Food-drug Interactions Research Articles

Are all types of food safe with prescribed medicines? A study of potential food-drug interactions in patients attending Medicine OPD

Background: In this era of polypharmacy in chronic disease such as hypertension and diabetes, there are more chances of food-drug interactions. Significant food-drug interaction can cause failure of drug therapy or serious adverse effect to patient. Objective: To assess the potential food-drug interaction (pFDI) patients attending Medicine outpatient department (OPD) at a tertiary-care teaching hospital in Valsad, Gujarat, India. Materials and Methods: The prescriptions of patients attending Medicine OPD were analyzed for demography of patients and pFDI. Freely available Drug Interaction Checker on Internet was used to analyze pFDI. Interactions were classified major, moderate, and minor according to severity and by their mechanism as pharmacokinetic or pharmacodynamic types. Statistical analysis was done using appropriate Microsoft Excel. Result: A total of 300 prescriptions were collected from study site; from those, 253 prescriptions were included in our study. From these, 128 (50.59%) were from male patients and 125 (49.41%) from female patients. The number of drugs prescribed to the individual patient was 4.4 ± 1.48 (range, 2–12). The frequency of pFDI per patient was 0.97 ± 1.03 (range, 0–5). The number of pFDI increased with increase in the age of patients and the number of drugs prescribed. Among 253 patients, 149 (59%) patients showed at least one pFDI, and 104 (41%) patients did not show pFDI. Among 243 pFDIs, 26 (10.69%) were pharmacodynamic and 217 (89.30%) pharmacokinetic types. In this study, four (1.65%) interactions were major, while those with moderate and minor severities accounted for 173 (71.19%) and 66 (27.16%), respectively. Conclusion: In this study, it was found that most of pFDIs were pharmacokinetic in nature and of moderate severity. Physician should be aware of significant food-drug interaction with food consumed by local community.

Molecular localization and characterization of multiple binding sites of organic anion transporting polypeptide 2B1 (OATP2B1) as the mechanism for substrate and modulator dependent drug–drug interaction

Schematic model of the relationship and locations of putative binding sites of substrates and modulators in OATP2B1. Drug–drug interaction and drug–food interaction on OATP2B1 can be predicted by clarification of multiple binding sites.

Does a contraindication yield therapeutic activity?

Many drug molecules are contraindicated since it is harmful to the patient. These drug products act by producing any of the adverse drug reaction or side effects. This can happen not only with the drug molecule but also with dietary supplements that we call it as drug-food interaction. These interactions either enhance or decrease the drug levels in the body; thereby the drug may reach either the toxic stage or may not reach minimum concentration to produce the activity respectively. The principle of this contraindication is taken into consideration to enhance the bioavailability of lower bioavailable drug substances at a lower dose. The presystemic metabolism causes lower bioavailability of many drugs. With this type of drug molecules, the drug metabolising enzyme inhibitor substances are contraindicated. But the current study shows even though these are contraindicated; by administering the lower dose of the principle drug molecule and enzyme inhibitor together can enhance the bioavailability and can yield therapeutic activity without producing the toxic reaction.

レポーター遺伝子導入培養細胞を用いた健康食品によるCYP1A1/1A2誘導の網羅的評価

Recently, the intake of health foods has been steadily increasing, in order to preserve health, and to cure and/or protect from diseases. At the same time, a noticeable increase in adverse drug reactions caused by health foods has been reported. Cytochrome P450 is a family of enzymes responsible for the metabolism of a wide variety of xenobiotics, including therapeutic agents and environmental chemicals. In this study, we investigated the effect of health foods on metabolism by using cultured cells expressing CYP1A1 and CYP1A2 gene reporters. Expressed CYP1A1 and CYP1A2 catalyze not only detoxification and activation of carcinogens but also the metabolism of drugs such as phenacetin and theophylline. Among 175 health food extracts examined, 20 extracts increased the CYP1A1 gene reporter activity, especially extracts of St John's wort, turmeric-containing health foods, garlic-containing health foods, and vitamin/mineral-containing health foods. In addition, these health foods increased CYP1A1 and CYP1A2 mRNA expression in HepG2 cells and human cryopreserved hepatocytes. These results indicate that health food-drug interactions might be mediated through CYP1A2 activities.

