**Author details**

**7. Conclusion**

20 Drug Discovery

harmful clinical consequences.

WHO and the Food and Agriculture Organization of the United Nations (FAO) recommend a daily intake of at least 400 grams or five servings of fruits and vegetables to aid in the pre‐ vention of chronic illnesses such as heart disease, cancer, diabetes, and obesity. As a conse‐ quence, there is an increased global consumer demand for fruits and vegetables, and some consumers purchase organic foods with the understanding that they are healthy. The use of natural products for improving human health has evolved independently in different re‐ gions of the world and production, use, attitudes, and regulatory aspects vary globally. Al‐ though modern medicine may be available in most countries for the treatment of many chronic degenerative diseases, folk medicine (phytomedicine) has remained popular for his‐ torical and cultural reasons. Although the significance of interactions between drugs is widely appreciated, little attention has been given to interactions between drugs and nu‐ trients. Most of the documented information about the effects of fruit and vegetables on me‐ tabolizing enzymes and drug transporters comes from preclinical studies. However, the possibility that these effects could occur in humans should not be ignored. Several clinical studies on the interactions of grapefruit juice and drugs have been conducted with impres‐ sive results. Most of the fruits and vegetables examined in this review contain a similar phy‐ tochemical mix to that of grapefruit juice. *In vitro* models and animal models have shown that many of these agents influence drug metabolizing enzymes and drug transporters. It is possible that other fruits and vegetables could have the same potential for fruit and drug interactions, and this should be taken into account. This review shows evidence of the influ‐ ence of fruit, vegetables or their components (phytochemicals) on the CYP3A4 enzyme, which metabolizes most drugs used by the human population. A more consistent approach to the evaluation of nutrient-drug interactions in human beings is therefore needed. Said ap‐ proach must be systematic in order to a) assess the influence of nutritional status, foodstuffs, or specific nutrients on a drug's pharmacokinetics and pharmacodynamics, and b) evaluate the influence of a drug on overall nutritional status or the status of a specific nutrient. In ad‐ dition to all this, we must account for the fact that we live in an era of very varied lifestyles. Some people are vegetarians, others take high doses of flavonoids or antioxidants as supple‐ ments, some ingest large amounts of bottled water from plastic bottles, or use chlorinated disinfectants. 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 com‐ pound. All of these factors could have an impact on the metabolism or transport of drugs in a individual, potentially altering pharmacological responses. Our knowledge regarding the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate po‐ tential risk of food-drug interactions should be intensified in order to prevent undesired and

Lourdes Rodríguez-Fragoso\* and Jorge Reyes-Esparza

\*Address all correspondence to: mrodriguezf@uaem.mx

Universidad Autónoma del Estado de Morelos, Facultad de Farmacia, Cuernavaca, México
