Green Tea

Author: Sonia Fassinotti
Date: 15/09/2010


"Better to be deprived of food for three days, than tea for one." (Ancient Chinese Proverb)

Archeological evidence suggests that people consumed tea leaves steeped in boiling water as many as 5,000 years ago. Botanical evidence indicates that India and China were among the first countries to cultivate tea. Today, tea is the most widely consumed beverage in the world, second only to water. Hundreds of millions of people drink tea around the world, and studies suggest that green tea Camellia Sinensis in particular has many health benefits.

Plant Description

The Camellia sinensis plant originally was cultivated in East Asia, this plant grows as large as a shrub or tree. Today, Camellia sinensis grows throughout Asia and parts of the Middle East and Africa.
There are three main varieties of tea derived from the leaves of the Camellia sinensis-- green, black, and oolong.

The difference between the teas is in their processing. Green tea is made from unfermented leaves and reportedly contains the highest concentration of powerful antioxidants called polyphenols. Antioxidants are substances that scavenge free radicals -- damaging compounds in the body that alter cells, tamper with DNA (genetic material), and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet rays from the sun, radiation, cigarette smoke, and air pollution) also give rise to these damaging particles. Many scientists believe that free radicals contribute to the aging process as well as the development of a number of health problems, including cancer and heart disease. Antioxidants such as polyphenols in green tea can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

What's It Made Of?

The healthful properties of green tea are largely attributed to polyphenols, chemicals with potent antioxidant properties. In fact, the antioxidant effects of polyphenols appear to be greater than vitamin C. The polyphenols in green tea also give it a somewhat bitter flavor.

Polyphenols contained in teas are classified as catechins. Green tea contains six primary catechin compounds: catechin, gallaogatechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate (also known as EGCG). EGCG is the most studied polyphenol component in green tea and the most active.
Green tea also contains alkaloids including caffeine, theobromine, and theophylline. These alkaloids provide green tea's stimulant effects. L-theanine, an amino acid compound found in green tea, has been studied for its calming effects on the nervous system.

Possible indications

Green tea has been extensively studied in people, animals, and laboratory experiments. Results from these studies suggest that green tea may be useful for the following health conditions:


Epidemiologic studies indicate that green tea consumption decreases cancer risk. These data are supported by the results of numerous preclinical studies, which have shown that green and black tea are potent inhibitors of carcinogenesis in various rodent models, including models for cancers of the skin, lung, esophagus, stomach, liver, duodenum, small intestine, pancreas, colon-rectum, and mammary gland.
Different tea preparations contain varying amounts of polyphenols, and epigallocatechin 3-gallate (EGCG) is the most abundant, best-studied, and possibly most potent (against cancer) polyphenol found in tea. Besides EGCG, which may account for 50% to 80% of the total antioxidant polyphenols called catechins in tea, other tea catechins include (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epicatechin. The achievable tissue concentrations of these polyphenols are in the low micromolar range, and therefore, anticarcinogenic effects observed with much higher concentrations in vitro may not be relevant to the in vivo anticarcinogenic process.
EGCG interacts with and binds numerous proteins to prevent carcinogenesis. EGCG has been reported to directly bind with the plasma proteins fibronectin, fibrinogen and histidine-rich glycoprotein, which may act as carrier proteins for EGCG. EGCG also binds with Fas, which might trigger the Fas-mediated apoptosis cascade. Laminin and the 67 kDa laminin receptor also interact with EGCG, and this binding seems to regulate the biological functions of the 67 kDa laminin receptor that have possible implications for prion-related diseases. Other directly bound protein targets include the intermediate filament protein, vimentin, ? chain–associated 70 kDa protein (ZAP-70) kinase, Fyn, insulin-like growth factor-1 receptor, and the molecular chaperone glucose-regulated protein 78. All of these directly bound proteins play important roles in carcinogenesis. Zap-70 plays a critical role in T cell receptor–mediated signal transduction and in the immune response of leukemia cells, and Fyn plays a major role in malignant cell transformation. Insulin-like growth factor-1 receptor plays a functional role in cell transformation and cancer formation, and glucose-regulated protein 78 is associated with the multidrug resistance phenotype of many types of cancer cells. The many targets of polyphenols that have been discovered and continue to be discovered are very likely dependent on the concentration of the tea polyphenol used and the specific cell, tissue, or organ—for example, proteins that bind EGCG in the lung, breast, colon, or skin might be very different from one another, and EGCG very likely targets multiple proteins in each tissue.

