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
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…. [andcould]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.

> What’s so good about agave syrup?
> Jacob Schor, ND, FABNO
> www.DenverNaturopathic.com
> March 1, 2012
>>> Reading this morning’s New York Times while watching a storm bluster outside our cabin windows I opened today’s recipe for a beet and berry smoothie that looks more than a little tasty:
> http://www.nytimes.com/2012/02/29/health/nutrition/mixed-berry-and-beet-smoot...
>> While the Times recipe looks quite good and I was about to forward it to all of you, I noticed that for sweetener they suggest honey or agave syrup.
>> When or how did agave syrup achieve status as a healthful equivalent of honey? I must assume some very good marketing firm has been at work.
>> The following information on agave syrup is quoted directly from a posting on Food Renegade’s website (http://www.foodrenegade.com/agave-nectar-good-or-bad/)
>>> “Native Mexican peoples do make a sort of sweetener out of the agave plant. It’s called miel de agave, and it’s made by boiling the agave sap for a couple of hours. Think of it as the Mexican version of authentic Canadian maple syrup.
>> "But this is not what agave nectar is. According to one popular agave nectar manufacturer, “Agave nectar is a newly created sweetener, having been developed in the 1990s.” In a recent article now posted on the Weston A. Price foundation’s website, Ramiel Nagel and Sally Fallon Morell write,
> Agave “nectar” is not made from the sap of the yucca or agave plant but from the starch of the giant pineapple-like, root bulb. The principal constituent of the agave root is starch, similar to the starch in corn or rice, and a complex carbohydrate called inulin, which is made up of chains of fructose molecules. Technically a highly indigestible fiber, inulin, which does not taste sweet, comprises about half of the carbohydrate content of agave.
>> "The process by which agave glucose and inulin are converted into “nectar” is similar to the process by which cornstarch is converted into high fructose corn syrup (HFCS). The agave starch is subject to an enzymatic and chemical process that converts the starch into a fructose-rich syrup—anywhere from 70 percent fructose and higher according to the agave nectar chemical profiles posted on agave nectar websites.
>> "Compare that to the typical fructose content of high fructose corn syrup (55%)!
> In a different article, Rami Nagel quotes Russ Bianchi, managing director and CEO of Adept Solutions, Inc., a globally recognized food and beverage development company, on the similarities between agave nectar and high fructose corn syrup:
>> “They are indeed made the same way, using a highly chemical process with genetically modified enzymes. They are also using caustic acids, clarifiers, filtration chemicals and so forth in the conversion of agave starches into highly refined fructose inulin that is even higher in fructose content than high fructose corn syrup.”
> So there you have it. Agave nectar is not traditional, is highly refined, and actually has more concentrated fructose than high-fructose corn syrup. It is not a “natural” sweetener.”
>>> [Dr Schor writing again]
> If agave syrup is just a sweeter version of high fructose corn syrup, why have so many health conscious shoppers become enamored with it? Clearly this isn’t evidence based. Searching PubMed for scientific journal articles describing agave syrup’s effect on health yields only 3 citations. A similar search on honey yields, 5,470 articles. There’s no comparison. Scientists are not singing praises for agave.
>> The most recent article on agave is revealing. Published in Physiology and Behaviour back in 2009, Figlewicz et al fed rats moderate amounts of different sweeteners including high fructose corn syrup or agave. Agave’s effect on the rats was similar to that of high fructose corn syrup except that “serum triglycerides were higher in the Agave” group. Looking at the overall effects of even moderate consumption the researchers wrote: “We conclude that even moderate consumption of fructose-containing liquids may lead to the onset of unfavorable changes in the plasma lipid profile and one marker of liver health, independent of significant effects of sweetener consumption on body weight.” [1]
>> High fructose syrup isn’t particularly healthy. We’ve known since the 1970s that high fructose aversely impacts cardiovascular risk factors. If anything agave, because of its higher fructose content, may be worse.
>> The only good thing about agave syrup is cost. Perhaps its expense may limit use. Let’s not let them fool us though. Agave syrup is not natural and not particularly good for us. Better stick to honey.
>>>> [1] Figlewicz DP, Ioannou G, Bennett Jay J, Kittleson S, Savard C, Roth CL.Effect of moderate intake of sweeteners on metabolic health in the rat. Physiol Behav. 2009 Dec 7;98(5):618-24. Epub 2009 Oct 6.
>> ................................................................
>>

>>> Foods that Fight Cancer > Jacob Schor ND
> Fellow of the American Board of Naturopathic Oncology
> February 25, 2012
>> There is a website link that I always mean to give to patients but that I confess, I often forget to. So here we go:
>> The American Institute of Cancer Research (AICR) is a highly effective charity that funds cutting-edge cancer research that focuses on diet and nutrition. Fundamental to their mission is to give people practical tools and information to help them prevent – and survive – cancer.>> Their website provides a host of valuable tools especially ongoing lists and detailed information on the foods that research now tells us are useful in fighting cancer. See:
> http://www.aicr.org/foods-that-fight-cancer/
>> You can sign up for free weekly recipe emails that incorporate cancer fighting foods on their home page: http://www.aicr.org/
>> If you simply try one new recipe a week, you can gradually shift your diet from what is commonly referred to as the SAD (standard American diet) way of eating to a diet that focuses on anti-cancer action.
>> AICR funds fascinating research and you can also subscribe to a biweekly research update on the same webpage.
>> I have been impressed by AICR for years. They translate the latest scientific research into practical things people can do to improve their health. They do this better than any other cancer fighting group that I know of.
>> Take a moment to sign up for their recipe mailings now.
>>> ................................................................
>

