Introduction
Epidemiology of tomato consumption and CVD risk reduction
Role of platelet hyperactivity in the development of CVD
Conditions lead to hyperactive platelets |
---|
Diabetes mellitus |
Insulin resistance |
Obesity |
Ageing |
Over nutrition, bad diets |
Sedentary lifestyles |
Oxidative stress, inflammation and hyperlipidemia |
Drugs, contraceptives |
Cancers |
Hypertension |
In vitro studies with water-soluble tomato extract on human blood platelet aggregation
Development of Fruitflow®: Compositional and structural aspects
Source | Cultivar | Ripeness | tAF isolated (mg/kg tomato fresh wt) | tAF IC50 against ADP agonist (mg/mL PRP) |
---|---|---|---|---|
UK | Fresh market cultivar (greenhouse grown) | Green | 212 ± 50 | 10.8 |
Fully ripe | 533 ± 35 | <1.0 | ||
Processing cultivar E6203 (greenhouse grown) | Green | 251 ± 64 | 15.6 | |
Fully ripe | 600 ± 77 | <1.0 | ||
Spain | Processing cultivar | Green | 377 ± 35 | 13.9 |
Fully ripe | 745 ± 43 | <0.5 | ||
Processing cultivar | Green | 352 ± 65 | 15.9 | |
Fully ripe | 698 ± 23 | <0.5 | ||
Chile | Processing cultivar (tunnel grown) | Green | 303 ± 54 | 12.7 |
Fully ripe | 712 ± 33 | <0.5 | ||
Processing cultivar (tunnel grown) | Green | 364 ± 12 | 10.3 | |
Fully ripe | 768 ± 42 | <0.5 |
Product | F1 | F2 | F3 | |||
---|---|---|---|---|---|---|
Mean | Range | Mean | Range | Mean | Range | |
Fresh tomato extract | 8095.6 | n/a | 410.3 | n/a | 1802.3 | n/a |
Commercial tomato paste* | 6014.2 | 4211.8–7207.1 | 263.0 | 22.9–433.6 | 1176.3 | 945.5–1404.9 |
Commercial tomato soup* | 3813.3 | 1089.1–5685.1 | 318.2 | 24.1–400.2 | 767.4 | 241.5–1586.6 |
Commercial tomato juice* | 5661.5 | 5649.1–5692.0 | 84.0 | 54.5–99.3 | 1146.3 | 896.4–1377.9 |
Commercial tomato sauce* | 4680.5 | 3599.8–5156.2 | 139.8 | 92.4–93.7 | 1155.8 | 823.8–1787.2 |
Fruitflow®
| 7874.6 | n/a | 389.2 | n/a | 2141.3 | n/a |
IC50 ADP | IC50 Collagen | IC50 TRAP | IC50 AA | |
---|---|---|---|---|
Antiplatelet activity of the standardized Fruitflow® 1 and Fruitflow® 2 ingredients, expressed as IC50 values | ||||
Fruitflow® 1 | <1.0 | <1.0 | <2.7 | <3.6 |
Fruitflow® 2 | <0.05 | <0.05 | <0.5 | <0.7 |
Human trials undertaken with Fruitflow® 1 and Fruitflow® 2
Early studies
Main body of studies undertaken with standardized Fruitflow® 1 and Fruitflow® 2
Study | Description | Main purpose | N/gender/study population | Duration /intervention | Outcome measures | Major results for intervention expressed as % change from baseline measurements at t = 3 h after supplementation, unless otherwise stated | ||
---|---|---|---|---|---|---|---|---|
Aggregation | Clotting times | Other | ||||||
1. O’Kennedy et al. 2006a | R, SB, PC crossover | Acute effect, onset and persistence | 27/M F healthy | Single dose Control (treacle) or FF1 equivalent to three daily doses, 195 mg tAF, in 50 mL or 200 mL OJ | Platelet aggregation Clotting times |
