[91] | NCT00345176 | Multicenter, randomized, double-masked, placebo-controlled phase 3 study | 7 years | Patients N = 4203 Age range: 50–85 years Age (mean ± SD): 73.1 ± 7.7 Sex: 56.8% Female | Primary randomization: G 1: AREDS formulation G 2: AREDS, L 10 mg, Z 2 mg G 3: AREDS, DHA 350 mg, EPA 650 mg G 4: AREDS, L 10 mg, Z 2 mg, DHA 350 mg, EPA 650 mg | No statistically significant reduction in progression to advanced AMD was observed (p = 0.12 for L + Z). |
Secondary randomization: G 1: AREDS supplement G 2: AREDS supplement with no beta carotene G 3: AREDS with low dose zinc (25 mg) G 4: AREDS supplement with no beta carotene and with low-dose zinc |
[92] | ISRCTN60816411 | Single-blind, randomized controlled clinical trial | 3 years | Patients N = 67 (52 completed Age (mean ± SD): 66 ± 8 Sex: 65.4% Female | G 1: 20 mg L, 0.86 mg Z G 2: 10 mg MZ, 10 mg L, 2 mg Z G 3: 17 mg MZ, 3 mg L, 2 mg Z | No statistically significant change in AMD grade between intervention groups (p = 0.29, Fisher’s exact test). |
[93] | ISRCTN 94557601 | Randomized double-masked placebo-controlled clinical trial | Each participant was followed up for up to 3 years | Patients N = 433 Age range: 50–95 years Age (mean ± SD): 75.9 ± 7.7 Sex: 57.3% Female | G1: A tablet was taken twice daily to deliver a daily dose of 12 mg L, 0.6 mg Z, 15 mg d-α-tocopherol, 150 mg ascorbic acid, 20 mg zinc oxide, and 0.4 mg copper gluconate G2: Placebo (made up of cellulose, lactose, and magnesium stearate) | 4.8 letters better BCVA was seen in active group than placebo group, which was statistically significant (p = 0.04). Visual acuity increased by 1.4 letters with 1-log-unit increase in serum lutein. Morphologic severity progressed slowly. |
[94] | ISRCTN 17842302 | Randomized clinical trial on participants with AMD | 60 weeks | Patients N = 14 Age range: 56–83 years Age (mean ± SD): 67.3 ± 8.5 | G1: Ascorbic acid 150 mg, cupric oxide 400 µg, DL-α-tocopherol 15 mg, zinc oxide 20 mg, lutein 12 mg, Z 0.6 mg, EPA 240 mg, DHA 840 mg G2: No supplement | A nonsignificant latency and reduced amplitudes of multifocal electroretinography (mfERG) was seen on supplement withdrawal (ring 3 N2 latency, p = 0.041 and ring 4 P1 latency, p = 0.016). |
[95] | - | Double-blind and placebo-controlled clinical trial | 140 days | Patients N = 100 Age range: 18–64 years Sex: 48% Female | G1: Placebo G2: 5 mg L G3: 10 mg L G4: 20 mg L (younger group) G5: 20 mg L (older group) | A linear, dose-dependent increase in macular pigment optical density (MPOD) was observed (p < 0.0001). |
[96] | NCT00763659 | A prospective, randomized double-blind, placebo controlled clinical trial on patients with non-exudative AMD | 12 months | Patients N = 172 Age (mean ± SD): 70 ± 10 Sex: 54.7% Female | G1: 10 mg L, 1 mg Z, 255 mg concentrated fish oil (100 mg DHA, 30 mg EPA), 60 mg vitamin C, 20 mg vitamin E, 10 mg zinc, 0.25 mg copper G2: 20 mg L, 2 mg Z, 500 mg concentrated fish oil (200 mg DHA, 60 mg EPA) and 120 mg vitamin C, 40 mg vitamin E, 20 mg zinc, 0.5 mg copper G3: Placebo | Statistically significant increase in MPOD was seen in both G1 and G2 (p < 0.001). Supplementation with L and Z improved and stabilized BCVA in AMD patients. |
[97] | - | Clinical trial on patients with unilateral wet AMD and patients with unilateral cCSC | 6 months | Patients N = 20 Age: >56 years Age (mean ± SD): 66 ± 4 Sex: 30% Female | Sante Lutax 20 plus DHA (20 mg L, 1 mg Z, and 200 mg DHA) | MPOD (p = 0.032) and contrast sensitivity (p < 0.05) improved. L, Z, DHA dietary supplement had beneficial effects. |
[98] | NCT00909090 | Randomized, double-blind, placebo-controlled clinical trial | 400 days | Patients N = 115 (109 completed) Age (mean ± SD): 23.2 ± 4 Sex: 59.6% Female | G1: 10 mg L, 2 mg Z G2: Placebo | MPOD (p < 0.0001), chromatic contrast (p < 0.0001) and photostress recovery time (p = 0.002) improved significantly. |
