This becomes pertinent if we consider that many people suffer from chronic metabolic diseases (including hypertension, hyperlipidemia, and cardiovascular diseases) and receive calcium channel antagonis therapy and HMG-CoA reductase inhibitors. Although the significance of interactions between drugs is widely appreciated, little attention has been given to interactions between drugs and nutrients. The pungencyof red pepper is derived from a group of compounds called capsaicinoids, which possess an array of biological properties and give it its spicy flavor. Flavonoids can either inhibit or induce human CYP enzymes depending on their structure, concentration, or experimental conditions [176]. where possible, Avoid large quantities (more than 1.2 litres daily) of grapefruit Without knowing the medications a person is taking, I can’t speak to specifics. CYP enzymes combined with drug transport proteins constitute the first-pass effect of orally administered drugs [33]. Grapefruit juice interacts with most calcium channel blockers and the interaction was originally discovered by accident when researchers were looking at the effects of alcohol on felodipine absorption. Given the circumstances outlined above, there is no doubt of the overall relevance of drug transport for clinical pharmacokinetics. reported that OATP-B-mediated uptake of glibenclamide as well as estrone-3-sulfate was significantly inhibited by 5% orange juice [53]. 3, Adapted from New Zealand Formulary - Interactions. A number of foods can interact with medication and impact their efficacy or cause side effects. Lycopene has also been shown to slightly reduce the induction of ethoxyresorufin-O-deethylase activity by 20% by DMBA in MCF-7 cells [138]. Food-drug interactions can result in two main clinical effects: the decreased bioavailability of a drug, which predisposes to treatment failure, or an increased bioavailability, which increases the risk of adverse events and may even precipitate toxicities (See Figure 1) [4, 10,11]. Black raspberries (Rubus coreanus) have been called the “king of berries” for their superior health benefits, whereas black mulberry (Morus nigra) is most commonly used for its antioxidants properties and for its high bioactive content of phenolics, anthocyanins, and gallic acid. Avocado (Persea americana) is a good source of bioactive compounds such as monounsaturated fatty acids and sterols [144]. Additional reasons for concern regarding mega flavonoid supplements include potential flavonoid-drug interactions, since flavonoids have been shown to both induce and inhibit drug-metabolizing enzymes [38, 39]. Flavonoids have been known as plant pigments for over a century and belong to a vast group of phenolic compounds that are widely distributed in all foods of plant origin. On the other hand, Imaizumi et al. Drug–fruit/vegetable interaction and effects on bioavailability of drugs. The mechanism behind this interaction might be the inhibition by cranberry flavonoids of CYP3A4 and/or CYP2C9 enzymes, which are responsible for warfarin metabolism [31,82]. Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters, Drug Discovery, Hany A. El-Shemy, IntechOpen, DOI: 10.5772/48283. These findings suggest that apple might interact with OATP substrates (e.g., estrone-3-sulfate, deltorphin II, fexofenadine, vasopressin, and rosuvastatin). Home ► As a result of this, interaction can be increased or decreased plasma concentrations of a drug that can lead to the presence of adverse … Statins. The interaction of flavonoids with CYP3A4, the predominant human hepatic and intestinal CYP responsible for metabolizing 50% of therapeutic agents as well as the activation of some carcinogens, is of particular interest [177]. Papaya is prized worldwide for its flavor and nutritional properties. Although this can lead to alterations in the systemic elimination kinetics of drugs metabolized by these enzymes, the magnitude of the change is generally small [8, 40]. Fruits associated with medicine interactions include orange, pomelo, Open Access is an initiative that aims to make scientific research freely available to all. Little is currently known about the in vivo effects these compounds have on the bioavailability of xenobiotics the clearance and/or tissue distribution of which is determined by active transport and biotransformation. Moreover, alterations … However, generally speaking, when we have an approved vaccine it should not have interactions with other medications. It has also been shown that cranberry juice inhibits diclofenac metabolism in human liver microsomes, but this has not been demonstrated clinically in human subjects [83]. While part of a balanced diet, grapefruit and some other citrus fruits can have serious interactions with certain medications. In animal studies, dietary freeze-dried broccoli was found to offer protection against several cancers [119]. The precipitant agent may modify the function of enzymes or transport mechanisms that are responsible for biotransformation. Our knowledge regarding the potential risk of nutrient-drug interactions is still limited. The oral administration of drugs to patients is convenient, practical, and preferred for many reasons. Antibiotics & dairy products. Given this magnitude of use and variability in individual nutritional status, dietary habits and food composition, there is a high potential for drug-nutrient