Evidence is emerging that specific combinations of phytochemicals may be far more effective in protecting against some diseases than isolated compounds (Table 1 and 2). Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. These include elderly patients, patients with cancer and/ or malnutrition, gastrointestinal tract dysfunctions, acquired immunodeficiency syndrome and chronic diseases that require the use of multiple drugs, as well as those receiving enteral nutrition or transplants. While epidemiological and preclinical data support the nutritional benefits of spinach and the safety of its consumption there are no publications about its effects on drug metabolizing enzymes and drug transporters. Indeed, in vitro and preclinical data in rats suggest that a variety of foodstuffs [27,28], including herbal teas [29,30] and vegetables and herbs [31,32] can modulate the activity of drug transporters. Uesawa and Mohri have demonstrated that nifedipine metabolism in rat intestinal and human hepatic microsomes are inhibited by preincubation with cranberry juice. American cranberry is a fruit used as a prophylactic agent against urinary tract infections [79]. As a result of these factors, vegetarians typically have a lower body mass index, low-density lipoprotein cholesterol levels, and lower blood pressure; a reduced ischemic heart disease death rate; and decreased incidence of hypertension, stroke, type 2 diabetes, and certain cancers that are more common among non-vegetarians [167]. Those findings have been corroborated by a clinical study that shows that FPP use can induce a significant decrease in plasma sugar levels in both healthy subjects and type 2 diabetic patients [115]. Modifying the intake of specific foods and/or their bioactive components seems to be a prudent, noninvasive, and cost-effective strategy for preventing some diseases in people who appear to be “healthy” [3]. Type II interactions affect absorption. In light of the wide ranging effects of grapefruit juice on the pharmacokinetics of various drugs, physicians need to be aware of these interactions and should make an attempt to warn and educate patients regarding the potential consequences of concomitant ingestion of these agents. When CYP3A4 is inhibited, it can result in increased concentrations of medicines Flavonoids can either inhibit or induce human CYP enzymes depending on their structure, concentration, or experimental conditions [176]. 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. CYP2C9, may be inhibited by pomegranate and cranberry juices.1. Given the circumstances outlined above, there is no doubt of the overall relevance of drug transport for clinical pharmacokinetics. Login to your personal dashboard for more detailed statistics on your publications. CYP enzymes combined with drug transport proteins constitute the first-pass effect of orally administered drugs [33]. to the Centre for Adverse Reactions Monitoring (CARM). Apple and its products contain high amounts of polyphenols, which show diverse biological activities and may contribute to beneficial health effects such as protecting the intestine against inflammation due to chronic inflammatory bowel diseases [108, 109]. Several clinical studies on the interactions of grapefruit juice and drugs have been conducted with impressive results. Therefore, patients consuming papaya and taking antidiabetic therapy could suffer from potential drug-food interaction. In vitro models and animal models have shown that many of these agents influence drug metabolizing enzymes and drug transporters. They cause either an increase or decrease in the oral bioavailability of a drug. Please report any suspected adverse medicine reactions and interactions The SLCO family is made up of the organic anion transporting polypeptides (OATP) [22]. By Jolanta Natalia Latosińska and Magdalena Latosińska. 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]. However, several reports have examined the effects of plant foods and herbal medicines on drug bioavailability. 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]. Inhibition of CYP activities by flavonoids has been extensively studied because of their potential use as blocking agents during the initial stage of carcinogenesis [174]. Cranberry juice may increase the bioavailability of CYP3A4 substrates (e.g., calcium antagonists or calcineurin inhibitors) as was discussed [61]. Broccoli (Brassica oleracea var. Lycopene has also been shown to slightly reduce the induction of ethoxyresorufin-O-deethylase activity by 20% by DMBA in MCF-7 cells [138]. On the other hand, Satoh et al. have shown that pepper ingestion reduces oral salicylate bioavailability, a likely result of the gastrointestinal effects of capsaicin [158]. Orange juice has also been shown to exert inhibitory effects on P-glycoprotein (P-gp)-mediated drug efflux. Pomegranate, for example, shares certain properties with grapefruit, suggesting that both could modify the bioavailability of drugs [55,56]. Statins. Opt for other fruits like kiwi fruit, blood oranges and other fresh produce instead, suggests Kennedy. 