The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 20 No. 1 • February 2017


GETTING CONNECTED WITH EGCG

EGCG is connected to lifespan
Lifespan is connected to stress
Stress is connected to obesity
Obesity is connected to cancer
Cancer is connected to diet
Diet is connected to eating
Eating is connected to drinking
And drinking—tea that is—
Is connected to Y O U.

—this silly ditty written by Sandy

The reality is that green tea (in particular, its major polyphenol EGCG (epigallocatechin 3-gallate), is an amazingly inexpensive source of important health benefits, which may include protection against neurodegenerative diseases and cognitive decline with aging to reducing stress-induced disorders to reducing the risk of cancer and cardiovascular disease to increasing lifespan of C. elegans and possibly even to reducing scarring after burns.

PROTECTION AGAINST INFLAMMATION BY EGCG

C-REACTIVE PROTEIN (CRP) REDUCED IN OLD RATS BY EGCG

Among its many benefits, EGCG has been reported in a number of studies to have anti-inflammatory activity. In one recent study (Kumaran, 2009), 3 months old and 24 months old male albino Wistar rats were studied. They were made hypercholesterolemic by being fed a diet of normal rat chow supplemented with 4% cholesterol and 1% cholic acid. Treated rats also received EGCG (100 mg/kg body weight/day) orally for 30 days. Unsurprisingly, the untreated old rats had abnormally elevated lipid levels, marker enzymes, and inflammatory enzymes in serum, as compared to the young rats. This EGCG dose is roughly equivalent to one of our green tea booster capsules taken three times a day, or 6 cups of green tea a day.

Results showed that treatment with EGCG partially reversed the elevated lipid levels and the inflammatory changes seen in the old rats. For example, elevated levels of TNF-alpha (tumor necrosis factor alpha), CRP (C-reactive protein), and fibrinogen (a clotting factor) were “reverted back to near control values upon supplementation of EGCG.” The authors add, “Plasma CRP, an acute phase reactant has proven remarkably robust as a marker of cardiovascular risk... (Kumaran, 2009). ”

As the researchers (Kumaran, 2009) noted in the introduction: “The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that is described best as an age-related inflammatory disease.”

EGCG AGAINST CANCER

One way that EGCG protects against cancer is to reactivate tumor suppressor genes that have been silenced by being methylated. DNA methylation is a method used in the body to make genes inaccessible for the purpose of being expressed. This can be reversed by reducing DNA methylation, which is what EGCG did in a recent study (Nandakumar, 2011). This is important, as DNA methylation increases with aging, one likely reason for the increasing susceptibility of older persons to get cancer.

Studies of green tea have revealed anti-cancer effects in a variety of different cancers, including stomach, small intestine, colon, lung, bladder, prostate, breast, oral cavity, prostate, melanoma, multiple myeloma, acute myelogenous leukemia, and chronic myelogenous leukemia, among others (Kumazoe, 2016). Several studies have shown that the active compounds in green tea extract are the catechins, with EGCG (epigallocatechin-3-gallate) as the most common form (Kumazoe, 2016).

PROSTATE CANCER INHIBITED BY EGCG

Despite some progress in the treatment of cancer, prostate cancer is still a major killer. Although it can often be brought into remission by blocking androgens, the cancer usually becomes insensitive to androgens and recurs in a different form—it can no longer be controlled by blocking androgens and is then very difficult to treat. Indeed, as of 2006, prostate cancer had become the second leading cause of cancer-related deaths among men in western countries (Bettuzzi, 2006).

A double-blind, placebo- controlled study of 60 men with high-grade prostate intraepithelial neoplasia, 30% of whom would be expected to develop prostate cancer within a year, reported that after a year only one tumor was found in the thirty men treated with green tea catechins (of which EGCG is the major component). The men took three capsules of 200 mg green tea catechins per cap each day for a year. The 30 men who received placebo had 9 tumors diagnosed. (Bettuzi, 2006) This study was particularly impressive considering that the men ALREADY had a form of early prostate cancer that was highly likely to progress to full blown prostate cancer.

In an epidemiological study of 49,920 Japanese men aged 40-69, consumption of green tea (5 or more cups a day) was associated with a dose dependent decrease in the risk of developing advanced prostate cancer, but not of local prostate cancer. The men were followed from 1990 (or 1993) to the end of 2004 (Kurahashi, 2008). These results show an association between green tea and a reduced risk of advanced prostate cancer but cannot be considered proof of causality.

