Ginger May Reduce Colorectal Cancer Risk

Study finds ginger has the potential to decrease eicosanoid levels

By Jacob Schor, ND, FABNO

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Reference

Zick SM, Turgeon DK, Vareed SK, et al. Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer. Cancer Prev Res (Phila). 2011;4(11):1929-1937.
 

Design

Randomized placebo-controlled trial
 

Participants

33 healthy participants who were at ‘normal risk’ for developing colorectal cancer, were not taking chronic medication, and had not taken aspirin or NSAIDs for 2 weeks prior were recruited; 16 were assigned to the ginger arm and 17 to a placebo arm. Data from all these were included in analysis, although 2 participants in the ginger and 1 in the placebo arm did not complete the full trial.
 

Study Medication and Dosage

Ginger root extract, 250 mg capsules (Pure Encapsulations dry root extract, normalized to 15 mg total gingerols) was the medication used in this study. The participants took 8 capsules per day with food, a total daily dose of 2.0 grams. This is equivalent to approximately 20 grams of fresh ginger root per day. Treatment continued for 28 days.
 

Outcome Measures

Participants underwent 2 flexible sigmoidoscopies, 1 before ginger treatment and the second 28 days after starting to take the ginger. The second procedure was performed as close as possible to 24 hours after the participant took the final dose of ginger. Four tissue samples were obtained during each procedure from 20–25 cm from the anal sphincter. Eicosanoid levels (including PGE2, 5-HETE, 12-HETE,15-HETE,13-HODE) in the biopsies were quantified, and levels were expressed per protein or per free arachidonic acid.
 

Key Findings

There were no significant differences in mean percentage change between baseline and day 28 for any of the eicosanoids, when normalized to protein. When normalized to free arachidonic acid, there was a significant decrease in mean percent change in PGE2 (P=0.05) and 5-HETE (P=0.04), and a trend toward significant decreases in 12-HETE (P=0.09) and 15-HETE (P=0.06). Ginger has the potential to decrease eicosanoid levels, perhaps by inhibiting their synthesis from arachidonic acid. Ginger also appears to be tolerable and safe.
 

Practice Implications

This study brings us a step closer toward knowing whether ginger could be used to prevent colorectal cancer (CRC). There are a growing number of reasons that we should consider this.
 
The first is that ginger acts as an anti-inflammatory and blocks both cyclooxygenase (COX) and lipoxygenase (LOX) enzymes that produce procancer eicosanoids. Aspirin protects against CRC, and it only blocks the COX enzymes. Evidence suggests that inhibiting both the COX and the LOX pathways will slow tumor growth more than inhibiting either pathway alone.
 
The second is that ginger has antitumor action independent of these anti-inflammatory effects. “The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression.”1 An extract of “ginger, can enhance the anticancer effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).”  Ginger extract “potentiated TRAIL-induced apoptosis in human HCT116 colon cancer cells and … this correlated with the up-regulation of TRAIL death receptor (DR) 4 and DR5.”  This was “not cell-type specific, as its expression was also up-regulated in prostate, kidney, breast, and pancreatic cancer cell lines.”2
 
As a side note, ginger has long been used to reduce chemotherapy-induced nausea, and a number of human trials have investigated this action.3,4,5,6,7
 
Two other studies on ginger were published last summer that deserve mention.
 
Writing in the July 25 issue of the International Journal of Cancer, Ju et al reported that a ginger extract “greatly enhances the number of tumor-infiltrating lymphocytes in murine tumors.” Tumor-infiltrating lymphocytes (TILs) play an important role in the immune response against tumors. Cancer patients have a better prognosis if they have a high number of tumor-reactive lymphocytes infiltrating their tumors.
 
Ju’s team found that CD8 T cells isolated from mice pretreated with ginger extracts, but not from control mice, infiltrated tumors and tumor-draining lymph nodes, suggesting that ginger extracts can be used to trigger tumor immunotherapy.8
 
In August 2011, Karna et al from the Georgia State University reported, “Whole ginger extract (GE) exerts significant growth-inhibitory and death-inductory effects in a spectrum of prostate cancer cells.”9 This is the first report to suggest ginger extract might be useful for prostate cancer. Feeding mice 100 mg/kg of ginger extract/day inhibited growth of prostate cancer xenografts in nude mice by approximately 56%, as shown by measurements of tumor volume.
 
