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Cancer Adjuvant Therapy
In 1997 the Life Extension Foundation suggested that cancer patients
ask their oncologist to consider lovastatin (80 mg a day) as adjunct therapy.
The recommendation was based on scientific studies indicating lovastatin
interfered with the cancer cell cycle and appeared to encourage cell death
(apoptosis) (Dimitroulakos et al. 2001). Lovastatin, sold under the name
Mevacor, is a fat-soluble statin drug, as are Zocor and Lipitor. Water-soluble
statin drugs such as Pravachol may not work as effectively against cancer
as the fat-soluble varieties, although one study showed Pravachol induced
significant benefits to a group of primary liver cancer patients (Wang
et al. 2000).
One of the concerns associated with low levels of CoQ10 is an increased
risk of developing cancer. CoQ10 has been reported to be effective in
inhibiting the progression of cancers and metastasis, even in patients
for whom all conventional treatment failed (Folkers et al. 1993; Lockwood
et al. 1995). CoQ10, acting as a nonspecific stimulant to the immune system,
increases blood levels of T-lymphocytes and improves the T4-T8 lymphocyte
ratio (Folkers et al. 1991). Contrast this with the energy loss and immune
suppression associated with conventional cancer therapies.
Dr. Karl Folkers, a pioneer in CoQ10 exploration, reported that in a
study of blood levels of CoQ10 in 116 breast cancer patients, 23.1% had
blood levels of CoQ10 below 0.5 mcg/mL. The incidence of breast cancer
cases with levels below 0.6 mcg/mL was 38.5%, higher percentages than
observed in healthy women. A subsequent study reported in the Journal
of Clinical Pharmacology and Therapeutics showed a statistically significant
relationship between the level of CoQ10 deficiency and breast cancer prognosis
(Folkers et al. 1997; Joliet et al. 1998).
Molecular Aspects of Medicine reported the results of an 18-month
study conducted in Denmark involving 32 breast cancer patients (Lockwood
et al. 1994). The patients had complicated medical profiles, that is,
some had involvement in axillary lymph nodes and others had distant metastasis.
The patients all received antioxidant therapy, consisting of vitamins
C, E, and beta-carotene, select minerals and trace minerals, along with
essential fatty acids, and 90 mg of CoQ10 a day. Their treatment was an
integrated approach that also included surgery, radiation therapy, and
chemotherapy. The survival rate during the 18-month study was 100%; a
follow-up evaluation at the 24-month interval indicated all participants
were still alive, although the expected deaths were four at 18 months
and six at 24 months. All 32 of the enrollees in the study reported improvement
in quality of life, stabilization of weight, a withdrawal from pain medications,
and no signs of further distant metastases; six of the 32 patients showed
apparent partial remissions.
Patients (n = 15) with myeloma showed a mean CoQ10 blood level of 0.67
± 0.17 mcg/mL. The incidence of a CoQ10 blood level below 0.7 mcg/dL
was 53.3%, which is higher than the 24.5% found among a group of nonmyeloma
patients (Folkers et al. 1997). Individuals with bloodborne tumors are
often saddened with the scarcity of nutritional material relevant to their
type of cancer. When links are found, patients and physicians should take
special note. The full clinical implication of this finding remains to
be explored.
Patients, with and without cancer, report a decrease in the incidence
of infection while taking CoQ10 (Bliznakov et al. 1970). This is particularly
important to the cancer patient, who often faces additional challenges
because of a suppressed immune system. Another extremely important characteristic
of CoQ10 is its antioxidant potential, stabilizing cell membranes and
preserving cellular integrity (Ernster et al. 1993).
One of the most potent chemicals used in cancer chemotherapy treatment
is Adriamycin (doxorubicin). A significant consequence of this drug is
cardiac damage, especially in older patients with established heart disease.
Italian researcher Dr. Mario Ghione discovered a depletion of CoQ10 in
the diseased hearts of animals after long-term Adriamycin administration.
When CoQ10 was given to a group of mice before Adriamycin therapy, 80-86%
survived; a control group (receiving Adriamycin but without CoQ10) had
only a 36-42% survival rate (Bertazzaoli et al. 1977; Cortes et al. 1978).
