Interactions with Dietary Supplements
Antioxidants
Cyclophosphamide requires activation by the liver through a process called oxidation. In
theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the
activation of cyclophosphamide. There is no published research linking antioxidant vitamins to
reduced cyclophosphamide effectiveness in cancer treatment. In a study of mice with vitamin A
deficiency, vitamin A supplementation enhanced the anticancer action of
cyclophosphamide.1 Another animal research report indicated that vitamin C may increase the effectiveness of
cyclophosphamide without producing new side effects.2 Preliminary human research
found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide
therapy increased the survival of people with small-cell lung cancer treated with
cyclophosphamide.3 It is too early to know if adding antioxidants to
cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be
toxic in high amounts.
Intravenous injections of the antioxidant,
glutathione, may protect the bladder from damage caused by cyclophosphamide. Preliminary
evidence suggests, but cannot confirm, a protective action of glutathione in the bladders of
people on cyclophosphamide therapy.4 There is no evidence that glutathione taken by
mouth has the same benefits.
Glutamine
Though cancer cells use glutamine as a fuel source, studies in humans have not found that
glutamine stimulates growth of cancers in people taking chemotherapy.5 6
In fact, animal studies show that glutamine may actually decrease tumor growth while
increasing susceptibility of cancer cells to radiation and chemotherapy,7
8 though such effects have not yet been studied in humans.
Glutamine has successfully reduced chemotherapy-induced mouth sores. In one trial, people
were given 4 grams of glutamine in an oral rinse, which was swished around the mouth and then
swallowed twice per day.9 Thirteen of fourteen people in the study had fewer days
with mouth sores as a result. These excellent results have been duplicated in
some,10 but not all11 double-blind research. In another study, patients
receiving high-dose paclitaxel and melphalan
had significantly fewer episodes of oral ulcers and bleeding when they took 6 grams of
glutamine four times daily along with the chemotherapy.12
One double-blind trial suggested that 6 grams of glutamine taken three times per day can
decrease diarrhea caused by
chemotherapy.13 However, other studies using higher amounts or intravenous
glutamine have not reported this effect.14 15
Intravenous use of glutamine in people undergoing bone marrow transplants, a procedure
sometimes used to allow very high amounts of chemotherapy to be used, has led to reduced
hospital stays, leading to a savings of over $21,000 for each patient given
glutamine.16
Melatonin
High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce
their side effects or improve drug efficacy. One study gave melatonin at night in combination
with the drug triptorelin to men with metastatic prostate cancer.17 All of these
men had previously become unresponsive to triptorelin. The combination decreased PSA
levels—a marker of prostate cancer progression—in eight of fourteen patients,
decreased some side effects of triptorelin, and helped nine of fourteen to live longer than
one year. The outcome of this preliminary study suggests that melatonin may improve the
efficacy of triptorelin even after the drug has apparently lost effectiveness.
N-acetyl cysteine
(NAC)
NAC, an amino acid–like supplement that possesses antioxidant activity, has been used in four human
studies to decrease the kidney and bladder toxicity of the chemotherapy drug
ifosfamide.18 19 20 21 These studies used
1–2 grams NAC four times per day. There was no sign that NAC interfered with the
efficacy of ifosfamide in any of these studies. Intakes of NAC over 4 grams per day may cause
nausea and vomiting.
