Herbal Medicine for Breast Cancer – Saffron

Continuing with my series of articles sharing the merits of certain herbs for breast cancer, the subject today is saffron and how it may be beneficial for breast cancer patients and thrivers.

Saffron (Crocus sativus) has been traditionally used as a spice, and it is quite expensive due to the fact that one crocus flower yields only a tiny amount of saffron. It is the stigma of the crocus flower – three brightly colored, fuzzy, hair like extensions – that is carefully picked in a fairly labor intensive process. So saffron is considered to be the most expensive spice in the world, and no wonder.

Interestingly, researchers are using not only the stigmas of the crocus but in some cases also the flower petals and leaves of the crocus. Some of the bioactive constituents of saffron include phytochemicals known as safranal, crocetin, crocin, and satiereal.

Research is revealing that saffron is much more than a spice, it is an amazing herb with some super-powers! It is the subject of many recent research studies which demonstrate its ability to ease depression and anxiety, obsessive-compulsive disorder, Alzheimer’s disease, coronary artery disease, hypertension, stomach disorders, dysmenorrhea, learning and memory impairment, and cancer. Saffron also has anti-inflammatory, anti-convulsant, anti-atherosclerotic, and antigenotoxic (protects your DNA) properties.

I know you’re here for help with breast cancer, though, so let’s get to what I’ve found in the research to support saffron being used for breast cancer patients and thrivers.

1. Promotes Antioxidant Activity

Antioxidants are required for the eradication of free radicals that are associated with damage to cells. Free radicals are especially damaging to DNA, and we want to negate their effects whenever possible. In 2017 research [1], crocin and crocetin from saffron were found to increase gluathione peroxidase and superoxide dismutase activity. These are super-important enzymes that aid the detoxification of free radicals.

2. Reduces Inflammation

Inflammation is a classic ploy used by cancer cells to promote its growth and spread, so typically we find that substances that reduce inflammation also reduce the viability of cancer cells.

A 2022 Chinese study [2] found that crocin suppressed inflammation in breast cancer cells, and also decreased the rapid growth (proliferation) of the cells.

3. May Prevent Cancer Promotion (Carcinogenesis)

The first step in the development of cancer is usually caused by some sort of a trigger – for instance, a toxic environment or an inflammatory process caused by a wonky gene, or a hormonal imbalance – which then starts a malignancy growing.

Saffron has been shown to help prevent the carcinogenesis process in at least three studies. [3]-[5]

4. DNA Protection

As mentioned before, protecting our DNA is important to keep cancer-promoting substances from damaging it.

Phytochemicals within saffron have been shown to prevent DNA damage caused by radiation, free radicals and inflammation. [6]

5. May Slow and Reverse Cancer Growth

Once a cell becomes malignant, it then reproduces rapidly (called proliferation) and without normal controls, and this is how a tumor develops. In a 2009 animal study [7], crocetin showed an ability to both slow and reverse cancer growth and induce apoptosis (planned cell death, lacking in cancer cells).

Preliminary research reported in 2007 [8] on estrogen and progesterone receptor positive (ER+, PR+) breast cancer cells in vitro indicated saffron inhibited the proliferation of these cells.

A 2015 cell study [9] found that crocin significantly inhibited the rapid proliferation of ER+ and PR+ breast cancer cells, and induced apoptosis.

A 2021 animal study [10] found that a combination of high-intensity interval training and saffron extract provided a synergistic effect which improved the reduction of breast tumors in mice and also had a role to play in modulating apoptosis pathways.

6. May Block Spread of Cancer (Metastasis)

If a cancer cell manages to survive despite our body’s attempts to stop its uncontrolled growth, it may go on to produce special molecules that help it to degrade the protein matrix between healthy cells (the “extracellular matrix”) and this allows it to invade healthy tissue, called metastasis.

A 2011 study [11] indicated crocetin inhibited the invasiveness of triple negative breast cancer cells by downregulating the production of an enzyme called matrix metalloproteinase which is involved in the degradation of the aforementioned extracellular matrix.