Natural polyphenols: Influence on membrane transporters.

Accumulated evidence has focused on the use of natural polyphenolic compounds as nutraceuticals since they showed a wide range of bioactivities and exhibited protection against variety of age-related disorders. Polyphenols have variable potencies to interact, and hence alter the activities of various transporter proteins, many of them classified as anion transporting polypeptide-binding cassette transporters like multidrug resistance protein and p-glycoprotein. Some of the efflux transporters are, generally, linked with anticancer and antiviral drug resistance; in this context, polyphenols may be beneficial in modulating drug resistance by increasing the efficacy of anticancer and antiviral drugs. In addition, these effects were implicated to explain the influence of dietary polyphenols on drug efficacy as result of food-drug interactions. However, limited data are available about the influence of these components on uptake transporters. Therefore, the objective of this article is to review the potential efficacies of polyphenols in modulating the functional integrity of uptake transporter proteins, including those terminated the effect of neurotransmitters, and their possible influence in neuropharmacology.

Know-how and Know-why Nutrients may be Less Bioaccessible and Less Bioavailable due to Proton Pump Inhibitor - Food Interactions and Incompatibilities Involving Metal-Aquo Complexes

Background: Proton pump inhibitors change gastric pH from around 2.0 to 2.5 to more than 4.0 for up to 16 hours per day and suppress gastric function widely. Risk factors assigned to long-term inhibition of gastric acidity arise from cleavage-resistance of peptides and glycosides, mucosal degeneration and leak, loss of bactericidal action, and modification of absorption kinetics of medicines and nutrients. This article aims to contribute to wisely use of proton pump inhibitors and to recommend nutritional options. Methods: A systematic online literature research was performed on usual platforms. Recommendations rely on a multidisciplinary focus group assessment. Explanations arising from the retrieved references were tested for consistency by titration of iron solution from acidic to basic pH while observing precipitation. Results and discussion: Literature describes bacterial overgrowth, community and hospital-acquired pneumonia, childhood asthma related to PPI treatments of mothers in pregnancy, sensitization to food allergens in the elderly and in pregnant women (as progesterone slows down gastric emptying), deterioration of intolerances, and various diseases such as celiac and inflammatory diseases. In addition to pathologies, bioavailability of medicines may be modified dramatically. For micronutrients, aquo-complexes of metal ions revealed to be a neglected issue in research of food-drug interactions arising from PPI treatments. To prevent these complications, a focus group from a clinical support team recommends intermittent and ondemand strategies, alternative antacids, avoidance of high allergenic food, buffering, pepsin replacement, stimulation of digestion and peristalsis, and physical activity, and medicines review and reconciliation. Conclusion: Proton pump inhibitor safety profiles are troubled by risk factors arising from inappropriate longterm use. Drugs’ bioavailability may increase as a result of mucosal hyperpermeability, or decrease as a result of altered dissociation. Care should be given to substrates with pKa<4.5 as well as to micronutrient supply. At least children and pregnant women should prefer alternative antacids.

Medicine Prescribing Preference and Patient Adherence: Perspectives of Indian Medical Practitioners

