Tea consumption and serum uric acid levels among older adults in three large-scale population-based studies in China

Hyperuricemia (HUA) is a major risk factor for several chronic conditions such as gout [1], cardiovascular diseases (CVDs) [2], diabetes [3], and hypertension [4]. HUA is also associated with increased hospitalization risks and healthcare expenditures [5]. The prevalence of HUA has been increasing throughout the world [6]. It was estimated that approximately 21.4% of American adults suffered from HUA [6], and the prevalence of HUA ranged from 13 to 25.8% in Asians [7‐10]. Thus, identifying modifiable risk factors of HUA is crucial for addressing this health public concern.

Tea (Camellia sinensis) is a common and popular beverage worldwide, especially in Asia [11, 12]. The association between tea consumption and levels of serum uric acid (SUA) was inconsistent among different studies. For example, some studies supported that tea consumption could reduce SUA levels in both human beings [13] and animals [14, 15]. However, other studies found that tea [16] or its extracts [17] were associated with a higher level of SUA. Non-significant association between tea consumption and SUA levels was also reported in previous research [18]. Thus, the impact of tea consumption on levels of SUA is far from conclusive and needs further clarifications.

Considering that HUA is a common chronic condition in the elderly, who are fond of drinking tea more than the young, understanding the health impact of tea consumption among older adults has important public health implications. Large-scale population-based studies, especially cohort studies, could provide cogent evidence on the relationship between exposures and outcome measures [19]. In the present analysis, we examined both cross-sectional and longitudinal associations between tea consumption and SUA levels in three large-scale datasetsof mainland China (the WGDS, the CHNS and the CLHLS). The findings would further elucidate the role of some tea-related nutrients (e.g., polyphenols) in the etiology of SUA-related conditions (e.g. gout) and help to design appropriate prevention strategy.

In this analysis, participants were from three population-based studies (WGDS, CHNS and CLHLS), and their characteristics were displayed in Table 1. The mean and range of participants’ ages at baseline were 67.7 ± 6.3 (60.0–93.0), 68.9 ± 6.8 (60.0–99.0) and 86.6 ± 12.3 (62.0–110.0) respectively. The category of tea drinking frequencies was by the criterion “6-times-per-week” among the habitual tea drinkers. Types of tea were considered in the WGDS study to explore a potential tea component effect.

The tea consumers had significantly higher SUA levels compared to those without the tea-drinking habit as shown in Fig. 1, and this tendency was consistent in the sex-subgroups as well as the whole datasetsfor all the three studies. Table 2 showed relationships between tea-drinking parameters and SUA levels, and the multiple linear regression analyses were fitted after adjusting for potential confounders. SUA levels were significantly associated with tea drinking status (Yes/No) in all models (P ≤ 0.05), agreeing with Fig. 1 above. We found that the participants with high frequencies of tea drinking (no less than 6 times per week) tended to have higher SUA levels compared to those with less tea-drinking frequencies. Significant associations (P < 0.05) were found for the adjusted linear regression models in all studies except Model 3 in CHNS. Furthermore, tea type played an important role, as green tea significantly increased SUA levels. For example, the SUA level of green tea increased by 18.69 (95%CI: 12.74, 24.64) compared to other tea types.

We further examined the relationship between SUA levels and tea-drinking by longitudinal cohort studies on the WGDS and the CLHLS as shown in Table 3. However, the changes of SUA levels had no relationship with tea-drinking parameters, with no statistical significance (P > 0.05) for all linear regression models adjusted for covariates such as age, sex, BMI and so on. To further explore the sex effect on longitudinal cohort studies, distributions of SUA levels in the follow-up periods were shown in Fig. 2, where the mean, standard deviation and range were displayed for men, women and the whole datasets. The SUA mean of men was found significantly larger than that of women among the sex-subgroups.

We further conducted the sex-stratified analysis on cross-sectional studies to explore the sex effect on SUA-tea correlations as shown in Table 4. The linear regression coefficients were from the adjusted models similar to Model 3 at Table 2. The relationships were found significant in gender subgroups in the WGDS and the CLHLS. Compared with Model 3 of Table 2 for the whole datasets, tea-SUA correlations in the sex-stratified analysis maintained significant in the WGDS and the CLHLS (P < 0.01), but were weakened in the CHNS for the tea drinking status (P > 0.05).

