In addition to its antioxidant, anti-cholesterol, and anti-fat properties …

Pu-erh Tea Offers
Anti-Cancer Benefits

… and may be of great value for breast, colon, stomach, and other cancers
By Will Block

I

t has been said that tea is a cup of life. Reading the leaves of the underlying message, it is a benefactor of life in many more ways than you can readily imagine. One special variety of tea, known as Pu-erh (poo-air), has been found to offer a wide variety of significant health benefits. Pu-erh is produced predominately in China’s Yunnan Province. There for the last two thousand years this non-white, non-green, non-oolong, non-black tea has been traditionally prepared in adherence to a complex fermentation process in which microorganisms play a crucial role in determination of its taste, color, fragrances, and most importantly its functional components. Pu-erh is one of the few teas that improves with age—surely a choice metaphor for its anti-aging benefits.

Tea from China’s Largest Diversity of Plant Life

Exotic and beautiful, Yunnan is located on the Southwest frontiers of China and is rich in natural resources, possessing the largest diversity of plant life in China. Yunnan Province features rough terrain which is dotted with cloud-veiled mountains and crisscrossed with meandering rivers. The Province has mild climate, abundant rainfall, and fertile land, all of which create ideal conditions for tea cultivation.

From the Wilderness to Cultivation

Historical records tell us that Yunnan domesticated the aboriginal tea, known as a “wild tea,” 2,100 years ago. Today’s Pu-erh is a successor to that original tea. Case in point, in 2007 a 1.1 lb Pu-erh teacake made from a 3,200 year old tree—still growing in Jinxiu Village, Fengqing County, Yunnan Province—sold for about $40,000 dollars. The tree from which it came is said to be the oldest human-planted tea tree in the world and its product is dubbed “Ancestor Tea.” With a diameter of 6 feet at its base, the tree is also the biggest tea tree in the world. It may also be the highest, growing at an altitude of 10,646 feet. There are many other ancient tea trees which fit into the fold of today’s Pu-erh. Together, these are indicative of the transition between the wild and cultivated types. Such ancient tea trees are regarded as the “living fossils” of Yunnan’s indigenous tea plants.

The History of Pu-erh Tea

The name Pu-erh is derived from the ethnic Pu people in Yunnan who were among the first to cultivate, produce, and drink tea there. They served it as tribute to the emperors as early as in the Chinese Shang (1766–1046 BCE) and Zhou Dynasties (1046–256 BCE). During the Song Dynasty (960–1279 CE), Pu-erh County became a famous market for trading tea and horses. In the Yunnan Dynasties, which span 600 years from 653–1253 CE, tea had become the most important commodity in the transactions undertaken by people of all ethnic groups in Yunnan. In the former part of the Qing Dynasty (1644 to 1912 CE), the reputation of the Pu-erh tea reached its climax.

The Stew of Teas and Their Molecular Ingredients

Through their research, life extension scientists Durk Pearson and Sandy Shaw learned about several weight-loss mechanisms reported in studies of various types of tea (Camellia sinensis), including green, oolong, black, and Pu-erh (see “Cocktail of Selected Teas for Better Health and Weight Loss” in the April, 2007 issue). What were the best combinations of tea types for weight loss they asked? Their search involved trying literally dozens of different teas and tea combinations. Of the various combinations of bioactive ingredients considered were: polyphenols; gallated and nongallated catechins; tannins; and monomers, oligomers, and polymers of tea catechins; and many more. There were complex interactions, so “the biological effects of each tea were found to depend on the different ‘cocktail’ of these ingredients and, importantly, on the chemical interactions and synergies of the ingredients. Producing a partially (oolong) or fully (black or Pu-erh) fermented tea results in an even more complex stew of molecular ingredients.”


Pu-erh is one of the few teas that
improves with age—surely a choice
metaphor for its anti-aging benefits.