>> Fasting, Cancer and Chemotherapy
> Jacob Schor, ND,> Fellow of the American Board of Naturopathic Oncology
> Feb 13, 2012
>>>> With the publication February 8 of Valter Longo’s most recent study on fasting and chemotherapy, we are close to the day when we tell our patients to fast during chemotherapy. In earlier publications, Longo informed us that fasting reduced chemotherapy toxicity during treatment. In this new paper published in Science Translational Medicine, Longo takes us a step further, presenting evidence that fasting enhances the benefit of chemotherapy by sensitizing cancer cells, making it more likely they will succumb to treatment.
>> Typically we like to only comment on human clinical trials and Longo’s study was conducted on mice not people. Nevertheless the information Longo has reported, is so compelling that it’s worth talking about now. >> Over the past five years, Valter Longo has introduced fasting into cancer treatment. Fasting protects normal cells in mice and very possibly in people, from the side effects caused by chemotherapy drugs. Up until this current study, the possibility still remained that fasting might also protect tumor cells from chemotherapy, decreasing the benefit of treatment. In this new paper the authors show that fasting actually increases the efficacy of chemotherapy in the treatment of melanoma, glioma, breast cancer and neuroblastoma.>> Fasting helps chemotherapy kill cancer cells. In some instances fasting was as effective as chemotherapy at inhibiting tumor growth. Fasting sensitized 15 of the 17 cancer lines tested to chemotherapy in vitro. Combining fasting with chemotherapy resulted in a synergistic 20-fold increase in cancer cell DNA damage while healthy cells were unaffected. This work suggests that fasting has the potential to sensitize a range of tumor types to chemotherapy treatment while at the same time increasing tolerance.
>> We were first introduced to Longo’s theory that fasting was helpful by an article about his work that appeared in 2008 in the journal Science. Valter Longo, a professor at the University of Southern California (USC) had, until his recent foray into cancer research, studied the effect of caloric restriction on life span. Animals who spend their lives hungry live longer than well-fed animals. Cutting calories slows the growth rate of cells and makes them more resistant to stress. Knowing this, Longo questioned whether this same reaction might be useful in cancer treatment. Slowing the growth rate of cells might offer protection against chemotherapy, which preferentially injures faster growing cells. Longo’s earlier research using yeast suggested that cancer cells might not be able to slow their growth rates when hungry the way healthy cells do. Thus fasting might have a two-fold effect during chemotherapy, protecting healthy cells while leaving cancer cells susceptible.
> [1]
>> Healthy cells when hungry become stress resistant; they budget their energy to protective and maintenance functions rather than spending energy on reproduction and growth.>> Longo tested his ‘hunger protects theory’ on yeast and then on mice. Mice who had been without food for 48 to 60 hours showed no signs of toxicity when given high doses of chemotherapy. Half of the control animals used in this experiment that were allowed to eat up to and during the chemo treatment died. While fasting lessened chemo side effects in this first report, tumor cells, at least neuroblastoma cells, remained sensitive to chemotherapy. [2]
>> Not unexpectedly, this 2008 paper created quite a stir. Oncologists warned their patients not to try this at home. Not surprisingly many patients did. Anecdotal stories from patients suggesting similar reduction in chemo side effects appeared. [3]
>> This led to a report published in the December 2009 issue of Aging. Safdie et al describe the results of human experiments they conducted with Longo. They described 10 cases in which patients diagnosed, “… with a variety of malignancies had voluntarily fasted prior to … and/or following … chemotherapy. None of these patients, who received an average of 4 cycles of various chemotherapy drugs in combination with fasting, reported significant side effects caused by the fasting itself other than hunger and lightheadedness. …. The six patients …. reported a reduction in fatigue, weakness, and gastrointestinal side effects while fasting. …. fasting did not prevent the chemotherapy-induced reduction of tumor volume or tumor markers. …the 10 cases presented here suggest that fasting in combination with chemotherapy is feasible, safe, and has the potential to ameliorate side effects caused by chemotherapies…” >> While Longo and colleagues were not ready to, “… establish practice guidelines for patients undergoing chemotherapy,” they had set an example that spurred our interest and that of our patients. [4]
>>> Why would fasting have such an impact on cancer. Monkeys on a long-term caloric restricted diets experience half the cancer rate as monkeys on a standard diet. But what about these short term diets? Short-term starvation (STS) is the term Longo now favors in his writing. STS changes a range of biological parameters, decreasing IGF-1, blood glucose and inflammatory cytokines in particular. STS causes healthy cells to rapidly switch to a ‘protected mode,’ which triggers significant changes in IGF-I and many other proteins and molecules and is capable of protecting mammalian cells and mice from various toxins, including chemotherapy. Longo coined the term “Differential Stress Resistance (DSR) to describe the ability of STS to trigger protective reactions in healthy cells but not in cancer cells. In the early yeast experiments, the effect was dramatic, a 1,000 fold difference in protection against chemotherapy induced oxidative stress between normal cells and cancer
> -like
> yeast cells. If even a fraction of this DSR were seen in humans it would still be clinically relevant, significantly impacting long-term survival. [4,5]
>> The current study found that fasting enhanced chemotherapy toxicity against various mouse cancer models including murine breast cancer, melanoma, glioma and neuroblastoma. >>> The greatest therapeutic effect was seen when fasting was combined with either doxorubicin (10 mg/kg) or cyclophosphamide (150 mg/kg). In the breast cancer mice, two fasting cycles along with chemo resulted in tumors less than half the size of those in mice treated with cyclophosphamide alone. Similar benefits were seen in the treatment of melanoma and glioma.
>> In neuroblastoma injected mice, 5 two-day periods of fasting spread over 34 days limited tumor size to half of that reached in normally fed mice.>> A combination of multiple fasting cycles and high dose chemotherapy resulted in cancer free survival in aggressive metastatic models in which murine breast cancer cells, melanoma cells, or neuroblastoma cells were injected into immunocompetent mice .[check this. Perhaps it was incompetent?] Fasting potentiated chemotherapy and extended the survival of all the mice models of metastatic cancer. Fasting the mice in combination with doxorubicin reduced the metastases of melanoma cells and to which organs to tumors settled compared to the normally fed mice. Fasting the mice reduced lung metastases by 35% and no metastases were detected in the liver or spleen of fasted mice.
>> Long-term survival (>180 days) occurred in 42% of murine neuroblastoma mice who underwent two cycles of fasting and high dose doxorubicin compared to 100% mortality in the mice who ate freely while undergoing similar chemotherapy treatment. In a model of pediatric malignancy that combined fasting with a chemotherapy cocktail of cisplatin and doxorubicin, 25% of the mice achieved long-term survival (>300 days) while all of the mice that ate freely died by day 75.>> These findings scream for our attention. Could it be this easy to increase cancer treatment effectiveness? > Prudence tells me that we need to write: ‘While this is concept has advanced from in vitro experiments to early animal trials, increased efficacy of treatment has not been proven in humans.’ >> On the other hand, what do we have to lose? Well weight is one thing that one loses during chemo and for a skinny and sick patient, fasting may not be a great idea. Still, Longo’s earlier human study suggests that because patients don’t feel as ill from chemo, once they start eating they quickly regain the weight they lost while fasting.
>> There is a broader more philosophical question that this study raises. The trend in medicine and especially oncology has been to customize treatment. In oncology treatment is prescribed based on cancer type, staging and more and more it is chosen based on specific genetic characteristics of the tumor cells. In the near future none of us will be surprised if treatments are custom tailored based on the patient’s individual genome. Fasting a patient is the opposite of this trend. Rather than employing individual genetic characteristics to fine tune treatment, fasting employs basic universal compensatory reactions that are shared not just by certain individuals but between species and kingdoms of living things. Rather than a specific treatment, it is a general treatment. If testing for and treating Her-2 neu receptor status is on one extreme of a spectrum than fasting is on the opposite end of this spectrum. It is probably not too great a generalization to suggest that mode
> rn
> medicine focuses on one end of this spectrum while traditional naturopathy and nature cure have focused on the opposite end. Fasting is squarely on our side of the line and our profession and our patients should be paying attention to this research.
>> Primary Reference:> Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy. Sci Transl Med. 2012 Feb 8.>> footnoted references:
> 1. Jennifer Couzin Can Fasting Blunt Chemotherapy's Debilitating Side Effects? Science 29 August 2008:
>> 2. Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, Longo VD. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20. Epub 2008 Mar 31.
>> 3. Jennifer Couzin CANCER RESEARCH: Can Fasting Blunt Chemotherapy's Debilitating Side Effects? Science 29 August 2008 321: 1146-1147
>> 4. Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 2009 Dec 31;1(12):988-1007.
>> 5. Longo VD, Fontana L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms.Trends Pharmacol Sci. 2010 Feb;31(2):89-98. Epub 2010 Jan 25.
>> 6. Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle. 2010 Nov 15;9(22):4474-6.>> 7. Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene. 2011 Jul 28;30(30):>>> ................................................................
>>