Dosage suggestions are 90-390 mg a day of CoQ10, taken with some fat
to enhance absorption. The American Journal of Health-System Pharmacy
reported that liver enzymes could become elevated when taking 300 mg of
CoQ10 a day for extended periods of time (Pepping 1999). Also, Folia Microbiologica
reported that mice injected with human small cell lung cancer cells and
then given high doses of CoQ10 had a diminished response to radiation
therapy compared to the non-supplemented group (Lund et al. 1998). Note:
Refer to the Cancer Chemotherapy and/or Cancer Radiation protocols along
with Cancer: Should Patients Take Dietary Supplements to read about the
appropriateness of supplementing with CoQ10 during chemotherapy or radiation
therapy.Food sources of CoQ10 include mackerel, salmon, and sardines along
with beef, peanuts, and spinach.
Conjugated Linoleic Acid (CLA)--is a trace fatty acid that inhibits tumor
formation and metastasis, suppresses arachidonic acid, and encourages
apoptosis
Researchers at the Roswell Park Cancer Institute (Buffalo, NY) showed
that CLA, derived mainly from dairy products, reduced the incidence of
breast cancer (Ip et al. 1999). Animal experiments showed that only 50%
of rats feeding on CLA butter developed mammary tumors when exposed to
high doses of known carcinogens, compared to 93% of the rats deprived
CLA. This research demonstrated for the first time that CLA in foods is
biologically active and that a food can offer significant protection against
cancer (Cornell News 1999).
Anticancer Research published supporting data that CLA (in both
test tube and animal models) demonstrates strong antitumor activity. Particularly
gratifying effects were observed regarding inhibition of growth and metastatic
spread of transplantable mammary tumors in severely immune deficient mice.
The mice were fed CLA for 2 weeks prior to inoculation with human breast
adenocarcinoma cells (107 MDA-MB468) and throughout the trial. CLA completely
abolished the spread of breast cancer cells to the lungs, blood, and bone
marrow. These results indicate that CLA blocks the local growth and spread
of human breast cancer via mechanisms independent of the immune system
(Visonneau et al. 1997; Banni et al. 1999; Ipet al. 1999).
The effects of CLA and beta-carotene were assessed on white blood cell
(lymphocyte) and macrophage function. CLA alone increased lymphocyte numbers
and their cell killing ability. Conversely, CLA inhibited interleukin-2
production (a desirable cytokine) and suppressed the ability of macrophages
to destroy foreign material. When given together, CLA and beta-carotene
interacted in an additive manner to increase lymphocyte production and
their cytotoxicity. In addition, beta-carotene was able to overcome the
inhibitory action of CLA on the phagocytic activity of macrophages (Chew
et al. 1997).
Note: The
Melanoma Center at the University of Pittsburgh Cancer Institute showed
a potential role for histamine in cancer immunotherapy. A Phase II trial
of IL-2 versus IL-2 and histamine in patients with metastatic melanoma
demonstrated a trend toward a superior survival benefit from IL-2 and
histamine for all patients enrolled and a statistically significant survival
benefit for patients with hepatic metastasis (Agarwala et al. 2001).
The effect of three different diets on the local growth and metastatic
potential of human prostatic carcinoma cells (DU-145) in severely immune-deficient
mice was studied. Animals were fed either a standard diet or diets supplemented
with 1% linoleic acid (LA) or 1% CLA for 2 weeks prior to inoculation
with cancer cells and throughout the 14-week study. Mice receiving the
LA-supplemented diet displayed significantly higher body weight, lower
food intake, and increased local tumor load as compared to the other two
groups of mice. Mice fed the CLA-supplemented diet exhibited not only
smaller local tumors, but also a significant reduction in lung metastasis
(Cesano et al. 1998). It was estimated that CLA inhibited the formation
of premalignant lesions by approximately 50%, while increasing apoptosis
in diseased cells (Ip et al. 2000).
CLA, in a dose-related fashion, has an ability to suppress arachidonic
acid (AA). Since AA produces inflammatory mediators that can promote cancer
at initiation and progression, CLA's ability to stifle AA elevates its
status as a chemopreventive (Miller et al. 2001; Urquhart et al. 2002).
In 1996, the Life Extension Foundation was in the forefront, recommendingCLA;
after evaluating the results of numerous studies, the Foundation presented
the promising anticarcinogenic nature of CLA to members. Relatively small
doses (3-4 grams of CLA) are effective. For example, young female rats
(still maturing) fed 0.8% of their diet from CLA achieved long-term protection
against breast cancer. The dose of 0.8% correlates positively to the recommended
daily dosage of 3-4 grams endorsed by the Foundation. A dose of six 1000-mg
CLA capsules (76%) each day is suggested for cancer patients, pregnant
and lactating women should avoid CLA.
