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. 2021 Dec 11;10(12):1978. doi: 10.3390/antiox10121978

Table 2.

Evidence of the effects of carotenoids on CVD health from randomized controlled trials.

Carotenoids Study Design Intervention Outcome References
Classical CVD Risk Factors
Lutein RCT, parallel, double-blinded,
Healthy subjects (n = 117)
10, 20 mg lutein for 12 weeks ↔ TG, LDL-C, HDL-C [38]
RCT, parallel, double-blinded,
Early atherosclerosis patients (n = 65)
20 mg lutein for 12 weeks ↓ TG, LDL-C
↔HDL
[36]
Zeaxanthin RCT, parallel,
Metabolic syndrome patients (n = 50)
14 g Goji berry for 45 days ↓ TC, LDL-C, VLDL-C
↑ HDL-C
[37]
β-cryptoxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 117)
β-cryptoxanthin-rich satsuma mandarin juice for 12 weeks ↔ LDL-C, HDL-C, TG, SBP, DBP [39]
Astaxanthin Meta-analysis Astaxanthin ↔ TC, LDL-C, HDL-C, TG [42]
Lycopene RCT, crossover, double-blinded,
Hypertensive
subjects (n = 46)
Tomato nutrient complex (equivalent to 5, 15 and 30 mg lycopene) for 8 weeks ↓ SBP [45]
Meta-analysis Lycopene or lycopene-rich foods ↓ LDL-C
↔ TC, HDL-C, TG
[41]
Meta-analysis Lycopene ↓ SBP
↔ DBP, TC, LDL-C, HDL-C, TG
[40]
Meta-analysis Tomato ↓ LDL-C,
↔ SBP, DBP, TC, HDL-C, TG
[40]
Oxidative Stress
LDL oxidation
Astaxanthin RCT, parallel, open labeled,
Healthy subjects (n = 24)
1.8, 3.6, 14.4, 21.6 mg astaxanthin for 2 weeks ↑ LDL lag-time [57]
Lycopene RCT, parallel, double-blinded,
CVD patients (n = 36),
Healthy subjects (n = 36)
7 mg Lycopene for 2 months ↔ ox-LDL [52]
RCT, parallel, single-blinded,
Healthy subjects (n = 225)
Tomato or 10 mg lycopene capsules for 12 weeks ↔ ox-LDL [53]
RCT, parallel, double-blinded,
Healthy subjects (n = 77)
6.5, 15, 30 mg lycopene for 8 weeks ↔ LDL oxidation rate [54]
Meta-analysis Lycopene ↔ LDL lag-time [55]
Carotenoid mixture RCT, crossover, double-blinded,
Healthy subjects (n = 31)
4.4 mg lutein, 6.0 mg β-carotene, 1.4 mg α-carotene, 4.5 mg lycopene, 11.7 mg bixin and 2.2 mg paprika for 3 weeks ↑ LDL lag-time [56]
Lipid oxidation/peroxidation products
Lutein RCT, parallel, double-blinded,
Healthy subjects (n = 117)
10, 20 mg lutein for 12 weeks ↓ MDA [38]
Zeaxanthin RCT, parallel,
Metabolic syndrome patients (n = 50)
14 g Goji berry for 45 days ↓ MDA [37]
RCT, parallel, double-blinded,
Healthy subjects (n = 40)
15 g Goji berry for 16 weeks ↓ 8-iso-PGF2α,
↔ MDA
[63]
Astaxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 58)
12 mg astaxanthin for 12 months ↔ F2-isoPs [91]
β-carotene RCT, parallel,
Healthy male workers
exposed to lead (n = 82)
10 mg β-carotene for 12 weeks ↓ MDA, LHP [60,62]
Lycopene RCT, parallel, double-blinded,
Healthy subjects (n = 77)
6.5, 15, 30 mg lycopene for 8 weeks ↔ MDA, HNE [54]
RCT, parallel, double-blinded,
Healthy males (n = 105)
30 mg lycopene for 3 weeks ↔ MDA [61]
RCT, parallel,
Postmenopausal females (n = 60)
Regular, lycopene-rich tomato juice (equivalent to 30 and 70 mg lycopene), 30 mg lycopene capsules for 6 months ↓ MDA [65]
RCT, crossover, double-blinded,
Healthy subjects (n = 26)
Tomato-based drink for 26 days ↔ 8-iso-PGF2α [64]
Total antioxidant capability
Lutein RCT, parallel, double-blinded,
Healthy subjects (n = 117)
10, 20 mg lutein for 12 weeks ↑ TAOC [38]
Zeaxanthin RCT, parallel,
Metabolic syndrome patients (n = 50)
14 g Goji berry for 45 days ↑ TAOC [37]
Lycopene RCT, parallel,
Postmenopausal females (n = 60)
Regular juice, lycopene-rich tomato juice (equivalent to 30 and 70 mg lycopene), 30 mg lycopene capsules for 6 months ↑ TAOC [65]
Carotenoid mixture RCT, crossover, double-blinded,
Healthy subjects (n = 31)
4.4 mg lutein, 6.0 mg β-carotene, 1.4 mg α-carotene, 4.5 mg lycopene, 11.7 mg bixin and 2.2 mg paprika for 3 weeks ↔ ORAC [56]
Antioxidant enzymes
Lutein RCT, parallel, double-blinded,
Healthy subjects (n = 117)
10, 20 mg lutein for 12 weeks ↔ SOD, GPx, CAT [38]
Zeaxanthin RCT, parallel,
Metabolic syndrome patients (n = 50)
14 g Goji berry for 45 days ↓ SOD
↑ CAT
[37]
β-carotene RCT, parallel,
Healthy male workers
exposed to lead (n = 82)
10 mg β-carotene for 12 weeks ↑ SOD, EC-SOD, CAT, G6PD
↓ GPx
↔ GR, GST
[60,62]
Lycopene RCT, parallel,
Postmenopausal females (n = 60)
