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Sunday 28 January 2018

The Science of Tea: Green Tea in Risk of Life Style Related Diseases

Kyle J. Norton

Green tea, is a precious drink processes numbers of health benefit known to almost everyone in Asia and Western world.

Lifestyle diseases are a class of diseases associated with the way a person or group of people lives, including atherosclerosis, heart disease, and stroke; obesity and type 2 diabetes....and diseases precipitated by smoking and alcohol and drug abuse.

Epidemiological studies suggested that lifestyle-related diseases may be preventable with the change of lifestyle accompanied with intake of some nontoxic agents.

Differentiation of the effect of green tea in attenuated risk and treatment of lifestyle related diseases was found to associate to some mechanisms involving numbers of aspect(1), particularly, in gene facilitation.

For examples, in animal model, green tea administration inhibited risk and symptoms and progression of chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis(1), through regulation of tumor necrosis factor (TNF-alpha) gene(2) in expression of inflammatory cytokines in promoted systematic inflammation in the acute phase of infection caused by damage and injure tissues, in modulated the activation of NF-kappaB(2) signalling pathway related to cellular response in induction of anti and pro inflammatory stimulation and transcription factor complex (AP-1) in initiation of inflammation against foreign invasion.

The inhibition of inflammatory cytokines expression reduced symptoms of pain, reddish skin, swelling without limiting the protective effect of the immune system to prevent damage tissues against invasion of foreign substances.

1. Dementia
Dementia is the loss of mental ability severed enough to interfere with people's every life.

 Alzheimer's disease is the most common type of dementia in aging people. About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age.

According to the 5.7-year prospective cohort study, using a questionnaire, information on daily green tea consumption and other lifestyle factors collected from elderly Japanese individuals aged 65 years or more, green tea consumption is associated to reduce risk of dementia with a incidence of rate of occurrence of 8.7%(3).

In intracerebroventricular (ICV) infusion of streptozotocin (STZ) animal model explicited chronic brain dysfunction involved long-term and progressive deficits in learning, memory, and cognitive behavior, along with a permanent and ongoing cerebral energy deficit, mice treated with green tea EGCG at a dose of 10mg/kg/day for 4 weeks, showed a significant improvement in reduced oxidative stress parameter against production of inflammatory and free radical expression(4).

These inhibitions can be seen in the diminished AChE activity, glutathione peroxidase activity as well as NO metabolites, and reactive oxygen species contents

The enhanced antioxidants status induced neuroprotective effect was result of EGCG injection in ameliorated inflammatory and free radical causes of cell death in brain of treated mice.

Dr. Tomata Y, the lead author(4) of the study said, "The lower risk of incident dementia was consistent even after selecting participants who did not have subjective memory complaints at the baseline."

More explicitly, in the finding of a natural food for reverse or delay of risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors involved development of dementia and late-life cognitive disorders, green tea with high amount of caffeine stimulate the psychoactive effects in attenuated cognitive impairment/decline and dementia through heightened alertness and arousal and improvement of cognitive performance(5).

Promisingly, such results have been proposed by several cross-sectional and longitudinal population-based studies, particular in patients with mild cognitive impairment and progression to dementia.

2. Alzheimer's disease
Alzheimer's disease is a neuro-degenerative condition of loss or decrease of cognitive and memory functions due to aging.

According to the Maternal and Infant Health, ASL NA 3 SUD, epigallocatechin and gallic acid, (-)-Epigallocatechin-3-Gallate (EGCG), found in green tea exerted a strong anti-inflammatory and anti oxidative properties in protection against neuronal damage and brain edema(6).

The study also stated that green tea may also contribute to reduced risk and treatment of AD by ameliorated chronic viral infection, one of the cause in responsible for AD's neuropathology.

Dr. Mandel SA(7). the lead author and expert in green tea study said, "tea drinking may decrease the incidence of dementia, AD, and PD. In particular, its main catechin polyphenol constituent (-)-epigallocatechin-3-gallate (EGCG) has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders".

Other researchers suggested that the efficacy of epigallocatechin and gallic acid, (-)-Epigallocatechin-3-Gallate (EGCG) in reduced risk of AD may be attributed to
* The antioxidant activity(7) in ameliorate production of ROS in induced risk of oxidative stress which has been found to associate to production of lipid peroxidation, leading to abnormal deposition of amyloid β (Aβ) peptide(7)
* Free radical over expression in aging people also vulnerable to imbalance of antioxidant and ROS
may have a negatively direct interaction with proteins, nucleic acids, and other molecules and may also alter their structures and functions in inducing risk AD.