A small clinical trial reported in September 2015 [12] involved thirteen patients with liver metastases. They were divided into two groups, and both groups received standard chemotherapy treatment. Patients in the control group received 50 mg of saffron in a capsule twice per day during chemotherapy, while the second group received only a placebo. Of the thirteen patients who started, only seven patients finished the study. Two of the four patients who took saffron showed a partial and complete response. No response was seen in the placebo group. Although not a particularly convincing study due to its small size, it would certainly be worth adding saffron to the diet – it couldn’t hurt.

A 2018 study [13] of mice with breast cancer found that crocin and crocetin significantly inhibited migration, cell mobility, and invasion, also impaired adhesion of tumor cells to the extracellular matrix. Crocin downregulated cancer promoting genes and upregulated genes associated with anti-cancer properties.

In 2020, Iranian researchers investigated crocin and crocetin against a mouse model of triple negative breast cancer [14]. They found that crocin and crocetin significantly inhibited migration, cell mobility and invasion, also reducing the ability of cancer cells to adhere to the extra cellular matrix, thus reducing the metastatic potential of cancer cells to migrate to other areas of the body.

7. May Block the Process of Angiogenesis

Another way by which growing tumors are able to thrive is by means of creating new blood vessels to fuel their rapid growth, a process called angiogenesis. Saffron extracts reduce levels of a vital signalling molecule called vascular endothelial growth factor (VEGF), and this can reduce the formation of new blood vessels.

A 2014 Iranian study [15] showed that a combination of saffron and a low frequency electro magnetic field (I love that the researchers had the temerity to use this combination!) were able to significantly decrease the expression of VEGF in ER+, PR+ breast cancer cells in vitro.

A 2019 study [16] found that crocin had a profound antiangiogenic effect on triple negative breast cancer cells, slowing the proliferation rate, inducing apoptosis and cell cycle arrest.

8. May Work Synergistically with Chemotherapy

Researchers at The First Hospital Affiliated of Liaoning Medical University, Jinzhou, China carried out some interesting research on saffron, published in 2017 [17]. They observed that the chemotherapy drug fluorouracil is not always effective with breast cancer, that some breast cancer cells still survive after fluorouracil treatment. They posited that the cells managed to survive through enhanced autophagy. Autophagy is the process of natural degradation of a cell that removes unnecessary or dysfunctional components. These cellular components are then recycled and used again in creating new cells. This is the body’s way of cleaning out damaged cells, in order to regenerate newer, healthier cells. The researchers in this study found that crocetin from saffron significantly increased the anti-cancer effects of fluorouracil on breast cancer cell growth, stating “Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells…”.

Another 2017 study [18] found that crocetin combined well with the chemotherapy drug cisplatin against esophageal cancer cells, working better against these cancer cells in combination than either one on its own.

9. May Inhibit Estrogen Receptor Alpha

Estrogen driven breast cancer signaling is mediated by a cellular receptor known as estrogen receptor alpha (ER-alpha). ER-alpha is the cellular receptor associated with the rapid proliferation of breast cells. Due to this fact, ER-alpha is the central focus in anti-estrogen breast cancer therapies such as Tamoxifen.

2020 research [19] indicated that crocetin derived from the leaves of the crocus plant had anti-cancer activity against ER+ PR+ breast cancer cells. Upon further investigation, researchers found that crocetin had an antiproliferative effect “possibly by inhibiting estrogen receptor alpha and HDAC2 mediated signalling cascade.”

Follow-on Benefits of Saffron for Cancer Patients/Thrivers

Eases Cancer-Related Fatigue

A 2022 randomized, double blind clinical trial [20] with 75 breast cancer patients found that a saffron-based beverage (it also included rosewater and honey) significantly eased fatigue in the group receiving the saffron drink.

Eases Depression

Many breast cancer patients taking the drug Tamoxifen or some of the other aromatase inhibiting drugs suffer from depression, this is one of the known side effects of these medications because estrogen is very much required for good brain health. Many oncologists then prescribe antidepressant drugs in the form of SSRIs (selective serotonin reuptake inhibitors) for their patients taking the estrogen blockers to help relieve the depression. However, some studies indicate that certain antidepressants can interfere with a particular enzyme (CYP2D6) produced by the liver, rendering Tamoxifen ineffective.

