Benefits
LDL cholesterol and the FDA plant sterol and stanol ester heart health claim
This heart health category rests on an FDA-authorized health claim and on LDL lowering. The claim covers diets low in saturated fat and cholesterol that include 1.3 g or more a day of plant sterol esters (in spreads or salad dressings) or 3.4 g or more a day of plant stanol esters (in spreads, salad dressings, snack bars or softgels), eaten in two servings at different times of day with other foods. No trial has shown fewer heart events.
LDL cholesterol lowering that rises with dose up to about 3 g a day
In pooled analyses of randomized trials, intakes of 0.6 to 3.3 g a day lowered LDL cholesterol by about 6 to 12%, rising with dose up to about 3 g a day; a mean 2.15 g a day lowered it by about 8.8%. Sterols and stanols gave similar results. Two of these analyses were led by Unilever staff; an analysis of 59 trials by university researchers found a similar drop.
Blood plant sterol levels and heart risk research
Plant sterol intake raises blood plant sterol levels a little. A pooled analysis of 17 observational studies (11,182 people) found no link between blood sitosterol or campesterol and cardiovascular disease, while a large genetic study found that carriers of rare variants raising sterol absorption had higher non-HDL cholesterol and more coronary artery disease. Event trials have not tested this.
Results with foods compared with capsules
In pooled trials, LDL drops were larger when plant sterols came in spreads, mayonnaise, salad dressing, milk or yogurt than in baked goods, juice or cereal bars, and a single morning dose had no significant effect. Capsule results differ: two placebo-controlled softgel trials found no significant LDL change (2 g a day for 4 weeks; a store-bought product for 28 days), while 1.8 g a day of sterol and stanol esters lowered LDL by 4.3%.
Blood beta-carotene and other carotenoid levels
In a pooled analysis of 41 randomized trials (3,306 people, about 2.5 g a day), blood beta-carotene fell by about 16% (about 10% after adjusting for the fall in cholesterol), with smaller drops in alpha-carotene and lycopene. Retinol and vitamin D did not change, adjusted vitamin E did not change, and values stayed within normal ranges. Two of the five authors worked for Unilever.
Mechanism of action
Less cholesterol absorbed from the gut
Plant sterols and stanols reduce cholesterol absorption in the intestine; an expert panel describes significant inhibition at 2 g a day. In a 1-year trial of stanol ester margarine, blood campesterol, a marker of cholesterol absorption, fell 36%, and the fall tracked the drop in total cholesterol. A European lipid guideline update adds that phytosterols increase cholesterol excretion.
Low uptake into the blood
Blood levels of plant sterols are about 500 times, and of plant stanols about 10,000 times, lower than cholesterol levels. The ABCG5 and ABCG8 transporters limit their buildup: when both copies of either gene lose function, more plant sterol is absorbed from the gut and less is cleared by the liver, the cause of sitosterolemia.
Plant sterols and plant stanols compared
Pooled dose analyses found no significant difference between the dose-response curves of plant sterols and plant stanols, and comparable curves when each was analyzed separately. The FDA claim states different intakes for the ester forms: 1.3 g a day for plant sterol esters and 3.4 g a day for plant stanol esters.
Dose timing and food form
A pooled dose-response analysis found a strong tendency (P = 0.054) toward slightly lower efficacy with one daily intake than with several, and a larger effect from solid than liquid foods only above 2 g a day. An independent analysis found no significant effect from a single morning dose. The FDA claim specifies two servings eaten at different times of day with other foods.
Clinical trials
Meta-analysis of randomized controlled studies (124 studies, 201 strata; average intake 2.1 g/day, range 0.2 to 9.0 g/day). Two of the three authors worked at Unilever R&D, a maker of sterol-enriched foods. (Ras et al. 2014, Br J Nutr)
Adults in 124 randomized controlled studies
Intakes of 0.6 to 3.3 g/day lowered LDL cholesterol by about 6 to 12% on average, rising with dose to about 12% near 3 g/day; plant sterols and stanols analyzed separately showed comparable dose responses. Doses above 4 g/day were too few and scattered to pool.
