Saffron

Scientific Name(s): Crocus sativus L. Family: Iridaceae

Common Name(s): Saffron

Clinical Overview

Uses of Saffron

Saffron increases oxygen diffusion in vivo and may possess antineoplastic activity.

Saffron Dosing

Abortifacient dose = 10 g, lethal dose = 20 g.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Documented emmenagogue and abortifacient effects. Large amounts (more than 5 g, which is greater than amounts used in food) have uterine stimulant and abortifacient effects. Information regarding use in lactation is unavailable. Avoid use.

Saffron Interactions

None well documented.

Saffron Adverse Reactions

Saffron has been implicated in 1 case of anaphylaxis and 15 cases of seasonable allergic symptoms.

Toxicology

Saffron is not generally associated with toxicity when ingested in culinary amounts.

Botany

True saffron is native to Asia Minor and southern Europe. Its blue-violet, lily-shaped flowers contain the orange stigmas (part of the pistil) and red style branches, 1 which are collected to produce the spice saffron. The plant is a bulbous perennial, growing 15 to 20 cm in height. Mature stigmas are collected by hand during a short blooming season. Over 200,000 dried stigmas, obtained from about 70,000 flowers, yield 0.5 kg of true saffron. 2 Saffron commands as much as $30 per ounce in the American market.

True saffron should not be confused with American saffron (safflower, Indian safflower), Carthamus tinctorius L. (family Asteraceae), that is produced from the tubular florets and is a lighter red than true saffron. The two often are used for the same purposes, and the less expensive American saffron is sometimes used to adulterate true saffron.

History

Saffron has been widely used for flavoring food and as a dye for cloth, where it continues to find use in underdeveloped countries and among back-to-basics artisans. Folkloric uses of saffron have included its use as a sedative, expectorant, aphrodisiac, and diaphoretic. Anecdotal reports from the tropical regions of Asia describe the use of a paste composed of sandalwood and saffron as a soothing balm for dry skin. During the 16th through the 19th centuries, saffron was used in various opioid preparations for pain relief. Laudanum contained sherry wine, opium, saffron, cinnamon, and cloves. Black-drop contained opium, nutmeg, saffron, and yeast. 3

Chemistry

The stigmas of C. sativus are rich in riboflavin, a yellow pigment, and vitamins. The crocus zeaxanthin-cleavage dioxygenase gene codes for the chromoplast enzyme that starts the production of the 3 major carotenoid derivatives crocetin, picrocrocin, and safranal, are found in saffron. 1 In addition, saffron contains crocin (a water-soluble carotenoid), 4 the major source of yellowish-red pigment. Upon drying, a hypothetical protocrocin of the fresh plant is decomposed into one molecule of crocin (a colored glycoside) and two molecules of picrocrocin (a colorless bitter glycoside). 5 Crocin is a mixture of glycosides: crocetin, a dicarboxylic terpene lipid, and alpha-crocin, a digentiobiose ester of crocetin. In addition, cis- and trans-crocetin dimethylesters have been identified. Similar compounds have been isolated from other members of the Iridaceae family. Gardenidin, a compound obtained from gardenias, has been shown to be identical to crocetin. The characteristic taste of the spice is attributed to the glycoside picrocrocin. Following hydrolysis, the compound yielded glucose and safranal, the main odiferous constituent. The essential oil derived from saffron is a complex mixture of more than 30 components, mainly terpenes and their derivatives. 5

Saffron Uses and Pharmacology

US patents have been issued for the proposed use of crocetin in the treatment of skin papillomas, spinal cord injuries, hypertension, and cerebral edema in cats. It also has been used to increase fermentation yields.

A study in mice concluded that the stigma and petal from saffron demonstrated antinociceptive and anti-inflammatory effects. 6

Research reveals no clinical data regarding the use of saffron for antinociceptive or anti-inflammatory effects.

