Life Extension Magazine June 2011
Proprietary Green Tea Extract Protects the Kidneys
By Nathaniel S.W. Luce
More than 26 million Americans suffer from chronic kidney disease—many without knowing it.1
Early detection is critical because, if caught in time with blood testing, many forms of kidney impairment are reversible.
If kidney damage is allowed to progress unchecked, a patient may have to rely on side effect–prone drugs,2,3 or even worse, dialysis sessions three times a week. Kidney dialysis patients suffer many ill effects, especially to their vascular systems, and their life spans are significantly shortened.
In 2011,a team of researchers reported that the green tea extract in Life Extension®’s green tea formula prevented kidney damage in lab animals given gentamicin,4 a commonly prescribed antibiotic notorious for its potential to induce profound damage to the kidneys, including end-stage renal failure.
In this article, the results of their compelling findings are detailed, along with the underlying mechanisms of action by which green tea extracts target multiple factors implicated in kidney damage. You will also discover compelling data on green tea’s capacity to support and promote system-wide health across a range of age-related conditions.
Proven Comprehensive Protection
Green tea has been used for millennia as a health-promoting drink, and its extracts are achieving recognition by serious scientists around the world.5,6 Green tea is rich in polyphenol compounds called catechins, of which epigallocatechin-3-gallate (EGCG) is the best-studied and has shown the greatest range of beneficial effects.5-7
In a recent investigative study, Dr. Francesco Marotta and colleagues at the ReGenera Research Group for Aging-Intervention in Milan, Italy, chose to use Life Extension’s green tea extract consisting of 98% polyphenols (including 45% EGCG) to ascertain if it could protect rats from kidney damage that results from the use of the antibiotic gentamicin.4
Gentamicin is an antibiotic that is widely used for treating urinary tract and kidney infections. Unfortunately, gentamicin has also become notorious for damaging vulnerable structures in the kidney, especially the tiny tubules where urine is produced. One of the ways in which gentamicin exerts its destructive effects is by triggering production of reactive oxygen species (ROS), while at the same time impairing natural antioxidant defenses. This one-two punch results in direct damage to kidney tubules, which is then complicated further by development of localized inflammatory changes.8
When Marotta’s group treated lab rats with gentamicin alone, they saw precisely those destructive changes in the animals’ kidneys, along with evidence in the urine of kidney malfunction and oxidative stress.4 But when they administered Life Extension’s green tea extract at the same time as a dose of gentamicin, they discovered that they could reverse most of those harmful results. Marotta’s findings, presented in early 2011, confirm earlier work revealing that green tea extracts exert powerful antioxidant and anti-inflammatory effects, both in the kidney and in other tissues.9,10 And since most age-related diseases involve the combination of oxidative stress and inflammation, that’s powerful news for people interested in using green tea as an important component of a science-based longevity program.
Potent Antioxidant and Anti-inflammatory Protection
Marotta’s work emphasizes the value and importance of using a highly-purified extract, rich in EGCG, to maximize protective effects. New studies continue to be published and confirm the important fact that EGCG acts at multiple targets to reduce the impact of oxidative stress and inflammation. It directly scavenges free radicals as a result of its chemical structure.11,12 Green tea’s EGCG also indirectly boosts levels of cellular antioxidant systems, such as those centered on glutathione, which normally buffer the amount of oxidative stress in cells and mitochondria.4,9
One major benefit of green tea extracts is that they suppress inflammation on multiple fronts. They reduce production of inflammatory cytokines, in part by suppressing the “master switch” of inflammation called nuclear factor-kappaB (NF-kB).10,13,14 That effect can help prevent inflammatory consequences from initiating and promoting cancer.14 EGCG also turns on inflammation-inhibiting biochemical pathways in immune system cells, further mediating anti-inflammatory effects.15
Green tea extracts exert a host of so-called “epigenetic” effects, which means that they promote the expression of beneficial genes and suppress many of those with deleterious effects.16,17 Highly-purified, EGCG-rich green tea extracts produce rapid increases in plasma antioxidant activity in humans.18,19 That may offer an advantage over simply drinking green tea, because the extract of EGCG is much more readily absorbed in dry powder form than it is from green tea beverages.18,20
By working on so many important targets of human aging, green tea and its numerous components provide a broad spectrum of protection against multiple degenerative diseases.