Bladder cancer. Only a few clinical studies have examined the relationship between bladder cancer and tea consumption. In one study that compared people with and without bladder cancer, researchers found that women who drank black tea and powdered green tea were less likely to develop bladder cancer. A follow-up clinical study by the same group of researchers revealed that bladder cancer patients (particularly men) who drank green tea had a substantially better 5-year survival rate than those who did not.
Breast cancer. Clinical studies in animals and test tubes suggest that polyphenols in green tea inhibit the growth of breast cancer cells. In one study of 472 women with various stages of breast cancer, researchers found that women who consumed the most green tea experienced the least spread of cancer (particularly premenopausal women in the early stages of breast cancer). They also found that women with early stages of the disease who drank at least 5 cups of tea every day before being diagnosed with cancer were less likely to suffer recurrences of the disease after completion of treatment. However, women with late stages of breast cancer experienced little or no improvement from drinking green tea. In terms of breast cancer prevention, the studies are inconclusive. In one very large study, researchers found that drinking tea, green or any other type, was not associated with a reduced risk of breast cancer. However, when the researchers broke down the sample by age, among women under the age of 50, those who consumed 3 or more cups of tea per day were 37% less likely to develop breast cancer compared to women who didn't drink tea.

Ovarian cancer. In a clinical study conducted on ovarian cancer patients in China, researchers found that women who drank at least one cup of green tea per day survived longer with the disease than those who didn' t drink green tea. In fact, those who drank the most tea, lived the longest. Other studies found no beneficial effects. (Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma 2006

Colorectal cancer. Clinical studies on the effects of green tea on colon or rectal cancer have produced conflicting results. Some clinical studies show decreased risk in those who drink the tea, while others show increased risk. In one study, women who drank 5 or more cups of green tea per day had a significantly lower risk of colorectal cancer compared to non-tea-drinkers. There was no effect in men, however. Other studies show that regular tea consumption may reduce the risk of colorectal cancer in women. Further research is needed before researchers can recommend green tea for the prevention of colorectal cancer.

Esophageal cancer. Studies in laboratory animals have found that green tea polyphenols inhibit the growth of esophageal cancer cells. However, clinical studies in people have produced conflicting findings. For example, one large-scale population-based clinical study found that green tea offered significant protection against the development of esophageal cancer (particularly among women). Another population-based clinical study revealed just the opposite -- green tea consumption was associated with an increased risk of esophageal cancer. In fact, the stronger and hotter the tea, the greater the risk. Given these conflicting results, further research is needed before scientists can recommend green tea for the prevention of esophageal cancer.

Lung cancer. While green tea polyphenols have been shown to inhibit the growth of human lung cancer cells in test tubes, few clinicial studies have investigated the link between green tea consumption and lung cancer in people and even these studies have been conflicting. One population-based clinical study found that Okinawan tea (similar to green tea but partially fermented) was associated with decreased lung cancer risk, particularly among women. A second clinical study revealed that green tea and black tea significantly increased the risk of lung cancer. As with colon and esophageal cancers, further clinical studies are needed before researchers can draw any conclusions about green tea and lung cancer.

Pancreatic cancer. In one large-scale clinical study researchers compared green tea drinkers with non-drinkers and found that those who drank the most tea were significantly less likely to develop pancreatic cancer. This was particularly true for women -- those who drank the most green tea were half as likely to develop pancreatic cancer as those who drank less tea. Men who drank the most tea were 37% less likely to develop pancreatic cancer. However, it is not clear from this population-based study whether green tea is solely responsible for reducing pancreatic cancer risk. Further studies in animals and people are needed before researchers can recommend green tea for the prevention of pancreatic cancer.

Prostate cancer. Laboratory studies have found that green tea extracts prevent the growth of prostate cancer cells in test tubes. In a large clinical study conducted in Southeast China researchers found that the risk of prostate cancer declined with increasing frequency, duration and quantity of green tea consumption. However, both green and black tea extracts also stimulated genes that cause cells to be less sensitive to chemotherapy drugs. Given this potential interaction, people should not drink black and green tea (as well as extracts of these teas) while receiving chemotherapy.

Skin cancer. The main polyphenol in green tea is epigallocatechin gallate (EGCG). Scientific studies suggest that EGCG and green tea polyphenols have anti-inflammatory and anticancer properties that may help prevent the onset and growth of skin tumors.

Stomach cancer. Laboratory studies have found that green tea polyphenols inhibit the growth of stomach cancer cells in test tubes, but clinical studies in people have been less conclusive. In two studies that compared green tea drinkers with non-drinkers, researchers found that people who drank tea were about half as likely to develop stomach cancer and gastritis (inflammation of the stomach) as those who did not drink green tea. However, a clinicial study including more than 26,000 men and women in Japan found no association between green tea consumption and stomach cancer risk. Some clinicial studies even suggest that green tea may increase the risk of stomach cancer.Further clinicial studies are underway to determine whether green tea helps reduce the risk of stomach cancer. Although green tea is considered safe for people at risk for stomach cancer, it is too soon to tell whether green tea reduces the likelihood of developing this disease.


