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Updated: Jun 4

Intro to CYP450 Drug Metabolism

Today we’re just skimming the surface of CYP450 drug metabolism and highlighting what you need to know for the CNS exam.

Enzymes are proteins that act as biological catalysts - they speed up chemical reactions in the body and we would not survive without them. We often talk about digestive enzymes and their role in breaking down sugars, proteins, and fats, but there are essential enzymes in every organ system.

When we say “Cytochrome P450 enzymes,” we’re referring to a superfamily of enzymes that play a major role in drug metabolism and bioactivation. All foreign substances that enter the body have to be processed in some way, and this family of enzymes is primarily response for the breakdown of xenobiotics in humans, which occurs primarily in the liver

Xenobiotic (n): a chemical substance found within an organism that is considered foreign to that organism.

Examples of xenobiotics are pharmaceutical drugs, environmental pollutants and pesticides, as well as other industrial chemicals, cosmetics, and food additives.

“The cytochrome P450 (CYP) enzyme family is the major enzyme system catalyzing the Phase I metabolism of xenobiotics, including pharmaceuticals and toxic compounds in the environment.” Read about this here!

As you may recall, there are three primary phases of liver detoxification:

  • Phase I: the generation of water-soluble intermediaries ← CYP450

  • Phase II: the neutralization of toxic water-soluble intermediaries

  • Phase III: the excretion of the neutralized intermediaries

Liver detox pathways and nutrients for CNS exam

Source: The Institute for Functional Medicine, 2006.

Of all the different CYP proteins that are present in the human body, six of them are involved in the metabolism of 90% of drugs. These proteins are CYP1A2, CYP2C9, CYP2D6, CYP3A4, and CYP3A5.The most important are CYP3A4 and CYP2D6. More about CYP450 Enzymes.

Like other enzymatic processes, their functions can be increased or decreased based on dietary intake, nutrient status, exposure to substances, other biological triggers, and more.

For the CNS practitioner (and for the CNS exam), it is very important to have an idea of what compounds increase and decrease the function of these enzymes, as foods and supplements that impact these enzymes can have significant effects on drug metabolism.

  • Increased activity: this increases the processing of drugs, which expels them from the body faster. As a result, the drug will be less active, less effective, and the individual taking it may not see any benefits.

    • An agonist is a substance that mimics the actions of a neurotransmitter or hormone (or other binding compound) to produce a response when it binds to a specific receptor in the brain.

  • Decreased activity: when this occurs, drug metabolism slows, and the drug (or other substrate) can build up in the body.

    • An antagonist is a ​substance that binds to and blocks the activation of certain receptors on cells, to prevent a biological response.

There are many known compounds that can increase (agonists) or decrease (antagonists) the speed at which these CYP450 enzymes function.

NOTE: There are many, many plant-based substances and chemical compounds that are agonists and antagonists on numerous enzymes, including CYP450 enzymes. Many of these compounds are mild and may gently guide enzyme function, while others have stronger impacts. For the CNS exam, you only need to focus on a few that have stronger impacts as they can significantly impact drug metabolism and cause dangerous outcomes.

Additionally, it is important to note that some foods and substances will have an inhibitory effect on one of the CYP450 enzymes, and an increasing effect on other CYP450 enzymes.

Example: Saint-John's wort, a common herbal remedy induces CYP3A4, but also inhibits CYP1A1, CYP1B1.

A few important CYP450 interactions to study for the CNS Exam:

These are the only CYP450 agonists and antagonists that I would bother memorizing for the CNS exam. In clinical practice, be sure to check medication interactions before adding in herbs, supplements, or a new food that has a high risk of medication interaction.

  • Most people on medications are advised to avoid both grapefruit and St. John’s Wort.

    • Saint-John's Wort, a common herbal remedy induces CYP3A4, but also inhibits CYP1A1, CYP1B1.

    • Grapefruit juice contains compounds with inhibitory effects on the CYP enzyme family, specifically CYP3A4-mediated metabolism of certain medications.

Grapefruit can slow down the metabolism of drugs, leading to stronger drug effects and an increased risk of toxicity or overdose.

  • Tropical fruit juices. At relatively high concentrations, starfruit juice has also been shown to inhibit CYP2A6 and other P450s.

  • Watercress is also a known inhibitor of the cytochrome P450 CYP2E1, which may result in altered drug metabolism for individuals on certain medications (e.g., anesthesia, acetaminophen, aspartame, nicotine, among others). Garlic is also a known CYP2E1 inhibitor in humans. Food amounts of garlic are not typically avoided, but high doses and/or supplement forms may be problematic.

  • Goldenseal, with its two notable alkaloids berberine and hydrastine, has been shown to alter P450-marker enzymatic activities (involving CYP2C9, CYP2D6, and CYP3A4).[33]

  • Tobacco smoking induces CYP1A2, increasing the speed at which drugs are metabolized.

  • Other foods that activate some of the CYP enzymes include charcoal-grilled foods and cruciferous vegetables (e.g. broccoli).

Fun fact: there is research to suggest that in some cases, these agonist responses may be beneficial, as they may help to attenuate side effects of medications without necessarily impacting efficacy, and in other cases making medications more effective. As usual, more research is needed, but we may soon uncover ways foods can mitigate medication side effects - an exciting possibility for the field of food & nutrition!

Additional Food & Drug Interactions to Memorize for the BCNS Exam

Although not all of these are specific to the CYP450 family of enzymes, here are some of the top drug-food interactions I recommend memorizing for the CNS exam.

  1. Calcium channel blockers and statins can interact with grapefruit juice.

  2. St. John’s Wort has a similar effect as SSRIs and therefore can have a harmful effect when taken together. (Serotonin syndrome.)

  3. MAOIs are monoamine oxidase inhibitors and can interact with the amino acid tyramine, so tyramine-rich foods are often avoided for those taking MAOIs.

  4. Levothyroxine, a synthetic T4 medication used for hypothyroidism, should be taken away from food and supplements.

  5. Warfarin efficacy is significantly impacted by the vitamin K in leafy greens (ex: kale).

  6. Additionally, alcohol interacts with many prescription and over the counter medications, and is itself a toxin that uses a lot of liver resources so clients on medication should always be advised to minimize their alcohol intake.

CNS Exam Practice Questions:

1 - The CYP 450 family of enzymes is responsible for what action in the body?

2 - ____ (leafy green) and _____ (allium) are CYP2E1 inhibitors in humans.

3 - T/F: Certain foods can influence how you respond to and detoxify anesthesia, acetaminophen, nicotine, and aspartame.

Watch the video to get the answers!

Additional Resources for this Topic:

Basic Review of the Cytochrome P450 System:

Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application:

The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain:

Cytochrome P450 - Wikipedia page:

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Preparing for the CNS exam? Looking for CNS test questions? Test your knowledge with our 10 practice CNS exam questions.


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