http://www.fda.gov/Safety/Recalls/ucm287838.htm?source=govdelivery">Rexall Issues Allergy Alert on Undeclared Shellfish in Calcium 1200mg plus Vitamin D 1000 IU Softgels

01/16/2012 08:08 PM EST

Today Rexall, Inc., of Deerfield Beach, Florida, announced a recall of Rexall Calcium 1200 mg plus 1000IU Vitamin D3, 60 softgels. The affected bottles actually contain a TABLET product, Triple Strength Glucosamine Chondroitin and MSM Tablets.

>>> Feverfew: part 2
> Nothing about this is simple
> Jacob Schor ND FABNO
> January 6, 2011
> www.DenverNaturopathic.com
>>> While one might think that feverfew’s long track record of safety in combination with the benign adverse effects profile seen in phase I trails might put it into a “try it, it won’t hurt” category, life may not be that simple.
>> Recently we sent out a newsletter reviewing the various studies that suggest feverfew parthenolide might be beneficial in treating multiple myeloma. The studies suggest a possibility of benefit and suggest low risk. Within hours of sending out that newsletter I received an email from a woman with multiple myeloma who told me that she had tried taking feverfew a few years ago and that while taking it all of her disease blood markers worsened.
>> That’s not what one wants to read before breakfast.
>> During the period that she experimented with feverfew, it seems she was also deficient in vitamin D. This may be important. Give me a few moments to explain.
>> In the December 2010 issue of Blood, Hassane et al from Weill Cornell Medical College, reported some interesting findings on feverfew parthenolide and acute myeloid leukemia. These researchers had previously reported that parthenolide “… can impair the survival and leukemogenic activity of primary human acute myeloid leukemia (AML) stem cells. However, despite the activity of this agent, PTL also induces cellular protective responses that likely function to reduce its overall cytotoxicity.” In other words, parthenolide while ‘impairing the cancer stem cells, also appeared somewhat protective, reducing overall cytotoxicty.
>> So Hassane’s group looked for other chemicals that might counter this protective effect and make parthenolide more toxic to the unwanted stem cells.>> They found that compounds acting along the phosphatidylinositol 3-kinase 9
> (PI3K) and mammalian target of rapamycin (mTOR) pathways enhanced the action of parthenolide and significantly decreased tumor burden. This would suggest that combining parthenolide with drugs that impact these two pathways might increase benefit. [1]
>>> By the way, for those of you who are curious about what “mTOR” means, this is an abbreviation for “mammalian targets of rapamycin. Rapamycin is a drug used in cancer chemotherapy. Before it was understood exactly how the drug worked, this somewhat vague name was applied to the chemical pathways on which the drug acted. The pathways targeted by the drug, in mammals.
>> Thus Hassane et al’s work suggests that feverfew might be more effective in combination with rapamycin.>> We should also pay attention to things that might enhance the effect of rapamycin. Resveratrol appears to do this. [2] In certain types of cancer, reseveratrol inhibits both mTOR and PI-3K pathways. [3] >> While we continue to see studies suggesting resveratrol has a favorable action on multiple myeloma, many of us still view its use with caution in multiple myeloma, recalling the SKG clinical trial on treating multiple myeloma with reseveratrol that was canceled due to apparently negative outcomes. [4]
>> Vitamin D may also impact mTOR pathways. [5] If so, a vitamin D deficiency may have a greater negative impact in combination with feverfew than one might have guessed. Perhaps this may be why my correspondent experienced a negative response to taking feverfew? An older paper (from 2002) tells us that vitamin D in combination with feverfew enhances differentiation of leukemia cells. Differentiation is a favorable sign, the cells appear less cancerous and more ‘normal.’ [6] Perhaps vitamin D deficiency causes an unfavorable response with feveverfew increasing rather than suppressing mTOR pathways?
>> What else besides resveratrol might have a favorable impact on feverfew action? >> Sulforaphane derived from sprouted broccoli may potentially block mTOR pathways, at least it does so in a mouse model of prostate cancer.
>> Wu et al reported in November 2011 that a curcumin derivative, tetrahydrocurcumin, impacts both the PI-3K and mTOR pathways. A few months earlier in July, Wong et al had announced that curcumin inhibited growth of leiomyosarcoma cells also by inhibiting these same pathways. While both rampamycin and curcumin slowed growth of these cancer cells, at high concentrations, only curcumin triggered apoptosis (cell suicide); rapamycin did not. >> Today’s take home lesson is that biology is rarely as simple as we would want. Although feverfew parthenolide would seem to be safe and potentially beneficial in the treatment of multiple myeloma, we should approach parthenolide use with caution. We should test vitamin D levels in the patient prior to instituting treatment with feverfew and raise the levels if low. We should then monitor blood markers with care as feverfew treatment is initiated and suspend use if adverse effects are seen. If a patient is stable on feverfew we might then consider adding sulforaphane and resveratrol. >>> References:
>> 1. Hassane DC, Sen S, Minhajuddin M, Rossi RM, Corbett CA, Balys M, Wei L, Crooks PA, Guzman ML, Jordan CT. Chemical genomic screening reveals synergism between parthenolide and inhibitors of the PI-3 kinase and mTOR pathways. Blood. 2010 Dec 23;116(26):5983-90. Epub 2010 Oct 1.
>> 2. He X, Wang Y, Zhu J, Orloff M, Eng C. Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011 Feb 28;301(2):168-76. Epub 2010 Dec 17.
>> 3. Jiang H, Shang X, Wu H, Gautam SC, Al-Holou S, Li C, Kuo J, Zhang L, Chopp M. Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells. J Exp Ther Oncol. 2009;8(1):25-33.
>> Free PMC Article
>> 4. http://www.myelomabeacon.com/news/2010/11/30/glaxosmithkline-halts-all-furthe...
>> 5. Lisse TS, Hewison M. Vitamin D: a new player in the world of mTOR signaling.
> Cell Cycle. 2011 Jun 15;10(12):1888-9. Epub 2011 Jun 15.
>> 6. Kang SN, Kim SH, Chung SW, Lee MH, Kim HJ, Kim TS. Enhancement of 1 alpha,25-dihydroxyvitamin D(3)-induced differentiation of human leukaemia HL-60 cells into monocytes by parthenolide via inhibition of NF-kappa B activity. Br J Pharmacol. 2002 Mar;135(5):1235-44.
>> 7. Keum YS, Khor TO, Lin W, Shen G, Kwon KH, Barve A, Li W, Kong AN. Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway. Pharm Res. 2009 Oct;26(10):2324-31. Epub 2009 Aug 8.
>> 8. Wu JC, Lai CS, Badmaev V, Nagabhushanam K, Ho CT, Pan MH. Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia HL-60 cells. Mol Nutr Food Res. 2011 Nov;55(11):1646-54. doi: 10.1002/mnfr.201100454. Epub 2011 Sep 19.
>> 9. Wong TF, Takeda T, Li B, Tsuiji K, Kitamura M, Kondo A, Yaegashi N. Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition. Gynecol Oncol. 2011 Jul;122(1):141-8. Epub 2011 Mar 29.
>>> ................................................................
>>> We hope you find the information in these newsletters useful, informative and hopefully entertaining. If you want your name removed simply leave a message at the office (303-337-4884) or go to the website: denvernaturopathic.com and unsubscribe, or reply with the message "REMOVE" in the subject line. If on the other hand you want to be added to the mailing list follow the prior instructions but subscribe. > We are posting most of these newsletters in our 'NEWS' section of the website. The website versions contain more complete references and often abstracts of the references quoted and links to the full text of many of the journal articles mentioned. You don't have to be a patient to sign up and we encourage you to get your friends on our mailing list so you don't have to keep forwarding the newsletters that you find interesting.

