Table 2.
Summary of long-term interventions.
| Reference | Duration | Study Design | Control | Participants a | Source of ACN | Daily Dose of ACN b | Effect on Blood Pressure c |
|---|---|---|---|---|---|---|---|
| Ataie-Jafari [38] | 6 weeks | Pre-post | - | 19 women with diabetes, age 53 ± 9, BMI 30 ± 4 | Sour cherry juice | 720 mg | <SBP, <DBP |
| Barona [39] | 4 weeks | Crossover | Double-blind, placebo-controlled | 24 male with, age 51 ± 10, BMI 32 ± 5 | Freeze-dried grape phenolic extract | 35 mg | <SBP, =DBP |
| Basu [40] | 8 weeks | Parallel arms | Controlled | 48 with MetS, age 50 ± 3, BMI 38 ± 2 | Freeze-dried blueberry beverage (control: water) | 742 mg | <SBP, <DBP |
| Broncel [41] | 8 weeks | Pre-post | - | 25 with MetS, age 42–65, BMI 31 ± 3 | Aronia extract | 300 mg | <SBP, <DBP |
| Chai [42] | 12 weeks | Parallel arms | Controlled | 34 overweight older adults, age 70 ± 4, BMI 28 ± 4 | Tart cherry juice (control: energy and sugar matched drink) | (451 mg total phenolics) | < SBP, =DBP |
| Cook [43] | 12 days | Crossover | Controlled | 15 athletes, age 38 ± 12, BW 76 ± 10 | Blackcurrant extract (control: no extract) | 105, 210, or 315 mg | = SBP, =DBP, <MAP with 210 and 315 |
| Cook [44] | 1 week | Crossover | Double-blind, placebo-controlled | 13 healthy male, age 26 ± 4, BMI 25 ± 3 | Blackcurrant extract | 315 mg | = SBP, =DBP, =MAP at rest, <SBP, <DBP, <MAP during isomeric contraction |
| Curtis [45] | 12 weeks | Parallel arms | Double-blind, placebo-controlled | 52 healthy postmenopausal women, age 58 ± 6, BMI 25 ± 4 | ACN-rich elderberry extract capsule | 500 mg | = SBP, =DBP |
| Davinelli [46] | 4 weeks | Parallel arms | Double-blind, placebo-controlled | 42 overweight, age 45–65, BMI 29 ± 4 | ACN-rich maqui berry extract | 486 mg | = SBP, =DBP |
| Desai [47] | 20 days | Parallel arms | Single-blind, placebo-controlled | 11 healthy, age 30 ± 10, BMI 24 ± 3 | Tart cherry juice | 540 mg | = SBP, =DBP pre or post exercise |
| Draijer [48] | 4 weeks | Crossover | Double-blind, placebo-controlled | 60 mildly hypertensive, age 58 ± 10, BMI 26 ± 4 | Grape and grape wine extracts | (800 mg total phenolics) | <SBP, <DBP with grape wine but not grape alone |
| Erlund [49] | 8 weeks | Parallel arms | Single-blind, placebo-controlled | 72 with CVD risk factors, age 58 ± 6, BMI 26 ± 3 | Berry mix (bilberries, lingonberries, black currant, strawberry, chokeberry, and raspberry) | 515 mg | <SBP, =DBP |
| Gurrola-Diaz [50] | 4 weeks | Parallel arms | Controlled | 73 healthy and 51 MetS patients, age 49 ± 7, BMI 29 ± 5 | Hibiscus sabdariffa extract powder (control: preventive diet) | 19 mg | = SBP, =DBP in healthy and MetS patients |
| Habanova [51] | 6 weeks | Pre-post | - | 36 healthy, age 48 ± 6, BMI 27 ± 4 | Frozen bilberries, 3 times a week | 456 mg, 3 times/week | = SBP, =DBP |
| Hassellund [52] | 4 weeks | Crossover | Double-blind, placebo-controlled | 31 moderately hypertensive male, age 41 ± 3, BMI 27 ± 3 | ACN capsule (isolated from bilberry and blackcurrant) | 640 mg | = sitting, supine, or 24h-ambulatory blood pressure, or blood pressure during stress test |
| Jeong [53] | 8 weeks | Parallel arms | Double-blind, placebo-controlled | 45 prehypertensive, age 57 ± 12, BMI 25 ± 3 | Dried unripe black raspberry powder | (1500 mg or 2500 mg powder) | <SBP with high dose, =DBP |
| Jeong [54] | 12 weeks | Parallel arms | Double-blind, placebo-controlled | 51 with MetS, age 59 ± 10, BMI 25 ± 4 | Dried unripe black raspberry powder | (750 mg of dry powder) | =SBP, =DBP |
| Johnson [55] | 8 weeks | Parallel arms | Double-blind, placebo-controlled | 48 postmenopausal women with pre- and stage 1-hypertension, age 59 ± 5, BMI 31 ± 6 | Freeze-dried blueberry powder mixed with water | 469 mg | <SBP, <DBP |