We must mention 1 additional study regarding eicosanoids, although it used curcumin, not ginger.
 
In March 2011 Robert Carroll et al from the University of Illinois reported on a randomized, controlled clinical trial they had completed giving 41 human volunteers doses of curcumin.  All participants were smokers with a history of 8 or more aberrant crypt foci (ACF) on a screening colonoscopy. It was already known that curcumin reduces PGE2 via COX inhibition in rats. Study participants took either 2 or 4 grams of curcumin per day for 30 days. 
 
While neither dose of curcumin reduced PGE2 or 5-HETE within the ACF, there was a significant (40%) reduction in ACF number in those participants taking the 4 g dose (P<0.005). The number of ACF was not reduced in the 2 g group. The 4 g group also had a significant, 5-fold increase in plasma curcumin levels.10 These researchers theorized that the poor absorption of curcumin would allow more to reach the colonic mucosal tissue, but could it be that increasing plasma levels through absorption would be associated with greater effect on ACF number?
 
This curcumin study raises the question of whether a ginger and curcumin combination might prove to have greater effect than either alone.
 
 
This curcumin study raises the question of whether a ginger and curcumin combination might prove to have greater effect than either alone. A 2009 paper suggests that a combination of the 2 has utility in healing skin abrasions in rats whose healing capacities had been suppressed with corticosteroid treatment.11
 
Zick et al’s recent study on ginger and eicosanoids moves us a step closer. Ginger may someday have an active role to play in CRC prevention.
 
For more research involving integrative oncology, click here.

About the Author

Jacob Schor ND, FABNO, is a graduate of National College of Naturopathic Medicine, Portland, Oregon, and now practices in Denver, Colorado. He served as president to the Colorado Association of Naturopathic Physicians and is on the board of directors of the Oncology Association of Naturopathic Physicians. He is recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the International Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clinician's Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians. His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal, where he is the Abstracts & Commentary editor.

References

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  2.  Yodkeeree S, Sung B, Limtrakul P, Aggarwal BB. Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: Evidence for an essential role of reactive oxygen species. Cancer Res. 2009;69(16):6581-6589.
  3.  Pillai AK, Sharma KK, Gupta YK, Bakhshi S. Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy.  Pediatr Blood Cancer. 2011;56(2):234-238.
  4.  Zick SM, Ruffin MT, Lee J, et al.  Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting.  Support Care Cancer. 2009;17(5):563-572.
  5.  Levine ME, Gillis MG, Koch SY, Voss AC, Stern RM, Koch KL.  Protein and ginger for the treatment of chemotherapy-induced delayed nausea. J Altern Complement Med. 2008;14(5):545-551.
  6.  Nanthakomon T, Pongrojpaw D.  The efficacy of ginger in prevention of postoperative nausea and vomiting after major gynecologic surgery. J Med Assoc Thai. 2006;89 Suppl 4:S130-S136.
  7.  Manusirivithaya S, Sripramote M, Tangjitgamol S, et al. Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin. Int J Gynecol Cancer. 2004;14(6):1063-1069.
  8.  Ju SA, Park SM, Lee YS, et al. Administration of 6-gingerol greatly enhances the number of tumor-infiltrating lymphocytes in murine tumors.  Int J Cancer. 2011 Jul 25. doi: 10.1002/ijc.26316. [
  9.  Karna P, Chagani S, Gundala SR, et al. Benefits of whole ginger extract in prostate cancer. Br J Nutr. 2011:1-12.
  10.  Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011;4(3):354-364.
  11.  Bhagavathula N, Warner RL, DaSilva M, et al. A combination of curcumin and ginger extract improves abrasion wound healing in corticosteroid-impaired hairless rat skin. Wound Repair Regen. 2009;17(3):360-366.