A 6‐month chronic toxicity study on green tea polyphenols in middle‐aged ovariectomized rats

Abstract

The project is to evaluate chronic toxicity and safety in middle‐aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. 182 SD were sham (n=39) or ovariectomized (OVX, n=143). Both sham and OVX‐control animals receiving no GTP were assigned for sample collection at baseline, 3, and 6 months. The remaining OVX animals were randomized into 0.15%, 0.5%, 1%, and 1.5% (wt/vol) GTP for 3 and 6 months. Routinely clinical observation was performed. Ophthalmologic examination (control, 1% and 1.5% GTP groups), blood for hematology and clinical chemistry, urine analysis were assessed at baseline, 3, and 6 months. Histologic examination was performed on all tissues from animals in both control and high dose groups at baseline and the end of study. No mortality or abnormal treatment‐related findings in clinical observations or ophthalmologic examinations were noted. No treatment‐related macroscopic or microscopic findings were noted for animals administered 1.5% GTP. There was no difference in baseline body weight among all OVX‐treated treatment groups. The OVX+1.5% GTP group had the smallest body weight of the OVX‐treated groups. No difference in food intake among all treatment groups. In all OVX‐treated groups, GTP supplementation decreased water consumption of rats in a dose‐dependent pattern. At 6 months, GTP intake did not affect complete hematology, clinical chemistry, and urinalysis, except for PO4 and BUN (increased); total cholesterol, BUN, LDH, and urine pH (decreased).This study reveals that the No‐Observed‐Effect Level (NOEL) of GTP is 1.5%, the highest dose used. Supported by NIH/NCCAM AT006691.

Tea Flavonoids for Bone Health: From Animals to Humans

“…73 The preliminary results showed no mortality or abnormal treatment-related effects, although OVX rats supplemented with GTP at 1.5% dosage had the smallest body weights. 71 In general, GTP intake up to 1.5% dosage for 6 months did not affect hematology, clinical chemistry, or urine analysis. It was observed that bone mass and strength significantly improved with GTP concentration in the drinking water.…”

“…It was observed that bone mass and strength significantly improved with GTP concentration in the drinking water. 71 Based on the bone histomorphometric analysis, GTP suppressed both bone formation and bone resorption at cancellous bone of tibia as well as periosteal and endocortical bone of tibia in a dose-dependent manner. 72 The study demonstrated osteoprotective benefits of GTP in OVX-treated animals only at high dosages (1% and 1.5%), and not at lower dosages.…”

“…In general, GTP intake up to 1.5% dosage for 6 months did not affect hematology, clinical chemistry, or urine analysis. It was observed that bone mass and strength significantly improved with GTP concentration in the drinking water 71. Based on the bone histomorphometric analysis, GTP suppressed both bone formation and bone resorption at cancellous bone of tibia as well as periosteal and endocortical bone of tibia in a dose-dependent manner 72.…”

“…In order to further demonstrate the effects of long-term green tea extraction bone health, Shen et al 71 72 conducted a 6-month dose–response study using middle-aged OVX rats, where they evaluated safety and bone efficacy in 182 6-month-old OVX rats supplemented with different dosages of GTP (0%, 0.15%, 0.5%, 1%, and 1.5%, wt/vol) in the drinking water. The 6-month study period was selected because 6 months of rats’ life is equivalent to 10 years of human life 73.…”

“…The 6-month study period was selected because 6 months of rats’ life is equivalent to 10 years of human life 73. The preliminary results showed no mortality or abnormal treatment-related effects, although OVX rats supplemented with GTP at 1.5% dosage had the smallest body weights 71. In general, GTP intake up to 1.5% dosage for 6 months did not affect hematology, clinical chemistry, or urine analysis.…”