Population-based clinical studies indicate that the antioxidant properties of green tea may help prevent atherosclerosis, particularly coronary artery disease. (Population-based studies means studies that follow large groups of people over time or studies that are comparing groups of people living in different cultures or with different dietary habits.) Researchers aren't sure why green tea reduces the risk of heart disease by lowering cholesterol and triglyceride levels. Studies show that black tea has similar beneficial effects. In fact, researchers estimate that the rate of heart attack decreases by 11% with consumption of 3 cups of tea per day. In May 2006, however, the U.S. Food and Drug Administration (FDA) rejected a petition from teamakers to allow tea labels to claim that green tea reduces the risk of heart disease. The FDA concluded that there is no credible evidence to support qualified health claims for green tea or green tea extract reducing the risk of heart disease.

High cholesterol

Research shows that green tea lowers total cholesterol and raises HDL cholesterol in both animals and people. One population-based clinical study found that men who drink green tea are more likely to have lower total cholesterol than those who do not drink green tea. Results from one animal study suggest that polyphenols in green tea may block the intestinal absorption of cholesterol and promote its excretion from the body. In another small study of male smokers, researchers found that green tea significantly reduced blood levels of harmful LDL cholesterol.

Inflammatory Bowel Disease (IBD)

Green tea may help reduce inflammation associated with Crohn's disease and ulcerative colitis, the two types of IBD. If green tea proves to be helpful for preventing colon cancer, this would be an added benefit for those with IBD because they are at risk for colon cancer.


Green tea has been used traditionally to control blood sugar in the body. Animal studies suggest that green tea may help prevent the development of type 1 diabetes and slow the progression once it has developed. People with type 1 diabetes produce little or no insulin, a hormone that converts glucose (sugar), starches, and other foods into energy needed for daily life. Green tea may help regulate glucose in the body.
A few small clinical studies have found that daily supplementation of the diet with green tea extract powder lowered the hemoglobin A1c level in individuals with borderline diabetes.
Researchers from University of Dundee, Scotland commented the insulin-like glucose-lowering properties of
epigallocatechin gallate (EGCG) in mammals. EGCG is known to act at least in part by repression of
gluconeogenic genes such as phosphoenolpyruvate carboxykinase. Their study shows EGCG exerts its
insulin mimetic effects at least in part by phosphorylation of the FOXOs through a mechanism that is similar
but not identical to insulin and IGF-1 induced FOXO phosphorylation.

Researchers from other group administrated rats with subtotal nephrectomy plus streptozotocin injection
with(-)-epigallocatechin 3-O-gallate (ECGG). After a 50-day administration period, EGCG treated groups
showed suppressed hyperglycemia, proteinuria, and lipid peroxidation, though there were only weak effects
on the levels of serum creatinine and glycosylated protein. These results suggest that EGCG ameliorates
glucose toxicity and renal injury, thus alleviating renal damage caused by abnormal glucose
metabolism-associated oxidative stress involved in renal lesions of diabetic nephropathy.

Liver disease

Population-based clinical studies have shown that men who drink more than 10 cups of green tea per day are less likely to develop disorders of the liver. Green tea also seems to protect the liver from the damaging effects of toxic substances such as alcohol. Animal studies have shown that green tea helps protect against the development of liver tumors in mice.
Results from several animal and human studies suggest that one of the polyphenols present in green tea, known as catechin, may help treat viral hepatitis (inflammation of the liver from a virus). In these studies, catechin was isolated from green tea and used in very high concentrations. It is not clear whether green tea (which contains a lower concentration of catechins) confers these same benefits to people with hepatitis.

Weight loss

Clinical studies suggest that green tea extract may boost metabolism and help burn fat. One study confirmed that the combination of green tea and caffeine improved weight loss and maintenance in overweight and moderately obese individuals. Some researchers speculate that substances in green tea known as polyphenols, specifically the catechins, are responsible for the herb's fat-burning effect.

Other uses

Drinking green tea has been found effective in a small clinical study for dental caries, or tooth decay. More studies need to be performed. Green tea may also be useful in inflammatory diseases, such as arthritis. Research indicates that green tea may benefit arthritis by reducing inflammation and slowing cartilage breakdown. Chemicals found in green tea may also be effective in treating genital warts and preventing symptoms of colds and influenza. Studies also show that drinking green tea is associated with reduced risk of all cause mortality.

Available Forms

Most green tea dietary supplements are sold as dried leaf tea in capsule form. Standardized extracts of green tea are preferred. There are also liquid extracts made from the leaves and leaf buds. The average cup of green tea contains between 50 - 150 mg polyphenols (antioxidants). Decaffeinated green tea products contain concentrated polyphenols. Caffeine-free supplements are available.

How to Take It

There are no known scientific reports on the pediatric use of green tea, so it is not recommended for children.
Depending on the brand, 2 - 3 cups of green tea per day (for a total of 240 - 320 mg polyphenols) or 100 - 750 mg per day of standardized green tea extract is recommended. Caffeine-free products are available and recommended.