The Mechanisms of Teas

Similar to black tea, Pu-erh tea is produced by fermentation. But it is different because it is aged to improve its quality, like a fine wine. Unlike other teas which auto-oxidize and become weaker with storage, Pu-erh becomes stronger. Thus Pu-erh is neither like green nor oolong nor black. It is a thing of its own (in Latin, sui generis). Although a few researchers have claimed that that some active substances in Pu-erh tea may be formed during the preservation period,1 the literature describing the chemistry and biological properties of Pu-erh tea is scarce. And its production techniques are quite varied and highly proprietary.

In their wide ranging study, the life extension researchers learned of many mechanisms—few of which are discussed outside the scientific literature—that have been reported in various studies. What they found is that different teas have different mechanisms that may account for some of their effects in reducing weight. Furthermore, they began to realize that these mechanisms went way beyond promoting weight loss, on to the promotion of better health and even the exciting possibility of contributing directly to longer lifespan.

Reducing Fat Synthesis by Inhibiting Fatty Acid Synthase

Chief among their findings was that certain teas can reduce fat synthesis by inhibiting fatty acid synthase (FAS), and at the same time: increase malonyl-CoA, the substrate for fatty acid synthase; increase energy expenditure; and uregulate PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha), a master regulator of mitochondrial biogenesis. Mitochondria are the energy production and management organelles within cells.

Slowing the Conversion of Dietary Calories to Fat

FAS is an enzyme that plays a crucial role in converting dietary calories to stored body fat in mammals. So it is of great interest reports that various types of tea contain biochemical inhibitors of FAS and that these are thought to contribute to their antiobesity effects.1–4 Two such potent FAS inhibitors, catechin gallate1 and epigallocatechin-3-gallate,5 have been found in tea.

However, there is a potential limitation on the activity of these FAS inhibitors in the typical Western diet, which is burdened with loads of digestible carbohydrates. High consumption of these can result in a large oversupply of malonyl-CoA, so much so that the substrate for FAS that is formed in the fat-synthesizing pathway from glucose largely may overpower any potential inhibition of FAS.

The Need to Maintain a Reduced Glycemic Diet

Consequently, Durk & Sandy concur that a reduced-glycemic-index diet is absolutely essential to benefit from the FAS inhibitors found in certain teas. Although the anti­obesity and anticancer effects (many human cancers overexpress FAS) of FAS inhibitors have been known for several years,6 there have been no Phase I trials to date, to the best of their knowledge, of such inhibitor drugs produced by pharmaceutical companies. On a regular American diet, FAS inhibitors will not work. That’s because the high-glycemic nature of the “normal” American diet results in the buildup of the substrate malonyl-CoA, which has now been identified as a key regulator of energy metabolism and food consumption,7,8 and this can override FAS inhibition.9


Of the various combinations of
bioactive ingredients considered
were: polyphenols; gallated and
nongallated catechins; tannins; and
monomers, oligomers, and polymers
of tea catechins; and many more.


Too Much Malonyl-CoA Inhibits the FAS Inhibitor

When FAS is inhibited, the large supplies of malonyl-CoA that stack up are interpreted by your brain as the result of your eating a huge meal and loading your FAS pathway with substrate, which results in your brain’s signaling the suppression of hunger and feeding behavior. It also results in the turning on of genes involved in energy expenditure and oxidative protection, as well as turning on PGC-1alpha, which performs a number of extremely interesting fat-loss and age-reversing tricks. These include increasing the creation of mitochondria in muscles, which increases energy expenditure by muscles; reducing the expression of atrophy genes in muscle during disuse or denervation; increasing the production of the fatigue-resistant slow-twitch muscle fibers; and suppressing reactive oxygen species and neurodegeneration. FAS inhibitors may be a caloric restriction (CR) mimic for many of CR’s effects by reversing the age-dependent decrease in PGC-1alpha.

FAS Inhibition Increases Energy Expenditure

Durk & Sandy also found that increased energy expenditure results from inhibiting FAS because its substrate, malonyl-CoA, is not turned into fat and just piles up. This is a signal that you are full of energy and turns on energy-expenditure mechanisms such as thermogenesis via upregulation of PGC-1alpha and PGC-1beta in muscles (by beta-adrenergic signaling from the brain) that include increasing uncoupling proteins (that allow the “wasting” of calories by using their energy to create heat) and increasing the creation of mitochondria in muscles. Loss of mitochondria is a very important aging process.