Regular, lycopene-rich tomato juice (equivalent to 30 and 70 mg lycopene), 30 mg lycopene capsules for 6 months ↔ SOD, GPx, CAT [65]
RCT, parallel, double-blinded,
Healthy males (n = 126)
6, 15 mg lycopene for 8 weeks ↑ SOD [71]
DNA damage
Lutein RCT, crossover,
Healthy subjects (n = 8)
15 mg lutein for 1 week ↔ DNA tail intensity [75]
RCT, parallel, double-blinded,
Postmenopausal females (n = 37)
12 mg lutein for 56 days ↓ DNA tail length [74]
β-carotene RCT, parallel, double-blinded,
Postmenopausal females (n = 37)
12 mg β-carotene for 56 days ↓ DNA tail length [74]
RCT, crossover,
Healthy subjects (n = 8)
15 mg β-carotene for 1 week ↓ DNA tail intensity [75]
Lycopene RCT, parallel, double-blinded,
Postmenopausal females (n = 37)
12 mg lycopene for 56 days ↓ DNA tail length [74]
RCT, crossover,
Healthy subjects (n = 8)
15 mg lycopene for 1 week ↓ DNA tail intensity [75]
RCT, parallel, double-blinded,
Healthy males (n = 105)
30 mg lycopene for 3 weeks ↔ 8-OHdG [61]
Meta-analysis Lycopene ↓ DNA tail length [55]
Carotenoid mixture RCT, parallel, double-blinded,
Postmenopausal females (n = 37)
4 mg lutein, 4 mg β-carotene and 4 mg lycopene for 56 days ↓ DNA tail length [74]
RCT, crossover, double-blinded,
Healthy subjects (n = 31)
4.4 mg lutein, 6.0 mg β-carotene, 1.4 mg α-carotene, 4.5 mg lycopene, 11.7 mg bixin and 2.2 mg paprika for 3 weeks ↓ 8-OHdG: creatinine [56]
Inflammatory Markers
Lutein/zeaxanthin Meta-analysis Lutein/zeaxanthin ↓ CRP
↔ IL-6, TNF-α
[80]
Astaxanthin Meta-analysis Astaxanthin ↓ CRP
↔ IL-6, TNF-α
[80]
β-cryptoxanthin Meta-analysis β-cryptoxanthin ↓ CRP
↔ IL-6, TNF-α
[80]
β-carotene Meta-analysis β-carotene ↔ CRP, IL-6 [80]
Lycopene Meta-analysis Lycopene ↓ IL-6
↔ CRP, TNF-α
[80]
Crocin Meta-analysis Crocin ↔ CRP, IL-6, TNF-α [80]
Overall carotenoids Meta-analysis Overall carotenoids ↓ CRP, IL-6
↔ TNF-α
[80]
Vascular Health Markers
Endothelial function
Zeaxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 40)
15 g Goji berry for 16 weeks ↔ FMD [85]
Lycopene Meta-analysis Tomato ↑ FMD [40]
RCT, parallel, double-blinded,
Healthy males (n = 126)
6, 15 mg lycopene for 8 weeks ↑ RH-PAT [71]
Arterial stiffness
β-cryptoxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 117)
β-cryptoxanthin–rich satsuma mandarin juice for 12 weeks ↔ PWV [39]
Astaxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 58)
12 mg astaxanthin for 12 months ↔ PWV, AI [91]
Lycopene RCT, parallel, double-blinded,
CVD patients (n = 36),
Healthy subjects (n = 36)
7 mg lycopene for 2 months ↔ PWV, AI [52]
RCT, parallel, single-blinded,
Healthy subjects (n = 225)
Tomato or 10 mg lycopene capsules for 12 weeks ↔ PWV [53]
Vascular structure
Lutein RCT, parallel, double-blinded,
Subjects with subclinical atherosclerosis (n = 144)
20 mg lutein for 12 months ↓ IMT [94]
Zeaxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 40)
15 g Goji berry for 16 weeks ↔ IMT [85]
Astaxanthin RCT, parallel, double-blinded,
Healthy subjects (n = 58)
12 mg astaxanthin for 12 months ↔ IMT [91]
Carotenoid mixture RCT, parallel, double-blinded,
Subjects with subclinical atherosclerosis (n = 144)
20 mg lutein and 20 mg lycopene for 12 months ↓ IMT [94]

Abbreviations: RCT, randomized controlled trial; TG, triglycerides; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; VLDL-C, very low-density lipoprotein cholesterol; SBP, systolic blood pressure; DBP, diastolic blood pressure; ox-LDL, oxidized low-density lipoprotein; LDL, low-density lipoprotein; MDA, malondialdehyde; 8-iso-PGF2α, 8-iso-prostaglandin F2α; LHP, lipid hydroperoxides; HNE, hydroxyl nonenal; F2-isoPs, F2-isoprostanes; ORAC, oxygen radical absorbance capacity; TAOC, total antioxidant capacity; SOD, superoxide dismutase; EC-SOD, extracellular superoxide dismutase; CAT, catalase; G6PD, glucose-6 phosphate dehydrogenase; GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione-S-transferase; DNA, deoxyribonucleic acid; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CRP, C-reactive protein; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α; FMD, flow-mediated dilatation; RH-PAT, reactive hyperemia–peripheral arterial tonometry; PWV, pulse wave velocity; AI, augmentation index; IMT, carotid artery intima–media thickness.