Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer

Abstract

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxy-eicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk.

Ginger in gastrointestinal disorders: A systematic review of clinical trials

“…however, it did not decrease eicosanoid levels in people at increased risk for colorectal cancer (Zick et al, 2015). Moreover, Zick et al reported no significant difference in eicosanoids level in 30 subjects at normal risk for colorectal cancer.…”

“…In a randomized clinical trial, 20 subjects at increased risk for colorectal cancer were assigned to receive either 2 g/day ginger or placebo for 28 days. They showed that ginger was tolerable and safe; however, it did not decrease eicosanoid levels in people at increased risk for colorectal cancer (Zick et al., ). Moreover, Zick et al.…”

“…However, ginger did not alter 15-hydroxyprostaglandin dehydrogenase (PGDH) protein expression in either increased or normal risk participants (Jiang et al, 2013). Some findings of other studies about beneficial effects of ginger and its constituents in GI cancer patients included: inhibition of COX and decrease in PGE2 concentrations in colorectal cancer (Levine et al, 2008), reduction in the incidence and multiplicity of adenomas (Zick et al, 2015), decrease in proliferation (hTERT and MIB-1) and differentiation (p21waf1/cip1) in colonocytes (Stoner, 2013), inhibition of CYP450, 1-aminobenzotriazole, and aldo-keto reductase in human liver microsomes, prevention of the formation of M14 and M15 and 18β-glycyrrhetinic acid in human liver microsomes (Chen, Soroka, Zhu, & Sang, 2013).…”

Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management

“…In this pilot study, 21 subjects with high risk for colorectal cancer were assigned to placebo or ginger group, administered with 2.0 g ginger daily for 28 days and baseline and 28‐day levels of prostaglandin E2, leukotriene B4, 13‐hydroxy‐octadecadienoic acids, and 5‐, 12‐, & 15‐hydroxy‐eicosatetraenoic acid were quantified in the colonic mucosa of the subjects. The study reported that ginger was not effective in decreasing eicosanoid levels in subjects at high risk for colorectal cancer . However, it should be noted that the study was a pilot study associated with limitations such as small sample size and large subject‐to‐subject variation in eicosanoid levels.…”

“…Although there exists no clinical trial that verified the efficacy of ginger in treating cancer in humans, there has been one clinical trial that investigated the role of ginger extract in chemoprevention of colorectal cancer . In this pilot study, 21 subjects with high risk for colorectal cancer were assigned to placebo or ginger group, administered with 2.0 g ginger daily for 28 days and baseline and 28‐day levels of prostaglandin E2, leukotriene B4, 13‐hydroxy‐octadecadienoic acids, and 5‐, 12‐, & 15‐hydroxy‐eicosatetraenoic acid were quantified in the colonic mucosa of the subjects.…”