| References | Disclaimer | Abstracts | Print Version
Cancer: Should Patients Take Dietary Supplements?
Dr. Simone explains the pathways through which antioxidants work to restrain
cancer:
- Antioxidants inhibit protein kinase C, restraining tumor cell division
and proliferation.
- Antioxidants inhibit oncogene expression, genes that give rise to
tumors.
- Antioxidants promote differentiation by altering growth factors. Undifferentiated
cells depart (in appearance) from the highly recognizable (differentiated)
cells of the tissue of origin. For example, healthy cells have a typical
appearance microscopically: A healthy liver cell cannot be mistaken
for a colon cell; or a colon cell cannot be mistaken for a kidney cell.
The greater the departure from the unique character of the cell (a lack
of differentiation) the greater the level of malignancy.
- Antioxidants block destruction imposed by free radicals, protecting
vital tissue from damage.
Dr. Hoffer adds that he has treated more than 1100 cancer patients with
high doses of vitamin C (most of whom were concurrently receiving chemotherapy)
(Hoffer et al. 1993a; Hoffer et al. 1993b; Hoffer 1994; Hoffer 1996).
Upon examining health histories, Hoffer found that the mean difference
in prolongation of life was heavily in favor of the use of vitamins. In
the first Hoffer/Pauling series published, patients on the Hoffer program
lived 10-20 times longer than patients not receiving vitamin C.
Various vital functions dependent on healthy antioxidant systems are
challenged during cancer. Collapse of internal defenses (either partial
or total) occurs through nutrient depletion as observed among cachexic
patients, that is, those individuals evidencing a profound state of general
ill health and malnutrition, marked by weakness and emaciation. (About
40% of cancer patients die due to malnutrition.) Also, naturally occurring
antioxidants and enzymes are often severely exhausted among cancer patients
undergoing aggressive therapies, leaving the patient defenseless in regard
to free-radical attack. Adjunctive antioxidant therapy is not adding something
foreign to the body but rather replacing natural substances withdrawn
as a result of treatment.
A valuable contribution to the quandary of whether to use antioxidants
with chemotherapy or radiation is available to physicians and patients
at http://www.thorne.com/altmedrev/.fulltext/5/2/152.html.
Drs. Davis Lamson and Matthew Brignall have abridged a lengthy dissertation
into accessible reference guides, showing antioxidant interactions (both
positive and negative) when coupled with traditional therapies, for example,
popular antioxidants (vitamins A, C, E, beta-carotene, and melatonin)
interlaced positively with radiotherapy, enhanc ing e therapeutic intent
(Lamson et al. 2000).
Exceptions to the reference guides routinely surface, but Lamson et al.
(1999) declare that (to date) only three agents, classified as antioxidants,
have been shown to decrease the effectiveness of radiation or chemotherapy
in vivo :
- N-acetyl-cysteine (NAC) reduced the therapeutic effect of anthracycline-type
chemotherapy agents (doxorubicin and bleomycin), which kill cells by
generating oxygen radicals. Alkylating agents (such as cisplatin) and
hormonal therapies were not affected.
- Beta-carotene decreased the effectiveness of antimetabolites (5-FU
and methotrexate). Conversely, beta-carotene increased the efficacy
of radiotherapy, as well as alkylating, anthracycline, and platinum
chemotherapy agents.
- Tangeretin (a flavonoid found in citrus fruit) reduced the chemotherapeutic
effect of platinum compounds such as cisplatin and carboplatin. Tangeretin
interfered with tamoxifen, a nonsteroidal antiestrogen used to treat
estrogen-dependent cancers (Bracke et al. 1999).
Dietary curcumin inhibited chemotherapy-induced apoptosis through inhibition
of reactive oxygen species. A 70% reduction in chemotherapy-induced apoptosis
in MCF-7, MDA-MB-231, and BT-474 human breast cancer cells was noted.
Supplemental curcumin as well as curcumin-containing foods were proposed
as being possible antagonists to conventional treatment. However, additional
studies are needed to determine whether breast cancer patients, undergoing
chemotherapy, should avoid curcumin supplementation (Somasundaram et al.
2002).
Dan Labriola, M.D., and Robert Livingston, M.D., suggest a plan for adjunctive
antioxidant therapy aimed at avoiding possible undesirable interactions
with conventional treatments. They acknowledge that a number of chemotherapeutic
agents are dependent upon reactive oxygen species for performance. Drs.
Labriola and Livingston refer to the period when conventional treatments
do their work as the protected zone. They contend that the protected zone
can last for varying amounts of time, depending on the drug, the procedure
and dosage, other drugs or treatments in the regime, and the patient's
overall health.
Pinpointing the protected zone and protecting this interval (a process
that requires the expertise and clinical judgment of a physician and an
oncology pharmacist) allows time for the cytotoxic agent to enact its
kill. The clinical objective is to avoid high antioxidant levels while
the drugs are still active and vulnerable to interference (Labriola et
al. 1999). Labriola, although criticized by some for astringency, advises
looking at the long-term prognosis, not the short-term "feel good"
response, obtained from antioxidants while undergoing aggressive therapies.