As a single ingredient isolated from green tea, epigallocatechin and gallic acid, (-)-Epigallocatechin-3-Gallate (EGCG) have been found to cause toxicity in some cases in medical literature. Therefore taking the ingredient in long term and overdoses may have a implication of liver damage.

In a animal study to evaluate the efficacy of Caffeic acid(8) in AD, mice rats randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group, mice fed with the phytochemical expressed a significant in increased learning deficit and cognitive function demonstrated by the Morris water maze task in compared control.

Fed mice also displayed of attenuated oxidative stress, inflammation, nuclear factor‑κB‑p65 protein expression (8)involved inflammatory cytokines production and suppressed caspase‑3 activity induced cell death and other mechanisms in the rats with AD.

The inflammatory process has shown to have an negative role in increased risk of AD, by causing neuroinflammation(8), including brain cells such as microglia and astrocytes and subsequently in promoted dysfunction and neuronal death. Therefore by suppressing production of inflammatory cytokins, caffeic acid expressed a significant reduction of AD risk.

The efficacy in contribution of cognitive improvement following caffeic acid(8)(9) application may be due to its antioxidant activity and restoration of cholinergic functions, as deficiency of cholinergic function has shown to effect cognition, behavior and activities of daily living.

3. Arthritis
Arthritis is a chronic condition characterized by painful inflammation and stiffness of the joints.

According to statistic, arthritis is the common autoimmune disorder affected over 50 millions world wide.

According to the College of Pharmacy, green tea epigallocatechin 3-gallate (EGCG) in preclinical studies displayed a significant effect in treatment of arthritic disease(12).

In vitro, application of green tea extract EGCG demonstrated activities in cartilage-preserving and chondroprotective action through reduced expression of proinflammatory IL-1β, TNFα, and IL-6
and modulated extracellular matrix (ECM)(11) turnover induced changes of the biomechanical environment of chondrocytes and accelerate the degradation of cartilage as well driving the progression of the disease in the presence of inflammation.

Normal extracellular matrix (ECM) is a composed collagen type II with function to provide tensile support for the tissue. 

In expression of proinflamatory factors researchers found that the over expression of proinflammatory cytokines IL-1 and IL-6 were associated correlatively in knee joints in arthritis and inhibition of IL-1 snd IL-6  by green tea EGCG IL-1 showed to reduce joint damage.

Some researchers also suggested that Interleukin 1 (IL-1)(11) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of pathological conditions leading to chronic inflammation.

In expression of tumor necrosis factor (TNF, tumor necrosis factor alpha,TNFα, cachexin, or cachectin), application of green tea inhibited the levels of TNFα in induction of synovial fibroblast cytotoxicity.

In the study to evaluate the possible effects of the administration of a green tea extract on the oxidative state of the liver and brain of adjuvant-induced arthritic rats, researchers indicated that green tea daily doses of 250 mg kg(-1) (59.8 mg catechins per kg) for 23 days displays a strong effect in decreased symptoms of arthritis by ameliorated diminutions in protein and lipid damage in liver, brain and plasma, through antioxidant effect in reduced levels of ROS(10) in stimulated free radical chain reaction to initiate production of pro inflammatory cytokines to precipitate chronic diseases.

Rats treated with green tea EGCG also showed a significant improvement in restored natural antioxidant glutathione (GSH) and protein thiol(10) levels produced by the body, by exhibiting the activities of the antioxidant enzymes.

Green tea injection also normalized the activity of glucose 6-phosphate dehydrogenase(10), which is increased in the liver of arthritic patients and considered as a risk factor for the development of arthritis. Increased activity glucose 6-phosphate dehydrogenase was associated to reactive oxygen species (ROS) generated in oxidative metabolism in inflicted damage on all classes of macromolecules.

Additional differentiation of green tea EGCG immunomodulatory effects and mechanisms on experimental arthritis induced by collagen-induced arthritis (CIA) in mice in compared to control received phosphate buffered saline (PBS), researchers found that application of green tea EGCG at dose of 10 mg/kg demonstrated a strong effect in ameliorated clinical symptoms and reduced histological scores in arthritic mice, through modulated the immune activity by induced over expression of the Nrf-2 antioxidant pathway(11), a major mechanism in the cellular defense against oxidative or electrophilic stress through detoxication and elimination.