Side effects and toxicity

The use of herbs is a time-honored approach to strengthening the body and treating disease. However, herbs contain active substances that can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, people should take herbs with care, under the supervision of a practitioner knowledgeable in the field of botanical medicine.
People with heart problems, kidney disorders, stomach ulcers, and psychological disorders (particularly anxiety) should not take green tea. Pregnant and breastfeeding women should also avoid green tea.
People who drink excessive amounts of caffeine (including caffeine from green tea) for prolonged periods of time may experience irritability, insomnia, heart palpitations, and dizziness. Caffeine overdose can cause nausea, vomiting, diarrhea, headaches, and loss of appetite. If you are drinking a lot of tea and start to vomit or have abdominal spasms, you may have caffeine poisoning.

Possible Interactions

If you are being treated with any of the following medications, you should not drink green tea or take green tea extract without first talking to your health care provider:
Adenosine -- Green tea may inhibit the actions of adenosine.
Antibiotics, Beta-lactam -- Green tea may increase the effectiveness of beta-lactam antibiotics by reducing bacterial resistance to treatment.
Benzodiazepines -- Caffeine (including caffeine from green tea) has been shown to reduce the sedative effects of benzodiazepines (medications commonly used to treat anxiety, such as diazepam and lorazepam).
Beta-blockers, Propranolol, and Metoprolol -- Caffeine (including caffeine from green tea) may increase blood pressure in people taking propranolol and metoprolol (medications used to treat high blood pressure and heart disease).
Blood Thinning Medications (Including Aspirin) -- People who take warfarin, a blood thinning medication, should not drink green tea. Since green tea contains vitamin K, it can make warfarin ineffective. Meanwhile, you should not mix green tea and aspirin because they both prevent platelets from clotting. Using the two together may increase your risk of bleeding.
Chemotherapy -- The combination of green tea and chemotherapy medications, specifically doxorubicin and tamoxifen, increased the effectiveness of these medications in laboratory tests. However, these results have not yet been demonstrated in studies on people. On the other hand, there have been reports of both green and black tea extracts stimulating a gene in prostate cancer cells that may cause them to be less sensitive to chemotherapy drugs. Given this potential interaction, people should not drink black and green tea (as well as extracts of these teas) while receiving chemotherapy for prostate cancer in particular.
Clozapine -- The antipsychotic effects of the medication clozapine may be reduced if taken fewer than 40 minutes after drinking green tea.
Ephedrine -- When taken together with ephedrine, green tea may cause agitation, tremors, insomnia, and weight loss.
Lithium -- Green tea has been shown to reduce blood levels of lithium
Monoamine Oxidase Inhibitors (MAOIs) -- Green tea may cause a severe increase in blood pressure (called a "hypertensive crisis") when taken together with MAOIs, which are used to treat depression. Examples of MAOIs include phenelzine and tranylcypromine.
Oral Contraceptives -- Oral contraceptives can prolong the amount of time caffeine stays in the body and may increase its stimulating effects.
Phenylpropanolamine -- A combination of caffeine (including caffeine from green tea) and phenylpropanolamine (an ingredient used in many over-the-counter and prescription cough and cold medications and weight loss products) can cause mania and a severe increase in blood pressure. The FDA issued a public health advisory in November 2000 to warn people of the risk of bleeding in the brain from use of this medication and has strongly urged all manufacturers of this drug to remove it from the market.


Finally I would like to suggest an interesting point of view of the position of the green tea among the other nutrients

2014-05-31T20:45:55 - Stefano Beccaria

Green Tea Catechins and their iron-chelating properties


Stefano Beccaria and Francesca Benedettini

Catechins are an important class of polyphenols present in large quantities in Green Tea (GT).
The name of this chemical family derives from catechu, which is the tannic juice or boiled extract of Mimosa catechu (Acacia catechu).

The catechins belong to the group of flavonols, part of the chemical family of flavonoids .
Flavonols or catechin polyphenols are more commonly found in tea and comprise 30-40 percent of the extractable solids of dried green tea.
The molecules possess two benzene rings (called the A- and B-rings) and a dihydropyran heterocycle (the C-ring) with a hydroxyl group on carbon 3.

There are two chiral centers on the catechin on carbons 2 and 3 so it has four diastereoisomers. Two of the isomers are in trans configuration and are called catechin and the other two are in cis configuration and are called epicatechin.
(+)-catechin is the most common catechin isomer while the most common epicatechin isomer is (-)-epicatechin.

(+)-Catechin and (-)-epicatechin are ubiquitous constituents of vascular plants, and frequent components of traditional herbal remedies, such as the Chinese medicine plant Uncaria rhynchophylla and others. The two isomers are mostly associated with cacao and tea constituents, but (+)-catechin is also found in green algae.

The catechins have many biological activities: we know that they can be protective against cancer and inflammatory and cardiovascular diseases because of their antioxidant activity.
Regarding the antioxidant activity, (+)-catechin has been demonstrated to be the most powerful scavenger between different members of the different classes of flavonoids. This characteristic seems due to the chemical structure of catechin, with the presence of the catechol moiety on ring B and the presence of a hydroxyl group activating the double bond on ring C.
Polyphenols have anti-oxidative properties due to their capacity of chelation of pro-oxidant metals like iron. So they are able to protect erythrocytes from oxidation (Effect of green tea on iron status and oxidative stress in iron-loaded rats).

