The Pharmacokinetic Profile of Crocetin in Healthy Adult Human Volunteers After a Single Oral Administration. Umigai N, Murakami K, Ulit MV, Antonio LS, Shirotori M, Morikawa H, Nakano T. Phytomedicine. 2011, 18, 575-8.

Research design: The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration.

Results: Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T_max) of crocetin ranging from 4.0 to 4.8 h. The mean values of C_max and AUC_{0–24 h} ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C_max and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half-life (T_1/2) of 6.1 to 7.5 h.

Conclusion: There were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as beta-carotene, lutein, and lycopene.

The Effect of Dietary Supplementation of Crocetin for Myopia Control in Children: A Randomized Clinical Trial. Mori K, Torii H, Fujimoto S, Jiang X, Ikeda SI, Yotsukura E, Koh S, Kurihara T, Nishida K, Tsubota K. Journal of Clinical Medicine. 2019, 8, 1179.

Research design: A multi-center randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between −1.5 and −4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks.

Results: A mixed-effects model was used for analysis, using both eyes. The change in SER in the placebo group, −0.41 ± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, −0.33 ± 0.05 D (p = 0.049). The AL elongation in the placebo group, 0.21 ± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (p = 0.046).

Conclusion: Dietary crocetin may have a suppressive effect against myopia progression and axial elongation in children. No adverse effects associated with crocetin administration were reported during the clinical study.

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice. Mori K, Kurihara T, Jiang X, Ikeda SI, Yotsukura E, Torii H, Tsubota K. Nutrients. 2020, 12, 180.

Research design: To investigate the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a −30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage.

Results: A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow.

Conclusion: 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model.

Feasibility Study and Evaluation of MegaCro™ Gardenia Used for Myopia. Yin Hui, Li Chunxiang. 2022.

Research design: This work was conducted to study and compare the effect of MegaCro™ Gardenia with Market Crocetin on cultured Human scleral fibroblasts (HSFs) under normal culture condition (37°C, 20% O2 and 5% CO2) and low O2 condition (37°C, < 1% O2 and 5% CO2).

Results: Both MegaCro™ Gardenia and Market Crocetin showed growth promotion effect on HSFs under normal culture condition, with 121 ± 4.2 % for Market Crocetin and 128 ± 7.3 % for MegaCro™ Gardenia at a concentration of 0.1 mg/mL respectively. While under low O2 condition, the growth promotion effect was only observed in the case of MegaCro™ Gardenia, with the highest viable cells (125.3 ± 5 %) at a concentration of 0.025 mg/ml. Market Crocetin tends to be more toxic than MegaCro™ Gardenia under low O2 condition, especially when its concentration is 0.025 mg/ml and above. In addition, the expression of IL-6 of HSFs treated with MegaCro™ Gardenia and Market Crocetin under low O2 was obviously lower than that of untreated HSFs.

Conclusion: MegaCro™ Gardenia showed a growth promotion effect of 20% better than Market Crocetin, and both MegaCro™ Gardenia and Market Crocetin reduced IL-6 expression under low O2 condition, which contribute to myopia control.