Life Extension Magazine June 2011
Proprietary Green Tea Extract Protects the Kidneys
By Nathaniel S.W. Luce
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.
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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.
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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.
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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.
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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.
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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.
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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.
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