EGCG also ameliorated experimental arthritis in mice by eliciting indoleamine-2,3-dioxygenase (IDO) through inhibition of pro-inflammatory cytokine interferon-gamma, astrocytes and microglia in facilitated production of dendritic cells (DCs)(11) in activation of the immune system to attack  the dendritic cell located on surface on the joint tissue.

Application of the EGCG also increased frequencies of T regs(11) which plays a dominant role in suppression of autoimmune pathology.

Some researchers suggested that increased Treg number and/or function in model systems may have a significant effect in both prevent and reverse arthritis disease.

4. Atherosclerosis
Atherosclerosis is medical condition characterized by the deposition of plaques of fatty material on the inner walls, causing to hardening of the arterial vessels.

According to statistic, mortality rate of coronary heart disease was about 60% in 2010 in compared to 30% of stroke and heart failure.

In the study to determine the effect of green tea bioactive epigallocatechin-3-gallate (EGCG) in ameliorated Porphyromonas gingivalis -induced atherosclerosis in a murine model, after injection of the extract EGCG, the tested mice than fed high-fat diets and injected with P. gingivalis three times a week for 3 weeks, observation at weeks 15 displayed a significant reduction of atherosclerotic plaques(14) accumulated in the branches of arteries, observed by Oil Red O staining

Polyphenol extract decreased infection of atherosclerotic lesion areas in the anatomic dilations of the ascending aorta through decreased expression of C-reactive protein, in regulated the acute phase of infection and monocyte chemoattractant protein-1 (MCP-1/CCL2) chemokines(14) in regulated migration and infiltration of monocytes/macrophages.of immune system in induced production of cytokines to counter foreign substances.

Green tea bioactive epigallocatechin-3-gallate (EGCG) not also improved LDL/very LDL cholesterol but also ameliorated ROS activity via antioxidant in induced low-density lipoprotein (LDL) oxidation(14), a leading indication of plague accumulation.

The efficacy of green tea epigallocatechin-3-gallate (EGCG) in reduced expression of atherosclerosis due to bacterial P. gingivalis was attributed to decrease secreted proteins with functions in stimulated inflammatory effects, such as chemokines (CCL2)(14) involv)ed in immunoregulatory and inflammatory processes, matrix metallopeptidase 9 (MMP-9)(14 in regulated pathological remodeling processes that involve inflammation, ICAM-1 (Intercellular Adhesion Molecule 1)(14) involvesd inflammation of capillary vessel walls, the mitochondrial chaperonin hsp60 in induction of inflammation,......

In the process to prevent plague to initiation of development of atherosclerosis through above implications, green tea epigallocatechin-3-gallate (EGCG) also increased levels of antioxidant defense enzyme (heme oxygenase-1 mRNA) HO-1 mRNA(14) levels in reduced expression of oxidative stress in induction of pathogenic inflammatory diseases.

The effect of epigallocatechin-3-gallate (EGCG) in inhibit the formation and development of atherosclerosis via its anti inflammatory capability also restricts the function of IL6 (interleukin 6)(16) in induced over expression of pro inflammatory cytokines and Angiotensin (Ang) II functions(16) in stimulated and increased vascular permeability through production of vascular endothelial cell growth factor CRP in initiated the pro inflammatory process.

Interleukin 6 is an interleukin with duo functions of pro inflammatory cytokines and anti inflammatory mytokines.

Antioxidant activities of EGCG also acted as free radical scavengers to prevent ROS to establish a chain reaction in induction of inflammatory effect in encouraging lipid accumulation in the inner wall of arteries, the leading cause of atherosclerosis.

ROS are free radical with function to mediate many pathophysiological processes, such as growth, migration, apoptosis and secretion of inflammatory cytokines,

Angiotensin is a hormone with function in regulated vasoconstriction in increased blood pressure.

Application of combined (-)-Epigallocatechin gallate (EGCG) +chitosan (CS) and aspartic acid (PAA)(16) demonstrated a significant effect in reduced risk and treatment of atherosclerosis through ameliorated lipid deposition in tested animals.

In compared to the effects of conventional medicine simvastatin with approximately successful treatment rate of lipid deposition of 15.6%, injection of (-)-Epigallocatechin gallate (EGCG) +chitosan (CS) and aspartic acid (PAA).exhibited over all treatment rate of 16.9%(15).

5. Asthma
Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing.

According to the joint study lead by the Ben Gurion University of the Negev, Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), a flavonoid found in green tea exhibited anti-oxidant/anti-inflammatory effects against various diseases, including asthma(17).

