TABLE 2.
Clinical studies with PS effects in humans.
| Disease/reference | Type of study and subjects | Treatment | Outcomes | ||||
| Cardiovascular risk | |||||||
| Lees et al. | CT type II hyperlipoproteinemic patients (n = 46). Duration: 7 years | Plant sterols preparations from two distinct sources and in 2 physical forms (soy sterols suspension (18 g/day) and powder (18 g/day) and tail oil sterols suspension (3 and 6 g/day) and powder (3 g/day)) | Decrease in plasma TC (12%, p = 0.001) and LDL-C (17%, p < 0.001) levels | ||||
| Miettinen et al. | RCT mild hypercholesterolemic patients (n = 153). Duration: one year | Sitostanol-ester margarine (n = 102; 1.8 and 2.6 g/day) and margarine without sitostanol (n = 51) | 10.2% and 14.1% decrease in serum TC and LDL-C levels in the sitostanol group and 0.1% and 1.1% in the control group, respectively (p < 0.001) | ||||
| Jones et al. | CT moderately hypercholesterolemic patients (men and women; n = 15). Duration: 21 days | Nonfat placebo and nonfat and low-fat beverages with added PS | PS absorption in the low-fat and nonfat beverages was not effective in changing HDL-C and triacylglycerol levels | ||||
| Ketomaki et al. | CT family with familial hypercholesterolemia. Duration: 3-4 weeks | Plant stanol and sterol esters on serum PS levels | Reduction in serum TC (14%) and LDL-c (17%) levels (p < 0.001) | ||||
| Plat et al. | RCT metabolic syndrome patients (n = 36). Duration: 9 weeks | Placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n = 9), and simvastatin + stanol drink (n = 8) | Stanol esters (2 g/day), simvastatin, or the combination decreased non-HDL-C (p < 0.001) and TAG (p < 0.01) levels; additional benefits were also seen when stanol esters were combined with simvastatin | ||||
| Racette et al. | CT adults receiving a PS-deficient diet (50 mgPS/200 kcal), supplemented with different PS doses (n = 18). Duration: 4 weeks | Three PS doses (59, 459, 2059 mg PS/day) | Moderate (459 mg/day) and high (2059 mg/day) dosages, dose-dependently improved biliary and dietary TC excretion (p < 0.01), and decreased intestinal TC absorption efficiency (p < 0.01) | ||||
| Lin et al. | RCT mildly hypercholesterolemic subjects (n = 21). Duration: 3 weeks | PS-controlled diet plus (1) ezetimibe placebo + PS placebo, (2) 10 mg ezetimibe/day + PS placebo, and (3) 10 mg ezetimibe/day +2.5 g PS/day | Reduction in intestinal TC absorption (p < 0.0001) and an increased fecal TC excretion (p < 0.0001) during ezetimibe administration plus PS, when compared to ezetimibe alone | ||||
| Ottestad et al. | RCT mild-to-moderate hypercholesterolemic patients (n = 41 men and women). Duration: 2 × 4 weeks | Soft gel capsules containing either PS (2.0 g/d) or sunflower oil | Daily PS intake in capsules did not decline TC (p = 0.74) or LDL-C (p = 0.32) levels | ||||
| Parraga-Martinez et al. | RCT hypercholesterolemic adult patients (n = 182). Duration: 12 months | Plant stanols (2 g/day) group and control group (receiving unsupplemented yogurt) | >10% reduction in plasma LDL-C levels was stated (p = 0.011) from baseline at both three months and one year of plant stanols consumption | ||||
| Cheung et al. | RCT adults (n = 221) without TC-lowering drugs or diabetes mellitus (41 men and 180 women). Duration: 3 weeks | PS-rich low-fat milk, containing 1.5 g PS/day (n = 110) or a conventional low-fat milk (n = 111) | PS group revealed a marked decline in serum LDL-C (−9.5%, p < 0.001), TC levels (p < 0.001), and diastolic blood pressure (p = 0.01) | ||||
| Cicero et al. | RCT mild-to-moderate hypercholesterolemic subjects (n = 90). Duration: 8 weeks | PS (800 mg), red yeast rice (5 mg monacolins), or both combined nutraceuticals | Additive lipid-lowering effect of PS and red yeast rice enhanced lipid parameters with a marked reduction in LDL-C (−20.5%, p < 0.001) and apolipoprotein B (−14.4%, p < 0.001) levels compared with individual treatments of these two nutraceuticals | ||||
| Weingartner et al. | RCT healthy volunteers, with no or mild hypercholesterolemia (n = 16). Duration: 4 weeks | Plant sterols (3 g/day) via a supplementedmargarine | Plant sterols led to a rise in serum levels of plant sterols (campesterol, p = 0.005; sitosterol, p < 0.001) and of TC synthesis (desmosterol, p = 0.006; lathosterol, p = 0.012) markers, without affecting serum TC and activating circulating monocytes or redox state | ||||
| Javanmardi et al. | RCT nonalcoholic fatty liver disease patients (n = 38). Duration: 8 weeks | PS group (n = 19, received 1.6 g PS supplement) and control group (n = 19, 1.6 g starch daily) | Compared to placebo, PS group remarkably enhanced LDL-C (p = 0.030), AST (p = 0.010), ALT (p = 0.001), and TNF-α (p = 0.006) levels. No differences were stated between the two groups with regard to TC, TG, HDL-C, VLDL-C, LDL-C/HDL-C, and TC/HDL-C ratios, gamma-glutamyl transferase, IL-6, hs-CRP, adiponectin, and leptin levels | ||||
