Nutrition and Cancer

[Guest guest]

http://www.annieappleseedproject.org/micsupforpts.html

Micronutrient Supplementation for Patients With Metastatic Cancer

 

James J. Stark, Cancer Treatment Research Foundation, Gary T. Anderson, Cancer

Treatment Research Foundation, Timothy C. Birdsall, Cancer Treatment Centers of

America, Daniel Nixon and Edith Zang, American Health Foundation, and Gerald M.

Haase, University of Colorado School of Medicine

 

Moderator's Note: As I send this information your way, I would like to clarify

the fact that although I agree with the concept of using mega amounts of

vitamins in cancer therapy I do not in any way condone using chemotherapy and

radiation as this article suggests. Chemo and radiation over time totally

destroy the body's immune capabilities and lessen the likelihood of recovery.

Nevertheless the article is sent to you as written in the hopes that someone

will in some way benefit from its contents.

Kind Regards, JoAnn

 

[Nutrition and Cancer 38(2):296-298, 2000. © 2000 Lawrence Erlbaum Associates,

Inc.]

 

A large percentage of Americans use some form of complementary and alternative

medicine to improve their health. The public perceives the vitamin, mineral, and

food supplements that constitute much of alternative medicine to be free of

toxicity or harm (1).

 

Our personal experience with scores of colleagues leads us to conclude that many

physicians, when faced with a cancer patient who wants to know whether taking

supplements is a good idea, will shrug their shoulders and say something to the

effect that they probably will do no good but should do no harm. Various recent

studies have demonstrated that 23-72% of cancer patients undergoing active

treatment use alternative therapies, probably with the belief that, at the very

worst, they can do no harm (2-4).

 

Support for the use of vitamin and mineral supplements has been incorporated

into the treatment approach of at least one major cancer program without

supporting data. At least one other major cancer center is incorporating

concepts of complementary and alternative medicine into its program on the basis

of a perceived need from the public at large (5,6).

 

Many dietary supplements act as antioxidants. Labriola and Livingston (7)

recently delved into theoretical reasons why antioxidants might interact

adversely with cancer chemotherapy drugs in a comprehensive review of the

subject. The likely site of interaction involves removal of free radical oxygen

from the milieu of the tumor cell with reduction in free radical-mediated

cytotoxicity.

 

Subsequent editorials and rebuttals have enlivened the debate (8-11). Agus and

colleagues (12) recently helped elucidate a mechanism by which tumor cells

sequester and accumulate high levels of intracellular vitamin C, which in theory

could interfere with the effects of chemotherapy.

 

On the other side of the debate, Lamson and Brignall (13,14) reviewed the

published data on antioxidant-chemotherapy interactions and concluded that the

vast majority of studies have demonstrated increased or no effect on

chemotherapy efficacy. Other proponents argue that several chemoprotective

agents such as mesna and amifostine are themselves antioxidants.

 

Smyth and colleagues (15) allege that glutathione, when added to cisplatin in

the treatment of ovarian cancer, leads to reduced chemotherapy-related toxicity

and an enhanced quality of life.

 

Ascorbic acid is said to reduce the toxicity of doxorubicin without affecting

its anti-tumor properties (16). Green tea, a potent antioxidant, may enhance the

effectiveness of doxorubicin as well (17). In vitro studies shed some light on

these issues. Prasad and co-workers (1 reported their results and those of

others in a review of this subject. Among other observations, they showed that

neuroblastoma cells cultured in the presence of various concentrations of

vitamin E suffered synergistic cell kill when exposed to ionizing radiation.

 

Taper and colleagues (19) showed in ascitic liver tumor-bearing mice that the

addition of vitamins C and K3 to standard chemotherapy resulted in a

prolongation of survival in the animals so treated. Kurbacher and associates

(20) demonstrated that vitamin C increased the cytotoxicity of doxorubicin,

cisplatin, and paclitaxel against MCF-7 and MDA-MB-231 breast carcinoma cell

lines.

 

Certain antioxidants have been shown to possess potent anticancer properties in

the laboratory when used in combination, whereas when they are given singly they

have no effect.

 

The experiments by Prasad and co-workers (1 using ascorbic acid, carotenoids,

-tocopherol, and retinoic acid in melanoma cell lines in vitro show a

synergistic antitumor effect without the use of chemotherapy and further

synergism when chemotherapy is added.

 

Although the relevance of such in vitro observations to the clinical setting is

not clear, these findings represent the best available evidence of potential in

vivo interactions and their relevance should be clarified by this and similar

trials. Circumstances in which vitamins alone have anticancer properties have

also been reviewed.

 

Human in vivo data on the interaction of micronutrients and chemotherapy are

sparse. Jaakkola and colleagues (21) attempted to show that patients with

small-cell lung cancer who ingested micronutrients in addition to their

chemotherapy program enjoyed a better outcome.

 

Their study was, however, uncontrolled, the number of subjects was small (n = 1,

and the median survival of their study group was virtually identical to that

published contemporaneously elsewhere. Furthermore, their claim of reduced

chemotherapy-associated toxicity was unsubstantiated in the body of the paper.

 

There are thus no adequately performed studies of the interaction of

antioxidants and standard chemotherapy in the treatment of metastatic

malignancy.

 

We believe that the time is right to study this issue and have launched a

project to attempt to further elucidate the nature of the interaction between

standard cancer chemotherapy and antioxidants and its impact on the lives of

patients with metastatic cancer.

 

Issues to be addressed include responsiveness to chemotherapy, duration of

survival, and quality of life. The ultimate goal of the project is to show a

prolongation of life with micronutrient supplementation, to show a shortening of

life if Labriola and Livingston (7) are correct, or to have the power to show no

difference.

 

A pilot study is being launched first to look at tolerability of this

micronutrient complex, compliance in this group of patients (given their altered

sense of well being and perception of taste), and evidence of oxidative damage

(as measured by urinary 8-OH-deoxyguanosine) before and during supplementation

(22).

 

We will measure levels of vitamins A, C, and E and -carotene before and during

supplementation to assess our ability to raise these levels with doses of

supplements utilized and to measure overall compliance with the regimen in

patients receiving cancer chemotherapy.

 

The optimal content for a program of micronutrient supplementation is unknown.

After much discussion, the combination of micronutrients, chosen empirically, is

as follows: a high-potency multivitamin (2 capsules twice a day), calcium

ascorbate (vitamin C, 4 g twice a day), mixed natural carotenoids standardized

to -carotene (30 mg twice a day), and d--tocopheryl succinate (vitamin E, 400 IU

twice a day).

 

The combination will be administered as several different commercially available

preparations.

 

Calcium ascorbate was chosen, rather than ascorbic acid, because there is no

associated gastrointestinal toxicity and no problem of solubility in the urine

with the calcium salt (23). As to the choice of vitamin E preparation,

-tocopheryl succinate has been found to be the most active form of vitamin E in

terms of inducing growth inhibition and cell differentiation in malignant

melanoma cell lines (24). Carini and colleagues (25) reported that -tocopheryl

succinate is more effective as an antioxidant than -tocopherol.

 

Patients will be surveyed for quality of life in addition to the objective data,

for compliance with the program, and for the ad hoc addition of supplements off

study. If the pilot study shows that the program is tolerable and compliance is

good, a large prospective randomized study will be done looking at outcome

(survival and quality of life) in patients so treated vs. patients given

placebo.

 

Patients with metastatic breast, colon, and lung cancer on conventional

chemotherapy will form the patient base; we estimate that several hundred

patients will be accrued over two to three years before the questions framed

above can be answered with certainty.

 

As part of the planning for this trial, some in our working group argued that

because the optimal combination is unknown, we should delay doing this trial

until more basic science work was accomplished. In light of the very public and

somewhat acrimonious nature of the debate, we believed that there was more to be

gained by initiating the study than by waiting.

_________________

 

JoAnn Guest

mrsjoguest

DietaryTipsForHBP

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