Friday, November 23, 2007

Everything you wanted to know about Green Tea and more...

From the - The George Mateljan Foundation

Health Benefits of Green Tea
Green tea is particularly rich in health-promoting flavonoids (which account for 30% of the dry weight of a leaf), including catechins and their derivatives. The most abundant catechin in green tea is epigallocatechin-3-gallate (EGCG), which is thought to play a pivotal role in the green tea's anticancer and antioxidant effects. Catechins should be considered right alongside of the better-known antioxidants like vitamins E and C as potent free radical scavengers and health-supportive for this reason.
Most of the research showing the health benefits of green tea is based on the amount of green tea typically consumed in Asian countries-about 3 cups per day (which would provide 240-320 mg of polyphenols). Just one cup of green tea supplies 20-35 mg of EGCG, which has the highest antioxidant activity of all the green tea catechins.
The health benefits of green tea have been extensively researched and, as the scientific community's awareness of its potential benefits has increased, so have the number of new studies. As of November 2004, the PubMed database contained more than 1,000 studies on green tea, with more than 400 published in 2004! Following is a brief summary of some of the high points of this most current research.
Green tea drinkers appear to have lower risk for a wide range of diseases, from simple bacterial or viral infections to chronic degenerative conditions including cardiovascular disease, cancer, stroke, periodontal disease, and osteoporosis. The latest studies provide a deeper understanding of the ways in which green tea:

Protects against Death from All Causes, Especially Cardiovascular Disease
In August 2006, a European study, published in the European Journal of Clinical Nutrition, found that tea is a healthier choice than almost any beverage, including pure water, because tea not only rehydrates as well as water, but provides a rich supply of polyhenols protective against heart disease.
Now, a Japanese study published in the September 2006 issue of JAMA, suggests that drinking green tea lowers risk of death due to all causes, including cardiovascular disease.
Shinichi Kuriyama, M.D., Ph.D., of the Tohoku University School of Public Policy, Sendai, Japan, and colleagues examined the association between green tea consumption and death due to all causes, cardiovascular disease (CVD), and cancer.
The study, which began in 1994, followed 40,530 adults, ranging in age from 40 to 79, in northeastern Japan for up to 11 years. Within this region, 80% of the population drinks green tea with more than half consuming at least 3 cups a day.
Compared with participants who consumed less than 1 cup of green tea per day, those drinking 5 or more cups a day had a significantly lower risk of death from all causes and, specifically, risk of death from CVD, with women receiving even stronger protection than men:

Green Tea Benefits
23% lower risk of dying from any cause
12% lower risk of dying from any cause
31% lower risk of dying from CVD
22% lower risk of dying from CVD
62% lower risk of dying from stroke
42% lower risk of dying from stroke

Only weak or neutral relationships were seen between black tea or oolong tea and all-cause or CVD mortality.
While this study found no cancer-preventive benefit from drinking green tea, other large studies, including a meta-analysis of 13 studies published July 2006 in Carcinogenesis (Sun CL et al), suggest that green tea reduces risk of breast cancer. In this study, compared to women who did not drink green tea, those consuming the most green tea were 22% less likely to develop breast cancer.
Often in studies, the effects of a certain health-promoting behavior are likely to be confounded by the fact that those who try to follow a healthy lifestyle practice a variety of healthy habits. In this study, however, since green tea is the most commonly consumed beverage in Japan, it is unlikely that study participants were choosing to drink green tea primarily for their health, and thus also unlikely that the significant drop in risk of death due to all causes and CVD was due to other habits related to health consciousness.
Given the significant benefit green tea can provide, even to those who are not especially health conscious, just imagine its health-protective potential as part of your healthy way of eating! If you simply cannot start your day without a cup of coffee, try enjoying a cup of green tea at your mid-morning break, with lunch or as an afternoon pick-me-up. You'll quickly discover green tea's irresistible combination of invigorating and calming qualities, plus its delicious flavor, make it one of your favorite healthy habits.

Protects against Coronary Artery Disease
In Japanese studies, green tea consumption has been found to be an independent predictor for risk of coronary artery disease. In one study, those drinking 5 or more cups of green tea each day were found to be 16% less likely to suffer from coronary artery disease. The relationship was so significant researchers concluded, "The more green tea patients consume the less likely they are to have coronary artery disease."
An elevation in the amount of free radicals in the arteries is a key event in many forms of cardiovascular disease. The latest research shows that green tea catechins inhibit the enzymes involved in the production of free radicals in the endothelial lining of the arteries. The arterial endothelium is a one-cell thick lining that serves as the interface between the bloodstream and the wall of the artery where plaques can form. By protecting the endothelium from free radical damage, green tea catechins help prevent the development of cardiovascular disease.

Inhibits Atherosclerosis
Green tea has been shown to effectively lower risk of atherosclerosis by lowering LDL cholesterol, triglycerides, lipid peroxides (free radicals that damage LDL cholesterol and other lipids or fats) and fibrinogen (a protein in the blood involved in the formation of blood clots), while improving the ratio of LDL (bad) to HDL (good) cholesterol.
In animal studies in which green tea was given in human equivalent doses to hamsters, atherosclerosis was inhibited 26-46% in those receiving the lower dose (equivalent in humans to 3-4 cups per day) , and 48-63% in those receiving the higher dose (10 cups a day in humans).

Special Benefits for Persons with High Triglycerides
Green tea may offer special heart-protective benefits for persons with high triglycerides, suggests a laboratory study, published in the February 2005 issue of the Journal of Nutrition.
A series of experiments revealed that the mix of catechins naturally found in green tea dose-dependently inhibit the activity of pancreatic lipase, the enzyme secreted by the pancreas that digests fat. As a result, the rate at which the body breaks down of fats into triglycerides, and the rise of triglyceride levels in the bloodstream that occurs after meals, is greatly slowed. Since a large rise in blood levels of triglycerides after a meal is a significant risk factor for coronary heart disease, drinking a cup of two green tea along with your meals is a good idea, especially if your triglyceride levels are higher than normal.