In the present analyses, we examined relationships between tea consumption and SUA levels for Chinese adults aged 60 years or older. Three large-samplestudies were accessed and compared for cross-sectional analyses, and regions investigated covered from Weitang Town of Suzhou City to the whole mainland of China. Furthermore, two datasets were selected for longitudinal studies with the follow-up periods of 4 and 6 years. In cross-sectional analyses SUA levels were found higher among tea consumers than non-tea consumers at baseline, but no significant associations were observed in longitudinal analyses. Our results added new knowledge to the role of tea-drinking in SUA levels by comparing different statistical analyses on three large-scale samples.

The arguments on associations between tea consumption and SUA levels have been reported in previous studies [15, 16, 26‐31]. Some studies demonstrated that SUA levels decreased for tea drinkers [15, 30]. In contrast, the results from two Asia studies (Singapore and Korean) showed positive associations between SUA levels and tea consumption [16, 29]. In addition, no association was reported in other population-based studies from either western or Asian countries [26‐28, 31]. The disagreement might be due to different approaches addressing how tea intake influences SUA levels. In rat experiments, green tea was found to decrease SUA levels [15]. Among previous epidemiological studies, cross-sectional analyses found either no association [26, 28] or positive connections [29]. While for longitudinal analyses connections could be positive [16], negative [30], or none [27, 31]. Due to the disagreements from different statistical analyses on various datasets, we conducted both cross-sectional and longitudinal analyses, and compared the studies between three large samples. Our longitudinal analyses showed no correlation between SUA levels and tea intakes, while the correlation appeared in our cross-sectional analyses. This study suggests no statistically significant association between SUA levels and tea intake.

The mechanics of how tea consumption might influence SUA levels have not been determined, and two tea components, tea polyphenols and caffeine, are mostly discussed in experiments [12, 15‐17, 26‐33]. Tea polyphenols can affect both the production and excretion of SUA [17]. On one hand, catechins and theaflavins are effective inhibitors of XO (xanthine oxidase) to the production of UA, which leads to SUA decrease [15]. On the other hand, catechins inhibit expression of OATP1 (organic anion transporter) [32], a secreting protein for UA excretion, and they could cause an upward trend of SUA [34]. Another component caffeine (1,3,7-trimethyl-xanthine) is a methyl-xanthine, which is the major component of coffee as well. There has been no clear explanation on how caffeine affects SUA. Caffeine is metabolized by demethylation into the urinary metabolite l-methylxanthine, which was found inhibitive effect on XO in in-vitro and vivo experiments of rats [35]. In other rat experiments caffeine was found inducing renal deterioration and high insulin sensitivity, which resulted in increase of SUA levels [36]. This could be related to the positive association between SUA levels and caffeine intake found in females in the epidemiologic study [29]. Furthermore, during the follow-up period of 4–6 years, possible changes of health conditions could influence SUA levels. Hyperuricemia was found associated with cardiovascular disease, renal disease, metabolic diseases, diabetes, hypertension and other diseases [37].

The strength of this study includes its prospective design and the population-based large sample size. It also has several limitations. First, the study samples consisted primarily consisted of older Chinese adults. The homogeneity of the study participants minimized confounding by socioeconomic status, but the generalizability of our data to other populations segments may be limited, such as younger generations and other racial or ethnic groups. Second, the information on tea consumption was self-reported and collected by questionnaires, which may lead to misclassifications of exposure. Because of the prospective nature of the analysis, these misclassifications tended to have attenuated our results towards the null. Third, although we controlled for a wide range of covariates including lifestyle factors, the possibility of unmeasured and residual confounding cannot be fully excluded. We did not assess whether participants had renal dysfunction, obesity, medications, thyroid, and related disorders, which may has changed the levels of SUA.

In conclusion, results from these three large and well-established population-based studies demonstrated a significant connection between tea consumption and SUA levels at baseline, but these provided no support for the longitudinal association in the follow-up of 4–6 years. Misclassification bias could have influenced the longitudinal association and the direction of the bias would be more likely towards the null in our study. Additional well-designed cohort studies with more precise measurement of tea consumption (e.g. cup capacity and tea concentration) and longer follow-up durations are needed to confirm our findings.