The study also demonstrated that the function of Kaempferol reduces oxidative stress through scavenging free radicals and superoxide radicals effects(17) and preserves the activity of various anti-oxidant enzymes(17) in attenuated production of pro inflammatory cytokines.

Evidence from in vitro and in vivo assays, postulated that aqueous fraction of green tea also exerts anti-asthmatic signaling activity in ovalbumin-induced asthmatic model(18).

In the study of mice induced asthma by an ovalbumin, aqueous extract of green tea displayed a potent anti-asthmatic activity by increasing the expression level of tumor necrosis factor-beta,(18) (a protein involved production of one of the inflammatory cytokine in the acute phase) and interferon-gamma(18) in displacement of immune function against microbial infection and decreased expression of anti-asthmatic cytokines in the lung.

Green tea alleviated asthmatic symptoms by increasing the expression of Th1 cell(18) in regulated the production of interferon-gamma and interleukin (IL)-2, proinflammatory cytokines and tumor necrosis factor.

Another green tea constituent, namely Chafuroside A (CFA), water-soluble flavone C-glycoside, in an experimental asthma/chronic obstructive pulmonary disease (COPD)-rat model, treatment with Chafuroside A at 0.5mg/kg, 1.0mg/kg could attenuate inflammatory symptoms and ameliorate antigen-induced airway inflammation, respectively(19).

Dr, Onoue S(19), the lead author in above study said, " A self-assembled micellar (SAM) formulation might be an efficacious approach for enhancing the therapeutic potential of CFA for treatment of inflammatory diseases".

Unfortunately, there are few reports suggested that green tea-induced asthma in tea-sensitive patients, as epigallociatechin gallate induced histamine release through IgE-mediated response

6. Chronic liver disease or cirrhosis
Liver cirrhosis is a condition of abnormal function of liver due to damage liver tissue replaced by scar tissue.
According to statistic, risk of liver cirrhosis is 1.6% in adult population.

Green tea polyphenols in reduced risk and treatment of patients with liver cirrhosis was found to associate to numbers of implication, involving various mechanisms.

In male SD rats model induced liver cirrhosis through carbon tetrachloride(CCL4), randomly assigned to 3 groups, including normal group, green tea extract (GTE) group and cirrhosis group, with GTE group and the cirrhosis group were injected subcutanuously 2 times/wk over 9 weeks with 40% Carbon tetrachloride (CCl4), researcher found that green tea treatment groups displayed a significant reduction of concentration of hydroxyproline(21), an amino acid produced during the hydrolysis of collagen initiate scar accumulation(21) in the liver damage tissue caused by CCl4) in compared to cirrhosis group.

Green tea exhibited antioxidant activities in decreased expression of malondialdehyde (MDA)(21), a highly toxic reactive species in precipitated liver damage induced by application of carbon tetrachloride(CCL4) and its extract ameliorated the liver damage cell in formation of cirrhosis through attenuating the expression of transforming growth factor beta 1 or TGF-β1(21) in initiated cell growth, cell proliferation.

In differentiation of 11 patients with hepatitis C and detectable viremia of 4 Child-Pugh (CP) class A cirrhosis, 4 Child-Pugh class B cirrhosis, and 3 noncirrhotic, researchers at the Thomas Jefferson University indicated that injection of a single oral dose of green tea extract 400 mg containing 94% pure EGCG demonstrated a strong effect in reduced cirrhosis over expression in induction of liver tumor growth by inhibiting the virus hepatitis in facilitate the production of ROS species(22) through chronic liver inflammation, according to the blood sample withdrawn from the patients without inducing liver toxicity.

Dr. Halegoua-De Marzio D(22), after taking into account of other con founders said, "A single 400-mg oral dose of EGCG was safe and well tolerated by all of the patients in the study" and disposition of EGCG was not significantly altered in these patients with cirrhosis".

In the concern of abnormal angiogenesis in patients with liver cirrhosis in induction of severe complications such as variceal haemorrhage and encephalopathy, Dr. Hsu SJ and colleges conducted a study to investigate the effect of green tea extract in Spraqtue-Dawley rats liver induced in by common BDL (bile duct ligation) in compared to control given distill water for 28 days and found that group treated with green tea extract expressed a strong implication in ameliorated the severity of portosystemic shunting, a rare malformation of the vessels supplying blood to the liver(20) caused by excessive shunting of blood from the liver portal vein to the lower and middle body into the right atrium of the heart due to liver cirrhosis in induction portal hypertension and one of complication of variceal haemorrhage in patient with chronic liver cirrhosis and mesenteric angiogenesis(20) in development of new blood vessels to supply oxygen and nutrients to initiate liver cancer.

