They were also not allowed to smoke 2 weeks before and throughout the study. Subjects were requested to fast for 10 h before and 4 h after drug administration during the blood sampling sessions.

Meals were standardized and consumed at 4 h and 10 h post-dosing. Drinking water was not allowed from 1 h pre-dose to 1 h post-dose except that needed for drug dosing at the time of blood sampling sessions. Subjects were asked to report any adverse effects at each visit to the study center. This was an open-label, three-phase randomized crossover study.

Subjects were given a single dose of rosuvastatin 10 mg Crestor ® , Astra Zeneca on 3 occasions: 1. with soy isoflavones extract. The green tea extract and soy isoflavones extract were given at a dose thought to contain EGCG mg once daily or isoflavones 80 mg once daily for 14 days before rosuvastatin dosing with at least a 4-week washout period between phases.

The herbal extracts were present as a powder which was taken in ml water at room temperature. Blood samples were taken at intervals from 0 to 24 h on the rosuvastatin dosing days.

During the study, subjects were frequently reminded of the requirements for diet restrictions, and they were requested to record their daily food intake, including the main meals, snacks and beverages of the day by using a simple food diary, which can help to monitor the food compliance during the study.

Green tea extract and soy isoflavones extract products were manufactured by the Hong Kong Institute of Biotechnology HKIB in accordance with Good Manufacturing Practice GMP.

Standard heavy metal, microbial and pesticides tests were performed to ensure the products fulfilled the safety requirement set out by the Department of Health in Hong Kong. Each green tea extract sachet claimed to contain mg standardized EGCG.

Each soy extract sachet claimed to contain 80 mg standardized total isoflavones. The plasma samples were prepared using liquid—liquid extraction with diethyl ether. Chromatographic separation was accomplished on an Xterra MS C18 column 50 × 2.

The mobile phase consisted of a gradient mixture of 0. The gradient was then returned to the initial mobile phase concentration in a chromatographic run of 8 min. The lower limit of quantification of rosuvastatin was 0. The linear range of the method was from 0.

DNA was extracted from the blood samples using High Pure PCR Template Preparation Kits Roche Applied Science. The pharmacokinetic parameters of rosuvastatin were calculated using non-compartmental methods with the aid of the computer program WinNolin version 2.

The maximum plasma concentration C max and time to C max t max were obtained directly from the observed concentration-time data. The primary outcome was the difference in rosuvastatin pharmacokinetic parameters with and without herb consumptions.

Logarithmic transformation was used for pharmacokinetic variables, except for t max. The pharmacokinetic parameters of rosuvastatin after consumption of green tea or soy isoflavones were compared with those when the drugs were taken without these herbs by repeated measures ANOVA, except for t max values for which the Friedman rank test was used.

The comparisons of the pharmacokinetic parameters and interactions among genotype groups were determined using ANOVA for normally distributed data or the Kruskal-Wallis test for skewed data. In a previous study, a herb-drug interaction between baicalin and rosuvastatin was related to different SLCO1B1 haplotype groups in 18 healthy Chinese subjects, with 6 in each haplotype group.

A similar sample size of 20 subjects was used in the current study to explore the potential herb-drug interactions and their relationship with the ABCG2 transporter polymorphism. The green tea extract product mainly contained — -epigallocatechingallate EGCG as it corresponded with the EGCG standard on the chromatogram, although the other 6 chemical markers were also present in small amounts.

The amount of EGCG within each sachet daily dose was The EGCG may have undergone some epimerization to gallocatechin gallate GCG during the extraction process which involved some heating and there was a small peak on the chromatogram close to the EGCG peak which was not identified or quantified, but may have been GCG.

The soy isoflavone product contained all 7 chemical markers, namely glycitin, daidzin, genistin, daidzein, glycitein, genistein and acetylgenistin in amounts of There were some other small unidentified peaks on the chromatogram which may represent other components of the extract that contribute to the total isoflavones.

In the 20 healthy Chinese male volunteers [mean ±SD age: Reduction in systemic exposure to rosuvastatin with EGCG was observed in 17 out of 20 subjects. Table 1. Demographics of the 20 study subjects in the rosuvastatin-herb interaction study.

Figure 1. Effects of green tea extract and soy isoflavones on the pharmacokinetics of rosuvastatin in 20 healthy subjects. Data are arithmetic mean ±SD. Table 2. Effect of green tea extract and soy isoflavones on the pharmacokinetic parameters of rosuvastatin in 20 healthy subjects.