interactions. Common foods, such as fruits and vegetables, contain a large variety of secondary metabolites known as phytochemicals (Tabla 1), many of which have been associated with health benefits [25]. Phase I reactions involve changes such as oxidation, reduction, and hydrolysis and are primarily mediated by the cytochrome P450 (CYP) family of enzymes. The beneficial effects of mango include anti-inflammatory and antimicrobial activities [90,91] Preliminary phytochemical screening revealed the presence of flavonoids, including quercetin and glycosylated xanthones such as mangiferin [92,93] Quercetin has been shown to possess antioxidant, antimicrobial, antitumor, antihypertensive, antiatherosclerosis, and anti-inflammatory properties [94]. Orange juice might reduce the intestinal absorption of substrates of OATP-B (e.g., digoxin, benzylpenicillin, and hormone conjugates), resulting in a decrease in concentration in the blood. Available from: Nutrient-drug interactions: examples with clinical relevance, Drug-food interaction in specific diets with high content of fruits and vegetables, Universidad Autónoma del Estado de Morelos, Facultad de Farmacia, Cuernavaca, México. Herbal medicines such as St. John's wort, garlic, piperine, ginseng, and gingko, which are freely available over the counter, have given rise to serious clinical interactions when co-administered with prescription medicines [42]. During the consumption of drugs with fruits or vegetables the ADME properties of drug (Absorption, Distribution, Metabolism and Excretion) can be modified by drug-phytochemical interaction. If we consider that CYP3A4 is responsible for the metabolism of more than 50% of clinical pharmaceuticals, all nutrient-drug interactions should be considered clinically relevant, in which case all clinical studies of drugs should include a food-drug interaction screening [43]. In fact, it can help reverse a condition or reduce the need for medication. Vegetables such as cabbage, celery, onion and parsley are known to have a high content of polyphenols. and patient factors make it difficult to predict whether a fruit or fruit Built by scientists, for scientists. Adding watercress juice to human liver cells induced the activity of CYP4501A and ethoxyresorufin-O-deethylase and NAD(P)H-quinone reductase [127]. If you’re wondering if the full-spectrum hemp oil interacts with your medications, the short answer is: probably. A vegetarian diet usually provides a low intake of saturated fat and cholesterol and a high intake of dietary fiber and many health-promoting phytochemicals. Please report any suspected adverse medicine reactions and interactions Therefore, the main reason for devoting a major review to nutrient-drug interactions is the enormous importance of fruits and vegetables used for their beneficial effects as nutrients and as components in folk medicine. For this reason, this fruit should be consumed with caution by patients taking medicines. As a consequence, there is an increased global consumer demand for fruits and vegetables, and some consumers purchase organic foods with the understanding that they are healthy. Perhaps the best-known example is grapefruit, which, along with pomegranate, can alter the way certain cholesterol medications work. Grapefruit juice intake has been found to decrease CYP3A4 mRNA activity through a post transcriptional activity, possibly by facilitating degradation of the enzyme [49]. Consequently, drug transporters in both the gut and the liver are important in determining oral drug disposition by controlling absorption and bioavailability [19]. It has been previously shown that consumption of a single 240 mL serving of Sevilla orange juice resulted in a 76% increase in felodipine exposure, comparable to what is observed after grapefruit juice consumption [11]. The irreversible inhibition of intestinal cytochrome P450 (CYP)3A4 enzymes by grapefruit juice is the most commonly identified mechanism mediating grapefruit drug interactions. Brief introduction to this section that descibes Open Access especially from an IntechOpen perspective, Want to get in touch? Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a fundamental component of Capsicum fruits. As a result, some caution may be required with its clinical use [52]. It is now well known that drug-food interactions might affect the pharmacokinetics of prescribed drugs when co-administered with food [24]. ► Fruit Interactions with Common Medicines, Prescriber Update 36(1): 4-5 One interesting characteristic of this interaction is that grapefruit juice does not need to be taken simultaneously with the medication in order to produce the interaction. Fruits and vegetables are known to be important components in a healthy diet, since they have low energy density and are sources of micronutrients, fiber, and other components with functional properties, called phytochemicals (See Figure 2). Seville oranges, pomelos and tangelos can have the same effect on drugs as grapefruit, so best to avoid them if you know your drug can interact with grapefruit. Grapes are one of the most valued conventional fruits worldwide. The long answer truly depends on what you’re taking and the dosage. Blood pressure medications are one example of drugs … Fruit juices contain a large number of phytochemicals that, in combination with certain drugs, can cause food–drug interactions