A Taste of Good Cheer: Saffron for the treatment of cancer related depression

Jacob Schor ND
Fellow of the American Board of Naturopathic Oncologists
February 2012
www.DenverNaturopathic.com
 
There is little about having cancer that warms the heart or that triggers glee.  On a list of stressful or depressing life experiences, cancer is near the top.  Thus we often find cancer patients are prescribed anti-depressant medications.  In certain cancers these medications may have drawbacks. 
 
For example it has long been a common practice to prescribe SSRI antidepressants to women taking tamoxifen as this both cheers them up and seems to reduce the drug’s side effects.  There is now concern that tamoxifen’s side effects decrease because the anti-depressants by interfering with the liver’s production of a particular enzyme (cyp2d6) render tamoxifen ineffective.
 
These same antidepressants may reduce bone growth.  Though not proven, slowing bone growth, aside from contributing to osteoporosis, may have another problem as it is generally believed that this could favor growth of cancer metastases in the bone.  We would prefer bones to be growing fast and staying strong.       
 
Thus I find myself more and more frequently suggesting to cancer patients who complain of depression that they take saffron.  The research, though limited, looks good.
 
The herb we call saffron consists of the stigma of a small crocus.  Harvesting saffron is highly labor intensive and the resultant cost so high that economics argue against utilizing saffron as a medicine.  Such cost concerns lose force if all that is required  is a minute quantity of saffron to gain benefit.       
 
Agha-Hosseini et al reported in 2008 that taking 30 mg/day of saffron orally benefited the symptoms of premenstrual syndrome (PMS). In their double-blinded- placebo controlled trial significant improvements were seen in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. It took 3-4 cycles to see results.  
 
These current papers follow four earlier randomized double-blinded placebo controlled human clinical trials in which saffron was shown to have significant benefit in treating depression. 
 
Two of these studies, one by Akhondzadeh et al and a second by Noorbala et al, both published in 2005, also used 30 mg of saffron a day in 6 week trials.  Akhondzadeh’s group compared the effect of saffron against placebo while Noobala compared saffron effect against the antidepressant medication fluoxetine [Prozac]. Saffron produced significantly better results as measured on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). Noobala reported that the saffron effect was “… similar to fluoxetine in the treatment of mild to moderate depression.”   
 
These researchers reported similar results in 2006 and 2007 but this time rather than using just the flower stigma, they used the flower petals.  In November 2006 Moshiri et al reported that petals taken orally (30 mg/day) were again more effective than placebo producing a significantly better outcome on Hamilton Depression Rating Scale (d.f.=1, F=16.87, p<0.001).          In March 2007, Akondzadeh et al reported that in an 8-week trial, petals (30 mg/day) were as effective as fluoxetine (10 mg/day) in treating mild to moderate depression.  There would be an obvious economic advantage to using either the petals or the whole flower instead of only the stigma.
 
Recent investigations suggest that saffron may have application in a variety of other disorders involving neuronal, cardiovascular and malignancy. Of particular interest to us are the recent papers suggesting a potential role in cancer treatment.       
 
In the last year a number of interesting papers have been published on this topic.
 
An October 2011 study suggests a saffron extract called crocetin  “… significantly enhanced the cytotoxicity induced by vincristine…” against cervical, NSCLC, ovarian and breast cancer cell lines.  Another October article describes using saffron in a liposomal form to increase cytoxoic action against HeLa and MCF-7 cells.   A May 2011 paper reported that, “…saffron exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis.”   An April 2011 paper, reported that crocetin, “… affects the growth of cancer cells by inhibiting nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis and hindering growth factor signaling pathways…”  Papers from both May 2011 and 2010 suggest a potential benefit against lung cancer. The more recent telling us that, “Saffron could decrease the cell viability in the malignant cells as a concentration- and time-dependent manner…. [and
 could]
be
considered as a promising chemotherapeutic agent in lung cancer treatment in future”          An October 2010 had reached a similar conclusion, “…. the extract exerts pro-apoptotic effects in a lung cancer-derived cell line and could be considered as a potential chemotherapeutic agent in lung cancer.”    A January 2011 paper reported that Crocetin inhibits invasiveness of breast cancer cells through downregulation of matrix metalloproteinases.”        Other papers have suggested possible utility in treating pancreatic cancer and lymphoma.      
 