Durk & Sandy began to realize that
these mechanisms went way beyond
promoting weight loss, on to the
promotion of better health and even
the exciting possibility of contributing
directly to longer lifespan.


Alpha-Glucosidase Inhibitors Reduce Fat Accumulation

Another mechanism whereby various teas to one degree or another reduce the accumulation of fat is through the inhibition of alpha-glucosidase (an enzyme found in the small intestine that is required for digestive breakdown of carbohydrate polymers, such as starch, into glucose). Catechins and theaflavins found in teas (theaflavins are found only in fermented teas, while catechins are most plentiful in green tea) have been identified as inhibitors of alpha-glucosidase.

Lipase Inhibitors

“Ancestor” tea tree in Yunnan
Pancreatic lipases are enzymes important in the digestion of fats. Hence, one way to decrease fatty acid uptake from the gut is to inhibit these enzymes. It has been reported that the inhibitory effects of oolong (partially fermented) tea polyphenols are due to pancreatic lipase.

Other Possible Mechanisms

Curiously, it has been reported that lovastatin, a cholesterol-lowering substance (it works by inhibiting the enzyme HMG-CoA reductase, which manufactures cholesterol) was found to exist naturally in some batches of Pu-erh tea. The finding of statins is not unprecedented in foods; lovastatin has also been reported in red yeast rice. The fermentation process that converts green tea to Pu-erh is exceedingly complex and involves a whole ecosystem of microorganisms, unlike fermentation to make beer or wine, where only yeast is used.

In one study, black, green, and oolong teas (Pu-erh was not tested) were shown to enhance insulin activity, thereby improving insulin sensitivity, which keeps blood glucose down. This study’s authors identified the predominant active ingredient as epigallocatechin gallate (EGCG), found in especially large amounts in green tea. They also reported that the addition of milk, nondairy creamers, and soy milk to tea decreased the insulin-enhancing activity. Durk & Sandy think that this effect is due to the biologically (and chemically) reactive polyphenols that bind to the proteins in these additives.


On a regular American diet, FAS
inhibitors wouldn’t work.


EGCG was also reported in another paper to repress hepatic (liver) glucose production. This could be due to EGCG’s insulin-enhancing effects, as one of the functions of insulin is to suppress hepatic gluconeogenesis (a process by which glucose is created). Another paper reported that glucose tolerance in healthy human volunteers was improved significantly after drinking 1.5 grams of green tea powder in 150 ml of hot water, as compared to hot water alone.


Durk & Sandy have developed
another formulation for their own
personal use, this one to help reduce
body fat when used with a low-
glycemic-index diet and also to
improve muscle function and increase
the creation of mitochondria.


A New Fat-Reducing Tea

As a result of their work, Durk & Sandy have developed another formulation for their own personal use, this one to help reduce body fat when used with a low-glycemic-index diet and also to improve muscle function and increase the creation of mitochondria. It is their hope that more attention will be paid in future research to the “other” teas (i.e., those other than green tea, upon which most of the attention of researchers has so far been focused). That is because these is existing evidence that the fermentation of green tea creates a huge range of new compounds not found in green tea itself that may be extremely useful for any health program.

Pu-erh Inhibits Tumor Cell Growth Activities

In a new study, using water extracts of Pu-erh tea, researchers analyzed the tumor cell growth inhibition activities on several genetically engineered mouse tumor cell lines.10 They found that at a concentration that did not affect wild type mouse embryo fibroblasts growth, Pu-erh tea extracts could inhibit tumor cell growth.