The soy isoflavones had no significant effect on the pharmacokinetics of rosuvastatin Figure 1 ; Table 2. Figure 2. Data are arithmetic mean. A , Baseline; B , After green tea extract; C , After soy isoflavones. Figure 3. The subjects did not report any adverse events during the periods of repeated intake of green tea extract or soy isoflavones or the single doses of rosuvastatin.

Beverages and food can interact with various medications and may alter their pharmacokinetic properties. In this study, we tested the hypothesis whether green tea or soy isoflavones would influence the pharmacokinetics of rosuvastatin, a commonly used statin, in Hong Kong Chinese subjects and whether genetic polymorphisms in drug transporters and drug metabolizing enzymes would affect the interactions.

The soy isoflavones had no significant effect on any of the pharmacokinetic parameters of rosuvastatin. Green tea or EGCG has also been reported to improve many cardiovascular risk factors, including plasma lipids, blood pressure, inflammatory biomarkers, oxidative stress, glucose and insulin resistance 31 — The mechanisms by which green tea exerts its purported cardiovascular protective effects are subjects of interest in the field.

Green tea catechin-enriched extracts are available over the counter as dietary supplements like vitamins and weight reduction pills and are widely and increasingly used by the general public, especially in those with increased cardiovascular risk, such as with hypercholesterolaemia.

However, in vitro and in vivo studies suggested that green tea polyphenols may affect the absorption and metabolism of drugs by affecting the expression or activities of drug-metabolizing enzymes and drug transporters It has been shown that green tea catechins inhibit the activities of CYP1A1, 1A2, 2A6, 2C9, 2E1, and 3A4 and may also induce the expression of CYP1A1, 1A2, 2D6, 2E1, 3A4 in cell lines 35 , Several studies have also indicated the inhibition of ABCB1 and ABCG2 activity by EGCG Roth et al.

showed that EGCG inhibited OATP1A2- and OATP2B1-mediated uptake of estronesulfate in a concentration-dependent manner in cells expressing these transporters On the other hand, EGCG was shown to activate OATP1B3 in in vitro studies Various compounds can induce transporters such as P-gp and possibly hepatic OATP1B transporters by activating the pregnane X receptor PXR The herbal medicine baicalin was shown to reduce the plasma concentrations of rosuvastatin in an OATP1B1 haplotype—dependent manner, suggesting the effect was mediated by induction of hepatic rosuvastatin uptake through OATP1B1 However, after giving the EGCG daily for 10 days, the systemic exposure of rosuvastatin was not significantly different from the baseline value before EGCG, although the AUC and C max values were intermediate between the values before and after a single dose of EGCG The effect of the single dose was thought to be due to inhibition of intestinal uptake transporters OATP2B1 or OATP1A2, considering that the predicted plasma concentration would be sufficient to inhibit OATP2B1 The authors speculated that long-term treatment might result in accumulation sufficient to inhibit liver uptake by OATP1B1 or to upregulation of enterocyte transporters.

In addition to EGCG, other gallated catechins in green tea, such as ECG, can inhibit OATP1A2, OATP1B1, and OATP2B1 Therefore, green tea may have a different effect from pure EGCG. Rosuvastatin undergoes little metabolism, but it is a substrate of multiple transporters, including OATPs and ABCG2 Similarly, inhibition of ABCG2 by green tea might also be predicted to result in increased plasma concentration of rosuvastatin.

However, in this study in healthy volunteers, treatment with green tea extract containing mainly EGCG was associated with reduced systemic exposure to rosuvastatin. This may be explained by an inhibitory effect of EGCG on the intestinal uptake transporters OATP2B1 or OATP1A2, like the single-dose study of Kim et al.

A study using cultured cells transfected with human P-gp or human BCRP showed no significant effect of green tea components EC, ECG, EGC, or EGCG on P-gp-mediated or BCRP-mediated dasatinib efflux, whereas some fruit juice components had a strong inhibitory effect Lack of effect of the ABCG2 polymorphism on the effect of green tea extract on rosuvastatin pharmacokinetic in the present study would also suggest that the effect is not medicated by ABCG2 induction.

Green tea was shown to significantly decrease the C max and AUC of nadolol by In vitro experiments revealed that nadolol is a substrate of OATP1A2 and green tea significantly inhibited OATP1A2-mediated nadolol uptake.

