Saffron

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Code: f331
Latin name: Crocus sativus
Family: Iridaceae
Common names: Saffron
This plant must be differentiated from the unrelated Meadow Saffron or Wild Saffron (Colchicum autumnale L.).
 
Spice
A spice, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Saffron is native to the Mediterranean. It may have been used by the Sumerians more than 5000 years ago. Muslims introduced it to Spain in the 8th century. Saffron is now also cultivated in India, Turkey, China, Italy and Greece, but Spain and Iran are the largest producers, together accounting for more than 80% of the world's production.

The saffron crocus is a fall-flowering ornamental with blue-violet flowers containing protruding orange stigmas. The spice saffron is the 3 tube-like, funnel-shaped stigmas of the saffron crocus. Each stigma is a tiny capsule that encloses the complex chemicals that make up saffron's aroma, flavour, and yellow dye. The stigmas are delicate and thread-like, and measure 2.5 to 4 cm. Harvesting saffron is done by hand and is very labour-intensive. Approximately 150 000 flowers are needed for a single kilogram of dried saffron. Saffron is understandably the most expensive spice in the world, but it is also very intense and can be effective in minute amounts. Turmeric may be passed off as ‘Indian Saffron’, and safflower and calendula flowers also produce a mislabelled product.

Saffron is used as a seasoning and as a food dye for pasta, cheese, rice dishes (paella, risotto milanese), soups, bouillabaisse, sauces, butter, cakes and liqueurs. It is also used in perfume.

The intense colour of saffron is caused by pigments of the carotenoid type, mostly by crocetine esters. The pigments of saffron include saffron yellow A and B (safflor yellow) and saffloamine A. (1)

Saffron is a traditional medicine for improving blood circulation and treating bruises. Saffron works against a wide spectrum of tumours, such as leukaemia, ovarian carcinoma and papilloma. It has low biochemical toxic effects on animals. In addition, saffron may be used to treat coronary heart disease and hepatitis, and to strengthen the immune system. (2) A review examines the cytotoxic, anticarcinogenic and antitumor properties of Saffron. (3)

Saffron may be confused with the similar-looking (but highly poisonous) genus Colchicum (family Liliaceae), the members of which are commonly called ‘autumn crocus’ or ‘meadow/wild saffron’. But colchicums have 6 stamens, while crocuses have only 3.

Allergen Description

Sera of saffron-allergic patients were found to have IgE against saffron proteins in the range of 11 to 70 kDa. (4) A 15.5 kDa profilin-like allergen was detected from the pollen and stamens, but in very low levels. Several proteins in the 27 to 67 kDa range were mainly the ones involved in the IgE-binding inhibition study. No allergenic components were demonstrated in pistils. (5)

The following allergens have been characterised:

Cro s 1, of unknown biological activity. (6, 7)

Cro s 2, a 12-16 dDa protein, a profilin. (6, 8, 9, 10)

Cro s 3, a 9 kDa protein, a lipid transfer protein. (6, 11)

A study of 6 patients with allergic rhinitis and positive skin-prick test to saffron extract were evaluated: 2 recombinant lipid transfer proteins were isolated (rCro s 3.01 and rCro s 3.02, of 9.15 kDa and 9.55 kDa respectively). The sequences obtained had a 47% identity with each other, and 51% and 43% with Pru p 3, the lipid transfer protein from peach. Specific IgE to the purified allergens was found in 50% of patients for rCro s 3.01, and 33% of the patients for rCro s 3.02 and Pru p 3. (11)

Potential Cross-Reactivity

Extensive cross-reactivity among the different individual species of the genus could be expected. (12)

Saffron extracts (containing a profilin allergen) were shown to have a significant degree of cross-reactivity with Lolium, Salsola, and Olea. (5) Sal k 4 (a profilin from saltwort) has been shown to have an amino acid identity of 68.4% with recombinant Cro s 2. (10) Cross-reactivity of saffron profilin (Cro s 2) has been demonstrated with the natural profilin of Cynodon dactylon (Bermuda grass) pollen, Poa pratensis (meadow grass) pollen, cantaloupe and tomato extracts, and the recombinant profilin of melon (rCuc m 2). (8) Amino acid sequence of Cro s 2 has also been shown to have a high degree of identity and similarity to other plant profilins. (9)

Cross-reactivity as a result of the lipid transfer protein in saffron and lipid transfer proteins from other plants is possible, but has not been described to date.

Clinical Experience

IgE-mediated reactions

Anecdotal evidence suggests that saffron may induce symptoms of food allergy in sensitised individuals; (13) however, few studies have been reported to date. It is possible that the allergy occurs more frequently than has been reported.