Cyclooxygenase-2 (COX-2) Inhibitors (Naturally Occurring)
Note: The following compendium drawn (in part) from Beyond Aspirin (Newmark
et al. 2000) underscores herbs that inhibit COX-2, an enzyme intricately
involved in the cancer process. Natural compounds usually have many mechanisms
of action; thus, the protective mechanisms common to the herb often extend
beyond enzyme inhibition and are described herein. Because of the synergism
of herbs, combinations are often of greater value than a single herb.
The COX-2-cancer connection is thoroughly discussed in the protocol Cancer
Treatment: The Critical Factors.
Berberine--Containing Herbs (Goldenseal, Barberry, Goldthread, and Oregon
Grape)
Berberine, strong and bitter in taste and found in various herbs, delivers
anti-inflammatory properties via COX-2 inhibition (Fukuda et al. 1999).
Kaempferol, a constituent of berberine, is a strikingly active inhibitor
of COX-2 activity (Chen et al. 1999; Newmark et al. 2000). Berberine is
unique, having the ability to inhibit COX-2 activity without involving
the beneficial COX-1 enzyme. Berberine, perhaps by impacting the production
of cyclooxygenase, influences the development of cancers at various sites:
- Berberine is effective against bladder cancers (Chung et al. 1999).
- Berberine suppressed colon carcinogenesis and inhibited COX-2 without
COX-1 inhibition. The COX-2 enzyme is abundantly expressed in colon
cancer cells and plays a role in tumorigenesis. The berberine-COX-2
connection appears to best explain the mechanism of berberine's anti-inflammatory
and antitumor-promoting effects (Fukuda et al. 1999, Newmark et al.
2000).
- Berberine-induced apoptosis in human leukemia cells (Kuo et al. 1995).
- Berberine inhibited the development of skin tumors (Kitagawa et al.
1986).
- Berberine has potent antitumor activity against human and rat malignant
brain tumors (Zhang et al. 1990). Studies using goldenseal, which contains
the alkaloid berberine, showed average cancer kill rate of 91% in rats,
over twice that seen in BCNU (a standard chemotherapy agent for brain
tumors). Rat studies used 10 mg/kg of berberine.
A suggested dose is three 250-mg capsules of goldenseal each day. The
preparation should be standardized to provide 5% hydrastine. Various respected
herbalists suggest that goldenseal should be cycled (rotated with other
herbals) rather than routinely administered. Goldenseal contains the alkaloids
berberine, hydrastine, and canadine.
Feverfew (Tanacetum parthenium)
The anti-inflammatory traits of Feverfew have an ability to inhibit the
COX-2 enzyme (Hwang et al. 1996). According to Newmark et al. (2000),
feverfew contains a lactone, or chemical compound called parthenolide.
Parthenolide, in turn, contains a variant of methylene-gamma-lactone (MGL)
that interacts with macrophages. The white blood cell-lactone interaction
suppresses a critical protein process, a repression that ultimately inhibits
the COX-2 enzyme. In addition, feverfew contains apigenin (a flavonoid)
and melatonin, both COX-2 inhibitors (Murch et al. 1997).
Researchers at Children's Hospital Medical Center (Cincinnati, Ohio)
explained another of parthenolide's anti-inflammatory traits: its ability
to inhibit NF-kB, the predecessor of a number of potentially damaging
cytokines (Sheehan et al. 2002). Recall that as inflammation is reduced
the risks of many degenerative diseases decrease as well (turn to the
protocol entitled Cancer Treatment: The Critical Factors to read about
the cytokine/cancer connection).
In addition, feverfew inhibits 5-lipoxygenase, an enzyme that metabolizes
AA. A byproduct of this metabolism (hydroxy-eicosatetraenoic acid or HETE)
feeds cancer cells and promotes angiogenesis, the development of new blood
vessels. Agents that inhibit the production of lipoxygenase should be
of particular interest to individuals taking COX-2 inhibitors; as the
COX-2 enzyme is inhibited, 5-lipoxygenase enzymes become activated (Pizzorno
2001).
A suggested dosage is 1-2 capsules of feverfew a day, standardized to
contain 600 mcg of parthenolide. Pregnant and lactating women should avoid
feverfew, as well as those showing allergic sensitivities.
Ginger (Zingiber officinalis)
From the scores of biologically active components contained in ginger,
some are specific for inhibiting COX-2 and others for inhibiting 5-lipoxygenase,
enzymes responsible for the formation of pro-inflammatory agents (prostaglandin
E2 and leukotriene B4) from AA. Ginger safely modulates COX-2 activity
but also brings balance to COX-1 (an enzyme responsible for gastric mucosal
integrity) in a manner vastly superior to synthetic NSAIDs (Newmark et
al. 2000; Reiter et al. 2001).