Thins the Blood and Helps Prevent Blood Clots
Green tea catechins help thin the blood and prevent the formation of blood clots by preventing the formation of pro-inflammatory compounds derived from omega-6 fatty acids, which are found in meats and polyunsaturated vegetable oils such as corn, safflower and soy oil. These pro-inflammatory compounds-specifically, arachidonic acid from which the inflammatory cytokines thromboxane A2 and prostaglandin D2 are derived-cause platelets to clump together.

Protects the Heart in Patients with Acute Cardiovascular Disease
The primary catechin in green tea, EGCG (epigallocatechin-3-gallate) confers such powerful protection that it can help prevent the death of heart muscle cells following ischemia/reperfusion injury. Ischemia is the medical term for a restriction in blood supply and therefore in oxygen and nutrients. When circulation is restored, oxidative damage occurs, and this is referred to as reperfusion injury.
EGCG prevents heart muscle damage by blocking the activation of inflammation-related compounds (including NF-kappa-B and STAT-1) that play a critical role in promoting the oxidative damage that kills heart cells in reperfusion injury. Researchers believe EGCG can be used to help minimize damage in patients with acute coronary artery disease.

Minimizes Damage and Speeds Recovery after a Heart Attack
Research conducted over the last several years by Dr. Anastasis Stephanou and his team at the UK's Institute of Child Health and published in the FASEB Journal, the journal of the Federation of Experimental Biology and the Journal of Cellular and Molecular Medicine has focused on EGCG's ability to block the action of the protein, STAT-1. Normally activated in cells after a heart attack or stroke, STAT-1 plays a major role in inducing cell death.
Not only does green tea minimize heart cell death after a heart attack or stroke, ECGC also appears to speed up heart cells' recovery from damage, allowing the tissues to recover more quickly and alleviating damage to organs. Dr. Stephanou, a molecular biologist, noted: "We're extremely encouraged by these findings and hope to implement them in the clinical setting to minimize cell death activation in patients with acute coronary heart disease."

Minimizes Damage to the Brain after a Stroke
EGCG has also been shown to protect brain cells by these same mechanisms and thus may help minimize the brain damage that occurs after a stroke. In one animal study, green tea was so effective in reducing the formation of free radicals in brain tissue that the researchers concluded, "Daily intake of green tea catechins efficiently protects the brain from irreversible damage due to cerebral ischemia, and consequent neurologic deficits."

Lowers Blood Pressure and Helps Prevent Hypertension
A study published in the July 2004 issue of the Archives of Internal Medicine found that among persons consuming tea regularly for at least one year, the risk of developing high blood pressure was 46% lower among those who drank ½ cup to 2 ½ cups per day, and 65% less among those consuming more than 2 ½ cups per day.
In another study, this one of rats bred not only have high blood pressure but also to be prone to strokes, those rats given green tea had significantly lower systolic and diastolic blood pressure compared to controls, who received plain water. The animals in this study, which was published in the January 2004 issue of the Journal of Nutrition, consumed the human equivalent of 1 liter (1.1 quarts or a little more than 4 cups) of green tea per day.

Helps Prevent the Development of Atherosclerosis and Cancer
In both atherosclerosis and cancer, cell growth and proliferation is central to the disease process. In atherosclerosis, plaques form in the lining of the arteries, which grow thicker and less elastic, impeding blood flow. In cancer, normal brakes on cells turn off, and they multiply out of control. Green tea can help stop abnormal cell proliferation.
Catechins, among the main active compounds in green tea leaves, shut down the primary relay station through which growth factors central to both atherosclerosis and cancer send their messages for growth. These relay stations, called tyrosine kinase receptors, are essential for the transmission of messages sent by platelet derived growth factor, insulin-like growth factor, epidermal growth factor, fibroblast growth factor, and vascular endothelial growth factor. The result is the prevention of or halting of the disease processes that depend upon excessive cellular growth.
Two other damaging factors that cause the cells lining our vasculature to proliferate are AGEs (advanced glycation end products) and MAPK (mitogen-activated protein kinase). AGEs form when sugars inappropriately bind to and distort proteins. MAPK activity is normally enhanced in the presence of elevated levels of LDL cholesterol. In laboratory studies, green tea polyphenols were shown to dose-dependently inhibit AGE-stimulated proliferation of vascular smooth muscle cells and to prevent the increase in MAPK normally seen when LDL levels are high.