Feverfew and Multiple Myeloma
Jacob Schor ND, FABNO
www.DenverNaturopathic.com
January 5, 2012

Studies on parthenolide, an extract from the common herb feverfew, suggest that it may have possible benefit for patients with multiple myeloma, enough so that we can now suggest they consider using them.

We first wrote about feverfew and its possible role in treating cancer about 6 years ago.
That newsletter is still posted at: http://denvernaturopathic.com/news/feverfew.html

At that time the theory that cancer tumors were the descendents of cancerous stem cells was just starting to be considered.   That feverfew/parthenolide could inhibit cancer stem cells was intriguing.  Over the last half decade acceptance of the stem cell theory of cancer has become more widespread. Dr. Siddhartha Mukherjee, author of “The Emperor of All Maladies: A Biography of Cancer,” wrote an interesting piece on stem cells for the New York Times that sums up the current understanding.  Titled “The Cancer Sleeper Cell,” Mukherjee’s article appeared in the Sunday Magazine section October 29, 2010.  It can be read at:
http://www.nytimes.com/2010/10/31/magazine/31Cancer-t.html?scp=6&sq=by+mukherjee+siddhartha&st=nyt

In light of this past history it’s worth looking at the half dozen or so papers suggesting feverfew for multiple myeloma.

The earliest paper that I’ve found on the topic was published July 2006

Cheng et al reported that they had cultured human multiple myeloma (MM) cells and exposed them to various dilutions of parthenolide while measuring growth rates.  Exposure to the parthenolide “… significantly inhibited the proliferation and viability of the MM cells time and dose-dependently (all P < 0.01), and significantly induced the cell apoptosis after 48 h in a dose-dependent manner (P < 0.01).”   Depending on concentration of parthenolide as many as 40% of the cells underwent apoptosis (cellular suicide). [at 10 micromol/L apoptosis rate was 40.9% +/- 3.1%]   [1]

In December of the same year Wang et al reported that parthenolide induced apoptosis in MM cells by increasing reactive oxygen species within the cells and that  activity of intracellular catalase is a crucial determinant of their sensitivity to parthenolide.    [2]

The next addition to our knowledge was an article by Suvannasankha et al from Indiana University in March 2008.  They explored the effects of parthenolide on multiple myeloma cells in the context of the bone marrow microenvironment. They reported that parthenolide inhibited growth of MM cells lines, including drug-resistant cell lines, and primary cells in a dose-dependent manner. Parthenolide canceled out the growth stimulating effects of cytokines interleukin-6 and insulin-like growth factor I.

In addition, parthenolide blocked interleukin-6 secretion from bone marrow stromal cells triggered by the adhesion of MM cells. Parthenolide cytotoxicity is both caspase-dependent and caspase-independent. The parthenolide actually triggers chemical changes within the myeloma cells that make them more sensitive to parthenolide so that over time lower amounts of parthenolide were required to inhibit growth. An additive effect and synergy were observed when parthenolide was combined with dexamethasone and TNF-related apoptosis-inducing ligand, respectively.   [3]

A paper by Kong et al published in October 2008 further details the various mechanisms of action rgr parthenolide has on multiple myeloma cells.
It inhibits the angiogenesis (building new blood vessels required to supply cells with oxygen and food) induced by multiple myeloma cells. It also decreases NF-kappaB activity and significantly suppresses the expression of VEGF and IL-6 mRNA and protein.  This might in part explain why parthenolide inhibited the angiogenesis induced by MM cells.  [4]

The most recent contribution is a June 2011 paper by Gunn et al that looked at the action of both parthenolide and andrographolide.  They were able to demonstrate that both products have a “potent” effect against multiple myeloma cancer stem cells and not just against the cancer cells. The later chemical tested andrographolide is a constituent of a tropical plant Andrographis paniculata and probably should be the subject of another newsletter as recent findings suggest that it too may possess desirable action action against a range of tumor types.  For example a December 2011 paper suggests it may enhance the effect of chemotherapy against ovarian cancer.   [5]

Given our long experience of using feverfew in treating migraine headaches and also the phase I trial that suggests low if any toxicity as mentioned in our earlier article, it seems reasonable for patients with multiple myeloma to try adding it to their treatment protocol.

References:

1. Chen ZC, Li QB, Shao J, Lü J, You Y, Zhong ZD, Zou P. [Proliferation inhibiting and apoptosis inducing effects of parthenolide on human multiple myeloma cells]. Zhonghua Yi Xue Za Zhi. 2006 Jul 25;86(28):1993-6.
 [Article in Chinese]

2. Wang W, Adachi M, Kawamura R, Sakamoto H, Hayashi T, Ishida T, Imai K, Shinomura Y. Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell sensitivity depends on catalase activity. Apoptosis. 2006 Dec;11(12):2225-35.

