Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial

  • Geoffrey K. Broadhead
  • John R. Grigg
  • Peter McCluskey
  • Thomas Hong
  • Timothy E. Schlub
  • Andrew A. ChangEmail author
Retinal Disorders



To assess the efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD).


Randomised, double-blinded, placebo-controlled crossover trial of 100 adults (> 50 years) with mild/moderate AMD and vision > 20/70 Snellen equivalent in at least one eye. Exclusion criteria included confounding visual lesions, or significant gastrointestinal disease impairing absorption. Participants were given oral saffron supplementation (20 mg/day) for 3 months or placebo for 3 months, followed by crossover for 3 months. Participants already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these. Primary outcomes included changes in best-corrected visual acuity (BCVA) and changes in multifocal electroretinogram (mfERG) response density and latency. Secondary outcomes included safety outcomes and changes in mfERG and BCVA amongst participants on AREDS supplements.


Mean BCVA improved 0.69 letters (p = 0.001) and mean-pooled mfERG latency reduced 0.17 ms (p = 0.04) on saffron compared to placebo. Amongst participants on AREDS supplements, mean BCVA improved 0.73 letters p = 0.006) and mean-pooled mfERG response density improved 2.8% (p = 0.038). There was no significant difference in adverse event occurrence (p > 0.10).


Saffron supplementation modestly improved visual function in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.


Clinical trials Age-related macular degeneration Saffron Electroretinogram Nutritional supplementation 



No authors have any conflicts of interest to declare. One previous researcher associated with this study who had no participant contact, was previously required to withdraw his involvement from the study due to a conflict of interest. This individual is not an author on this manuscript. Preliminary data from this study was presented at the Royal Australian College of Ophthalmologists Annual Congress, Melbourne, Victoria, Australia, November 2016.


No funding was received for this research. No funding was associated with the design, conduct or data analysis of this trial. Dr. Chang has previously acted as a consultant for Novartis, Bayer and Alcon.

Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licencing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Klein R, Lee KE, Gangnon RE, Klein BE (2013) Incidence of visual impairment over a 20-year period: the Beaver Dam Eye Study. Ophthalmology 120:1210–1219CrossRefGoogle Scholar
  2. 2.
    Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431CrossRefGoogle Scholar
  3. 3.
    Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444CrossRefGoogle Scholar
  4. 4.
    Chew EY, Clemons TE, Agron E et al (2013) Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology 120:1604–1611CrossRefGoogle Scholar
  5. 5.
    Age-Related Eye Disease Study Research Group (2001) A randomized placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 119:1417–1436CrossRefGoogle Scholar
  6. 6.
    Age-Related Eye Disease Study 2 Research Group (2013) Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA 2309:2005–2015Google Scholar
  7. 7.
    Purushothuman S et al (2013) Saffron pre-treatment offers neuroprotection to nigral and retinal dopaminergic cells of MPTP-treated mice. J Parkinsons Dis 3:77–83Google Scholar
  8. 8.
    Akhondzadeh S, Shafiee Sabet M, Harirchian MH et al (2010) A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology 207:637–643CrossRefGoogle Scholar
  9. 9.
    Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 50:761–786CrossRefGoogle Scholar
  10. 10.
    Mohamadpour AH et al (2013) Safety evaluation of Crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 16:39–46Google Scholar
  11. 11.
    Falsini B et al (2010) Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 51:6118–6124CrossRefGoogle Scholar
  12. 12.
    Piccardi M et al (2012) A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Alternat Med 2012:429124CrossRefGoogle Scholar
  13. 13.
    Age-Related Eye Disease Study Research Group (2001) The age-related eye disease study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the age-related eye disease study report number 6. Am J Ophthalmol 132(5):668–681CrossRefGoogle Scholar
  14. 14.
    Age-Related Eye Disease Study Research Group (2001) The age-related eye disease study (AREDS) system for classifying cataracts from photographs: AREDS report no. 4. Am J Ophthalmol 131:167–175CrossRefGoogle Scholar
  15. 15.
    Phipps JA, Dang TM, Vingrys AJ, Guymer RH (2004) Flicker perimetry losses in age-related macular degeneration. Invest Ophthalmol Vis Sci 45:3355–3360CrossRefGoogle Scholar
  16. 16.
    Hood DC, Bach M, Brigell M et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13CrossRefGoogle Scholar
  17. 17.
    McCulloch DL et al (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12CrossRefGoogle Scholar
  18. 18.
    Murray IJ et al (2013) Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study. Invest Ophthalmol Vis Sci 54:1781–1788CrossRefGoogle Scholar
  19. 19.
    Souied EH, Delcourt C, Querques G et al (2013) Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the nutritional AMD treatment 2 study. Ophthalmology 120:1619–1631CrossRefGoogle Scholar
  20. 20.
    Schleicher M, Weikel K, Garber C, Taylor A (2013) Diminishing risk for age-related macular degeneration with nutrition: a current view. Nutrients 5:2405–2456CrossRefGoogle Scholar
  21. 21.
    Bisti S, Maccarone R, Falsini B (2014) Saffron and retina: neuroprotection and pharmacokinetics. Vis Neurosci 31:355–361CrossRefGoogle Scholar
  22. 22.
    Chen L, Qi Y, Yang X (2015) Neuroprotective effects of crocin against oxidative stress induced by ischemia/reperfusion injury in rat retina. Ophthalmic Res 54:157–168CrossRefGoogle Scholar
  23. 23.
    Ishizuka F et al (2013) Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice. Eur J Pharmacol 703:1–10CrossRefGoogle Scholar
  24. 24.
    Ma L, Dou HL, Huang YM et al (2012) Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. Am J Ophthalmol 154:625–634CrossRefGoogle Scholar
  25. 25.
    Berrow EJ, Bartlett HE, Eperjesi F, Gibson JM (2013) The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy -- a randomised controlled trial. Br J Nutr 109:2008–2014CrossRefGoogle Scholar
  26. 26.
    Ambrosio L et al (2015) The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD. Doc Ophthalmol 131:125–135CrossRefGoogle Scholar
  27. 27.
    Yavas GF, Kusbeci T, Inan UU (2014) Multifocal electroretinography in subjects with age-related macular degeneration. Doc Ophthalmol 129:167–175CrossRefGoogle Scholar
  28. 28.
    Hood DC, Frishman LJ, Saszik S, Viswanathan S (2002) Retinal origins of the primate multifocal ERG: implications for the human response. Invest Ophthalmol Vis Sci 43:1673–1685Google Scholar
  29. 29.
    Yang S et al (2016) Photoreceptor dysfunction in early and intermediate age-related macular degeneration assessed with mfERG and spectral domain OCT. Doc Ophthalmol 132:17–26CrossRefGoogle Scholar
  30. 30.
    Li J, Tso MO, Lam TT (2001) Reduced amplitude and delayed latency in foveal response of multifocal electroretinogram in early age related macular degeneration. Br J Ophthalmol 85:287–290CrossRefGoogle Scholar
  31. 31.
    Gerth C et al (2003) Assessment of multifocal electroretinogram abnormalities and their relation to morphologic characteristics in patients with large drusen. Arch Ophthalmol 121:1404–1414CrossRefGoogle Scholar
  32. 32.
    Wu Z, Ayton LN, Guymer RH, Luu CD (2014) Comparison between multifocal electroretinography and microperimetry in age-related macular degeneration. Invest Ophthalmol Vis Sci 55:6431–6439CrossRefGoogle Scholar
  33. 33.
    Age-Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no 9. Arch Ophthalmol 119:1439–1452CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Geoffrey K. Broadhead
    • 1
    • 2
    • 3
  • John R. Grigg
    • 1
  • Peter McCluskey
    • 1
  • Thomas Hong
    • 2
    • 3
  • Timothy E. Schlub
    • 4
  • Andrew A. Chang
    • 1
    • 2
    • 3
  1. 1.Save Sight InstituteThe University of SydneySydneyAustralia
  2. 2.Sydney Institute of Vision ScienceSydneyAustralia
  3. 3.Sydney Retina Clinic & Day SurgerySydneyAustralia
  4. 4.Sydney School of Public HealthThe University of SydneySydneyAustralia

Personalised recommendations