For July 25, 2004
THE MOSS REPORTS
This week I discuss the potential medicinal uses of saffron, a spice harvested from a member of the humble crocus family. Could this spice, cherished by civilizations ancient and modern, hold as yet untapped benefits in the treatment and prevention of cancer? A growing number of respected scientists believe that yes, it could. For the past thirty years I have been studying the field of cancer therapy and prevention, monitoring developments in the world of oncology, helping cancer patients and their families weigh up the benefits and drawbacks of treatments both conventional and alternative. As a product of these long years of research I have written The Moss Reports, a series of more than two hundred individual reports on different kinds of cancer. If you or someone you love has received a diagnosis of cancer, a Moss Report can provide you with the key to understanding the best that conventional and alternative medicine have to offer. You can order a Moss Report on your specific cancer type by calling Diane at 1-800-980-1234 (814-238-3367 from outside the US), or by visiting our website: http://www.cancerdecisions.com We look forward to helping you.
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Pictured above: Crocus |
The health-conscious public may turn out to be "wild about saffron," too, at least if Dr. Fikrat I. Abdullaev 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. Abdullaev currently heads a team of nine 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, where he received his PhD in 1970. He has another doctorate from the Ukranian Academy of Science in Kiev. From 1990-1993 he was a visiting scientist at Rutgers University in New Jersey. Dr. Abdullaev is the author of over 120 scientific papers and abstracts, and several patents. He is fluent in many languages and is thus ideally positioned to lead an international investigation into saffron's medicinal properties.
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Pictured above: Dr.
Abdullaev's research team in front of the National Institute
of Pediatrics Click on photo for a larger image |
A Traditional Medicine
The word 'saffron' is found in recognizable form in even the most
ancient languages. The medicinal use of saffron dates back to ancient
times and is mentioned in the works of Hippocrates, Galen and the
other great clinicians. Some of the many traditional uses of saffron
include the 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, Azerbaijanian
pakhlava, and Indian desserts and sauces. It is also found in Swedish,
Cornish and Pennsylvania Dutch holiday breads.
The intense orange color of saffron is a hint as to 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
gotten little scientific recognition as a potential source of new
medicines.
That may soon change. Dr. Abdullaev and Dr. Jose Antonio Fernandez of Spain co-chaired the First International Symposium on Saffron Biology and Biotechnology, held 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 that symposium were recently published as ISHS's Acta Horticulturae 650.
Click or go here to see a description of ISHS Acta Horticulturae
650:
http://www.actahort.org/books/650/
Saffron contains over a hundred components, but the three most interesting appear to be:
Crocin, which is responsible for saffron's orange
color
Picrocrocin, which is responsible for its bitter
taste; and
Safranal, which is responsible for its odor and
aroma.
Although in his home town of Baku, Azerbaijan, Dr. Abudallaev worked on various natural and synthetic substances, 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, chemoprevention does not refer to chemotherapy, but to the use of natural or synthetic substances, alone or in combination, to prevent the development of diseases such as cancer.)
Saffron is produced from the 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 also in Dr. Abdullaev's native 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 (i.e., non-crocus derived) versions on the market. For example, Indian safflower, Carthamus tinctorius L., a member of the daisy family, or Compositae, is lighter red than true saffron, but is sometimes used to adulterate the real thing. In ancient, as well as modern, times adulteration has been a problem. Medieval folk took saffron adulteration very seriously: there are historical records of 15th century saffron scammers being burned in the market-place along with their adulterated saffron. On another occasion three persons convicted of the same crime were buried alive, according to an informative article on saffron in the 1911 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 underdeveloped countries. It is so intensely colorful that one grain of powdered saffron imparts a distinctly yellow tint to ten gallons of water. Saffron-robed priests are a common sight in India and saffron is the chosen color of the Hindu nationalist parties in India.
Despite its popularity as a culinary spice in so many countries, Americans rarely use saffron in their cooking, perhaps because of its great cost. One gram of saffron (i.e., 1/28th of an ounce) costs around $10 in US supermarket. The main reason for saffron being so expensive is that it is still cultivated and harvested by hand, as it has been for several millennia, and it takes over 200,000 of the stigmas, obtained from 70,000 flowers, to yield one pound of true saffron.
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Pictured above: A
traditional saffron harvesting |
Is Saffron Toxic?
Perhaps because of a mistaken association with the poisonous meadow
saffron, Colchicum autumnale, saffron has an ill-deserved reputation
as being somewhat toxic, but Dr. Abdullaev 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
(Abdullaev F, et al., unpublished data). Saffron has also been shown
to be non-mutagenic (i.e., it does not cause mutations).
