Ginger and chemotherapy induced nausea:

Jacob Schor ND FABNO

May 15, 2009

Today’s Denver Post contains a front page story from the Associated Press reporting that ginger extracts reduce nausea caused by chemotherapy.  It is an interesting story but hardly news.  We’ve been using ginger for this purpose for as long as I’ve been in practice.  What’s going on here? Why the sudden excitement? http://www.denverpost.com/ci_12374731

The first thing to recall is that the American Society of Clinical Oncology is set to hold their annual meeting later this month.  This meeting is big in the world of cancer.  I have colleagues who attend and I look forward to learning the new and valuable information they glean from the presentations.  Of course much of the information is esoteric and related to relative efficacy of new or revised chemotherapy protocols.  Still, interesting and useful tidbits show up.

Actually this information is exciting.  More exciting because the researchers spent years performing earlier research that led up to this study and ASCO has not only accepted it but is promoting it. 

I feel like I’ve woken up this morning in an alternate universe where the medical powers freely accept the power of natural medicine.  Here’s the same story in today’s Bio-Medicine webpage http://www.bio-medicine.org/medicine-news-1/Ginger-Eases-Nausea-From-Chemo-45967-1/

The same story as we read in our Denver paper has been reprinted word for word in like a bazillion other news sites, online and in print.  ASCO’s webpage allows us to download the original abstract and get the basic information. http://www.abstract.asco.org/AbstView_65_35351.html

Patients who had already undergone chemotherapy and experienced nausea despite taking the standard anti-nausea drugs were randomized to receive either placebo or varying sized doses of ginger. (0.5 to1.5 grams per day). In all 644 patients went through the study, the lower doses, 0.5 to 1.5 grams worked the best, reducing nausea very significantly, almost by half.

These news stories don’t mention another paper on pretty much the same topic published just this month, May 2009, in Supportive Cancer Care.  This study followed 162 patients and used slightly higher doses of ginger, ranging between 1 and 2 grams per day.  The researchers were unable to see any measurable benefit from using ginger.  As the authors wrote,

“There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting.” 

Here’s an interesting point,

“ Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received.”

What is aprepitant?  According to Wiki: “Aprepitant is manufactured by Merck & Co. under the brand name Emend for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It was approved by the FDA in 2003.” 

OK, ginger is good in moderate doses but we need to be careful mixing it with the drug patients are often prescribed for nausea. 

Though not apparent in reading either of these abstracts there is an apparent difference pointed out at least in the news stories.  In the ASCO study that suggests ginger works so well, patients were given ginger starting a full 3 days prior to receiving chemotherapy.  It may be that this is key to effectiveness.

A September 2007 paper by Hickock and Morrow, who are among the authors of the new ASCO paper, describes the research and rationale that led them to start the study they are now presenting.   They moved ahead with this larger study based on positive results they had seen in earlier smaller trials.

Full text of this early paper is available for free at: http://cigjournals.metapress.com/content/19tq751436655506/

(find and click on the tiny little link that says pdf on this page to download the full paper)

Reading the small print in this paper reveals they weren’t using straight store bought ginger spice but a standardized product that contained 1.5% gingerols, zingerone and shogaol by weight.

Other authors have published papers describing similar positive benefits over the years.

In June 2008, Levine et al reported that a combination of high protein meals and ginger were helpful in reducing nausea from chemo. Their study size though was quite small, only 28 patients.

But results have been inconsistent.

A 2004 paper published in the International Journal of Gynecological Cancer tried ginger on 43 patients receiving cisplatin and found no benefit in its use.

Interesting Sharma et al found a positive effect against cisplatin induced vomiting 7 years prior.  But they were using dogs as test subjects. 

This idea that ginger might be helpful is not new.  I recall that we suggested ginger for this purpose when I was a student 20 years ago.

In some studies it helps, in others it doesn’t.  Perhaps the benefit varies with dosing.  For the time being it makes sense to pattern our use after the current Morrow and Hickock study;   In order to prevent chemotherapy triggered nausea, start taking moderate doses of ginger , 0.5 to1 gram per day, three days prior to getting chemo and continue taking it for three more days after receiving chemo.  Again, they used a standardized extract not plain ground ginger from the spice rack.  Benefit may well vary with the type of chemo received.  Mixing chemo with the drug Emend might be a mistake.

References:

Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients.