Today we understand cancer, regardless of its type, to be the result of a multi-stage process. Cancer initiation involves early DNA damage or modification by toxins, radiation, or infectious agents. The accumulation of mutagens in genes that regulate cell proliferation is the underlying intiating event. Cancer promotion occurs as a result of internal factors, often involving inflammatory factors. Once a tumor begins to grow, it invades tissue by secreting enzymes that “melt” the surrounding matrix and by generating new blood vessels in the process called angiogenesis. Finally, cancers multiply and spread when they shed small bundles of malignant cells that secrete their own adhesion molecules, helping them find fertile ground for establishing new tumors far from the original primary site.
We now know that we can intervene at each of these steps, and green tea polyphenols, especially EGCG, are active against most of them.21 Because cancers are hard to cure, much interest is focused on ways that green tea extracts can provide chemoprevention, stopping cancers long before they become clinically evident.22
Green tea extracts prevent DNA damage through their antioxidant properties, and they also trigger innate DNA repair mechanisms to quickly patch up damage before it is transmitted to new cells.23 In human studies, consumption of green tea or its catechins rapidly reduce DNA damage throughout the body, resulting in reduced excretion of damaged DNA fragments in the urine.”24,25
EGCG’s anti-inflammatory characteristics add another layer of protection, helping to reduce production of inflammatory cytokines in stressed tissue. This has been well-documented in people at known risk for colon cancer, which is among the most common adult malignancies. Colon cancers usually begin as benign polyps that undergo malignant change in response to local inflammatory factors in the intestine. Green tea extracts may slow or stop that transition by reducing production of inflammatory cytokines.26
When nascent cancers start to grow, EGCG-rich green tea extracts quash their spread by several mechanisms. They prevent expression of a vascular endothelial growth factor (VEGF), which is required for generation of new blood vessels to feed the growing tumor.27,28 And they down-regulate production of tissue-melting proteins called matrix metalloproteinases (MMPs) that are essential for both local and metastatic spread to occur.29,30
Finally, cancer cells can be triggered to undergo programmed death, or apoptosis; green tea extracts are among the many nutraceuticals capable of inducing apoptosis via many different mechanisms in cancer cells.12,31
Human studies bear out these remarkable laboratory findings. Green tea extracts produce a rapid clinical response in at least 69% of women with human papilloma virus (HPV) lesions on their cervixes, which in turn dramatically reduces their risk of cervical cancer.32 Another virus, HTLV-1, is causatively associated with adult T-cell leukemia, and daily consumption of a green tea extract significantly reduced the number of viral particles in infected people.33
Dramatic findings are appearing with regard to prostate cancer and green tea extracts. Human prostate tissue rapidly accumulates tea polyphenols such as EGCG after oral supplementation.34 Men with certain biopsy findings called HG-PIN (high-grade prostatic intraepithelial neoplasia) are at a 30% risk of developing prostate cancer within a year, making them candidates for urgent intervention.35 When Italian oncologists treated men who had HG-PIN with a green tea extract, they found only a 3% rate of cancer development, compared with 30% in the control group.35 Symptom scores and overall quality of life improved as well. A subsequent study demonstrated long-term effects of the supplement, reducing new cancer diagnoses by nearly 80%.36
Later studies have consistently shown reduction in risk of advanced prostate cancer in men, often reducing their odds for developing the cancer by nearly 50%.37 And green tea extracts can reduce levels of the prostate-specific antigen (PSA), while inhibiting production of factors that enhance tumor spread.28
A virtually identical risk reduction (51%) has been shown in adults at risk for colon cancer.38 In that study, the size of new tumors was also smaller in the green tea extract group than in the control group.
