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In spite of all our efforts, cardiovascular disease is still the leading cause of death in both men and women in the United Kingdom¹ (see Figure 1 and 2). There is a wealth of evidence to show that a healthy and varied diet including functional foods including plant sterols, plant stanols, soya and / or oats can play a significant role in improving heart health. This article focuses on the LDL cholesterol lowering role of plant sterols and stanols and in particular plant stanol ester, and discusses its mechanism of action.

Figure 1 and Figure 2. Top 10 Causes of Death in the UK. (Office of National Statistics (2005); General Register Office (2005) Edinburgh, Scotland; General Register Office (2005) Northern Ireland)

LOW DENSITY LIPOPROTEIN: THE LOWER, THE BETTER

The circulating level of low density lipoprotein (LDL) cholesterol is probably the best studied and strongest predictor of CVD risk. Both epidemiological^2-13 and clinical studies show that blood LDL cholesterol is a validated marker^{14-17, 18-25} for CVD and has heightened the focus on LDL cholesterol management. The data is best summed up by the rule of thumb that 1% reduction in LDL cholesterol equals 1% reduction in CVD risk.²⁶ The current recommendations for LDL cholesterol from the Joint British Societies is below 3 mmol/L²⁷, although the strength and clarity of the relationship suggests that the lower LDL-cholesterol, the better²⁶.

THE ROLE OF DIET IN HEART HEALTH

Diet and lifestyle have a major impact on modifiable risk factors and are a key communication point in expert recommendations around the world.^{28, 29} The role of various dietary fats in heart health^{30, 31} and in particular the negative impact of saturated fats has long been understood. Major dietary intervention studies,^32-34 clearly show that diet can play a central role in reducing heart problems and should be an initial approach to reduce LDL cholesterol.

PLANT STEROLS AND STANOLS

In light of the importance of diet in the maintenance of heart health safe and efficacious dietary options are demanded that help reduce LDL cholesterol. Plant sterols and stanols provide such benefits. Plant sterols are structurally similar to cholesterol apart from an extra (m)ethyl side chain. The saturated derivatives of plant sterols are plant stanols. Esterifying plant stanols - adding a fatty acid, typically oleic acid, through an esterification process - to plant stanol ester makes it easy to incorporate in a variety of foods (see Figure 3 and Figure 4). This fatty acid gets broken off the plant stanol in the digestive tract, where the free plant stanol can block the cholesterol absorption. The main type of plant stanol ester is sitostanol ester.

Figure 3. Molecular structures of cholesterol, sitosterol and sitostanol.

Figure 4. The molecular structure of a plant stanol esterified with oleic acid.

The most influential study regarding plant stanol ester efficacy in relation to cholesterol lowering is the North Karelia plant stanol ester trial, which was published in The New England Journal of Medicine.³⁵ This involved 153 moderately hypercholesterolemic individuals who consumed rapeseed oil margarine type spreads, with or without sitostanol ester (2.6g sitostanol daily) for 6 months. Thereafter, half the treatment group continued with sitostanol ester 2.6g sitostanol daily) and the other half reduced their intake to 1.8g. At 12 months LDL cholesterol decreased by 14% from baseline, or by 13% when compared with placebo margarine group. The serum cholesterol in the group consuming 2.6g daily was slightly higher than in those consuming 1.8 g indicating consumption of about 1.8g of plant stanol ester daily effectively reduces blood LDL cholesterol over a long period. The effect was consistent and lasting so long a subjects were compliant.

Incremental cholesterol lowering as part of a heart healthy diet
Importantly, significant, additive LDL reductions are observed when plant stanol ester is used as part of a low fat diet. Hallikainen and Uusitupa³⁶ reported that subjects on a low fat diet (AHA Step 2 - ~26% of calories from fat) that included a stanol ester fortified margarine observed a significant reduction in serum lipids, 8.6% reduction in total cholesterol and 13.6% reduction in LDL cholesterol.

Together with the low fat diet a reduction of LDL cholesterol of almost 24% was achieved.

In a similar trial³⁷ subjects ate plant stanol in margarine with a diet containing 30% of calories from fat and observed similar reductions in circulating lipids.

Incremental effect to statins
Additional benefit is also achieved when plant stanol ester is used in conjunction with statin therapy. Blair et al³⁸ studied the effect of a plant stanol ester margarine in subjects taking statin therapy, but who still had elevated levels of LDL cholesterol (≥ 3,38 mmol/L). Both women and men who had been taking a stable dose of statin for at least 90 days consumed 3g of plant stanols daily or a control margarine.

Blood LDL cholesterol levels were reduced from baseline by 16%, 17% and 17% at 2, 4 and 8 weeks, respectively in the plant stanol ester group and by 8%, 8% and 7%, respectively, in the control group. With the net benefit of the additional 10% reduction, the plant stanol ester spread significantly enhanced the statin therapy.

