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Saffron Extract Improves Retinal Function in Patients with Early Age-Related Macular Degeneration


Reviewed: Piccardi M, Marangoni D, Minnella AM, et al. 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;[epub ahead of print]. doi: 10.1155/2012/429124.

Common signs of early age-related macular degeneration (AMD) include large, soft drusen (subretinal pigment epithelial deposits that are co-characteristic of, but not uniquely associated with, AMD); hyper/hypopigmentation of the retinal pigment epithelium (RPE); and mild-to-moderate loss of central vision. In the late stages of the disease, the RPE atrophies, severely impairing central vision — a major cause of irreversible vision loss in the elderly.

Several factors have been associated with the risk for photoreceptor degeneration/dysfunction in AMD patients. Some documented risk factors appear to be oxidative and/or proinflammatory in nature,1-3 while corresponding protective factors are antioxidant and/or anti-inflammatory.4-6 In an earlier randomized clinical trial,7 the investigators reported that short-term (three month) saffron (Crocus sativus, Iridaceae) supplementation improved retinal flicker sensitivity in patients with AMD. In this clinical trial, the authors report on their longitudinal, open-label study that evaluated whether the observed functional benefits of saffron supplementation are reproducible over a longer follow-up duration.

Twenty-nine patients (mean age = 69.3 ± 7 years) with a diagnosis of bilateral early AMD were recruited over an eight-month period from outpatients of the eye, ear, nose, and throat department of the Università Cattolica del Sacro Cuore in Rome, Italy. Sixteen men and 13 women underwent standard general and ophthalmic examinations. Clinical diagnosis of early AMD was established by direct and indirect ophthalmoscopy, as well as retinal biomicroscopy, when any of the following lesions in the macular area of one or both eyes was identified: soft distinct or indistinct drusen, areas of hyperpigmentation associated with drusen, or areas of hypopigmentation of the RPE associated with drusen, without any visibility of choroidal vessels.

The patients had to have a best-corrected visual acuity of 0.5 or better in the studied eye, central fixation (to see clearly by using the center of the visual field), normal color vision, no signs of other retinal or optic nerve disease, and clear optical media (eyes that do not have cataracts, corneal scars, or other obstructions).

Patients underwent a clinical examination and a focal electroretinogram (fERG)-derived macular (18°) flicker sensitivity estimate at baseline and every three months over a 15-month period of treatment and follow-up. The treatment material was 20 mg of saffron daily (Zaffit™; Hortus Novus; L’Aquila, Italy).

The main outcome was fERG sensitivity derived from the estimated response amplitude thresholds. (fERGs measure the rapid change in the resting ocular potential caused by exposure to a flash of light and can provide information about the macular function.) Visual acuity was a secondary outcome. The authors reported an overall increase in fERG amplitude soon after the first three months of supplementation, followed by stabilization over the subsequent follow-up period. Mean fERG threshold decreased by 0.3 log units compared with baseline values (P<0.01) and remained stable during the follow-up period.

At the third month of supplementation, mean visual acuity improved by two Snellen lines (chart commonly used by eye professionals to measure visual acuity) compared to baseline values (P<0.01) and remained stable during the study period. All patients reported improved vision, particularly improved contrast and color perception, reading ability, and vision at low levels of luminous intensity. Periodic funduscopic examination did not show any significant change in drusen number or size, or in the extent of RPE abnormalities.

These results show that saffron supplementation may induce a long-term, stable improvement in retinal function, as measured by fERG responses. The changes in fERG threshold after supplementation were within-session consistent, reproducible, and durable over the 15-month follow-up period.

According to the authors, this study is limited by “its open-label nature, which may have affected mainly the subjective patients’ results, and the assumed stability of the main outcome measure, the fERG, without treatment.”

The improved macular function, the authors said, may result from the combined activity of saffron’s phytochemical compounds, especially the carotenoid derivatives crocin and crocetin, which possess antioxidant properties and may act through a protective mechanism similar to that seen with carotenoid supplementation. Results from an earlier study in rats8 showed that saffron may protect photoreceptors against retinal stress, maintaining both morphology and function, and probably downregulating programmed cell death.

The authors note that their results can be applied only to patients in the early or moderate stage of AMD. Whether saffron supplementation exerts a beneficial protective effect in patients with more advanced stages of the disease is unknown. Also unclear is how saffron’s efficacy compares with that of other available antioxidant supplements. According to the authors, “While further studies are needed to define the upper beneficial limit of saffron supplementation, the present approach seems to be promising for a long-term treatment of early retinal dysfunction associated with AMD.”

The saffron pills and additional support were provided by Hortus Novus.

—Shari Henson


  1. Hageman GS, Anderson DH, Johnson LV, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005;102(20):7227-7232.
  2. Hollyfield JG, Bonilha VL, Rayborn ME, et al. Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med. 2008;14(2):194-198.
  3. Rivera A, Fisher SA, Fritsche LG, et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet. 2005;14(21):3227-3236.
  4. Age-Related Eye Disease Study Research Group. 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. 2001;119(10):1417-1436.
  5. Weismann D, Hartvigsen K, Lauer N, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress.Nature. 2011;478(7367):76-81.
  6. Wong WT, Kam W, Cunningham D, et al. Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. Invest Ophthalmol Vis Sci. 2010;51(12):6131-6139.
  7. Oppel-Sutter M. Saffron supplementation improves visual acuity symptoms of early age-related macular degeneration. HerbClip. November 15, 2010 (No. 101061-412). Austin, TX: American Botanical Council. Review of Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration by Falsini B, Piccardi M, Minnella A, et al. Invest Ophthalmol Vis Sci. 2010;51(12):6118-6124.
  8. Maccarone R, Di Marco S, Bisti S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthalmol Vis Sci. 2008;49(3):1254-1261.