Further studies are needed to investigate the mechanisms underlying the interaction between rosuvastatin and EGCG. The most likely mechanisms appear to be inhibition of intestinal uptake by OAPT1A2 or activation of liver uptake by induction of OATP1B3 or OATP1B1.

The former might be expected to reduce the lipid lowering effect of rosuvastatin whereas the latter might increase it. This study has several limitations that need to be considered. Firstly, this study only assessed one dosage for each herb product e. It is known that interactions between herbs and drugs may be dose-dependent.

Evaluating a higher dose or a lower dose may help to provide a better understanding of the interaction between statins and green tea or soy isoflavones.

Secondly, it has been shown that taking EGCG 8 or 4 h before sunitinib administration had no effect on the pharmacokinetics of sunitinib in rats, whereas taking the two together reduced the bioavailability of sunitinib probably because of a physical reaction between the two compounds 49 , suggesting separation of dosing of green tea and drugs may reduce any herb-drug interaction.

To maximize the possibility of finding an interaction between statins and green tea, subjects were taking green tea extract and statins simultaneously on the dosing day, so that a physical interaction between the two substances cannot be excluded.

It would be useful to assess whether the separation of dosing has different effects. During the study, we instructed the study participants to take the study product on an empty stomach at least 1 h before breakfast after overnight fasting to enhance the bioavailability of EGCG and to reduce the variations in EGCG bioavailability caused by food.

They were requested not to take alcohol, tea, grapefruit juice, caffeine, soybean milk or dietary supplements and herbal products 2 weeks before and throughout the study. Subjects were educated about the importance of their compliance to the herbs and dietary restrictions for this research at the beginning of the study and they were reminded frequently of these requirements.

The compliance to instructions on EGCG and soy isoflavones intake or dietary restrictions was monitored by using a food diary. This approach inevitably relied on the subjects' cooperation and honesty and may not be objective, but it was a practical way to conduct the study. It would be important to further evaluate the mechanisms responsible for the observed interactions and to assess whether these pharmacokinetic interactions have any impact on the lipid-lowering effect of statins in patients requiring long-term statin therapy.

There was no significant effect of soy isoflavones on rosuvastatin pharmacokinetics. Further studies should be performed to investigate the underlying mechanisms responsible for this observed interaction and to assess the clinical relevance in patients receiving long-term statins.

The studies involving human participants were reviewed and approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee with reference number CRE Written informed consent was obtained from the individual s for the publication of any potentially identifiable images or data included in this article.

WZ and MH analyzed the data and wrote this manuscript. BT designed the research project. HL, EW, CL, CW, and CH performed the experiments. BT and CH revised this manuscript. All authors contributed to the article and approved the submitted version.

The FDA issued a public health advisory in November to warn people of the risk of bleeding in the brain from use of this medication and has strongly urged all manufacturers of this drug to remove it from the market.

Reviewed By: Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ.

Review provided by VeriMed Healthcare Network. Main Campus: Chesterfield, MO Locations. BACK TO TOP. E-mail Form. Email Results Name: Email address: Recipients Name: Recipients address: Message:.

Possible Interactions with: Green Tea Camellia sinensis; Green Tea If you are being treated with any of the following medications, you should not drink green tea or take green tea extract without first talking to your health care provider: Adenosine -- Green tea may inhibit the actions of adenosine, a medication given in the hospital for an irregular and usually unstable heart rhythm.

All Video Images Tog. The Basics. Advanced Study. Green tea Myocardial infarction German chamomile Gastritis Pancreatitis Nail disorders HIV and AIDS Fever of unknown origin Leukemia. Related Information. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

GT is containing polyphenols that interfere with many drugs. The most important of these polyphenol compounds is epigallocatechingallate EGCG , which most of the reported interactions are due to the presence of EGCG.

Interaction of GT with different drugs occurs in the context of both pharmacodynamics and pharmacokinetics that includes drug absorption, metabolism, and renal excretion. The mechanisms of these interactions consist of increase in the concentration included several medications such as melatonin, midazolam, and amlodipine consuming after GT; these interactions can be toxic.

Additionally, it has been reported that serum levels of several drugs such as nadolol, digoxin, amoxicillin, and clozapine are decreased and their efficacy are reduced when they simultaneously administer with GT.

