Dietary incorporation of plant sterols and stanols is recommended for blood cholesterol reduction (1
). Berger et al. reviewed clinical trials on efficacy of plant sterols as cholesterol lowering agents and reported that the consumption of plant sterols/stanols have been reported to reduce low density lipoprotein (LDL) cholesterol levels by 5–15% (3)
. Reasons for such large variations need to be investigated.
Earlier studies that have tested the efficacy of plant sterols/stanols as cholesterol lowering agents incorporated plant sterols/stanols into either regular or low fat spreads (8
). Since it appears counterintuitive to use a high fat food product to deliver a cholesterol lowering agent, clinical trials have been conducted to test the efficacy of plant sterols/stanols incorporated into low fat products (14)
. A number of clinical trials have tested the efficacy of plant sterols/stanols incorporated into low fat foods including low fat milk (15
), low fat yoghurt (16
), bakery products (21)
, orange juice (22
), cereal bars (24)
and low and non-fat beverages (25
). However, although plant sterols/stanols that are incorporated into low fat food have been shown to reduce blood cholesterol (24
), the same food carrier tested in different trials gave different magnitude in LDL cholesterol reduction. Plant sterol/stanol enriched yoghurt and milk drinks have resulted in LDL cholesterol reduction in the range of 5–14% in various clinical trials (29)
. The study by Clifton et al. (30)
compared the effect of plant stanol esterified to fatty acids and incorporated in a number of food matrices including bread, breakfast cereal, milk and yoghurt on plasma lipids. Plant stanol esters in low fat milk were almost three times more effective than in bread and cereal in lowering plasma cholesterol levels. Whether all plant sterols/stanols enriched low fat food matrices are efficacious as plant sterol/stanol enriched spread carrier in lowering blood cholesterol has not been studied thoroughly. It remains to be determined which food matrices are viable carriers to deliver an effective dose of plant sterols/stanols.
The optimal number of servings per day of plant sterol/stanol containing products was addressed in only one study. Plat et al. (31)
showed that 2.5 g of plant stanols in margarines and shortenings consumed for four weeks once per day at lunch or divided over three meals, lowered LDL cholesterol levels to a similar extent, about 10%. The intake of a single dose of plant sterol/stanol enriched products is thought to increase consumers’ compliance and adds convenience. However, further studies using a single dose of plant sterols/stanols consumed either at breakfast (18
), or with lunch or the principal meal (19
) yielded conflicting results. For example, when plant sterol enriched margarine was consumed with breakfast, no reduction in cholesterol levels was observed (32)
, in spite of the previously demonstrated efficacy as a single serving at lunch (31)
. In another study, intake of the single dose of plant sterols provided in yoghurt drinks with lunch resulted in a larger decrease in LDL levels than the intake of same dose of plant sterols provided 30 min before breakfast (19)
. Since plant sterol/stanol products are being marketed for consumption once a day, it remains to be investigated whether the effect of single dose of plant sterols/stanols consumed at different time of the day is comparable to that consumed as multiple dosages throughout the day.
Several potential modifiers for the effect of plant sterol/stanol supplementation on reduction of LDL levels were studied in some trials, including age and gender, baseline LDL levels, and genetic profile. Again, results from various studies are inconsistent. For example, baseline LDL levels have been shown to modify the effect of plant sterols/stanol in some (35
), but not other studies (8
). Furthermore, identification of effect modifiers in the cholesterol lowering action of plant sterols/stanol will help target individuals who may benefit more from such an intervention.
Accordingly, instead of conducting additional randomized clinical trials to resolve the disagreement surrounding the influence of the aforementioned factors on the cholesterol lowering action of plant sterols/stanols, it was considered that an appropriate meta-analysis could be used as an alternative novel approach. Previous meta-analyses have studied the efficacy of plant sterols/stanols as cholesterol lowering agents. The first (4)
looked at the cholesterol lowering action of plant sterols/stanols added to fat spreads mostly in the form of margarines. Another (5)
looked at the efficacy and safety of plant sterols/stanols as cholesterol lowering agents, but since 2003 a number of clinical trials have examined the efficacy of low fat foods containing plant sterols/stanols and observed substantially weaker effects. A recent meta-analysis (6)
sought to investigate effects of plant sterols/stanol in lowering total and LDL cholesterol levels of familial hypercholesterolemia subjects. Two previous meta-analyses conducted on plant sterols/stanols were non-systematic reviews (4
), which failed to describe how reviewers searched, selected and evaluated the quality of studies. Narrative reviews are qualitative summaries of a certain topic (7)
. While systematic meta-analyses include a comprehensive search of the primary studies on a specific clinical question, selection of studies by using clear eligibility criteria, critical evaluation of the quality of studies, and generating results using a pre-specified method (7)
Meta-analysis is a statistical tool that generates pooled estimates of effects from the results of randomized controlled trials (7)
. It is an unbiased tool to assess an intervention and may lead to resolution of controversy. Therefore, a systematic meta-analysis could resolve the apparent controversy concerning the influences of food carrier, frequency and time of intake, as well as subjects’ baseline characteristics on cholesterol lowering action of plant sterols/stanols.
The objectives of the present meta-analysis were to more precisely quantify the effect of plant sterol/stanol enriched products on LDL cholesterol concentrations and to identify and quantify the effect of subjects’ characteristics, food carrier, frequency and time of intake.