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Cancer Adjuvant Therapy
Vitamin A--offers protection against radiation induced tissue damage,
down-regulates telomerase activity, and is involved at almost every juncture
of cancer control
Retinoids induce cell differentiation, control cancer growth and angiogenesis,
repair precancerous lesions, prevent secondary carcinogenesis and metastasis,
and act as an immunostimulant. After FAR therapy (5-fluorouracil-retinol
palmitate with radiation and surgery), the disease-specific, 5-year survival
was nearly 50% in various head and neck cancers (Yamamoto 2001). Retinoids,
at pharmacological levels, assist in preventing the appearance of secondary
tumors following curative therapy for epithelial malignancies.
It is well-established that a vitamin A deficiency (in laboratory animals)
correlates with a higher incidence of cancer and an increased susceptibility
to chemical carcinogens. This is in agreement with epidemiological studies,
which indicate that individuals with a lower dietary vitamin A intake
are at a higher risk of developing cancer (Sun et al. 2002). The chemotherapeutic
possibilities surrounding vitamin A areplentiful.
Two vitamin A analogs currently in large chemoprevention, intervention
trials, or epidemiological studies are all-trans-retinoic acid (ATRA)
and 13-cis-retinoic acid (13-cis-RA).
Note: Retinoic
acid is biologically active in two forms: all- trans- retinoic acid and
9-cis-retinoic acid. Vitamin A and 13-cis-RA are converted to these biologically
active forms.
Thirty-two women with previously untreated cervical carcinoma (ages 14-60)
were treated for at least 2 months using oral 13-cis-RA (1 mg per kg body
weight a day) and alpha-interferon subcutaneously (6 million units daily):
16 of the women (50%) had major reactions, including four complete clinical
responses. Remission occurred in 15 of the patients within 2 months and
in one patient within 1 month; toxicity to treatment was described as
manageable (Espinoza et al. 1994). The positive results were replicated
in other studies using a similar model (Hansgen et al. 1998, 1999).
The role of 13-cis-RA on a human prostate cancer cell line (LNCaP) was
studied. It was found that 13-cis-RA significantly inhibited PSA secretion
and the ability to form new tumors. It was also noted that tumors that
appeared (having escaped 13-cis-RA inhibition) were smaller compared to
tumors in nontreated animals (Dahiya et al. 1994). During the course of
13-cis-RA therapy, prostate cancer cells became more differentiated, that
is, they resembled (microscopically) normal prostate cells.
A combination of phenylbutyrate and 13-cis-RA as a differentiation and
anti-angiogenesis strategy against prostate cancer was evaluated. Phenylbutyrate,
considered nontoxic, is used to arrest tumor growth and induce differentiation
of premalignant and malignant cells. Tissue examination of tumors showed
decreased cell proliferation and increased apoptosis, as well as reduced
microvessel density in animals treated with 13-cis-RA and phenylbutyrate;
tumor growth was inhibited by 82-92%. In contrast, researchers reported
13-cis-RA and phenylbutyrate, when used singularly, were suboptimal in
terms of clinical benefit (Pili et al. 2001).
A pilot study conducted at M.D. Anderson Cancer Center found ATRA alone
ineffective as a long-term treatment for chronic myelogenous leukemia
(CML). Only four of 13 subjects showed a transient, nonsustaining indication
of an anti-leukemic effect (Cortes et al. 1997). However, combinations
of therapeutic agents that included ATRA were promising in the treatment
of CML. The combination included alpha-interferon plus ATRA, which reduced
proliferation 50-60% (Marley et al. 2002).
Cisplatin (a popular chemotherapeutic agent) shares a similar chemotherapeutic
profile with ATRA (the ability to induce cytotoxicity through apoptosis).
A combination of ATRA and cisplatin induced apoptosis in significantly
more cancer cells, particularly in ovarian and head and neck carcinomas,
than either drug alone (Aebi et al. 1997). A combination of ATRA and IL-2
showed therapeutic value in treating resistant metastatic osteosarcoma,
a malignant tumor of the bone (Todesco et al. 2000).
For decades, researchers have searched for ways to minimize the damage
to the heart during Adriamycin therapy. Adriamycin, though relatively
effective, damages the heart muscle. Several animal studies indicated
that supplemental vitamin A reduced Adriamycin-induced inflammation and
preserved heart tissue. Vitamin A appears not only to counter Adriamycin
damage, but also to increase survival in animals (Tesoriere et al. 1994).
Vitamin A extends similar protection to patients using cisplatin, a drug
often used for bladder and ovarian cancer, as well as small cell carcinoma.
Radiation-induced lung injury frequently limits the total dose of thoracic
radiotherapy that can be delivered to a patient undergoing treatment,
restricting its effectiveness. Animal studies suggest that supplemental
vitamin A may reduce lung inflammation after thoracic radiation and modify
radiotherapy damage to the lungs (Redlich et al. 1998).
Vitamin A (in dosages of 25,000 IU a day) offers significant protection
against radiation-induced tissue damage. Various cancer patients use more
than 100,000 IU of a water-soluble vitamin A liquid a day, a dosage that
must be supervised by a physician. Do not supplement with vitamin A if
the cancer involves the thyroid gland or if the liver is damaged. Both
professionals and patients should consult Appendix A to read about avoiding
vitamin A toxicity. Good food sources of vitamin A include liver and fish
liver oils, green and yellow fruits and vegetables such as apricots, asparagus,
broccoli, cantaloupe, carrots, collards, papayas, peaches, pumpkins, spinach,
and sweet potatoes. High-potency water-soluble vitamin A is available
as a dietary supplement.
Vitamin C (ascorbic acid)--has a chemotherapeutic effect on many cancers,
promotes collagen production, sequestering the tumor, and reduces the
toxicity of conventional therapies
Linus Pauling, winner of the Nobel Prize for chemistry in 1954 and the
Nobel Prize for Peace in 1963, believed strongly that vitamin C could
play an important role in cancer treatment. Dr. Pauling suggested 10 grams
of vitamin C a day for patients with advanced cancer for whom conventional
treatments had ceased to be of benefit (Cameron et al. 1993). Over an
8-year period, 500 patients with varying stages and types of cancer were
treated with vitamin C therapy. Those receiving 10 grams of vitamin C
a day improved their state of well-being, as measured by increased appetite
and mental alertness, as well as a decreased need for pain-killing drugs.
A retrospective analysis showed that those using vitamin C lived considerably
longer than those not supplemented.
Various clinics are using intravenous vitamin C and with positive results.
Dr. Hugh Riordan, recognized as a world authority on this procedure, practices
from Wichita, KS, at the Center for the Improvement of Human Functioning
International. Dr. Riordan's vitamin C story began in 1984 when he treated
his first cancer patient; a 70-year-old renal cell carcinoma patient with
metastasis to the lung and liver, using injectable vitamin C. Renal cell
carcinoma has only a 5% response rate.
The initial treatment began with 15 grams of vitamin C administered intravenously
2 times a week; showing excellent tolerance, the vitamin C dosage was
increased to 30 grams twice weekly. Within 6 weeks, the patient showed
a favorable response to treatment and at the 12-week interval was pronounced
tumor-free. The patient lived 14 additional years and died of congestive
heart failure with no evidence of tumors.
In light of the favorable initial response to intravenous (IV) vitamin
C, ascorbic acid was investigated. Vitamin C is preferentially toxic to
tumor cells, that is, it kills tumor cells but not normal cells.
In low doses, vitamin C assumes the nature of an antioxidant; in high
dosages, vitamin C changes roles and becomes a prooxidant, inducing peroxide
production. Tumor cells have a relative catalase deficiency, an enzyme
necessary to detoxify hydrogen peroxide to water and oxygen. A 10- to
100-fold difference in catalase concentrations exists between tumor cells
and normal cells. Without the protection of catalase, peroxide accumulates
in cancerous cells, along with aldehydes (toxic byproducts of the reaction),
causing death to malignant cells. On the other hand, normal, healthy tissues
have the protection of the detoxification enzyme and are spared destruction
by peroxide and aldehyde. Vitamin C, a virtually nontoxic nutrient (Bowie
et al. 2000), could cause a transient diarrhea if not absorbed properly.
Vitamin C is safe compared to standard chemotherapeutics and has an ability
to preserve immune function. Many patients succumb, not because of cancer,
but rather from a post-chemotherapeutic toxicity, resulting from a damaged
immune system. Vitamin C protects the immune system. Vitamin C is preferentially
toxic to many types of cancer cells, including 20 different melanoma cell
lines. Ovarian cell lines are more susceptible to vitamin C-induced toxicity
than pancreatic cells. Breast cancer appears to be one of the most responsive
cancers to IV vitamin C.
Much higher concentrations of vitamin C are required to kill cancer cells
than originally thought, about 600 mg/dL. Also, as the density of the
cells increases, the efficacy of vitamin C decreases. It is extremely
difficult to reach vitamin C concentrations greater than 200 mg/dL even
when administered intravenously (Riordan et al. 2000). To increase the
sensitivity of tumor cells to vitamin C, other approaches need to be employed.
Alpha-lipoic acid, a water- and lipid-soluble antioxidant that recycles
vitamin, enhances the toxic effect of ascorbic acid. Lipoic acid decreases
the dose of vitamin C required to kill tumor cells from 700 to 120 mg/dL
(Riordan et al. 2000). Vitamin C toxicity is further enhanced by 1000
mcg of vitamin B12, which forms cobalt ascorbate, a benign but cancer-cell-toxic
agent. Vitamin K, selenium, quercetin, niacinamide, biotin, and grape
seed extract are also regarded as potentiation factors.
The goal is to achieve and maintain 400 mg/dL of vitamin C in the plasma.
At this concentration, every cancer cell line so far tested has been found
to be sensitive to vitamin C. After reaching an ascorbic acid peak, as
occurs during infusion, the level returns to near baseline levels 24 hours
after the IV infusion.
Vitamin C has an ability to increase collagen production. Vitamin C is
required for the hydroxylation of proline, which in turn is required for
collagen production. Vitamin C has the ability to inhibit enzymes that
degrade or break down the extracellular matrix. Vitamin C dramatically
increased the collagen within tumor cells, an act that tended to immobilize
the cells
Vitamin C (supported by lipoic acid) has been used as a cancer therapy.
It is strongly advised that patients contact a physician trained in administering
infusions and monitoring progress. By giving vitamin C intravenously,
doctors can achieve a blood saturation that far exceeds that attained
by administering vitamin C orally (200% versus 2%). A high dose of vitamin
C is critical to achieve tumor cell kill.
A Hickman line allows large doses of vitamin C to be self-administered
at home on a daily to weekly basis over a period of months, modulating
down or up in frequency according to response. Otherwise the treatment
can be administered as an outpatient. Contraindications to vitamin C therapy
are few but include individuals with kidney failure and on dialysis, as
well as those with hemochromatosis. Also, physicians should screen patients
for a red blood cell glucose-6 phosphate dehydrogenase deficiency, a rare
condition whose presence can lead to a hemolytic crisis involving red
blood cell breakdown.
Large doses of vitamin C should be reached gradually to establish tolerance.
For example, 15 grams for one or two sessions and then 50 grams to 100
grams if necessary. The exact dose is determined by the individual's plasma
saturation immediately after an infusion. The therapy should not be stopped
abruptly because a rebound effect could result in scurvy. Patients should
allow weeks or even months to wean off the treatment, with oral vitamin
C therapy used on the days between infusions.
A 10-year research project using high dose IV vitamin C has been completed.
While a number of orthomolecular physicians are using IV vitamin C therapy,
it is recommended that Dr. Riordan's protocol become the backbone of the
therapy. Instructions are available to physicians upon request from the
center (Riordan et al. 2003).
Center for the Improvement of Human
Functioning
3100 North Hillside Avenue
Wichita, KS 67219
(316) 682-3100
Other chemotherapeutic credits awarded
to vitamin C:
- Vitamin C prolongs the lives of animals undergoing conventional cancer
treatment by protecting normal cells against chemotherapy-induced toxicity;
in tandem, vitamin C increases the cytotoxicity targeted at the cancer
(Antunes et al. 1998; Giri et al. 1998). When 5-FU was administered
together with vitamin C, the tumor cell kill rate was boosted from 38
to 95.5%. X-ray therapy decreased cancer growth 72%, but adding vitamin
C to the regime decreased cancer growth by 98.2%. Full spectrum antioxidants
rather than isolated nutrients are suggested (Prasad et al. 1999; Moss
2000).
- Infection: Heliobacter pylori increases the risk of developing stomach
cancer (Uemura et al. 2001), as well as pancreatic cancer (Stolzenberg-Solomon
et al. 2001). High doses of vitamin C inhibit the growth of H. pylori,
both in vitro and in vivo (Zhang et al. 1997). A study showed vitamin
C levels to be consistently low in individuals with the H. pylori infection
(The Analyst 2002).
- Frequent intake of vitamin C from food and supplement sources was
associated with a protective effect against multiple myeloma, particularly
among Caucasians. African Americans benefited less from ascorbic acid
intake (Brown et al. 2001).
- NF-kB is a central mediator of altered gene expression during inflammation
and is implicated in cancer. Vitamin C inhibited the activation of NF-kB
by multiple stimuli, including IL-1 and TNF-alpha (Bowie et al. 2000).
It should be re-emphasized that oral vitamin C does not bestow equal
benefits compared to intravenous vitamin C. If a patient with a solid
tumor elects to use oral vitamin C, ascorbic acid buffered with sodium
may produce better results. If the cancer is blood-borne (leukemia, lymphoma,
or myeloma), ascorbic acid crystals buffered with calcium appears to offer
greater efficacy. The majority of the patients use 6-12 grams a day. Food
sources of vitamin C are berries, citrus fruits, papayas, and pineapple,
as well as tomatoes, broccoli, Brussels sprouts, dandelion and mustard
greens, peas, red peppers, and spinach.
Vitamin D--promotes differentiation, inhibits angiogenesis, regulates
cell division
Current recommendations to avoid natural sunrays to thwart the possibility
of deadly melanoma may be allowing other endangerments. For more than
50 years, medical literature has affirmed that regular sun exposure is
associated with a substantial decrease in death rates from certain types
of cancers. It is estimated that moderate sun exposure without sunscreen
- enough to stimulate vitamin D production but not enough to damage the
skin - could prevent 30,000 cancer deaths in the United States each year
(Ainsleigh 1993). The most damaging of the sun's rays occur between the
hours of 10 a.m. and 3 p.m. and are thus the hours demanding the greatest
watchfulness.
Evidence points to a prostate, breast, and colon cancer belt in the United
States, which lies in northern latitudes under more cloud cover than other
regions (Studzinski et al. 1995). Certain regions in the United States,
such as the San Joaquin Valley cities and Tucson, AZ; Phoenix, AZ; Albuquerque,
NM; El Paso, TX; Miami, FL; Jacksonville, FL; Tampa, FL; and Orlando,
FL; have a lower incidence of breast and bowel cancers. Conversely, New
York; Chicago; Boston; Philadelphia; New Haven, CT; Pittsburgh; and Cleveland,
OH; have the highest rates of breast and intestinal cancer of the 29 major
cites in the United States. The greater hours of year-round sunlight correlate
to a lower rate of breast and intestinal cancer in the U.S.A.
Vitamin D is formed in the skin of animals and humans by the action of
shortwave UV light, the so-called fast-tanning sunrays. Precursors of
vitamin D in the skin are converted into cholecalciferol, a weak form
of vitamin D3, which is then transported to the liver and kidneys where
enzymes convert it to 1,25-dihydroxycholecalciferol, the more potent form
of vitamin D3 (Sardi 2000). Although vitamin D exists in two molecular
forms, vitamin D3 (cholecalciferol) found in animal skin and vitamin D2
(ergocalciferol) found in yeast, vitamin D3 is believed to exhibit more
potent cancer-inhibiting properties and is therefore the preferred form.
Dark-skinned people require more sun exposure to produce vitamin D because
the thickness of the skin layer (the stratum corneum) affects the absorption
of UV radiation. Black human skin is thicker than white skin and thus
transmits only about 40% of the UV rays needed for vitamin D production.
Darkly pigmented individuals who live in sunny equatorial climates experience
a higher mortality rate from breast and prostate cancer when they move
to geographic areas that are deprived of sunlight exposure in winter months
(Angwafo 1998; Sardi 2000).
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