The effect of green tea GTP extract in reduced progression of liver cirrhosis was attributed to the suppression of hypoxia-inducible factor 1-alpha (HIF-1α) (20)in expression of liver disease of diverse etiologies, including chronic liver diseases caused by viral infection, excessive alcohol consumption and activation of protein kinase B (Akt)(20) in regulated infectious liver cell survival, cell-cycle progression,... and levels of VEGF(20) in reflection of increased portal hypertension or decreased hepatic regenerative activity or the combination of both.

Dr.Hsu SJ(20), the lead author said after the conclusion, "GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.

7. Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a condition of lung disease caused by obstruction of air flow in normal breathing.

In a total of 13,651 adults from three Dutch cities examined from 1994 to 1997. observation of dietary intake estimated using a food frequency questionnaire, and flavonoid(23)(24) intake calculated using specific food composition tables, showed a significant effect of flavonoid intake regularly in reduced risk COPD(24).

According to the returned questionnaire, total catechin, flavonol, and flavone intake was positively associated with FEV1 in air flow of a deep breath(24) and inversely associated with chronic cough and breathlessness(24), common symptoms of chronic obstructive pulmonary disease (COPD).

More specified, Dr. Tabak C(24), the lead author said, "Flavonol and flavone intake was independently associated with chronic cough only".

Chafuroside A (CFA), a water-soluble flavone C-glycoside(25), isolated from oolong tea, in oral administration exhibited at 0.5mg/kg or higher exhibited a profound effect in attenuated inflammatory symptoms in a dose-dependent manner, in experimental asthma/chronic obstructive pulmonary disease (COPD)-like model.

Biomarker profiling revealed that the CFA/SAM at 0.1mg CFA/kg equipotent to CFA at 1.0mg/kg testing result also expressed protective activity against antigen-induced airway 
inflammation(25).

8. Type 2 diabetes

Diabetes is a condition characterized with insufficient insulin entering the bloodstream to regulate the glucose,  caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

According to the Third Military Medical University(26), regular consumption of green tea or green tea extract improved insulin sensitivity and glycaemic control in populations with diabetics.

In the review of literature found in data base of PUBMED, The Cochrane Library, EMBASE, ISI Web of Knowledge, Chinese Biomedical Literature Database and Chinese Scientific Journals Fulltext of 17 trials comprising a total of 1133 subjects suggested that green tea consumption significantly reduced the fasting glucose and hemoglobin A1c (Hb A1c) concentrations by -0.09 mmol/L and -0.30%, respectively(26).

Observed by the high Jadad score studies, green tea significantly reduced fasting insulin concentrations -1.16 μIU/mL in compared to non green tea drinker group(26).

The evaluation of green tea drink (T2 and T3) prepared by adding catechins and epigallocatechin gallate, major constituents isolated from green tea (EGCG) @ 550 mg/500 mL against non drinker group acted as control (T1), mice fed with T2 and T3 expressed a significant reduced cholesterol and LDL levels and serum glucose and insulin levels(27) with no difference in all functional drink groups but control.

Dr. Ahmad RS(27), the lead author said, "In contrast to lipid profile, experimental drink containing EGCG reduced the trait better than catechins based functional drink".

The compared diabetic effects of 3 selected tea water extracts (TWE) and tea pomace extracts (TPE) and by on rat intestinal α-glucosidase activity in vitro as well as hypoglycemic effects in vivo, insisted that in male Sprague-Dawley (SD) rats fed with tea extracts improved levels of blood glucose level at 30 min after oral intake (0.5 g/kg body wt) in compared to the control in sucrose-loaded SD rat, probably through activation of antioxidants properties in free radical scavenging(28).

Indeed, tea pomace extract in the study exerted a significantly inhibition of intestinal α-glucosidase, in delayed glucose absorption resulting in suppressing postprandial hyperglycemia(28).

9. Cardiovascular disease
Cardiovascular disease are chronic medical condition characterized of narrowed or blocked blood vessels that can lead to a heart attack including chest pain (angina).

According to statistic, heart disease is the second leading cause of death, claiming more than 48,000 lives every year.in Canada.

The differentiation of green tea bioactive polyphenols epigallocatechin gallate or EGCG in risk of cardiovascular disease researchers at the joint study lead by the Colorado State University found that application of EGCG activated the expression of the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor(30) in stimulated transcription of antioxidative genes in protection of cell against oxidative stress in induction of CVD.