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. If you are taking any medications, check the drug safety information carefully for any food interactions. These results suggest that other vegetables with a high content of isothiocyanates, such as those of the family Cruciferae (e.g., cabbage, cauliflower, Brussels sprouts, watercress, broccoli, and kale) and the genus Raphanus (radishes and daikons) may have pharmacological and toxicological implications in humans. Most of the fruits and vegetables examined in this review contain a similar phytochemical mix to that of grapefruit juice. How fruit juice interacts CYP3A-mediated aromatic hydroxylation and epoxidation of resveratrol are possible, resulting in a reactive p-benzoquinone methide metabolite which is capable of binding covalently to CYP3A4, leading to inactivation and potential drug interactions. While dietary polyphenols may be beneficial in the correct amount, but too much may not be good and combining them with medication should be avoided. 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. Such adversities have spurred various pre-clinical and in vitro investigations on a series of other herbal remedies, with their clinical relevance yet to be established. As will be discussed in this chapter, potential problems occur when patients taking medicines regularly also consume certain fruits or vegetables. March 2015, Medicine interactions with grapefruit juice are well-known. The interaction between grapefruit juice and drugs has been potentially ascribed to a number of constituents [27]. with medicine metabolism. Adding watercress juice to human liver cells induced the activity of CYP4501A and ethoxyresorufin-O-deethylase and NAD(P)H-quinone reductase [127]. Acting alone or in concert with each other, they can affect the pharmacokinetics and pharmacodynamics of a drug. Variability in fruit strains, environmental conditions, processing procedures, These findings suggest that apple might interact with OATP substrates (e.g., estrone-3-sulfate, deltorphin II, fexofenadine, vasopressin, and rosuvastatin). These sandwiches contain beef, cheese, and sausage. About Its high isothiocyanate and flavonoid content demands additional research to evaluate possible nutrient-drug interactions. Papaya is prized worldwide for its flavor and nutritional properties. Due to their high content of fruits and vegetables, all these diets contain a large proportion of antioxidant vitamins, flavonoids, and polyphenols [169]. Pomegranate is a rich source of several chemicals such as pectin, tannins, flavonoids, and anthocyanins. Fruits associated with medicine interactions include orange, pomelo, pomegranate, cranberry, grape, apple, and grapefruit. Read more on risky herb-drug combos and avoiding lethal drug combos (free), and use our Interaction Checker (subscribers only) to find out which herbs and supplements interact with your drugs. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. Their biological properties, however, have been largely attributed to high levels of various phenolic compounds, as well as the interactive synergies among their natural phytochemical components (e.g., ellagic acid, quercetin, gallic acid, anthocyanins, cyanidins, pelargonidins, catechins, kaempferol and salicylic acid). Carrots induce phenolsulfotransferase activity [123] and decrease CYP1A2 activity [122]. advertised as other flavours. 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. 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]. © 2013 The Author(s). The observed induction and inhibition of CYP enzymes by natural products in the presence of a prescribed drug has (among other reasons) led to the general acceptance that natural therapies can have adverse effects, contrary to popular beliefs in countries with active ethnomedicinal practices. Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters, Drug Discovery, Hany A. El-Shemy, IntechOpen, DOI: 10.5772/48283. have reported capsaicinoid-induced changes of glucose in rats. medicines, it is not a complete list. The irreversible inhibition of intestinal cytochrome P450 (CYP)3A4 enzymes by grapefruit juice is the most commonly identified mechanism mediating grapefruit drug interactions. Observed drug-phytochemical interactions, in addition to interactions among dietary micronutrients, indicate possibilities for improved therapeutic strategies. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Another group of compounds that has been detected in grapefruit juice are the furanocoumarins (psoralens), which are known to be mechanism-based inactivators of CYP450. juices or concentrates are frequently used as bases for fruit drinks, often Type I are ex vivo bioinactivations, which refer to interactions between the drug and the nutritional element or formulation through biochemical or physical reactions, such as hydrolysis, oxidation, neutralization, precipitation or complexation. But even healthy foods, including fruits and vegetables, can cause unintended and possibly dangerous interactions with certain medications. Tomatoes (Lycopersicon esculentum) and tomato-based products are a source of important nutrients and contain numerous phytochemicals, such as carotenoids, that may influence health (carotenoids such as phytofluene, phytoene, neurosporene, γ-carotene, and ζ-carotene) [133,134]. 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. 3, Adapted from New Zealand Formulary - Interactions. This diet, however, varies across at least 16 countries bordering the Mediterranean Sea. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. 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]. Such inhibition of the enteric CYP3A activity by a single exposure to pomegranate juice appears to last for approximately 3 days [56]. Upon hydrolysis, glucoraphanin produces several products that include the bioactive isothiocyanate sulforaphane. 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. Resveratrol is an electron-rich molecule with two aromatic benzene rings linked by an ethylene bridge. These properties have been attributed to foods that are rich sources of numerous bioactive compounds such as phytochemicals [2]. ⺠Prescriber Update Some of these food types are broken down into tyramine, which is then metabolized by monoamine oxidase enzyme. These findings suggest that cranberry juice might affect the plasma concentration of nifedipine in humans as well [84]. with common medicines. Grapefruit can change how the body processes statins—especially atorvastatin (Lipitor), simvastatin (Zocor) and lovastatin (Mevacor)—and increase your risk for side effects like liver … Fruit baskets are a great gift idea, especially for the person who has everything; however, seemingly innocent citrus gifts may interact with some medications. In addition, various dietary components can have pharmacological activity under certain circumstances [12]. Dietary changes can alter the expression and activity of hepatic drug metabolizing enzymes. According to the U.S. National Library of Medicine, drugs that may interact with omeprazole include the following: Antiretrovirals such as rilpivirine-containing products ... and there may be other foods and beverages that interact with this drug.) Grapefruit juice was chosen as the mixer for its bitter taste, to disguise whether not alcohol was present. Two major capsaicinoids, dihydrocapsaicin (DHC) and capsaicin (CAP) are responsible for up to 90% of the total pungency of pepper fruits. This experience is one of the several ways foods interact with the drugs we take for healthy living. This means that guava could interact with P-gp substrates such as digoxin, fexofenadine, indinavir, vincristine, colchicine, topotecan, and paclitaxel in the small intestine. Izzo [81] described a total of eight cases of interaction between cranberry juice and warfarin, leading to changes in international normalized ratio (INR) values and bleeding. Response.redirect "/searchResults.asp?q=" & q Calcium-Rich Foods + Antibiotics. In some cases, you may need to avoid certain foods altogether during your treatment or … Organic anion-transporting polypeptides (OATPs) are membrane transport 1. 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]. this Site | FAQs | 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]. Previous studies have shown that a single ingestion of watercress inhibits the hydroxylation of chlorzoxazone, an in vivo probe for CYP2E1, in healthy volunteers [126]. If you must drink grapefruit juice, ask your doctor to prescribe another statin that is not affected by it. Increased fruit and vegetable consumption can also help displace food high in saturated fats, sugar or salt. Extracts and metabolites of this plant, particularly those from the leaves and fruit, possess useful pharmacological activities [100]. What other fruits or juices may also affect your drug in a similar way to grapefruit juice. Hidaka et al. Grapes are one of the most valued conventional fruits