There is generally very little clinical information on the safety of long-term consumption of green tea extract supplements. The limited number of published studies were either short-term or with a small sample size, and most of them were not randomized controlled trials. This is the first placebo-controlled randomized study to evaluate the safety of long-term ingestion of green tea extract in postmenopausal women. This study demonstrated that supplementation of 500-mg GTP daily for 24 weeks did not cause any safety concern (Table ) with regard to liver function (in terms of AST, ALT, Bil, and ALP levels) as well as kidney function (in terms of Crt and BUN levels).
Considering a typical commercial decaffeinated green tea bag that contains approximately 80-100 mg green tea flavanols per serving [22
], the GTP daily dose (500 mg with 99.25% purity) used in this study was approximately equivalent to beverage prepared by 5-6 commercial decaffeinated tea bags. On the other hand, our previous animal study showed that GTP supplementation through 0.5% GTP in drinking water benefited bone remodeling in ovariectomized middle-aged rats [2
]. This dose of GTP consumption by rats in that study was comparable to the dosage employed in the present study. GTP dosages similar to our study have been adopted in study populations with different health issues. However, the study periods were generally short (up to 12 weeks) in most studies with the following two exceptions. Matsuyama et al. [14
] reported that 24 weeks of beverage ingestion containing catechin (576 mg daily) ameliorated serious obesity and cardiovascular disease risk factors without raising any safety concerns in obese Japanese children (aged 6-16 years). Janjua et al. [15
] reported that GTP supplementation (500 mg with 70% catechin daily) for two years did not demonstrate a significant benefit superior to placebo in improving clinical or histological photoaging parameters of women's skin (aged 25 to 75 years). However, none of these studies investigated GTP's safety in terms of possible liver and kidney damages through monthly blood tests. Further, the sample sizes of these published studies were small.
In this study, we observed decreasing trends in the levels of serum Bil, ALP, Crt, Ca, and Pi over the study period (Table ). However, such trends disappeared when analyzing interaction between the time factor and the two treatment factors (GTP and TC), suggesting possible body's adaptation to intervention stimuli over time.
In the present study, the four adverse events observed in different treatment arms were judged as unlikely related to the study protocol. Previous studies reporting adverse events with green tea extract supplementation, including acute liver failure in a few isolated case reports [23
], in controlled human intervention trials [27
], and in epidemiological studies suggested that possible medication contamination and other unknown factors may have contributed to hepatotoxicity [29
]. Hepatotoxicity might also possibly be due to unusual dosing protocols, such as fasting, or a genetic variation (single nucleotide polymorphisms) in phase I and phase II enzymes in some affected individuals [30
No adverse event attributed to TC was observed or reported in this study. This is in agreement with previous studies reported by us and others [16
]. TC, featuring gentle, slow and flowing movements, has been considered a safe exercise with very low risk of injury. As expected, TC did not influence any parameters related to liver and kidney function, except for a decreasing trend of serum Pi with time, which became not significant considering interaction between time and TC (Table ). In addition, there was no interaction between GTP supplementation and TC exercise on liver and kidney function in the present study.
The present results show that 24 weeks of TC exercise confers beneficial effects on postmenopausal women in terms of improving their role-emotional and mental health (Table ). The favorable profiles of TC on mental health in the present study are consistent with those reported by Ko et al. [32
] in healthy women, and by Abbott et al. [33
] in patients with tension headaches. The positive impact of TC on the role-emotional domain also agrees with findings by Abbott et al. [33
]. On the other hand, after involving GTP treatment, the interaction among time, GTP and TC was not significant (P
> 0.05) in the domain of either role-emotional or mental health. Although time × TC did reach statistical significance, but time × GTP did not reach statistical significance, therefore, resulting in no significance in the results of time × GTP × TC.
This is the first study investigating the effect of GTP supplementation on quality of life, and the result showed no effect. There was also no evidence supporting that selenium supplementation benefited quality of life in apparently healthy elderly (aged 60-74) in a double-blind, placebo-controlled intervention [34
]. Another study found that vitamin E intake did not change quality of life in patients with amyotrophic lateral sclerosis [35
]. Although all these supplements (GTP, selenium, vitamin E) are considered to be functional in protecting cells from oxidative stress, these published studies along with the present study seem to suggest no benefit of these supplements in quality of life.