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The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies

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Abstract

Background

Cytochrome P450s (CYPs) are a class of hemoproteins involved in drug metabolism. It has been reported that body composition, proportion of dietary macronutrients, fasting and nutritional status can interfere with the activity of drug-metabolizing CYPs.

Objectives

The present systematic review was conducted to summarize the effect of obesity, weight reduction, macronutrients, fasting and malnutrition on the CYP-mediated drug metabolism.

Methods

PubMed (Medline), Scopus, Embase and Cochrane Library databases and Google Scholar were searched up to June 2020 to obtain relevant studies. The PRISMA guidelines were employed during all steps. Two reviewers independently extracted the information from the included studies. Studies investigating CYPs activity directly or indirectly through pharmacokinetics of probe drugs, were included. Increase in clearance (CL) or decrease in elimination half-life (t½) and area under the curve (AUC) of probe drugs were considered as increase in CYPs activity.

Results

A total of 6545 articles were obtained through searching databases among which 69 studies with 126 datasets fully met the inclusion criteria. The results indicated that obesity might decrease the activity of CYP3A4/5, CYP1A2 and CYP2C9 and increase the activity of CYP2E1. The effect of obesity on CYP2D6 is controversial. Also, weight loss increased CYP3A4 activity. Moreover, CYP1A2 activity was decreased by high carbohydrate diet, increased by high protein diet and fasting and unchanged by malnutrition. The activity of CYP2C19 was less susceptible to alterations compared to other CYPs.

Conclusion

The activity of drug-metabolizing CYPs are altered by body composition, dietary intake and nutritional status. This relationship might contribute to drug toxicity or reduce treatment efficacy and influence cost-effectiveness of medical care.

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Authors and Affiliations

  1. Department of Clinical Nutrition, Student Research Committee, Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Science, Tabriz, Iran

    Meysam Zarezadeh

  2. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Saedisomeolia

  3. School of Medicine, Western Sydney University, Sydney, NSW, 2560, Australia

    Ahmad Saedisomeolia

  4. Faculty of Medical Sciences and Technologies, Science and Research Branch, Azad University, Tehran, Iran

    Mahoor Shekarabi

  5. Student’s Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Masoud Khorshidi

  6. Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Emami

  7. Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Daniel J. Müller

  8. Pharmacogenetic Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Daniel J. Müller

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  1. Meysam Zarezadeh
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Contributions

AS and DJM designed research; MZ and AS conducted research; MZ, MK and ME screened studies; MZ, MK and ME extracted data and MZ, AS and DJM. wrote the paper. AS had primary responsibility for final content. All authors read and approved the final manuscript.

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Correspondence to Ahmad Saedisomeolia.

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Meysam Zarezadeh: No conflicts of interest. Ahmad Saedisomeolia: No conflicts of interest. Mahoor Shekarabi: No conflicts of interest. Masoud Khorshidi: No conflicts of interest. Mohammad Reza Emami: No conflicts of interest. Daniel J. Müller: No conflicts of interest.

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Zarezadeh, M., Saedisomeolia, A., Shekarabi, M. et al. The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies. Eur J Nutr 60, 2905–2921 (2021). https://doi.org/10.1007/s00394-020-02421-y

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