Anticancer Properties Of SaffronMarch 2015
By Jennifer Provos
As more positive data accumulates about the health benefits of the Mediterranean diet, researchers are uncovering new applications for the spice saffron, which is a Mediterranean diet constituent.
In multiple studies, scientists are finding that saffron has the unique ability to both slow and reverse cancer growth!1
Saffron’s cancer-preventive properties include inhibiting the promotion of tumors and preventing chemical modifications to DNA that can activate cancer genes or induce new cancer-causing mutations.2-4
Additionally, saffron has been shown to help reduce the harmful effects produced by chemotherapy drugs.
Chemo drugs can induce genetic damage that may lead to new cancers, making standard chemotherapy a double-edged sword and limiting its effectiveness.5 Research has found that the abundant carotenoids in saffron offer direct protection against chemotherapy-induced DNA damage.5
Along with its chemoprevention abilities, saffron contains a host of beneficial, biologically active compounds that have been shown to protect heart and blood vessel tissue,6 ease the impact of diabetes and other metabolic disorders,7 and slow or even reverse cognitive and mood disorders associated with aging.8
This spice with ancient origins is finding new use in the battle against the onslaughts of aging.
Saffron consists of the dried dark red or yellow “stigmas” of the crocus flower, Crocus sativus.9 In addition to its culinary uses, saffron has a long history as a potent component of traditional medical systems.2,5,10-13
Like most plant derivatives, saffron contains a multitude of bioactive molecules, many of which have been shown to have specific benefits in the body. Chief among these molecules are crocin, crocetin, and safranal, members of the carotenoid family of molecules that also includes forms of vitamin A.4,14
These compounds have been shown to exert multiple favorable effects in laboratory studies, including improved oxygen diffusion (which enhances lung performance and brain oxygenation), improved treatment of atherosclerosis and arthritis, protection of liver tissue against damage by chemical toxins, and protection of bladder tissue against chemical damage.3
Let’s now take a closer look at how saffron and its constituents beneficially effect cancer, heart disease, metabolic disorders, and cognitive disorders.
Comprehensive Cancer Chemoprevention
Cancer is one of the world’s leading causes of death, killing about 8 million people each year.2,10,14 While the bulk of mainstream medical research has been aimed at treating cancers once they appear,12 wiser researchers search for natural molecules that might derail the development of cancer very early in its development. This admirable goal is known as chemoprevention, as opposed to chemotherapy.
In this search, saffron has emerged as a contender for effective chemoprevention because it acts at multiple stages in the complex set of events that lead to a full-blown tumor.10,15,16 Let’s look at how saffron works as a chemopreventive agent one stage at a time:
Saffron and its constituents start working long before a cell undergoes transformation into a malignant cancer cell.
The first step in cancer development, or carcinogenesis, is some kind of trigger that initiates malignant transformation. This may be an environmental toxin, a stray oxygen radical, or invasion with certain viruses. Saffron components have been shown to help prevent carcinogenesis caused by each of these triggers.
In one study, the saffron derivatives crocin and diglucosylcrocetin were shown to inhibit tumor cell markers emerging on the surface of virally infected cells in laboratory experiments.17 In another study, when hamsters were orally treated with saffron prior to administration of a powerful chemical carcinogen, tumor formation was completely prevented, demonstrating its ability to prevent the initial stage of cancer.18
Saffron extracts and specific components have also been shown to potently prevent DNA damage caused by free radicals, radiation, and inflammation, thereby reducing the risk of new cancer formation.5,19
Inhibits The Rapid Spread Of Cancer Cells
Once a cell has been triggered to become malignant, it then proliferates, or reproduces rapidly and without normal controls, to produce a developing tumor. Studies show that saffron is able to suppress—and in some cases reverse—the proliferation of certain human cancer cells in culture.
