Effects of matcha green tea on the pharmacokinetics of nadolol in rats

by Eslam T. Mashaqbeh, Tamam El-Elimat, Osama Y. Alshogran, Iyad Hamzeh, Zahraa M. Obeidat, Ahmed H. Al Sharie, Feras El Hajji

The concurrent use of herbal dietary supplements with prescription medications raises safety concerns due to the potential for clinically significant interactions. Matcha, a shade-grown green tea consumed as an ultra-fine powder, is rich in catechins that may inhibit the transport of P-glycoprotein (P-gp) substrates such as nadolol. This study investigated the effects of administering single and multiple doses of matcha on the pharmacokinetics of nadolol in an in vivo animal model. Male Sprague-Dawley rats (n = 32) were randomly assigned to four groups. Group 1 (negative control) was administered normal saline followed by a single oral dose of nadolol (10 mg/kg). Group 2 (matcha single-dose) was administered a single dose of matcha (250 mg/kg) whisked in normal saline, followed by nadolol (10 mg/kg) after 30 min. Group 3 (positive control) received itraconazole (50 mg/kg), followed by nadolol (10 mg/kg) after 30 min. Group 4 (matcha multiple-dose) received matcha (250 mg/kg daily for 21 days) before administering nadolol (10 mg/kg) on day 21. Blood samples were collected at 0, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 8 and 24 h. Nadolol concentrations in plasma were measured by a validated high-performance liquid chromatography with fluorescence detection (HPLC-FL) method. Pharmacokinetic parameters were estimated using the PK solver add-in for Microsoft Excel. To ensure quality control, caffeine, a key marker compound of matcha green tea, was quantified using HPLC with ultraviolet detection (HPLC-UV). A single oral dosage of matcha (250 mg/kg) had no statistically significant effects on the pharmacokinetics of nadolol compared to the control group (p > .05). Although the multiple-dose matcha group showed an increase in C_max (~45%), AUC_0-t (~18%), and AUC_0-∞ (~22%) for nadolol compared to the control group, these differences were not statistically significant (p > .05). In contrast, the t½ (h) of nadolol increased significantly from 4.0 ± 1.6 in the control group to 7.7 ± 4.2 (p = .039) in the matcha multiple-dose group. Itraconazole co-administration significantly increased systemic exposure (AUC) of nadolol (p = .009), confirming the validity of the animal model. Caffeine, a key marker compound in matcha tea, was quantified at 4.18 ± 0.44% w/w of dry matcha tea powder, equivalent to 41.8 ± 4.4 mg/g. This is the first study to explore the potential pharmacokinetic interaction between matcha tea and nadolol. Single and multiple oral doses of matcha green tea had negligible effects on most pharmacokinetic parameters of nadolol, except for an increased half-life in the multiple-dose group. Further research is needed to establish the clinical relevance of this interaction before definitive recommendations on the safety of matcha tea and nadolol coadministration can be made.

Research on Eating and Adolescent Lifestyle (REAL) 2.0: 15-year follow-up study of eating disorders and weight-related trajectories, mental health and substance use health from early adolescence to early adulthood--a Canadian cohort profile

Purpose

Few studies have examined how psychosocial risk and protective factors in adolescence shape mental health outcomes and other multimorbid conditions in adulthood, particularly among Canadian youth. The Research on Eating and Adolescent Lifestyle (REAL) 2.0 study was a 15-year follow-up cohort study designed to investigate how early etiological factors, including body image and disordered eating symptoms in adolescence, contribute to the development of eating, weight-related concerns, mental health and substance use health problems in early adulthood. In this paper, we describe the REAL 2.0 cohort’s demographic and clinical characteristics alongside an overview of the study procedures, laying the groundwork for collaboration on future learnings with this unique data.

Participants

The cross-sectional REAL study initially surveyed middle and high school students from 2004 to 2010 (n=3043) across 43 schools in the Ottawa, Canada region. Of those, respondents in grade 7 or 9 (n=1197 from 25 of the 43 original schools) were asked to participate in a longitudinal arm of the study that consisted of yearly follow-ups. From the longitudinal cohort, there were 278 participants (29.1% male; M_age=28.6) from those who consented to be re-contacted (n=912), who completed the REAL 2.0 survey electronically (30.4%), providing comprehensive data on demographic, clinical, eating and weight-related behaviour, psychological, social, environmental and substance use health factors in adulthood.

Findings to date

9.4% of REAL 2.0 participants met DSM-5 criteria for an eating disorder, while 17.6% met criteria for disordered eating. Moderate to severe anxiety was reported by 28% of participants, while 21.6% experienced moderate to severe depressive symptoms. Regarding substance use, 16.9% engaged in hazardous drinking, 16.9% used cannabis daily or almost daily, and 4.3% reported daily tobacco use.

Future plans

REAL 2.0 has the potential to answer multiple research questions about several mental health outcomes, but its priority focus is to answer questions related to risk and protective factors of multimorbidity in adulthood. Additionally, profiling work, linked to health service utilisation data for systems planning work and predictive modelling studies are secondary goals. By leveraging the Health Data Nexus (HDN) platform, we welcome collaboration with interested researchers who would like to utilise the breadth of data both in adolescence and adulthood to answer other pertinent aetiological questions in mental health and substance use health outcomes. Future plans to conduct additional follow-ups remain feasible.