3. Suvannasankha A, Crean CD, Shanmugam R, Farag SS, Abonour R, Boswell HS, Nakshatri H. Antimyeloma effects of a sesquiterpene lactone parthenolide. Clin Cancer Res. 2008 Mar 15;14(6):1814-22.

4. Kong F, Chen Z, Li Q, Tian X, Zhao J, Yu K, You Y, Zou P. Inhibitory effects of parthenolide on the angiogenesis induced by human multiple myeloma cells and the mechanism. J Huazhong Univ Sci Technolog Med Sci. 2008 Oct;28(5):525-30. Epub 2008 Oct 10.

5. Yunos NM, Beale P, Yu JQ, Huq F. Synergism from the combination of oxaliplatin with selected phytochemicals in human ovarian cancer cell lines. Anticancer Res. 2011 Dec;31(12):4283-9.

................................................................

We hope you find the information in these newsletters useful, informative and hopefully entertaining. If you want your name removed simply leave a message at the office (303-337-4884) or go to the website: denvernaturopathic.com and unsubscribe, or reply with the message "REMOVE" in the subject line.  If on the other hand you want to be added to the mailing list follow the prior instructions but subscribe.
We are  posting most of these newsletters in our 'NEWS' section of the website.  The website versions contain more complete references and often abstracts of the references quoted and links to the full text of many of the journal articles mentioned. You don't have to be a patient to sign up and we encourage you to get your friends on our mailing list so you don't have to keep forwarding the newsletters that you find interesting.