For example, one compelling study found that colon cancer cells that were treated with either saffron extract—or its major component, crocin—displayed sharp and significant reductions in proliferation, to as low as 2.8% of the rate seen in untreated cells.4 A similar reduction in proliferation was demonstrated in non-small cell lung cancer and breast cancer cells in culture. 4,9 It is important to note that in none of these studies did saffron or its constituents display damage to healthy, normal cells.4,9
Crocetin, another major saffron constituent, has been found to inhibit proliferation of pancreatic cells in culture as well.20 And in live animal studies, crocetin produced marked regression of pancreatic tumors that were induced when aggressive pancreatic cancer cells were directly injected into mice. Importantly, in this study, the crocetin was given orally, and only after the tumors were already detectable, demonstrating crocetin’s potent ability not only to slow, but to reverse cancer growth!20
Triggers Programmed Cell Death
Another important way in which developing cancer cells can be stopped in their tracks is through the mechanism known as apoptosis, or programmed cell death. All normal body cells contain a genetic program that induces the cell to die under specific conditions. This is a vital means of removing damaged cells and preventing overgrowth of normal tissues. Cancer cells, however, typically lose their responsiveness to the apoptosis signal, effectively becoming “immortal,” and hence, deadly.
Saffron has been shown to trigger apoptosis in a variety of cancer cell lines, which is seen as an essential component of any cancer-control or cancer-prevention method.11,19-21 In fact, all three major components of saffron—crocin, crocetin, and safranal—have shown powerful apoptosis-inducing properties.2,22,23
If a cancer cell survives attempts to quash it by blocking proliferation or apoptosis, it may go on to produce specialized molecules that help it degrade the protein matrix between healthy cells, allowing it to invade otherwise-healthy tissue.24 This is how cancers spread locally, and it is also a major mechanism in metastasis, the spread of malignant cells throughout the body.25-27
The saffron constituent crocetin has now been shown to downregulate production of one such protein-degradation molecular type, known as matrix metalloproteinase.24 This action has been shown to prevent breast cancer cells from penetrating and invading both local tissues and those in other parts of the body by metastasis.24
Still another means by which growing tumors are able to thrive is through the induction of new blood vessel growth, a process known as angiogenesis. Considerable scientific effort has been devoted to developing drugs that can block angiogenesis, thereby starving a developing tumor of the nutrients and oxygen it needs to sustain growth.28
Recent studies support the use of saffron extracts in reducing levels of a vital signaling molecule called vascular endothelial growth factor (VEGF), which markedly reduces new blood vessel formation in the tumor mass.29
Studies Show Saffron Prevents The Deadliest Human Cancers
As you just read, extensive data has provided persuasive evidence that saffron can prevent, mitigate, and even reverse many of the changes that lead a healthy cell to turn cancerous. As a result, a growing body of literature now supports the use of saffron for the prevention of several of the most aggressive and deadly human cancers, including liver, lung, and stomach cancers.
Liver cancer is an increasing public health threat, partly the result of the growing number of toxins in our environment and partly the result of increasing prevalence of the hepatitis C virus, especially in people born in the Baby Boom generation.30
In rats given a powerful chemical that produces liver cancer, a two-week pretreatment course of saffron significantly reduced the number and size of cancerous nodules developing in the animals’ livers.15 Sub-microscopic study of the affected cells showed that saffron achieved this effect by sharply reducing the levels of oxidant and inflammatory signaling that contributes to malignant cell growth and also by inducing apoptosis, which helped to stop tumors from growing.15
Lung cancer is another major cancer that continues to be a leading cause of death, even as rates of smoking decline. Saffron extracts have now been used to reduce the viability of lung cancer cells in culture, inducing cell death by apoptosis.31
In studies of stomach cancer, another rapidly increasing cancer worldwide, crocetin enhanced apoptosis and slowed tumor progression, while boosting blood levels of protective compounds that further suppress cancer development.32 In one study, a water extract of saffron produced similar effects in an animal model of stomach cancer. 33
To date, saffron, its extracts, and its individual components crocin, crocetin, and safranal have demonstrated compelling preventive effects against cancers of the lung, liver, colon, breast, pancreas, stomach, bone, and blood.9,32,34-39 Saffron has an impressive safety profile, with no evidence of toxic effects on healthy tissues or harmful effects on blood coagulation.5,40
Saffron And Metabolic Disorders
Saffron has been shown to have powerful effects against diabetes and its side effects. High blood sugar levels are dangerous because they increase glycation, which results in the oxidation and inflammation that damages body tissues.41-43 Saffron extracts help bring blood sugar levels under control by enhancing glucose uptake and improving insulin sensitivity in muscle tissue. 44 This is vital because muscle cells are the largest users of glucose in the body.