Cater et al³⁹ also studied the effect of plant stanol ester in 10 subjects with a positive history for CHD and a fasting LDL cholesterol level between 2.6 - 3.3 mmol/L. Subjects on a stable-dose statin therapy consumed either a control or a plant stanol ester spread for 2 months. Blood LDL cholesterol was 15% lower during the phase with plant stanol ester spread in comparison with the phase with placebo spread.

The evidence supporting the efficacy of plant sterols and stanols has been corroborated by many other trials using various foods forms, including margarine, yoghurt and yoghurt.^{35-37, 40-47} Table One summarises these and other interventions.^{35-37, 39-53}

A recent meta analysis indicates an average 10% or 0.37 mmol/L reduction in LDL cholesterol is achieved when 2 grams of plant stanol is included in the diet. The recommended daily amount of plant stanol is 2 grams as there is little extra benefit from consuming higher amounts.⁵⁴

A good tool for people with diabetes
Also worth noting are the significant LDL lowering effects of plant stanol ester in people living with Type 2 diabetes^{55, 56} as lipid management is a very important part of their care.

THE MECHANISM OF ACTION

Blocking the absorption of dietary and re-circulated biliary cholesterol in the gastrointestinal (GI) tract is central to the LDL lowering of plant stanols and sterols. An important factor in cholesterol absorption is the formation of micelles, the vehicle which ‘traps' cholesterol and presents it to the cells of the intestine for absorption.^{57, 58}

When sterols/stanols are present in the GI tract they ‘compete' with cholesterol for space in the micelle. This competition is likely due to the greater hydrophobicity.^{59, 60} As the concentration of plant stanol/sterol is increased in the GI tract the micellar solubility of cholesterol is decreased. The unabsorbed cholesterol is then excreted with the faeces.

The reduced efficiency of absorption of cholesterol by plant stanol has been demonstrated in a variety of studies.^{59, 61-63} In some cases, cholesterol absorption has been reported to be inhibited by up to 65%.^{47, 64, 65} Increases in faecal cholesterol and total faecal sterols are also observed which indicates a decrease in absorption.⁴⁷ It is important to note that studies show that plant stanol itself is virtually not absorbed, also suggesting that the a blocking mechanism is at work.⁶⁶

Reduction of cholesterol absorption leads to lower LDL cholesterol levels by affecting the cholesterol pool available to the liver. The cholesterol pool in the body is regulated by a homeostatic mechanism that balances cholesterol absorption and cholesterol synthesis. Reduced absorption of cholesterol results in the up-regulation of LDL receptors and increased clearance of LDL from the circulation.⁶⁷

CHOLESTEROL LOWERING FOODS

Two other popular cholesterol lowering foods, oatmeal containing β- glucan and soy protein are worth mentioning. Recent meta analyses^{68, 69} have indicated their cholesterol lowering ability.

On a per gram basis, when considering data that reflect reasonable daily intake ranges (2-10 grams), oat fibre consumption leads to a modest LDL cholesterol reduction of 0.037 mmol/L/gram oat fibre. This equates to an average reduction of 5% at the recommended 3 grams of β- glucan (equals 3 bowls of oats) per day. Although higher intakes may lead to greater decreases in LDL, consumers may have difficulty eating more than 3 grams oat fibre per day.

Analyses of 41 studies regarding the efficacy level of soy⁶⁹ shows that consumption of 25 grams or more soy protein will lead to an overall LDL reduction of 4 - 5 % or about 0.11 mmol/L. The meta analysis shows a linear LDL lowering response to soy protein consumption. The recommended daily intake of soy protein for cholesterol lowering is 25 grams (equals to about 3x250ml glasses of soy milk), higher amounts may be more difficult to consume on a regular basis. It is worth noting that substituting soy for meat may be a useful strategy to a reduce saturated fat intake.

As with the other ingredients, the intake of plant stanols/sterols can be spread out over the day or the 2 gram amount can also be taken all at once.⁵² Products with varied amounts are available in the market place. Thus, while higher intakes of soy and oat are possible, it may prove difficult to accommodate such high levels on a regular basis. While soy and oat fibre should certainly be part of a consumer's heart healthy regimen, the addition of plant stanols/sterols represents a more potent way of conveniently enhancing their LDL cholesterol lowering efforts. The once a day strategy may be more convenient and help promote better compliance.

From a cost perspective, a recent pricing survey (see Table Two) reveals that stanol containing spreads and oatmeal (beta-glucan) are particularly cost effective- though it is worth noting that the degree of lowering is higher for plant stanol on a similar weight basis.

CONCLUSION

Diet and lifestyle play a central role in modifying risk factors associated with heart problems. Plant stanols/sterols, one of the most studied and effective classes of functional food ingredients on the market, significantly reduces LDL cholesterol. They are available in convenient and economical formats that can help consumers achieve their cholesterol lowering goals. When the need for adjuncts to diet and statin therapy arise plant stanols/sterols is an option which should be considered by health care professionals in the maintenance of cardiac health.

References

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