>>> A Christmas without mistletoe
> December 2011
>> A drought in Texas has decimated that state’s wild mistletoe and made it so difficult to find that our country’s mistletoe industry has been effectively shut down. >> http://www.nytimes.com/2011/12/22/garden/a-mistletoe-shortage-threatens-a-hol...
>> This leaves me saddened as I have always treasured seeing the odd sprig of mistletoe displayed as part of the season’s decorations. It is a fitting reminder of how deeply our holiday celebrations are linked to the ancient traditions. Seeing it is also an excuse to look at the new journal articles that have been published over the preceding year.
>> Thinking about mistletoe’s history is also a welcome antidote to what are now referred to as the ‘Christmas Wars.’ As David Sirota writes in this morning’s Denver Post, there seems to be a yearly battle between the those who are offended by the blurry line between church and state and those who would want the line shifted closer to their way of thinking.
> http://www.denverpost.com/opinion/ci_19610671
>> Mistletoe continues to play a role in our holiday celebrations and this is an interesting reminder of how deeply rooted our winter celebrations are in Druidic cultures.
>> Mistletoe is winter fruiting and an evergreen; the leaves stay green as they produce berries in the dead of winter. Because of this trait, early cultures revered the plant as a symbol of immortality and rebirth. When every thing else in the world appeared frozen and dead, mistletoe is full of life. For people deeply connected with the natural world, this winter rebirth stood out.
>> Though I am sitting here about to start reviewing the publications in the medical literature on mistletoe, we must digress and first acknowledge mistletoe’s historic and religious significance. >> In an earlier world, the fifth day following the new moon that follows the winter solstice, was the day on which Druid priests harvested mistletoe. With ritual ceremony, they cut the mistletoe down from oak trees using a golden sickle while their attendants caught the branches in their robes before the mistletoe touched the ground. >> Mistletoe (Viscum alba) is a parasitic plant that lives on trees. Although the leaves contain some chlorophyll, a mistletoe plant can’t make enough food to feed itself; it obtains most of its nutrition from the host tree. Birds eat mistletoe seeds and then carry them from tree to tree. The seeds will not sprout until the berries are digested. After birds digest the berries, they excrete the seeds as a gooey mass that sticks to whatever it lands on. This adhering mass of bird crap seed and mistletoe seed, which is also widely called a ‘viscum’, is the origin of our word, viscous. If this viscous Viscum seed excrement lands on a tree, the seed sprouts, sending roots through the bark and into the tree to draw water and nourishment. Mistletoe spends its entire life cycle never touching the earth, an attribute that gave it early mystic significance. >> The association of mistletoe with an easing of the social norms on who one might kiss goes back to the Norse story of Frigga and Balder.
>> This is a story of overprotective motherhood. Frigga, the goddess of love and beauty and probably hovering motherhood, did her best for Balder, her favorite son. She went all through the world and secured promises from all beings and things that sprang from the four elements--fire, water, air, and earth, that they would not hurt her son Balder. The Achilles heel of this plan of course was mistletoe. Mistletoe it was thought came from nowhere. It sprang from none of the four elements. If it sprang from anything, it sprang from bird poop but at the time of the story, this route of seed transmission was overlooked. The story goes that Loki, the sly evil spirit of Norse mythology, made an arrow of mistletoe and tricked Balder’s blind brother Hoder into shootiing Balder through the heart with it.
>> Frigga does a lot of weeping in the story and in the cold winter, her tears turn into the white berries of mistletoe. The berries of this immortal plant wake Balder back to life and the plant becomes a symbol of undying love.>> There is another and perhaps better explanation for this kissing under mistletoe tradition. Mistletoe is an abortifacient; it both prevents pregnancy from occurring or prevents a pregnancy from going to term. It no doubt acted as an early but effective form of birth control. Mistletoe was apparently consumed in adequate quantities during the early Druidic seasonal feasts to prevent pregnancies. People figured out that during the ‘mistletoe season’ promiscuous behavior did not lead to the expected consequences. We preserve this early Druidic pragmatism when we act out the belief that what happens under the mistletoe stays under the mistletoe, that is it allows promiscuity without repercussion.
>> Though this may seem irrelevant to the current science, this long prehistoric tradition of mistletoe having magical attributes is relevant in appreciating the modern cancer research on using mistletoe extracts. People expect magical results from mistletoe and it’s hard to filter out fact from belief when it comes to effectiveness. Mistletoe treatments cannot but have significant placebo effect.