The benefits of this effect have been validated in numerous animal studies. When diabetic rats were fed saffron or its components safranal or crocin, they experienced significant reductions in fasting blood sugar levels.45-47 Some studies have demonstrated significant improvements in lipid profiles as well, with reductions in cholesterol and triglycerides.48
As a result of saffron’s effect on glucose-induced oxidant damage, saffron has shown great promise for preventing the debilitating effects associated with diabetes, including diabetic neuropathy, diabetic encephalopathy, and diabetic nephropathy.
Although the mechanism behind diabetic neuropathy (damage to nerve fibers) is unclear, it appears to involve sugar-induced oxidant damage to nerve cells.49 A study of human brain cells in culture showed that saffron extract markedly decreases the sugar toxicity that causes the damage.49
In extreme cases, diabetics may develop a brain condition called diabetic encephalopathy, which is thought to arise from the same causes as diabetic neuropathy. In an animal study, saffron supplementation (the human equivalent dose of 448 to 896 mg per day) not only improved cellular antioxidant systems, but more importantly, decreased cognitive deficits associated with the condition.50
Diabetics also develop substantial risk for kidney disease, or diabetic nephropathy, again in part a result of glucose-induced oxidant damage. One study demonstrated that when diabetic rats were pretreated with the saffron constituent crocin, they experienced improvement in kidney function.51
And, in a startling study, supplementation with the saffron constituent safranal reduced oxidative lung damage in diabetic rats, helping to reduce lung distress.52
Underlying the development of diabetes often is metabolic syndrome, which is a common result of Western dietary and lifestyle habits. Metabolic syndrome (the combination of obesity, high blood sugar, lipid abnormalities, and hypertension) is an important risk factor for cardiovascular diseases, and hence represents an important point for interventions to reduce cardiovascular death.53
Numerous studies have demonstrated that saffron supplementation in humans with metabolic syndrome has many beneficial effects:
- It reduces levels of “heat shock proteins,” which are markers of cellular stress,53
- It reduces snacking and increases the sense of fullness after a meal (satiety),54
- It can prevent metabolic syndrome development in patients taking olanzapine, a common drug used in psychiatry.55
Saffron And Cardiovascular Disease
Saffron, a major component of the Mediterranean diet, has been linked with some of the beneficial effects associated with the diet—including lower rates of cardiovascular disease.6 In fact, saffron offers dual protection for your heart: It helps to protect against cardiovascular disease and it helps reduce the damage that occurs if a heart attack does happen.
Scientists are now uncovering some of the major mechanisms by which saffron protects cardiovascular tissue. Cardiovascular disease results in part from multiple factors that lead to inflammation, oxidant damage, and loss of tissue and organ function. As you’ve read, saffron is able to potently reduce oxidant stress and inflammation. But its cardiovascular benefits don’t stop there.
