Bladder infections in otherwise healthy pre-menopausal and non-pregnant women tend to be uncomplicated and are classified as lower urinary tract infections (UTIs).  UTIs are amongst the most common infections in women and Escherichia coli (E. coli) is the organism that is the most common, responsible for about 75-95% of uncomplicated UTIs.

Trimethoprim-sulfamethoxazole (TMP/SMX), aka co-trimoxazole, and brand names, Bactrim or Septra, is an inexpensive antibiotic and generally well tolerated and effective.  However, due to its common use, resistance to E. coli strains with this antibiotic has increased significantly, and as many as 20% of cases will be resistant, which is why other first line antibiotics are often chosen.

The genesis of this current study is that there are laboratory studies that have shown antimicrobial effects of green tea catechins against E. coli as well as synergistic effects between the catechins and antibiotics such as the co-trimoxazole against E. coli.

This randomized, blinded, placebo-controlled trial was conducted in Iran.  Healthy premenopausal, non-pregnant women ages 18-50 with acute uncomplicated cystitis were included in the study.  After urine collection, women were given four 500 mg capsules of green tea extract or placebo before bed, daily for 3 days.  All of the patients also received the TMP/SMX at two 480 mg tablets twice daily for 3 days.  Each gram of green tea contained approximately a total phenol content of 283 mg and 65 mg of epigallocatechin gallate (EGCG).  The urine was then tested again in each group, on the fourth day.

Results:  Among the 107 eligible women patients, 70 completed the trial.  Women in the green tea group showed a statistically significant decrease in the prevalence of cystitis symptoms at each time point (recorded daily).  The presence of symptoms was as follows:                 

Baseline: Green tea 68%; placebo 75%
After 1 day: Green tea 61%; placebo 74%
After 2 days: Green tea 34%; placebo 67%    
After 3 days: Green tea 2%; placebo 63%

In addition, the addition of the green tea resulted in a statistically significant improvement in the urinalysis in terms of color, bacteria, and white blood cells.  No patients, in either group, had a recurrence of their UTI after 2 weeks.  After 4 weeks, 1 in the green tea group had a recurrence and after 6 weeks, 2 in the TMP/AMX only group had a recurrence. 

Commentary:  One of the unique things in the study design was that the green tea extract was given in a bolus, all four capsules at once, and in the evening.  The rationale of the researchers was that the EGCG was better retained in the bladder all night, noting that more than 90% of the urinary EGCG is excreted in the first 8 hours of administration, therefore all at once and in the evening before bed would theoretically enhance its effectiveness, if they did not urinate until morning.

A word of caution about green tea extracts:

You might be interested in a report on green tea extracts that came to my attention in 2020 and was recently pointed out to me again, to be included for this column. (Ouyang J, et al. Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect. Oxid Med Cell Longev. Published online Aug 12, 2020)

It pointed out the susceptibility of green tea extracts to generate reactive oxygen species (ROS) via autooxidation and exhibit prooxidant effects.  This leaves us with a dual role of Epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea.   While most of us are familiar with antioxidant properties of EGCG, under certain conditions, it can act as a proxidant, with the subsequent benefits and harms of prooxidants.  There may be a dose limit to EGCG such that harm, toxicity, and in particular liver damage can be avoided.

In a safety study of EGCG in humans, the no-observed adverse effect level (NOAEL) was reported to be 600 mg/day and the acceptable daily intake of EGCG for humans was reported to be 322 mg EGCG/day (Yates A. A., Erdman J. W., Jr., Shao A., Dolan L. C., Griffiths J. C. Bioactive nutrients – time for tolerable upper intake levels to address safety. Regulatory Toxicology and Pharmacology. 2017; 84:94–101).

Some European regulatory agencies proposed that the tolerable upper intake level of EGCG should be 300 mg per day for humans. (Yates A. A., Erdman J. W., Jr., Shao A., Dolan L. C., Griffiths J. C. Bioactive nutrients – time for tolerable upper intake levels to address safety. Regulatory Toxicology and Pharmacology. 2017;84:94–101). After reviewing the evidence from interventional clinical trials, The European Food Safety Authority (EFSA) concluded that an intake of 800 mg or more of EGCG/day could lead to elevated transaminases based on a review of interventional clinical trials. (Younes M., Aggett P., Aguilar F., et al. Scientific opinion on the safety of green tea catechins. EFSA Journal. 2018;16(4))

A review of safety data and human adverse events of EGCG, authors advised to consider a safe level to be 704 mg per day EGCG in beverage form and 338 mg per day in bolus form (Hu J., Webster D., Cao J., Shao A. The safety of green tea and green tea extract consumption in adults – results of a systematic review. Regulatory Toxicology and Pharmacology. 2018; 95:412–433)

100 g dry weight of green tea contains about 7000 mg EGCG, and 100 g of green tea infusion contains approximately 70 mg EGCG.

In my experience, 49 out of 50 premenopausal non-pregnant women with uncomplicated UTIs can be successfully treated with a combination of herbal ingredients if dosed aggressively (formulas typically would contain cranberry extract, buchu leaf, Oregon grape root, pipsissewa, uva ursi and marshmallow root); occasionally I might add mannose powder, along with a robust intake of water.  On the atypical occasion that I prescribe an antibiotic, I will consider adding the dosing of green tea extract for 3 days used in the current study, whether the antibiotic is TMX/SMP or another. 

Reference: 

Kheirabadi K, et al.  Green tea as an adjunctive therapy for treatment of acute uncomplicated cystitis in women:  A randomized clinical trial.  Complementary Therapies in Clinical Practice 2019;34:13-16