Saffron has photoreceptor- and neuro-protecive effects in macular degeneration

Saffron is reported as a treatment for macular degeneration

Saffron is an ancient spice that has been used across Europe and Asia for its fascinating colour and invigorating aroma.

Saffron for its effects on cellular targets and for possessing many beneficial effects in age-related macular degeneration (AMD), an eye problem prevalent among seniors aged 50 and over, is a superior ingredient for an optimal eye health nutritional supplement, to help promote eye health and stop vision loss. Saffron contains carotenoids crocin and crocetin that have shown strong protective effects on retinal cells, helping restore function and structure of retinal cells damaged by oxidative stress in age-related macular degeneration.1,2

A recent clinical study has shown that taking oral supplementation of saffron for three months in patients with early stage age-related macular degeneration induced a significant improvement of retinal function, creating a hope that saffron may be the natural answer to vision loss from macular degeneration.  The effects, however, disappeared when patients stopped taking the saffron pills. No adverse side effects were noticed in patients. 2 According to Professor Silvia Bisti who carried out the research in patients with age-related macular degeneration, ‘Patients’ vision improved after taking the saffron pill’ 3,4.

In a 15-month follow-up study, the clinicians observed that patients continued to get the benefits of the supplement for as long as they took the saffron capsules. In the extended study patients experienced:

“improvement in contrast and colour perception, reading ability, and vision at low luminances, all ultimately leading to a: substantial improvement in the patients’ quality of life.”

This new study showed that taking saffron supplementation for long term presents a safe natural solution to help prevent eyesight loss in old age, and as reported:

“no adverse systemic side effects were recorded.” 4-a

The beneficial effects of saffron in early age-related macular degeneration is unique, not seen with AREDS formulation which is most effective in slowing the progression of disease in individuals with high risk of developing the advanced form of AMD, i.e., progression from intermediate AMD to advanced AMD. Vision loss due to age-related macular degeneration has debilitating effects on quality of life, and therefore any successful intervention at the early stage can lead to significant improvement in quality of life in individuals affected by macular degeneration.

Saffron is a spice that contains the antioxidant carotenoids crocin and crocetin among other ingredients, with strong antioxidative, and cell-/neuro-protective properties. 5

The antioxidant property of crocin is stronger than alpha-tocopherol, and can prevent the formation of peroxidized lipids, and can partly restore superoxide dismutase (SOD) activity. 6

The first report on eye health benefits of saffron in macular degeneration and its main active compound, crocin, came from Xuan and co-workers in 1999 that suggested crocin and its analogs can be used to treat ischemic retinopathy and/or age-related macular degeneration. They showed that crocin analogs significantly increased blood flow in the retina and choroid, and thus can prevent cell death. 7

Saffron also protects eye from damaging effects of bright light, which is a risk factor causing damage and degeneration of macula of the eye, which lead to AMD. The carotenoid crocin has protective effect against blue light- and white light-induced rod and cone death in bovine and primate retinal cell cultures. 8 Saffron’s protective effect against light damage on photoreceptors appears to be via maintaining both morphology and function of photoreceptors, 9  and especially by regulations of genes involved in maintaining integrity of cell structure. 1

Light exposure leads to photoreceptor degeneration, and several epidemiologic studies have suggested that long-term history of exposure to light may have some impact on the incidence and progression of age-related macular degeneration, and saffron might be a natural solution to protect eyes from light damage. 10,11


Crocetin, which is another carotenoid in saffron, significantly inhibited photoreceptor degeneration and retinal dysfunction in in-vitro and in-vivo models. This retinal protective effect was shown to be mediated by inhibiting an increase in caspase-3 and -9. 12

A recent microarray study showed that saffron appears to have direct regulatory effect on oxidative protection of retina by regulating expression of retinal genes with neuroprotective functions (for example: Crot, Optn, Edn2, Smarcad1, Gpx3), particularly the most regulated gene are those that are adversely regulated by light-induced photoreceptor damage. 1

The neuroprotective property of saffron have been further investigated on retinal ganglion cells (RGCs) after retinal ischaemia/reperfusion (IR) injury. Recent results showed that crocin acted through activation of the PI3K/AKT signalling pathway preventing retinal IR-induced apoptosis of RGCs. 13

A recent study  investigated the effects of oral administration of crocetin on damage induced by N-methyl-D-aspartate (NMDA) in the murine retina. NMDA injection activated caspase-3/7 and increased expression of cleaved caspsase-3 in the ganglion cell layer (GCL) and inner nuclear layer (INL). crocetin inhibited both of these processes. The protective effect  was attributable to oral administration of crocetin , which prevented NMDA-induced retinal damage via inhibition of the caspase pathway. 14

Scientific references:

1- Natoli R, Zhu Y, Valter K, Bisti S, Eells J, Stone J (2010). Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Mol Vis 16: 1801-1822.

2- Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S. (2010). Saffron Supplementation Improves Retinal Flicker Sensitivity in Early Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 51: 6118-6124.



4-a – Piccardi M, Marangoni D, Minnella AM, et al. (2012). A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evidence-Based Complementary and Alternative Medicine. Volume 2012, doi:10.1155/2012/429124.

5- Schmidt M, Betti G, Hensel A. (2007). Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 157: 315-319.

6- Ochiai T, Ohno S, Soeda S, Tanaka H, Shoyama Y, Shimeno H. (2004). Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha-tocopherol. Neurosci Lett  362:61-64.

7- Xuan B, Zhou YH, Li N, Min ZD, Chiou GC. (1999). Effects of crocin analogs on ocular blood flow and retinal function. J Ocul Pharmacol Ther 15:143-152.

8- Laabich A, Vissvesvaran GP, Lieu KL, Murata K, McGinn TE, Manmoto CC, Sinclair JR, Karliga I, Leung DW, Fazwi A, Kubota R. (2006). Protective effect of crocin against blue light- and white light-mediated photoreceptor cell death in bovine and primate retinal primary cell culture. Invest Ophthalmol Vis Sci 47: 3156 – 3163.

9- Maccarone R, Di Marco S, Bisti S. (2008). Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthalmol Vis Sci 49: 1254 –1261.

10- Taylor HR, West S, Muñoz B, Rosenthal FS, Bressler SB, Bressler NM. (1992). The long-term effects of visible light on the eye. Arch Ophthalmol 110:99-104.

11- Thomas BB, Seiler MJ, Aramant RB, Samant D, Qiu G, Vyas N, Arai S, Chen Z, Sadda SR. (2007). Visual functional effects of constant blue light in a retinal degenerate rat model. Photochem Photobiol 83: 759-765.

12- Yamauchi M, Tsuruma K, Imai S, Nakanishi T, Umigai N, Shimazawa M, Hara H. (2010). Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity. Eur J Pharmacol 650:110-119.

13. Qi Y, Chen L, Zhang L, Liu WB, Chen XY, Yang XG. (2012). Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway.Exp Eye Res. 29;107C:44-51. doi: 10.1016/j.exer.2012.11.011.

14. Ohno Y, Nakanishi T, Umigai N, Tsuruma K, Shimazawa M, Hara H. (2012). Oral administration of crocetin prevents inner retinal damage induced by N-methyl-D-aspartate in mice. Eur J Pharmacol. 5;690(1-3):84-9. doi: 10.1016/j.ejphar.2012.06.035.




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