[99] | NCT10528605 | Randomized, double-blind, placebo controlled trial on patients with early AMD | 2 years | Patients N = 112 Age: >50 years Age (mean ± SD): 69.1 ± 7.3 Sex: 57.4% Female | G1: Placebo G2: 10 mg L G3: 20 mg L G4: L 10 mg, Z 10 mg | MPOD, retinal sensitivity, N1P1 response densities in ring 1 and ring 2 increased significantly in G2, G3, G4 (all p < 0.05) |
[100] | ISRCTN54990825 | A double-blind, placebo-controlled | 12 weeks | Healthy subjects N = 32 Age range: 18–25 years | G1: Placebo G2: 6.18 mg L, 0.73 mg Z, 0.53 mg MZ (total 7.44 mg) G3: 10.86 mg L, 1.33 mg Z, 0.94 mg MZ (total 13.13 mg) G4: 22.33 mg L, 2.70 mg Z, 2 mg MZ (total 27.03 mg) | Serum level increased linearly with increased dose. Group 3 showed the highest ratio of MPOD change, which was statistically significant (p = 0.021). |
[101] | - | Randomized, double masked, placebo-controlled trial | 10 years | Patients and healthy subjects N = 39,876 Age range: ≥45 years Age (mean): 53.5 (no cataract), 61 (cataract) Sex: 100% Female | β-carotene, vitamin A, and vitamin E | Only 2031 people developed cataract. Most of them were smokers, had high BMI, and reported a history of hypertension, diabetes, and high cholesterol. Higher dietary intakes of L/Z (p = 0.04) and vitamin E (p = 0.03) significantly decreased the risk of cataract. |
[102] | - | Prospective study | 5 years | Patients and healthy subjects N = 400 Age range: 50–86 years Sex: Both male and Female | No supplement was provided. Serum concentrations of individual carotenoids, α- and γ-tocopherol were determined | Serum carotenoids did not have significant association with nuclear cataract prevention (p = 0.13). |
[103] | - | Cohort study | 10 years | Patients and healthy subjects N = 5925 Age range: 43–84 years Sex: Both male and Female | Intake of L and Z was assessed using a food frequency questionnaire | L (intake in the distant past) had protective influence on the development of nuclear cataracts (p = 0.002). |
[104] | - | Prospective study | 8 years | Patients and healthy subjects N = 36,644 Age range: 45–75 years Sex: 0% Female | Dietary questionnaire was used to assess | A statistically significant lower risk of cataract in higher intakes of L and Z was observed (p = 0.03). No impact of other carotenoids (α-carotene, β-carotene, lycopene, and β-cryptoxanthin) are found in cataract prevention |
[105] | - | Prospective cohort study | 12 years | Patients and healthy subjects N = 77,466 Age range: 45–71 years | Food frequency questionnaire was used to assess | Foods rich in carotenoids (L and Z) decreased the risk of cataracts (22%) (p = 0.04). |
[106] | NCT00000145 | Clinic-based, baseline cross-sectional and prospective cohort study | 9.6 years | Patients N = 3115 Age range: 55–80 years Sex: Both male and Female | Food frequency questionnaires | No significant association of L plus Z intake with the development of nuclear or cortical lens opacity. |
[107] | NCT00000145 | 11-center age-related eye disease study double-masked clinical trial | 6.3 years | Patients N = 4757 Age range: 55–80 years Sex: 56% Female | G1: Antioxidants (β-carotene 15 mg, vitamin C 500 mg; vitamin E, 400 IU) G2: Antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and β-carotene, 15 mg) + zinc 80 mg + copper 2 mg G3: Zinc 80 mg + copper 2 mg G4: Placebo | No statistically significant effect was observed on the progression or prevention of cataract, age-related macular degeneration, age-related lens opacities, or visual acuity loss. |