A concentrated saffron extract has been shown to limit the growth of experimental tumor colony cells by inhibiting cellular nucleic acid synthesis. 7

Saffron compound activated macrophages in vitro, showing a potential defense against tumors. 8

Crocetin showed a dose-dependent inhibitory effect on DNA, RNA, and protein synthesis in cervical carcinoma and lung adenocarcinoma. However, it had no inhibitory effect on colony formation, suggesting that crocetin alone is not the cytotoxic portion of saffron. 9

In a study comparing the inhibitory effect on cancer cells of 3 components of saffron, crocin demonstrated greater activity than picrocrocin or safranal. 10 Crocin was shown to be highly effective in inhibiting leukemic cells. 4

Orally administered saffron (200 mg/kg) has been shown to increase the lifespan of mice with a variety of intraperitoneally transplanted and topical cancers, suggesting that the product may have the potential to act as an anticancer agent. 11 , 12

A study in rats demonstrated cytotoxic activity of crocin against colon adenocarcinoma. Interestingly, only female rats showed decreased tumor growth and increased survival time, suggesting this activity may be hormone related. 13

Saffron can potentially prevent ethanol and acetaldehyde effects, as shown in a rat study. 14

The cytotoxic mechanism of cyclophosphamide was enhanced in the presence of crocetin and in hyperthermia. 15

Chemopreventive studies examining the efficacy of saffron need to be performed.

A German patent has been granted for a topical preparation that contains a mixture of opium, quinine, and saffron, which is used in the prevention of premature ejaculation. An aqueous extract of the corm (underground bulb) in combination with salicylic acid and vegetable oils is said to restore hair growth in baldness and has been granted an Australian patent.

Perhaps the most poorly understood of saffron's actions is its ability to increase oxygen diffusion. Atherosclerosis may be initiated by hypoxia at the vascular wall, and this hypoxia may be caused by a decreased rate of oxygen diffusion from the red blood cells. 16 A way to counteract such diffusion decreases would be to use a drug that increases oxygen diffusion in plasma. Although few compounds appear to do this, crocetin has been found to bring about an 80% increase in the oxygen diffusivity of plasma. 17

A patent was issued for the use of crocetin to increase oxygen diffusion into solutions such as plasma (US patent 3 788 468 January 29, 1974). Crocetin binds strongly to serum albumin. 18

Injections of crocetin in rabbits fed 1% cholesterol diets for 4 to 5 months have been found to decrease cholesterol and triglyceride levels. 16 , 17 Serum cholesterol levels were 50% lower in the crocetin-treated animals than in the controls. The triglyceride level of the crocetin group remained in the normal range while the controls increased by 2000%. Vascular (aortic) damage was much less severe in the rabbits that received crocetin. The mechanism for these effects is poorly understood.

Crocetin is found in crocus styles and algae. Epidemiologic evidence suggests that the low incidence of cardiovascular disease in parts of Spain may be related to the liberal, almost daily consumption of saffron. Algae in Japanese diets may have a similar protective effect. 19

Saffron combined with hematoxylin-eosin or hematoxylin-phyloxin is used as a staining method in various procedures (ie, examining giant cell tumors, 20 cell death, 21 and airway smooth muscle orientation). 22

Limited data make it difficult to extrapolate the effects observed following crocetin injections in animals with the oral consumption of saffron in humans.

Dosage

Abortifacient dose = 10 g, lethal dose = 20 g.

Pregnancy/Lactation

Documented emmenagogue and abortifacient effects. 23 , 24 Large amounts (more than 5 g, which is greater than amounts used in food) have uterine stimulant and abortifacient effects. Information regarding use in lactation is unavailable. Avoid use.

Interactions

None well documented.

Adverse Reactions

Anaphylactic reactions (eg, angioedema, urticaria) occurred in a farmer 21 years of age after ingesting a meal containing saffron rice and mushrooms. Positive responses to saffron, with negative results to other ingredients, in scratch test and radioallergosorbent assay (RAST) testing for IgE strongly suggest that saffron caused this reaction. 25

Seasonal occupational allergy, including rhino-conjunctivitis, bronchial asthma, and cutaneous pruritus, occurred in 15 exposed workers. Skin prick and RAST tests were positive for saffron. Onset of symptoms correlated with the saffron season (October-November). 26

Cross-reactivity has been demonstrated between saffron and Lolium, Salsola, and Olea. 26

Toxicology

There is no evidence to support saffron's reported emmenagogue (induces or increases menstruation) or abortifacient effects. Large doses of the stigmas have been reported to act as sedatives, 2 and fatalities occurring from the use of saffron as an abortifacient have been cited. 27 The saponin-containing corm is toxic to young animals. The lethal dose is 20 g and the abortifacient dose is 10 g. The following effects were reported after ingestion of 5 g: severe purpura, thrombocytopenia, and severe bleeding. 28

One study demonstrated that saffron was nonmutagenic and nontoxic, although doses were not mentioned. 29 Nevertheless, saffron is generally not associated with toxicity when ingested in culinary amounts.

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