What Are MAOIs and How Do They Work?
Monoamine oxidases (MAOs) are enzymes found throughout the body, including the brain, liver, and gut. Their primary job is to break down and inactivate monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine, which are crucial for mood regulation [1.2.1]. Monoamine Oxidase Inhibitors (MAOIs) are substances that block the action of these enzymes. By inhibiting MAOs, these substances increase the availability of these key neurotransmitters in the brain [1.9.1].
There are two main types of MAO enzymes [1.9.1]:
- MAO-A: Primarily breaks down serotonin, norepinephrine, and melatonin. Inhibiting MAO-A is often associated with antidepressant effects [1.9.2].
- MAO-B: Focuses on breaking down phenethylamine and has a significant role in metabolizing dopamine [1.9.1]. MAO-B inhibitors are often used in the management of Parkinson's disease [1.9.2].
Many natural compounds exhibit inhibitory effects on one or both of these enzymes, but their potency and safety vary dramatically.
Prominent Natural MAO Inhibitors
Several herbs are well-known for their MAO-inhibiting properties. However, their primary mechanism of action can be complex and may not solely be due to MAO inhibition.
- St. John's Wort (Hypericum perforatum): While once thought to work primarily as an MAOI, research shows it has only very weak MAO-inhibiting effects at therapeutic doses [1.6.1, 1.6.5]. Its antidepressant action is now believed to stem more from its ability to inhibit the reuptake of serotonin, norepinephrine, and dopamine, similar to synthetic antidepressants [1.6.1]. In very high doses, it may act as an MAOI [1.6.2].
- Curcumin (from Turmeric): This polyphenol has been shown to inhibit both MAO-A and MAO-B [1.5.2, 1.5.3]. Studies suggest curcumin can increase serotonin and dopamine levels, partly through this inhibitory action [1.5.2]. Its mechanism is considered a mixed type of competitive and noncompetitive inhibition [1.5.1].
- Rhodiola rosea (Golden Root): This adaptogenic herb demonstrates potent antidepressant activity by inhibiting both MAO-A and MAO-B [1.7.1, 1.7.2]. One of its active compounds, rosiridin, shows significant inhibition of MAO-B [1.7.1].
- Passionflower (Passiflora incarnata): Contains harmala alkaloids, which are known as reversible inhibitors of MAO-A (RIMAs) [1.9.1]. It is traditionally used for its sedative effects [1.4.4].
- Syrian Rue (Peganum harmala) and Banisteriopsis caapi (Ayahuasca Vine): These plants contain potent harmala alkaloids like harmine and harmaline, which are strong, reversible MAO-A inhibitors [1.2.1, 1.4.5]. They are primarily used for their psychoactive effects and are not considered typical dietary supplements due to their potency and associated risks [1.2.1].
- Other Herbs: A wide array of other plants and herbs contain compounds with MAOI activity, including licorice, green tea, ginkgo biloba, and kava [1.4.1, 1.4.3, 1.4.4].
Foods and Spices with MAO-Inhibiting Properties
Certain common foods and spices also exhibit MAO-inhibiting effects, although typically to a lesser degree than concentrated herbal extracts. These include:
- Cinnamon
- Cloves
- Nutmeg [1.2.1]
- Oregano [1.4.1]
- Black Pepper [1.2.4]
- Cocoa [1.3.3]
Additionally, research has shown that extracts from various fruits and vegetables like kiwifruit, cucumber, and red chicory can inhibit MAO-A and MAO-B in vitro [1.3.4].
Comparison: Natural vs. Pharmaceutical MAOIs
| Feature | Natural MAOIs | Pharmaceutical MAOIs |
|---|---|---|
| Potency | Varies widely from very weak (foods) to very potent (Syrian Rue). Often less potent than pharmaceuticals [1.5.1]. | Standardized and typically highly potent. |
| Regulation | Generally sold as dietary supplements, with little FDA oversight on purity or dose. | Strictly regulated by the FDA for safety, quality, and efficacy. |
| Side Effects | Can cause significant side effects and interactions, including the dangerous tyramine reaction and serotonin syndrome [1.8.1]. | Well-documented side effects and a strict protocol for avoiding dietary and drug interactions [1.8.2]. |
| Accessibility | Widely available over-the-counter in health food stores and online. | Prescription only. |
| Tyramine Interaction | High risk with potent natural MAOIs. Requires strict dietary avoidance of tyramine-rich foods [1.8.1]. | High risk, especially with older, irreversible MAOIs. A core safety warning for this drug class [1.8.2]. |
Critical Safety Warning: Tyramine and Serotonin Syndrome
The most significant danger associated with using MAOIs, whether natural or pharmaceutical, is the risk of life-threatening interactions.
The Tyramine Reaction (Hypertensive Crisis): MAO enzymes, particularly MAO-A, are responsible for breaking down tyramine, a compound found in many foods [1.8.1]. When MAO is inhibited, consuming tyramine-rich foods can lead to a massive buildup of tyramine, causing a sudden, dangerous spike in blood pressure known as a hypertensive crisis [1.8.2, 1.8.4]. Symptoms include a severe headache, sweating, rapid heartbeat, chest pain, and confusion [1.8.4]. This reaction has been dubbed the "cheese effect" because aged cheeses are very high in tyramine [1.10.1].
Foods High in Tyramine to AVOID include [1.3.1, 1.10.1, 1.10.2]:
- Aged cheeses (cheddar, blue cheese, brie, parmesan)
- Cured and processed meats (salami, pepperoni, sausage)
- Fermented foods (sauerkraut, kimchi, miso, soy sauce)
- Overripe fruits (bananas, avocados)
- Certain alcoholic beverages (red wine, tap beer)
- Yeast extracts (Marmite, Vegemite)
Serotonin Syndrome: Combining MAOIs (including natural ones like St. John's Wort) with other substances that increase serotonin, such as SSRI antidepressants, can cause a potentially fatal condition called serotonin syndrome [1.8.1, 1.11.1]. This is caused by an excessive amount of serotonin in the body and can lead to symptoms like agitation, confusion, high fever, muscle rigidity, and seizures [1.8.2].
Conclusion
Yes, natural MAO inhibitors exist in a wide variety of plants, foods, and spices. Compounds in herbs like Rhodiola and Curcumin, and more potent alkaloids in plants like Syrian Rue, can inhibit the MAO enzymes. However, their natural origin does not mean they are safe. The risk of severe interactions with common foods (the tyramine effect) and other medications (serotonin syndrome) is very real and can be life-threatening. The potency of these natural products is unregulated, making safe dosing difficult. Due to these significant dangers, it is absolutely critical to consult with a qualified healthcare professional before considering the use of any substance with MAO-inhibiting properties, especially if you have existing health conditions or are taking any other medications.
For more information on the interactions of herbal supplements, one authoritative resource is the National Center for Complementary and Integrative Health (NCCIH). For example, their page on St. John's Wort and Depression provides valuable safety information.