Meeting: 2009 ASCO Annual Meeting

Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 9511)

Author(s): J. L. Ryan, C. Heckler, S. R. Dakhil, J. Kirshner, P. J. Flynn, J. T. Hickok, G. R. Morrow; University of Rochester Medical Center, Rochester, NY; Wichita CCOP, Witchita, KS; HOACNY CCOP, Syracuse, NY; Metro-MN CCOP, St. Louis Park, MN

Abstract:

Background: Despite the widespread use of antiemetics, post-chemotherapy nausea and vomiting continue to be reported by up to 70% of patients receiving chemotherapy. Ginger (Zingiber Officinale), an ancient spice, is used by practitioners worldwide to treat nausea and vomiting. We conducted a multi-site, phase II/III randomized, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for chemotherapy-related nausea in cancer patients at the University of Rochester-affiliated Community Clinical Oncology Program (CCOP) member sites. Methods: Cancer patients who experienced nausea following any chemotherapy cycle and were scheduled to receive at least three additional cycles were eligible. Patients were randomized into four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. All patients received 5-HT3 receptor antagonist antiemetics on Day 1 of all cycles and took three 250mg capsules of ginger or placebo twice daily for six days starting three days before the first day of the next two cycles. Patients reported the severity of nausea during the morning, afternoon, evening, and night on a 7-point semantic rating scale ('1' = 'Not at all Nauseated' and '7' = "Extremely Nauseated") for Days 1-4 of each cycle. The goal was to determine if ginger was more effective than placebo in controlling chemotherapy-related nausea in participants given a 5-HT3 receptor antagonist antiemetic. Results: A total of 644 patients were accrued (90% female, mean age = 53). Breast (66%), alimentary (6.5%), and lung (6.1%) cancers were the most common cancer types. Analysis of covariance (ANCOVA) examined change in nausea in the four study arms on Day 1 of cycles 2 and 3. All doses of ginger significantly reduced nausea (p=0.003). The largest reduction in nausea occurred with 0.5g and 1.0g of ginger. Also, time of day had a significant effect on nausea (p<0.001) with a linear decrease over 24 hours for patients using ginger. Conclusions: Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea during the first day of chemotherapy. Supported by NCI PHS grants 1R25CA10618 and U10CA37420.

Support Care Cancer. 2009 May;17(5):563-72. Epub 2008 Nov 13.

    Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting.

    Zick SM, Ruffin MT, Lee J, Normolle DP, Siden R, Alrawi S, Brenner DE.

    Departments of Family Medicine, University of Michigan, Ann Arbor, MI, USA, szick@med.umich.edu.

    GOALS OF WORK: Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown. MATERIALS AND METHODS: We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT(3) receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding. MAIN RESULTS: There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group. CONCLUSIONS: Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT(3) receptor antagonists and/or aprepitant.

Support Care Cancer. 2009 May;17(5):563-72. Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting.

    Zick SM, Ruffin MT, Lee J, Normolle DP, Siden R, Alrawi S, Brenner DE.

    Departments of Family Medicine, University of Michigan, Ann Arbor, MI, USA, szick@med.umich.edu.

    GOALS OF WORK: Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown. MATERIALS AND METHODS: We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT(3) receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding. MAIN RESULTS: There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group. CONCLUSIONS: Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT(3) receptor antagonists and/or aprepitant.

Support Cancer Ther. 2007 Sep 1;4(4):247-50.

    A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

    Hickok JT, Roscoe JA, Morrow GR, Ryan JL.

    James P. Wilmot Cancer Center at the University of Rochester, NY.

    Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

  J Altern Complement Med. 2008 Jun;14(5):545-51.

    Protein and ginger for the treatment of chemotherapy-induced delayed nausea.

    Levine ME, Gillis MG, Koch SY, Voss AC, Stern RM, Koch KL.

    Department of Psychology, Siena College, Loudonville, NY 12211, USA. mlevine@siena.edu

    BACKGROUND: Nausea that develops during the period that begins 24 hours after the administration of chemotherapy is called delayed nausea, and occurs in many patients with cancer. Meals high in protein decrease the nausea of motion sickness and pregnancy, possibly by reducing gastric dysrhythmias. Ginger also has antinausea properties. OBJECTIVES: To explore the use of protein meals with ginger for the treatment of the delayed nausea of chemotherapy. DESIGN: Twenty-eight (28) patients with cancer receiving chemotherapy for the first time were assigned to 1 of 3 groups. For 3 days beginning the day after their chemotherapy, Control Group patients continued with their normal diet, Protein Group patients consumed a protein drink and ginger twice daily, and High Protein Group patients consumed a protein drink with additional protein and ginger twice daily. OUTCOME MEASURES: Patients recorded in a diary each day whether they had experienced nausea, whether their nausea had been frequent, whether their nausea had been bothersome, and whether they had needed any antiemetic medication. Gastric myoelectrical activity was assessed in 5 patients before and after ingestion of a high protein meal and ginger. RESULTS: Reports of nausea, frequent nausea, and bothersome nausea were significantly less common among High Protein Group patients than among Control and Protein Group patients. Furthermore, significantly fewer patients in the High Protein Group used antiemetic medication. Differences between the Protein and Control groups were not statistically significant. In the 5 patients who had tests of gastric myoelectrical activity performed, a significant decrease in gastric dysrhythmia occurred after ingestion of the protein and ginger. CONCLUSIONS: High protein meals with ginger reduced the delayed nausea of chemotherapy and reduced use of antiemetic medications. Protein with ginger holds the potential of representing a novel, nutritionally based treatment for the delayed nausea of chemotherapy.