Another obvious issue with antidepressants is that they tend to have a wide range of problematic side effects including sexual dysfunction, nausea, headaches, weight gain, agitation, nervousness, and even suicidal thoughts.

To make matters worse, antidepressant use has been shown to retard bone growth and lead to osteoporosis. [21] [22]

Breast cancer patients may already have issues with osteoporosis due to some of the medications they are on, but quite apart from that, when bone growth is retarded, this could open the door for cancer metastases in the bone. We need our bones to be growing normally and staying strong.

Clinical trials involving actual humans have been carried out and reported in 2013 [23] and 2014 [24] which indicate saffron is extremely beneficial for the treatment of depression.

In addition, a 2021 clinical trial involving seventy-two patients with non-metastatic Her2 positive or triple negative breast cancer [25] indicated that crocin significantly decreased anxiety and depression in the group receiving crocin. An additional benefit in the crocin group was a reduction in chemotherapy related toxicity.

2005 research [26] comparing saffron to fluoxetine (Prozac) found that a 30 mg capsule of C. sativus was just as good as 20 mg of Prozac in relieving mild to moderate depression.

May Aid Weight Loss

We know that obesity is one of the risk factors for breast cancer. In addition, after going through the gamut of treatments for breast cancer, many also have a tendency to gain weight, and this is a problem particularly with hormone driven breast cancer because adipose tissue (fat cells) create estrogen.

Saffron contains a phytochemical called satiereal, which in a 2010 clinical trial [27] was able to help decrease food cravings, overeating, and between-meal snacking for a group of mildly overweight, female volunteers. They lost an average of two pounds after eight weeks, and no special diet was employed.

Cholesterol (Lipid) Lowering Activity

One area that researchers are investigating for treating breast cancer is that of lowering cholesterol. Many studies have shown that reducing specific enzymes responsible for the synthesis of cholesterol also appears to have a positive effect on reducing or shrinking breast tumors, and studies on saffron indicate that it does this very well.

I have also noticed in my research reading on various herbs and essential oils that most of the ones that have anti-cancer activity also have cholesterol-lowering properties, which I found very interesting. They are also anti-bacterial, leading me to suspect that there may be a bacterial aspect involved in breast cancer, which I discuss in this article: The Breast, Its Microbiome and Ways to Improve It 

Back to cholesterol-lowering. Statin drugs have been investigated for their effect against breast tumors, but of course these also come with side effects. Iranian researchers reported in 2020 [28] that crocetin and crocin from saffron decreased both cholesterol and triglyceride levels in tumor-bearing mice. In fact, crocetin worked better than a well-known statin drug in inhibiting hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, which is responsible for synthesis of cholesterol.

Since many of us also have issues with elevated cholesterol levels after breast cancer treatments (and past a certain age), it looks like saffron can be of assistance there too.

So there you have it – I think after reading this you might agree with me that incorporating some saffron into our daily diet might well be worthwhile.

Four Ways To Get Saffron Into Your Body

1.  Ingest it – Just cook with it. Although this is the easiest method, it is also more difficult to get a therapeutic dose.

2.  Make your own saffron tincture. Here’s how to do that:

Take 1 gram of dried saffron and place it into a one-ounce dropper bottle (this takes patience – here’s a tip. Get a funnel and using chop sticks jam the threads into the bottle). 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 (your choice). Let the mixture sit for a few days.  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.

3.  Make a cup of saffron tea daily with about 10 strands of saffron in it.

4.  Take Optimized Saffron in supplement form from a reputable source like Life Extension.

References:

[1] Comparative Study on The Preventive Effect of Saffron Carotenoids, Crocin and Crocetin, in NMU-Induced Breast Cancer in Rats – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241521/
[2] Crocin attenuates NF-kB-mediated inflammation and proliferation in breast cancer cells by down-regulating PRKCQ – https://pubmed.ncbi.nlm.nih.gov/35447530/
[3] Membrane Associated Antitumor Effects of Crocine-, Ginsenoside- and Cannabinoid Derivates – http://www.ncbi.nlm.nih.gov/pubmed/10810367
[4] Saffron Reduction of 7,12-dimethylbenz[a]anthracene-induced Hamster Buccal Pouch Carcinogenesis – https://www.ncbi.nlm.nih.gov/pubmed/23621267
[5] Comparative Study on The Preventive Effect of Saffron Carotenoids, Crocin and Crocetin, in NMU-Induced Breast Cancer in Rats – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241521/
[6] The Anticancer Effect of Saffron in Two P53 Isogenic Colorectal Cancer Cell Lines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488489/
[7] Crocetin Inhibits Pancreatic Cancer Cell Proliferation and Tumor Progression in a Xenograft Mouse Model – https://www.ncbi.nlm.nih.gov/pubmed/19208826
[8] Inhibition of Breast Cancer Cell Proliferation by Style Constituents of Different Crocus Species – https://www.ncbi.nlm.nih.gov/pubmed/17352254
[9] Antitumor effects of crocin on human breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723791/
[10] Treatment-induced tumor cell apoptosis following high-intensity interval training and saffron aqueous extract in mice with breast cancer – https://pubmed.ncbi.nlm.nih.gov/33861725/
[11] Crocetin Inhibits Invasiveness of MDA-MB-231 Breast Cancer Cells via Downregulation of Matrix Metalloproteinases – https://www.ncbi.nlm.nih.gov/pubmed/20803418
[12] Effect of Saffron on Liver Metastases in Patients Suffering from Cancers with Liver Metastases: a Randomized, Double Blind, Placebo-controlled Clinical Trial – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599117/
[13] A Comparative Study on Anti-Invasion, Antimigration, and Antiadhesion Effects of the Bioactive Carotenoids of Saffron on 4T1 Breast Cancer Cells Through Their Effects on Wnt/ß-Catenin Pathway Genes – https://pubmed.ncbi.nlm.nih.gov/29969282/
[14] Anti-metastatic properties of a potent herbal combination in cell and mice models of triple negative breast cancer – https://pubmed.ncbi.nlm.nih.gov/31926253/
[15] The Synergic Effects of Crocus Sativus L. and Low Frequency Electromagnetic Field on VEGFR2 Gene Expression in Human Breast Cancer Cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009095/
[16] Antiangiogenic effect of crocin on breast cancer cell MDA-MB-231 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940218/
[17] Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy – https://pubmed.ncbi.nlm.nih.gov/28351329/
[18] Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway – https://cancerci.biomedcentral.com/articles/10.1186/s12935-017-0468-9
[19] Isolation, purification and characterization of naturally derived Crocetin beta-d-glucosyl ester from Crocus sativus L. against breast cancer and its binding chemistry with ER-alpha/HDAC2 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042633/
[20] Efficacy and safety of Jollab (a saffron-based beverage) on cancer-related fatigue in breast cancer patients: A double-blind randomized clinical trial – https://pubmed.ncbi.nlm.nih.gov/35767970/
[21] The Impact of Psychotropic Medications on Bone Health in Youth – https://pubmed.ncbi.nlm.nih.gov/30246221/
[22] Antidepressant Use Linked to Bone Loss – https://www.nih.gov/news-events/nih-research-matters/antidepressant-use-linked-bone-loss
[23] Saffron (Crocus Sativus L.) And Major Depressive Disorder: a Meta-analysis of Randomized Clinical Trials – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643654/
[24] Crocin, the Main Active Saffron Constituent, as an Adjunctive Treatment in Major Depressive Disorder: a Randomized, Double-blind, Placebo-controlled, Pilot Clinical Trial – https://www.ncbi.nlm.nih.gov/pubmed/25484177
[25] Amelioration of anxiety, depression, and chemotherapy related toxicity after crocin administration during chemotherapy of breast cancer: A double blind, randomized clinical trial – https://pubmed.ncbi.nlm.nih.gov/34164855/
[26] Hydro-alcoholic Extract of Crocus Sativus L. Versus Fluoxetine in the Treatment of Mild to Moderate Depression: a Double-blind, Randomized Pilot Trial – http://www.ncbi.nlm.nih.gov/pubmed/15707766
[27] Satiereal, a Crocus Sativus L Extract, Reduces Snacking and Increases Satiety in a Randomized Placebo-controlled Study of Mildly Overweight, Healthy Women – https://pubmed.ncbi.nlm.nih.gov/20579522/
[28] Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430959/