Background: Indian Pharmaceutical market is well known for generic medicines and the government also promotes them due to their affordability. These medicines are manufactured by big, medium and small size companies and their quality are generally checked by analytical methods though real evaluation of medicines can only be ensure by medical practitioners (MP) who prescribe them which is based on therapeutic responses and adverse effects they notice. Perspectives of MP about prescribed medicines, price, therapeutic responses, adverse effects and their awareness about different interactions are valuable and may initiate for better treatment and healthcare system. Method: A survey of 111 MP was conducted on one to one basis in a form of questionnaire. Frequency, percentage, Chi square and Friedman test were applied to check the association and rank between different attributes. Results: Branded generic is preferred over innovator branded generic and generic by 63.1% of MP because 64.9% believe it has good therapeutic response and 68% experienced it has mild adverse effects while only 0.9% assumed it has high adverse effect. Only generic considered as highly affordable but it is prescribed moderately or less preferably. Self study is the main source of medicine information for MP but all of them do not have excellent or good drug-drug and drug-food interactions knowledge. Patients only adhere to their 70-90%, 40-60% and 10-30% instructions according to 33.3%, 45.9% and 16.2% MP respectively. Conclusion: There is excessive demand of high quality generic products for better safety of patients irrespective of its affordability. Efficient training programs are required for some MP to improve average interactions knowledge. Patient non-adherence needs prior attention by implementing patient involvement in treatment decision and educating them. Key words: Doctor, Generic, Healthcare, Medicine, Medical practitioner, Patient adherence.

Are We Getting the Best Return on Investment From Clinical Drug-Drug Interaction Studies?

Are We Getting the Best Return on Investment From Clinical Drug-Drug Interaction Studies?

Association of flavonoid-rich foods and statins in the management of hypercholesterolemia: a dangerous or helpful combination?

Statins and dietary modifications are the cornerstone of hypercholesterolemia management. Although it is well known that possible adverse effect of statins can occur due to drug-drug interactions, food-drug interactions are a commonly overlooked aspect. In particular, flavonoids could interfere with statins' bioavailability through different mechanisms, such as competition with cytochrome P450 (CYP) enzymes, esterases, uridine diphosphate glucuronosyltransferases and transporters (P-glycoprotein, multi-drug resistance-associated proteins, organic anion transporting polypeptides, breast cancer-resistance protein and monocarboxylate transporters). Transporters are characterized by low substrate specificity and flavonoid- rich foods could interfere with the bioavailability of all statins at this level. On the other hand, in addition to being substrates of drug metabolism/ transport systems, flavonoids are also able to modulate gene expression of enzymes and transporters. Therefore, long-term transcriptional induction may increase the clearance of statins, despite flavonoids act as competitive inhibitors after bolus consumption. In humans, major interactions were observed between grapefruit juice and statins that are substrates of P-glycoprotein/CYP3A, but other fruit juices also affect the bioavailability of statins that are not metabolised by CYP. Even if flavonoids could play a role in the prevention of hypercholesterolemia, the question whether there's a helpful or dangerous association between flavonoid-rich foods and statins, due to the interactions between flavonoid-rich foods and statins and the potential associated adverse effects of statins, remain unanswered. Therefore, the anamnesis of patients must include detailed information about their eating habits and the present review suggests monitoring and reporting any possible case of interaction between a prescribed statin and food.

The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR.

Objective:The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population.Methods:This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal’s algorithm. Awareness was evaluated based on the patients’ knowledge of warfarin’s affect and food–drug interactions.Results:The mean TTR of patients was 49.52±22.93%. The patients with hypertension (55.3%), coronary artery disease (23.2%), congestive heart failure (24.5%), or smoking habit (20.8%) had significantly lower TTR levels than the others. Of the total number of patients, 42.6% had a mechanical valve, 38.4% had non-valvular atrial fibrillation (AF), and 19% had other indications for warfarin. Patients with other indications had lower TTR levels than those with mechanical valve and non-valvular AF (p=0.018). Warfarin awareness decreased in higher age groups. The knowledge of warfarin’s food–drug interactions was 55%. People with higher warfarin awareness had higher TTR levels. Patients with ≤8 INR monitoring/year had lower TTR levels (46.4±25.3 vs. 51.1±21.3, respectively, p<0.001) and lower awareness (44.6% vs. 60.6%, p<0.001) than patients with ≥8 INR monitoring/year. In this study, 20.1% of the patients had a bleeding event (major bleeding 15.8%, minor bleeding 84.2%) within a year.Conclusion:Both the mean TTR ratios and awareness of the Turkish population on warfarin therapy were found to be low. It was thought that low TTR levels of the Turkish population may be caused by the low awareness of warfarin, warfarin’s food–drug interactions, and high rates of concomitant diseases. (Anatol J Cardiol 2016; 16: 595-600)

Adverse food–drug interactions

Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

Advances in Inhibitors of FXa.

Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for people's morbidity and mortality and have severely affected the people's quality of life all over the world. According to WHO statistics, an average of 17 million people are killed by the thromboembolic diseases each year globally. Therefore, the prevention and treatment of thromboembolic diseases have received widespread attention in recent years. Based on thrombotic mechanism, anti-thrombotic drugs are mainly divided into anticoagulants, antiplatelet agents and direct thrombolytic drugs. In particular, anticoagulants such as vitamin K antagonists (VKAs), unfractionated heparin (UFH), and low-molecular-weight heparins (LMWHs) have become the main therapies for pre-treatment of thromboembolic disorders. However, the limitations of traditional anticoagulants such as slow onset of action, dose-adjusted requirement, drug-drug and drug-food interactions have restricted their improvement in the clinical treatment. The mechanism of the thromboembolic disorders has indicated that coagulation factor Xa (fXa) plays a pivotal role in the blood coagulation cascade. Thus, selective inhibition of fXa by diminishing the amplified generation of thrombin without affecting the pre-existing thrombin levels can provide better antithrombotic effect, thereby causing less impairment of primary hemostasis. In this paper, we mainly introduce the recent advances of fXa inhibitors, with focus on their biological activity and structure-activity relationship (SAR) information. In particular, the inspirations from the structures of the fXa inhibitors and their future direction are highlighted.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine

Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissolution characteristics of the API. Therefore, a BCS biowaiver-based approval of nifedipine containing IR oral dosage forms cannot be recommended for reformulated/new multisource drug products or for major scale-up and postapproval changes to the existing drug products.

Identify practice gaps in medication education through surveys to patients and physicians.

BackgroundEffective communication and education formats between health care providers and patients about medication use are associated with patients’ satisfaction, recall of information, and eventually their health status. Limited research exists on physician-delivered education interventions, as well as on whether the current content of medication education and delivery formats satisfies the needs of both patients and physicians. Our objective was to identify the practice gaps regarding medication education content and delivery.MethodsSeparate surveys were obtained from ambulatory care patients presenting to the outpatient pharmacy for medication pickups, and physicians working at the hospital clinics.ResultsA total of 108 patients completed the patient survey, and 116 hospital clinic physicians completed the physician survey. Female patients had a higher degree of concern regarding medication information compared with male patients (4.04±0.65 versus 3.58±0.66, P=0.001). Physicians were less likely to educate patients regarding their medications’ on drug–drug interactions (24.3%), drug–food interactions (24.3%), and what to do about their prescriptions if an adverse reaction is experienced (24.3%) during physician–patient encounters. Patients’ most desired education format was physician counseling (82.4%) and the second most desired education format was pharmacist counseling (50.9%). Medication device demonstration (7.0%) was the least used educational format delivered to patients by physicians, and patients would like to see an increased education delivery format through medication device demonstration (Method desired [MD] – Method received [MR] =12.0%). Patients would like to see expanded roles of patient focused handout (MD-MR=22.2%), telephone consultation (21.2%), pharmacist counseling (12.9%), the use of medication database embedded within the hospital information system (12.2%) and device demonstration (12.0%).ConclusionThis study illustrates that there are practice gaps in current medication education both in terms of content and delivery format. The study provided valuable information in designing and implementing future education activities that are drivers of good medication use and adherence.

Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.Trial RegistrationClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780

Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities.

The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, unpredictable pharmacokinetics and pharmacodynamics, and the potential for significant drug-drug and food-drug interactions. The DOACs were developed to overcome these limitations while maintaining or surpassing warfarin’s efficacy and safety profiles. All four DOACs have similar or better efficacy and safety compared with warfarin and are therefore valuable alternatives for the prevention of stroke and SEE in patients with nonvalvular AF. Understanding the subtle differences in the DOACs’ pharmacology, phase 3 study designs, and trial outcomes will allow for a more tailored approach in selecting the right oral anticoagulant for each patient.

