Monday 21 May 2012

Sniffing Saffron

Jacob Schor, ND, FABNO

A particularly curious paper was published in the June 2011 issue of Phytomedicine.  In it, H. Fukui and colleagues tell us that sniffing at saffron is stimulus enough to trigger hormonal changes in young women. 

This was a double-blinded, placebo-controlled study involving just a short period of exposure ( 20 minutes) to the saffron.

Forty-seven female college students took part in the study.  Of these, 36 were randomly assigned to a saffron group and 11 assigned to a control group. Each sniffed at either a dilute solution of saffron or a for 20 minutes. 

The experimental solutions of saffron were diluted in to such a degree that the smell of saffron could not be sensed. The control was 76% ethanol only.


The way the experiment worked is that the women submitted saliva samples before and after a twenty-minute period of sample inhalation. After the second sample was collected, they took a psychological test (the State-Trait Anxiety Inventory: STAI) to measure their anxiety levels.  Their saliva samples were tested for levels of cortisol, testosterone and estrogen.

Honestly, who would think that sniffing at anything for twenty minutes would make much of a difference?  But according to these researchers,  sniffing this unrecognizable solution of diluted saffron had a significant effect on these young women.  Their cortisol levels  went down and their estrogen levels went up.  Sniffing the plain ethanol used as a placebo also caused changes; it increased cortisol and decreased estrogen levels. 

Anxiety levels went down in the saffron sniffing group.  [1]  

That smelling saffron had any effect comes as a welcome surprise.  
Saffron consists of the stigma of a small crocus named in Latin, Crocus sativus.  Harvesting saffron is so labor intensive that typically saffron is considered too expensive to use as medicine. But if all a patient needs to do to get benefit is sniff the stuff, well than cost is not longer an issue.

A research group reported about three years ago that taking 30 mg/day of saffron orally improved PMS symptoms. It took 3-4 menstrual cycles to see results.  

So really saffron treatments are not that expensive.  If you figure 30 mg/day for 100 days then the total amount of saffron needed is just 3 grams.  Google tells me that saffron is currently selling online for $20/gram.  Thus $60 should buy enough bulk saffron to try this experiment with patients.  Of course this is bulk saffron.  Ground, diluted and encapsulated, the saffron would cost more.

There are at least four randomized double-blinded placebo controlled human clinical trials in which saffron was found effective in treating depression.  

Two of these studies, used 30 mg of saffron a day in 6-week trials.  One compared saffron against placebo while the other compared saffron effect against the antidepressant Prozac. Saffron worked far better than the placebo, having a benefit comparable with Prozac. [3,4]  

The studies just mentioned used saffron made from the flower stigma.  Two newer studies used flower petals instead.  The results were the same as those gotten using actual saffron. Flower petals from the saffron crocus work far better than placebos to control  depression. [5]    They too work about as well as Prozac.[6]  There’s an obvious advantage to using the petals.  They’ve got to cost less than saffron.  

In a way all of these trials are a progression from most expensive to least expensive forms of saffron.  Saffron is the most expensive, smell, well what does that cost?  It’s not clear from this study whether smell alone will work as well as the stigma or flower petal treatments.

As strange as all this sounds, this study isn’t the only example of smells having medical impact.  We can find other examples of benefits from smells when we search for research on ‘aromatherapy.’ Aromatherapy using lavender extracts lowers anxiety in both adult and pediatric surgical patients. [7,8]    

Other relatively recent studies suggest that saffron might be food for a range of medical conditions, in particular cancer. [9] 

In the last twelve months there have been a bunch of interesting papers published on saffron and cancer. 

An October 2011 study says the saffron extract crocetin  increases the ability of the chemo drug vincristine to kill cervical, lung, ovary and breast cancer cell.[10]    Another Another study describes using saffron alone to kill cervical and breast cancer cells. [11]  A May 2011 paper reported that, “…saffron exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis.” [12]  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…”[13]  Papers from both May 2011 and 2010 suggest a potential benefit against lung cancer.[14]  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.”[15]      A January 2011 paper reported that Crocetin inhibits invasiveness of breast cancer cells through downregulation of matrix metalloproteinases.”[16]      Other papers have suggested possible utility in treating pancreatic cancer and lymphoma. [17,18, 19]      

While the prospect of treating cancer through ‘saffron aromatherapy’ is tempting, the crocetin fraction used in these cancer studies is probably not delivered via aroma.  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 for its cancer killing action, is the portion of the plant chemistry that acts as a color dye.  It conveys color more than odor or taste and probably didn’t reach the nose of these women.  

Thus, while it would be tempting to tell cancer patients to start ‘sniffing’ saffron, if we actually want to kill cancer cells, the patients will probably have to actually swallow saffron pills. 

At this point the truth is that there are no human published about using saffron to treat cancer.  We can be pretty sure that saffron does work to reduce anxiety and treat depression.  So we can suggest saffron to cancer patients to lower their feelings of depression.  At the same time we can hope that as a side effect the saffron helps cure their cancer.

Though in theory it should be cheaper to use the petals of the saffron crocus than actual saffron stigma, who knows where we can buy these petals?  It might just be easier and for the time, cheaper to use saffron.  We certainly should not be surprised to discover some herb company selling capsules of saffron petal in the near future.  

1. Fukui H, Toyoshima K, Komaki R. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine. 2011 Jun 15;18(8-9):726-30. 

2. 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.

3. 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.

4. 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.

5. 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.

6. 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. 

7. Braden R, Reichow S, Halm MA. The use of the essential oil lavandin to reduce preoperative anxiety in surgical patients. J Perianesth Nurs. 2009 Dec;24(6):348-55.

8. Nord D, Belew J. Effectiveness of the essential oils lavender and ginger in promoting children's comfort in a perianesthesia setting. J Perianesth Nurs. 2009 Oct;24(5):307-12.

  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.

  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. doi: 10.1038/aps.2011.109. 

  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.




www.DenverNaturopathic.com
Jacob Schor, ND, FABNO

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