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Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women.

ABSTRACT: Botanical dietary supplements produced from hops (Humulus lupulus) containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Because of the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and postmenopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for the enzymes CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. The observed area under the time-concentration curves were unaffected, except for alprazolam which decreased 7.6% (564.6 ± 46.1 h·μg/L pre-hop and 521.9 ± 36.1 h·μg/L post-hop; p-value 0.047), suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2, CYP2D6, or CYP3A4/5. The serum obtained after consumption of the hop extract was analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry to confirm compliance. Abundant Phase II conjugates of the hop prenylated phenols were observed including monoglucuronides and monosulfates as well as previously unreported diglucuronides and sulfate-glucuronic acid diconjugates.

SUBMITTER: van Breemen RB

PROVIDER: S-EPMC8071352 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Drug interactions represent a major issue in clinical settings, especially for critically ill patients such as those with cardiovascular disease (CVD) who require cardiothoracic surgery (CTS) and receive a high number of different medications. A cross-sectional study aimed at evaluating the exposure and clinical significance of drug-drug (DDIs) and drug-dietary supplement interactions (DDSIs) in patients admitted for CTS in the University Hospital of Crete Greece. DDIs were evaluated regarding underlying pharmacological mechanisms upon admission, preoperation, postoperation, and discharge from CTS clinic. Additionally, upon admission, the use of dietary supplements (DSs) and if patients had informed their treating physician that they were using these were recorded with subsequent analysis of potential DDSIs with prescribed medications. The study employed 76 patients who were admitted for CTS and accepted to participate. Overall, 166 unique DDIs were identified, with 32% of them being related to pharmacokinetic (PK) processes and the rest (68%) were related to possible alterations of pharmacodynamic (PD) action. CVD medications and drugs for central nervous system disorders were the most frequently interacting medications. In total, 12% of the identified DDIs were of serious clinical significance. The frequency of PK-DDIs was higher during admission and discharge, whereas PD-DDIs were mainly recorded during pre- and postoperation periods. Regarding DS usage, 60% of patients were using DSs and perceived them as safe, and the majority had not informed their treating physician of this or sought out medical advice. Analysis of medical records showed 30 potential combinations with prescribed medications that could lead in DDSIs due to modulation of PK or PD processes, and grapefruit juice consumption was involved in 38% of them. An increased burden of DDIs and DDSIs was identified mostly upon admission for patients in CTS clinics in Greece. Healthcare providers, especially prescribing physicians in Greece, should always take into consideration the possibility of DDIs and the likely use of DS products by patients to promote their well-being; this should only be undertaken after receiving medical advice and an evidenced-based evaluation.

Project description:(1) Background: Women bodybuilders use extreme diets, dietary supplementation, and training regimes to sculpt their physiques. Women's participation in bodybuilding competitions has increased since the 1980s. Currently, studies on their dietary intake and supplement use are limited. Their dietary intake may be of poor quality and low in several micronutrients, while supplement use appears to be omnipresent. Thus, the aim of this study was to examine and compare the dietary intake, supplement use, and diet quality of in-season and off-season women bodybuilders. (2) Methods: In a cross-sectional design, we compared dietary intake, supplement use, and diet quality between seasons in women bodybuilders (n = 227). An online questionnaire was developed, validated, and administered to assess all non-dietary and supplement variables. The Automated Self-Administered 24 h Dietary Assessment Tool was used to collect four 24 h dietary recalls. The Healthy Eating Index-2015 (HEI-2015) was used to calculate diet quality. The analysis of covariance and Welch's t-tests were used to assess the differences between in-season and off-season women bodybuilders' dietary intake, supplement, and HEI-2015 variables. (3) Results: In-season competitors reported consuming significantly less energy, carbohydrates, and fat but more protein than off-season competitors. All competitors consumed excess protein, while in-season competitors consumed excess fat and off-season competitors consumed less energy than the physique athlete nutrition recommendations. All competitors' micronutrient intakes were above the Dietary Reference Intakes. Supplements were used by all competitors, and the mean number used was similar between seasons. The HEI-2015 scores were not significantly different between seasons yet were below the US Dietary Guidelines for Americans. (4) Conclusion: Women bodybuilders would benefit from health education to achieve physique athlete nutrition recommendations, improve diet quality, and safe/efficacious supplement use to reach physique goals and improve overall health.

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Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women.

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