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Black pepper contains 2-7.4% piperine. Piperine inhibits CYP.

Hepatic Gene Expression Changes in Mouse Models with Liver-specific Deletion or Global Suppression of the NADPH-Cytochrome P450 Reductase Gene

  • NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. "
  • In human adults, dysfunctional CPR proteins have been linked to disordered steroidogenesis

Curcumin, Piperine, and Capsaicin: A Comparative Study of Spice-Mediated Inhibition of Human Cytochrome P450 Isozyme Activities.
Curcumin, Piperine, and Capsaicin: A Comparative Study of Spice-Mediated Inhibition of Human Cytochrome P450 Isozyme Activities.

Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction

  • The authors conclude that CYP2E1 shows no large differences between species, and extrapolation between species appears to hold quite well. In contrast, the species-specific isoforms of CYP1A, -2C, -2D and -3A
    • CYP3A1 is one of the CYPs inhibited by piperine, and it is also one that differs between mice and humans, it seems.

The Cytochrome P450 Epoxygenase Pathway Regulates the Hepatic Inflammatory Response in Fatty Liver Disease
Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory effects.... and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH

Overview: How Is Alcohol Metabolized by the Body?
Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase

Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid

  • Dietary omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert a wide range of beneficial effects on human health1,2,3. However, the molecular mechanisms for the beneficial actions of omega-3 PUFAs remain poorly understood. It was conventionally thought that omega-3 PUFAs have a suppressive effect on the formation of bioactive lipid mediators derived from omega-6 arachidonic acid (AA), such as prostaglandins and leukotrienes4. However, recent studies have shown that they also serve as precursors of anti-inflammatory lipid mediators5,6. E-series resolvins are lipid mediators derived from EPA that actively dampen inflammation to maintain tissue homeostasis7,8,9,10,11.
  • The biosynthesis of PUFA-derived lipid mediators is mainly initiated by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes

Thoughts

  1. People have been eating black pepper on steak for a long time without any apparent connection to liver disease
  2. However, the combination of alcohol with the supression of CYP may lead to problems