August 2019 Issue

Green Tea Catechins
By Carrie Dennett, MPH, RDN, CD
Today’s Dietitian
Vol. 21, No. 8, P. 18

These antioxidants aren’t panaceas but do show promise in fighting certain diseases.

Green tea has a decades-old reputation as a fat-burning, cancer-fighting elixir in a cup, in part because of its role in traditional—and healthful—Asian diets, but also because of its catechins, a group of polyphenols largely found in tea, cocoa, and berries. Search for “tea and health” on PubMed and you’ll find thousands of studies, some high quality and based on strong evidence but many not.1 Unfortunately, results of many laboratory studies have been unreasonably extrapolated to human health, with the resulting weak claims picked up and spread through popular media.

If you were to trace the phytochemical “family tree,” catechins are types of flavanols, which are types of flavonoids, which are types of polyphenols. The main catechins are catechin, epicatechin, epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG). High concentrations of catechins can be found in red wine, broad beans, black grapes, apricots, and strawberries. Epicatechin concentrations are high in apples, blackberries, broad beans, cherries, black grapes, pears, raspberries, and cocoa/chocolate.

However, one of the richest, best-studied, and most attention-grabbing sources of catechins is the Camellia sinensis plant, from which green, black, white, and oolong teas derive. EGC, ECG, and EGCG are found in high concentrations in oolong, black, and green teas, but particularly in green tea because the leaves are dried and steamed instead of fermented (fermentation converts some of the catechins into more complex theaflavins and other flavonoids).1-3

Traditional Medicine Goes Modern
C sinensis historically has been used for medicinal purposes. EGCG accounts for about two-thirds of the catechins in green tea and thus has attracted the most attention in the scientific community.2,3

Catechins, especially EGCG, have strong antioxidant activity and are notable for their ability to scavenge free radicals.1,2 These antioxidant capabilities are significant, because inflammation and oxidative stress—the imbalance between pro-oxidants and antioxidants that results in free radical damage—are considered underlying causes of many chronic diseases, including CVD, type 2 diabetes, neurodegenerative diseases, and cancer.4 Catechins also can bond to proteins, lipids, and nucleic acids, and their ability to bind to proteins may be an important mechanism behind their anticancer and other health-promoting properties.1,5 It’s thought that the benefits of tea primarily come from its catechins, but also from its smaller amounts of quercetin and other polyphenols—as well as its alkaloids, such as caffeine and theobromine.1 So, despite the hype around EGCG, it’s not all about the EGCG.

“That’s a traditional approach in pharmacology, to study a pure compound,” says Chung Yang, PhD, a distinguished professor at Rutgers University in New Brunswick, New Jersey, who studies the pharmacology and other aspects of green tea and health. He agrees that not all of green tea’s benefits are from the EGCG. “I think it’s probably an additive effect of not just the catechins but the other constituents,” Yang says, pointing out that caffeine may aid in weight management and that tea contains theanine, an amino acid that research suggests may promote a relaxed but alert mental state and confer other health benefits.6

Nagi Kumar, PhD, RD, FADA, director of cancer chemoprevention at Moffitt Cancer Center & Research Institute in Tampa, Florida, says that, although many clinical trials have emphasized the efficacy of EGCG, they all used a catechin supplement that contained all the catechins present naturally in green tea. “This is because in vitro and in vivo studies have clearly shown that all the catechins are required to provide the cancer-preventive effects seen with green tea catechins,” she says. “If EGCG is given only as a single catechin, the cancer prevention effects are not observed—proving once again the synergistic effects of these natural substances and the need to provide these supplements as they appear in nature.”

Overall, the strongest evidence for the beneficial effects of tea catechins comes from laboratory and animal studies, with epidemiologic studies and randomized controlled trials being less conclusive.1 Because EGCG behaves differently in cell culture studies (in vitro) than it does in animals and humans (in vivo), in part because the bioavailability of green tea catechins is fairly low, in vitro studies need to be interpreted carefully.1,2 The amount of EGCG needed to have a biological effect in many in vitro studies is higher than the levels typically detected in blood or tissue from human and animal studies.2

“In the laboratory studies, you can select the optimal conditions to observe an effect,” Yang says. “In animal studies, the concentration might be higher than in human studies, and all of the animals in a study are the same, except the group taking the catechins. In humans, many factors can interfere—genetic factors, dietary factors, other lifestyle factors.” For example, he says that even though there’s very strong evidence in laboratory studies, some epidemiologic studies show a cancer-protective effect, while others don’t. Human intervention studies, however, are a different story. “Usually we choose high-risk populations, and we study them for six months to two years, maybe five at most,” he says. “That’s not a long-term study.” He points out that these studies also miss the early part of participants’ life histories—including previous tea consumption or lack of it.

