AST: Aspartate Transaminase; ALT: Alanine Transaminase; BP: Blood Pressure; CVD: Cardiovascular Disease; DBP: Diastolic Blood Pressure; SBP: Systolic Blood Pressure.

Smoking has been linked to uncontrolled blood pressure (BP). It is well known that BP levels change with age. Systolic blood pressure (SBP) increases from adolescence until old age, while diastolic blood pressure (DBP) increases until age 50 years and then decreases [1]. The risk of cardiovascular disease (CVD) mortality increases gradually throughout the range of BP starting at pre-hypertensive ranges of SBP (120–139 mmHg) and DBP (80–89 mmHg) [2]. Therefore, small changes in BP through dietary interventions may have a significant impact on reducing the risk especially among former and current smokers.

A large number of animal and epidemiologic studies as well as small-size clinical trials have investigated the relationship between tea consumption and BP, with inconsistent outcomes [3-7]. Despite of these conflicting results, green tea extracts (GTE) have been increasingly used by the general population as an ingredient in different dietary supplements. Some concerns have been raised about the safety of the intake of high doses of GTE. A systematic review revealed that in most cases, there were multiple agents involved and the committee recommended taking GTE with meals [8]. However, drinking green tea has not been associated with liver injury or serum aminotransferase elevations [9].

Therefore, we examined in the context of a randomized, controlled, doubled blinded trial the efficacy of regular black and green tea drinking in reducing BP among current and former smokers. We also examined the impact of black and green tea consumption on liver enzymes in this population of middle-aged and elderly former and current smokers.

Study population

We recruited current and former smokers between 40 and 80 years of age. Subjects were screened to exclude regular tea drinkers, pregnant women, history of cancer, current drug or alcohol abusers, individuals with an abnormal liver function blood test or those currently being treated with antidepressants. The study was approved by the Institutional Review Board of the University of Arizona, and all of the subjects provided informed consent before enrollment.

Study protocol

The study protocol and data collection procedures were described in details elsewhere [10]. In brief, the study was a 3-arm double-blinded randomized placebo-controlled tea intervention trial. Each subject was randomly assigned to drink 4 cups (12 oz. each) of black tea, green tea, or placebo tea daily for 6 months. Study participants were asked to maintain the beverage consumption pattern (4 cups/day) for 6 months, returning to the clinic at monthly intervals. Blood and urine samples were collected at baseline, mid study (month 3) and end of the study (month 6). SBP (in mmHg) and DBP (in mmHg) were measured at least 3 times with a minimum 5-minute interval, by using Omrom MX3 plus automated oscillometric Blood Pressure Monitor (O-HEM- 742-E; Matsusaka, Japan), according to standard operating procedures, by a well-trained research specialist. BP measurements were performed after participants had been seated for at least 5 minutes. Levels of serum glucose, ALT, and AST were determined at the central laboratory affiliated with the University of Arizona.

Statistical methods

Descriptive analyses were conducted by gender. Primary end points were changes in SBP, DBP, glucose, and liver enzymes (AST and ALT) from baseline to 6 months after commencement of intervention. Tests for significance of the change (pre-intervention versus post-intervention values) in SBP, DBP, AST and ALT were performed by gender. Results were expressed as mean ± standard deviation (SD). Multiple linear regression models were used to estimate the main effects of black and green tea intake on SBP, DBP, glucose, AST and ALT with or without adjustment for potential confounders. Data presented are adjusted for smoking status and years of smoking. Statistical tests were two-sided with a significant level of 0.05. All statistical analyses were conducted using Stata Statistical Software (Stata 12).

Of the 154 randomized participants, 146 (80 females and 66 males) current and former smokers completed the 6-month intervention. There were no statistically significant differences by gender, smoking variables, or treatment group between those who completed the study and those who did not. Among those who completed the study, compliance to the tea intervention was >95%.