Song Dynasty Pu-erh Tea Party
The researchers also found that Pu-erh tea extracts down-regulated the expression of mutant p53 in tumor cells at the protein level as well as messenger RNA* level. Curiously, while p53 (also known as protein 53 or tumor protein 53) is a tumor suppressor protein that in humans is encoded by the TP53 gene, p53 is crucial in multicellular organisms. There, it regulates the cell cycle and thus functions as a tumor suppressor that is involved in preventing cancer. However, a mutant p53 will no longer bind DNA in an effective way, and, consequently, another needed protein will not be available to act as the “stop signal” for cell division. Thus, mutant p53 can cause cells to divide uncontrollably, and form tumors.


* Messenger RNA (mRNA) encodes a chemical “blueprint” for a protein product. This molecule is transcribed from DNA, and its function is to carry coding information to the sites where proteins are created: the ribosomes. At these sites, the nucleic acid polymer is translated into a polymer of amino acids (in other words, a protein).



At a concentration that did not affect
wild type mouse embryo fibroblasts
growth, Pu-erh tea extracts could
inhibit tumor cell growth.


The researchers also found that Pu-erh tea treatment could slightly down-regulate both the heat-shock proteins HSP70 and HSP90 in tumor cells. These data reveal the action of Pu-erh tea on tumor cells and suggest the possible mechanism for Pu-erh tea action, which explained its selectivity in inhibiting tumor cells without affecting wild type cells. Altogether, the data sheds light on the application of Pu-erh tea as an anti-tumor agent with low side effects.


The data sheds light on
the application of Pu-erh tea as
an anti-tumor agent with
low side effects.


The Importance of Selectively Killing Tumor Cells

The toxicity of chemotherapeutic drugs has become one of the dominant issues in chemotherapy. New developments in cancer fields have focused more and more on cancer prevention, early diagnosis, and personalized medicine. Accordingly, chemicals which target tumor specific molecules and selectively kill tumor cells have become one of the most popular topics in drug screening.

In the Pu-erh/p53 study using the wild type control and genetically engineered tumor cell lines as the screening system, the researchers could easily differentiate the toxicity of drug treatment to normal cells from the tumor cell growth inhibition activity. As well, the specific genetic background provided advantages in identifying the molecular target of the treatment.


Green tea has been reported to
operate as a anti-tumor reagent.


Pu-erh Different than Other Anti-Tumor Agents

Green tea has been reported extensively to operate as an anti-tumor reagent. The benefits have been mainly attributed to its antioxidant components, such as EGCG, and multiple tumorigenic proteins were found to be regulated by EGCG, albeit at different concentrations. The tumor promoting factors DNA methyltransferase, epidermal growth factor receptor, hepatocyte growth factor receptor, insulin-like growth factor 1 receptor (IGF1R), matrix metalloproteinase, vascular endothelial growth factor A and BCL-2 have been found to be down-regulated by EGCG. At the same time, EGCG has been found to up-regulate tumor suppressor p53. When taken together, this evidence provides the basis for the selective inhibition of tumor growth by green tea while not affecting wild type cells.

Low Toxicity Because of Long Use

Pu-erh tea, due to its special fermented processing and the incorporation of microbes, is thought to be different from green tea in terms of its tumor cell growth inhibition activity, and also with regard to its molecular targets. The bioavailability of Pu-erh tea’s components might be increased by the way it is made through microbial fermentation. Nonetheless, concluded the researchers, because Pu-erh tea has such a long history of use, its toxicity to normal cells should be very limited. It also has been reported that the safe dosage for two breeds of commonly used laboratory rats could be 5000 mg/kg/day, a very large amount.


Pu-erh selectively inhibits tumor cell
growth at a concentration that does
not affect wild type cells.


In the current study, the investigators showed that Pu-erh tea has comparable tumor cell growth inhibition activity with black tea and green tea. However, several independent groups have shown that the fermentation process of Pu-erh tea could reduce its total catechins and related antioxidant activity. Thus, it is reasonable to speculate that the tumor cell growth inhibition activity of Pu-erh tea is due to other natural compounds and further studies are needed to clarify this.


This is good news for fighting tumors
of the breast, colon, stomach, liver,
bronchus, lung, and brain,
among others.