Protects against Cancer
In the last ten years, green tea's cancer-preventive effects have been widely supported by epidemiological, cell culture, animal and clinical studies. For cancer prevention, the evidence is so overwhelming that the Chemoprevention Branch of the National Cancer Institute has initiated a plan for developing tea compounds as cancer-chemopreventive agents in human trials.
When confronted with a cancerous cell, green tea becomes the plant kingdom's Arnold Schwarzenegger, helping to terminate cancer cells in a remarkable number of ways.
Laboratory cell culture studies show that green tea polyphenols are powerful triggers of apoptosis (cell suicide) and cell cycle arrest in cancerous but not in normal cells. (Cell cycling is the process cells go through to divide and replicate.)
These anticancer actions have been assumed to be due to the powerful antioxidant effects of green tea's catechins, especially epigallocatechin-3-gallate (EGCG). This is a reasonable assumption, given that a number of studies have shown that green tea possesses remarkable antioxidant properties. In one study published in the November 2004 issue of Mutation Research, EGCG's protective antioxidant effects against several carcinogens were found to be 120% stronger than those of vitamin C.
But while green tea's antioxidant prowess is impressive, recent studies show it is far from the only way in which this multi-talented beverage protects us against cancer.
One of these mechanisms is green tea's ability to inhibit angiogenesis, the development of new blood vessels. Cancer cells, which are constantly attempting to divide and spread, have an endless appetite that can only be temporarily quieted by increasing the number of blood vessels that supply them with nutrients. By inhibiting angiogenesis, green tea helps starve cancer.
Studies also show that green tea works at the genetic level, shutting off genes in cancerous cells that are involved in cell growth, while turning on those that instruct the cancer cells to self-destruct. EGCG has even been found to work as a pro-oxidant or free radical, but just inside cancer cells, where it causes so much damage that the cancer cells' self-destruct mechanisms are triggered.
A study of ECGC's effects on keratinocytes (the major type of epidermal or skin cell) found that this green tea compound has yet another means of correcting cancer-that of turning on the genes that direct the cancer cell to return to normal.
Green tea's anticancer effects include its ability to inhibit the overproduction of the enzyme cyclooxygenase (COX)-2, a protein whose overproduction has been implicated as a factor in many diseases, including arthritis and cancer. COX-2 has an enzyme counterpart, called COX-1, which may be helpful to leave untouched when preventing overproduction of COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen (which inhibit both COX-1 as well as COX-2), and specific COX-2 inhibitors such as Vioxx and Celebrex (which inhibit only COX-2), have been considered as possible agents in the prevention of some forms of cancer, but their severe toxic side effects on normal cells limit their usefulness. In studies of prostate cancer cells, EGCG appears to block only COX-2 and to have no negative side effects.
Phytonutrients in green tea, specifically, its catechins, increase the production and activity of detoxification enzymes in humans, and may enhance our ability to detoxify carcinogens, shows research supported by the National Cancer Institute. 42 healthy volunteers refrained from tea or tea-related products for one month, after which blood samples were taken to assess the activity and levels of their glutathione S-transferases (GST), a major group of detoxification enzymes. Volunteers then consumed green tea catechins in amounts equivalent to consuming between 8-16 cups of green tea each day. GST activity was greatly enhanced in those whose baseline GST activity was low-those most susceptible to damage from carcinogens. Cancer Epidemiol Biomarkers Prev.2007 Aug;16(8):1662-6.

Prostate Cancer
EGCG provides other benefits specific to prostate cancer prevention. A study published in the December 2004 issue of the International Journal of Cancer found that EGCG significantly inhibited, in a dose-dependent manner, the production of prostate-specific antigen (PSA), a marker for prostate cancer risk. Not only did EGCG lower PSA levels, but it also suppressed all the activities of PSA which were examined that promote prostate cancer.

Green tea polyphenols halt prostate cancer at multiple levels
The polyphenols in green tea help prevent the spread of prostate cancer by mobilizing several molecular pathways that shut down the proliferation and spread of tumor cells, while also inhibiting the growth of blood vessels that supply the cancer with nourishment, according to research published in the December 2004 issue of Cancer Research.

Green tea polyphenols:
decrease insulin-like growth factor-1 (IGF-1), while increasing levels of IGF binding protein-3, which binds IGF-1, further diminishing its activity. (Increased levels of IGF-1 are associated not only with prostate cancer, but cancers of the breast, lung and colon.)
inhibit key cell survival proteins, promoting apoptosis or programmed cell death in cancer cells.
reduce the expression of several compounds (urokinase plasminogen activator and matrix metalloproteinase 2 and 9) involved in the metastasis and spread of cancer cells.
reduce the amount of vascular endothelial growth factor (VEGF), which develops new blood vessels to carry nutrients to developing tumors. All these effects were seen in this animal study within 6 months of continuous infusion. While obviously impractical for humans, the study suggests that daily consumption of green tea may be highly protective.
Choosing to regularly drink green tea and eat fruits and vegetables rich in the carotenoid, lycopene, may greatly reduce a man's risk of developing prostate cancer, suggests research published the Asia Pacific Journal of Clinical Nutrition (Jian L, Lee AH, et al.)
In this case-control study involving 130 prostate cancer patients and 274 hospital controls, men drinking the most green tea were found to have an 86% reduced risk of prostate cancer compared, to those drinking the least.
A similar inverse association was found between the men's consumption of lycopene-rich fruits and vegetables such as tomatoes, apricots, pink grapefruit, watermelon, papaya, and guava. Men who most frequently enjoyed these foods were 82% less likely to have prostate cancer compared to those consuming the least lycopene-rich foods.
Regular consumption of both green tea and foods rich in lycopene resulted in a synergistic protective effect, stronger than the protection afforded by either, the researchers also noted.

Practical Tips:
Get in the habit of drinking green tea and eating lycopene-rich foods.
Take a quart of iced green tea to work and sip throughout the day or take it to the gym to provide prostate protection while replenishing fluids after your workout.
Pack a ziploc bag of apricots and almonds in your briefcase or gym bag for a handy snack.
Start your breakfast with a half grapefruit or a glass of papaya or guava juice.
Begin lunch or dinner with some spicy tomato juice on the rocks with a twist of lime. Snack on tomato crostini: in the oven, toast whole wheat bread till crusty, then top with tomato sauce, herbs, a little grated cheese, and reheat until the cheese melts.
Top whole wheat pasta with olive oil, pine nuts, feta cheese and a rich tomato sauce for lunch or dinner.
Drinking 5 cups of green tea a day may cut the risk of advanced prostate cancer in half, shows data collected in The Japan Public Health Center-based Prospective Study. The JPHC Study followed 49,920 Japanese men aged from 40 to 69 from 1990 to 2004. Compared to men who drank less than one cup of green tea per day, those consuming 5 or more cups daily reduced their risk of developing advanced prostate cancer by 48%! If you don't already drink green tea, consider making this energizing, delicious beverage a healthy habit. Over half a million new cases of prostate cancer are diagnosed each year world wide, and, incidence of the disease, which is the direct cause of more than 200,000 deaths annually, is increasing with a rise of 1.7% over 15 years. Am J Epidemiol. 2007 Sep 29.

