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Preventing/Treating Possible Side Effects of Chemotherapy
Using Glutamine for Protection Against Chemotherapy Toxicity
By taking glutamine, it might be possible to prevent/delay the onset of peripheral neuropathy due to taxane chemotherapy.

I began to experience peripheral neuropathy following the first Taxotere infusion, notwithstanding 20 mg of Decadron IV as pre-medication. Paresthesais (burning, tingling) in my legs/feet and hands began about 6 hours after infusion and escalated with each treatment. I asked my medical oncologist and urologist about drugs to lessen this toxicity and both said that there are none and if the patient cannot tolerate it, the condition becomes dose- or treatment-limiting.

However, after I was suffering from deep nail neuropathy, a fellow PCa patient told me about glutamine as a protectant against chemotherapy toxicities. Glutamine is a neutral gluconeogenic amino acid that is vital in whole-body nitrogen metabolism and it is depleted by many traumas such as surgery, infections, and cancer. Replacement thereof is necessary for the body to function properly. Powdered glutamine is readily available in drug stores and health food stores and costs about $45 for 500 grams. Its most common use is by body builders or athletes following a strenuous work-out.

A significant body of peer-reviewed trials and reports exist detailing the chemoprotectant qualities of glutamine. Saverese, et al. (1) reported that up to 75% of Taxol patients experience myalgias (muscular pain) and arthralgias (joint pain) and that 10 g p.o. t.i.d. (orally, 3 X/day) is a cost-effective, nontoxic method of preventing/lessening these toxicities. Vahdat (2) reported that 10 g p.o. t.i.d. for 4 days started 24 hours after chemo infusion significantly reduced peripheral neuropathy, dysethesias (numbness) in fingers/toes, deterioration of gait, and paresthesais (burning, tingling) resulting from Taxol infusions. Fahr, et al. (3) reported that glutamine may decrease tumor growth by enhancing NK (natural killer) cells. Rouse K, et al. (4) reported that oral glutamine enhances the selectivity of antitumor drugs by protecting normal tissues and possibly sensitizing tumor cells to chemotherapy treatment related injury.

(Note 1: added by editor: Bill Aishman feels that the "24 hours after chemo" statement doesn't matter -- his recommendation based on his own experience is to take it all the time when on chemotherapy(7 days/week) or more specifically "my feet are a mess and I definitely see a difference when I don't take it)."

(Note 2: glutamine is a white powder that doesn't dissolve well. Stir well and use a cold to warm to hot liquid when mixing it. The decomposition temperature of glutamine is 185ºC -- well above the boiling point of water(100ºC.) Thus, it would seem that glutamine is ok to mix with hot drinks. It has no taste of its own.)

Klimberg, et al (5) reported that a tumor acts as a ‘glutamine trap’ depleting the host of glutamine and resulting in cachexia (weight loss); supplemental glutamine does not make tumors grow, but in fact results in decreased growth through stimulation of the immune system; and when given with chemotherapy, glutamine protects the host and increases the selectivity of therapy for the tumor. Anderson, et al (6) states that oral glutamine (as a mouthwash) is simple to use and increases the comfort of many patients at high risk of developing stomatitis (mouth sores) as a result of intensive cancer chemotherapy. Miller (7) reported that the use of glutamine seems to prevent gut and oral toxic side-effects, and may increase the effectiveness of some chemotherapy drugs. Myers CE (8) states that the body’s need for glutamine can increase dramatically following injury, infection, or the progression of cancer and in these cases, the need for glutamine can exceed the ability of the body to supply it; glutamine is one of the major energy sources needed for the gastrointestinal tract cells to recover from chemotherapy; a glutamine mouthwash 2 X/day will dramatically lessen stomatitis (mouth sores) in patients on chemotherapy; glutamine plays a critical role in the body’s ability to defend itself against cancer.

In summary, significant benefits are claimed in medical literature for glutamine supplementation during chemotherapy (and during radiation): a.) it provides the necessary energy-producing amino acid to replace that which is lost during chemotherapy, b.) it minimizes chemotherapy side effects, including neuropathy, arthralgia (joint pain), myalgia (muscular pain), paresthesias (burning, tingling sensations), dysethesias (impairment of sensation), and stomatitis (mouth sores); by eliminating or lessening these side effects, it is possible to extend the duration or dose of chemotherapy to induce apoptosis (cell death), c.) it prevents cachexia (weight loss), and d.) it enhances the immune system to produce natural killer (NK) cells, thus suppressing tumor growth.