An important finding from the study, to repeat, is that Pu-erh selectively inhibits tumor cell growth at a concentration that does not affect wild type cells. At the concentration used, Pu-erh’s selective inhibition of tumor cells would greatly reduce the non-specific cytotoxicity thus providing a way for cancer prevention or treatment that potentially helps avoid the current problem of cytotoxicity caused by most conventional chemotherapy drugs.

Furthermore, the current study reveals that Pu-erh down-regulates the expression of p53 mutant at both mRNA and protein levels. Consequently, Pu-erh tea might eliminate the growth advantage of tumor cells with mutant p53. It is widely known that at least 50% of human tumors have p53 mutation, and that mutant p53 proteins induce cancerous function, impact tumor progression, and contribute to metastasis. Once again, targeting mutant p53 has become one important strategy in drug screening and personalized cancer treatment. Due to its down-regulation of mutant p53, Pu-erh tea has a significant potential in cancer treatment with low side effects.

Also worth repeating, the heat-shock proteins HSP70 and HSP90 have been targeted for cancer therapy due to their high expression level in tumor cells and their chaperon-like characteristics for other cancer causing proteins, e.g., mutant p53. Importantly, the researchers also found that Pu-erh tea treatment could slightly down-regulate both HSP70 and HSP90 protein levels in tumor cells.

Pu-erh May Help Fight Breast and Other Cancers

The point to drive home is that the data showed that the same concentration of Pu-erh tea solution did not cause p53 stabilization or activation of its downstream pathways in the wild type cells. And again, analysis did not show any growth inhibition of wild type cells by Pu-erh tea treatment. These new findings reveal the action of Pu-erh tea on tumor cells and provide a possible mechanism for Pu-erh tea’s selectivity in splendid tumor cells without affecting wild type cells. This is good news in the fight against tumors of the breast, colon, stomach, hematopoietic and reticuloendothelial systems, liver and intrahepatic bile ducts, bronchus and lung, and brain.

References

  1. Chiang CT, Weng MS, Lin-Shiau SY, Kuo KL, Tsai YJ, Lin JK. Pu-erh tea supplementation suppresses fatty acid synthase expression in the rat liver through downregulating Akt and JNK signalings as demonstrated in human hepatoma HepG2 cells. 2005 Oncol Res 16:119-28.
  2. Zhang R, Xiao W, Wang X, Wu X, Tian W. Novel inhibitors of fatty-acid synthase from green tea (Camellia sinensis Xihu Longjing) with high activity and a new reacting site. Biotechnol Appl Biochem 2006 Jan;43(Pt 1):1-7.
  3. Yeh CW, Chen WJ, Chiang CT, Lin-Shiau SY, Lin JK. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects. Pharmacogenomics J 2003;3(5):267-76.
  4. Ikeda I, Hamamoto R, Uzu K, Imaizumi K, Nagao K, Yanagita T, Suzuki Y, Kobayashi M, Kakuda T. Dietary gallate esters of tea catechins reduce deposition of visceral fat, hepatic triacylglycerol, and activities of hepatic enzymes related to fatty acid synthesis in rats. Biosci Biotechnol Biochem 2005 May;69(5):1049-53.
  5. Brusselmans K, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV. Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells. Int J Cancer 2003 Oct 10;106(6):856-62.
  6. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000 Jun 30;288(5475):2379-81.
  7. Hu Z, Cha SH, Chohnan S, Lane MD. Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc Natl Acad Sci U S A 2003 Oct 28;100(22):12624-9.
  8. Hu Z, Dai Y, Prentki M, Chohnan S, Lane MD. A role for hypothalamic malonyl-CoA in the control of food intake. J Biol Chem 2005 Dec 2;280(48):39681-3.
  9. Wolf G. The regulation of food intake by hypothalamic malonyl-coenzyme A: the MaloA hypothesis. Nutr Rev 2006 Aug;64(8):379-83.
  10. Zhao L, Jia S, Tang W, Sheng J, Luo Y. Pu-erh tea inhibits tumor cell growth by down-regulating mutant p53. Int J Mol Sci 2011;12(11): 7581-93.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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