Nutraceutical Study name Study type Number of participants/studies analyzed Duration Intervention Summary of findings References Olive oil NUTRAOLEUM Clinical trial 58 5 months 30 mL/d of three virgin olive oils (VOOs): (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes), (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes), and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm) Improved plasma HDL levels [35 ] VOHF Clinical trial 33 3 weeks VOO (80 mg·kg-1 ), FVOO (500 mg·kg-1 ), and FVOO enriched with phenolic compounds from thyme FVOOT (500 mg·kg-1 ; 1 : 1) Enhanced HDL content [36 , 37 ] n-3 PUFAs DART Clinical trial 2.033 6 months Advised to eat about 300 g/week of oily fish or fish oil supplements giving an equivalent amount of n-3 PUFAs 29% reduction in all-cause mortality [311 ] GISSI-Prevenzione Clinical trial 11.324 3.5 years Supplements of n-3 PUFA (1 g/d), vitamin E (300 mg/d), both, or none 20% reduction for total deaths [52 ] JELIS Clinical trial 18.645 5 years EPA (1800 mg/d) with statin or statin 19% reduction in major coronary events [51 ] Meta-analysis 7.951 Reduced overall mortality and sudden death [2 ] Meta-analysis 77.917 No significant associations with CHD events and death [56 ] Omega-FMD Clinical trial 74 3 months Supplements of n-3 PUFA (2 g/d) or placebo No improvement of endothelial function indices [57 ] ASCEND Clinical trial 15,480 7.4 years Supplements of n-3 PUFA (1 g/d) or placebo No reduction in the rates of nonfatal serious adverse events [58 ] REDUCE-IT Clinical trial 19.212 4.9 years Supplements of icosapent ethyl (4 g/d) or placebo 25% reduction in primary composite cardiovascular endpoint [60 ] Flavonoids Zutphen Elderly Study Prospective cohort study 805 5 years Reduced risk of CHD mortality [99 ] Rotterdam Study Prospective cohort study 4807 5.6 years reduced incidence of MI [100 ] The Caerphilly study Prospective cohort study 1900 14 years No change in incidence of ischemic heart disease [101 ] The Health Professionals Study Prospective cohort study 45589 2 years No association between tea consumption and CVD [102 ] FLAVO Clinical trial 37 4 weeks (-)-epicatechin (100 mg/d), quercetin-3-glucoside(160 mg/d), or placebo Only (-)-epicatechin improved endothelial function and reduced inflammation [103 ] SCFAs Umbrella meta-analysis 31 (meta-analysis) 7-24% reduction in CHD and stroke [108 ] Meta-analysis 752,848 12.4 years 23% reduction in CVD mortality [109 ] Vitamins ASAP Clinical trial 520 3 years d-Alpha-tocopherol (182 mg/d), slow-release vitamin C (500 mg/d), both, or placebo Delayed progression of atherosclerosis [153 , 154 ] Women’s Health Study Clinical trial 39.876 10.1 years Natural-source vitamin E (600 IU) on alternate days Reduced cardiovascular mortality in healthy women [155 ] MRC/BHF Clinical trial 20.536 5 years Vitamin supplementation (vitamin E, 600 mg/d; vitamin C, 250 mg/d; β -carotene, 20 mg/d) No significant reduction in the incidence of cardiovascular events and CVD-related mortality [156 ] GISSI-Prevenzione Clinical trial 11.324 3.5 years Supplements of n-3 PUFA (1 g/d), vitamin E (300 mg/d), both, or none [52 ] VEAPS Clinical trial 353 3 years DL alpha-tocopherol (400 IU/d) or placebo [157 ] HOPE Clinical trial 9.541 4.5 years Natural-source vitamin E (400 IU/d) or placebo [158 ] SU.VI.MAX Clinical trial 1.162 Combination of antioxidants (vitamin C, 120 mg/d; vitamin E, 30 mg/d; beta carotene, 6 mg/d; selenium, 100 μ g/d; zinc 20 mg/d) or placebo [159 ] Meta-analysis 51 (trials) No significant reduction in mortality and cardiovascular risk [160 ] Meta-analysis 15.871 No significant reduction in mortality and cardiovascular risk [161 ] CARET Clinical trial 18.314 6 years Beta-carotene (30 mg/d) and vitamin A (25000 IU/d) or placebo 26% increase of CVD-related mortality [162 ] Meta-analysis Meta-analysis 2,000,000 No prevention of heart attacks, strokes, or cardiovascular death [164 ] Reduced risk of CHD incidence