If one collectively considers these benefits it is reasonable to assume that there is a strong potential for increased survival as a result of glutamine supplementation during chemotherapy (or radiation).

However, two reports (9) state that since tumors require glutamine, providing dietary glutamine may stimulate growth in some tumors. Myers (8) addresses this issue by stating that while glutamine is needed for tumor growth, it also plays a critical role in the ability of our body to defend itself against cancer. Myers continues with a caution to not treat yourself with glutamine without first discussing this in detail with your doctor.

Obviously, I am taking oral glutamine now and intend to notify my medical oncologist that I will be taking 10 g X 4/day during any renewed chemotherapy treatments, since there appears to be no side-effects. Glutamine is most effective in powder form; it is odorless and tasteless and should be mixed with a cool drink, as hot drinks lessen the effectiveness. A discussion of glutamine (and other amino acids), suggested dosing schedules, and suggested support additives thereto can be found in a book by Sahley, et al. (10).

At the suggestion of a PCa friend I also searched another chemoprotectant that seems to be very effective. I found 22 trials and reports detailing the efficacy of Amifostine (Ethyol) to relieve most toxicities from cancer chemotherapy. But after searching and briefing the 22 reports, I retrieved the specification sheets regarding the drug and decided that I definitely prefer glutamine as my chemoprotectant. Amifostine is infused immediately before chemotherapy, but you must have 2 pre-medicines to protect from the protectant; you must be laying down (supine position) and your vital signs are checked every 5 minutes; it can cause severe nausea and vomiting; systolic blood pressure may decrease significantly and the infusion must be stopped; you must drink sufficient liquids because amifostine causes severe dehydration; you may experience hypocalcemia (burning, tingling, muscle cramps) during infusion, dizziness, flushing, and/or hiccups.

While amifostine seems to be effective in eliminating/reducing chemotoxicity, this solution seems worse than the effects of chemotherapy toxicities and I prefer glutamine (simple to use, with no reported side-effcts) as my chemoprotectant.

Copyright © 2002 Bill Aishman

blaishman@worldnet.att.net

NOTE: I am not a doctor and can not give medical advice. I am not a medical researcher. I am a prostate cancer patient and I performed this layman’s analysis for my own decision-making purposes. In conjunction with a medical team, every cancer patient must make their own decisions regarding treatment options. I make no claim that this analysis is definitive or complete. Every HRPC patient should thoroughly review the Life Extension Foundation’s web site www.lef.org Prostate Cancer-Late Stage. I invite any and all additive contributions to my analysis that will provide patients a framework which will enhance their ability to make informed decisions regarding the use of chemotherapy protocols in their struggle with prostate cancer.

References.

(1) Saverese D, et al: Glutamine Treatment of Paclitaxel-Induced Myalgias and Arthralgias. J Clin Oncol;Vol 16,No 12:3918-19, 1998.

(2) Vadhat L: Reduction of Paclitaxel-Induced Peripheral Neuropathy With Glutamine. Chemotherapy Foundation Symposium XVII;Nov 8-11, 2000, abstract 41.

(3) Fahr MJ, et al.: Glutamine enhances immunoregulation of tumor growth. JPEN J Parenter Entral Nutr 1994 Nov-Dec;18(6):471-6.

(4) Rouse K, et al.: Glutamine enhances selectivity of chemotherapy through chenges in glutathione metabolism. Ann Surg 1995 Apr;22(4):420-6.

(5) Klimberg VS, et al.: Glutamine, Cancer, and its Therapy. Am J Surg 1996 nov;172(5):418-24.

(6) Anderson PM, et al.: Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998 Oct 1:83(7):1433-9.

(7) Miller AL: Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev 1999 Aug;4(4):239-48.

(8) Myers CE: Prostate Forum, March 2000;Vol 5, No 34.

(9) Altern Med Rev 1999;4:239-48; and J Surg Res 1990;48:319-23.

(10) Heal with Amino Acids and Nutrients; Billie J Staley, Ph.D. , et al.