Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy

Nutrients. 2019 Oct 15;11(10):2461. doi: 10.3390/nu11102461.

Abstract

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations.

Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity.

Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: -0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up.

Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Keywords: ABCA4 gene mutation; antioxidants; focal electroretinogram; neuroprotection; personalized medicine; photoreceptors; retinal function; saffron.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antioxidants / administration & dosage*
  • Antioxidants / adverse effects
  • Child
  • Crocus*
  • Cross-Over Studies
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Electroretinography
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Oxidative Stress / drug effects*
  • Phenotype
  • Pilot Projects
  • Prospective Studies
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / physiopathology
  • Stargardt Disease / diagnosis
  • Stargardt Disease / drug therapy*
  • Stargardt Disease / genetics
  • Stargardt Disease / physiopathology
  • Time Factors
  • Treatment Outcome
  • Visual Acuity / drug effects*
  • Young Adult

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • Antioxidants

Associated data

  • ClinicalTrials.gov/NCT01278277