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INTERNATIONAL CONGRESS OF

PharmacoGenetics

• Impact of Nutritional Factors on Pharmacogenetic Profiles and Drug Response

• Reza Kalantari,^1,* Mohammad Azadbakht,² Nila Navaei,³
  1. Research Institute for Herbal Medicines and Metabolic Disorders, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  2. Professor, Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  3. Pharm.D Candidate Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  
  
  
• Introduction: Pharmacogenetics tailors medications to the individual's enzymes, transporters, and receptors. These findings do not elucidate the variability of pharmacological responses that are not inherited. A recent study revealed that food affects drug safety, efficacy, gene expression, and pharmacogenetics. Nutrigenomics posits that nutrition, bioactive compounds, and macro- and micronutrients may influence the activity of ADME enzymes. The diet influences CYP 1A2, 2C9, 2C19, and 3A4 enzymes. The efficacy and lifetime of drugs may vary with these enzymes—bioactive compounds including polyphenols, flavonoids, caffeine, omega-3 fatty acids, vitamins, and probiotics. Green tea EGCG inhibits CYP1A2, CYP2C9, and CYP3A4, hence influencing the metabolism of caffeine and statins. Resveratrol elevates R- and S-warfarin levels by 58.6% and 48.8%, respectively. It facilitates the prevention of blood clot formation—increases from 1.73 to 2.64 INR. Chronopharmacokinetics investigates the circadian rhythms of drug and enzyme metabolism. The microbiome influences the absorption of medications. These attributes are associated with genetic diversity and therapeutic effectiveness.
• Methods: A comprehensive literature review examined the impact of dietary variables on pharmacogenetic pathways, focusing on studies completed from 2023 to 2025. The search terms included in our research comprised "nutrigenomics," "pharmacogenetics," "CYP450," "food-gene interaction," "resveratrol-warfarin interaction," and "chronopharmacokinetics" throughout PubMed, Scopus, and ScienceDirect. Clinical trials, encompassing both in vitro and in vivo studies, along with meta-analyses, constituted the criterion. The primary criteria for data extraction included vitamin type, target enzyme or transporter, genetic variations, pharmacokinetic features, and clinical importance.
• Results: Flavonoids and Polyphenols Polyphenols and flavonoids can modify CYP450 enzyme-associated metabolic pathways. EGCG inhibits CYP1A2, CYP2C9, and CYP3A4, potentially decelerating the metabolism of coffee, statins, and chemotherapeutic agents. Resveratrol increases plasma R-warfarin levels by 58.6% and S-warfarin levels by 48.8%, elevating the INR from 1.73 to 2.64. In individuals possessing CYP2C9 and CYP2C19 genetic variations, these interactions are more pronounced. Caffeine and the CYP1A2 Gene Type Caffeine, a substrate of CYP1A2, signifies metabolic variability. Research participants consist of hyperinducers (CYP1A21F/*1F, *1A/*1F; n = 15) and normal metabolizers (CYP1A21A/*1A, *1C/*1F, *1C/*1C; n = 9). This classification employs CYP1A2 genotypes. The genotype was correlated with metabolism (r = 0.97) in a study on the caffeine-paraxanthine metabolic ratio. Fatty Acids Omega-3 Omega-3 fatty acids facilitate UGT-mediated glucuronidation, hence aiding in the elimination of many pharmaceuticals. Omega-3 may influence the efficacy and interactions of medications due to UGT genetic differences. It is essential to consider nutrition and heredity when determining drug dose. Gut Microbiota and Probiotics Alterations in gut microbiota due to high-fiber diets and probiotics may influence medication absorption. Microbiome enzymes modify the structure and efficacy of medications. A meta-analysis of 85 studies (32 randomized controlled trials, 28 cohort studies, 25 preclinical models) revealed that microbiota significantly influence drug metabolism (SMD = 0.45, 95% CI: 0.30-0.60, p < 0.001). Bacteroides enhances the lethal metabolite of irinotecan, elevating gastrointestinal toxicity by a factor of 3.2. Eggerthella lenta diminishes digoxin absorption and efficacy by 53%. Enterococcus faecalis metabolizes L-DOPA into dopamine, reducing its therapeutic effectiveness. Stomach bacteria may influence immunotherapy and chemotherapy. Treatment may be enhanced by probiotics and fecal microbiota transplantation (FMT). Chronopharmacokinetics Circadian rhythms influence drug metabolic transporters and enzymes. For treatments with brief therapeutic windows, synchronizing drug delivery with the patient's biological cycles can enhance efficacy and mitigate adverse effects. Diverse individuals require varying dose regimens according to circadian biology.
• Conclusion: The study demonstrated that food, gut microbiota, and circadian rhythms influence pharmacological responses and pharmacogenetic profiles. Animal and in vitro studies can reveal pathways; however, genetic diversity, lifestyle decisions, and environmental influences complicate human application. Diet, microbiomes, and circadian rhythms influence medication degradation and effectiveness. Restriction: 1- Animal and in vitro investigations yield the majority of quantitative evidence, rather than clinical trials. 2- Drug and nutritional habits can influence pharmacogenetic testing. 3- The impact of prolonged dietary habits on pharmacogenetic pathways is currently unclear. 4- Genetic differences, epigenetic modifications, and microbiota makeup influence functionality. Notwithstanding these constraints, the results suggest that nutrition should be incorporated into pharmacogenetic testing and personalized treatment. Patients must evaluate their microbiome, dose, dietary intake, warfarin, and other medications with a restricted therapeutic index. Circadian rhythms, gut microbiota, and nutrition influence gene expression and an individual's drug sensitivity. Drug metabolism is influenced by environmental factors, sex, hormones, genetics, and epigenetics. Pharmacogenetics, chronopharmacokinetics, and nutrigenomics are very useful tools for clinicians when they need to choose a prescription and figure out how much to give. To get the most out of anticoagulants and lower the chance of side effects, patients should keep track of how many polyphenols they eat and take their medicine at the same time every day. There are several ways to make precision medicine better. We require additional research to establish standards for chronobiology, microbiota, diet, biological pathways, and the long-term therapeutic benefits of drugs.
• Keywords: Nutrigenomics, Pharmacogenetics, Drug Metabolism, Personalized Medicine, Chronopharmacokinetics