Breast cancer cells respond in a remarkable way to green tea extracts, switching from the difficult-to-treat estrogen receptor- (ER)-negative types to ER-positive cells that are amenable to treatment with standard drugs.17 Green tea extracts also favorably regulate breast cancer tumor suppressor genes.39
There’s ample epidemiological evidence showing that green tea consumption helps modulate the risk of cardiovascular diseases.40-42 Until recently, though, the underlying mechanisms were unknown.43 As our picture of the real causes of atherosclerosis has become clearer, however, we’ve also begun to see how the catechins in green tea can operate at multiple targets to reduce our risk.44
Oxidation and inflammation are the earliest steps in producing endothelial dysfunction, the dangerous changes in blood vessel-lining tissues that can lead to arterial wall stiffening and ultimately to plaque formation. EGCG and other green tea catechins act powerfully to improve endothelial function.45-47 They enhance production of beneficial nitric oxide (NO), which in turn signals vessel walls to relax and dilate in response to blood flow.44,48,49
Green tea extracts reduce blood pressure in human subjects.50,51 Improved endothelial function is one mechanism, but others are active as well. Green tea desensitizes calcium-signaling channels through effects on the cardiac enzyme troponin, improving heart function during the relaxation (diastolic) phase.52 And green tea extracts also inhibit angiotensin-converting enzyme (ACE), which bumps up blood pressure.43 Finally, green tea extracts reduce dangerous cardiac remodeling in overweight and obese animals, limiting vessel stiffness and reducing cardiovascular risk.53
Green tea extracts helps to favorably modify lipid profiles, reducing levels of low-density lipoprotein (LDL) that, when oxidized, triggers additional inflammation and contributes to growing arterial plaques.50,51,54 And circulating markers of inflammation, particularly those triggered by obesity, are reduced by green tea extracts, while those such as adiponectin, which reduce fat-related inflammation, are bolstered.55
By virtue of their antioxidant characteristics, and their ability to modulate gene expression, green tea extracts can help fight the dangerous ischemia/reperfusion (IR) injury that follows a heart attack or stroke.56 IR injury creates a “storm” of oxidants and cytokines that can do more damage than the original event. Numerous animal studies reveal the extent to which EGCG improves the ischemic environment, triggering biochemical pathways that limit the extent of IR injury.40,57,58
But perhaps the most exciting news of all about green tea and cardiovascular disease is its potential effect on body composition, particularly on fat stores, now known to be the source of dangerous cytokines that set us up for most chronic conditions. Animal and human studies demonstrate that EGCG-rich green tea extracts can reduce fatness, limit fat-related cytokine production, and help reduce body weight.50,59
Obesity, and even moderate overweight, are precursors of the metabolic syndrome and type 2 diabetes, leading some researchers to refer to the entire syndrome as “diabesity.”60 EGCG and other catechins in green tea fight obesity by many different mechanisms.61 EGCG is a thermogenic compound, that is, it triggers the body to burn fat and produce heat, helping to consume fat stores even at rest.62-64 EGCG also improves glucose control and modifies body composition through alterations in gene expression in laboratory animals fed a high-fat diet.65
Green tea extracts improve satiety, the feeling of fullness after eating.66 This effect may help reduce total caloric intake. The extracts also produce mild carbohydrate malabsorption, inhibiting sugars from rapidly entering the bloodstream after a meal.67
EGCG acts via several mechanisms to reduce the amount of fat the body puts away in adipocytes, for example by limiting fat cells’ response to insulin stimulation.68 EGCG also directly inhibits an enzyme vital for formation of triglycerides, helping to reduce the body’s total burden of these dangerous fats.69 Green tea extracts can limit fat synthesis in liver cells as well.70
