sterols in the blood by blocking the absorption of the plant sterols as well as cholesterol. Plant sterols, by increasing the sterol content in the intestine, also raise the blood level of plant sterols. Reducol® because it is a sterol/stanol mixture tends to have an intermediate effect on blood levels of plant sterols (Figure 2).
Figure 2: Comparison Of The Effects Of Ingested Sterols, Reducol®, and Stanols On Plasma Levels Of Plant Sterols.
Graphing data points: Sterols S=+32 %, C=+69 %; Reducol® mixture S= -10%, C= +12%; Stanols S= -36%, C=-38 %.
The data in Figure 2 were taken from studies by Amundsen et al 2004; Gylling et al 1995; Jones et al 1998; Jones et al 1999; Ketomaki et al 2003; Vanstone et al 2002; and Weststrate & Meijer, 1998.
There are other differences between the plant sterol and stanol forms. Stanols are not as effective as sterols at low doses. At a dose of 0.8 g/day, stanols were not effective in lowering LDL cholesterol (Hallikainen et al 2000), whereas sterols were effective (Hendriks et al 1999). On the other hand, published data indicates the LDL cholesterol lowering effect of sterols is not as well sustained as that of stanols over the long term. O’Neill et al presented evidence in 2005 showing that elevated blood levels of plant sterols suppressed bile acid synthesis, thereby diminishing their cholesterol lowering efficacy. In contrast, plant stanols reduced plant sterol absorption and maintained their cholesterol-lowering efficacy.
It is generally considered that the cholesterol lowering effect of plant sterols and stanols reaches a maximum at a dosage near 2-3 g/day (Demonty et al 2009). Only two known studies have explored the dose range between 3 and 9 g/day. One was a study by Davidson et al in 2002. The Davidson study indicated that the effect of sterols was maximal by 3 g/day. The other was a study on stanols (Mensink et al 2010). Unlike sterols, stanols showed additional cholesterol lowering at higher doses (see Figure 3).
Also shown in Figure 3 is a dose response curve for Reducol® (Pritchard et al 2000) compared with the dose response curve for stanols. Both Reducol® and stanols caused a continuous reduction in LDL-C with no sign of plateau formation. The curve for Reducol® is shifted to the left showing that Reducol® is more effective than stanols in the lower dose range.
Figure 3: Dose Response Curve For Reducol® Compared With Stanols
Data for Reducol® from Pritchard et al 2000; Data for stanols from Mensink et al 2010. (Graphing data: Reducol® 0.9g, -7.4%; 1.8g, -8.6%, 3.6g, -13.2%) (Stanols – 3g -8.9%; 6g, – 13.5%; 9g, -18.6%)
At the lowest dose tested, 0.9 g/day, Reducol® still showed good efficacy, more closely resembling sterols than stanols. Efficacy at the lower end of the dose range is more important than that at the high end. The usual recommended dosage for plant sterols and stanols is about
1.5 to 2 g/day. There is a tendency for long-term consumers of plant sterols and stanols to use less than half the recommended dose (Scientific Committee on Foods, 2002).
Reducol®, a mixture of plant sterols and stanols, combines the advantages of both forms in terms of efficacy. And, Reducol® does this while maintaining near normal levels of blood sterols. Reducol® has an additional advantage: Reducol® is manufactured only from a non-GMO source of plant sterols and stanols. This is particularly important in regions such as the European Union, which require food labels to inform the consumer when a product is from a GMO (genetically engineered) source. Currently, food labels in the USA are not required to carry a GMO label.
Health Claims For Plant Sterols and Stanols:
Health Regulatory Authorities around the world recognize the benefit of plant sterols and stanols in lowering LDL cholesterol, and health claims to that effect are allowed on food labels. Two examples are:
Foods containing at least 0.4 g of phytosterols per serving eaten twice a day for a total daily intake of at least 0.8g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease.
Plant sterols/stanols have been shown to lower/reduce blood cholesterol. High cholesterol is a risk factor in the development of coronary heart disease.