worldwide. There are transporters on the lateral membrane the primary function of which is pumping drugs back into the blood circulation from the hepatocytes. The SLC superfamily encompasses a variety of transporters, including the organic anion transporters (OAT, SLC22A), the organic cation transporters (OCT, SLC22A), the electroneutral organic cation transporters (OCTN, SLC22A), the equilibrative nucleoside transporters (ENT, SLC29), the concentrative nucleoside transporters (CNT, SLC28), the apical Na+−dependent bile salt transporter (ASBT, SLC10), the monocarboxylate transporters (MCT, SLC16), and the peptide transporters (PEPT, SLC15) [21]. and patient factors make it difficult to predict whether a fruit or fruit Dairy products such as milk, yogurt, and cheese can interfere with … 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). Further research regarding the potential toxicities associated with flavonoids and other dietary phenolics is required if these plant-derived products are to be used as therapy. Phytochemicals extracted from avocado can selectively induce several biological functions [147,148]. Most people sometimes buy sandwiches from fast-food restaurants. For this reason, this fruit should be consumed with caution by patients taking medicines. In other cases, as with the antihistamine fexofenadine (Allegra), grapefruit and grapefruit juice decrease both the blood levels of the drug and its effectiveness. Colored grapefruit juice and white grapefruit juice are equally effective in producing drug interactions. Brief introduction to this section that descibes Open Access especially from an IntechOpen perspective, Want to get in touch? How? Watercress juice can increase the enzymes SOD and GPX in blood cells in vitro and in vivo [128]. The vegan dietary category may be more comparable across countries and cultures because avoiding all animal products leaves little choice but to include large quantities of vegetables, fruit, nuts, and grains for nutritional adequacy. Depending on your situation, it may be necessary to allow a certain time between the moment you eat and the moment you take your medication. It has been shown that, before reaching the systemic circulation, the metabolism of orally ingested drugs (‘first-pass metabolism’ or ‘presystemic clearance’) has clinically relevant influences on the potency and efficacy of drugs. Consumption of most types of orange juice does not appear to alter CYP3A4 activity in vivo [55]. These proteins can be inhibited by orange, apple, and grapefruit juices. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too. Help us write another book on this subject and reach those readers. proteins which facilitate substance uptake. The major furanocoumarin present in grapefruit is bergamottin, which demonstrated a time- and concentration-dependent inactivation of CYP enzymes in vitro [49]. The isothiocyanate sulforaphane decreased the enzyme activities hepatocytes associated with CYP1A1 and 2B1/2, namely ethoxyresorufin-O-deethylase and pentoxyresorufin-O-dealkylase, respectively, in a dose-dependent manner [120]. It has been suggested that some constituents of pomegranate juice, most probably punicalagin, may impair the metabolic functions of the intestine (specifically sulfoconjugation) and therefore might have effects upon the bioavailability of drugs [89]. pomegranate, cranberry, grape, apple, and grapefruit. reported that OATP-B-mediated uptake of glibenclamide as well as estrone-3-sulfate was significantly inhibited by 5% orange juice [53]. On the other hand, Imaizumi et al. Most of the documented information about the effects of fruit and vegetables on metabolizing enzymes and drug transporters comes from preclinical studies. Metabolic food-drug interactions occur when a certain food alters the activity of a drug-metabolizing enzyme, leading to a modulation of the pharmacokinetics of drugs metabolized by the enzyme [12]. 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. Consumption can also help displace food high in saturated fats, sugar or salt Gate,... Fruits like kiwi fruit, possess useful pharmacological activities [ 153 ] beta-cryptoxanthin and benzyl isothiocyanates 113! And some other citrus fruits and cheese the liver plays a key in! Dietary micronutrients, indicate possibilities for improved therapeutic strategies London, SW7 2QJ, UNITED KINGDOM oral of. 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Furanocumarins present in foods or generated within the stomach and intestines with each other, they may be taking and., carotenoid, terpenoid and triterpene have been found in high levels of CYP1A1 mRNA, protein and...
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