These biochemical changes have real impact in human studies. Obese men and women lose more weight when restricting calorie intake and supplementing with green tea extracts than do control subjects who only restrict calorie intake.50,71-77 Body composition is also favorably affected by green tea supplements, with reduction in visceral fat stores and significant reductions in waist circumference.50,74,78
Exercise remains a key component of any good weight loss program, and green tea supplements help exercising people lose even more weight safely.79 Blood pressure, LDL, and markers of inflammation are also typically reduced in obese patients using green tea supplements.16,50,59,72,76
Green tea extracts fight the diabetes/metabolic syndrome components of diabesity as well. Green tea extracts help control blood sugar and reduce levels of hemoglobin A1c, the blood marker associated with chronically elevated glucose.74,80 Green tea extract improves insulin sensitivity and glucose tolerance in animal and human studies, while burning fat through its thermogenic effects.81-85 Finally, the reduction in LDL and increase in high-density lipoprotein (HDL) seen with a polyphenol-rich nutrient blend including green tea, pomegranate, and vitamin C has a powerful beneficial effect on diabetic patients, who are at risk for cardiovascular complications.86
In early 2011, a team of researchers reported that the same green tea extract contained in Life Extension’s green tea formula prevented kidney damage in an animal model using gentamicin, a commonly prescribed antibiotic notorious for damaging and even destroying the kidneys. Green tea extracts are rich in catechins, flavonoid molecules with potent antioxidant and anti-inflammatory effects. Their multi-targeted mechanisms of action have also been shown to support system-wide health against cancer, cardiovascular disease, unhealthy body weight, and decreased insulin sensitivity.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Available at: www.kidney.org/kidneydisease/ckd/index.cfm#facts. Accessed March 18th, 2011.
2. Available at: http://www.mayoclinic.com/health/steroids/HQ01431. Accessed April 1, 2011.
3. Available at: http://www.mayoclinic.com/health/ace-inhibitors/HI00060/NSECTIONGROUP=2. Accessed April 1, 2011.
4. Marotta F, Naito Y, Lorenzetti A, et al. Old age and renal susceptibility to drugs. High-purity green tea ameliorates renal oxidative damage induced by gentamicin in aged rats. Presented at: VII European Congress IAGG- EU Region. Healthy and active ageing for all Europeans “II.” April 14-17, 2011. Bologna, Italy.
5. Wolfram S. Effects of green tea and EGCG on cardiovascular and metabolic health. J Am Coll Nutr. 2007 Aug;26(4):373S-88S.
6. Moderno PM, Carvalho M, Silva BM. Recent patents on Camellia sinensis: source of health promoting compounds. Recent Pat Food Nutr Agric. 2009 Nov;1(3):182-92.
7. Feng WY. Metabolism of green tea catechins: an overview. Curr Drug Metab. 2006 Oct;7(7):755-809.
8. Quiros Y, Ferreira L, Sancho-Martínez SM, et al. Sub-nephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein. Kidney Int. 2010 Nov;78(10):1006-15.
9. Salem EA, Salem NA, Kamel M, et al. Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure. Ren Fail. 2010;32(10):1210-5.
10. El-Mowafy AM, Al-Gayyar MM, Salem HA, El-Mesery ME, Darweish MM. Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling. Phytomedicine. 2010 Dec 1;17(14):1067-75.
11. Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010;15(11):7792-814.
12. Zhang H, Cao D, Cui W, Ji M, Qian X, Zhong L. Molecular bases of thioredoxin and thioredoxin reductase-mediated prooxidant actions of (-)-epigallocatechin-3-gallate. Free Radic Biol Med. 2010 Dec 15;49(12):2010-8.
13. Byrav DS, Medhi B, Vaiphei K, Chakrabarti A, Khanduja KL. Comparative evaluation of different doses of green tea extract alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats. Dig Dis Sci. 2010 Nov 17.
14. Gutierrez-Orozco F, Stephens BR, Neilson AP, Green R, Ferruzzi MG, Bomser JA. Green and black tea inhibit cytokine-induced IL-8 production and secretion in AGS gastric cancer cells via inhibition of NF-kappaB activity. Planta Med. 2010 Oct;76(15):1659-65.
15. Hong Byun E, Fujimura Y, Yamada K, Tachibana H. TLR4 signaling inhibitory pathway induced by green tea polyphenol epigallocatechin-3-gallate through 67-kDa laminin receptor. J Immunol. 2010 Jul 1;185(1):33-45.