| Kardum [56] | 4 weeks | Pre-post | - | 20 abdominally obese postmenopausal women, age 53 ± 5, BMI 36 ± 4 | Glucomannan-enriched aronia juice-based supplement | 25 mg | <SBP, =DBP |
| Kardum [57] | 12 weeks | Pre-post | - | 29 healthy women, age 35 ± 8, BMI 23 ± 4 | Glucomannan-enriched aronia juice-based supplement | 25 mg | = SBP, =DBP |
| Kardum [58] | 4 weeks | Pre-post | - | 23 pre- or stage 1 hypertensive, age 48 ± 10, weight 82 ± 20 | Aronia juice | 358 mg | <SBP, <DBP, < average 24 h BP |
| Karlsen [59] | 3 weeks | Parallel arms | Placebo-controlled | 118 adults, age 61 ±?, BMI 25 ±? | Purified ACN capsule from bilberry and blackcurrant | 300 mg | =SBP, =DBP |
| Kelley [60] | 4 weeks | Pre-post | - | 18 healthy, age 50 ± 4, BMI 26 ± 4 | Fresh sweet cherries | (280 g fresh cherries) | =SBP, =DBP at the end of the trial and after 1 month |
| Kent [61] | 12 weeks | Parallel arms | Controlled | 49 older adults, age 80 ± 6, BMI 26 ± 3 | Cherry juice (control: ACN free apple juice) | 138 mg | <SBP, =DBP |
| Khan [62] | 6 weeks | Parallel arms | Placebo-controlled | 66 healthy adults, age 52 ± 10, BMI 29 ± 6 | Blackcurrant juice, low or high dose | 40 mg or 143 mg | =SBP, =DBP |
| Kolehmanen [63] | 8 weeks | Parallel arms | Controlled | 27 with MetS, age 51 ± 6, BMI 32 ± 4 | Bilberries (400 g fresh) | 1381 mg | =SBP, =DBP |
| Lehtonen [64] | 20 weeks | Parallel arms | Controlled | 61 women, age 43 ±?, BMI 29 ±? | 163 g mix of 18 berries (control: lifestyle intervention) | (equivalent to 163 g fresh berries) | =SBP, =DBP |
| Lee [65] | 8 weeks | Parallel arms | Double-blind, placebo-controlled | 63 overweight or obese, age 31 ± 9, BMI 28 ± 2 | ACN-rich black soybean extract | 31.45 mg | =SBP, =DBP |
| Li [66] | 24 weeks | Parallel arms | Double-blind, placebo-controlled | 58 with type II diabetes, age 58 ± 3, BMI 24 ± 3, | ACN capsules (isolated from bilberry and black currant) | 320 mg | <SBP, =DBP |
| Loo [67] | 16 weeks | Crossover | Single-blind, placebo-controlled | 37 with mild hypertension, age 40–70, BMI 26 ± 3 | Cold-pressed Aronia juice and oven-dried Aronia powder | 1024 mg | <daytime DBP (recorded over 15 hours), =SBP |
| Lynn [68] | 6 weeks | Parallel arms | Controlled | 47 healthy adults, age 38 ± 6, BMI 24 ± 3 | Tart cherry concentrate, (control: energy matched drink) | 274.5 mg | =SBP, =DBP |
| Matsumoto [35] | 2 weeks | Crossover | Double-blind, placebo-controlled | 11 healthy, age 39 ± 12, BMI? | Blackcurrant ACN extract | (7.7 mg/kg) | =SBP, =DBP after 30 minutes typing workload |
| McAnulty [69] | 3 weeks | Parallel arms | Controlled | 20 smokers, age 28 ± 4, BMI 29 ± 3 | Blueberry 250 g | =SBP, =DBP, = ACE activity | |
| McAnulty [70] | 6 weeks | Parallel arms | Placebo-controlled | 25 healthy, age 43 ± 12, BMI 26 ± 4 | Freeze-dried blueberry powder, equivalent to 250 g berries | <aortic systolic pressures, <SBP, =DBP, <DBP in the subset of prehypertensive subjects (9 subjects) | |
| Naruszewicz [71] | 6 weeks | Parallel arms | Double-blind, placebo-controlled | 44 post myocardial infarction patients, receiving statin therapy, age 66 ± 8, BMI 27 ± 3 | 255 mg/day Aronia flavonoid extract | 64 mg | <SBP, <DBP |
| Nilsson [72] | 5 weeks | Crossover | Controlled | 40 healthy, age 63 ± 1, BMI 24 ± 1 | Mixed berry drink (1/3 blueberries, 1/9 blackcurrant, 1/9 elderberry, 1/9 lingonberry, 1/9 strawberry, 2/9 tomato), or sugar-matched control | 248 mg | =SBP, =DBP |
| Ohguro [73] | 4 weeks | Crossover | Double-blind, placebo-controlled | 12 healthy, age 39 ± 8, BMI? | Blackcurrant ACN extract | 50 mg | < intraocular pressure, =SBP, =DBP |