Recent studies have demonstrated saffron’s potential for protecting against heart attacks and strokes by reducing blood pressure and improving blood lipid profiles.56,57 Crocin markedly decreases blood concentrations of triglycerides and total and low-density (“bad”) cholesterol, while raising levels of high-density (“good”) cholesterol.57 In some animal studies, blood cholesterol was reduced by as much as 50%. 6 A recent study published in Phytotherapy Research demonstrated for the first time that crocetin could also significantly reduce mean blood pressure in hypertensive rats. 58
In a mechanism similar to the common calcium channel blocking drugs, saffron inhibits the inflow of calcium into smooth muscle cells in artery walls and in heart muscle tissue, a process known to constrict arteries and raise blood pressure.59-62
In addition, studies have shown that crocin can reduce both visible and molecular evidence of heart attack in laboratory rats by rebalancing the oxygen status of individual heart muscle cells.63,64 Remarkably similar effects have been demonstrated using both crocetin and saffron itself to protect heart tissue from damaging low blood flow.65,66
And in experimentally induced heart attacks, saffron supplementation in animals was shown to significantly reduce the size of the infarction, or area of dying tissue that occurs during a heart attack.67
It is common for people to experience heart rhythm disturbances (arrhythmias) following a heart attack. Saffron extracts have been shown to reduce susceptibility to life-threatening arrhythmias by remodeling the structure of the heart’s normal pacemaker (the atrioventricular node, or “AV node”). 68
Saffron And Strokes
Saffron has also been demonstrated to have beneficial effects in stroke victims. The most common form of stroke is an ischemic stroke, which can be thought of as a heart attack of the brain, because like a heart attack, it is also caused by a sharp reduction or interruption of blood flow.69,70
When blood flow is restored to the brain, it unfortunately leads to something called “reperfusion injury,” which is tissue damage that occurs when the blood supply returns to the area as a result of oxidative damage and inflammation. This is the main factor in brain damage following an ischemic stroke.
A study done on rat models of ischemic stroke demonstrated that crocin reduced the damaging effects of oxidant molecules produced when blood flow was restored, which can ultimately help to limit the negative effects of the stroke.71
In a compelling validation of the benefits of this effect, another study published in Phytotherapy Research demonstrated that both the herb itself and its constituent crocin improved spatial cognitive performance in rats following an experimental stroke.72
Saffron And Your Brain
Because oxidation, inflammation, and glucose damage are harmful to brain health, scientists are turning to saffron as a potential neuroprotective agent against both neurodegenerative diseases and mood disorders such as depression, which affects upwards of one-fifth of the US population.73-76
Animal studies reveal antidepressant effects of saffron extracts on performance in behavioral models of depression,77 and for symptoms of obsessive-compulsive disorder (OCD).84
Human studies using low doses of saffron have produced even more impressive results as follows:
- Saffron (30 mg per day) significantly reduced depression scores on a standard rating scale when compared to placebo,73,78,79
- Saffron (30 mg per day) was found to be similar in effectiveness to the standard antidepressant drugs imipramine and fluoxetine in the treatment of mild to moderate depression,80,81
- Saffron (30 mg per day) reduced erectile dysfunction, a common side effect produced by treatment with the antidepressant drug fluoxetine,82
- Saffron (30 mg per day) was more effective than placebo in relieving symptoms of premenstrual syndrome when used over two menstrual cycles.83
Loss of cognitive function is one of the most common, most feared consequences of aging. Studies show that saffron has promise in preventing or ameliorating some of those effects. A 16-week trial of saffron (30 mg per day) showed that the supplement was superior to placebo in patients with early, probable Alzheimer’s disease. The same dose, for 22 weeks, proved similar in effect to the prescription drugs memantine and donepezil in a comparable population.85,86
In laboratory models of neurodegenerative diseases such as Alzheimer’s, saffron and its extracts demonstrate protection against excitotoxicity, the overactivity of certain kinds of nerve cells that produces long-term degeneration of brain tissue. 87 And animal studies have shown that saffron supplementation can antagonize the cognitive effects of Alzheimer’s disease induced by chemical treatments.88,89
The ancient spice saffron has been used for millennia as a treatment and preventive agent against cancer, heart disease, metabolic conditions, and other conditions we now recognize as symptoms of aging.12,90-92
Modern science is vindicating these uses, demonstrating that saffron and its constituent molecules protect a myriad of body tissues and organs against the fundamental processes that induce aging, such as oxidant damage, inflammation, toxic exposures, and high glucose.
In particular, saffron is showing promising chemopreventive properties against many different forms of cancer. Many of the same mechanisms that make it so potent against cancer also make it a powerful tool in reducing the impact of diabetes and the metabolic syndrome, of cardiovascular disease and stroke, and of depression and neurodegenerative disorders.
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