The serum concentration of rhodamin , quinidine, and doxorubicin have increased when these drugs were co-administered with GT.

Here are 10 science-based benefits of green tea extract. Many studies show that green tea can help you lose weight. It contains bioactive substances that can make you burn more calories, even at rest. It's easy to make a quick and healthy breakfast from wholesome, nutritious foods.

Here are the 12 healthiest foods to eat in the morning. Matcha is a type of powdered green tea. It is very high in antioxidants and has numerous health benefits for your body and brain.

Phosphatidylcholine is known to boost cognition, but its potential benefits don't stop there. Here's what you should know about this herbal remedy.

A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Nutrition Evidence Based EGCG Epigallocatechin Gallate : Benefits, Dosage, and Safety. By Ansley Hill, RD, LD — Updated on April 26, Share on Pinterest.

What is EGCG? Naturally found in various foods. May offer powerful health benefits. Dosage and possible side effects. The bottom line. How we reviewed this article: History. Apr 26, Written By Ansley Hill. Share this article.

Read this next. Green Tea vs Black Tea: Which One Is Healthier? By Sharon O'Brien MS, PGDip. By Arlene Semeco, MS, RD and Alyssa Northrop, MPH, RD, LMT. How Green Tea Can Help You Lose Weight. By Kris Gunnars, BSc.

The 12 Best Foods to Eat in the Morning. Evaluating a higher dose or a lower dose may help to provide a better understanding of the interaction between statins and green tea or soy isoflavones.

Secondly, it has been shown that taking EGCG 8 or 4 h before sunitinib administration had no effect on the pharmacokinetics of sunitinib in rats, whereas taking the two together reduced the bioavailability of sunitinib probably because of a physical reaction between the two compounds 49 , suggesting separation of dosing of green tea and drugs may reduce any herb-drug interaction.

To maximize the possibility of finding an interaction between statins and green tea, subjects were taking green tea extract and statins simultaneously on the dosing day, so that a physical interaction between the two substances cannot be excluded.

It would be useful to assess whether the separation of dosing has different effects. During the study, we instructed the study participants to take the study product on an empty stomach at least 1 h before breakfast after overnight fasting to enhance the bioavailability of EGCG and to reduce the variations in EGCG bioavailability caused by food.

They were requested not to take alcohol, tea, grapefruit juice, caffeine, soybean milk or dietary supplements and herbal products 2 weeks before and throughout the study.

Subjects were educated about the importance of their compliance to the herbs and dietary restrictions for this research at the beginning of the study and they were reminded frequently of these requirements. The compliance to instructions on EGCG and soy isoflavones intake or dietary restrictions was monitored by using a food diary.

This approach inevitably relied on the subjects' cooperation and honesty and may not be objective, but it was a practical way to conduct the study. It would be important to further evaluate the mechanisms responsible for the observed interactions and to assess whether these pharmacokinetic interactions have any impact on the lipid-lowering effect of statins in patients requiring long-term statin therapy.

There was no significant effect of soy isoflavones on rosuvastatin pharmacokinetics. Further studies should be performed to investigate the underlying mechanisms responsible for this observed interaction and to assess the clinical relevance in patients receiving long-term statins. The studies involving human participants were reviewed and approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee with reference number CRE Written informed consent was obtained from the individual s for the publication of any potentially identifiable images or data included in this article.

WZ and MH analyzed the data and wrote this manuscript. BT designed the research project. HL, EW, CL, CW, and CH performed the experiments. BT and CH revised this manuscript.

All authors contributed to the article and approved the submitted version. This study was supported by the Health and Health Services Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. We thank the other member of the research team, especially Ms. Swen Ip, Ms. Eliza Choy, and Dr. Benny Fok, for their excellent assistance and Ms.

Emily Poon for her help with the genotyping. We are also very grateful to the healthy volunteers for their participation in this research. Khan J, Deb PK, Priya S, Medina KD, Devi R, Walode SG et al.

Dietary flavonoids: cardioprotective potential with antioxidant effects and their pharmacokinetic, toxicological and therapeutic concerns.

doi: PubMed Abstract CrossRef Full Text Google Scholar. Liperoti R, Vetrano DL, Bernabei R, Onder G. Herbal medications in cardiovascular medicine. J Am Coll Cardiol. Shaito A, Thuan DTB, Phu HT, Nguyen THD, Hasan H, Halabi S et al. Herbal medicine for cardiovascular diseases: efficacy, mechanisms, and safety.