The newer anti-nausea drugs prescribed for people taking chemotherapy lead to greatly
reduced nausea and vomiting for most people. Nonetheless, these drugs often do not totally
eliminate all nausea. Natural substances used to reduce nausea should not be used instead of
prescription anti-nausea drugs. Rather, under the guidance of a doctor, they should be added
to those drugs if needed. At least one trial suggests that NAC, at 1,800 mg per day may reduce
nausea and vomiting caused by chemotherapy.22
Selenium
Patients being treated with cyclophosphamide and cisplatin for ovarian cancer were given a multivitamin preparation, with or without 200 mcg
of selenium per day. Compared with the group not receiving selenium, those receiving selenium
had a smaller reduction in white blood cell count and fewer chemotherapy side effects such as
nausea, hair loss, weakness, and loss of appetite.23
Spleen
Extract
Patients with inoperable head and neck cancer were treated with a spleen peptide preparation
(Polyerga®) in a double-blind trial during chemotherapy with cisplatin and
5-FU.24 The spleen preparation had a significant stabilizing effect on certain
white blood cells. People taking it also experienced stabilized body weight and a reduction in
the fatigue and inertia that usually accompany this combination of chemotherapy agents.
Beta-carotene and
Vitamin E
Chemotherapy frequently causes mouth sores. In one trial, people were given approximately
400,000 IU of beta-carotene per day for three weeks and then 125,000 IU per day for an
additional four weeks.25 Those taking beta-carotene still suffered mouth sores, but
the mouth sores developed later and tended to be less severe than mouth sores that formed in
people receiving the same chemotherapy without beta-carotene.
In a study of chemotherapy-induced mouth sores, six of nine patients who applied vitamin E
directly to their mouth sores had complete resolution of the sores compared with one of nine
patients who applied placebo.26 Others have confirmed the potential for vitamin E
to help people with chemotherapy-induced mouth sores.27 Applying vitamin E only
once per day was helpful to only some groups of patients in another trial,28 and
not all studies have found vitamin E to be effective.29 Until more is known, if
vitamin E is used in an attempt to reduce chemotherapy-induced mouth sores, it should be
applied topically twice per day and should probably be in the tocopherol (versus tocopheryl)
form.
Vitamin
A
A controlled French trial reported that when postmenopausal late-stage breast cancer patients
were given very large amounts of vitamin A (350,000–500,000 IU per day) along with
chemotherapy, remission rates were significantly better than when the chemotherapy was not
accompanied by vitamin A.30 Similar results were not found in premenopausal women.
The large amounts of vitamin A used in the study are toxic and require clinical
supervision.
Zinc
Irradiation treatment, especially of head and neck cancers, frequently results in changes to
normal taste sensation.31 32 Zinc supplementation may be protective
against taste alterations caused or exacerbated by irradiation. A double-blind trial found
that 45 mg of zinc sulfate three times daily reduced the alteration of taste sensation during
radiation treatment and led to significantly greater recovery of taste sensation after
treatment was concluded.33
Multivitamin-mineral
Many chemotherapy drugs can cause diarrhea,
lack of appetite, vomiting, and damage to the gastrointestinal tract. Recent anti-nausea
prescription medications are often effective. Nonetheless, nutritional deficiencies still
occur.34 It makes sense for people undergoing chemotherapy to take a high-potency
multivitamin-mineral to protect against deficiencies.
Taurine
Taurine has been shown to be depleted in people taking chemotherapy.35 It remains
unclear how important this effect is or if people taking chemotherapy should take taurine
supplements.
Thymus
peptides
Peptides or short proteins derived from the thymus gland, an important immune organ, have been
used in conjunction with chemotherapy drugs for people with cancer. One study using thymosin
fraction V in combination with chemotherapy, compared with chemotherapy alone, found
significantly longer survival times in the thymosin fraction V group.36 A related
substance, thymostimulin, decreased some side effects of chemotherapy and increased survival
time compared with chemotherapy alone.37 A third product, thymic extract TP1, was
shown to improve immune function in people treated with chemotherapy compared with effects of
chemotherapy alone.38 Thymic peptides need to be administered by injection. People
interested in their combined use with chemotherapy should consult a doctor.
1. Ghosh J, Das S. Role of vitamin A in prevention and treatment of
sarcoma 180 in mice. Chemotherapy 1987;33:211–8.
2. Taper HS, de Gerlache J, Lans M, Roberfroid M. Non-toxic potentiation
of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer
1987;40:575–9.
