Skip to main content

Advertisement

SpringerLink
Log in

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

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

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

Methods

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.

Results

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).

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  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 120:1210–1219

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431

    Article  CAS  PubMed  Google Scholar 

  3. Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444

    Article  CAS  PubMed  Google Scholar 

  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 120:1604–1611

    Article  PubMed  PubMed Central  Google Scholar 

  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 119:1417–1436

    Article  PubMed Central  Google Scholar 

  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 2309:2005–2015

    Google Scholar 

  7. Purushothuman S et al (2013) Saffron pre-treatment offers neuroprotection to nigral and retinal dopaminergic cells of MPTP-treated mice. J Parkinsons Dis 3:77–83

    CAS  PubMed  Google Scholar 

  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 207:637–643

    Article  CAS  PubMed  Google Scholar 

  9. Bathaie SZ, Mousavi SZ (2010) New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr 50:761–786

    Article  CAS  PubMed  Google Scholar 

  10. Mohamadpour AH et al (2013) Safety evaluation of Crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 16:39–46

    PubMed  PubMed Central  Google Scholar 

  11. Falsini B et al (2010) Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 51:6118–6124

    Article  PubMed  Google Scholar 

  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 2012:429124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):668–681

    Article  Google Scholar 

  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 131:167–175

    Article  Google Scholar 

  15. Phipps JA, Dang TM, Vingrys AJ, Guymer RH (2004) Flicker perimetry losses in age-related macular degeneration. Invest Ophthalmol Vis Sci 45:3355–3360

    Article  PubMed  Google Scholar 

  16. Hood DC, Bach M, Brigell M et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13

    Article  PubMed  Google Scholar 

  17. McCulloch DL et al (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12

    Article  PubMed  Google Scholar 

  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 54:1781–1788

    Article  CAS  PubMed  Google Scholar 

  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 120:1619–1631

    Article  PubMed  Google Scholar 

  20. Schleicher M, Weikel K, Garber C, Taylor A (2013) Diminishing risk for age-related macular degeneration with nutrition: a current view. Nutrients 5:2405–2456

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bisti S, Maccarone R, Falsini B (2014) Saffron and retina: neuroprotection and pharmacokinetics. Vis Neurosci 31:355–361

    Article  PubMed  Google Scholar 

  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 54:157–168

    Article  CAS  PubMed  Google Scholar 

  23. Ishizuka F et al (2013) Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice. Eur J Pharmacol 703:1–10

    Article  CAS  PubMed  Google Scholar 

  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 154:625–634

    Article  CAS  PubMed  Google Scholar 

  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 109:2008–2014

    Article  CAS  PubMed  Google Scholar 

  26. Ambrosio L et al (2015) The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD. Doc Ophthalmol 131:125–135

    Article  CAS  PubMed  Google Scholar 

  27. Yavas GF, Kusbeci T, Inan UU (2014) Multifocal electroretinography in subjects with age-related macular degeneration. Doc Ophthalmol 129:167–175

    Article  PubMed  Google Scholar 

  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 43:1673–1685

    PubMed  Google Scholar 

  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 132:17–26

    Article  PubMed  Google Scholar 

  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 85:287–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gerth C et al (2003) Assessment of multifocal electroretinogram abnormalities and their relation to morphologic characteristics in patients with large drusen. Arch Ophthalmol 121:1404–1414

    Article  PubMed  PubMed Central  Google Scholar 

  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 55:6431–6439

    Article  PubMed  Google Scholar 

  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 119:1439–1452

    Article  PubMed Central  Google Scholar 

Download references

Acknowledgments

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.

Funding

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.

Author information

Authors and Affiliations

  1. Save Sight Institute, The University of Sydney, 8 Macquarie Street, Sydney, NSW, 2000, Australia

    Geoffrey K. Broadhead, John R. Grigg, Peter McCluskey & Andrew A. Chang

  2. Sydney Institute of Vision Science, Sydney, Australia

    Geoffrey K. Broadhead, Thomas Hong & Andrew A. Chang

  3. Sydney Retina Clinic & Day Surgery, Sydney, Australia

    Geoffrey K. Broadhead, Thomas Hong & Andrew A. Chang

  4. Sydney School of Public Health, The University of Sydney, Sydney, Australia

    Timothy E. Schlub

Authors
  1. Geoffrey K. Broadhead
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John R. Grigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter McCluskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy E. Schlub
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew A. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew A. Chang.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Broadhead, G.K., Grigg, J.R., McCluskey, P. et al. Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial. Graefes Arch Clin Exp Ophthalmol 257, 31–40 (2019). https://doi.org/10.1007/s00417-018-4163-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-018-4163-x

Keywords

Search

Navigation