Exciting recent clinical studies suggest that green tea extracts (standardised for green tea catechins or GTCs) could play a valuable role in the treatment of early stage chronic lymphocytic leukaemia (CLL) and prostate cancer.
In the case of CLL, the Mayo clinic initiated a small phase I trial1 after the report of four cases of remission or regression of the disease in green tea users.2 The proprietary green tea extract used was relatively well-tolerated by the trial participants. The majority of patients saw a decline in lymphocyte (small white blood cell) count and/or lymphadenopathy (enlarged lymph nodes). Specifically, among the 12 patients with palpable enlarged lymph nodes at the beginning of the trial, 11 (92%) experienced at least a 50% reduction.
White blood cell counts dropped 31%!
After the highly promising phase I dose-finding trial, a phase II trial was launched. A relatively high dose of extract (containing 4,000 mg/day of the major green tea catechin epigallocatechin 3-gallate [EGCG]) was selected for the open-label study. This was the highest dose used in the phase I trial. Preliminary results were recently released at an annual meeting of the American Society of Clinical Oncology.3 At the time of the reporting 31 patients had completed six months of green tea treatment and another 11 were still part way through the trial. One patient has experienced a partial remission, 31% demonstrated a sustainable lowering of lymphocyte count and 66% had a reduction of more than 50% in lymphadenopathy. Such a massive dose of green tea extract was not without its drawbacks however: 43% of patients exhibited elevated liver enzymes (more on this later), 30% experienced abdominal pain and 57% complained of nausea.
High-grade prostatic intraepithelial neoplasia (HG-PIN) is the most common premalignant lesion seen before prostate cancer develops. A HG-PIN diagnosis means you are at substantial risk (around 30%) for developing prostate cancer in the year following that diagnosis. Currently there’s no conventional medical treatment available for HG-PIN if it is detected in a prostatic biopsy. But green tea may hold the key to a natural approach.
Following some promising results from experimental models, a group of Italian scientists initiated a double-blind, placebo-controlled, proof-of-principle clinical study into the potential role of a green tea extract in patients with HG-PIN.4 Sixty men received either a placebo or 600mg/day of GTCs for one year. At the end of the trial, only one tumour was diagnosed in the green tea group (3% incidence) versus nine in the control group (30% incidence) (p < 0.01 for green tea versus placebo). Prostate specific antigen (PSA) levels did not change significantly, although they were lower in the green tea group at nine and 12 months. There were also improvements in the International Prostate Symptom Score (IPSS) and quality of life score in men with coexisting benign prostatic hyperplasia who received the green tea.
80% protection against prostate cancer!
A key question that arose from this study was whether the progression to prostate cancer was merely delayed by the green tea intervention. To answer that question the authors initiated a follow-up study two years later in a subset of 22 men from the initial study (nine from the placebo arm and 13 from the green tea arm).5 Neither group had received any green tea supplementation over the two years. In all, three more prostate cancers were detected following biopsy, two in the placebo group and another one in the green tea group. The final difference in cancer prevalence was highly statistically significant (p < 0.01) and suggested that one year of green tea consumption provided a long-lasting 80% protection against prostate cancer progression from HG-PIN.
Green tea intake may also slash the risk of having an aggressive form of prostate cancer in half. The incidence of prostate cancer is much lower in Asia. A large study was initiated to investigate whether green tea is linked to this lower prostate cancer risk. The Japanese Public Health Centre-based Prospective Study included 49,920 men aged 40 to 69 years.6 These men completed a questionnaire at baseline about their green tea consumption. They were then followed for 11 to 14 years. During this time, 404 men were newly diagnosed with prostate cancer.
Advanced prostate cancer risk was slashed in half
No statistically significant association was seen between green tea consumption and localised prostate cancer risk. Of course, localised prostate cancer is the less dangerous form of the disease. However, green tea consumption was associated with a decreased risk of advanced prostate cancer in a dose-dependent manner. The adjusted relative risks or hazard ratios were as follows: 1.00 (reference) for <1 cup/day, 1.12 for 1-2 cups/day, 0.86 for 3-4 cups/day and 0.60 for ≥5 cups/day. Using different adjustments for confounding variables, the relative risk dropped even lower to 0.52 for ≥5 cups/day or, in other words, down to half the risk.