The protonated phenolic group is not a particularly good ligand for metal cations, but once deprotonated, an oxygen center is generated that possesses a high charge density. Although the pKa value of most phenols is in the region of 9.0-10.0, in the presence of suitable cations for instance iron(III) or copperII), the proton is displaced at much lower pH values, e.g., 5.0-8.0. Thus metal chelation by phenols can occur at physiological pH values. For chelation, bidentate ligands are much more powerful scavengers of metal cations than monodentate ligands, thus catechol binds iron(III) tightly at pH 7.0, whereas phenol does not (Metal chelation of polyphenols).

Green tea (Camellia sinensis) contains at least five catechin derivatives including epigallocatechin (EGC), catechin, epicatechin (EC), epigallocatechin 3-gallate (EGCG) and epicatechin 3-gallate (ECG), of which EGCG and ECG are the major constituents, whose peculiar property regards the iron-chelating capacity.

A highly toxic form of iron, non-trasferrin-bound iron (NTBI), is formed when the iron-binding capacity of transferrin has been exceeded. Uptake of plasma NTBI into tissues contributes to increased intracellular labile iron pool and it potentially can catalyze the formation of radically oxygen species through the Fenton reaction:
(1) Fe2+ + H2O2 → Fe3+ + HO• + OH–
(2) Fe3+ + H2O2 → Fe2+ + HOO• + H+

Polyphenols bind to ferric iron and they inhibit iron absorption.
(Effect of green tea on iron status and oxidative stress in iron-loaded rats)

Effects of GT on hepatic iron overload

Liver is affected by secondary iron overload in transfusions dependent β-thalassemia patients. The redox iron can generate reactive oxidants that damage biomolecules, leading to liver fibrosis and cirrhosis. Iron chelators are used to treat thalassemias to achieve negative iron balance and relieve oxidant-induced organ dysfunctions.
Thalassemia patients with iron-overload suffer from endocrinal gland malfunctions, liver fibrosis and cardiac arrhythmia. Eventually, this condition will be fatal unless suitable iron chelation therapy is managed. When transferrin in thalassemia plasma is fully saturated with iron, a toxic form of iron called non-transferrin-bound iron (NTBI) is detectable.
Labile iron pool (LIP) is redox-active and highly increased in iron overload, as a result of changes in iron import and ferritin degradation. It plays a role in free radical generation and is the main target of chelators.
Desferrioxamine (DFO) and deferiprone (DFP) chelation can decrease levels of ferritin and NTBI in the plasma compartment and the amount of iron burden in the liver of hereditary sideroblastic anemia patients and β-thalassemia major patients. The main target organs of chelation therapy are the liver and heart which accumulate a large amount of iron in cytosolic ferritin, hemosiderin and transitory pool. Green tea contains at least five catechins, of which EGCG and ECG are the major constituents, whose anti-oxidative and metal-chelating properties can protect cells from free-radicals imbalance and toxicity in many pathologic conditions.
Green tea can effectively lower the liver iron concentrations of iron-loaded thalassemic mice by three mechanisms:
1. the interference of intestinal iron absorption;
2. the chelation of plasma NTBI before intering into liver cells;
3. the mobilization of transient and storage pools of hepatic iron.
It can be speculated that green tea extract containing high EGCG and ECG contents could be utilized as phytochemical iron-chelating agents or adjunctive agents with oral iron chelators (eg. deferiprone and deferasirox) in iron-overload patients with β-thalassemia in the future. It is possible that green tea chelation will give compliance, be cost effective and produce minimal side effects to the chelated patients.

Neuroprotective effect of GT catechins trough their iron-chelating properties

One of the major pathology of progressive neurodegenerative diseases is the accumulation of iron in the degenerating neurons; various metals have been implicated in the pathophysiology of certain neuropsychiatric diseases (most of all copper and iron). Iron is more abundant in substantia nigra, globus pallidus and dentate gyrus, all regions known to be associated with neurodegenerative diseases. Ionic iron participates in Fenton chemistry, generating cytotoxic oxygen radicals, the most potent being the hydroxyl radical that is particularly reactive with lipid membranes. In Alzheimer’s disease (AD), iron promotes both deposition of amyloid beta (Ab) peptides and induction of oxidative stress, which is associated with the cerebral amyloid-containing plaques. In addition, iron may contribute to AD via regulation of amyloid precursor protein (APP) translation, resulting from the existence of an iron-responsive element (IRE-type II) in the 59UTR region of APP mRNA.
The involvement of metals in protein deposition in neurological disorders has encouraged the development of iron chelators as a major new therapeutic strategy. The chelator drug desferrioxamine and the antibiotic clioquinol have shown a neuroprotective activity but have some side effects: desferrioxamine is a very poor brain penetrating agent and clioquinol is highly toxic. The MAO A and B inhibitor has also shown neuroprotective activity as iron chelator. The ability of GT polyphenols to act as metal chelators and to have access to the brain makes them a novel promising therapeutic approach for treating AD, PD, and amyotrophic lateral sclerosis (ALS), in which accumulation of iron has been found.