In compared to statins, the conventional medicine may be effective in reduced heart attacks and strokes(30) in people at moderate and high risk but it can also cause cancers and multi-drug resistance cancer, EGCG ameliorated risk of CVD without giving rise to adverse effects.

In EGCG efficacy in risk of cardiovascular disease and metabolic syndrome by searching literature published online of major scientific databases, from 1995 to 2017, scientists found that EGCG exhibits a wide range of therapeutic properties including associated with the inhibition of LDL cholesterol in reduced risk of plague accumulated in the arterial wall in elevated risk of atherosclerosis, attenuated angiotensin II (AngII)(29) through inhibiting transcription factor NF-κB(29) in induced abnormal enlargement, or thickening of the heart muscle, and reduced risk of highly oxidative enzyme myeloperoxidase(MPO)(29) activity in promoted myocardial infarction, as level of myeloperoxidase(MPO) is considered as a biomaker used in assessment of risk of heart attack.

EGCG also exerted significant and profound effects in ameliorated risk of diabetes through lowering plasma glucoses and gycated haemoglobin level, inhibited pro inflammatory factors in elevated inflammation in the early phase of acute infection and chronic infection as well as blocking expression of ROS(29) in stimulated free radical chain reaction through its antioxidant activity.

Dr. Eng QY(29), after taking into account of other con founders, siad, "EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases".

In a total of 9 studies including 259,267 individuals satisfied the criteria and guideline included in the meta-analysis.by examining published literature in evaluated the association between green tea consumption, CVD, and ischemic related diseases. up to October 2014, researchers indicated that for non green tea drinker, risk of CVD was 1.19, intracerebral hemorrhage was 1.24 and cerebral infarction was 1.15 in compared to people who drank <1 cup green tea per day(31).

People who drank 1-3 cups of green tea per day had a reduced risk of myocardial infarction 0.81, and stroke 0.64 in compared compared to those who drank <1 cup/day and who drank ≥4 cups/day had a reduced risk of myocardial infarction of 0.68 in compared to those who drank <1 cup/day(31).

And for people who consumed ≥10 cups/day of green tea were also shown to have lower LDL in compared to group who drank <3 cups/day(31).

Dr. Pang J, the lead author at the final stage of the experiment said, "(The) meta-analysis provides evidence that consumption of green tea is associated with favorable outcomes with respect to risk of cardiovascular and ischemic related diseases".

The results finding of all studies confirmed that consumption of green tea is associated with favorable outcomes with respect to risk of cardiovascular disease as well as expression of various serum markers in compilation of how green tea initiated protective activity against CVD.

10. Metabolic syndrome
Metabolic Syndrome is a group of risk factors used to calculate the incidence of early onset of diabetes and cardiovascular diseases.

In a total of 35 obese participants with metabolic syndrome randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day), blood samples collected from green tea and green tea extract treated groups showed a significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively in compared to control group(33).

The study also found that the efficacy of green tea in ameliorated early progression of metabolic syndrome is attributed to the improved expression of serum antioxidant enzymes(33) (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity(33) in inhibited free radicals in exhibition of pro inflammatory cytokins.

Furthermore, in the total of 55 obese men and women recruited, injection of 280 and 360 g GTRB provided daily totals of 123.2 and 158.4 mg caffeine, and 188.3 and 242.1 mg of epigallocatechin gallate significantly reduced expression of metabolic syndrome(33) in attenuated weigh gain, high-density lipoprotein-cholesterol, triglycerides, and glucose concentrations(33).

More importantly, the study also found that administration of green tea also reduced levels of blood pressure in obese subjects but can not maintain the weigh loss after study.

Other researchers in the investigation of decaffeinated green tea extract (GTE) and voluntary running exercise (Ex) alone or in combination against obesity and metabolic syndrome in high fat (HF) fed C57BL/6J mice, insisted that combination of green tea injection and exercise treatment reduced final body mass (27.1% decrease)(34) and total visceral fat mass (36.6% decrease)(33), levels of fasting blood glucose (17% decrease)(34), plasma insulin (65% decrease)(34), and insulin resistance (65% decrease)(34) compared to HF-fed mice.

11. Renal disease
Renal Disease is an impaired function in toxin elimination for more than a specific time as a result of kidney damage or injure.

In mice fed with a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks).showed a decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-β (AS-β)by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) involved oxidize nutrients for energy conversion by 87%(36).

Flavanols (polyphenols) are rich phytochemicals isolated from green tea, particularly in the expression in form of most bioactive flavanol EGCG.