3. Jaakkola K, Lahteenmaki P, Laakso J, et al. Treatment with antioxidant
and other nutrients in combination with chemotherapy and irradiation in patients with
small-cell lung cancer. Anticancer Res 1992;12:599–606.
4. Nobile MT, Vidili MG, Benasso M, et al. A preliminary clinical study
of cyclophosphamide with reduced glutathione as uroprotector. Tumori
1989;75:257–8.
5. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation
in cancer patients receiving chemotherapy: A double-blind randomized study Nutr
1997;13:748–51.
6. van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral
glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity.
Cancer 1994;74:2879–84.
7. Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am
J Surg 1996;172:418–24.
8. Souba WW. Glutamine and cancer. Ann Surg
1993;218:715–28 [review].
9. Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy
induced stomatitis: a pilot study. J Lab Clin Med 1996;127:223–8.
10. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the
duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer
1998;83:1433–9.
11. Okuno SH, Woodhouse CO, Loprinzi CL, et al. Phase III controlled
evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil
(5-FU)-based chemotherapy. Am J Clin Oncol 1999;22:258–61.
12. Cockerham MB, Weinberger BB, Lerchie SB. Oral glutamine for the
prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous
bone marrow transplantation. Ann Pharmacother 2000;34:300–3.
13. Muscaritoli M, Micozzi A, Conversano L, et al. Oral glutamine in the
prevention of chemotherapy-induced gastrointestinal toxicity Eur J Cancer
1997;33:319–20.
14. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation
in cancer patients receiving chemotherapy: A double-blind randomized study Nutr
1997;13:748–51.
15. Van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral
glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity.
Cancer 1994;74:2879–84.
16. MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of
Glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J
Am Diet Assoc 1994;94:1263–6.
17. Lissoni P, Cazzaniga M, Tancini G, et al. Reversal of clinical
resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin:
Efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone.
Eur Urol 1997;31:178–81.
18. Holoya PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide
toxicity with oral acetylcysteine. Sem Oncol 1983;10(suppl 1):66–71.
19. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine’s
preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62–5.
20. Loehrer PJ, Williams SD, Einhorn LH. N-Acetylcysteine and ifosfamide
in the treatment of unresectable pancreatic adenocarcinoma and refractory testicular cancer.
Sem Oncol 1983;10(suppl 1):72–5.
21. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced
hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.
22. De Blasio F et al. N-acetyl cysteine (NAC) in preventing nausea and
vomiting induced by chemotherapy in patients suffering from inoperable non small cell lung
cancer (NSCLC). Chest 1996;110(4, Suppl):103S.
23. Sieja K, Talerczyk M. Selenium as an element in the treatment of
ovarian cancer in women receiving chemotherapy. Gynecol Oncol
2004;93:320–7.
24. Borghardt J, Rosien B, Gortelmeyer R, et al. Effects of a spleen
peptide preparation as supportive therapy in inoperable head and neck cancer patients.
Arzneimittelforschung 2000;50:178–84.
25. Mills EED. The modifying effect of beta-carotene on radiation and
chemotherapy induced oral mucositis. Br J Cancer
1988;57:416–7.
26. Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment
of chemotherapy-induced mucositis. Am J Med 1992;92:481–4.
27. Lopez I, Goudou C, Ribrag V, et al. Treatment of mucositis with
vitamin E during administration of neutropenic antineoplastic agents. Ann Med Intern
[Paris] 1994;145:405–8.
28. Lopez I, Goudou C, Ribrag V, et al. Traitement des mucites par la
vitamine E lors de l’administration d’anti-neoplasiques neutropeniants. Ann
Med Interne 1994;145:405–8.
29. Legha SS, Wang YM, Mackay B, et al. Clinical and pharmacologic
investigation of the effects of alpha-tocopherol on Adriamycin cardiotoxicity. Ann NY Acad
Sci 1982;393:411–8.