EGCG regulates APP generation/processing and Ab formation
The capacity of catechins to neutralize excess of free iron may have a direct implication to AD; APP is post-transcriptionally regulated by iron regulatory proteins (IRPs), which are labile iron pool-sensitive cytosolic RNA proteins, binding specifically to the IREs located in the 59 or 39 untranslated regions of iron metabolism- associated mRNAs. Thus, reduction of the free-iron pool by EGCG chelation may lead to suppression of APP mRNA translation, by targeting the IRE-II sequences in the APP 59 UTR. Furthermore, wine and GT polyphenols are able to inhibit formation, extension, and destabilization of Aβ fibrils, and to protect against Aβ-induced neurotoxicity. Attenuation of APP synthesis and consequential Aβ production by EGCG could be of therapeutic value for AD therapy, as increased generation of Aβ plays a central role in AD plaque formation.
The other important pharmacological action of EGCG is related to the recent observation that EGCG promotes the generation of the soluble N-terminal fragment, soluble APP-alpha (sAPPa), via PKC-dependent activation of the enzyme a-secretase, thereby increasing the production of the nontoxic sAPPa.

GT catechins and induction of iron/hypoxia-responsive genes
The chelation of iron affects not only the post-transcriptional regulation of iron homeostasis-related mRNAs (e.g., TfR, ferritin), but also the induction of genes regulated by the transcription factor hypoxia inducible factor-1 (HIF-1), a master regulator orchestrating the coordinated induction of an array of genes sensitive to hypoxia. The target genes of HIF are especially related to angiogenesis, cell proliferation/survival, and glucose/iron metabolism. In this context, iron was recently shown to overcome HIF-1 activation by the GT catechins, EGCG and epicatechin-3-gallate (ECG), as well as by DFO. In fact, both HIF-1 and IRP2 share a common iron-dependent proteasomal degradation pathway, by the action of key iron and oxygen sensors prolyl hydroxylases, which become inactivated by iron chelation. Thus, the reduction in the free-iron pool by EGCG chelation may result in the inhibition of prolyl hydroxylases and consequently, in the concerted activation of both HIF and IRP2. As IRPs and HIF-1 coordinate the expression of a wide array of genes involved in cellular iron and glucose homeostasis, survival and proliferation, their activation could be of major importance in neurodegenerative diseases.

In conclusion, GT catechins may be recognized as multifunctional, brain-permeable iron chelators that can prevent or delay neuronal death in the degenerating human brain. Being of natural origin, they may not exert toxic side effects inherent to synthetic drugs.

Multifunctional Activities of Green Tea Catechins in Neuroprotection

Green Tea Catechins are being recognized as multifunctional compounds for neuroprotection. They act as radical scavengers, iron chelators and modulators of pro-survival genes, and PKC signaling pathway. The use of EGCG as a natural, non-toxic, lipophilic brain permeable neuroprotective drug is advocated for ‘ironing out iron’ from those brain areas where it preferentially accumulates in neurodegenerative diseases. Thus, green tea catechins may have potential disease-modifying action.

Controversial aspects about the relationship between Green Tea Catechins and iron/hypoxia-responsive genes

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that induces oxygen-regulated genes in response to reduced oxygen conditions (hypoxia). Expression of the oxygen-regulated HIF-1alpha subunit correlates positively with advanced disease stages and poor prognosis in cancer patients. Green tea catechins are believed to be responsible for the cancer chemopreventive activities of green tea. The results of this study (Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: potential adverse effects of cancer chemoprevention with high-dose green tea extracts) suggest that intended cancer chemoprevention with high-dose green tea extracts may be compromised, by the ability of tea catechins to promote tumor cell survival pathways associated with HIF-1 activation.

Many articles report that Green Tea Catechins stabilize HIF preventing its degradation (the above mentioned article about neuroprotection; Inactivation of prolyl hydroxylase domain (PHD) protein by epigallocatechin (EGCG) stabilizes hypoxia-inducible factor (HIF-1α) and induces hepcidin (Hamp) in rat kidney; Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1a, this article shows the anti-cancer activity of ECGC trough the induction of expression of a micro-RNA, following the stabilization of HIF).
There are also some articles who state that the anti-cancer activity of GT Catechins is linked to the inhibition of activation of HIF-1alfa (EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression; Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1).

Therefore, more studies are needed to fully understand the mechanisms that regulate the interactions between Green Tea Catechins and the transcriptional pathways of HIF and to clarify precisely the role of these interactions in carcinogenesis.