Animal studies indicated that the orally-administered amount that kills half 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 happened. Saffron has a folk reputation for bringing an end to an unwanted pregnancy. 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 has been consumed for millennia, it seems a perfectly safe substance.
Effects on Cancer
What will interest most readers, of course, is the possible therapeutic
effect of saffron on cancer. And, indeed, a growing body of laboratory
evidence indicates that saffron does have anticancer effects. The
anticancer potential of saffron was first pointed out in papers
by the Indian scientist S.C. Nair in 1991. Dr. Abdullaev confirmed
and extended Nair's findings the following year. Later, scientists
from Greece (Petros A. Tarantilis in 1994) and Spain (Julio A. Escribano
in 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 instance, 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 a saffron extract prevented the formation of soft tissue sarcomas in mice. Most excitingly, saffron extracts have been shown to significantly prolong - by almost three-fold - the life spans of mice undergoing experimental chemotherapy with the toxic anticancer drug, cisplatin. They 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 reducing 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) that is one of cisplatin's most serious side effects. This potential use of saffron has gone largely unexplored by conventional oncology since it was first pointed out 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 that even 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, S. C. 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. Abdullaev 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 might therefore have an important role in cancer chemoprevention (Riverón-Negrete 2002).
How might saffron exert 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 (Abdullaev 1992a and Abdullaev 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. Abdullaev 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" (Abduallev 2002). Because the relationship between saffron and cancer is an important concern, he says, comprehensive, in-depth studies need to be conducted. He suggests the following four initial research projects:
--Define the mechanism or mechanisms involved in the therapeutic
properties of saffron
--Investigate the mechanisms involved in saffron cancer chemoprevention
--Determine the biologically active components of saffron
--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. Abdullaev calls 'saffronology.' With the publication of the proceedings of the First International Conference on saffron we expect to hear a lot more about this emerging discipline.
Practical Considerations
If readers want to increase their own intake of saffron there are
many places to obtain 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 I myself use is "The Gathering of
Saffron", imported from La Mancha, Spain. It consists of whole
strands (i.e., it is not powdered). However, much of the saffron
coming out of Spain actually originates in Iran, the world's number
one producer.
One ounce of saffron can generally be found on the Internet for between $30 and $40. The redder the saffron, generally, the more potent it will be. If you are lucky enough to have an ethnic specialty grocery store nearby, you may obtain it even more cheaply. A little goes a long way. I paid just $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 a little left.
Saffron is a promising agent and Dr. Abdullaev is a tireless proponent of its virtues. So there will undoubtedly be many new developments in this field. I will keep readers apprised of the unfolding of the colorful field of saffronology.
--Ralph W. Moss, Ph.D.
References:
Abdullaev FI, Frenkel GD.
Effect of saffron on cell colony formation and cellular nucleic
acid and protein synthesis. BioFactors 3(3): 201–
204, 1992a.
Abdullaev FI, Frenkel GD. The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. BioFactors 4(1): 43–45, 1992b.
Abdullaev F. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med Vol. 227(1):20–25,2002.
Abdullaev F.I., 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. Rev Invest Clin 54, 5. 430-436, 2003a
Abdullaev F.I., 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
Duke, JA. Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press, 1985.
el Daly ES. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Belg 53(2): 93–95, 1998.
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 Lett 100:23-30, 1996
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. Nutr Cancer 35(2): 120–126, 1999.
Martinez, Mercedes. Investigan
el extracto de azafrán por su efecto anticarcinógeno.
Diario Medico, November 10, 2003. Retrieved on July 13,
2004 from:
http://www.diariomedico.com/edicion/noticia/0,2458,411949,00.html
Nair SC, Salomi MJ, Pannikar. B, Pannikar KR. Modulatory effects of the extracts of saffron and Nigela sativa against cisplatinum induced toxicity in mice. J Ethnopharmacol 31:75–83, 1991(a)
Nair SC, Pannikar B, Pannikar KR. Antitumour activity of saffron (Crocus sativus). Cancer Lett 57(2): 109–114,1991(b).
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): 51–54,1992.
Riverón-Negrete L, et al. The Combination of Natural and Synthetic Agents – A New Pharmacological Approach in Cancer Chemoprevention. Proc. West. Pharmacol. Soc.2002; 45:74-75.
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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IMPORTANT DISCLAIMER
The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.
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