Oxidative phosphorylation (OXPHOS) protein ATP synthase-β (AS-β)(36) plays a key role in energy production and regulated the generation of free radicals, and apoptosis through respiratory chain.

Mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) in reduced risk of gene mutation through oxidative phosphorylation (OXPHOS)(36)

Dr. Rehman H(36), the lead author said," Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB".

In support of the efficacy of green tea for treatment of renal disease, the study of F40 rats randomly divided into 4 groups. Group 1 acted as control; group 2 received contrast medium (intravenous iodixanol, 10 mL/kg, as a single dose); group 3 received contrast medium and then green tea extract for 3 days (10 mg/kg/d, intraperitoneal); and group 4 first received green tea and then contrast medium, researchers showed that group treated with green tea had significantly higher overall scores than the control group(37).

Treatment group also expressed a significant improvement in progression of renal degeneration caused by nephrotoxicity of contrast media.

Unfortunately, according to the joint study lead by the China Medical University, GT inhibited the elimination of indoxyl sulfate (IS) and p-cresyl sulfate (PCS), a highly protein-bound nephro-cardiovascular toxins may deteriorate the renal function in CRF rats(35)

Indoxyl sulfate(IS), a circulating uremic toxin has found to associate to the development of glomerular sclerosis and interstitial fibrosis.

P-Cresyl sulfate (pCS) is also an uremic toxin generated by intestinal bacteria
which has an implication to worsen outcome of patients with chronic kidney disease and increased cardiovascular burden.

Iin experiment mice also showed a significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN), an indication of further kidney damage after ingestion of green tea catechin(36).

Dr. Peng YH(36), the lead author said, "GT consumption might also exacerbate the pathologies of CKD and CVD in end-stage CKD patients even under hemodialysis treatment. Therefore, we suggest that CKD patients should avoid drinking large quantity of tea beverages before benefits or risks to CKD patients assessed by future clinical studies. In conclusion".

12. Stroke
Stroke is a medical condition of emergency caused by reduced or interrupted blood circulation to the brain, such as blocking artery induced ischemic stroke and leaking or bursting of a blood vessel precipitated hemorrhagic..

According to statistic, in US, every year, approximately 795,000 people suffer a stroke, a leading cause of serious and long-term disability.

The review of medical literature published online suggested that green tea with strong inhibition of high blood pressure, a primary risk factor of stroke through its antioxidant and vasodilative activities induced by phytochemical flavonoids in improved blood circulation to the brain. Although increased acute blood pressure was found in some studies, this acute effect did not translate into significant alterations in ambulatory blood pressure during regular tea consumption(41).

The impact of tea or catechin consumption precipitated nitric oxide formation, as an essential gas signal molecule to protect the brain against in facilitated ischemic stroke and hemorrhagic stroke by relaxed vascular smooth muscle cells(41) and induced vasodilatation through regulating network of blood vessel and peripheral nerve tissues.

Amazingly, catechin also reduced NO levels through endothelial function by increased platelets aggression in post stroke.

In fact, green tea theanine, a bioactive chemical constituents also found to process anti stroke development through stimulating NO production of the cells in the inner wall of arteries in reduced risk of vascularconstrction and promoted blood circulation, thus decreasing risk of an artery-blocking clot, a major cause of stroke,

Glutamate molecule found in theanine may also play an important role in attenuated risk of stroke through neuroprotective effect(41)by decreased middle cerebral artery occlusion and cerebral infarction caused by blocking or narrowing the arteries in supplying blood and oxygen to the brain.

According to the study of 82 369 Japanese (aged 45-74 years; without cardiovascular disease [CVD] or cancer in 1995 and 1998 for Cohort I and II, respectively) received 13 years of mean follow-up through the end of 2007. green tea consumption of green tea 2 to 3 and ≥ 4 cups/d showed a significant effect in reduced risk of stroke with the multivariable-adjusted hazard ratios of 0.86 (0.78-0.95) and 0.80 (0.73-0.89), respectively in compared to non drinkers(38). And Higher green tea consumption reduced the risks of stroke subtypes, especially in intracerebral hemorrhage(38).

Other researchers suggested that green tea efficacy in reduced risk of stroke may be also associated to antioxidant effect in protection of endothelial function in blood circulation by reduced high blood cholesterol induced plaque build-up in the arteries(41) in blocking blood flow to the brain, particularly in reactive oxygen species (ROS) precipitation of lipid peroxidation.