As COX-2 and 5-lipoxygenase are repressed, two distinct metabolic pathways
are inhibited, one leading to the synthesis of prostaglandins and the
other leading to the production of HETEs. Prostaglandin E2 (PGE2) (produced
from COX-2-arachidonic acid interactions) promotes cellular proliferation,
and 5-HETE is considered indispensable fuel for tumor growth (prostate
in particular).
It has been speculated that therapeutic dosages of ginger inhibit PGE2
by up to 56%. As ginger slows down 5-lipoxygenase and 5-HETE production,
cell death is stimulated in both hormone responsive and nonresponsive
human prostate cancer cells (Suekawa et al. 1986; Ghosh et al. 1998).
Leukotrienes, produced by lipoxygenase, are considered 1000 times more
reactive than histamine. Ginger has more 5-lipoxygenase inhibitors than
any other botanical source (Newmark et al. 2000).
Ginger may also be useful in overcoming nausea that accompanies chemotherapy
and toxicity associated with the breakdown products of cancerous tissue.
James Duke, Ph.D., distinguished botanist and author, has high regard
for ginger, adding that it has a major advantage over other antiemetics
because of its safety profile. Ginger's antioxidant activity adds another
plus to a booming list of anticancer credits. A suggested dosage is 2
grams of ginger a day.
Green Tea
Salicylic acid, the main anti-inflammatory component of aspirin, is a
naturally occurring compound found in green tea, having COX-2 inhibiting
qualities. The polyphenols and flavonoids contained in green tea are also
COX-2 inhibitors (Noreen et al. 1998).
Mayo Clinic researchers showed that green tea consumption inhibited cancer
growth (Paschka et al. 1998). They identified the green tea polyphenol
EGCG (epigallocatechin gallate) as the most potent inhibitor of cancer
cell proliferation. Japanese researchers pinpointed the types of cancer
most responsive to green tea (breast, esophageal, liver, lung, skin, and
stomach) by surveying cancer-free individuals who consumed 4-6 cups of
green tea a day.
The odds ratio of stomach cancer decreased to 0.69 with a high intake
of green tea (7 cups or more a day) (Inoue et al. 1998). Another study
conducted in Yangzhong (a region in China with a high incidence of chronic
gastritis and gastric cancer) showed the amount and duration of green
tea consumption governed the rate of stomach cancer. Frequent long-term
green tea drinkers had approximately 50% less risk of developing gastric
cancer compared to individuals consuming little or no tea (Setiawan et
al. 2001). Green tea reduces the damaging effects of nitrites in the acidic
environment of the stomach with greater efficiency than vitamin C.
The growth of non-Hodgkin's lymphoma cells, transplanted in mice, was
reduced by 50% when green tea was a part of the animal's diet. Cyclophosphamide,
a chemotherapeutic drug, administered at the maximum tolerable dose, was
unable to replicate similar benefits (Bertolini et al. 2000). Part of
green tea's anticancer profile includes an antimutagenic factor that helps
DNA replicate accurately (Uhlenbruck et al. 1998).
PGE2 is thought to stimulate tumor promotion in precancerous and cancerous
cells (August et al. 1999; Bertolini et al. 2000). Of 14 subjects, 10
(71%) demonstrated a response to green tea, as evidenced by at least a
50% inhibition of PGE2 in rectal mucosa.
EGCG appears to normalize the cell growth cycle and prompt apoptosis
in cancer cells by inhibiting NF-kB, a growth vehicle cancer cells use
to escape cell regulatory control (Ahmad et al. 2000). EGCG strongly and
directly inhibits telomerase, an enzyme (normally dormant from birth)
that delivers immortal status to cancer cells (Naasani et al. 1998).
Cigarette smokers who drink green tea have a 45% lower risk of lung cancer
compared to non-tea drinkers. Even though Japan has one of the highest
numbers of smokers in the world, they have one of the lowest rates of
lung cancer of any developed nation, a protection thought to be delivered
by green tea.
The number of anticarcinogens, antioxidants, and anti-proliferative agents
found in green tea (carotenoids, chlorophyll, polysaccharides, vitamins
C and E, and numerous flavonoids) explains why some researchers advocate
using a broad-spectrum extract, replicating the plant's total constituents.
Considering the vastness of green tea’s anti-cancer effects, incorporating
green tea into the diet 5-10 cups a day (or five 350-mg capsules three
times a day of a 95% polyphenol extract) would appear to be wise for individuals
concerned with cancer.
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