Mayapple / Podophyllum

Medically reviewed by Prof. Giorgi Pkhakadze, MD, MPH, PhD — GMJ Editorial Board

What is Mayapple / Podophyllum?

Mayapple (Podophyllum peltatum) is a native North American plant that grows in woodland areas across the eastern United States and southeastern Canada. Also known as American mandrake, wild mandrake, or ground lemon, this perennial herb belongs to the barberry family (Berberidaceae). The plant produces a single white flower in spring, followed by a yellow, lemon-shaped fruit in summer.

While the ripe fruit is edible when fully mature, all other parts of the mayapple plant—including roots, rhizomes, leaves, stems, and unripe fruit—contain potent compounds called podophyllotoxins that are highly toxic to humans. The rhizome (underground stem) has been used historically in traditional medicine by Native American tribes, but due to its dangerous nature, mayapple is classified as unsafe for dietary supplement use and is banned or heavily restricted in many jurisdictions.

Health benefits & uses

Limited evidence: Historically, mayapple extracts have been investigated for potential anti-cancer properties due to compounds like podophyllotoxin, which serves as a precursor to FDA-approved cancer medications etoposide and teniposide. However, these pharmaceutical derivatives are synthesized and purified in laboratory settings under strict medical supervision.

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No credible evidence: Traditional uses included treatment of warts, constipation, and various skin conditions, but these applications lack scientific validation and pose significant safety risks. The therapeutic window between potentially beneficial effects and toxic doses is extremely narrow, making self-medication with mayapple preparations extremely dangerous.

It’s crucial to understand that any potential benefits are far outweighed by serious safety concerns, and mayapple should never be used as a dietary supplement or home remedy.

How it works

Mayapple contains podophyllotoxin and related lignans that interfere with cellular division by binding to tubulin, a protein essential for cell structure and mitosis. This mechanism can potentially inhibit rapidly dividing cells, which is why derivatives are used in cancer chemotherapy under medical supervision.

However, these compounds are non-selective and can damage healthy cells throughout the body, particularly affecting the gastrointestinal tract, nervous system, and other rapidly dividing tissues. The plant’s toxicity stems from its ability to disrupt fundamental cellular processes necessary for normal body function.

Dosage

No safe dosage exists for mayapple supplements. There is no established recommended daily allowance (RDA) or tolerable upper limit (UL) because the plant is considered too dangerous for dietary supplement use. Even small amounts can cause severe poisoning.

Any use of mayapple or its derivatives should only occur under strict medical supervision in pharmaceutical preparations where the active compounds have been isolated, purified, and precisely dosed. Self-medication with mayapple in any form is strongly discouraged by health authorities.

Food sources

The only potentially safe part of the mayapple plant is the fully ripe fruit, which has been consumed traditionally in small quantities. However, even ripe mayapple fruit should be approached with extreme caution, as it can cause digestive upset in some individuals and may still contain trace amounts of toxic compounds.

Mayapple is not available as a legitimate dietary supplement in most markets due to safety concerns. Any products claiming to contain mayapple should be avoided, as they may pose serious health risks.

Safety & side effects

Mayapple is extremely toxic and can cause severe, potentially fatal poisoning. Symptoms of mayapple toxicity include:

• Severe nausea and vomiting
• Diarrhea and abdominal pain
• Difficulty breathing
• Neurological symptoms including confusion and coma
• Kidney and liver damage
• Bone marrow suppression
• Cardiovascular collapse

Deaths have been reported from mayapple poisoning, particularly in children who may be attracted to the fruit. The margin between any potentially therapeutic dose and a toxic dose is virtually non-existent, making any use extremely risky.

Interactions

Due to mayapple’s dangerous nature, it should not be combined with any medications or supplements. The plant’s compounds could potentially interact with:

• Blood-thinning medications
• Chemotherapy drugs
• Medications affecting the liver or kidneys
• Central nervous system depressants

However, these interactions are theoretical concerns since mayapple should not be used at all outside of controlled pharmaceutical preparations.

Who should be cautious

Everyone should avoid mayapple supplements and preparations. Specific populations at particularly high risk include:

• Pregnant and breastfeeding women
• Children and adolescents
• Individuals with liver or kidney disease
• People taking any medications
• Those with compromised immune systems
• Individuals with gastrointestinal disorders

No population should consider mayapple safe for supplemental use.

Frequently asked questions

Is mayapple legal to purchase as a supplement?

In most jurisdictions, mayapple is either banned for supplement use or heavily restricted due to safety concerns. Products containing mayapple are generally not legally available as dietary supplements in the United States and many other countries.

Can mayapple treat cancer naturally?

While compounds from mayapple are used to create FDA-approved cancer medications, the raw plant is extremely dangerous and should never be used for self-treatment. Cancer treatment requires precise dosing and medical supervision that is impossible to achieve with plant preparations.

Are there safe alternatives to mayapple?

For any health concerns that might lead someone to consider mayapple, safer evidence-based alternatives exist. Consult with healthcare providers about appropriate treatments rather than using dangerous plant preparations.

What should I do if I’ve been exposed to mayapple?

Seek immediate medical attention if you or someone else has ingested any part of the mayapple plant (except possibly fully ripe fruit in very small amounts). Contact poison control or emergency services, as mayapple poisoning can be fatal.

Is mayapple the same as mandrake?

Mayapple is sometimes called American mandrake, but it’s different from European mandrake (Mandragora officinarum). Both plants are toxic and should be avoided, but they belong to different botanical families and have different toxic compounds.