A report was published on a patient who experienced a severe anaphylactic reaction a few minutes after eating risotto ai funghi, a yellow rice dish prepared with saffron and mushrooms. The skin test and RAST were positive for saffron. The 21-year-old developed a severe anaphylactic reaction (with violent abdominal cramps, laryngeal oedema, and generalised urticaria) a few minutes after the meal. He was taken to a nearby hospital, where he collapsed at the entrance. (1)

Occupational exposure to the pollen of saffron may occur, resulting in occupational asthma and allergic rhinitis. In a study evaluating 50 saffron workers, 3 were sensitised to saffron pollen and stamen proteins. Skin- and serum-specific IgE were detected. One patient had asthma, confirmed by a positive bronchial provocation test, and two patients complained of rhinoconjunctivitis, confirmed with a positive conjunctival provocation test. In all 3, symptoms developed during excision of stigmas from the saffron flowers, a process which allows the inhalation of pollen and stamen particles. Of a general allergic population of 237 with respiratory symptoms attending an allergy clinic and not exposed to saffron flowers, 10 patients were shown to have skin- and serum-specific IgE to saffron pollen extracts, which could be due to cross-reactivity with other taxonomically related pollens. The pistil, unlike the stamen and pollen, did not cause sensitisation. (5, 14)

Other reactions

In a study of 38 saffron-allergic individuals, skin-prick tests with saffron pollen were positive in 70%. (4)

Contact dermatitis to safflower leaves and flowers used as an adulterant of the spice saffron has been reported. (15)

Occupational airborne contact dermatitis from saffron bulbs has been described. (16)

See under Allergen Exposure for detail concerning the danger of confusion with the genus Colchicum (family Liliaceae).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

1. Wüthrich B, Schmid Grendelmeyer P, Lundberg M. Anaphylaxis to saffron. Allergy 1997;52(4):476-7.

2. Deng Y, Guo ZG, Zeng ZL, Wang Z. Studies on the pharmacological effects of saffron (Crocus sativus L.) -- a review [Chinese] Zhongguo Zhong Yao Za Zhi. 2002;27(8):565-8.

3. Abdullaev FI. Biological effects of saffron. Biofactors. 1993;4(2):83-6.

4. Varasteh AR, Vahedi F, Sankian M, Kaghazian H, Tavallaie S, Abolhassani A, Kermani T, Mahmoudi M. Specific IgG Antibodies (Total and Subclasses) against Saffron Pollen: A Study of Their Correlation with Specific IgE and Immediate Skin Reactions. Iran J Allergy Asthma Immunol 2007;6(4):189-95.

5. Feo F, Martinez J, Martinez A, Galindo PA, Cruz A, Garcia R, Guerra F, Palacios R. Occupational allergy in saffron workers. Allergy 1997;52(6):633-41.

6. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/ 2010.

7. Valenta R, Twaroch T, Swoboda I. Component-resolved diagnosis to optimize allergen-specific immunotherapy in the Mediterranean area. J Investig Allergol Clin Immunol 2007;17 Suppl 1:36-40.

8. Sankian M, Shirazi FG, Arafi M, Moghadam M, Varasteh A. Production and Characterization of Monoclonal Antibody against Saffron Pollen Profilin, Cro s 2. Iran J Immunol 2008;5(3):156-62.

9. Varasteh AR, Moghadam M, Vahedi F, Kermani T, Sankian M. Cloning and expression of the allergen Cro s 2 Profilin from Saffron (Crocus sativus). Allergol Int 2009;58(3):429-35.

10. Assarehzadegan MA, Amini A, Sankian M, Tehrani M, Jabbari F, Varasteh A. Sal k 4, a new allergen of Salsola kali, is profilin: a predictive value of conserved conformational regions in cross-reactivity with other plant-derived profilins. Biosci Biotechnol Biochem 2010;74(7):1441-6.

11. Gómez-Gómez L, Feo-Brito F, Rubio-Moraga A, Galindo PA, Prieto A, Ahrazem O. Involvement of lipid transfer proteins in saffron hypersensitivity: molecular cloning of the potential allergens. J Investig Allergol Clin Immunol 2010;20(5):407-12.

12. Yman L. Botanical relations and immunological cross-reactions in pollen allergy. 2nd ed. Pharmacia Diagnostics AB. Uppsala. Sweden. 1982: ISBN 91-970475-09.

13. Moneret-Vautrin DA, Morisset M, Lemerdy P, Croizier A, Kanny G. Food allergy and IgE sensitization caused by spices: CICBAA data (based on 589 cases of food allergy). Allerg Immunol (Paris) 2002;34(4):135-40.

14. Pascual C, Crespo JF, Martin M. Actualizacion en alergenos alimentarios. Rev Esp Alergol Inmunol Clin 1993;3:125-31.

15. Van der Willigen AH, van Joost T, Stolz E, van der Hoek JC. Contact dermatitis to safflower. Contact Dermatitis 1987;17(3):184-6.

16. Martinez FV, Munoz Pamplona MP, Urzaiz AG, Garcia EC. Occupational airborne contact dermatitis from saffron bulbs. Contact Dermatitis 2007 Oct;57(4):284-5. 

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.