Cinnamaldehyde from cinnamon oil was found to be 100% bioaccessible in both fasted and fed gastrointestinal environments, and it rapidly metabolized in the liver within minutes, according to a recent study.
Researchers examined the bioaccessibility, metabolic clearance, and xenobiotic receptor interactions of cinnamaldehyde—the principal compound in cinnamon oil. They aimed to assess potential herb–drug interactions associated with cinnamon oil supplementation.
Using fasted and fed state simulated gastric (pH 1.65 and 4.52) and intestinal (pH 6.45 and 4.92) fluids, the researchers determined that cinnamaldehyde was 100% bioaccessible under all tested conditions. Concentrations following 2-hour incubations reached 270 ± 20 μg/mL in fasted gastric fluid and up to 320 ± 40 μg/mL in fed state intestinal fluid. This high solubility and chemical stability indicated that cinnamaldehyde from cinnamon oil remains intact during gastrointestinal transit, rendering it available for absorption.
To evaluate metabolic clearance, cinnamaldehyde was incubated with human liver microsomes (HLMs) and S-9 fractions. In HLMs, cinnamaldehyde demonstrated a half-life (T1/2) of 4.84 ± 0.05 minutes and an intrinsic clearance (CLint) of 143.30 ± 0.12 mL/min/kg; over 90% was metabolized within 10 minutes. In S-9 fractions, clearance was even more rapid (T1/2 = 1.97 ± 0.07 minutes; CLint = 358.32 ± 14 mL/min/kg). When tested as part of cinnamon oil, cinnamaldehyde showed a slightly lower stability (HLM CLint = 200.69 ± 2.90 mL/min/kg), which suggested that other oil constituents may modulate its biotransformation.
To assess xenobiotic receptor activation, luciferase reporter assays were conducted in HepG2 and LS174T cells. Cinnamon oil and cinnamic acid activated the pregnane X receptor (PXR) by more than threefold at 20 μg/mL in LS174T cells, while cinnamaldehyde showed no effect. For the aryl hydrocarbon receptor (AhR), cinnamon oil induced dose-dependent activation and peaked at 13.47-fold at 10 μg/mL. Neither cinnamaldehyde nor cinnamic acid activated AhR.
Cytochrome P450 inhibition assays revealed that neither cinnamaldehyde nor cinnamon oil inhibited CYP3A4 or CYP2D6 at concentrations up to 50 μg/mL. However, modest inhibition was observed for CYP2C9 (IC50 range, 30–43 μg/mL) and CYP1A2 (IC50, 21.5–28.5 μg/mL).
While cinnamaldehyde exhibits high gastrointestinal bioaccessibility and rapid metabolic clearance, cinnamon oil may pose a moderate risk for PXR- and AhR-mediated HDIs.
The authors noted that the clinical relevance remains uncertain and recommended further pharmacokinetic studies to evaluate potential interactions in patients using cinnamon-derived supplements.