School of Pharmacy, Regis University, 3333 Regis Blvd, Denver, CO, H-28, USA.
Ir J Med Sci. 2022 Oct;191(5):2357-2365. doi: 10.1007/s11845-021-02828-4. Epub 2021 Nov 4.
Dietary supplement use has continued to rise. In addition to supplement-drug interactions, it is prudent to consider how dietary supplements may interact with a patient's specific pharmacogenetics. Variations in genes associated with CYP 450 enzymes have evidence of impacting drug metabolism and adverse effects.
This research was performed to evaluate CYP P450 enzyme activity of the top 15 dietary supplements used in the USA in order to initiate pharmacogenetic considerations specific to commonly used dietary supplements.
The most common dietary supplements used in the USA were obtained from the National Health and Nutrition Examination Survey (NHANES). Primary literature detailing supplement CYP P450 activity was compiled from PubMed using MeSH search terms: supplement name(s), cytochrome P450 enzymes, metabolism, and pharmacokinetics. Additional resources utilized for documented CYP enzyme genotypes were the pharmacogenetic databases from Clinical Pharmacogenetics Implementation Consortium and The Pharmacogenomic Variation Consortium.
Of the 15 most common dietary supplements used in the USA, 53% (cranberry, echinacea, garlic, ginkgo biloba, ginseng, melatonin, milk thistle, and valerian) exhibit CYP P450 metabolism, with some having possible induction activity as well. Melatonin and garlic are substrates of CYP1A2 and CYP2C19, respectively. Additionally, there is evidence of echinacea having possible CYP3A4 induction activity.
CYP P450 activity is an important consideration for any patient but becomes increasingly critical if patients have certain CYP P450 phenotypes that impact metabolism. These popular supplements have the potential for changes in supplement exposure, and adverse effects based on pharmacogenetic profiles. Furthermore, these sites of metabolism are shared with many medications, setting the stage for possibly more profound interactions between medications and supplements. This paper highlights the mechanisms in which dietary supplements may constitute a risk for patients with certain CYP P450 phenotypes. Further research is needed in the area of dietary supplements and their pharmacogenomic implications.
膳食补充剂的使用持续增加。除了补充药物相互作用外，谨慎考虑膳食补充剂如何与患者特定的药物遗传学相互作用也很重要。与 CYP450 酶相关的基因变异有影响药物代谢和不良反应的证据。
本研究旨在评估美国使用的前 15 种膳食补充剂的 CYP P450 酶活性，以启动针对常用膳食补充剂的特定药物遗传学考虑。
从国家健康和营养调查（NHANES）中获取了美国最常用的膳食补充剂。使用 MeSH 搜索词从 PubMed 中详细编译了补充 CYP P450 活性的主要文献：补充剂名称、细胞色素 P450 酶、代谢和药代动力学。用于记录 CYP 酶基因型的其他资源是临床药物遗传学实施联盟和药物基因组变异联盟的药物遗传学数据库。
在美国使用的 15 种最常见的膳食补充剂中，有 53%（蔓越莓、紫锥菊、大蒜、银杏、人参、褪黑素、奶蓟草和缬草）表现出 CYP P450 代谢，其中一些还具有可能的诱导活性。褪黑素和大蒜分别是 CYP1A2 和 CYP2C19 的底物。此外，有证据表明紫锥菊可能具有 CYP3A4 诱导活性。
CYP P450 活性是任何患者都需要考虑的重要因素，但如果患者具有影响代谢的特定 CYP P450 表型，则这种考虑变得更加关键。这些流行的补充剂有可能改变补充剂的暴露量，并根据药物遗传学特征产生不良反应。此外，这些代谢部位与许多药物共享，为药物和补充剂之间可能更深刻的相互作用奠定了基础。本文强调了膳食补充剂可能构成具有特定 CYP P450 表型的患者风险的机制。需要在膳食补充剂及其药物基因组学意义领域进行进一步研究。
