The expanding global reach of phytosterols and phytostanols in finished goods is impressive. Invention and innovation are marrying these plant-derived lipid metabolism response modifiers with a plethora of edible formats, including chocolates, dairy, granola bars and cereals, juice, and even water and tortilla chips.
By sheer numbers, the preferred format appears to be foods and beverages, which runs counter to the usual dynamics (at least in the US) of solid-dosage formats. What is most provocative, and which merits scrutiny, is the efficacy associated with this latter format in light of the majority of the evidence base.
Back in the 1950s, researchers first explored the influence of various phytosterols, especially beta-sitosterol (in solid dose formats), upon blood lipids in hyperlipidaemic individuals. The doses used were massive by today?s standards — 5-10g daily — and the results were variable.1,2
The near totality of the evidence base supporting the hypolipidaemic efficacy of sterols and stanols rests with food formats, predominantly those that comprise a fat matrix.3 Indeed, one of the most frequently cited studies used to illustrate nonefficacy employed a liquid capsule format. In this nonrandomised study, a dose of 3g/day sitostanol in a capsule (sitostanol:safflower oil; 4:1) was administered to subjects on a low-fat, low-cholesterol diet and had no appreciable reduction in LDL cholesterol.4 The amount of fat (oil) present in this dose format was calculated to be less than 1/20th of that needed to solubilise the stanol.5
Phytosterols and stanols typically exist in a crystalline state, and are poorly soluble. At room temperature, only 0.01 per cent phytosterols are soluble in water, their solubility in vegetable oil being only three per cent, while that of stanols (in oil) is less than one per cent.6 This was the major thrust that fostered the development of esterified forms, which display superior solubility in water and oil.
Early attempts to address this concern reduced the crystal size by physical grinding or through the use of suspensions.7 Recent investigations have revealed that lecithin can exert profound solubilising and anti-crystallisation effects, which may translate into greater efficacy by achieving a mixed micelle state in the gut, believed to be essential to the efficacy of sterols and stanols.5,8,9
There do not appear to be any randomised, controlled clinical trials among populations with hyperlipidaemia, describing statistically significant hypolipidaemic effects with tableted or encapsulated dosage forms of stanols or sterols lacking a crystallisation modifier.3 Indeed, an executive from a company marketing a stanol/sterol mixture, present in various dietary supplements, confirmed the absence of, and need for, such studies in late 2004.10 In a recent randomised, controlled study employing a tableted spray-dried lecithin-soy stanol preparation, subjects receiving the stanol preparation (1.26g/day), which exhibited a rapid disintegration profile, demonstrated a 10 per cent decline in LDL cholesterol, not observed among placebo or slow-disintegrating stanol-lecithin dose users.11 Unfortunately, a positive control with a rapid disintegrating, equal stanol quantity but lecithin-free dose form was not used.
A different study with the same composition but at a higher dose (1.8g/day soy stanols), administered to subjects on a stable dose of statin therapy, revealed an additional LDL-lowering effect not seen with placebo.12 It would appear that format-specific clinical validation is needed for sterol and stanol products in solid-dosage forms.
Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond: [email protected]
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