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WELCOME TO SAFFRONOLOGY "I'm just wild about Saffron," sang Donovan in his 1967 hit Mellow Yellow. Saffron mentioned in that popular song was not a spice, but a girl (who, if my memory serves me well, was equally wild about Donovan). However, the sentiment is turning out to be descriptive of a different kind of "flower power" than we ever envisioned during that period which is often referred to as "Summer of Love". This is the power of the garden crocus-or more specifically, its three bright-red stigmas-from which saffron is derived. The health-conscious public may turn out to be "wild about saffron," too, at least if Dr. Fikrat I. Abdullayev [also spelled Abdullaev via Russian] has his way. According to this innovative researcher from the former Soviet Republic of Azerbaijan, as well as a growing cohort of like-minded scientists, the world's most expensive culinary ingredient may also be recognized as one of the most healthful. It holds promise against a host of diseases, including cancer. Dr. Abdullayev currently heads a team of nine researchers at the National Institute of Pediatrics in Mexico City. He also holds an appointment at the Laboratory of Genome Biochemistry of the Institute of Botany, Azerbaijan Academy of Sciences, in Baku where he received his PhD in 1970. He has another doctorate from the Ukrainian Academy of Sciences in Kyiv. From 1990 to 1993 he was a visiting scientist at Rutgers University in New Jersey. Abdullayev is the author of more than 120 scientific papers and abstracts, and holds several patents. Fluent in several languages he is, thus, ideally positioned to lead an international investigation into the medicinal properties of saffron. A Traditional Medicine The word "saffron" is found in recognizable form in many ancient languages. The medicinal use of saffron dates back to ancient times and is mentioned in the works of Hippocrates, Galen, and other great clinicians. Some of its traditional uses include: treatment of cough, flatulence, stomach disorders, insomnia, uterine bleeding, scarlet fever, colds, and cardiovascular disease. Today, however, it is best known as a flavoring and colorant in various foods: Spanish paella, Italian risotto, French bouillabaisse, Mexican fiambre, Arabic lamb and chicken dishes, Iranian plov, Azerbaijani pakhlava, and Indian desserts and sauces. It is also found in Swedish, Cornish and Pennsylvania Dutch holiday breads. The intense orange color of saffron hints of its medicinal nature. It is particularly rich in carotenoids, which are antioxidants that protect the body from free radical damage. But despite its impeccable credentials as an antioxidant, saffron has, until recently, received little scientific recognition as a potential source of new medicines. That may soon change. Dr. Abdullayev and Dr. Jose Antonio Fernandez of Spain co-chaired the First International Symposium on Saffron Biology and Biotechnology in Albacete, Spain, in October 2003. This historic meeting was organized under the auspices of the International Society for Horticultural Science (ISHS) and drew about 90 participants from 20 countries. The proceedings of the symposium were recently published as ISHS's Acta Horticulturae 650. Saffron contains more than 100 components, but the three most promising appear to be: Crocin, which is responsible for its orange color; Picrocrocin, which provides its bitter taste; and Safranal, which gives its aroma. Although Dr. Abudallayev worked on various natural and synthetic substances in Baku, his main interest since the 1980s has been the "extremely promising strategy" of chemoprevention. Despite the presence of the forbidding prefix 'chemo-' in that word, chemo-prevention does not refer to chemotherapy, but to the use of natural or synthetic substances, alone or in combination, which serves to prevent the development of diseases such as cancer. Saffron is produced from dried stigmas, which are the pollen-receiving parts of the flower of Crocus sativus L. This blue-violet crocus is actually a member of the Iris family. Commercially, saffron is mainly cultivated in Iran, but can also be found in Azerbaijan, France, Greece, India, Italy, Spain, China, Israel, Morocco, Turkey, Egypt and Mexico. Saffron is not always what it appears to be. There are also some false or non-crocus derived versions on the market; for example, an Indian safflower (Carthamus 10 tinctorius L., a member of the daisy family), or Compositae, a saffron of lighter red coloration which is sometimes