Ovarian Cancer
Green tea consumption has been shown to enhance survival in women with ovarian cancer. In a study published in the November 2004 issue of the International Journal of Cancer, women with ovarian cancer who drank at least 1 cup of green tea daily had a 56% lowered risk of death during the 3 years of the study compared to non-tea drinkers. A laboratory study of human ovarian cancer cells published in the September 2004 issue of Gynecologic Oncology explains why: EGCG not only suppresses the growth of ovarian cancer cells, but also induces apoptosis (cell suicide) in these cells by affecting a number of genes and proteins.
An epidemiological (population) study published in the December 2005 issue of the Archives of Internal Medicine, adds more evidence that enjoying a cup or two of tea each day may significantly lower a woman's risk of ovarian cancer.
Data from numerous other studies has suggested that both green and black tea may offer protection against various cancers, with tea polyphenols thought to be the most likely protective agents. In this research, Susanna Larsson and Alicja Wolk from the National Institute of Environmental Medicine, Stockholm, Sweden, decided to look specifically at the relationship between tea consumption and ovarian cancer.
Participants in their study were 61,057 Swedish women aged 40-76 years who were in the Swedish mammography cohort and had completed a validated 67 item food frequency questionnaire at baseline (between 1987-1990), after which the women were followed an average of 15.1 years.
Analysis of the data found that even women who averaged less than one cup of tea per day had an 18% lower risk of ovarian cancer than non-tea-drinkers.
Those who drank one cup per day had a 24% lower risk, and those who drank two or more cups of tea per day had a 46% lower risk of ovarian cancer than non-tea-drinkers.
Each additional cup of tea per day was associated with an 18% lower risk of ovarian cancer. Although higher tea consumption was generally associated with other health-promoting behaviors, including higher consumption of fruits and vegetables, when compared to the lifestyle behaviors of those who seldom or never drank tea, the large drop in ovarian cancer risk seen as tea consumption increased does suggest that tea is likely to offer significant protection.

Breast Cancer
Recent studies have also identified two mechanisms through which green tea works against breast cancer. Not only does EGCG inhibit the activity of telomerase, an enzyme that plays a key role in cell division, in breast cancer cells, but it also offers help to women with estrogen-negative breast cancer, a form of breast cancer that is very hard to treat successfully.
Estrogen-negative breast cancer cells express high amounts of the epidermal growth factor Her-2/neu, while in the more treatable estrogen-positive form of breast cancer, estrogen-receptor alpha (ERalpha) is expressed. According to a study published in the October 2004 issue of Molecular and Cellular Biology, EGCG induces the expression of ERalpha rather than Her-2/neu in breast cancer cells.

Brain Tumors in Children
Green tea's ability to inhibit telomerase may also translate into help for children with the most common malignant brain tumors of childhood, primitive neuroectodermal tumors. Telomerase's activity allows cancer cells to avoid the normal limits on the number of times a cell can replicate before it self-destructs. In a study published in the January 2004 issue of Neuro-oncology, investigators found that telomerase activity was at least five times higher in children with these brain tumors than in normal brain cells and that EGCG strongly inhibited telomerase activity in a dose-dependent manner.

Colorectal Cancer
Green tea may also reduce the increased risk for colon cancer caused by a high fat diet. An animal study published in the journal Nutrition and Cancer in 2003 found that when green tea was given along with a diet high in omega 6 fat (in the form of corn oil), the amount of pro-inflammatory compounds produced in the colon (5-lipoxygenase, leukotriene A4 hydrolase, and leukotriene B4) was significantly lower, as was the resulting number of precancerous colon cells (aberrant crypt foci). Green tea consumption even reduced the amount of abdominal fat produced in the animals that received it compared to controls.

Regular Green Tea Drinking Cuts Colorectal Cancer Risk in Half
To evaluate the link between green tea consumption and colorectal cancer risk, researchers followed 69,710 Chinese women ranging in age from 40 to 70 for 6 years.
Women who regularly drank green tea when the study began were 37% less likely to develop colorectal cancer compared to infrequent green tea drinkers. Women who continued to drink green tea regularly throughout the study fared even better, reducing their risk of colorectal cancer by 57%.: Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1219-23..

Practical Tip: Enjoy green tea as both a hot and iced beverage.
Brew green tea with thinly sliced ginger and lemon, or sprigs of spearmint. Add one teaspoon of honey per cup, stir and serve hot, or use half the amount of hot water (or twice the amount of tea), allow the tea to brew and cool, then combine half and half with fruit juice, such as peach, pineapple or papaya. Blend and pour over ice.
Make green tea chai by brewing green tea in hot vanilla soy milk. Top with a dash each of cinnamon, black pepper, ginger and allspice.

Gallstones and Biliary Tract Cancers
Green tea lowers risk of gallstones and biliary tract cancers, suggests a large population-based, case-control study led by Ann Hsing of the National Cancer Institute, Bethesda, Maryland, and published in the International Journal of Cancer, June 2006.
Hsing's team gathered demographic, medical and dietary data from 627 individuals with biliary tract cancer, 1037 persons with gallstones, and 959 randomly selected controls in Shanghai, China.
Among women, after taking account of age, education and body mass index, those who consumed at least one cup of tea each day for at least 6 months had a 27% reduced risk of developing gall stones, a 44% reduced risk of getting gallbladder cancer, and 35% reduced risk of bile duct cancer. Among men, most tea drinkers were cigarette smokers, which likely affected their results. Men's risk of biliary disease was lower with tea consumption, but the drop in risk was not considered statistically significant.