The authors of the Japanese study point out other investigations into the effects of tea drinking on prostate cancer risk have yielded conflicting results (including those from the large Ohsaki study). They suggest that possible reasons for this include in some cases not identifying the type of tea consumed (green or black) and in others not identifying the type (stage) of the prostate cancer.
Looking into the green tea liver damage link
Although green tea is generally well tolerated there does appear to be a small risk of a potential downside from its use, particularly when high-dose extracts are used. A number of disturbing cases have appeared in the literature suggesting that extracts of green tea made with an ethanol (alcohol) and water extract might be responsible for triggering liver damage in susceptible individuals. A specific extract linked to most cases was commercialized in France in February 1999 and subsequently in other countries as a weight loss product. The first published case described a 50-year-old female patient who was hospitalised in August 2000 with jaundice.7
An open-label clinical trial examining the efficacy of this green tea product for weight loss noted an increase in transaminases (liver enzymes indicative of liver damage) in one of 70 patients.8 Another case of liver damage published in 2003 described a 46-year-old female patient who sought treatment in October 1999 for jaundice and weakness.9
Following this, three similar cases were described in the literature up to 200510,11,12 and a total of 13 cases had been reported to the French health authorities by 2003.13 In one case, the patient required a liver transplant.12 The marketing authorisation for the specific green tea product was withdrawn in France and Spain and eventually the company voluntarily withdrew the product from other countries.
However, Bjornsson and Olsson have since described another five cases that were reported to the Swedish Adverse Drug Reactions Advisory Committee between 2005 and 2007.14 All of these were associated with a different proprietary product largely containing an ethanolic extract of green tea. They also reviewed another 15 cases of liver damage linked to green tea, mostly from France (including the cases mentioned above) and Spain, but also including one from Canada and some from the US.
Another letter in response to the Swedish experience claimed that in fact 34 cases had been reported, either to the health authorities or in medical journals.15 Accidental rechallenge in a few instances appeared to confirm the association of the liver damage with green tea. Other cases have since been reported and in 2014, a concentrated extract of green tea was linked to severe acute hepatitis in a 63-year-old German woman.16 Fortunately, she had a rapid and sustained recovery when she stopped taking the product.
The cases described above for an ethanolic green tea extract are typical of what is called ‘an idiosyncratic, drug-induced reaction’. This means that components in the green tea extract triggered an immune attack on the liver in a rare and unpredictable way. The evidence implicating that the extract produced the reaction is strong and such a reaction has been observed for other herbs, such as germander and chaparral. But the curious fact is that green tea has been commonly consumed in vast quantities by millions of people as a beverage, with no previous implication of it being involved in liver damage. In fact, many health benefits have been attributed to the regular consumption of green tea. So what are the factors involved which have caused such a benign substance to become potentially dangerous to health?
Green tea safely used for 50 centuries
The most obvious difference to long-standing traditional use is the way the green tea was prepared. When you drink green tea as a beverage, it’s extracted with hot water. For the weight-loss products discussed earlier, the green tea was extracted with a high percentage of ethanol. There could be some factor in green tea extracted by the ethanol that triggers the damage to liver cells in susceptible people. Perhaps some protective factor is lost when alcohol is used as the extraction solvent. Or it could be the high concentration in a single dose that those extracts provide.
There is one case report of a man who developed jaundice and liver damage after drinking six cups a day of a green tea tisane (regularly brewed tea).17 When green tea was re-introduced to the man the connection appeared to be confirmed. The authors themselves noted: “These findings are surprising, since tea beverages have been consumed for almost 50 centuries, and in vitro and in vivo studies in rats suggested that green tea has hepatoprotective properties”. If an aqueous extract of green tea does cause occasional liver damage, it must be with an extremely low frequency, much lower than for a concentrated ethanolic extract. Otherwise more cases would have been reported, given that green tea is consumed by hundreds of millions (if not billions) of people.
On the basis of the current evidence, green tea is best used as a dried aqueous (hot water) extract in tablet and capsule supplement products, matching with its traditional use.
To your better health,
Nutrition & Healing
Vol. 8, Issue 12 – December 2014
Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.