Stefano Beccaria and Francesca Benedettini

2014-01-16T15:18:24 - FabianaCamilla GiannoccaroDosio

Green tea as anti-tumor factor

Green tea (camellia sinensis Theaceae) has many benefic effects related to its content of specific polyphenols (GTPs) chemicals with potent antioxidant properties.

Anti-cancer properties

GTPs have been demostrated to have different interactions and roles within the cell, and they appear to have anti-metastatic and anti-angiogenic properties. Accumulating evidence shows that daily intake of green tea is protective against several lethal diseases and that green tea consumpion decreases cancer risk.

Pro-apoptotic action

Apoptosis is a programmed cell death and inducing apoptosis in tumor cells is a primary mechanism of action of certain anti-tumor drugs.
Many studies have shown that GTPs could protect against apoptosis in normal cells and induce apoptosis of cancer cells which are more susceptible to apoptosis induced by EGCG than normal counterparts.
Thus the anti-tumor mechanism of green tea appears to include the induction of apoptosis by EGCG through production of H2O2, inhibition of cell-cycle progression, and activation of the mitogen-activated protein kinase cascade.

In addiction, it has been proposed the involvement of the direct binding of EGCG to Fas, one of the death receptor proteins on the surface membrane of cells, to initiate the trasduction of signal for apoptosis. The Fas-Fas ligand system is one of the major pathways operating in the apoptotic cascade.

Anti-metastatic effect

It has been reported that EGCG inhibits the adhesion of cancer cells to endothelial cell layers. It was also found that EGCG prevented cancer cells from attaching to fibronectin and laminin, two main components of the endothelial basement membrane.

These findings (obtained by using in vitro and in vivo models) suggested green tea to have an anti metastatic effect. The experiments with artificially reconstituted basement membrane indicated that the green tea infusion and its constituent catechins prevented cancer cells from the penetration through the basement membrane.

Telomerase inhibition

The proliferative capacity of human cells is regulated by telomerase and a critical rule for telomerase activation in tumor progression and tumor maintenance has been well established by numerous studies. In fact, most (80-90%) cancer cells possess telomerase activity. EGCG, at low concentrations corresponding to plasma levels obtained after drinking a few cups of green tea, has been shown to inhibit telomerase. Continuous treatment of human monoblastoid leukemia cells (U937) with a nontoxic dose of EGCG lead to a progressive telomere shortening and eventually to a reduction of growth rate.

Anti-angiogenic properties

It is now recognized that the formation of a new blood vessel network within a tumor represents an important requirement for the progression of the tumor itself. Tumor angiogenesis has thus become one of the most promising therapeutic target in cancer medicine.
There is evidence in the literature indicating that GTPs can contribute to cancer prevention by the inhibition of angiogenesis.
EGCG targets include the phosphorylation of the VEGF receptor-2 and the capacity of endothelial cell to form capillary-like structures.
The effects of catechins were tested using in vitro models of angiogenesis. EGCG inhibited the binding of VEGF to its cell surface receptor in a concentration-dependent manner.

VEGF is a unique, potent angiogenic protein that has specific chemotactic effects on vascular endothelial cells. Various regulators and signal transduction pathways have been implicated in regulating VEGF expression. Recently, we reported that Erk-1 and Erk-2 are important in the signalling cascade that leads to overexpression of VEGF mRNA. In human colon cancer cells, EGCG inhibited angiogenesis by blocking Erk-1 and Erk-2 activation and VEGF expression. The exact mechanism by which ECGC inhibits the activation of Erk-1 and − 2 is not known. One possible explanation is that EGCG could inhibit kinases that are involved in Erk-1 and − 2 activation (EGCG inhibits tumor growth by inhibiting VEGF induction in human colon carcinoma cells, 2001)
Since the VEGF gene promoter has several AP-1 binding sites, EGCG could inhibit the induction of VEGF by decreasing the activation of the transcription factor AP- 1.
Taken together, the data reviewed above suggest that EGCG may block the early event of VEGF induction by inhibiting both the activation of Erk-1 and − 2 and the binding of transcription factor AP-1 to the VEGF promoter, thereby inhibiting the induction of VEGF transcription.
Other studies have evaluated the use of GTPs, specifically EGCG, as an inhibitory agent that can potentially suppress tyrosine phosphorylation at adherence junction sites, as well as inhibit the activation of the Akt survival pathway following stimulation by VEGF.
(Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green tea, 2001)

Green tea catechins at non-cytotoxic levels have been proved capable of suppressing chronically induced cellular carcinogenesis in breast cells, by blocking ERK activation, cell proliferation and DNA damages. (Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis, 2011).

The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface to the DNA in the nucleus of the cell. The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, including MAPK/ERK which communicate by adding phosphate groups to other proteins, which act as an "on" or "off" switch. This is also known as the Ras-Raf-MEK-ERK pathway.
When one of the proteins in the pathway is mutated, it can be stuck in the "on" or "off" position, which is a necessary step in the development of many cancers. Components of the MAPK/ERK pathway were discovered when they were found in cancer cells. Chemical compounds or drugs that reverse the "on" or "off" switch are being investigated as cancer treatments.