Toxicokinetics of lefetamine and derived diphenylethylamine designer drugs-Contribution of human cytochrome P450 isozymes to their main phase I metabolic steps.

Lefetamine was first marketed in the 1940s as an opioid analgesic. Since withdrawal symptoms were observed during treatment, it became a controlled substance. Its N-ethyl and N-iso-propyl derivatives appeared on the illicit drug market in 2008. Metabolism studies for lefetamine and these derivatives showed that N-dealkylation was the initial step for all three substances in rats. The involvement of the ten most important human cytochrome P450 (CYP) isozymes in this N-dealkylation should be studied now. Studies showed the involvement of CYP1A2, CYP2B6, CYP2C19, and CYP3A4 in N-dealkylation of all three compounds and additionally CYP2D6 for lefetamine and NEDPA. All kinetic profiles followed classic Michaelis-Menten kinetics. Using the relative activity factor approach, the following net clearances were calculated: for lefetamine 8% by CYP1A2, 72% by CYP2B6, 2% by CYP2C19, 1% by CYP2D6, and 17% by CYP3A4; for NEDPA 27% by CYP1A2, 30% by CYP2B6, 23% by CYP2C19, 4% by CYP2D6, and 17% by CYP3A4; for NPDPA 18% by CYP1A2, 24% by CYP2B6, 28% by CYP2C19, and 30% by CYP3A4. In addition, calculated data were compared to chemical inhibition studies in human liver microsomes. Due to the involvement of at least four enzymes in the initial metabolic steps, the risk of CYP-related drug-drug or drug-food interactions should be low.

Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review.

The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food–drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food–drug interactions within paediatric populations.

Rivaroxaban for the treatment and prevention of thromboembolic disease.

A number of direct oral anticoagulants are now available and offer alternative strategies for anticoagulation therapy. Rivaroxaban, a direct oral Factor Xa inhibitor, is approved for use across several thromboembolic indications. This article aims to provide an overview of the key pharmacological characteristics of rivaroxaban and the rationale and evidence for the use of different dose regimens across its licenced indications, and offer practical guidance to healthcare professionals on responsible use. References were sourced via PubMed searches using the search string (rivaroxaban AND (pharmacokinetics OR pharmacodynamics OR (clinical studies) OR (drug interaction)) NOT review NOT (children OR pediatrics OR paediatrics OR adolescent)). Rivaroxaban exhibits predictable pharmacokinetics and pharmacodynamics, and thus does not require routine coagulation monitoring, unlike vitamin K antagonists (e.g. warfarin). Rivaroxaban also has a lower potential for drug-drug and food-drug interactions compared with warfarin; however, co-administration with strong inhibitors of both cytochrome P450 3A4 and P-glycoprotein is not recommended. The data indicate that dose adjustment is not necessary for age, gender or body weight. The dosing regimens of rivaroxaban vary depending on the indication, and phase III studies have demonstrated a favourable benefit-risk profile of rivaroxaban compared with traditional standard of care. Rivaroxaban may offer an anticoagulant option that could simplify and improve the management of patients with thromboembolic disorders.

Green Tea and Bone Marrow Transplantation: From Antioxidant Activity to Enzymatic and Multidrug-resistance Modulation

Epigallocatechin-3-gallate (EGCG), the main flavonoid of green tea (GT), could play an active role in the prevention of oxidative-stress-related diseases, such as hematologic malignancies. Some effects of EGCG are not imputable to antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma non-enzymatic antioxidant capacity (NEAC). However, hyperuricemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, both before and after bone marrow transplantation (BMT). Besides this, food–drug interactions could be associated with GT consumption and could have clinical implications.The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways were discussed, with particular reference to the potential role of GT and EGCG in BMT. Moreover, on reviewing data on NEAC, isoprostanes, uric acid, and various enzymes from human studies on GT, its extract, or EGCG, an increase in NEAC, without effect on isoprostanes, and contrasting results on UA and enzymes were observed.Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems.