Summary of biologically active dose of plant sterols for optimal cholesterol lowering

Several studies [19,20,28,32,33,40,58] using intakes of 800–1000 mg of plant sterols per day have shown biologically/clinically significant (5% or more) reductions in LDL cholesterol levels, relative to control, or at least showed a statistically significant treatment effect relative to the starting LDL cholesterol level at the beginning of the treatment period, independent of control. Other studies [27,37] with a similar dosage range did not meet the above criteria for biological reduction of LDL levels, or achieve statistical significance. Some studies showed that 800–1000 mg/d of free plant sterol equivalents can decrease the absorption of cholesterol, which is indicative, but not necessarily predictive, of actual LDL cholesterol lowering [22,28,32,59].

It has been shown that increasing the dosage beyond 1000 mg per day of free sterol equivalents increased LDL cholesterol lowering efficacy or consistency of response leading to more statistically significant results [32,37,40]. Increasing the dosage beyond 1000 mg per day of free sterol equivalents did not further increase LDL cholesterol lowering efficacy [19].

In humans, there is a good likelihood that a dose of 0.8–1.0 g of free sterol equivalents per day, properly solubilized, administered in 2–3 servings with a meal, will reduce LDL cholesterol by 5% or more and that this reduction in LDL cholesterol will correlate with an approximate 6–10% reduction in CHD risk at age 70 [35,36]. However, at this dosage level, it is likely that not all individuals will achieve a 5% reduction in LDL cholesterol [20].

Clinical relevance of LDL-cholesterol-lowering by plant sterols

As previously noted, it is generally agreed that high blood cholesterol level (especially LDL cholesterol) is a risk factor for coronary heart disease (CHD). Oxidation of excess LDL cholesterol leads to arterial wall plaque build up, which then restricts blood flow and increases blood pressure. Unless, hypercholesterolemia and hypertension are treated, these factors are associated with increased risk of coronary heart disease (myocardial infarction) and stroke [35].

Therefore, the clinical relevance of LDL-cholesterol lowering lies in the potential for plant sterols to reduce the actual risk of CHD. As already described, there is an impressive body of scientific data demonstrating cholesterol-lowering by plant sterols. However, it is pertinent to tease out from published studies, those providing the highest level of evidence for a clinically-important effect. Two reviews have addressed this issue [60,61]. Law [60] estimated that consumption of 2 g of equivalents of plant sterol or stanol per day would reduce heart disease risk 25%. But only a randomized clinical trial using CHD as an endpoint, could provide certainty of the effectiveness of plant sterols in reducing heart disease incidence. But for a clinical trial to detect a 12–20% reduction in coronary heart disease incidence would require 10,000–15,000 patients with CHD (and more for healthy people). Even if such a trial were feasible, it would probably still be underpowered to detect any rare adverse events (undesirable side effects) [61]. Thus, we must judge the effectiveness of plant sterol doses on their theorized ability to reduce CHD incidence, using LDL cholesterol as a marker.

Low fat versus high fat background diet

Dietary cholesterol consumption is 250–500 mg/d, and normally half is absorbed, while bilary cholesterol production is 600–1000 mg/d. Since plant sterols impair the absorption of both bilary and dietary cholesterol, it is not surprising that they are effective even when consumed in low fat diets [62,63], although evidence from some studies suggests them to be more effective when consumed with diets containing cholesterol [21,64,65]. In a study by Denke [21], plant stanols were given in capsules and not blended with fatty matrix, which limits their cholesterol-lowering action. In addition, compliance was monitored by capsule counting and not by direct supervision, which decreased compliance monitoring. Mussner et al. [65] found esterified phytosterols in spreads to reduce LDL cholesterol about 5.4%, but the reduction was 11.6% in those tertiles having the highest intake of dietary cholesterol. Recent studies have shown plant sterols to be effective even if consumed with Step I diets [38,40,66]. Similarly, Judd et al. [67] showed that high doses of vegetable oil sterol esters lowered LDL cholesterol to about the same level, whether the basal diet was a typical American diet or a Step I type of diet, suggesting dramatic changes in usual fat intake are not necessary, if plant sterols are consumed concurrently.