> Rudolf Steiner originated the modern use of mistletoe for cancer treatment. Steiner (1861-1925) was the Austrian philosopher behind a belief system called Anthroposophy, something Wikipedia describes as, “a movement based on the notion that there is a spiritual world accessible to pure thought through a path of self-development.” [Whatever exactly that means.] In modern terms, we might want to write this off as just another cult but that would do Steiner and his followers, of which there are still many, a great injustice. Steiner came up with many practical applications for his philosophy and worldview that are still with us, including biodynamic agriculture, anthroposophical medicine, eurythmy and the one we are probably the most familiar with, Waldorf Education. > Steiner’s followers who practice Anthroposophical Medicine developed a fermented preparation of mistletoe called Iscador.> Iscador is well accepted in Germany, Switzerland and Northern Europe as an approved cancer treatment. Today, mistletoe extracts are the most frequently prescribed unconventional cancer therapies in Germany and in some other European countries. In Europe, approximately 60 to 70 percent of cancer patients use some form of mistletoe. Whether or not mistletoe is actually effective for treating cancer has been debated for years. A number of positive studies appeared in the German medical literature in the late 1980’s and early 1990s.> Yet while well accepted in Europe, mistletoe is uncommon in the United States. The American Cancer Society has long condemned it and for years warned against people against using it. Their website is a reliable source of negative research on Iscador.> The most important of these negative studies is from Eggermont and his colleagues, who compared Iscador to interferon in treating melanoma. Between 1988 and 1996, the European Organization for Research and Treatment of Cancer Melanoma Group performed a prospective, randomized phase III trial that compared the effects of several types of interferon or Iscador against an untreated control group. High-risk patients were randomized and followed until their first progression or death. In the end, there was no apparent difference in either disease free survival or overall survival in any of the interferon groups or the Iscador patients over the control group. In other words, taking Iscador didn’t do these patients any good. [1] Of course, one has to keep this in perspective. Pretty much nothing works well for treating melanoma. While Iscador was no miracle cure but this should not be a great surprise, nothing else is either.
> There are reports in the literature of cases that appear to respond to Iscador. A 1989 article in Thorax describes a case of small cell lung cancer that got better with Iscador treatment. [2] Still for the most part, we don’t hear much about Iscador in the United States, except for a small flurry of interest when Suzanne Summers admitted she was using it.> In 2006, was a big year for Iscador research with quite a few interesting studies published. In January, an Israeli group reported reviewing 15 different prospective studies on Iscador and finding that most reported positive results. [3] The same researchers published a paper in Anticancer Research in February describing their success at using Iscador to treat fluid build up in the abdomen of patients with advanced cancer.[4] In March, a Russian study reported that Iscador improved quality of life measurements of patients undergoing chemotherapy and radiation for breast cancer.[5] In June, French researchers published a paper comparing Iscador (made from oak mistletoe) against mistletoe extracts prepared from apple or pine grown mistletoes. They suggested that, at least in part, the effect of mistletoe involves mediation of nitric oxide production. [6] > A June 2006 paper compared the genetic characteristics of various breast cancer cell lines and their response to various mistletoe extracts.[7] Another June study, described the characteristics of cell death caused by mistletoe in multiple myeloma and lymphoma. The faster growing the tumor cells were, the more effective mistletoe was at killing them. [8] Still another June study comparing the effect of mistletoe on various types of cancer cells, found that colon and rectal cancer cells had the least response. [9] In July a paper published in the International Journal of Immunology described the effects of Iscador on immune function and theorized how these changes could fight cancer. [10] > In September, Anticancer Research published a paper authored by Swiss doctors comparing various mistletoe extracts to see which was most effective against pediatric brain tumor cells.[11] > Despite the popularity of Iscador in Europe, it is still rare to see it used in the United States, even among alternative providers. The American Cancer Society opposes its use and routinely posts warnings that it is ineffective or even dangerous on their website. The intensity of this opposition is what reminds me of the annual ‘Christmas Wars.’ People have strong opinions. Much of the intensity in this debate on the merits of mistletoe could possibly stem back to its association with pagan religions and with Steiner’s ‘philosophical cult.’ Thus it is no wonder that it is difficult to sort through the pros and cons. Both the proponents and the opponents to its use may be swayed by unacknowledged beliefs unrelated to its potential for therapeutic benefit. Let us hope that time and unbiased researchers will soon sort this out.