Overall characteristics of the study population by gender are shown in Table 1. Our data showed that women have significantly lower SBP (p=0.03) and DBP (p=0.005) as well as lower blood glucose (p=0.001) and ALT (p=0.002) levels compared to men. There were no significant differences in baseline characteristics between the three intervention groups (data not shown).

Table 1: Overall characteristics of the study population by gender.

Unadjusted means of baseline and 6-month (end of intervention) clinical data per group are shown in Table 2 for females and Table 3 for males.

Table 2: Females clinical outcomes at baseline and month 6 by intervention group. *P < 0.05

Table 3: Males clinical outcomes at baseline and month 6 by intervention group.

The adjusted mean changes in SBP, DBP, glucose, AST and ALT by tea group compared to placebo are shown in Table 4. Our data showed a significant decrease in SBP (4 mmHg) among females after 6 months of drinking black tea (p=0.01). Green tea consumption was associated with a significant decrease (p=0.035) in serum ALT among females.

Table 4: Mean change (95% CI) in clinical outcomes by tea group compared with placebo.

SBP and DBP are associated with cardiovascular mortality at thresholds lower than the current hypertension definition. Published data revealed that throughout middle and old age, BP is strongly and directly associated with CVD and overall mortality, without any evidence of a threshold down to at least 115/75 mmHg (2). In women and men with normal SBP levels, DBP did not influence cardiovascular mortality after adjustment for age and SBP, however, in both genders, CVD mortality increased with the increase in SBP [11-13]. Small decreases in SBP can have a significant effect on cardiovascular outcomes. Several studies have showed that measuring SBP alone would be effective in screening for CVD risk in large populations [14]. Therefore, even relatively small reductions in population SBP can be considered of major interest to public health.

In our current study, we found that black tea consumption for 6 months was associated with significant decrease of SBP among women. A recent systematic review of 10 trials showed that consumption of green or black tea can reduce BP in individuals within pre-hypertensive and hypertensive ranges [15]. The beneficial effects of tea intake on BP were mainly observed when the duration of consumption was slightly ≥ 12 weeks [16].

There are a number of potential mechanisms for BP lowering effect by black tea. In addition to their antioxidant properties, tea flavonoids reduce plasma concentrations of endothelin-1 which could contribute to reduced vascular tone and lower BP [17]. Published data showed that regular ingestion of black tea significantly improved brachial artery vasodilator functions among people with elevated serum lipids [18] and reversed endothelial vasomotor dysfunction in patients with CVD [19]. A recent meta-analysis reported that endothelial function can be improved by tea consumption [20].

Serum AST and ALT are known as biomarkers for liver health. Our data showed that regular green tea consumption was associated with significant decrease in serum ALT among females. Recently published randomized clinical trials reported that GTE supplementation decreased ALT and AST levels after 12-week period in patients with non-alcoholic fatty liver disease [21-23]. Based on our results, daily tea consumption of green or black tea does not impair liver function in former or current smokers.

Our study has demonstrated that long-term regular consumption of black tea can result in significantly lower SBP in middle-aged and elderly women with normal to high-normal range BP. Given that a large proportion of the general populations have BP within the range included in this trial, make the results applicable to women at increased risk of hypertension.

Conception and design: I. A. Hakim, R. B. Harris, L. L. Garland, H.-H. Sherry Chow.

Development of methodology: I. A. Hakim, R. B. Harris, H.-H. Sherry Chow.

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): I. A. Hakim and H.-H. Sherry Chow.

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): I. A. Hakim, R. B. Harris, and H.-H. Sherry Chow.

Writing, review, and/or revision of the manuscript: I. A. Hakim, R. B. Harris, L. L. Garland, H.-H. Sherry Chow.

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): I.A. Hakim and data manager.

Study supervision: I. A. Hakim, L. L. Garland, H.-H. Sherry Chow.

This work was supported by a grant (DOD PR 023104) from the Department of Defense and the University of Arizona Cancer Center Support Grant (CA023074) from the National Cancer Institute (Bethesda, MD). Tea pouches were provided by Unilever Bestfoods, New Jersey, USA for the tea supply.