Front Pharmacol. Tomlinson B, Hu M, Lee VW. In vivo assessment of herb-drug interactions: possible utility of a pharmacogenetic approach?

Mol Nutri Food Res. Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Ronis MJJ. Effects of soy containing diet and isoflavones on cytochrome P enzyme expression and activity.

Drug Metabol Rev. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK et al. Statin-associated muscle symptoms: impact on statin therapy-european atherosclerosis society consensus panel statement on assessment, aetiology and management.

Eur Heart J. Turner RM, Pirmohamed M. Statin-Related myotoxicity: a comprehensive review of pharmacokinetic, pharmacogenomic and muscle components. J Clin Med. Zeng W, Tomlinson B. Causes and outcome of rhabdomyolysis in patients admitted to medical wards in the prince of wales hospital.

Ann Transl Med. Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB et al. Statin safety and associated adverse events: a scientific statement from the american heart association.

Arterioscler Thromb Vasc Biol. Xiang Q, Chen S-q, Ma L-y, Hu K, Zhang Z, Mu G-y et al. Association between SLCO1B1 TC polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenom J. Nikolic D, Banach M, Chianetta R, Luzzu LM, Pantea Stoian A, Diaconu CC et al. An overview of statin-induced myopathy and perspectives for the future.

Expert Opinion Drug Safety. Liu J-E, Liu X-Y, Chen S, Zhang Y, Cai L-Y, Yang M et al. Euro J Clinic Pharmacol. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F et al.

SLCO1B1 variants and statin-induced myopathy—a genomewide study. New Engl J Med. Hu M, Lee MH, Mak VW, Tomlinson B. Effect of central obesity, low high-density lipoprotein cholesterol and C-reactive protein polymorphisms on C-reactive protein levels during treatment with Rosuvastatin 10 mg Daily.

Am J Cardiol. Tomlinson B, Hu M, Lee VW, Lui SS, Chu TT, Poon EW et al. ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. Carr DF, Francis B, Jorgensen AL, Zhang E, Chinoy H, Heckbert SR et al.

Genomewide association study of statin-induced myopathy in patients recruited using the UK clinical practice research datalink. Clinic Pharmacol Therapeutics. Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ et al.

Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Windass AS, Lowes S, Wang Y, Brown CD. The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. Rouhi-Boroujeni H, Rouhi-Boroujeni H, Heidarian E, Mohammadizadeh F, Rafieian-Kopaei M.

Herbs with anti-lipid effects and their interactions with statins as a chemical anti-hyperlipidemia group drugs: a systematic review. ARYA atherosclerosis. PubMed Abstract Google Scholar.

Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L. The effect of green tea on simvastatin tolerability. Ann Intern Med. Alvarez AI, Real R, Pérez M, Mendoza G, Prieto JG, Merino G.

Modulation of the activity of ABC transporters P-glycoprotein, MRP2, BCRP by flavonoids and drug response. J Pharmaceutic Sci. Xiang Y, Liu S, Yang J, Wang Z, Zhang H, Gui C. Investigation of the interactions between flavonoids and human organic anion transporting polypeptide 1B1 using fluorescent substrate and 3D-QSAR analysis.

Biochimica et Biophysica Acta BBA -Biomembranes. Lee VW, Chau TS, Leung VP, Lee KK, Tomlinson B. Clinical efficacy of rosuvastatin in lipid management in Chinese patients in Hong Kong. Chin Med J Engl. Eng QY, Thanikachalam PV, Ramamurthy S. Molecular understanding of Epigallocatechin gallate EGCG in cardiovascular and metabolic diseases.

J Ethnopharmacol. Finally, the related papers are given in our review. GT is containing polyphenols that interfere with many drugs. The most important of these polyphenol compounds is epigallocatechingallate EGCG , which most of the reported interactions are due to the presence of EGCG.

Interaction of GT with different drugs occurs in the context of both pharmacodynamics and pharmacokinetics that includes drug absorption, metabolism, and renal excretion. The mechanisms of these interactions consist of increase in the concentration included several medications such as melatonin, midazolam, and amlodipine consuming after GT; these interactions can be toxic.

Additionally, it has been reported that serum levels of several drugs such as nadolol, digoxin, amoxicillin, and clozapine are decreased and their efficacy are reduced when they simultaneously administer with GT.