Table 1.
Characteristics of the nine included clinical studies on oral supplementation of saffron or saffron-derived bioactive compounds
| Author (Year) | Study design | Sample size, n | Working diagnosis | Dosage | Duration, m | Main outcomes |
|---|---|---|---|---|---|---|
| Broadhea et al. (2019) [ 44 ] | Randomized, double-blind, placebo-controlled trial. | 100 | Mild to moderate ARMD. | 20 mg/d. | 3 | Modest improvement in BCVA and mfERG response density and latency. |
| Marangoni et al. (2013) [ 73 ] | Longitudinal, interventional study. |
33 | Bilateral early ARMD. | 20 mg/d. | 11 | Significant improvements in fERG sensitivity and amplitude. The improvements in retinal function remained stable throughout the follow-up period. No significant differences in the clinical and fERG improvements were observed across different variants of the CFH or ARMS2 genes. |
| Broadhead et al. (2024) [ 42 ] | Open-label, single-arm extension trial. | 93 | Mild to moderate ARMD. | 20 mg/d. | 12 | Mean mfERG response density was significantly higher in rings 1 and 2 as well as overall. No significant changes in mfERG response density in rings 3–6 and latency in any of the rings. |
| Piccardi et al. (2012) [ 74 ] | Longitudinal, interventional, open-label study. |
29 | Bilateral early ARMD. | 20 mg/d. | 14 | Retinal sensitivity, or the reciprocal value of the estimated fERG amplitude threshold, was the main outcome. Retinal flicker sensitivity significantly improved, as measured by fERG, with mean sensitivity increased by 0.3 log units after 3 months and maintained throughout the follow-up. Visual acuity improved by two Snellen lines. |
| Falsini et al. (2010) [ 75 ] | Randomized, double-blind, placebo-controlled, crossover trial. |
25 | Bilateral early ARMD. | 20 mg/d. | 3 | Patients’ fERG amplitudes increased significantly compared to both baseline and placebo. Decreased fERG thresholds compared to baseline. Placebo supplementation did not result in significant changes in fERG amplitude or threshold. Conclusion: Short-term saffron supplementation improves retinal flicker sensitivity in patients with AMD. |
| Majeed et al. (2021) [ 76 ] | Open-label trial. | 40 | Early-stage dry-type ARMD. | 5 mg/d. | 3 | Improvement in subjective visual symptoms such as diminished and distorted vision scores. At the start of the study, 77.5% of participants had abnormal Amsler grid aberration scores; by day 90 of saffron treatment, only 40% of patients had abnormal Amsler grid aberration scores. |
| Lashay et al. (2016) [ 46 ] | Randomized, double-blind, placebo-controlled trial. |
60 | Wet (30 patients) and dry (30 patients) ARMD. | 30 mg/d. | 6 | In patients with dry AMD, no statistically significant difference in macular thickness measured by OCT between the saffron and placebo groups were detected at 6 months. However, a statistically significant improvement in ERG amplitude was detected in the saffron group compared to placebo at 3 months. In patients with wet AMD, a significant decrease in macular thickness was determined in the saffron group compared to placebo at the 6-months follow-up, and a significant improvement in ERG amplitude were detected in the saffron group compared to the placebo group at 3 months. However, these ERG improvements decreased by 6 months. |
| Piccardi et al. (2019) [ 77 ] | Randomized, double-blind, placebo-controlled trial. |
31 | ABCA4-related STG/FF. | 20 mg/d. | 6 | After saffron supplementation, fERG amplitude remained unchanged from the baseline. After placebo supplementation, fERG amplitude tended to decrease from baseline fERG timing and visual acuity was unchanged throughout the follow-up. |
| Sepahi et al. (2018) [ 78 ] | Randomized, double-blind, placebo-controlled trial. |
60 | Refractory DME. | 5 or 15 mg/d crocin. | 3 | Crocin 15 mg tablets yielded significant improvements in HbA1c, CMT, and BCVA compared to that of the placebo group. Crocin 5 mg tablets also yielded clinical improvements in these parameters; however, the differences were not statistically significant. |
Abbreviations: ARMD, age-related macular degeneration; BCVA, best-corrected visual acuity; mfERG, multifocal electroretinogram; fERG, flicker electroretinogram; OCT, optical coherence tomography; STG/FF, stargardt disease/fundus flavimaculatus; and DME, diabetic macular edema.