Interactions with Dietary Supplements
Acetyl-L-carnitine
Acetyl-L-carnitine in the amount of 1,000 mg three times per day for eight weeks has been
shown to improve nerve damage (neuropathy) caused by cisplatin.1
Antioxidants
Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some
oncologists recommend that patients avoid supplementing antioxidants if they are undergoing
chemotherapy. Limited test tube research occasionally does support the idea that an
antioxidant can interfere with oxidative damage to cancer cells.2 However, most
scientific research does not support this supposition.
A modified form of vitamin A has been
reported to work synergistically with chemotherapy in test tube research.3 Vitamin C appears to increase the effectiveness of
chemotherapy in animals4 and with human breast cancer cells in test tube
research.5 In a double-blind study, Japanese researchers found that the combination
of vitamin E, vitamin C, and N-acetyl cysteine (NAC)—all
antioxidants—protected against chemotherapy-induced heart damage without interfering
with the action of the chemotherapy.6
A comprehensive review of antioxidants and chemotherapy leaves open the question of whether
supplemental antioxidants definitely help people with chemotherapy side effects, but it
clearly shows that antioxidants need not be avoided for fear that the actions of chemotherapy
are interfered with.7 Although research remains incomplete, the idea that people
taking chemotherapy should avoid antioxidants is not supported by scientific research.
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.8 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.9 Others have confirmed the potential for vitamin E to
help people with chemotherapy-induced mouth sores.10 Applying vitamin E only once
per day was helpful to only some groups of patients in another trial,11 and not all
studies have found vitamin E to be effective.12 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.
In a preliminary study, the addition of oral vitamin E (300 IU per day) to cisplatin
chemotherapy significantly reduced the incidence of drug-induced damage to the nervous system
(neurotoxicity).13 A similar protective effect was seen in another trial in which
600 IU of vitamin E per day was used.14
Calcium and Phosphate
Cisplatin may cause kidney damage, resulting in depletion of calcium and
phosphate.15
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.16
17 In fact, animal studies show that glutamine may actually decrease tumor growth while
increasing susceptibility of cancer cells to radiation and chemotherapy,18
19 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.20 Thirteen of fourteen people in the study had fewer days
with mouth sores as a result. These excellent results have been duplicated in
some,21 but not all,22 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.23
One double-blind trial suggested that 6 grams of glutamine taken three times per day can
decrease diarrhea caused by
chemotherapy.24 However, other studies using higher amounts or intravenous
glutamine have not reported this effect.25 26
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.27
Glutathione
High-dose cisplatin therapy is associated with kidney toxicity and damage, which may be
reduced by glutathione administration.28 29 30 31
Nerve damage is another frequent complication of high amounts of cisplatin. Preliminary
evidence has shown that glutathione injections may protect nerve tissue during cisplatin
therapy without reducing cisplatin’s anti-tumor activity.32 33
34 There is no evidence that glutathione taken by mouth has the same benefits.
Magnesium and Potassium
Cisplatin may cause excessive loss of magnesium and potassium in the urine.35
36 Preliminary reports suggest that both potassium and magnesium supplementation may be
necessary to increase low potassium levels.37 38 Severe magnesium
deficiency caused by cisplatin therapy has been reported to result in seizures.39
Severe magnesium deficiency is a potentially dangerous medical condition that should only be
treated by a doctor. People receiving cisplatin chemotherapy should ask their prescribing
doctor to closely monitor magnesium and potassium status.
Melatonin
Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of
chemotherapy with cisplatin plus etoposide and
cisplatin plus 5-FU.40
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.41 It makes sense for people undergoing chemotherapy to take a high-potency
multivitamin-mineral to protect against deficiencies.
N-acetyl
cysteine
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.42 43 44 45 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.46
Selenium
In one human study, administration of 4,000 mcg per day of a selenium product,
Seleno-Kappacarrageenan, reduced the kidney damage and white blood cell–lowering effects
of cisplatin.47 The amount of selenium used in this study is potentially toxic and
should only be used under the supervision of a doctor. In another study, patients being
treated with cisplatin and cyclophosphamide 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.48
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.49
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.
Sodium
Cisplatin may cause depletion of sodium due to kidney damage which sometimes occurs in people
treated with cisplatin.50
Taurine
Taurine has been shown to be depleted in people taking chemotherapy.51 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.52 A related
substance, thymostimulin, decreased some side effects of chemotherapy and increased survival
time compared with chemotherapy alone.53 A third product, thymic extract TP1, was
shown to improve immune function in people treated with chemotherapy compared with effects of
chemotherapy alone.54 Thymic peptides need to be administered by injection. People
interested in their combined use with chemotherapy should consult a doctor.
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.55 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.56 57 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.58
1. Bianchi G, Vitali G, Caraceni A, et al. Symptomatic and
neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral
acetyl-L-carnitine. Eur J Cancer 2005;41:1746–50.
2. Witenberg B, Kalir HH, Raviv Z, et al. Inhibition by ascorbic acid of
apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem
Pharmacol 1999;57:823–32.
3. Sacks PG, Harris D, Chou T-C. Modulation of growth and proliferation
in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with
chemotherapeutic agents. Int J Cancer 1995;61:409–15.
4. Taper HS et al. Non-toxic potentiation of cancer chemotherapy by
combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575–9.
5. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C)
improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast
carcinoma cells in vitro. Cancer Letters 1996:103–19.
6. Wagdi P, Fluri M, Aeschbacher B, et al. Cardioprotection in patients
undergoing chemo- and/or radiotherapy for neoplastic disease. Jpn Heart J
1996;37:353–9.
7. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in
chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209–40
[review].
8. Mills EED. The modifying effect of beta-carotene on radiation and
chemotherapy induced oral mucositis. Br J Cancer
1988;57:416–7.
9. Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment
of chemotherapy-induced mucositis. Am J Med 1992;92:481–4.
10. 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.
11. 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.
12. 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.
13. Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of
vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin
Oncol 2003;21:927–31.
14. Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis
against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology
2005;64:26–31.
15. Threlkeld DS, ed. Antineoplastics, alkylating agents, cisplatin
(CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and
Comparisons, Feb 1999, 652a–2d.
16. 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.
17. 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.
18. Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am
J Surg 1996;172:418–24.
19. Souba WW. Glutamine and cancer. Ann Surg
1993;218:715–28 [review].
20. Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy
induced stomatitis: a pilot study. J Lab Clin Med 1996;127:223–8.
21. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the
duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer
1998;83:1433–9.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Fontanelli R, Spatti G, Raspagliesi F, et al. A preoperative single
course of high-dose cisplatin and bleomycin with glutathione protection in bulky stage IB/II
carcinoma of the cervix. Ann Oncol 1992;3:117–21.
29. Plaxe S, Freddo J, Kim S, et al. Phase I trial of cisplatin in
combination with glutathione. Gynecol Oncol 1994;55:82–6.
30. Di Re F, Bohm S, Oriana S, et al. Efficacy and safety of high-dose
cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced
epithelial ovarian cancer. Cancer Chemother Pharmacol 1990;25:355–60.
31. Tedeschi M, De Cesare A, Oriana S, et al. The role of glutathione in
combination with cisplatin in the treatment of ovarian cancer. Cancer Treat Rev
1991;18:253–9 [review].
32. Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity
and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin:
Results of a double-blind, randomised trial. Ann Oncol 1997;8:569–73.
33. Colombo N, Bini S, Miceli D, et al. Weekly cisplatin ±
glutathione in relapsed ovarian carcinoma. Int J Gynecol Cancer
1995;5:81–6.
34. Cascinu S, Cordella L, Del Ferro E, et al. Neuroprotective effect of
reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized
double-blind placebo-controlled trial. J Clin Oncol 1995;13:26–32.
35. Buckley JE, Clark VL, Meyer TJ, Pearlman NW. Hypomagnesemia after
cisplatin combination chemotherapy. Arch Intern Med 1984;144:2347.
36. Threlkeld DS, ed. Antineoplastics, Alkylating Agents, Cisplatin
(CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and
Comparisons, Feb 1999, 652a–2d.
37. Rodriguez M, Solanki DL, Whang R. Refractory potassium repletion due
to Cisplatin-induced magnesium depletion. Arch Intern Med 1989;149:2592–4.
38. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A
consequence of magnesium deficiency. Arch Intern Med 1992;152:40–5.
39. van de Loosdrecht AA, Gietema JA, van der Graaf WT. Seizures in a
patient with disseminated testicular cancer due to cisplatin-induced hypomagnesaemia. Acta
Oncol 2000;39:239–40.
40. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and
increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic
solid tumour patients with poor clinical status. Eur J Cancer
1999;35:1688–92.
41. Dreizen S et al. Nutritional deficiencies in patients receiving
cancer chemotherapy. Postgrad Med 1990;87(1):163–70.
42. Holoya PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide
toxicity with oral acetylcysteine. Sem Oncol 1983;10(suppl 1):66–71.
43. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine’s
preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62–5.
44. 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.
45. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced
hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.
46. 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.
47. Hu Y-J, Chen Y, Zhang Y-Q, et al. The protective role of selenium on
the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace
Elem Res 1997;56:331–41.
48. Sieja K, Talerczyk M. Selenium as an element in the treatment of
ovarian cancer in women receiving chemotherapy. Gynecol Oncol
2004;93:320–7.
49. 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.
50. Threlkeld DS, ed. Antineoplastics, Alkylating Agents, Cisplatin
(CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and
Comparisons, Feb 1999, 652a–2d.
51. Desai TK, Maliakkal J, Kinzie JL, et al. Taurine deficiency after
intensive chemotherapy and/or radiation. Am J Clin Nutr 1992;55:708–11.
52. 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.
53. 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.
54. 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.
55. Israel L, Hajji O, Grefft-Alami A, et al. Augmentation 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.
56. Henkin RI. Prevention and treatment of hypogeusia due to head and
neck irradiation. JAMA 1972;220:870–1.
57. Mossman KL, Henkin RI. Radiation-induced changes in taste acuity in
cancer patients. Int J Radiat Oncol Biol Phys 1978;4:663–70.
58. 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.
59. 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.
60. Kupin VJ. Eleutherococcus and Other Biologically Active Modifiers
in Oncology. Moscow: Medexport, 1984, 21.
61. Kupin VI, Polevaya YB, Sorokin AM. Eleutherococcus extract treatment
for immunostimulation in cancer patients. Vopr Onkol 1986;32:21–6 [in
Russian].
62. 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.
63. Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and
protection by silibinin. Nephrol Dial Transplant 1996;11:55–62.
64. Invernizzi R, Bernuzzi S, Ciani D, Ascari E. Silymarine during
maintenance therapy of acute promyelocytic leukemia. Haemotologia
1993;78:340–1.
65. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger)
used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242–4.
66. 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. Mattes RD. Prevention of food aversions in cancer patients during
treatment. Nutr Cancer 1994;21:13–24.