The effect of green tea in reduced insulin resistance in healthy adults may also contribute to lower risk of stroke, according to the cohort of 1509 nondiabetic participants from the Northern Manhattan Study (mean [SD] age, 11 [10] years; 64.2% women; 58.9% Hispanics)(42).

Dr. Arab L (41)said, "Regardless of their country of origin, individuals consuming >or=3 cups of tea per day had a 21% lower risk of stroke than those consuming <1 cup per day (absolute risk reduction, 0.79; CI, 0.73 to 0.85). The proportion of heterogeneity not explained by chance alone was 23.8%".

13. Depression
Depression is a normal response as part of our daily lives such as the loss of s job, the death of a love one, and illness, affecting the way you eat, sleep, and the way you feel about yourself.

Over 30 million Americans suffer from depression and the amount is increasing in an alarming rate.

In a cross-sectional study of consumption of green tea and coffee ascertained with a validated dietary questionnaire and the amount of caffeine intake estimated from these beverages, green tea consumption is associated to reduce symptoms of depression, depending to amount of intake(43).

In comparison to amount intake of participants, the study also found that participants consumed ≥4 cups green tea/d had a 51% significantly lower prevalence odds(43)of having depressive symptoms than those consumed less than 1 cup/d.

Dr. Pham NM(43), the lead author in the study said, "higher consumption of green tea, coffee and caffeine may confer protection against depression".

In vivo, green tea(GT) and GABA green tea (GGT) also expressed a protective activity of against post-stroke depression (PSD)(44), a common consequence of stroke, according to joint study lead by the Pavia University.

In a mouse model of post-stroke depression, GGT and GT enhance the activity in the modulation of depressive symptoms(44) through decrease oxidative stress, increased antioxidant endogenous defenses, including polyphenol, theanine, glutamine, etc......

The review of Embase, PubMed, and Chinese National Knowledge Infrastructure databases from their inception through August 2014, tea consumption of more than 3 cups a day showed a significant decrease in the risk of depression of 37% (RR = 0.63, 95% CI: 0.55-0.71)(45), in compared to individuals with lower tea consumption and those with higher tea consumption.

14. Obesity
Obesity is a medical condition of excess body fat accumulated overtime. A person is considered an obese if excess body weight relatively to the height is over 30 in BMI index.

According to the University of the Punjab, Epigallocatechin gallate, a polyphenol found in tea plants exhibited anti obesity effect(46) through modulation of the PPAR[gamma] pathway in metabolism involved fat cells/adipose tissues.

In animal study, the chemical constituent stopped the adipogenic cell differentiation through different proteins and transcription factors in expression of adipocyte formation(47) which is considered as fat cell development in contribution to obesity.

Dr. Javaid MS(47), the lead author in the study said, "Docking analysis of PPAR gamma and epigallocatechin gallate demonstrated that epigallocatechin gallate binds with PPAR gamma at its active site and blocks its activity".

Animal induced by high fat diet, green tea Epigallocatechin 3-gallate (EGCG),exerted anti obesity effects through reduced plasma glucose and alleviate complications of diabetes(47) by attenuating advanced glycation end products (AGEs) formation involved proteins or lipids expression.

Dietary EGCG tested in C57BL/6 mice induced by high-fat diet with or without ECGC for 17 weeks and compared to a control group placed on low-fat diet for the same period, also showed a significanty reduced weight gain, plasma glucose, insulin level, liver and kidney weight, which can be seen in obesity in compared control mice(48).

Green tea Epigallocatechin 3-gallate (EGCG fed mice novally decreased the levels of AGEs(advanced glycation end product)(48) in both plasma and liver while inhibiting the receptor for AGE (RAGE) expression(48) of activating Nrf2, antioxidant response and enhanced anti oxidative stress ratio of GSH/GSSG.

Other searchers opinionated that the effect of green tea in reduced fat/adipose tissues accumulation in obese subject is a result of the pro-oxidant action of EGCG, in de activated cellular production of reactive oxygen species(49), through indication of adenosine monophosphate-activated protein kinase in suppressed gene and protein expression of enzymes and transcription factors involved in adipogenesis and lipogenesis(fat and adiposed metabolism).


Take together, there is no doubt that green tea with abundantly bioactive phytochemicals may be considered as a functional food to reduce risk, progression and treatment of lifestyle related diseases, but change of lifestyle is always recommended. However, intake of green extract should be taken with extreme care as some cases of acute liver toxicity were reported.

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Author Biography
Kyle J. Norton (Scholar, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Sources
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