Lung Cancer
While we certainly do not recommend smoking, if you or someone you love smokes, or if you must be around smokers and are exposed to second hand smoke, drinking green tea can offer some protection against lung cancer. A human pilot study recently confirmed the protective effects of green tea against lung cancer seen in cell culture and animal studies. The study, published in the November 2004 issue of Molecular Nutrition and Food Research evaluated the effect of green tea (5 cups per day) on 3 heavy smokers (>10 cigarettes a day) and 3 individuals who had never smoked. When the study subjects were drinking green tea, DNA damage caused by smoking was decreased, cell growth was inhibited, and cellular triggers for apoptosis (cell suicide) in abnormal cells increased.
Another larger four month study of heavy smokers involving 100 women and 33 men found that levels of urinary 8-hydroxydeoxyguanosine, a marker of free radical damage to DNA, dropped significantly in individuals drinking decaffeinated green but not black tea.
Decaffeinated green tea was especially effective in reducing DNA damage in individuals who lack the genetic ability to produce normal amounts of an enzyme called glutathione S-transferase, which plays a key role in the liver's ability to detoxify many of the carcinogens found in cigarette smoke. Individuals whose genetic inheritance does not include the GSTM1 and GSTT1 variants of the genes that instruct the cell to produce glutathione S-transferase are more susceptible to developing many different cancers. For these individuals, green tea may be especially beneficial.
Bladder Cancer
Research by a multi-departmental team from UCLA has produced valuable insights into how green tea extract might be capable of acting against the invasive growth of bladder cancer tumors. Green tea extract has been shown, via a mechanism that affects cell movement, to target cancer cells while leaving healthy cells alone.
For cancer to grow and spread, the malignant cells must be able to move, and their movement depends on a process called actin remodeling, which itself is carefully regulated by complex signaling pathways, including the Rho pathway.
By inducing Rho signaling, green tea causes cancer cells to mature more rapidly and to bind together more closely, a process called cell adhesion. Both their increased maturity and cell adhesion inhibit cancer cells' mobility, according to Rao, senior author of the study, published in the February 2005 issue of Clinical Cancer Research, in which green tea's effects on Rho signaling were noted.
"Cancer cells are invasive and green tea extract interrupts the invasive process of the cancer…In effect, the green tea extract may keep the cancer cells confined and localized, where they are easier to treat and the prognosis is better," explained Rao.
About 56,000 new cases of bladder cancer are diagnosed each year, making it the fifth most common cancer in the United States. About half of all bladder cancers are believed to be related to cigarette smoking. Bladder cancer can be difficult to detect in the early, most treatable stages, yet, when not found early, the tumors can be aggressive, and more than half of patients with advanced cancers experience recurrences. In the next phase of his research, Rao and his team will analyze urine from bladder patients, looking particularly for biomarkers associated with actin remodelling and the activation of the Rho pathway, to determine which subset of patients might benefit most from green tea.

Improves the Efficacy of Cancer Drugs While Lessening Their Negative Side-Effects
In the fight against cancer, green tea polyphenols are team players, helping cancer-killing drugs do their job. In a study published in the October 2004 issue of the Journal of Pharmacy and Pharmacology, green tea polyphenols caused drug-resistant cancer cells, which were able to extrude or push out one of the most commonly used cancer drugs, doxorubicin, to retain the drug, which could then destroy them. According to a study published in the August 2004 issue of Cancer Letters, another compound in green tea, the amino acid theanine, reduces the negative side effects of doxorubicin by increasing the level of one of the body's most important internally produced antioxidants, glutathione, in normal tissues in the liver and heart-but not in tumors.

Understanding How Green Tea Fights Cancer
Spanish and British scientists have discovered at least one of the mechanisms through which green tea helps to prevent certain types of cancer, according to a study published in the March 2005 issue of Cancer Research.
ECGC, a catechin present in green tea in amounts about 5 times higher than in black tea, inhibits the enzyme dihydrofolate reductase (DHFR), which cancer cells need to be able to grow, and which is a well recognized target of anti-cancer drugs.
Scientists decided to look at ECGC after they realized the green tea catechin looks a lot like the cancer drug methotrexate, which prevents cancer cells from making DNA by inhibiting the DHFR enzyme. They discovered that ECGC kills cancer cells in the same way as the drug.
Although ECGC binds strongly to DHFR, which is essential in both healthy and cancerous cells, it does not bind as tightly as methotrexate, so its side effects on healthy cells are less severe than those of the drug.
ECGC's binding to DHFR may also explain why women who drink large amounts of green tea around the time they conceive and early in their pregnancy may have an increased risk of having a child with spina bifida or other neural tube disorders.
Women are advised to take supplements of folic acid when trying to conceive and during the first trimester (the first 3 months) of pregnancy because it is during this time period that the baby's neural tube is developing. Folic acid helps ensure normal development and protects against spina bifida by enabling the production of the enzyme DHFR. While a cup or two of green tea is unlikely to pose a problem, drinking large amounts of green tea could decrease the activity of DHFR, increasing risk of neural tube defects.