Pretreatment of cells with concentrations of EGCG as low as 0.3 m inhibited HGF-induced Met phosphorylation and downstream activation of AKT and ERK. Treatment with 5.0 m EGCG blocked the ability of HGF to induce cell motility and invasion.
These combined in vitro studies reveal the possible benefits of green tea polyphenols as cancer therapeutic agents to inhibit Met signaling and potentially block invasive cancer growth. (The green tea catechins inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells, 2006)

Health-promoting effects of green tea, 2012
Dietary prevention of cancer: Anticancer and Antiangiogenic properties of green tea polyphenols, 2005


Inhibition of tumour invasion and angiogenesis are important areas of research in tumour biology. The usefulness of green tea as a natural, non-toxic chemopreventive agent has been appreciated for at least 10 years. Recently, several laboratory studies have indicated that green tea, more specifically EGCG, offers beneficial effects with regard to inhibiting tumour progression and angiogenesis. Further research is necessary to define the molecular mechanism(s) by which green tea, and EGCG in particular, inhibit angiogenesis and tumour growth.

"One cup does all disorders cure
With two your troubles will be fewer
Three to the bones more vigor give
With four forever you will live
As young as on your day of birth
A true immemorial on the earth"
(Chinese proverb)

2012-07-13T21:30:43 - Silvia Varvello


Green tea catechins (GTC) are polyphenolic compound present in the unfermented dried leaves of the plant Camellia sinensis. Reports have shown that green tea extract intake (GTC 270 mg to 1200 mg/day) may reduce body weight and fat. Since the global prevalence of obesity has increased considerably in the last decade, this period presented a surge in studies investigating the potential of green tea as a natural agent of weight loss, with a view to confirming and elucidating the mechanisms underlying its effect on the body.
There are several proposed mechanisms whereby GTC may influence body weight and composition. While several unimodal mechanisms have been postulated, a more plausible explanation of the observed results might involve a multimodal approach. The predominating hypothesis is that GTC inhibits the enzymes catechol-O-methyltransferase, phosphodiesterase, acetyl-CoA carboxilase, fatty acid synthase and impeding absorption of fat via the gut.

The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms, 2011
Green tea catechins, caffeine and body weight regulation, 2010

The inhibition of catechol-O-methyltransferase (the enzyme that degrades norepinephrine) augmented the sympathetic nervous system activity stimulating thermogenesis and in this way increasing energy expenditure and promoting the oxidation of fat. The sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general. Caffeine, naturally present in green tea may act synergistically with GTC to increase energy expenditure and fat oxidation.

Antiobesity effects of green tea catechins: a mechanistic review, 2011

Norepinephrine is a catecolammine which bounds beta3 receptor and this stimulates an increase in cAMP levels. cAMP activates PKA which transfer the terminal ATP phosphate to perilipin (in Serine) and to hormone sensitive lipase (HSL). Phosphorylation activates HS lipase and causes a conformationale change in perilipin which moves away from triglycerides allowing HSL to act. HSL functions to hydrolyze the first (or third) fatty acid from a triacylglycerol molecule, freeing a fatty acid and diglyceride. It is also known as triglyceride lipase, while the enzyme that cleaves the second fatty acid in the triglyceride is known as diglyceride lipase, and the third enzyme that cleaves the final fatty acid is called monoglyceride lipase. The diglyceride and monoglyceride enzymes are tens to hundreds of times faster and are not sensitive to hormone. They are activated by the presence of mono- and diglycerides.


Insulin is a pancreatic hormone with several functions in carbohydrate and fat metabolism. One of its roles is activating phopshodiesterase which convert cAMP in AMP, this interrupts the activation of PKA. If GTC inhibits phosphodiesterase, PKA acts increasing lipolysis.

Finally, targets of PKA are also acetyl-CoA carboxilase and fatty acid synthase, the two enzymes regulating fatty acids synthesis. If these are inhibited, less fatty acids will be produced and stored in adipocytes.

In conclusion, GTC promotes lipolysis and inhibits metabolic processes leading to an increase in fatty acid level.

Several studies were conduced to test the effectiveness of catechins on metabolism, particularly on thermogenesis and fat oxidation.

Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans, 1999
The effects of epigallocatechin-3-gallate on thermogenesis and fat oxidation in obese men: a pillot study, 2007

Results shown that energy expenditure did not differ significantly between people treated with EGCG (epigallocatechin-3-gallate, the most important catechin in green tea) and placebo group; however respiratory quotient (RQ) values were signoficantly lower with EGCG compared to the placebo. This findings suggest that EGCG alone has the potential to increase fat oxidation in men and may thereby contribute to the anti-obesity effects of green tea.

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