| Ferguson et al. | RCT hypercholesterolemic individuals (n = 70). Duration: four weeks | Placebo (n = 18, no PS or curcumin), PS (n = 17, 2 g/day), curcumin (n = 18, 200 mg/day), and PS + curcumin (2 g/day + 200 mg/day) | Curcumin addition to PS led to a complementary TC-lowering effect, larger than PS therapy alone (p < 0.0001), with no adverse effects | ||||
| Clifton et al. | RCT volunteers with a TC > 5.5 mmol/L (n = 50). Duration: 2 × 4 weeks | Breakfast wheat biscuit (2 g PS) and standard wholegrain wheat breakfast cereal biscuit | LDL-C lowering effect between wholegrain wheat biscuits and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L (5.6%, p = 0.001) | ||||
| San Mauro-Marín et al. | RCT gender differences in LDL-C lowering activity of PS (n = 30 women and 24 men). Duration: 2 × 3 weeks | 2.2 g/day of added PS in 700 ml milk | PS-enriched milk intake led to a decrease in LDL-C levels in men | ||||
| Cancer | |||||||
| Berges et al. | RCT patients with benign prostatic hyperplasia (n = 200). Duration: 6 months | Β-sitosterol (20 mg, which contains a mixture of PS), three times/day or placebo | Remarkable improvement (p < 0.01) in symptoms score and urinary flow parameters, thus revealing the ß-sitosterol effectiveness | ||||
| Klippel et al. | RCT patients with benign prostatic hyperplasia (n = 177). Duration: 6 months | β-sitosterol (130 mg) and placebo | Marked improvements (p < 0.01) in symptoms score and quality of life index and an increase in Qmax and a decrease in postvoid residual urinary volume | ||||
| Mendilaharsu et al. | CCS lung cancer cases (n = 463) and hospitalized controls (n = 465). Duration: 3 years | Plant sterols intake, through food frequency questionnaire | Highest quartile intake of PS led to a 50% reduction in lung cancer risk (OR 0.29, 95% CI, 0.14–0.63) | ||||
| De Stefani et al. | CCS gastric cancer cases (n = 120) and controls (n = 360). Duration: 2 years | Plant sterols, through food frequency questionnaire | Highest PS intake was inversely related to gastric cancer risk (OR 0.09, 95% CI, 0.02–0.32) | ||||
| McCann et al. | CCS Ovarian cancer cases (n = 124) and controls (n = 696). Duration: 2 years | Impact of food diet, via detailed food frequency questionnaire | A lower risk was documented for women in the highest quintile of stigmasterol intake (OR 0.42, 95% CI, 0.20–0.87) | ||||
| Normen et al. | CS colon (n = 620) and rectal (n = 344) cancer cases. Duration: 6.3 years | No association was found between PS intake and a lower cancer risk | |||||
| Gestational diabetes | |||||||
| Li et al. | RCT women with gestational diabetes mellitus (n = 206). Duration: 16 weeks | Margarine spread with (n = 102) or without (n = 104) PS | In PS-rich margarine spread, TAG (p = 0.017), TC (p = 0.032), and LDL-C (p = 0.027) levels were remarkably reduced, while HDL-C (p = 0.041) increased compared to baseline; also, fasting plasma glucose (p = 0.021) and serum insulin (p = 0.018) levels, insulin check index (p = 0.035), and ß-cell function (p = 0.029) were also remarkably improved | ||||
| Gao et al. | RCT women with gestational diabetes mellitus (n = 244). Duration: 13 weeks | Margarine spread with (n = 123) or without (n = 1 21) PS | PS-rich margarine spread had benefits on maternal diabetic symptoms, namely, in improving lipid composition (TC, p = 0.03; LDL, p = 0.02; HDL, p = 0.03) and glucose metabolism (p = 0.03), decreasing the incidence of neonatal complications | ||||
| Immunomodulation | |||||||
| De Smet et al. | CT healthy subjects (n = 14). Duration: 4 h | Snake with or without plant stanol esters (4 g/day) | No changes in genes profiles expression; T-cell function-involved pathways were downregulated in the jejunum | ||||
| Brull et al. | RCT asthmatic patients (n = 58). Duration: 2 + 8 weeks | Plant stanol-rich soy-based yogurts (4 g stanols/day) or control yogurts | Higher antibody titers against hepatitis A virus (three and four weeks postvaccination, p = 0.037 and p = 0.030, respectively) and marked reductions in plasma total Ig-E, IL-1β (p < 0.05), and TNF-α (p < 0.05) levels in treated group | ||||
| Osteoporosis | |||||||
| Granado-Lorencio et al. | RCT postmenopausal women (n = 38). Duration: 4 weeks | β-cryptoxanthin (0.75 mg/day) and PS (1.5 g/day), single or combined | β-cryptoxanthin combined with PS led to marked changes in TC (p = 0.0047), HDL-C (p = 0.0057), and LDL-C (p = 0.0014) levels and bone turnover markers | ||||
AST, aspartate aminotransferase; ALT, alanine aminotransferase; CT, clinical trial; CS, cohort study; CCS, case–control study; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; LDL-c, low-density lipoprotein cholesterol; PSs, phytosterols; RCT, randomized controlled trial; TC, total cholesterol; TAG, triacylglycerol; VLDL-C, very-low-density lipoprotein cholesterol.