Meta-analysis of 84 randomized controlled trials (141 arms) in adults; the first author worked at Unilever R&D. (Demonty et al. 2009, J Nutr)
Adults in 84 randomized controlled trials
A mean 2.15 g/day lowered LDL cholesterol by 0.34 mmol/L (8.8%). Higher starting LDL gave larger absolute drops. Dose responses did not differ significantly between sterols and stanols or between fat-based and non-fat foods; solid foods beat liquids only above 2 g/day.
Meta-analysis of 59 randomized trials published from 1992 to 2006, by McGill University researchers. (Abumweis et al. 2008, Food Nutr Res)
Adults in 59 randomized trials
Plant sterol products lowered LDL cholesterol by 0.31 mmol/L versus placebo, with significant differences between trials. Drops were larger with higher starting LDL and with spreads, mayonnaise, salad dressing, milk and yogurt; a single morning dose had no significant effect.
Randomized double-blind trial: 102 people ate margarine providing 1.8 or 2.6 g/day sitostanol and 51 ate the same margarine without it for one year. The abstract does not state the funder. (Miettinen et al. 1995, N Engl J Med)
153 randomly selected adults with mildly high blood cholesterol
Total cholesterol fell 10.2% versus a 0.1% rise with control, and LDL cholesterol fell 14.1% versus 1.1% (between-group difference 21 mg/dL, P < 0.001). Triglycerides and HDL cholesterol did not change.
Systematic review and meta-analysis of 15 randomized controlled trials; four of the eight authors were employees of Nestle research centers. The trials measured blood lipids, not heart events. (Han et al. 2016, Sci Rep)
500 adults already treated with statins
Compared with statins alone, stanol or sterol enriched diets lowered total cholesterol and LDL cholesterol by a further 0.30 mmol/L each; HDL cholesterol and triglycerides did not change.
Double-blind randomized placebo-controlled crossover trial: softgels with 2.0 g/day phytosterols or sunflower oil for 4 weeks each, with a 3-week washout. The pre-specified primary outcome, LDL cholesterol, did not differ between periods (-0.1 mmol/L, P = 0.32), nor did total cholesterol (P = 0.74). Registered as NCT00485095. (Ottestad et al. 2013, Atherosclerosis)
41 men and women with mild to moderately raised blood fats
No significant difference between the capsule and placebo periods on the pre-specified primary outcome; the authors point to the importance of the delivery format.
Single-center randomized single-blind trial with 8 arms (190 completers), including placebo and other supplement arms (SPORT, NCT04846231). The plant sterol arm took Nature Made CholestOff Plus, 2 softgels twice a day per the registry. The primary outcome, percent change in LDL cholesterol at 28 days, did not decrease significantly versus placebo. Funded by AstraZeneca. (Laffin et al. 2023, J Am Coll Cardiol)
Adults with a raised 10-year risk score, across 8 study arms
No significant difference from placebo on the primary outcome after 28 days; adverse event rates were similar across groups.
Randomized double-blind placebo-controlled crossover replication study of 1.8 g/day esterified plant sterols and stanols in softgels alongside the NCEP Therapeutic Lifestyle Changes diet. The PubMed record lists non-government research support without naming the funder. (McKenney et al. 2014, J Acad Nutr Diet)
30 adults (8 men, 22 women) with primary hypercholesterolemia
Placebo-adjusted LDL cholesterol fell 4.3%, non-HDL cholesterol 4.1% and total cholesterol 3.5% (P < 0.01); triglycerides and HDL cholesterol did not change significantly.
Meta-analysis of 41 randomized controlled trials (3,306 subjects; average intake 2.5 g/day); two of the five authors worked at Unilever R&D. Cholesterol-standardized beta-carotene fell 10.1%. (Baumgartner et al. 2017, Eur J Nutr)
3,306 subjects in 41 randomized trials
Blood beta-carotene fell 16.3%, alpha-carotene 14.4% and lycopene 12.3%; retinol and vitamin D did not change, and adjusted tocopherol levels did not change. Values stayed within normal ranges.
Randomized trial with a control group; the intervention combined balanced diet advice with stanol ester spreads (mean 1.1 g/day stanols in pregnancy, 1.4 g/day one month after birth), and infants were followed to 1 year. (Laitinen et al. 2009, Br J Nutr)
21 pregnant women and their infants
Length of gestation, infant growth and infant serum beta-carotene at 1 and 6 months did not differ between groups; infants' adjusted beta-carotene was lower at 1 month in the spread group. The authors call for larger studies.