Improves Insulin Sensitivity in Type 2 Diabetes
Population studies suggest that green tea consumption may help prevent type 2 diabetes. A number of animal studies are beginning to explain why. New studies suggest that green tea may improve glucose tolerance and insulin sensitivity in individuals with diabetes. In one study, after receiving green tea for 12 weeks, diabetic rats had lower fasting blood levels of glucose, insulin, triglycerides and free fatty acids compared to controls, and the ability of their adiopcytes (fat cells) to respond to insulin and absorb blood sugar greatly increased.
In another study by the same research group, diabetic rats were separated into three groups and followed for 12 weeks. One group was given with standard rat chow and water (the control group), the second group received a high fructose diet and water (fructose group), and the third group got the same high fructose diet and green tea (green tea group). By the end of the study, the fructose group had high blood sugar, high insulin levels, and high blood pressure, while the animals receiving green tea along with a high fructose diet showed improvement in all three.
A study published in the August 2004 issue of BMC Pharmacology, in which oral glucose tolerance tests were given to healthy humans after they consumed green tea, showed that it increased the body's ability to utilize blood sugar.
Another interesting animal study compared the effects of a Western diet, a vegetarian diet and a Japanese diet, each with or without green tea. Blood sugar concentrations were highest in the animals on the Western diet followed by the Vegetarian diet with the Japanese diet producing the lowest blood sugars. When supplemented with green tea, blood sugar levels dropped in rats on all three diets, with those on the Japanese diet having not only the lowest blood sugars but also rating the best on other risk factors for type 2 diabetes. Rats on the Japanese diet that also were given green tea had the lowest triglycerides and cholesterol as well as the highest ratio of beneficial omega-3 fatty acids to potentially inflammatory omega-6 fatty acids. The researchers concluded that Japanese eating habits combined with drinking green tea might help prevent type 2 diabetes.
One of the mechanisms through which green tea improves insulin sensitivity has recently been identified in laboratory studies that show that epigallocatechin 3-gallate (EGCG) does a good deal more to prevent type 2 diabetes than lower the production of free radicals. EGCG also works on the genetic level, causing a reduction in the number of messenger RNAs that direct liver cells to produce the enzymes involved in the creation of glucose (sugar).

Protects against Kidney Disease
An animal study published in the January 2005 issue of Pharmacological Research suggests yet another beneficial effect of green tea consumption: the prevention of kidney dysfunction in persons who must take powerful immunosuppressant drugs, for example, after an organ transplant.
One such drug, cyclosporine A, while a very effective immunosuppressant, also markedly elevates the production of free radicals highly toxic to the kidneys. In this study, rats given green tea as their drinking water along with cyclosporine A produced far fewer damaging free radicals than rats given plain water. In addition, a number of other indicators of kidney function (serum creatinine, blood urea nitrogen, uric acid and urinary excretion of glucose) were significantly better in rats given green tea.
Another animal study published in May 2004 in the Annals of Nutrition & Metabolism explains why. Diabetic rats given green tea catechins and then exposed to a kidney-damaging drug, streptozotocin, produced less than half the amount of superoxide radicals (a particularly damaging type of free radical) compared to diabetic rats on a catechin-free diet. As a result, a cellular waste product formed by free radical damage to fats, lipofuscin, was almost 200% higher in the diabetic rats who did not receive green tea catechins compared to those who did.

Builds Bone
Researchers at the University of Tokyo have shown drinking green tea may significantly increase bone mineral density.
Their study, presented at the International Osteoporosis Foundation World Congress on Osteoporosis, Toronto, Canada, June 5, 2006, included 655 women aged 60 years or older. Participants completed a questionnaire about their consumption of green tea, milk, cheese, yogurt, fish, vegetable, tofu, natto (a soy food), meat and coffee; smoking, alcohol consumption, physical activity and use of anti-osteoporosis bisphosphonate drugs like Fosamax.
For each dietary item, subjects were divided into two groups: 1) those who consumed the item five or more days per week, and 2) those who consumed the item fewer than five days per week. The researchers then measured the bone mineral density (BMD) of the women's lumbar spines, as well as blood markers for osteoporosis risk, including levels of calcium, phosphorus, parathyroid hormone, alkaline phosphatase, osteocalcin, and vitamin D.
Women who drank green tea 5 or more days per week had an average BMD significantly higher (0.808 grams of hydroxyapatite-form calcium per square centimeter) than those drinking green tea less than 5 days per week (0.738 grams per square centimeter).
Green tea drinkers' bone-density advantage persisted even after results were adjusted for age, body mass index, other dietary items, smoking, alcohol, physical activity and use of osteoporosis drugs.
The Tokyo team hypothesized the catechin flavonoids in green tea provided the benefits via estrogenic effects known to build bone strength and/or induce apoptosis ("suicide") in bone-destroying cells called osteoclasts. Both mechanisms are similar to the ways in which bisphosphonate drugs like Fosamax prevent bone loss. But while these potent drugs can provoke inflammatory eye disorders, abdominal pain, nausea, vomiting, dyspepsia and diarrhea, green tea is not only completely safe, but a delicious beverage that offers a legion of other health benefits.

Green Tea Provides Bone Benefits Similar to Calcium or Exercise
Australian researchers report that bone mineral density (BMD) is 2.8% greater in tea drinkers than non-drinkers. The study involved 1,500 women (age range from 70-85) in a 5-year prospective trial looking at the effects of calcium supplements on osteoporotic fracture. Not only was tea drinkers' total BMD 2.8% higher than non-tea drinkers, but over the course of 4 years, tea drinkers lost an average of 1.6% of their total hip BMD, while non-tea drinkers lost more than twice as much (4%).
The 4 primary polyphenols in tea (epigallocatechin gallate (EGCG), epigallocatechin, epicatechin gallate, and epicatechin) were identified as being responsible. Green tea contains between 30-40% of water-extractable polyphenols, while black tea contains between 3-10%. "A recent review suggests that flavonoids from green tea may be associated with increases in BMD via a potent stimulatory effect on osteoblast function," noted lead researcher Amanda Devine. (Osteoblasts are the cells responsible for producing new bone.) Am J Clin Nutr. 2007 Oct;86(4):1243-7.

Prevents Osteoporosis and Periodontal diseases
Excessive bone loss is a characteristic feature not only of osteoporosis but of periodontal disease. Green tea supports healthy bones and teeth both by protecting osteoblasts (the cells responsible for building bone) from destruction by free radicals, and by inhibiting the formation of osteoclasts (the cells that break down bone).
Another benefit of green tea consumption for those with periodontal disease: green tea short circuits the damaging effects of the bacteria most responsible for gum disease, Porphyromonas gingivalis. P. gingivalis causes gum damage by producing toxic byproducts such as phenylacetic acid and by stimulating the activity and production of enzymes called metalloproteinases (MMPs), which destroy both the mineral and organic constituents that make up the matrix of our bones. Epigallocatechin-3-gallate (EGCG) inhibits P. gingivalis' production of both phenylacetic acid and MMPs.

Protects the Liver from Alcohol and Other Harmful Chemicals
Alcohol metabolism results in the production of damaging free radicals that can overwhelm the liver's supply of antioxidants, resulting in liver injury. In a study published in the January 2004 issue of Alcohol in which rats were chronically intoxicated with alcohol for 4 weeks, green tea prevented damage to their livers.
Other animal research shows that epigallocatechin-3-gallate (EGCG) protects the liver against the free radicals generated when mice are exposed to carbon tetrachloride, a toxic chemical solvent. Without the protection afforded by EGCG, carbon tetrachloride exposure resulted in the production of numerous free radicals that destroyed a significant amount of the animals' liver cells. With EGCG, free radical production and liver injury was so greatly reduced that researchers suggested green tea should be used in the treatment of liver disease.
Unlike some herbs, green tea's protective effects do not appear to affect two of the liver enzymes most often responsible for detoxifying and eliminating drugs, cytochrome P-450 2D6 and 3A4. This suggests that green tea might be safely consumed when taking medications primarily dependent upon the CYP2D6 or CYP3A4 pathways of metabolism. Hopefully, future research studies will bear out this potential benefit.
On the other hand, one study found that Japanese green tea did increase the activity of the CYP1A1 enzyme. Researchers hypothesized that the increase in activity of this liver enzyme may be one of the ways in which green tea helps protect against cancers caused by various dietary carcinogens.

Promotes Fat Loss
Green tea not only promotes fat loss, but specifically, the loss of visceral fat-fat that accumulates in the tissues lining the abdominal cavity and surrounding the intestines (viscera) and internal organs. Unlike fat deposits on the hips and thighs (which result in the so-called "pear" body shape), visceral fat (which produces the "apple" body shape) is highly associated with increased risk for metabolic syndrome and type 2 diabetes.
Green tea contains three major components that promote fat loss: catechins, caffeine and theanine. Studies suggest that green tea compounds promote fat loss by inhibiting both gastric and pancreatic lipase, the enzymes that digest triglycerides, and fatty acid synthetase, the enzyme responsible for synthesizing fatty acids into the form in which they can be stored in the body's adipose (fat) cells.
In a study published in the January 2004 issue of In Vivo in which mice were fed diets containing 2% green tea powder for 16 weeks, visceral fat decreased by 76.8% in those receiving green tea compared to the control group. Green tea also decreased blood levels of triglycerides (the chemical form in which most fats exist in the body).
A human study, published in the January 2005 issue of the American Journal of Clinical Nutrition, confirms green tea's ability to not only reduce body fat, but damage to LDL cholesterol as well. After 12 weeks of drinking just one bottle of green tea each day, 38 normal-to-overweight men in Tokyo had a significantly lower body weight, BMI, waist circumference, body fat mass and amount of subcutaneous fat compared to men given a bottle of oolong tea each day. After a 2 week diet run-in period, the men were divided into two groups, one of which drank a bottle of green tea containing 690 mg of catechins, while the other group drank a bottle of oolong tea containing 22 mg catechins. Not only did the men drinking green tea lose weight and fat, but the amount of their LDL cholesterol damaged by free radicals also dropped significantly. Since atherosclerotic plaques develop when cholesterol circulating in the bloodstream is damaged or oxidized, green tea's ability to prevent these oxidation reactions may explain some of its protective effects against cardiovascular diseases.

Increases Exercise Endurance
Green tea extract given to lab rats over a 10-week span increased the amount of time the animals could swim before becoming exhausted by as much as 24%.
Green tea's catechins appear to stimulate the use of fatty acids by liver and muscle cells. In muscle cells, the ability to burn more fat translates into a reduction in the rate at which glycogen, the form in which carbohydrates are stored for ready access in muscle, is used up, thus allowing for longer exercise times. Green tea's effect on muscle cells' ability to take in and burn fatty acids, speeding up fat breakdown, is also thought to be the reason why it helps weight loss.
The idea for the experiment came from the fact that skeletal muscles utilize carbohydrates, lipids (fats) and amino acids (protein) as energy sources, but the ratio in which they are used varies with the intensity and type of the exercise, and the level of the individual's fitness. During endurance exercise, the use of too much carbohydrate is undesirable because it triggers insulin secretion, which, in turn, both inhibits the burning of fatty acids and stimulates lactic acid production. (Lactic acid buildup is what causes that sore achy feeling in your muscles when you exercise.) Conversely, enhanced availability and utilization of free fatty acids reduces carbohydrate utilization, which in turn spares glycogen (the form in which carbohydrates are stored in muscle for quick use) and suppresses lactic acid production, resulting in an increase in endurance."
Drinking a single cup of green tea before exercise, however, will not be effective. One single, higher "dose" of green tea did nothing to improve lab rats' performance. The animals had to receive green tea daily, and endurance increased gradually over the 10 weeks of the study. To match the beneficial effect on test animals' endurance capacity seen in the experiments, the researchers estimate a 165-pound athlete would need to drink about 4 cups of green tea daily.