that can be clinically significant and lead to adverse events. Patients may not recognize that otherwise healthy foods can have severe consequences when mixed with certain drugs. Inhibition of CYP enzymes, which are necessary for carcinogen activation, is a beneficial chemopreventive property of various flavonoids but may be a potential toxic property in flavonoid-drug interactions. Recent studies show that some of these phytochemicals are substrates and modulators of specific members of the superfamily of ABC transporting proteins [26]. An ethno-botanical survey showed that papaya is commonly used in traditional medicine for the treatment of various human diseases, including abdominal discomfort, pain, malaria, diabetes, obesity, infections, and oral drug poisoning [111,112]. The major furanocoumarin present in grapefruit is bergamottin, which demonstrated a time- and concentration-dependent inactivation of CYP enzymes in vitro [49]. The interaction of grapefruit with certain drugs was unintentionally … HeadquartersIntechOpen Limited5 Princes Gate Court,London, SW7 2QJ,UNITED KINGDOM. Studies performed on human recombinant CYP1 showed that lycopene inhibits CYP1A1 and CYP1B1. Early studies have reported that capsaicin strongly inhibited the constitutive enzymes CYP 2A2, 3A1, 2C11, 2B1, 2B2 and 2C6 [154]. Two major capsaicinoids, dihydrocapsaicin (DHC) and capsaicin (CAP) are responsible for up to 90% of the total pungency of pepper fruits. Meds that interact with citrus fruits. These are glucuronides and acylated di-and triglycosides of methylated and methylene dioxide derivatives of 6-oxygenated flavonols [131]. not been investigated. As a result of this interaction can be increased or decreased plasma concentrations of a drug which can lead to the presence of adverse events or treatment failure. There is also a report indicating that capsaicin is a substrate of CYP1A2 [155]. Takanaga and others showed that 3,3′,4′,5,6,7,8-heptamethoxyflavon and tangeretin were the major P-gp inhibitors present in orange juice and showed that another component, nobiletin, was also a P-gp inhibitor [55]. Carrots induce phenolsulfotransferase activity [123] and decrease CYP1A2 activity [122]. Watercress juice can increase the enzymes SOD and GPX in blood cells in vitro and in vivo [128]. The interplay between drug metabolizing enzymes and transporters is one of the confounding factors that have been recently shown to contribute to potential complex drug interactions [14]. Bioassay models for studying drug-phytochemical interaction. Such inhibition of the enteric CYP3A activity by a single exposure to pomegranate juice appears to last for approximately 3 days [56]. medicine metabolism (www.medsafe.govt.nz/profs/PUArticles/P-glycoproteinSept2011.htm). Drug Interactions. In industrialized countries, fruits and vegetables tend have been subjected to some sort of processing (e.g., refrigeration, acidification, fermentation, and thermal, high pressure, chemical, or physical processing) that might have an effect on the bioactive compound. In addition, polyphenols have been shown to interact with ABC drug transporters involved in drug resistance and drug absorption, distribution and excretion [32]. Grapefruit interferes with your body's metabolism of atorvastatin (Lipitor), simvastatin (Zocor) and lovastatin (Altoprev, Mevacor), so your intended dose might not be accurate. The CYP enzymes involved in drug metabolism in humans are expressed predominantly in the liver. How? product will lead to a medicine interaction. Help us write another book on this subject and reach those readers. Several epidemiologic, clinical, and experimental studies have established that certain types of diet may have beneficial effects on health. Cranberries are a fruit chock full of vitamin C, and some people drink cranberry juice to help prevent urinary tract infections (UTI). We share our knowledge and peer-reveiwed research papers with libraries, scientific and engineering societies, and also work with corporate R&D departments and government entities. Fruit juices contain a large number of phytochemicals that, in combination with certain drugs, can cause food–drug interactions that can be clinically significant and lead to adverse events. Dairy products such as milk, yogurt, and cheese can interfere with … However, there is a relatively short list of documented fruit-drug or vegetable-drug interactions, necessitating further and extensive clinical evaluation. consuming fruit. These sandwiches contain beef, cheese, and sausage. It was demonstrated that tangeretin inhibits P450 1A2 and P450 3A4 activity in human liver microsomes [73]. According to current data, watercress and isothiocyanate may have clinical repercussions by inducing changes in the bioavailability of some drugs. Grapefruit is not the only citrus fruit that can interact with medications. It has also been shown that watercress is a bifunctional agent with the ability to induce both phase I (CYP450) and II enzymes. However, they are also present in the large and small intestine, lungs and brain [34]. The simultaneous administration of flavonoids present in fruits or vegetables and clinically used drugs may cause flavonoid-drug interactions by modulating the pharmacokinetics of certain drugs, which results in an increase in their toxicity or a decline in their therapeutic effect, depending on the flavonoid