The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies.
Cytochrome P450
Drug metabolism
Macronutrients
Nutritional status
Obesity
Systematic review
Journal
European journal of nutrition
ISSN: 1436-6215
Titre abrégé: Eur J Nutr
Pays: Germany
ID NLM: 100888704
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
24
10
2019
accepted:
19
10
2020
pubmed:
4
11
2020
medline:
13
8
2021
entrez:
3
11
2020
Statut:
ppublish
Résumé
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. The present systematic review was conducted to summarize the effect of obesity, weight reduction, macronutrients, fasting and malnutrition on the CYP-mediated drug metabolism. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 33141242
doi: 10.1007/s00394-020-02421-y
pii: 10.1007/s00394-020-02421-y
doi:
Substances chimiques
Pharmaceutical Preparations
0
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2905-2921Informations de copyright
© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.
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