Table 2.
RCTs of polyphenols (anthocyanins, catechins, flavanols and flavonols) in CVD risk.
| Group (Class) | Author/ Date | Jadad Score | Design (Follow up) | (n) Population | Intervention | Outcomes | Significant Results |
|---|---|---|---|---|---|---|---|
| Flavonoids (Anthocyanins) | Kuntz (2014) [33] | 4 | 2B, PCB, X (14 days) | (30) Healthy females | 330 mL/day beverages (PCB, juice or smoothie with 8.9, 983.7 and 840.9 mg/L ACN, respectively) | Inflammatory and oxidative stress biomarkers | ↑ SOD and CAT after ACN. ↓ MDA after ACN ingestion. |
| Flavonoids (Anthocyanins) | Curtis et al. (2009) [34] | 5 | PCB, PA (12 weeks) | (57) Postmenopausal women | 500 mg/day ACN vs. PCB | BP, CHO metabolism, lipids profile, inflammatory biomarkers, platelet reactivity | No significant effect |
| Flavonoids (Anthocyanins) | Hassellund et al. (2013) [35] | 5 | 2B, PCB, X (4 weeks) | (31) Pre-hypertensive males | 640 mg/day ACN vs. PCB | Lipids profile, CHO metabolism, inflammatory and oxidative stress biomarkers | ↑ HDLc and glucose after anthocyanin versus PCB treatment. No effects were observed on inflammation or oxidative stress in vivo, except for vWf |
| Flavonoids (Anthocyanins) | Dohadwala et al. (2011) [36] | 4 | Open-label, (2 and 4 hour acute study) | (15) CAD subjects | 835 mg total polyphenols, 94 mg anthocyanins vs. PCB | Vascular function | No significant effect |
| Flavonoids (Anthocyanins) | Dohadwala et al. (2011) [36] | 4 | X, 2B, PCB (4 weeks, 2 week washout) | (44) CAD subjects | 835 mg total polyphenols, 94 mg anthocyanins vs. PCB | Vascular function | ↓ Carotid femoral pulse wave activity |
| Flavonoids (Catechins) | Miyazaki et al. (2013) [37] | 4 | 2B, PCB (14 weeks) | (52) Healthy subjects | 630.9 mg/day Green Tea Catechins vs. Ctrl | CVD risk markers | No significant effect |
| Flavonoids (Catechins) | de Maat et al. (2000) [38] | 3 | 1B, PCB, PA (4 weeks) | (64) Healthy subjects | Black tea (3 g/day), green tea (3 g/day), green tea polyphenol isolate capsules (3.6 mg/day) and mineral water. | Inflammatory and endothelial markers | Negative correlation between the levels of the antioxidant β-carotene and the inflammation markers IL6 and fibrinogen |
| Flavonoids (Catechins) | Widmer et al. (2013) [39] | 3 | 2B, Ctrl (4 months) | (52) Early atherosclerosis | 30 mL/day simple Olive Oil vs. 30 mL/day of EGCG-supplemented Olive Oil | EF, inflammation and oxidative stress | Only significant when merging data of both groups the EF was improved. |
| Flavonoids (Catechins) | Nagao et al. (2007) [40] | 4 | 2B, PA (12 weeks) | (240) Visceral fat-type obesity | Green tea containing 583 mg/day catechins (catechin group) vs. 96 mg/day catechins (Ctrl group) | Anthropometric measurements, body fat composition and CVD risk | ↓ body weight, BMI, body fat ratio, body fat mass, waist circumference, hip circumference, visceral fat area, and subcutaneous fat area, SBP, LDLc |
| Flavonoids (Flavanols) | Farouque et al. (2006) [41] | 5 | 2B, PCB (6 weeks) | (40) Healthy males | Flavanol-rich chocolate bar and cocoa beverage (total flavanols, 444 mg/day) vs. matching isocaloric PCBs (total flavanols, 19.6 mg/day) | EF and adhesion molecules | No significant effect |