> A meta-analysis published in December 2009 provides what would appear to be strong objective evidence that mistletoe lengthens survival times in cancer patients. Data from 49 studies on the clinical effects of Iscador were combined and the effect on survival times of cancer patients calculated. These outcomes were expressed as hazard ratios (HR). The combined data yielded a ‘meta-study’ of 3,388 patents treated with Iscador and 7,253 untreated controls. The conclusion was that, “…treatment of cancer patients with the mistletoe extract Iscador is associated with a better survival…”[12] >> Mathhes et al described using Iscador in combination with chemotherapy for treating pancreatic cancer in June 2010.[13] Keep in mind though that they looked at using Iscador to enhance the effect of chemotherapy. There are some readers who will misinterpret these kinds of studies and think that Iscador might be effective instead of chemotherapy. >> Eisenbraun et al reported in January 2011 that Iscador used in conjunction with chemotherapy for breast cancer reduced side effects and improved quality of life. In their study 89% of the patients reported benefit.[14] > We will miss mistletoe this holiday season. It is a symbol that our modern holiday celebrations transcend our current religious beliefs and come to us from far back in a pre-history that traces its roots to a world view that predates our current religions.
> References:
>> 1. Kleeberg UR, Suciu S, Brocker EB, Ruiter DJ, Chartier C, Lienard D, Marsden J,> Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer. 2004 Feb;40(3):390-402.>> 2. Bradley GW,Clover A.Apparent response of small cell lung cancer to an extract of mistletoe and homoeopathic treatment.Thorax. 1989 Dec;44(12):1047-8.>>> 3. Bar-Sela G, Gershony A, Haim N.Harefuah. [Mistletoe (Viscum album) preparations: an optional drug for cancer patients?] 2006 Jan;145(1):42-6, 77.>>> 4. Bar-Sela G, Goldberg H, Beck D, Amit A, Kuten A. Reducing malignant ascites accumulation by repeated intraperitoneal administrations of a Viscum album extract. Anticancer Res. 2006 Jan-Feb;26(1B):709-13>> 5. Semiglazov VF, Stepula VV, Dudov A, Schnitker J, Mengs U. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res. 2006 Mar-Apr;26(2B):1519-29>> 6. Mossalayi MD, Alkharrat A, Malvy D. Nitric oxide involvement in the anti-tumor effect of mistletoe (Viscum album L.) extracts Iscador on human macrophages. Arzneimittelforschung. 2006 Jun;56(6A):457-60>> 7. Eggenschwiler J,Patrignani A,Wagner U, Rehrauer H, Schlapbach R,Rist L,et al. Gene expression profiles of different breast cancer cells compared with their responsiveness to fermented mistletoe (Viscum album L.) extracts Iscador from oak (Quercus), pine (Pinus), white fir (Abies) and apple tree (Malus) in vitro. Arzneimittelforschung. 2006 Jun;56(6A):483-96.>> 8. Kovacs E, Link S, Toffol-Schmidt U. Cytostatic and cytocidal effects of mistletoe (Viscum album L.) quercus extract Iscador. Arzneimittelforschung. 2006 Jun;56(6A):467-73.>> 9. Harmsma M,Ummelen M, Dignef W,Tusenius KJ,Ramaekers FC. Effects of mistletoe (Viscum album L.) extracts Iscador on cell cycle and survival of tumor cells. Arzneimittelforschung. 2006 Jun;56(6A):474-82.>> 10. Heinzerling L, von Baehr V, Liebenthal C, von Baehr R, Volk HD. Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo. J Clin Immunol. 2006 Jul;26(4):347-59. Epub 2006 May 17. >> 11. Zuzak TJ, Rist L, Eggenschwiler J, Grotzer MA, Viviani A. Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe). Anticancer Res. 2006 Sep-Oct;26(5A):3485-92. >> 12. Ostermann T, Raak C, Bussing A. Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review. BMC Cancer. 2009 Dec 18;9(1):451.>> 13. Matthes H, Friedel WE, Bock PR, Zänker KS. Molecular mistletoe therapy: friend or foe in established anti-tumor protocols? A multicenter, controlled, retrospective pharmaco-epidemiological study in pancreas cancer. Curr Mol Med. 2010 Jun;10(4):430-9.
>> 14. Eisenbraun J, Scheer R, Kröz M, Schad F, Huber R. Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract. Phytomedicine. 2011 Jan 15;18(2-3):151-7.>>> "Here we must mention the reverence felt for this plant by the Gauls. The Druids -- for thusly are their priests named - hold nothing more sacred than the mistletoe and the tree that bears it, as long as that tree be an oak.... Mistletoe is very rarely encountered; but when they do find some, they gather it, in a solemn ritual....> "After preparing for a sacrifice and a feast under the oak, they hail the mistletoe as a cure-all and bring two white bulls there, whose horns have never been bound before. A priest dressed in a white robe climbs the oak and with a golden sickle cuts the mistletoe, which is caught in a white cloak. Then they sacrifice the victims, begging the god, who gave them the mistletoe as a gift, to make it propitious for them. They believe that a potion prepared from mistletoe will make sterile animals fertile, and that the plant is an antidote for any poison. Such is the supernatural power with which peoples often invest even the most trifling things"> Pliny the Elder (23-79 AD)
>

http://www.fda.gov/Safety/Recalls/ucm284456.htm?source=govdelivery">Starwest Botanicals Recalls Starwest Organic Celery Seed. Due to Potential Salmonella Contamination.

12/21/2011 03:46 PM EST

Starwest Botanicals is voluntarily recalling Starwest Organic Celery Seed (Whole) because it has potential to be contaminated with Salmonella. The product is packaged in Mylar 1lb and 2 oz pouches. Salmonella is an organism that can cause serious and sometimes fatal infections in young children, frail or elderly people, and others with weakened immune systems.