C 50 mL: ADP: 6.8 (1.5)
C 200 mL: ADP: 2.9 (3.4)
FF 195 mg tAF 50 mL: ADP: −23.1 (9.8)P<0.001,*
FF 195 mg tAF 200 mL: ADP: −17.8 (5.1)P<0.001,* |
C 50 mL: PT: 0.3 (2.7) TCT: 1.9 (1.8)
C 200 mL: PT: 0.3 (2.7) TCT: 1.9 (1.8)
FF 195 mg tAF 50 mL: PT: 0.8 (1.8) TCT: −2.9 (1.2)
FF 195 mg tAF200 mL: PT: 0.8 (1.8) TCT: −2.9 (1.2) | |
2. O’Kennedy et al. 2006b | R, DB, PC crossover | Acute effect, size of effect, dose–response | 93/M F healthy | Single dose Control (treacle) in 200 mL juice or FF1 equivalent to one daily dose, 65 mg tAF in 200 mL juice or FF1 equivalent to three daily doses, 195 mg tAF, in 200 mL juice | Platelet aggregation Clotting times |
C: ADP: −2.6 (2.9) Coll: −7.3 (2.4)
FF 65 mg tAF:
ADP: −12.7 (3.1)
P<0.01,*
Coll: −14.5 (2.5)
P = 0.003,*
FF 195 mg tAF:
ADP: −21.3 (2.9)
P<0.001,*
Coll: −18.0 (2.8)
P=0.003,*
|
C:
PT: 0.8 (0.7) TCT: 1.8 (1.2)
FF 65 mg tAF:
PT: 3.5 (2.4) TCT: 0.2 (1.1)
FF 195 mg tAF:
PT: 0.1 (0.7) TCT: 1.2 (1.3) | |
3. O’Kennedy et al (unpublished) | R, DB, PC crossover | Chronic effect | 22/M F healthy | 28d daily supplementation with samples every 14 days Control (treacle) in 200 mL juice or FF1 equivalent to one daily dose, 65 mg tAF, in 200 mL juice | Platelet aggregation Clotting times |
C 14d:
ADP: −1.5 (5.5)
FF 65 mg tAF 14d:
ADP: −19.0 (4.1)
P=0.0004,*
FF 65 mg tAF 28 d:
ADP: −28.2 (4.1)
P=0.0001,*
|
C 14d:
PT: 0.0 (1.5) TCT: 2.3 (3.0)
FF 65 mg tAF 14d:
PT: −3.3 (1.5) TCT: 3.1 (3.0)
FF 65 mg tAF 28 d:
PT: −1.4 (1.5) TCT: −2.7 (3.0) | |
4. O’Kennedy et al (unpublished) | R, DB, PC crossover | Acute effect, different formats of FF (liquid and powder forms) | 45/M F healthy | Single dose Control (treacle and cellulose powder) or FF1, FF2a or FF2b equivalent to one daily dose, 65 mg tAF, given as capsules | Platelet aggregation Clotting times TxA2 generation in response to collagen |
C:
ADP: −8.7 (3.9) Coll: −0.9 (2.9)
FF1 65 mg tAF:
ADP: −17.2 (3.7)
P<0.001,*
Coll: −15.6 (2.6)
P<0.001,*
FF2a 65 mg tAF:
ADP: −15.5 (3.8)
P<0.001,*
Coll: −14.4 (2.8)
P<0.001,*
FF2b 65 mg tAF:
ADP: −13.5 (3.8)
P<0.001,*
Coll: −11.6 (2.7)
P<0.001,*
|
C:
PT: 0.4 (0.7) TCT: 0.6 (1.3)
FF1 65 mg tAF:
PT: 0.3 (0.7) TCT: 0.5 (1.3)
FF2a 65 mg tAF:
PT: 0.6 (0.7) TCT:0.4 (1.3)
FF2b 65 mg tAF:
PT: 1.3 (0.8) TCT: 0.1 (1.3) |
C:
TxB2: 6.8 (8.3)
FF1 65 mg tAF:
TxB2: −25.1 (8.3)
P=0.0008,*
FF2a 65 mg tAF:
TxB2: −33.5 (8.3)
P=0.0003,*
FF2b 65 mg tAF:
TxB2: −36.8 (8.3)
P<0.0001,*
|
5. O’Kennedy et al (unpublished) | R, positive C crossover | Over-consumption safety study | 20/MF healthy | Single dose and 5d daily dose FF1 equivalent to one daily dose, 65 mg tAF, given in 250 mL juice, or FF1 equivalent to four daily doses, 260 mg tAF, given in 1L juice either once or once per day for 5 days. | Platelet aggregation Clotting times |