The component likely responsible for the cortisol lowering effect reported by Fukui et al is in likelihood a volatile agent, such as safranal.        Crocetin, the saffron fraction typically investigated in these cytoxic reports, is a component generally considered to be a dye.  It conveys color more than odor or taste. 
 
At this point, while no human trials of saffron for treating cancer have been published, we can certainly justify saffron use by cancer patients to help relieve complaints of anxiety.  That these medications might also convey a cytoxic effect is a possibility and one that we will certainly be watching the literature for over the coming years to see if it is confirmed.  Though in theory the petals of the saffron crocus may be far more economical, it is unclear whether they are yet commercially available.  Certainly some enterprising botanical supplier should be taking advantage of this lower price and seemingly equivalent efficacy in the near future and supplying capsules of crocus petals.
 
 
 
 
The high price of saffron as a raw ingredient is probably why we are not seeing saffron capsules for sale at the local health food store.  I’ve read estimates that by the time a supplement reaches a store shelf that the original cost of ingredients has been increased by a factor of 5-6 times.  That is, using saffron as an example, if one gram of saffron costs $20, a bottle of saffron capsules may need to sell for $100 to $120.
 
As a result I’ve been suggesting that patients ‘make their own’ saffron tincture to take. 
 
In order to make a month’s supply of saffron tincture purchase 1 gram of saffron.  Costco currently has an excellent Spanish saffron in their spice section for less than $15 a gram.  Savory Spice has excellent saffron at a competitive price.
 
Put the saffron in a one-ounce dropper bottle.        This takes patience.  I find a funnel and chop stick (used to jam the threads) aid the process.  Add one Tablespoon of boiling water.  The funnel helps here as well.  Let the saffron steep in the water for several hours.  Now add one Tablespoon of distilled alcohol; brandy, whiskey, gin, Everclear, vodka (it’s your choice).  You should let the mixture sit for a few days, but I rarely bother.
 
The 30 mg/day dose of saffron used in the research studies on depression equals slightly more than 18 drops of this extract per day.  There is no known toxicity to saffron that we know of so one can certainly take more than this. 
 
 
References:
 
 
1. Agha-Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. BJOG. 2008 Mar;115(4):515-9.
 
2. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res. 2005 Feb;19(2):148-51.
 
3. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol. 2005 Feb 28;97(2):281-4. Epub 2005 Jan 6.
 
4. Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006 Nov;13(9-10):607-11. Epub 2006 Sep 18.
 
5. Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):439-42.
 
6. Bathaie SZ, Mousavi SZ. New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr. 2010 Sep;50(8):761-86.
 
7. Zhong YJ, Shi F, Zheng XL, Wang Q, Yang L, Sun H, et al. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms. Acta Pharmacol Sin. 2011 Oct 10.
 
8. Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm Biol. 2011 Oct;49(10):1039-45.
 
9. Amin A, Hamza AA, Bajbouj K, Ashraf SS, Daoud S. Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology. 2011 May 23. doi: 10.1002/hep.24433.
 
10. Gutheil WG, Reed G, Ray A, Dhar A.        Crocetin: an Agent Derived from Saffron for Prevention and Therapy for Cancer.        Curr Pharm Biotechnol. 2011 Apr 5.
 
11. Samarghandian S, Tavakkol Afshari J, Davoodi S. Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction.  Appl Biochem Biotechnol. 2011 May;164(2):238-47.
 
12. Samarghandian S, Boskabady MH, Davoodi S. Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line.
Pharmacogn Mag. 2010 Oct;6(24):309-14.
 
13. Chryssanthi DG, Dedes PG, Karamanos NK, Cordopatis P, Lamari FN. Crocetin inhibits invasiveness of MDA-MB-231 breast cancer cells via downregulation of matrix metalloproteinases. Planta Med. 2011 Jan;77(2):146-51. Epub 2010 Aug 27.
 
14. Bakshi H, Sam S, Rozati R, Sultan P, Islam T, Rathore B, et al. DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev. 2010;11(3):675-9.
 
15. Dhar A, Mehta S, Dhar G, Dhar K, Banerjee S, Van Veldhuizen P, et al. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009 Feb;8(2):315-23.
 
16. Bakshi HA, Sam S, Feroz A, Ravesh Z, Shah GA, Sharma M. Crocin from Kashmiri saffron (Crocus sativus) induces in vitro and in vivo xenograft growth inhibition of Dalton's lymphoma (DLA) in mice.
Asian Pac J Cancer Prev. 2009;10(5):887-90.
 
 
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