Interactions with Dietary Supplements
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.1 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.2 Vitamin C appears to increase the effectiveness of
chemotherapy in animals3 and with human breast cancer cells in test tube
research.4 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.5
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.6 Although research remains incomplete, the idea that people
taking chemotherapy should avoid antioxidants is not supported by scientific research.
A new formulation of selenium
(Seleno-Kappacarrageenan) was found to reduce kidney damage and white blood
cell–lowering effects of cisplatin in
one human study. However, the level used in this study (4,000 mcg per day) is potentially
toxic and should only be used under the supervision of a doctor.7
Glutathione, the main antioxidant found
within cells, is frequently depleted in individuals on chemotherapy and/or radiation.
Preliminary studies have found that intravenously injected glutathione may decrease some of
the adverse effects of chemotherapy and radiation, such as diarrhea.8
Folic
acid
In cancer treatment, methotrexate works by blocking activation of folic acid. Folic
acid-containing supplements may interfere with methotrexate therapy in people with
cancer.9 Methotrexate therapy can lead to folic acid deficiency. People using
methotrexate for cancer treatment should ask their prescribing doctor before using any folic
acid-containing supplements. There is no concern about folic acid supplementation for people
with cancer using chemotherapy drugs other
than methotrexate.
Until recently, it was believed that methotrexate helped people with rheumatoid arthritis also by interfering with folic
acid metabolism. However, this is not necessarily so, as some studies have shown that folic
acid supplementation in amounts ranging from 5–50 mg per week did not alter the efficacy
of methotrexate in the treatment of rheumatoid arthritis.10 11
12 Many doctors now believe that people with rheumatoid arthritis taking methotrexate
should supplement large amounts of folic acid. In separate double-blind trials, 5 mg per week
of folic acid and 2.5–5 mg per week of folinic acid (an activated form of folic acid)
have substantially reduced side effects of methotrexate without interfering with the
therapeutic action in rheumatoid patients.13 14 Folic or folinic acid
was taken at a different time from methotrexate and sometimes only five days per week. Daily
(as opposed to weekly) supplementation with folic acid (5 mg per day for 13 days) was found to
reduce blood levels of methotrexate;15 however, the researchers in this study
suggest that the reduction in blood methotrexate levels by folic acid does not necessarily
mean that the folic acid is interfering with the therapeutic action of the drug. It is
possible that the lower blood levels of methotrexate are simply an indication that the drug is
being taken up more rapidly by the cells as a result of folic acid supplementation. In most of
the studies cited here, folic acid supplementation was begun 24 hours after the administration
of methotrexate. Because of the uncertainty regarding this interaction, persons taking
methotrexate for rheumatoid arthritis who are considering supplementation with folic acid
should first consult with their doctor.
People who are prescribed methotrexate to treat severe psoriasis experience fewer side effects if they also
supplement high amounts (5 mg per day) of folic acid.16 As is the case with
methotrexate and rheumatoid arthritis, supplementing folic acid did not interfere with the
activity of methotrexate. Such high levels of folic acid should not be taken without clinical
supervision.
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.17
18 In fact, animal studies show that glutamine may actually decrease tumor growth while
increasing susceptibility of cancer cells to radiation and chemotherapy,19
20 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.21 Thirteen of fourteen people in the study had fewer days
with mouth sores as a result. These excellent results have been duplicated in
some,22 but not all23 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.24
One double-blind trial suggested that 6 grams of glutamine taken three times per day can
decrease diarrhea caused by
chemotherapy.25 However, other studies using higher amounts or intravenous
glutamine have not reported this effect.26 27
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.28
Animal studies have demonstrated that administration of methotrexate with intravenous or
oral glutamine may enhance the ability of methotrexate to kill tumor cells, while decreasing
methotrexate toxicity and improving survival.29 30 31
32 33 34 The effects of oral glutamine supplementation in humans
taking methotrexate remains unknown.
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.35 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.36 37 38 39 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.40
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.41 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.42 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.43 Others have confirmed the potential for vitamin E
to help people with chemotherapy-induced mouth sores.44 Applying vitamin E only
once per day was helpful to only some groups of patients in another trial,45 and
not all studies have found vitamin E to be effective.46 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.47 Similar results were not found in premenopausal women.
The large amounts of vitamin A used in the study are toxic and require clinical
supervision.
In a study of children with cancer who were receiving high-dose methotrexate,
administration of 180,000 IU of vitamin A on the day before methotrexate treatment reduced the
severity of intestinal damage caused by the drug.48 Because of the complex nature
of cancer therapy and the large amount of vitamin A involved, this treatment should be done
only with the supervision of a doctor.
Zinc
Irradiation treatment, especially of head and neck cancers, frequently results in changes to
normal taste sensation.49 50 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.51
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.52 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.53 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.54 A related
substance, thymostimulin, decreased some side effects of chemotherapy and increased survival
time compared with chemotherapy alone.55 A third product, thymic extract TP1, was
shown to improve immune function in people treated with chemotherapy compared with effects of
chemotherapy alone.56 Thymic peptides need to be administered by injection. People
interested in their combined use with chemotherapy should consult a doctor.
PABA
(para-aminobenzoic acid)
PABA can increase methotrexate levels, activity, and side effects.57 The incidence
and severity of this interaction remains unclear.
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