passed off as the real thing. In ancient, as well as modern times, adulteration has always been a problem. Medieval folk took saffron adulteration very seriously. There are historical records of 15th century saffron frauds being burned in the market place along with their adulterated saffron. On another occasion, three persons convicted of that same crime were buried alive, according to an informative article on saffron in the 1911 edition of the Encyclopedia Britannica. One must also make sure not to confuse saffron with an entirely different plant called "meadow saffron" (Colchicum autumnale). This species also has medicinal uses, but unlike true saffron, meadow saffron can be very poisonous and should be strictly avoided by would-be herbalists. Saffron is not only used as a food flavoring and colorant, but as a dye for clothing, especially in developing countries. It is so intensely colorful that one grain of powdered saffron imparts a distinctly yellow tint that can dye 10 gallons of water. Saffron-robed priests are a common sight in India and saffron is the choice color of the Hindu nationalist parties in India. Despite its popularity in many countries as a culinary spice, Americans rarely use saffron in their cooking, perhaps because of its great expense. One gram of saffron (1/28th of an ounce) costs around $10 in U.S. supermarkets. The main reason why saffron is so expensive is that it is still cultivated and harvested by hand, as it has been for several millennia. One pound of true saffron requires more than 200,000 of the stigmas gathered from 70,000 flowers. Is Saffron Toxic? Perhaps because of a mistaken association with the poisonous meadow saffron, saffron has the ill-deserved reputation of being somewhat toxic. Dr. Abdullayev has established that saffron is safe when taken in dietary amounts. He has shown that oral administration of saffron extract at concentrations from 0.1 to 5 grams per kilogram of body weight (g/kg) is nontoxic in mice (Abdullayev F, et al., unpublished data). Saffron has also been shown to be non-mutagenic. That means that it does not cause mutations. Animal studies have shown that the orally administered amount that kills half of the tested animals (the so-called LD50) was 20.7 grams per kilogram. A dose of 5 grams per kilogram would be the equivalent to a 165-pound human eating up 13.4 ounces at one sitting. There is only one circumstance known to me in which this unlikely scenario has occurred. Saffron according to folk tradition is able to induce abortion in the case of unwanted pregnancies. There is no evidence to support the effectiveness of this method, but ethnobotanist James Duke, PhD, has reported that fatalities have occurred from overdoses taken for this purpose. However, in the relatively small quantities in which saffron is usually consumed, it seems to be a perfectly safe substance. Effects on Cancer Saffron is known for its possible therapeutic effect on cancer. And, indeed, a growing body of laboratory evidence indicates that saffron does have anticancer effects. This property was first described in papers by the Indian scientist S.C. Nair in 1991. Dr. Abdullayev confirmed and extended Nair's findings the following year. Later, scientists from Greece (Petros A. Tarantilis, 1994) and Spain (Julio A. Escribano, 1996) supported these results. In the last decade, research on saffron's antitumor effects has been published in about 40 experimental and review articles. Just as saffron is produced in many parts of the world, so anticancer research on saffron is also a multinational effort, and involves scientists from Azerbaijan, Greece, Hungary, India, Japan, Mexico, Spain, USA and other countries. For example, extracts of saffron have been shown to inhibit the formation of tumors and/or to retard tumor progression in a variety of experimental animal systems. The topical application of a saffron extract has been shown to inhibit both the initiation and the promotion of cancer by a common carcinogen, DMBA, which is used to induce skin cancer for experimental purposes. Researchers found that feeding mice with a saffron extract prevented the formation of soft tissue sarcomas. The exciting news is that saffron extracts have been shown to significantly prolong-almost by three-fold-the life spans of mice undergoing experimental chemotherapy with the toxic anticancer drug, cisplatin. Saffron also partially prevented the decrease in body weight, hemoglobin levels and leukocyte counts associated with that form of chemotherapy (Nair, 1991). Another