Coumarin isn’t liver toxic in humans

I wanted to quickly address the issue of coumarin in cinnamon, as many people use this as a basis for determining what type of cinnamon to eat due to concerns over its purported liver-toxic effects.

Rest assured, coumarin isn’t toxic to the liver in humans.

Coumarin can be metabolized into a variety of products within the liver, but the two principle ones are 7-hydroxycoumarin (7-HC) and coumarin 3,4-epoxide, which rapidly degrades to o-hydroxyphenylacetaldehyde (o-HPA) and then to o-hydroxyphenylactic acid (o-HPAA).​1​ It’s these latter products that are liver toxic — 7-HC is not.

Humans produce mostly the non-toxic 7-HC metabolite.

We can thank studies in mice and rats, which are species that rely almost entirely on the o-HPA pathway to metabolize coumarin, for the widespread belief that coumarin is liver toxic. But that simply isn’t the case in humans due to difference in metabolism.

That being said, because humans rely on the CYP2A6 enzyme to metabolize coumarin into 7-HC, people with polymorphisms that slow this enzyme’s activity could be at an increased risk of adverse effects on the liver. ​2​

For instance, a study of 110 European adults found the excretion rate of 7-HC to be 20–100% of the ingested coumarin dose.​3​ Yet, other studies have found that the variation for the excretion of the liver-toxic metabolites is only 1–7%,​4,5​ suggesting that there are other benign pathways of metabolism. Accordingly, any increased risk in those with CYP2A6 polymorphisms would be minor.

Summing up

Coumarin is believed to be liver-toxic, but that’s not the case in humans. Some small proportion of humans may be at an increased risk for toxicity if they have polymorphisms that slow CYP2A6 activity, but that risk increase is minor. Enjoy your cinnamon.


  1. 1.
    Lake B. Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. Food Chem Toxicol. 1999;37(4):423-453. doi:10.1016/s0278-6915(99)00010-1
  2. 2.
    Abraham K, Wöhrlin F, Lindtner O, Heinemeyer G, Lampen A. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res. 2010;54(2):228-239. doi:10.1002/mnfr.200900281
  3. 3.
    Rautio A, Kraul H, Kojo A, Salmela E, Pelkonen O. Interindividual variability of coumarin 7-hydroxylation in healthy volunteers. Pharmacogenetics. 1992;2(5):227-233. doi:10.1097/00008571-199210000-00005
  4. 4.
    Meineke I, Desel H, Kahl R, Kahl G, Gundert-Remy U. Determination of 2-hydroxyphenylacetic acid (2HPAA) in urine after oral and parenteral administration of coumarin by gas-liquid chromatography with flame-ionization detection. J Pharm Biomed Anal. 1998;17(3):487-492. doi:10.1016/s0731-7085(97)00224-0
  5. 5.
    Shilling W, Crampton R, Longland R. Metabolism of coumarin in man. Nature. 1969;221(5181):664-665. doi:10.1038/221664b0