| Flavonoids (Flavanols) | Berry et al. (2010) [42] * | 4 | 2B, X (2 h, 3–7 days washout) | (21) overweight/obese subjects | HF, 701 mg or LF, 22 mg cocoa | BP, HR, FMD | ↑ DBP after exercise were attenuate by HF, improvement of FMD with HF |
| Flavonoids (Flavanols) | Davison et al. 2008 [43] * | 4 | 2B, PCB, PA (12 weeks) | (98) overweight/obese subjects | 902 mg cocoa flavanols/day vs. 36 mg cocoa flavanols/day With/without exercise protocol | BP, HDLc, LDLc, TG, HOMA, FMD | ↑ FMD at 6 and 12 weeks with HF vs. LF, ↑ DBP, BP mean, improvement in HOMA (independent of exercise) |
| Flavonoids (Flavanols) | West et al. (2014) [44] | 3 | 2B, PCB, X (4 weeks, 2 weeks washout) | (30) Middle-aged overweight | 37 g/day of dark chocolate and a sugar-free cocoa beverage (total flavanols = 814 mg/day) vs. low-flavonol chocolate and cocoa free beverage (total flavanols = 3 mg/day) | EF, BP | ↑ Basal and peak diameter of the brachial artery and basal blood flow volume. |
| Flavonoids (Flavanols) | Faridi et al. (2008) [45] | 4 | X, Ctrl, 1B (1 days, 7 days washout) | (45) Overweight subjects | Solid dark chocolate bar (821 mg flavanols) vs. cocoa-free PCB bar (0 mg flavanols) | EF, BP | Solid dark chocolate improved EF; also ↓ BP |
| Flavonoids (Flavanols) | Faridi et al. (2008) [45] | 4 | X, Ctrl, 1B (1 days, 7 days washout) | (44) Overweight subjects | Sugar-free cocoa (805.2 mg flavanols), sugared cocoa (805.2 mg flavanols), vs. PCB (0 mg flavanols). | EF, BP | Liquid cocoa ingestion improved EF; sugar-free cocoa ↓ BP |
| Flavonoids (Flavanols) | Davison et al. (2010) [46] | 3 | 2B, PA (6 weeks) | (52) Men and postmenopausal women with untreated mild HT | 33, 372, 712 or 1052 mg/day of cocoa flavanols | 24-h BP | No significant effect |
| Flavonoids (Flavanols) | Grassi et al. (2008) [47] | 3 | X, Ctrl, 1B (15 days) | (19) HT with Impaired glucose tolerance | Flavonol-rich dark chocolate (110.9 mg epicatechin, 36.12 mg catechin, 2.5 mg quercetin, 0.03 mg kaempferol, and 0.2 mg isorhamnetin)/d or flavonol-free white chocolate (0.04 mg/day catechins) | EF, IR, β-cell function, BP, CRP, TC | ↓ IR, BP, TC, LDLc. ↑ insulin sensitivity, EF |
| Flavonoids (Flavanols) | Flammer et al. (2012) [48] | 3 | 2B, PCB (2 hours) | (20) CHF patients | 40 g Flavonol rich chocolate (624 mg total flavanols) vs. 28.4 g Ctrl chocolate (0 mg flavanols | EF and platelet function in the short term | Improvement of vascular function in patients with CHF |
| Flavonoids (Flavanols) | Flammer et al. (2012) [48] | 3 | 2B, PCB (2 and 4 weeks) | (20) CHF patients | 40 g/day Flavonol rich chocolate (624 mg total flavanols) vs. 28.4 g/day Ctrl chocolate (0 mg flavanols) | EF and platelet function in long term by FMD | Improvement of vascular function in patients with CHF |
| Flavonoids (Flavanols) | Heiss et al. (2010) [49] | 3 | Ctrl, 2B, X (30 days) | (16) CAD patients | High-flavanol intervention (375 mg/day) and a macronutrient- and micronutrient-matched low-flavanol intervention (9 mg/day) twice daily | EF and enhancement and function of circulating angiogenic cells | ↑ EF, CD34+/KDR+-Circulating angiogenic cells. ↓ SBP |
| Flavonoids (Flavanols) | Horn et al. (2013) [50] | 3 | 2B, X (30 days) | (16) CAD patients | High-flavanol intervention (375 mg/day) and a macronutrient- and micronutrient-matched low-flavanol intervention (9 mg/day) twice daily | Circulating endothelial micro particles, markers of endothelial integrity, EF | ↑ Endothelial micro-particles and EF. Improvement of endothelial integrity |