Protects against Cognitive Decline, Alzheimer's Disease and Parkinson's Disease
Damage to brain cells in Parkinson's, Alzheimer's and other neurodegenerative diseases seems to result from the combination of a number of damaging factors including excessive inflammation and increased levels of iron, both of which lead to increased free radical production, exhaust the brain's supply of protective antioxidants and trigger the production of certain proteins, such as amyloid-beta, which promote apoptosis (cell suicide).
Green tea catechins, until recently thought to work simply as antioxidants, are now known to invoke a wide spectrum of neuroprotective cellular mechanisms. These include iron chelation, scavenging of free radicals, activation of survival genes and cell signaling pathways, and regulation of mitochondrial function. (The mitochondria are the energy production factories inside our cells. When they are not working properly, they generate many free radicals and little energy.) The end result is a significant lessening of damage to brain cells.
Iron accumulation in specific brain areas and free radical damage to brain cells are considered the major damaging factors responsible for a wide range of neurodegenerative disorders including both Parkinson's and Alzheimer's disease.
In the brain, epigallocatechin-3-gallate (EGCG) has been shown to act as an iron chelator, binding to and removing iron, thus preventing it from contributing to the production of free radicals. In addition to removing iron, EGCG also increases the activity of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase, further helping to decrease free radical damage.
Another active compound in green tea, epicatechin (EC), reduces the formation of a protein called amyloid-beta. Plaque-like deposits of amyloid-beta in the brain are a defining characteristic of Alzheimer's disease.
Animal studies conducted at the Douglas Hospital Research Centre, McGill University, Quebec, Canada, suggest that a daily cup or two of either black or green tea may reduce the risk of age-related degenerative brain disorders such as Alzheimer disease.
The researchers looked at the protective effects of two tea extracts and their main constituents, epigallocatechin gallate and epicatechin gallate, which are highly concentrated in green tea, on dying nerve cells. Both black and green tea extracts and catechins strongly blocked death of neurons (brain nerve cells) When researchers exposed cultured neurons to amyloid alone, its effects were so toxic that the brain cells died, but when the cell cultures received amyloid immediately followed by tea extracts and catechins, the neurons were rescued and survived.
Green tea polyphenols have also demonstrated the ability to affect cell signaling pathways, in particular the MAPK pathways, which are triggered by oxidative stress (free radicals), and themselves set in motion a series of chemical reactions so damaging that they can result in brain cell death. MAPK signaling pathways inside brain cells are thought to play a critical role in neurodegenerative diseases.
Another important cell signaling pathway beneficially affected by EGCG, the PKC pathway, is also thought to play an essential role in the regulation of cell survival and programmed cell death.
Although no human studies on Alzheimer's disease have yet reported benefit from tea consumption, recent population studies have shown that simply consuming 2 or more cups of green tea daily reduces risk of cognitive decline and Parkinson's disease.

Green Tea Keeps Elders Mentally Sharp - Research Showing Multiple Ways
Green tea helps slow the age-related decline in brain function seen as declining memory, cognitive impairment, dementia and Alzheimer's, shows a human study published in the February 2006 issue of the American Journal of Clinical Nutrition.
Researchers at Japan's Tohoku University studied 1003 subjects over age 70, comparing their green tea intake and mental sharpness, using a Mini-Mental State Examination, a well-accepted standardized test for measuring cognitive function.
Drinking more than 2 cups a day of green tea slashed odds of cognitive impairment in elderly Japanese men and women by 64%! And a Japanese cup of green tea is much smaller than its American counterpart-only about 3.2 fluid ounces.
And at every level of cognitive impairment-from minimal to severe-those drinking the most green tea experienced significantly less mental decline than those drinking the least:
Compared with elderly Japanese who drank less than 3 cups a week, those drinking more than 2 cups a day had a 54% lower risk of age-related declines in memory, orientation, ability to follow commands and attention.
Those drinking 4 to 6 cups of green tea a week (1 cup a day) had a 38 lower risk of declines in brain function.
Green tea's primary protective agent is thought to be its catechin phytonutrient epigallocatechingallate or EGCG. Research shows this highly potent antioxidant:
helps prevent the formation of B-amyloid, a protein whose accumulation is recognized as causing Alzheimer's (Basianetto S, Eur J Neurosci Jan 2006).
protects brain cells by chelating (removing) iron, which might otherwise produce destructive free radicals (Reznichenko L, J Neurochem, March 2006).
helps prevent oxidative stress-induced brain cell death by "talking" to brain cells' genes responsible for cell cycling and survival. Specifically, EGCG tells the genes in neurons to decrease production of caspase 3, an enzyme involved in initiating programmed cell death. (Park HJ, Life Sci Jan 2006; Levites Y. J Biol Chem, 2002)
promotes memory-related learning ability by protecting cells in the hippocampus, a part of the brain involved in spatial cognition and memory-related learning ability, from free radical damage (Haque AM, J Nutr April 2006).
Green Tea Fights the FluA cup of green tea may help prevent or lessen the duration of the flu. In a lab study, published in the November 2005 issue of Antiviral Research, EGCG dramatically inhibited influenza virus replication in cell culture in all the subtypes of influenza virus tested. EGCG appears to suppress viral RNA synthesis by altering the properties of the viral membrane.
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Orthomolecular Formulations - O M EXTEND
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Christopher Wiechert, C.N.C.


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