Consumption of baby kale increased cytochrome P450 1A2 (CYP1A2) activity and influenced bilirubin metabolism in a randomized clinical trial

Authors: Charron, Craig; Novotny, Janet; JEFFERY, ELIZABETH - University Of Illinois; Kramer, Matthew; ROSS, SHARON - National Cancer Institute (NCI, NIH); SEIFRIED, HAROLD - National Cancer Institute (NCI, NIH)

Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/5/2019
Publication Date: 10/31/2019
Citation: Charron, C.S., Novotny, J.A., Jeffery, E., Kramer, M.H., Ross, S., Seifried, H. 2019. Consumption of baby kale increased cytochrome P450 1A2 (CYP1A2) activity and influenced bilirubin metabolism in a randomized clinical trial. Journal of Functional Foods. 64:103624. https://doi.org/10.1016/j.jff.2019.103624.
DOI: https://doi.org/10.1016/j.jff.2019.103624

Interpretive Summary: Consumption of Brassica vegetables has been linked with reduced cancer risk. This protection likely occurs partly due to the modification of metabolizing enzymes in the body that detoxify and remove foreign chemical compounds, often referred to as xenobiotics. The enzymes are called xenobiotic metabolizing enzymes (XMEs). The objective of this study was to determine if eating kale changes XMEs in the body. Twenty-five subjects were separated into two groups. For 14 days, one group ate a basal diet supplemented with steamed baby kale and raw daikon radish, while the other group ate the basal diet supplemented with control vegetables (peas, green beans, white corn). Urine samples were collected on days 8 and 15, and blood samples were collected on days 1, 8, and 15. Then the procedure was repeated except that subjects switched groups (those who had been on the kale diet went on the control diet, and those who had been on the control diet went on the kale diet) and urine and blood samples were collected on the same days. The activity of the XME known as CYP1A2 was increased by the kale diet and was 16.4% and 15.2% higher, respectively, on days 8 and 15 compared to control. CYP1A2 activity was generally higher in males than in females. A marker of metabolism called conjugated bilirubin was reduced by the kale diet and decreased from 19.4 to 14.3 to 9.5% of total bilirubin on days 1, 8, and 15, respectively. This change may be explained by increased activity of the XME known as MRP2. Other XMEs measured in this study were not affected by diet. These results show that consumption of baby kale induces CYP1A2 and may induce MRP2. The implications of these results for cancer risk will be clarified as the functions of these XMEs become better understood. This trial was registered at clinicaltrials.gov as NCT02346812. This information will be used by scientists to increase understanding of how Brassica vegetables modualte cancer risk.

Technical Abstract: Brassica vegetables may modulate cancer risk by regulation of xenobiotic metabolizing enzymes (XMEs). In a randomized crossover study, the effect of kale consumption on CYP1A2, CYP2A6, XO, and NAT2 activity was determined by urinary caffeine metabolite ratios, UGT1A1 activity by serum bilirubin concentrations, and GSTA protein and GST activity in blood by ELISA. Adults (n=25) consumed a basal diet supplemented with kale and radish for 14 days or control vegetables. The kale diet increased CYP1A2 activity by 16.4% on day 8 and 15.2% on day 15 compared to control. Conjugated bilirubin was reduced by the kale diet, decreasing from 19.4 to 14.3 to 9.5% of total bilirubin on days 1, 8, and 15, respectively, which may be explained by induction of MRP2. Other XMEs were not affected by diet. The implications of these results for cancer risk will be clarified as the functions of these XMEs become better understood.