How Catechins Work
The proposed mechanisms of green tea catechins include far more than antioxidant activity. For example, catechins can bind to specific regulatory proteins and enzymes, modulating specific signaling and metabolic pathways. Both of these mechanisms can help prevent metabolic syndrome, type 2 diabetes, CVD, and cancer.1

Bioavailability of catechins is low, largely because they’re unstable under physiological conditions. This makes it difficult to attain a therapeutic dose, even when administered intravenously, and getting them to reach target tissues remains a challenge.7 However, catechins that don’t end up in the blood still may have effects in the gastrointestinal tract. Catechins’ ability to bind to lipids and proteins—including digestive enzymes—decreases the lipids’ and proteins’ absorption, which may help prevent weight gain and lower cholesterol. Intestinal microbes can degrade catechins, yet the resulting metabolites may have biological activity—an area that needs more research.1,8

Although catechins have antioxidant properties, they also can become pro-oxidant, generating reactive oxygen species (ROS), which include free radicals, although this may be more likely in an isolated cell culture than in living humans.1 Nevertheless, ROS can work against us by contributing to cell death (apoptosis), advanced aging, and diseases such as atherosclerosis and cancer, or work for us by activating internal defense systems and regulating signaling between cells. In other words, it appears that the proposed benefits of catechins may come from their ability to both generate and scavenge ROS.2 Catechins also have secondary antioxidant effects by inducing the body’s natural antioxidant enzymes, inhibiting pro-oxidant enzymes and producing enzymes needed for phase II of the body’s detoxification process.4

State of the Science

Because of its low bioavailability, it’s unclear whether the anticancer effects of EGCG observed in vitro can be extrapolated to animals and humans.9,10 Observed mechanisms from in vitro studies include apoptosis, interruption of the cell cycle and cell signaling pathways, and suppression of proinflammatory molecules.2 However, there’s limited understanding about the mechanisms by which green tea catechins might have cancer-preventive effects in humans. It’s likely that green tea catechins have multiple mechanisms that act synergistically to prevent cancer, and they may work in tandem with chemotherapy drugs.3,5

Recent systematic reviews and meta-analyses have found that green tea consumption was associated with reduced risk of breast and ovarian cancers,11,12 and both in vitro and in vivo studies have established chemoprotective effects, although with some inconsistencies between studies.13,14 Catechins also appear to act synergistically with tamoxifen, the most commonly prescribed breast cancer drug therapy.15

Kumar says some of the clinical trials evaluating green tea catechins for prostate cancer prevention are promising, but more research is needed. She says this research needs to be systematic, the way it would be in the drug discovery model—sometimes referred to as “from bench to patient”—which requires developing green tea compounds based on data from population studies, using in vitro studies to understand the mechanisms and early effectiveness in target tissues, then evaluating safety and effective doses in vivo with phase I and II trials in humans before embarking on phase III trials. “This systematic process was lacking in earlier studies, as most people thought that these were just natural supplements, so it was OK to proceed to phase III without systematic evaluation,” she says. “Our group is changing this mindset.”

Although trials for cancer prevention have been inconsistent, possibly because of the challenges of running long-term studies, Kumar says interest in green tea research isn’t waning.1 Her group just received a $3.1 million grant from the National Cancer Institute to evaluate the safety, efficacy, and mechanisms by which green tea catechins prevent progression of prostate cancer in a randomized, double-blinded clinical trial. “Green tea catechins influence several hallmarks of carcinogenesis, including prostate carcinogenesis, with an acceptable safety profile, making them attractive candidates for chemoprevention,” she says.16

Of note, Yang says green tea shouldn’t be drunk too hot, as frequent consumption of tea hotter than 140° F is associated with a significantly increased risk of esophageal cancer.17

Cardiometabolic Disease
So what avenues of research likely hold the most promise? “I think in terms of practical applications, still the prevention of obesity, diabetes, and cardiometabolic disease,” Yang says. “Tea consumption is associated with lower death rates from cardiovascular disease.”

