Cinnamon Supplements May Interact With Prescription Medications

Sprinkling cinnamon on your morning coffee probably won’t do much more than improve its taste, but what if you’re taking it in supplement form? Would it have any health perks, then? Or health detriments?

Researchers at the University of Mississippi investigated how cinnamaldehyde, cinnamon’s main active compound, behaves in the body. Their findings suggest that while the spice is safe in small doses, higher concentrations could affect how some medications are processed.

The study was published in Food Chemistry: Molecular Sciences.

The growing use of cinnamon supplements

Cinnamon, derived primarily from the bark of Cinnamomum species, has been used for centuries as a culinary spice and a component of traditional medicine systems across cultures. Beyond its distinctive flavor, the spice has been valued for its potential therapeutic properties, including effects on blood sugar regulation, inflammation and cardiovascular health. Recently, these perceived benefits have led to a surge in the availability and use of cinnamon-based dietary supplements, particularly in concentrated forms such as oils or extracts.

Cinnamaldehyde contributes significantly to cinnamon’s characteristic aroma and is often credited with many of its proposed health effects. The bioactive compound is found in high concentrations in Cassia cinnamon, a commonly available and inexpensive variety.

“In contrast, true cinnamon from Sri Lanka carries a lower risk due to its reduced coumarin content,” said co-author Dr. Amar Chittiboyina, an associate director of the National Center for Natural Products Research (NCNPR) at the University of Mississippi. “Coumarin's anticoagulant properties can be hazardous for individuals on blood thinners.”

While culinary use poses little concern, the growing popularity of cinnamon supplements has prompted questions about their safety – especially in individuals who are taking prescription medications.

Relatively little is known about how cinnamaldehyde is processed by the body or how it might influence the metabolism of drugs. Specifically, there is limited information on whether cinnamaldehyde interacts with the body’s drug-processing enzymes or nuclear receptors such as the pregnane X receptor (PXR) and the aryl hydrocarbon receptor (AhR), both of which regulate the activity of enzymes involved in drug clearance.

 

 

Previous clinical work has shown cinnamaldehyde to be undetectable in plasma after oral ingestion, suggesting rapid metabolism and limited systemic exposure. However, the health effects of its metabolites and receptor activation remain to be studied in humans.

This lack of detailed understanding has motivated researchers to explore the biochemical fate of cinnamaldehyde more thoroughly.

“Despite its vast uses, very few reports were available to describe the fate of cinnamon's major component – cinnamaldehyde,” said corresponding author Dr. Shabana Khan, a principal scientist at NCNPR at the University of Mississippi. “Understanding its bioaccessibility, metabolism and interaction with xenobiotic receptors was important to evaluate how excess intake of cinnamon would affect the prescription drugs if taken at the same time.”

 

Can cinnamon activate drug-processing pathways?

Khan and the team examined how cinnamaldehyde behaved under simulated digestive and metabolic conditions. The study first assessed bioaccessibility by incubating cinnamon oil in simulated gastric and intestinal fluids that mimic both fasted and fed states.

Cinnamaldehyde remained stable and fully soluble in all tested conditions, with 100% bioaccessibility, suggesting that it can readily reach the gut lining after oral ingestion.

The researchers then investigated metabolic stability using human liver microsomes and S-9 liver fractions – models commonly used to simulate the body’s drug metabolism. The S-9 fraction, which includes both phase I and phase II liver enzymes, allowed the team to assess additional metabolic pathways beyond initial oxidation.

Cinnamaldehyde was rapidly oxidised into cinnamic acid in both systems, with a metabolic half-life ranging from ~2–5 minutes. This rapid conversion points to high first-pass metabolism, indicating that cinnamaldehyde is quickly cleared from the body via the liver.

 

 

The team also looked at whether cinnamaldehyde and its metabolites activate two key nuclear receptors involved in drug metabolism: PXR and AhR.

Cinnamaldehyde alone did not activate either receptor. However, cinnamic acid and cinnamon oil, at higher concentrations, activated PXR in intestinal and liver-derived cells. Cinnamon oil also strongly activated AhR, an effect not observed with cinnamaldehyde or cinnamic acid, suggesting that minor components in the oil, possibly flavonoids, may be responsible.

Cinnamaldehyde and cinnamon oil moderately inhibited two drug-metabolising enzymes, CYP2C9 and CYP1A2, but showed no significant inhibition of CYP3A4 or CYP2D6, which are major enzymes responsible for clearing many common medications.

What these findings mean for supplement users

The observed activation of xenobiotic receptors and modest inhibition of certain liver enzymes suggest that concentrated forms of cinnamon, such as oils or capsules, may alter how the body processes some medications.

“Health concerns could arise if excessive amounts of supplements are consumed without the knowledge of a health care provider or prescriber of the medications,” said Khan.

“Overconsumption of supplements could lead to a rapid clearance of the prescription medicine from the body, and that could result in making the medicine less effective,” she added.

However, the current data comes from controlled laboratory models, and the clinical significance of these interactions remains uncertain.

“We know there's a potential for cinnamaldehyde to activate these receptors that can pose a risk for drug interactions. That’s what could happen, but we won't know exactly what will happen until we do a clinical study,” said co-author Dr. Bill Gurley, a principal scientist at NCNPR at the University of Mississippi.

From a public health perspective, moderate use of cinnamon as a culinary spice is considered safe and unlikely to pose health risks. The concern arises with the use of concentrated supplements, which may deliver much higher doses of cinnamaldehyde than typically encountered through food.

“People who suffer from chronic diseases – like hypertension, diabetes, cancer, arthritis, asthma, obesity, HIV, AIDS or depression – should be cautious when using cinnamon or any other supplements. Our best advice is to talk to a health care provider before using any supplements along with the prescription medicine,” said Khan.

“By definition, supplements are not meant to treat, cure or mitigate any disease,” she said.

 

Reference: Husain I, Gurley BJ, Kothapalli HB, et al. Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde. Food Chem: Mol Sci. 2025;10:100237. doi: 10.1016/j.fochms.2024.100237

This article is a rework of a press release issued by the University of Mississippi. Material has been edited for length and content.