30. Israel L, Hajji O, Grefft-Alami A, et al. Agumentation par la
vitamine A des effets de la chimiotherapie dans les cancers du sein metastases apres la
menopause. Ann Med Interne 1985;136:551–4.
31. Henkin RI. Prevention and treatment of hypogeusia due to head and
neck irradiation. JAMA 1972;220:870–1.
32. Mossman KL, Henkin RI. Radiation-induced changes in taste acuity in
cancer patients. Int J Radiat Oncol Biol Phys 1978;4:663–70.
33. Ripamonti C, Zecca E, Brunelli C, et al. A randomized, controlled
clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste
alterations caused by head and neck irradiation. Cancer 1998;82:1938–45.
34. Dreizen S et al. Nutritional deficiencies in patients receiving
cancer chemotherapy. Postgrad Med 1990;87(1):163–70.
35. Desai TK, Maliakkal J, Kinzie JL, et al. Taurine deficiency after
intensive chemotherapy and/or radiation. Am J Clin Nutr 1992;55:708–11.
36. Cohen MH, Chretien PB, Ihde DC, et al. Thymosin fraction V and
intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung
cancer. JAMA 1979;241:1813–5.
37. Macchiarini P, Danesi R, Del Tacca M, Angeletti CA. Effects of
thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung
cancer patients. Anticancer Res 1989;9:193–6.
38. Shoham J, Theodor E, Brenner HJ, et al. Enhancement of the immune
system of chemotherapy-treated cancer patients by simultaneous treatment with thymic extract,
TP-1. Cancer Immunol Immunother 1980;9:173–80.
39. Lersch C, Zeuner M, Bauer A, et al. Nonspecific immunostimulation
with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea
extracts (Echinacin) in patients with far advanced colorectal cancers: Preliminary results.
Cancer Invest 1992;10:343–8.
40. Kupin VJ. Eleutherococcus and Other Biologically Active Modifiers
in Oncology. Moscow: Medexport, 1984, 21.
41. Kupin VI, Polevaya YB, Sorokin AM. Eleutherococcus extract treatment
for immunostimulation in cancer patients. Vopr Onkol 1986;32:21–6 [in
Russian].
42. Scambia G, De Vincenzo R, Ranelletti FO, et al. Antiproliferative
effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin.
Eur J Cancer 1996;32A:877–82.
43. Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and
protection by silibinin. Nephrol Dial Transplant 1996;11:55–62.
44. Invernizzi R, Bernuzzi S, Ciani D, Ascari E. Silymarine during
maintenance therapy of acute promyelocytic leukemia. Haemotologia
1993;78:340–1.
45. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger)
used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242–4.
46. Pace JC. Oral ingestion of encapsulated ginger and reported self care
actions for the relief of chemotherapy-associated nausea and vomiting.
Dissertation Abstr Int 1987;8:3297.
47. Carl W, Emrich LS. Management of oral mucositis during local
radiation and systemic chemotherapy: A study of 98 patients. J Prosthet Dent
1991;66:361–9.
48. Toi M, Hattori T, Akagi M, et al. Randomized adjuvant trial to
evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast
cancer. Cancer 1992;70:2475–83.
49. Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies
versus chemotherapy as adjuvant treatment after curative resection of operable breast
cancer. Anticancer Res 1995;15:2907–12.
50. Mitomi T, Tsuchiya S, Iijima N, et al. Randomized, controlled study
on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The
Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum
(Kanagawa). Dis Colon Rectum 1992;35:123–30.
51. Threlkeld DS, ed. Antineoplastics, Alkylating Agents, Nitrogen
Mustards, Cyclophosphamide. In Facts and Comparisons Drug Information. St. Louis, MO:
Facts and Comparisons, Aug 1997, 647–d.
52. Mattes RD. Prevention of food aversions in cancer patients during
treatment. Nutr Cancer 1994;21:13–24.