A 2004 paper in the International Journal of Gynecological Cancers showed no benefit. Int J Gynecol Cancer. 2004 Nov-Dec;14(6):1063-9.

    Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.

    Manusirivithaya S, Sripramote M, Tangjitgamol S, Sheanakul C, Leelahakorn S, Thavaramara T, Tangcharoenpanich K.

    Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Dusit district, Bangkok, Thailand. sumonmalm@hotmail.com

    To determine whether ginger had antiemetic effect in cisplatin-induced emesis, we conducted a randomized, double-blinded crossover study in 48 gynecologic cancer patients receiving cisplatin-based chemotherapy. Subjects were randomly allocated to regimen A or regimen B in their first cycle of the study. All patients received standard antiemetics in the first day of cisplatin administration. In regimen A, capsules of ginger root powder were given orally 1 g /day for 5 days, starting on the first day of chemotherapy. In regimen B, placebo was given on the first day and metoclopramide was given orally thereafter for 4 days. The patients were then crossed over to receive the other antiemetic regimen in their next cycle of chemotherapy. Among 43 evaluable patients who received both cycles of treatment, success in controls of nausea and emesis were not significantly different between the two regimens in both acute and delayed phases. Restlessness, as a side effect, occurred more often in metoclopramide arm compared to ginger arm (P=0.109). In conclusion, addition of ginger to standard antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-induced emesis. In delayed phase, ginger and metoclopramide have no statistically significant difference in efficacy.

Int J Gynecol Cancer. 2004 Nov-Dec;14(6):1063-9. Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.

    Manusirivithaya S, Sripramote M, Tangjitgamol S, Sheanakul C, Leelahakorn S, Thavaramara T, Tangcharoenpanich K.

    Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Dusit district, Bangkok, Thailand. sumonmalm@hotmail.com

    To determine whether ginger had antiemetic effect in cisplatin-induced emesis, we conducted a randomized, double-blinded crossover study in 48 gynecologic cancer patients receiving cisplatin-based chemotherapy. Subjects were randomly allocated to regimen A or regimen B in their first cycle of the study. All patients received standard antiemetics in the first day of cisplatin administration. In regimen A, capsules of ginger root powder were given orally 1 g /day for 5 days, starting on the first day of chemotherapy. In regimen B, placebo was given on the first day and metoclopramide was given orally thereafter for 4 days. The patients were then crossed over to receive the other antiemetic regimen in their next cycle of chemotherapy. Among 43 evaluable patients who received both cycles of treatment, success in controls of nausea and emesis were not significantly different between the two regimens in both acute and delayed phases. Restlessness, as a side effect, occurred more often in metoclopramide arm compared to ginger arm (P=0.109). In conclusion, addition of ginger to standard antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-induced emesis. In delayed phase, ginger and metoclopramide have no statistically significant difference in efficacy.

J Ethnopharmacol. 1997 Jul;57(2):93-6.

    Antiemetic efficacy of ginger (Zingiber officinale) against cisplatin-induced emesis in dogs.

    Sharma SS, Kochupillai V, Gupta SK, Seth SD, Gupta YK.

    Department of Pharmacology, All India Institute of Medical Sciences, New Delhi.

    Effect of ginger (Zingiber officinale Roscoe, Zingiberaceae) extracts (acetone, 50% ethanolic and aqueous) were investigated for antiemetic activity against emesis induced by 3 mg/kg cisplatin (the 100% emetic dose i.v.) in-healthy mongrel dogs. The acetone and 50% ethanolic extract at the doses of 25, 50, 100 and 200 mg/kg p.o. exhibited significant protection while aqueous extract at these doses was ineffective against cisplatin emesis. The acetone extract was more effective than ethanolic extract. However, both were less effective when compared to 5-HT3 receptors antagonist-granisetron. Neither of the ginger extract was effective against apomorphine-induced emesis. The findings suggest that ginger could be an effective and cheap antiemetic adjunct to cancer chemotherapy.


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