16. Yun JM, Jialal I, Devaraj S. Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers. Br J Nutr. 2010 Jun;103(12):1771-7.
17. Li Y, Yuan YY, Meeran SM, Tollefsbol TO. Synergistic epigenetic reactivation of estrogen receptor-alpha (ERalpha) by combined green tea polyphenol and histone deacetylase inhibitor in ERalpha-negative breast cancer cells. Mol Cancer. 2010;9:274.
18. Benzie IF, Szeto YT, Strain JJ, Tomlinson B. Consumption of green tea causes rapid increase in plasma antioxidant power in humans. Nutr Cancer. 1999;34(1):83-7.
19. Chow HH, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res. 2003 Aug 15;9(9):3312-9.
20. Henning SM, Niu Y, Lee NH, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. Am J Clin Nutr. 2004 Dec;80(6):1558-64.
21. Yang CS, Wang X. Green tea and cancer prevention. Nutr Cancer. 2010 Oct;62(7):931-7.
22. Laurie SA, Miller VA, Grant SC, Kris MG, Ng KK. Phase I study of green tea extract in patients with advanced lung cancer. Cancer Chemother Pharmacol. 2005 Jan;55(1):33-8.
23. Katiyar SK. Green tea prevents non-melanoma skin cancer by enhancing DNA repair. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.
24. Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU. Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):242-9.
25. Luo H, Tang L, Tang M, et al. Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis. 2006 Feb;27(2):262-8.
26. August DA, Landau J, Caputo D, Hong J, Lee MJ, Yang CS. Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):709-13.
27. Tsao AS, Liu D, Martin J, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prev Res (Phila). 2009 Nov;2(11):931-41.
28. McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila). 2009 Jul;2(7):673-82.
29. Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A. Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines. Oncol Rep. 2010 Sep;24(3):747-57.
30. Farabegoli F, Papi A, Orlandi M. (-)-Epigallocatechin-3-gallate down-regulates EGFR, MMP-2, MMP-9 and EMMPRIN and inhibits the invasion of MCF-7 tamoxifen-resistant cells. Biosci Rep. 2011 Apr;31(2):99-108.
31. Lee MH, Han DW, Hyon SH, Park JC. Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-kappaB. Apoptosis. 2011 Jan;16(1):75-85.
32. Ahn WS, Yoo J, Huh SW, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev. 2003 Oct;12(5):383-90.
33. Sonoda J, Koriyama C, Yamamoto S, et al. HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking. Cancer Sci. 2004 Jul;95(7):596-601.
34. Henning SM, Aronson W, Niu Y, et al. Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. J Nutr. 2006 Jul;136(7):1839-43.
35. Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006 Jan 15;66(2):1234-40.
36. Brausi M, Rizzi F, Bettuzzi S. Chemoprevention of human prostate cancer by green tea catechins: two years later. A follow-up update. Eur Urol. 2008 Aug;54(2):472-3.
37. Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008 Jan 1;167(1):71-7.
38. Shimizu M, Fukutomi Y, Ninomiya M, et al. Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3020-5.
39. Fix LN, Shah M, Efferth T, Farwell MA, Zhang B. MicroRNA expression profile of MCF-7 human breast cancer cells and the effect of green tea polyphenon-60. Cancer Genomics Proteomics. 2010 Sep-Oct;7(5):261-77.
40. Liou YM, Hsieh SR, Wu TJ, Chen JY. Green tea extract given before regional myocardial ischemia-reperfusion in rats improves myocardial contractility by attenuating calcium overload. Pflugers Arch. 2010 Nov;460(6):1003-14.
41. Ou HC, Song TY, Yeh YC, et al. EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling. J Appl Physiol. 2010 Jun;108(6):1745-56.
42. Mulvihill EE, Huff MW. Antiatherogenic properties of flavonoids: implications for cardiovascular health. Can J Cardiol. 2010 Mar;26 Suppl A:17A-21A.
43. Persson IA, Persson K, Hagg S, Andersson RG. Effects of green tea, black tea and Rooibos tea on angiotensin-converting enzyme and nitric oxide in healthy volunteers. Public Health Nutr. 2010 May;13(5):730-7.