[108] | NCT00345176 | Randomized, double-masked, controlled clinical trial, cohort study. | 5 years | Patients N = 4203 Age range: 50–80 years Sex: 56.8% Female | G1: Control group G2: L 10 mg and Z 2 mg G3: Docosahexaenoic acid (DHA 350 mg) and eicosapentaenoic acid (EPA 650 mg) G4: L 10 mg and Z 2 mg, docosahexaenoic acid (DHA 350 mg) and eicosapentaenoic acid (EPA 650 mg) | Carotenoid supplementation did not have any significant positive or negative impact on the high mortality rate observed in people having age-related macular disease. |
[109] | - | Randomized, double-masked, placebo-controlled trial | 12 years | Patients and healthy subjects N = 22,071 Age range: 40–84 years Sex: 0% Female | β-carotene (50 mg) or placebo | β-carotene supplementation had no overall beneficial or harmful effect on cataract or cataract extraction. |
[110] | NCT00000479 | Randomized, double masked, placebo-controlled trial | 2.1 years | Patients and healthy subjects N = 39,876 Age: ≥45 years Sex: 100% Female | G1: β-carotene G2: Placebo | No large beneficial or harmful effect was found on the development of cataract. |
[111] | - | Multi-centered, prospective, double-masked, randomized, placebo-controlled trial | 3 years | Patients N = 445 Age (mean ± SD): 66.2 ± 8.9 Sex: 59.3% Female | G1: 6 mg β-carotene, 200 mg α-tocopherol acetate (Vitamin E) and 250 mg ascorbic acid G2: Placebo | A small, statistically significant reduction in the progression of age-related cataract was observed after three years of treatment (p = 0.048). |
[112] | NCT00342992 | Randomized, double-blind, placebo-controlled clinical trial | 5 to 8 years (median 6.6 years) | Patients N = 1828 Age range: 50–69 years Sex: 0% Female | G1: α-tocopherol 50 mg/day, G2: β-carotene 20 mg/day, G2: A combination of the two G4: placebo | No influence of supplementation on cataract prevalence. |
[113] | NCT0140845 | Prospective, randomized, double-masked multicenter study | 24 months | Patients N = 126 Age (mean ± SD): 75.3 ± 7.6 Sex: 58.7% Female | G1: Carotenoids (5 mg of L and 1 mg of Z) + (560 mg of DHA, 420 mg GLA, 80 mg of vitamin C, 10 mg of vitamin E, 2 mg of vitamin B6, 200 g of Vitamin B9, 1 g of vitamin B12, 10 mg of Zinc) G2: Placebo + (560 mg of DHA, 420 mg GLA, 80 mg of vitamin C, 10 mg of vitamin E, 2 mg of vitamin B6, 200 g of Vitamin B9, 1 g of vitamin B12, 10 mg of Zinc) | Carotenoid supplementation did not improve MPOD, which was exacerbated by cataract and age-related macular degeneration. |
[114] | - | Randomized, double-blind, placebo-controlled supplementation study | 2 years | Patients N = 17 Age range: 55–73 years Sex: 86.7% Female | G1: 12 mg of all-trans-lutein, 3 mg of 13/15-cis-lutein, 3.3 mg of alpha-tocopherol G2: 100 mg of alpha-tocopherol G3: Placebo (0.06 mg of alpha-tocopherol, 0.23 mg of gamma-tocopherol, 500 mg of corn oil) | L has beneficial effect on age-related cataracts, whereas alpha-tocopherol was not beneficial. |
[115] | NCT01269697 | Phase 3, double-blind, randomized clinical trial | 6 months | Healthy subjects N = 120 Age range: 40–70 years Age (mean ± SD): 56.7 ± 6.6 Sex: 71.7% Female | G1: L 5 mg, Z 1 mg, vitamin C (90 mg), vitamin E (15 mg), zinc (7.5 mg), copper (<0.5 mg), and resveratrol (0.5 mg), 33 mg of fish oil (50% ω-3) G2: Placebo | An increase in plasma L and Z concentrations was observed (p < 0.005) but no elevation of MPOD was found. |
[116] | NCT00029289 | Double-masked randomized placebo-controlled clinical trial with a crossover design | 24 weeks | Patients N = 34 Age (mean ± SD): 49.2 ± 9 Sex: 61.8% Female | G1: L 10 mg/d for 12 weeks, 30 mg/d for next 12 weeks, followed by placebo for 24 weeks G2: Placebo 24 weeks, followed by L 10 mg/d for 12 weeks, followed by 30 mg/d for next 12 weeks | Significantly improved visual field (p = 0.038), slightly improved visual acuity. L 10–30 mg/day for up to 6 months was safe. |