| Flavonoids (Flavanols) | Balzer et al. (2008) [51] | 5 | 2B, PCB, three-period X (2 h) | (10) Diabetic subjects | Single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg) | EF | Single ingestion of flavanol-containing cocoa was dose-dependently acute increases in circulating flavanols and EF |
| Flavonoids (Flavanols) | Balzer et al. (2008) [51] | 5 | 2B, PCB, PA (30 days) | (41) Diabetic subjects | 963 mg/day Flavanol-rich cocoa vs. nutrient-matched Ctrl (75 mg/day flavanols) | EF | Flavanol-containing cocoa ↑ baseline EF |
| Flavonoids (Flavonols) | Larson et al. (2012) [52] | 3 | 2B, PCB, X (1 days, 7 days washout) | (5) Healthy males | 1095 mg quercetin aglycone vs. PCB | Angiotensin-converting enzyme, endothelin-1, BP | No significant effect |
| Flavonoids (Flavonols) | Conquer et al. (1998) [53] | 3 | 2B (28 days) | (27) Healthy subjects | 4 capsules (1.0 g quercetin/day) vs. rice flour PCB | BP, lipids profile, thrombogenic risk factors | No significant effect |
| Flavonoids (Flavonols) | Suomela et al. (2006) [54] | 3 | 2B, PCB, X (4 weeks, 4 weeks washout) | (14) Healthy males | Oat meal with 78 mg/day flavonol aglycones (sea buckthorn) vs. Ctrl | CVD risk markers | No significant effect |
| Flavonoids (Flavonols) | Edwards et al. (2007) [55] | 3 | 2B, PCB, X (28 days) | (41) Prehypertension and hypertension | 730 mg quercetin/day vs. PCB | BP, oxidative stress | ↓ BP in hypertensive group |
| Flavonoids (Flavonols) | Larson et al. (2012) [52] | 3 | 2B, PCB, X (1 days, 2 days washout) | (12) HT stage 1 males | 1095 mg quercetin aglycone vs. PCB | Angiotensin-converting enzyme, endothelin-1, BP | ↓ BP in Hypertensive men |
8-iso-PGF2α, 8-iso-prostaglandin F2α; 1B, one-blind, 2B, double-blinded; ACN, anthocyanins; Apo, apolipoprotein; BMI, body mass index; BP, blood pressure; CAD, chronic artery disease; CAT, catalase; CHF, chronic heart failure; CHO, carbohydrate; CRP, C-reactive protein; hsCRP, high sensitivity c-reactive protein; Ctrl, control, CVD, cardiovascular disease; DXA, Dual-energy X-ray absorptiometry; EF, endothelial function; EGCG, epigallocatechin gallate; ESRD, European and North American end-stage renal disease; FM, fat mass; FFM, fat-free mass; FMD, flow mediated dilation; HDLc, high-density lipoprotein cholesterol; HOMA, homeostasis model assessment; HR, heart rate; HT, hypertension; sICAM, soluble intercellular adhesion molecule; IGF-1, insulin-like growth factor-1; IR, insulin resistance; IL, interleukin; LDLc, low-density lipoprotein cholesterol; MDA, malonaldehyde; MPFF, micronized purified flavonoid fraction; MPI, milk protein isolate; NTG, nitro-glycerine-mediated dilation; PA, parallel design, PAI-1, plasminogen activator inhibitor-1; PCB, placebo, PBMCs, peripheral blood mononuclear cells; PS, plant sterols; PWV, pulse wave velocity; QUICKI, quantitative insulin sensitivity check index; SBP, systolic blood pressure; SOD, superoxide dismutase; TC, total cholesterol; TGF, transforming growth factor; T2D, type 2 diabetes; VCAM, soluble vascular cellular adhesion molecule; vWf, von Willebrand factor; X, crossover design. * Included after proofreading.