| Ohguro [74] | 2 years | Parallel arms | Double-blind, placebo-controlled | 21 glaucoma patients, age 61 ± 7, BMI? | Blackcurrant ACN extract | 50 mg | < intraocular pressure, =SBP, =DBP |
| Qin [75] | 12 weeks | Parallel arms | Double-blind, placebo-controlled | 120 dyslipidemic, age 55 ± 5, BMI 26 ± 4 | ACN capsule (from bilberry and blackcurrant) | 160 mg | =SBP, =DBP |
| Puupponen-Pimia [76] | 8 weeks | Parallel arms | Controlled | 37 overweight with MetS, age 51 ± 7, BMI 32 ± 4 | 300 g frozen berries (raspberries, strawberries, and cloudberries) | (equivalent to 300 g fresh berries) | =SBP, =DBP |
| Riso [77] | 6 weeks | Crossover | Placebo-controlled | 18 male with risk factors for CVD, age 48 ± 10, BMI 25 ± 3 | Wild blueberry drink | 400 mg | =SBP, =DBP |
| Skoczynska [78] | 6 weeks | Pre-post | - | 58 male with mild hypercholesterolemia, age 54 ± 6, BMI 28 ± 3 | Aronia juice 250 mL | 90 mg | <SBP after 12 weeks, <DBP after 6 and 12 weeks |
| Sikora [79] | 8 weeks | Pre-post | - | 23 with untreated MetS (BMI 31 ± 4), reference group with 25 treated MetS patients (BMI 29 ± 3) and 20 healthy controls (BMI 23 ± 1) | Aronia extract supplements or ACE-inhibitors | 60 mg | <SBP, <DBP, <ACE activity |
| Stull [80] | 6 weeks | Parallel arms | Double-blind, placebo-controlled | 32 obese with insulin-resistance, age 52 ± 3, BMI 37 ± 1 | Blueberry powder added to smoothie smoothie and yogurt | 580 mg | =SBP, =DBP |
| Stull [81] | 6 weeks | Parallel arms | Double-blind, placebo-controlled | 44 adults, age 57 ± 2, BMI 36 ± 1 | Blueberry powder added to smoothie and yogurt | 580 mg | =SBP, =DBP |
| Thompson [82] | 4 weeks | Crossover | Double-blind, placebo-controlled | 16 sedentary, age 38 ± 12, BMI 23 ± 2 | ACN capsule | 320 mg | =SBP, =DBP |
| Tjelle [83] | 12 weeks | Parallel arms | Double-blind, placebo-controlled | 134 prehypertensive or hypertensive, age 52 ± 6, BMI 26 ± 3 | Mixed berry fruit juice (red grape, aronia, cherry, and bilberry) or same juice enriched with black currant press residue | 43 mg or 210 mg | <SBP in both juice groups, more pronounced if high BP baseline value, =DBP |
| Udani [84] | 4 weeks | Pre-post | - | 10 overweight, age 28 ±?, BMI 27 ± 2 | 100 g açai pulp | 0.77 mg/mL ACN (density unknown) | =SBP, =DBP |
| Whyte [85] | 6 months | Parallel arms | Double-blind, placebo-controlled | 122 older adults, age 71 ± 4, BW 71 ± 4 | Whole wild blueberry powder 1 or 2 g, or extract 200 mg | 2.7, or 5.4 or 14 mg | <SBP with extract, but not with powders, at 3 and 6 months |
| Xie [86] | 12 weeks | Parallel arms | Placebo-controlled | 49 healthy former smokers, age 35 ± 3, BMI 26 ± 1 | 500 mg aronia extract | 45.1 mg | =SBP, =DBP |
| Zhang [87] | 12 weeks | Parallel arms | Double-blind, placebo-controlled | 72 patients with nonalcoholic fatty liver disease, age 46 ± 8, BMI 27 ± 3 | ACN capsules (isolated from bilberry and black currant) | 320 mg | =SBP, =DBP |
| Zhu [88] | 24 weeks | Parallel arms | Double-blind, placebo-controlled | 146 hypercholesterolemic, age 56 ± 6, BMI 27 ± 2 | ACN capsules (isolated from bilberry and black currant) | 320 mg | =SBP, =DBP |
a Age (in years) and BMI (in kg/m2) data expressed as mean ± SD. When data was reported as SEM, SD was calculated as SEM*SQRTparticipant. When BMI was unreported, weight in kg is reported instead. A question mark (?) indicates unreported data. b When daily ACN dose is unreported, the best alternative information is reported in parentheses. c Only blood pressure data is reported in this table. Other outcomes of the studies are not reported. SBP: systolic blood pressure; DPB: diastolic blood pressure; MetS: Metabolic Syndrome; MAP: mean arterial pressure; ACE: angiotensin-converting enzyme; > or <: statistically significant increase or decrease; =: no significant change.