EGCG INCREASES LIFESPAN OF CAENORHABDITIS ELEGANS

The famous model organism, C. elegans, a free living soil nematode worm, subject of numerous studies including studies of various treatments on lifespan, was in this study (Abbas, 2009) treated with EGCG (220 µm daily) throughout their complete lifespan. The mean lifespan of the treated worms was 16.11% greater than the untreated worms. In addition, when the animals were exposed to lethal oxidative stress, the EGCG-treated worms had a 65.05% increased survival.

GREEN TEA CATECHINS SLOW AGE-ASSOCIATED SENESCENCE IN MICE

For many people, their greatest fear of aging is a loss of mental capabilities or outright dementia. Hence, protecting the brain from decline with age is a powerful motivation.

One study of green tea catechins (with EGCG being the most abundant of these in the tea) followed SAMP10 mice especially bred to have accelerated brain aging (Unno, 2004). The treated mice received free access to food and tap water containing 0.02% green tea catechins for 12 months, while controls had free access to food but plain tap water during the same period. This is roughly equivalent to 400 mg per day of green tea catechins for an adult human (as calculated by body surface area to convert from the mouse dose). The animals were tested for their learning and memory abilities.

One of their memory tests involved the mice receiving a shock when they entered a dark area. Mice normally prefer the dark, so it was instinctive for them to seek darkness and avoid light. However, receiving a shock in dark areas caused the mice to learn to avoid dark areas. Staying in the light area for 300 seconds was used as a measure of the animals’ memories of the shock. Entering the dark area of a chamber divided into dark and light areas was consider a “failure.” The results showed that “[t]he failure ratio [the number of failures out of the total number of entries into the chamber] was significantly lower among the 12-month-old mice that had received GT-catechins than among similarly aged control mice.”

“Among the 12-month-old SAMP10 mice that had been given catechin water, there were fewer individuals with both marked cerebral atrophy and a longer learning time.” The authors discussed possible mechanisms for these results. They explained that green tea has potent antioxidant effects, but in addition to that, they induce increased expression of antioxidant enzymes. The researchers concluded that the preventive effects of GT catechins on brain senescence in these senescence-accelerated mice “may indicate a beneficial effect in maintaining the quality of life during old age.”

EGCG MAY REDUCE SCARRING

After reading about the benefits of EGCG described above, it may not seem nearly as important that it may reduce scarring after burns. But severe (hypertrophic) scars can, in addition to being unsightly, result in “itching, redness, and hard nodular scar tissue often with abnormal sensation.” Worst of all, they “can result in functional loss especially over joints such as in the hand.” This loss of function is the result of contracture as the hard scar tissue inhibits motion (Mehta, 2016).

The prevention and treatment of hypertrophic scars has not improved during recent years, even though survival following extensive burns has improved. Remedies for these severe scars are not readily available. Hence, it is good news that a widely available, inexpensive, and safe constituent of green tea (EGCG, epigallocatechin 3-gallate) has been shown “to inhibit a number of intracellular signalling pathways and reduce expression of pro-fibrotic molecules...” such as vascular endothelial growth factor (VEGF), TGF-beta1 (transforming growth factor beta-1), and CTGF (connective tissue growth factor) which promote the development of hypertrophic scars. (Mehta, 2016)

References

Abbas and Wink. Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in Caenorhabditis elegans. Planta Med. 75:216-21 (2009).

Bettuzzi et al. 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. 66(2):1234-40 (2006).

Kumaran et al. Attenuation of the inflammatory changes and lipid anomalies by epigallocatechin-3-gallate in hypercholesterolemic diet fed aged rats. Exp Gerontol. 44:745-51 (2009).

Kumazoe and Tachibana. Anti-cancer effect of EGCG and its mechanisms. Func Foods Health Dis. 6(1):70-8 (2016).

Kurahashi et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidem. 167(1):71-77 (2008).

Nandakumar et al. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis. 32(4):537-44 (2011).

Nehta et al. The evidence for natural therapeutics as potential anti-scarring agents in burn-related scarring. Burns Trauma. 4:15 (2016).

Unno et al. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Geront. 39:1027-34 (2004).

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