44. Hodgson JM, Croft KD. Tea flavonoids and cardiovascular health. Mol Aspects Med. 2010 Dec;31(6):495-502.
45. Kim W, Jeong MH, Cho SH, et al. Effect of green tea consumption on endothelial function and circulating endothelial progenitor cells in chronic smokers. Circ J. 2006 Aug;70(8):1052-7.
46. Alexopoulos N, Vlachopoulos C, Aznaouridis K, et al. The acute effect of green tea consumption on endothelial function in healthy individuals. Eur J Cardiovasc Prev Rehabil. 2008 Jun;15(3):300-5.
47. Nagaya N, Yamamoto H, Uematsu M, et al. Green tea reverses endothelial dysfunction in healthy smokers. Heart. 2004 Dec;90(12):1485-6.
48. Oyama J, Maeda T, Kouzuma K, et al. Green tea catechins improve human forearm endothelial dysfunction and have antiatherosclerotic effects in smokers. Circ J. 2010;74(3):578-88.
49. Reiter CE, Kim JA, Quon MJ. Green tea polyphenol epigallocatechin gallate reduces endothelin-1 expression and secretion in vascular endothelial cells: roles for AMP-activated protein kinase, Akt, and FOXO1. Endocrinology. 2010 Jan;151(1):103-14.
50. Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity (Silver Spring). 2007 Jun;15(6):1473-83.
51. Nantz MP, Rowe CA, Bukowski JF, Percival SS. Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study. Nutrition. 2009 Feb;25(2):147-54.
52. Tadano N, Du CK, Yumoto F, et al. Biological actions of green tea catechins on cardiac troponin C. Br J Pharmacol. 2010 Nov;161(5):1034-43.
53. Rickman C, Iyer A, Chan V, Brown L. Green tea attenuates cardiovascular remodelling and metabolic symptoms in high carbohydrate-fed rats. Curr Pharm Biotechnol. 2010 Dec;11(8):881-6.
54. Sung H, Min WK, Lee W, et al. The effects of green tea ingestion over four weeks on atherosclerotic markers. Ann Clin Biochem. 2005 Jul;42(Pt 4):292-7.
55. Bakker GC, van Erk MJ, Pellis L, et al. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach. Am J Clin Nutr. 2010 Apr;91(4):1044-59.
56. Akhlaghi M, Bandy B. Dietary green tea extract increases phase 2 enzyme activities in protecting against myocardial ischemia-reperfusion. Nutr Res. 2010 Jan;30(1):32-9.
57. Song DK, Jang Y, Kim JH, Chun KJ, Lee D, Xu Z. Polyphenol (-)-epigallocatechin gallate during ischemia limits infarct size via mitochondrial K(ATP) channel activation in isolated rat hearts. J Korean Med Sci. 2010 Mar;25(3):380-6.
58. Yanagi S, Matsumura K, Marui A, et al. Oral pretreatment with a green tea polyphenol for cardioprotection against ischemia-reperfusion injury in an isolated rat heart model. J Thorac Cardiovasc Surg. 2011 Feb;141(2):511-7.
59. Matsuyama T, Tanaka Y, Kamimaki I, Nagao T, Tokimitsu I. Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children. Obesity (Silver Spring). 2008 Jun;16(6):1338-48.
60. Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2010 Nov 2.
61. Grove KA, Lambert JD. Laboratory, epidemiological, and human intervention studies show that tea (Camellia sinensis) may be useful in the prevention of obesity. J Nutr. 2010 Mar;140(3):446-53.
62. Dulloo AG, Duret C, Rohrer D, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec;70(6):1040-5.
63. Hursel R, Westerterp-Plantenga MS. Thermogenic ingredients and body weight regulation. Int J Obes (Lond). 2010 Apr;34(4):659-69.
64. Boschmann M, Thielecke F. The effects of epigallocatechin-3-gallate on thermogenesis and fat oxidation in obese men: a pilot study. J Am Coll Nutr. 2007 Aug;26(4):389S-95S.
65. Chen N, Bezzina R, Hinch E, et al. Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet. Nutr Res. 2009 Nov;29(11):784-93.
66. Josic J, Tholen Olsson A, Wickenberg J, Lindstedt S, Hlebowicz J. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: a randomized controlled trial. Nutr J. 2010 Nov 30;9(1):63.
67. Zhong L, Furne JK, Levitt MD. An extract of black, green, and mulberry teas causes malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers. Am J Clin Nutr. 2006 Sep;84(3):551-5.
68. Hsieh CF, Tsuei YW, Liu CW, et al. Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways. Planta Med. 2010 Oct;76(15):1694-8.
69. Kao CC, Wu BT, Tsuei YW, Shih LJ, Kuo YL, Kao YH. Green tea catechins: inhibitors of glycerol-3-phosphate dehydrogenase. Planta Med. 2010 May;76(7):694-6.
70. Park HJ, Dinatale DA, Chung MY, et al. Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice. J Nutr Biochem. 2010 Jul 22.
71. Auvichayapat P, Prapochanung M, Tunkamnerdthai O, et al. Effectiveness of green tea on weight reduction in obese Thais: A randomized, controlled trial. Physiol Behav. 2008 Feb 27;93(3):486-91.
72. Di Pierro F, Menghi AB, Barreca A, Lucarelli M, Calandrelli A. Greenselect Phytosome as an adjunct to a low-calorie diet for treatment of obesity: a clinical trial. Altern Med Rev. 2009 Jun;14(2):154-60.
73. Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes (Lond). 2009 Sep;33(9):956-61.
74. Nagao T, Meguro S, Hase T, et al. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity (Silver Spring). 2009 Feb;17(2):310-7.
75. Tsai CH, Chiu WC, Yang NC, Ouyang CM, Yen YH. A novel green tea meal replacement formula for weight loss among obese individuals: a randomized controlled clinical trial. Int J Food Sci Nutr. 2009 Sep 7:1-9.
76. Basu A, Sanchez K, Leyva MJ, et al. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J Am Coll Nutr. 2010 Feb;29(1):31-40.
77. Westerterp-Plantenga MS. Green tea catechins, caffeine and body-weight regulation. Physiol Behav. 2010 Apr 26;100(1):42-6.
78. Wang H, Wen Y, Du Y, et al. Effects of catechin enriched green tea on body composition. Obesity (Silver Spring). 2010 Apr;18(4):773-9.
79. Maki KC, Reeves MS, Farmer M, et al. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr. 2009 Feb;139(2):264-70.
80. Fukino Y, Ikeda A, Maruyama K, Aoki N, Okubo T, Iso H. Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities. Eur J Clin Nutr. 2008 Aug;62(8):953-60.
81. Venables MC, Hulston CJ, Cox HR, Jeukendrup AE. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr. 2008 Mar;87(3):778-84.
82. Hininger-Favier I, Benaraba R, Coves S, Anderson RA, Roussel AM. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat. J Am Coll Nutr. 2009 Aug;28(4):355-61.
83. Ramadan G, El-Beih NM, Abd El-Ghffar EA. Modulatory effects of black v. green tea aqueous extract on hyperglycaemia, hyperlipidaemia and liver dysfunction in diabetic and obese rat models. Br J Nutr. 2009 Dec;102(11):1611-9.
84. Qin B, Polansky MM, Harry D, Anderson RA. Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats. Mol Nutr Food Res. 2010 May;54 Suppl 1:S14-23.
85. Roghani M, Baluchnejadmojarad T. Hypoglycemic and hypolipidemic effect and antioxidant activity of chronic epigallocatechin-gallate in streptozotocin-diabetic rats. Pathophysiology. 2010 Feb;17(1):55-9.
86. Fenercioglu AK, Saler T, Genc E, Sabuncu H, Altuntas Y. The effects of polyphenol-containing antioxidants on oxidative stress and lipid peroxidation in Type 2 diabetes mellitus without complications. J Endocrinol Invest. 2010 Feb;33(2):118-24.