Indeed, large cohort studies in Japan have found an association between increased green tea consumption and decreased risk of CVD-related death, although consumption may have to meet or exceed seven cups per day.2 In human intervention studies, the strongest evidence is for reducing metabolic syndrome.1

Catechins may inhibit specific enzymes and modulate signaling pathways, helping to prevent type 2 diabetes and metabolic syndrome.1,8 Animal studies have demonstrated that EGCG can improve endothelial function and insulin sensitivity and reduce blood pressure, and several randomized controlled trials in humans have shown a benefit from green tea catechins in reducing features of metabolic syndrome, including waist circumference, LDL cholesterol, blood pressure, and insulin resistance. However, other trials haven’t observed those benefits. This may be simply due to variation in study lengths and participant characteristics, but clearly more well-controlled, long-term studies are needed.2,18

Cognitive Health
Oxidative stress and generation of free radicals play a role in neurodegenerative diseases, just as they do in cancer and CVD. Both clinical and epidemiologic studies have shown that green tea consumption may have a protective effect against neurodegenerative diseases and cognitive impairment, but, again, at consumption levels far above average.2

Several observational studies have found an association between tea intake and lower rates of Parkinson’s disease, although a few have found no effect. On the other hand, studies focusing on Alzheimer’s disease largely have failed to find a significant benefit from green tea intake, but results are more promising when looking at cognitive impairment.19 Most of the cross-sectional studies conducted in the last dozen years found an association between increased green tea consumption and lower prevalence of cognitive impairment, and longitudinal studies have found similar results. However, randomized controlled trials have been inconclusive.20

Inflammatory Bowel Disease
Catechins’ anti-inflammatory and antioxidant properties also make them a potential tool for managing inflammatory bowel disease, a chronic inflammatory disease of the intestine, most frequently manifesting as ulcerative colitis or Crohn’s disease. It’s thought that catechins also may inhibit the abnormal activity of immune-related cells, prevent gastrointestinal lesions from worsening, and improve the functioning of the tight junctions between cells lining the intestine. However, at this time there are few animal or human studies to support these theories.21

Viral Illnesses
In in vitro studies, catechins minimize the propensity of the influenza virus to infect and proliferate, in part by inhibiting its ability to interact with the cell membrane when it invades a cell. Epidemiologic studies and randomized controlled trials have found a significantly lower incidence of influenza in individuals with higher consumption of green tea or, in the case of the clinical trials, green tea capsules.22,23 It’s possible that these antiviral properties may help inhibit other viruses, including HIV, hepatitis B and C, herpes simplex, Ebola, and Zika.24

How to Counsel Clients
Researchers have observed beneficial effects on weight, metabolic syndrome, and type 2 diabetes with intake of three to four 8-oz cups of green tea per day, which supplies about 600 to 900 mg of catechins, but lower levels of intake would still add to the total intake of polyphenols in the diet.1 Taking enough green tea polyphenol products to equal the amount of EGCG in eight to 16 cups of green tea each day may overcome the issues with poor bioavailabilty,7 as encapsulation can make the catechins more bioavailable.10 However, using high doses may not be ideal due to some evidence of toxicity.7 Although green tea is considered safe and has a long history of use, taking high levels of green tea extract–derived dietary supplements has caused liver toxicity in some individuals, especially those with preexisting conditions or medications that already impact the liver.1,25,26

“I think for the people taking catechins for weight reduction, liver toxicity could be a concern,” Yang says, adding that there are about 30 to 40 case reports about liver toxicity in individuals using catechin supplements for weight reduction. He says that when catechin intake stops, people generally recover.26 However, if excess consumption continues, the toxic effect could be serious.

In addition, catechins’ ability to bind to minerals, proteins, lipids, and other biomolecules—while conferring some health benefits—could contribute to nutrient deficiencies and other problems when ingested in levels far above what could be reasonably consumed through drinking tea.1 Furthermore, the tannin content of green tea can interfere with intestinal absorption of some nutrients and drugs, although there’s little research in this area.3

Yang has been researching green tea for 30 years, and he says the research has become more mature, perhaps tempering the highs of early optimism. “Those are not miracle molecules. Green tea happens to have some beneficial health effects. It’s just one of the many things we can consume that may benefit health, and it’s better than many other beverages we might drink.” His bottom-line advice? “Tea is a healthful beverage, especially if you like it and enjoy drinking it.”

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times, owner of Nutrition By Carrie, and author of Healthy for Your Life: A Holistic Guide to Optimal Wellness.


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