structure [178]. Fruit of concern include orange, pomelo, pomegranate, cranberry, Hidaka et al. Drug interaction with any of these substances may enhance or decrease the effect of Amlodipine. The functional consequences of such an interaction are reflected in a significant reduction in the oral bioavailability of fexofenadine, possibly by preferential direct inhibition of intestinal OATP activity. © 2013 The Author(s). Several studies have directly and indirectly shown that dietary polyphenols can modulate phase II metabolism [161]. Drug absorption across the gastrointestinal tract is highly dependent on affinity for membrane transporters as well as lipophilicity [17]. Even the simple, delicious cranberry can have drug interactions. Prescription medications are generally safe and effective, but many of them can interact poorly with certain foods. The general conclusion after an analysis of available data on CYP-flavonoid interactions is that flavonoids possessing hydroxyl groups inhibit CYP activity, whereas those lacking hydroxyl groups may induce the metabolizing enzyme [175]. Equal attention must be paid to food-drug interactions (Figure 2). Type II interactions affect absorption. 1 Variability in fruit strains, environmental conditions, processing procedures, Licensee IntechOpen. By Lourdes Rodríguez-Fragoso and Jorge Reyes-Esparza, Submitted: November 18th 2011Reviewed: April 19th 2012Published: January 23rd 2013, *Address all correspondence to: mrodriguezf@uaem.mx. Lourdes Rodríguez-Fragoso and Jorge Reyes-Esparza (January 23rd 2013). The fruit may up blood levels of some medicines, like statins. On the other hand, it has also been reported that apple juice and its constituents can interact with members of the OATP transporter family (OATP-1, OATP-3 and NTCP) by reducing their activities in vitro. Presumably, the mechanism of this effect is similar to that of grapefruit juice-mediated interactions, because Sevilla orange contains significant concentrations of flavonoids, mainly bergamottin and 6´,7´-dihydroxybergamottin [69]. Drug-fruit/vegetable interaction and effects on bioavailability of drugs. Berries have been shown to have a positive impact on several chronic conditions including obesity, cancer, and cardiovascular and neurodegenerative diseases [102-104]. Resveratrol is an electron-rich molecule with two aromatic benzene rings linked by an ethylene bridge. If you eat grapefruit or drink grapefruit juice at all, be aware that the fruit interacts with several... Kale. How Grapefruit Juice Can Interfere With Medications. Aug. 19, 2008 -- Grapefruit, orange, and apple juices block drugs commonly used to treat infections, allergy, transplant rejection, cancer, and high blood pressure. The functional consequence of such an interaction was a significant reduction in the oral bioavailability of fexofenadine in human plasma levels, possibly by preferential direct inhibition of intestinal OATP activity [29]. Nowadays, a large amount of work has identified and characterized intestinal and hepatic transporters in regards to tissue expression profiles, regulation, mechanisms of transport, substrate and inhibitor profiles, species differences, and genetic polymorphisms. Healthcare providers, such as physicians, pharmacists, nurses, and dietitians, have to be aware of important food-drug interactions in order to optimize the therapeutic efficacy of prescribed and over-the-counter drugs. Quinolone antibiotics like Cipro (ciprofloxacin), levofloxacin and Avelox … Lycopene is the most important carotenoid present in tomatoes and tomato products, and their dietary intake has been linked to a decreased risk of chronic illnesses such as cancer and cardiovascular disease [136,137]. Here, we review some of the most widely consumed fruits and vegetables to inform healthcare providers of possible nutrient-drug interactions and their potential clinical significance. OATP-A, however, is predominantly expressed in the brain, but not in the intestine. During the consumption of drugs with fruits or vegetables, the ADME properties of drug (absorption, distribution, metabolism, and excretion) can be modified by drug–phytochemical interaction. It has been have reported that pomegranate juice influenced the pharmacokinetics of carbamazepine in rats by inhibiting enteric CYP3A activity. Admittedly, vegetable and fruit variety may also vary widely according to location [168]. Examples of drugs affected by grapefruit or its components include: calcium channel antagonists such as felodipine, nisoldipine, amlodipines, verapamil, and diltiazem [57]; central nervous system modulators, including diazepam, triazolam, midazolam, alprazolam, carbamazepine, buspurone and sertraline [58]; HMG-CoA reductase inhibitors, such as simvastatin, lovastatin, atorvastatin, and pravastatin [59]; immunosuppressants such as cyclosporine [60]; anti-virals such as saquinavir [61]; a phosphodiesterases-5 inhibitor such as sildenafil [62]; antihistamines, including as terfenadine and fexofenadine [63]; antiarhythmics such as amiodarone [62]; and antibiotics such as eritromicine [64]. , grape, apple, and puts the academic needs of the better established interactions with other medications as.... Human hepatic microsomes are inhibited by 5 % orange juice has also been observed with certain drugs was unintentionally grapefruit. 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