The table summarises the results of randomised double blind trials in adults that compared the ability of polyunsaturated margarines with and without added plant sterols to lower cholesterol. The effect of selection for comparatively high concentrations of serum cholesterol in some trials was modest and, with the exception of one small trial,13
mean serum concentrations of low density lipoprotein (LDL) cholesterol in the control groups ranged from 3.0 mmol/l to 4.5 mmol/l (median 3.8 mmol/l), close to the age-specific mean found in the Western world. The randomised comparisons in three trials suggested that there was little difference in the extent to which sterols or stanols lower cholesterol concentrations (although the confidence intervals are consistent with the evidence above that stanols are better).1,12,14
The table shows the reduction in LDL cholesterol in each trial; the reductions in total cholesterol concentrations were similar and there was little change in serum concentrations of high density lipoprotein cholesterol or triglyceride.
The figure shows the reduction in concentration of LDL cholesterol achieved in each trial and the dose of plant sterol or stanol. The reduction in the concentration of LDL cholesterol at each dose is significantly greater in older people than in younger people. The dose-response relation is continuous up to a dose of about 2 g of plant sterol or stanol per day. At higher doses no further reduction in LDL cholesterol is apparent, confirming the evidence of a plateau identified by earlier non-randomised studies.17
At doses of
2 g per day the average reduction in serum LDL cholesterol was 0.54 mmol/l (14%; 95% confidence interval 0.46 to 0.63 mmol/l) for participants aged 50-59,3,6,8,11
0.43 mmol/l (9%; 0.37 to 0.47 mmol/l) in participants aged 40-49,1,4,5,13
and 0.33 mmol/l (11%; 0.25 to 0.40 mmol/l) for those aged 30-391,2,5,10
; this trend was statistically significant (P=0.005). At a dose of 2 g per day (the amount added to an average daily portion of fortified margarine) the reduction in LDL cholesterol is likely to be at least 0.5 mmol/l for those aged 50-59 and 0.4 mmol/l for those aged 40-49.
Data from observational studies and randomised trials indicate that in people aged 50-59 the reduction in LDL cholesterol of about 0.5 mmol/l would reduce the risk of heart disease by about 25% after about two years.22
In younger people the proportionate reduction in risk would be similar (the reduction in cholesterol concentrations is smaller but the association between cholesterol and heart disease is stronger).22
Trials of six different interventions to lower serum cholesterol have all found a reduction in the incidence of heart disease (these interventions include four pharmacologically unrelated drugs, a reduction in dietary saturated fat, and ileal bypass surgery).22,23
Nothing except a reduction in cholesterol is common to the six interventions, and for each intervention the proportionate reduction in mortality from heart disease is commensurate with the reduction in cholesterol concentration.17,18
Margarines with plant sterols or stanols thus reduce the risk of heart disease by one quarter: this is the reduction expected from the decrease in serum cholesterol.
This is an impressive result for a dietary change that, price apart, is modest. It is larger than the effect that could be expected to occur if people ate less animal fat, and it is all the more impressive in light of the fact that despite the extensive promotion of healthy eating there has been little reduction in average serum cholesterol concentrations in many countries. Recent surveys in England found that mean cholesterol concentrations are only 1-2% lower than those of 25 years ago.24,25
For a person replacing butter with a plant sterol margarine the reduction in cholesterol would be even greater. Replacing butter with ordinary polyunsaturated margarines lowers total serum and LDL cholesterol by about 0.3 mmol/l,26,27
so the overall reduction would be about 0.7 mmol/l, or as much as any cholesterol lowering drug except statins.
Efficacy in combination with low fat diets
One non-randomised study found only a small average reduction in LDL cholesterol concentrations (0.16 mmol/l) despite participants taking 3 g of plant stanols daily.28
The participants were on a low fat and low cholesterol diet, and the result was interpreted as suggesting that plant sterols are ineffective when dietary fat, dietary cholesterol, or LDL cholesterol concentrations are low. This is unlikely. In two recent randomised trials of stanol margarines in which participants were on low fat, low cholesterol diets, the reductions in serum concentrations of LDL cholesterol were similar to those found in other trials in which the intake of dietary fat was higher.4,9
Plant stanols were equally effective in patients taking statins who had mean LDL cholesterol concentrations of only 2.9 mmol/l.6
Other explanations for the discrepancy are more plausible: chance (at the upper confidence interval of the result, an LDL cholesterol reduction of 0.43 mmol/l is what might be expected) or the fact that the stanol was administered in capsules and not esterified and blended into the fat of a meal. (Sterols administered in capsules may not disperse fully or dissolve in the gut, limiting their ability to reduce the absorption of cholesterol.9