study showed that when saffron was combined with two other substances, the amino acid cysteine and the antioxidant vitamin E, it had a protective effect against the toxicity of cisplatin. Together, these three protective agents significantly reduced blood urea nitrogen, serum creatinine and blood glucose levels, as well as reduced many other harmful chemical changes in the body (el Daly, 1998). Taken together, these studies indicate that saffron (with or without other substances, such as antioxidants or their precursors) has the potential to alleviate the toxicity of cisplatin, including the nephrotoxicity (damage to the kidneys), which is one of cisplatin's most serious side effects. This potential use of saffron has gone largely unexplored by conventional oncology since it first became known in 1991. In fact, a search of all abstracts from the American Society of Clinical Oncology (ASCO) meetings of the last 11 years turns up hundreds of papers on cisplatin toxicity, but not a single one mentions the word 'saffron' or 'crocus'. It is an astonishing omission, considering the damage that platinum-containing drugs, such as cisplatin, can do. In other studies, Nair and colleagues showed that the oral administration of saffron extract inhibited the growth of mouse tumors that were derived from three different kinds of cancer cells (S180, DLA and EAC), and significantly increased (again by two- to three-fold) the life spans of treated tumor-bearing mice (Nair, 1997b). Later, these same Indian authors reported that giving saffron by mouth to lab animals significantly slowed the growth of two different kinds of cancer cells (DLA and S-180). The authors suggested that the increased levels of carotenes and Vitamin A may have accounted for this anticancer effect. Interestingly, when saffron extract was encapsulated with lipids and then injected into the mice, there was an increase in the antitumor effect of this extract towards several solid tumors, including EAC tumor cells that had formerly been insensitive to orally administered saffron extract (Nair, 1992). In 1999, Spanish scientists reported that crocin, one of the carotenoids isolated from saffron, increased the survival time and decreased the growth of colon cancer in female rats, without, however, having any significant effects on the tumors in male animals. This raised the possibility that the selective antitumor action of crocin in female rats might be modulated by some as yet unidentified hormonal factor (Garcia-Olmo, 1999). Dr. Abdullayev and his colleagues have also found that naturally occurring saffron extract, in combination with two synthetic compounds, sodium selenite or sodium arsenite, may have a synergistic effect with saffron and may, therefore, have an important role in cancer chemoprevention (Riverón-Negrete, 2002). How might saffron produce these effects? Some test tube (in vitro) studies with human malignant cells have shown that saffron inhibits the synthesis of nucleic acid (DNA or RNA) in cancer cells but has no effect on overall protein synthesis (Abdullayev, 1992a and 1992b). It has also been observed that saffron increases the intracellular levels of a substance called reduced glutathione as well as glutathione-related enzymes. This suggests a possible antioxidant activity for this herbal compound. Dr. Abdullayev has suggested that saffron and its constituents be tried clinically as "alternative anticancer agents, which alone, and in combination with other synthetic substances may have the potential for the prevention and the treatment of certain forms of cancer" (Abdullayev, 2002). Because the relationship between saffron and cancer is an important concern, he says, comprehensive, in-depth studies need to be conducted. Abdullayev suggests the following four initial research projects: (1) Define the mechanism or mechanisms involved in the therapeutic properties of saffron; (2) Investigate the mechanisms involved in saffron cancer chemoprevention; (3) Determine the biologically active components of saffron and (4) Perform human studies to define efficacy of saffron in cancer treatment and prevention. Of course, the scarcity and relative expense of saffron may pose an obstacle to prevention or treatment trials using this agent. This underscores the need to develop indoor cultivation methods in order to achieve the highest quality of saffron at the lowest possible price. The results of current research provide the scaffolding to construct a platform for a new scientific discipline that Dr. Abdullayev calls "saffronology". With the publication of the proceedings of the First International Conference on Saffron, we can expect to hear much more about this emerging discipline. Practical Considerations If readers want to increase their own intake of saffron, there are many places to purchase it. However, the local supermarket is not the best place. You may be shocked to see how few strands you get in a standard bottle. And, besides, since it is so expensive and still so relatively unknown, the stock at the supermarket may not be the freshest. The brand that I myself use is called "The Gathering of Saffron", which is imported from La Mancha, Spain. It consists of whole strands (not powdered). However, one should note that much of the saffron coming out of Spain actually originates in Iran, the World's No. 1 saffron producer. One ounce of saffron can generally be found on the Internet for between $30 and $40. In general, the redder the saffron in color, the more potent it is. If you are lucky enough to have an ethnic specialty grocery store nearby, you may obtain it much cheaper. A little goes a long way. I paid only $20 for an ounce of saffron in the Indian neighborhood of Jackson Heights, New York. That was three years ago and although I use saffron liberally, I still have some left. Saffron is a promising agent and Dr. Abdullayev is a tireless proponent of its virtues. So, undoubtedly, there will be many new developments in this field. References to the article: 1. Abdullaev FI, Frenkel, G.D. Effect of saffron on cell colony formation and cellular nucleic acid and protein synthesis. BioFactors, 3(3): 201204, 1992a. 2. Abdullaev FI, Frenkel G.D. The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. BioFactors, 4(1): 4345, 1992b. 3. Abdullaev, F. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biology and Medicine, Vol. 227(1): 2025, 2002. 4. Abdullaev FI, Cabalerro-Ortega H, Riveron-Negrete L, Pereda-Miranda R, Rivera-Luna R, Hernandez JM, Perez-Lopez I, Espinosa-Aguirre JJ. Evaluacion in vitro del potencial quimiopreventivi del azafran. Revista de Investigacion Clinica, 54(5): 430-436, 2003. 5. Abdullaev FI, Riveron-Negrete L, Cabalerro-Ortega H, Hernandez JM, Perez-Lopez I, Pereda-Miranda R, Espinosa-Aguirre JJ. Use of in vitro assays to assess the antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.) Toxicology In Vitro, 17: 731-736, 2003b. 6. Duke, JA. Handbook of Medicinal Herbs. Boca Raton, Florida: CRC Press, 1985. 7. el Daly ES. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. Journal de Pharmacie de Belgique, 53(2): 9395, 1998. 8. Escribano , Alonso GL, Coca-Prados M, and Fernandez JA. Crocin, safranal and picrocrocin from saffron (Crocus sativus L,) inhibit growth of human cancer cells in vitro. Cancer Letters, 100:23-30, 1996. 9. Garcia-Olmo DC, Riese HH, Escribano J, Ontañon J, Fernandez JA, Atienzar M, Garcia-Olmo D. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rats. Nutrition and Cancer, 35(2): 120126, 1999. 10. Martinez, Mercedes. Investigan el extracto de azafrán por su efecto anticarcinógeno. Diario Medico, November 10, 2003. Search: diariomedico.com. 11. Nair SC, Salomi MJ, Pannikar. B, Pannikar KR. Modulatory effects of the extracts of saffron and Nigela sativa against cisplatinum induced toxicity in mice. Journal of Ethnopharmacology, 31:7583, 1991(a). 12. Nair SC, Pannikar B, Pannikar KR. Antitumour activity of saffron (Crocus sativus). Cancer Letters, 57(2): 109114, 1991(b). 13. Nair SC, Salomi MJ, Varghese CD, Pannikar B, Pannikar KR. Effect of saffron on thymocyte proliferation, intracellular gluthathione levels and its antitumor activity. BioFactors, 4(1): 5154,1992. 14. Riverón-Negrete L, et al. The combination of natural and synthetic agents: a new pharmacological approach in cancer chemoprevention. Procedures of the Western Pharmacology Society, 45:74-75, 2002. 15. Tarantilis PA, Morjani H, Polissiou M, and Manfait M. Inhibition of growth and induction of differentiation promyclocytic leukemia (HL-60) by carotenoids from Crocus sativus L. Anticancer Res, 14: 1913-1918, 1994.
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Could
saffron, cherished by civilizations, both ancient and modern,
hold, as yet, untapped benefits in the treatment and prevention
of cancer? Could it be that those delicate thin, hair-like stamens
that produce a brilliant reddish-orange dye belonging to the
flowers of a humble crocus family (Crocus sativus) really offer
hope to cancer patients? A growing number of respected scientists
are convinced of the possibility.