FF 65 mg tAF in 250 mL:
ADP: −13.0 (2.8)
P=0.0001
TRAP: −17.9 (4.0)
P<0.0001
FF 260 mg tAF in 1L:
ADP: −3.1 (2.8)*
TRAP: 1.2 (3.6)*
FF 260 mg tAF in 1L, 5d:
ADP: −3.5 (2.7)* TRAP: −0.6 (4.1)* |
FF 65 mg tAF in 250 mL:
PT: −0.3 (0.5) TCT: 0.7 (0.6)
FF 260 mg tAF in 1L:
PT: −0.5 (0.4) TCT: −0.9 (0.6)
FF 260 mg tAF in 1L, 5d:
PT: −1.0 (0.4) TCT: −0.5 (0.5) | |
6. O’Kennedy et al (unpublished) | R, positive C crossover | Matrix effects | 9/MF healthy | Single dose FF2 equivalent to one daily dose, 65 mg tAF, in juice (positive control) or FF2 equivalent to one daily dose, 65 mg tAF, in yoghurt or FF2 equivalent to four daily doses, 260 mg tAF, in yoghurt | Platelet aggregation Clotting times |
FF2 65 mg tAF (juice):
ADP: −18.4 (8.2)
P<0.05
Coll: −18.0 (6.3)
P<0.016
FF2 65 mg tAF (yoghurt):
ADP: −13.7 (5.6)
P=0.033
Coll: −9.4 (5.3)
FF 260 mg tAF (yoghurt):
ADP: −25.7 (7.6)
P=0.006
Coll: −12.4 (5.3)
P=0.010
|
FF2 65 mg tAF (juice):
PT:0.1 (0.5) TCT: −0.3 (1.6)
FF2 65 mg tAF (yoghurt):
PT: −0.1 (0.5) TCT: 0.7 (1.6)
FF 260 mg tAF (yoghurt):
PT: 0.2 (0.5) TCT: −0.3 (1.6) | |
7. O’Kennedy et al (submitted for review) | R, DB, PC crossover | Comparison of a single dose of FF to a single dose of 75 mg ASA, and to 7d of 75 mg ASA | 47/MF healthy | Single dose and 7d supplement Control (treacle or cellulose powder) either as a single dose or once daily for seven days or FF1 equivalent to one daily dose, 65 mg tAF, given as a capsule or 75 mg ASA given as a capsule or 75 mg ASA given as a capsule once daily for 7 days | Platelet aggregation Clotting times TxA2 generation in response to collagen/AA PFA − 100 closure time |
C:
ADP:0.8 (4.8) Coll: −3.1 (3.9) AA: −0.6 (5.6)
FF 65 mg tAF:
ADP: −26.3 (5.3)
P=0.005, *
Coll: −9.7 (4.2)
P=0.018, *
AA: −15.8 (6.0)
P<0.001
ASA 75 mg single dose:
ADP: −26.7 (5.9)
P<0.001, *
Coll: −23.5 (4.6)
P<0.001, *
AA: −56.5 (6.4)
P<0.001, *
ASA 75 mg 7d:
ADP: −26.3 (5.3)
P<0.001, *
Coll: −49.8 (4.2)
P<0.001, *
ASA: −88.5 (6.0)
P<0.001, *
|
C:
PT: −0.8 (1.7) TCT: −1.4 (1.1) aPTT: 0.0 (1.2)
FF 65 mg tAF:
PT: 1.1 (1.1) TCT: 1.1 (1.1) aPTT: 1.7 (1.3)
ASA 75 mg single dose:
PT: −3.5 (1.9) TCT: −1.3 (1.2) aPTT: 1.4 (1.4)
ASA 75 mg 7d:
PT: −0.8 (1.8) TCT: −0.5 (1.2) aPTT: 1.2 (1.3) |
C:
TxB2 (coll): −2.2 (5.8) TxB2 (AA): −1.74 (6.5) PFA-100: 5.9 (8.4)
FF 65 mg tAF:
TxB2 (coll): −34.1 (6.3)
P<0.001, *
TxB2 (AA): −39.8 (6.8)
P<0.001, *
PFA -100: 47.6 (8.4)
P<0.001, *
ASA 75 mg single dose:
TxB2 (coll): −69.3 (6.8)
P<0.001, *
TxB2 (AA): −62.8 (7.2)
P<0.001, *
PFA -100: 56.7 (8.4)
P<0.001, *
ASA 75 mg 7d:
TxB2 (coll): −91.4 (6.3)
P<0.001, *
TxB2 (AA): −99.0 (6.9)
P<0.001, *
PFA-100: 127.8 (10.4)
P<0.001, *
|