Jeff Bland, Ph.D., scientist and educator, reported at the Comprehensive
Cancer Care 2001 Conference that leaders in the field endorse pulse therapy
as the appropriate means of administering nutritional support concurrent
with toxic treatment. Reentering with supplementation 2-3 days after the
large chemotherapeutic bolus allows time for a massive cancer kill followed
by a period of rebuilding (Bland 1999; 2001). If conventional treatment
is the patient's election, this dosing pattern appears to allow the body
the full effects of conventional treatment, plus the benefit of an antioxidant
program a few days later. Juices, rich in antioxidants, may (according
to Dr. Bland) also merit caution during the few days of the protected
zone.
Dr. Keith Block, director of the Block Medical Center and the Institute
for Integrated Cancer Care, although in favor of antioxidant therapy,
admits the ultimate answer is not available. The downside to the equation
is that individuals with cancer are not able to wait for proof. The general
theme of Comprehensive Cancer Care 2001 (presenting the best of worldwide
research) was that it appears unreasonable and heartless to totally withhold
materials that (to date) show survival enhancement. Dr. Block concluded:
"I would not (personally) take chemotherapy if antioxidants were
not also on board" (Block 2001). Dr. Block believes that factoring
in circadian rhythms regarding chemotherapeutic administration influences
toxicity and anticancer activity and best serves the patient's welfare.
Dr. Block has a highly esteemed practice in Evanston, Illinois, (847)
492-3040.
An opposing view (regarding antioxidant therapy) comes from Dr. Rudolph
Salganik, a Russian scientist currently at the University of North Carolina.
Dr. Salganik states that free radicals, generated through chemicals and
radiation, should be allowed to work unencumbered, that is, without interference
from antioxidants. According to Dr. Salganik, apoptosis or regulated cell
death eliminates unwanted and damaged cells, including those precancerous
and cancerous. He continued, "Since reactive oxygen species (ROS)
act as essential apoptotic mediators, we [our team] reasoned that increasing
ROS levels might enhance apoptosis and thereby slow tumor growth."
A brain tumor was used as the model to test the impact of an antioxidant-depleted
diet, that is, a diet capable of increasing ROS levels compared to an
antioxidant-enriched diet on tumor growth.
The antioxidant-depleted diet dramatically increased apoptosis in mouse
tumor cells but did not affect normal tissue. Salganik says that the presence
of increased oxidant stress within tumors indicates that the likely mechanism
of apoptosis is via ROS and DNA oxidative impairment. As reactive oxygen
species promoted apoptosis, tumor growth was inhibited; in contrast, the
antioxidant-rich diet had no impact on the growth of the tumor. The Salganik
team concluded that when the multitudes of oxidants are not suppressed
by antioxidants, they mediate apoptosis, or cell death, the exact intent
of cytotoxic therapies (Salganik et al. 2000).
Dr. Salganik later reported that intake of exogenous antioxidants (vitamins
E, C, and beta-carotene) could protect against cancer and other degenerative
processes in individuals with innate or acquired high levels of reactive
oxygen species (ROS). Screening populations (for high or low levels of
ROS) could provide a scientifically grounded application for antioxidant
supplementation, a program that could vastly contribute to the nation's
overall health (Salganik 2001).
Positive Results of High Dose Antioxidant Therapy During Chemotherapy
and Radiation
Studies have demonstrated that antioxidant vitamins can enhance the efficacy
of certain chemotherapeutic agents on tumor cells in culture (Prasad et
al. 1994; Prasad 2003). Antioxidant vitamins could be an important adjuvant
to standard treatment of human cancers (Prasad et al. 1999).
An in vitro study was undertaken to ascertain if antioxidant
vitamins could enhance the cytotoxic and apoptotic effects of paclitaxel
and carboplatin on non-small cell lung cancer ( Pathak et al. 2002).
The human non-small cell lung cancer cell line H-520 was treated with
a mixture of the antioxidant vitamins C, E, and beta-carotene and paclitaxel
and carboplatin, both individually and in combination of various doses
in different sequences. The mixture of antioxidant vitamins by itself
led to 15% apoptosis. Simultaneous treatment of paclitaxel and carboplatin
produced 40% apoptosis, while paclitaxel treatment 24 hours prior to carboplatin
treatment caused 54% apoptosis. However, the most significant improvements
in the degree of apoptosis were observed when cells were pretreated with
an antioxidant vitamin mixture immediately before treatment with paclitaxel
and carboplatin (70% apoptosis) or pretreated with the antioxidant vitamin
mixture 24 hours prior to treatment with paclitaxel, which was then followed
24 hours later by treatment with carboplatin (89% apoptosis).
The apoptotic effects of paclitaxel and carboplatin are enhanced by antioxidant
vitamin pretreatment. Further, the most promising sequence of agents that
emerged in this study was the pretreatment with the antioxidant vitamin
mixture 24 hours prior to treatment with paclitaxel, which was then followed
24 hours later by treatment with carboplatin.
Another clinical trial was conducted to examine the outcome of treatment
with paclitaxel and carboplatin alone and in combination with an antioxidant
vitamin mixture of 60 mg a day of beta-carotene, 1025 mg a day of alpha-
tocopherol, and 6100 mg a day of ascorbic acid on 65 cancer patients with
squamous cell carcinomas (n = 37), adenocarcinomas (n = 16), large cell
carcinomas (n = 6), and poorly differentiated carcinoma (n = 6). The outcome
was very encouraging with overall survival at 33% after 1 year with the
treatment of paclitaxel and carboplatin alone, and 54% when patients were
treated with paclitaxel and carboplatin combined with the antioxidant
vitamin mixture. Although the study was limited due to the small number
of patients, the research confirms a need for further clinical trials
to examine the role of vitamins in the treatment and management of cancer
(Unpublished 2002).
For a comprehensive report on the use of antioxidants during cancer therapy,
refer to the Cancer
Chemotherapy and Cancer
Radiation Therapy protocols.
The Molecular Effects of Folic Acid
Few people have ever heard the word methylation, yet this word holds
the promise of unlocking the doors to understanding, preventing, and curing
cancer. Although methylation is a biochemical reaction that occurs millions
of times a day in every cell in the body, it has not been very well studied.
Its connection to cancer is now under intense scrutiny because methylation
acts as a switch to activate or deactivate cancer genes (Momparl i er
et al. 2001; Sasaki et al. 2001).
Cancer is fundamentally cellular growth gone wild. It can involve any
organ of the body, but the one factor cancers have in common is that they
are made of wildly proliferating cells. Normal cells replicate themselves,
then stop. Cancer cells race through all normal checkpoints of cellular
growth without stopping, and they cease to communicate with other cells.
Striking new research shows that the same pathological mechanism causes
all of this strange behavior: methylation dysfunction.
Methylation research has opened up new avenues for the detection, prevention,
and the eventual cure of cancer (Cairns et al. 2001; Goessl et al. 2001;
Weihrauch et al. 2001). It has been repeatedly shown that methylation-deficient
diets and/or exposure to chemicals deplete methylation and cause cancer
(Issa et al. 1996; Chen et al. 2001; Kim et al. 2001). Both events can
be prevented and, to some extent, reversed by methylation-enhancing supplements,
which include folic acid, SAMe, vitamin B12, and trimethylglycine (TMG)
(Wilcken et al. 1985; Loehrer et al. 1996; Kuan et al. 2002). How can
a person know if his/her level of methylation is below the healthy level?
Homocysteine can be used as a rough guide to methylation status (until
methylation testing becomes widespread). If homocysteine levels are elevated,
methylation is likely depressed (Yi et al. 2000).
DNA methylation is influenced by diet and methylation supplementation
may reverse the progression of cancer in the early stages. It is not known,
however, at what point cancer becomes irreversible. At this point, supplementation
to enhance methylation would not be desirable inasmuch as methylation
is also required for the synthesis of new cells, including cancer cells.
For now, it is important to know that diet and exposure to chemicals can
alter DNA methylation patterns and activate or deactivate genes involved
in cancer (Fenech 2001). These alterations can be prevented, and potentially
reversed, by dietary factors that enhance methylation, such as folic acid.
There are concerns that high doses of folic acid, vitamin B12, and S-adenosylmethionine
(SAMe) may not be beneficial to the cancer patient until the disease is
brought under control. A consensus does not exist among experts, and we
must thus rely on the consistency of the published scientific data indicating
that moderate supplementation with methylation-enhancing agents would
appear to prolong survival. A moderate approach would involve 800 mcg
of folic acid, no more than 1000 m c g of vitamin B12, with SAMe intake
limited to around 800 mg daily. Some argue that only 200 mcg a day of
folic acid and B12 be taken and SAMe be avoided by those with active cancer.
It should be reassuring, however, that all human (and animal) studies
published to date show that folic acid improves survival.
The most recent human study of folic acid and human cancer was conducted
on 42 patients afflicted with head and neck squamous cell carcinoma. Doctors
evaluated the cancer patient's blood levels of folic acid and homocysteine
in relation to two control groups without cancer. Compared to the control
groups, the folate level in the cancer patients was 38% lower and the
homocysteine level was 22% higher. The differences in serum levels of
folate and homocysteine might arise from tumor development and consequent
metabolic alterations, or might precede and promote tumor progression.
If low folate is a risk factor for head and neck cancer, it might suggest
a role for folate as a novel preventive agent both in patients with precancerous
lesions and in patients with treated head and neck squamous cell carcinoma
at risk for regional recurrence and second primary tumors (Almandori et
al. 2002).
|