COMPLEMENTARY THERAPIES, continuedVitamin E
--is an antioxidant that can protect smokers, reduces radiation damage, potentiates chemotherapy, and inhibits many types of cancers
The inhibitory role of vitamin E in the growth of a number of human tumor cells, as well as its defensive functions in overcoming treatment-induced toxicity have been examined. The impact of vitamin E (perhaps acting through its antioxidant strengths) is significant, as evidenced by the following studies:
- After examining 29,000 male smokers in Finland, researchers found that high blood levels of alpha-tocopherol reduced the incidence of lung cancer by approximately 19%. The relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development (Woodson et al. 1999).
- A combination of vitamin E and pentoxifylline (PTX), a drug that inhibits abnormal platelet aggregation, allowing more blood to reach irradiated areas, resulted in a 50% regression of superficial radiation-induced fibrosis (the proliferation of fibrous connective tissue) in half of the patients studied (Gottlober et al. 1996; Delanian 1998). A suggested dosage is 800 mg a day of PTX and 1000 IU per day of vitamin E.
- An anti-melanoma effect obtained from vitamin E succinate in vivo has been reported (Malafa et al. 2002).
- Gamma-tocopherol inhibits COX-2 activity, demonstrating anti-inflammatory properties (Jiang et al. 2001; Life Extension Magazine 2002).
- The use of vitamin E, in combination with vitamins A and C, led to a four-fold reduction in p53 mutations (Brotzman et al. 1999). This is an extremely important finding because p53 mutations indicate a more malignant, aggressive form of cancer.
- Men with a high intake of vitamin E are 65% less likely to develop colorectal adenomas (precursors to colon cancer) compared to men with low vitamin E intake (Tseng et al. 1996).
- Lower morbidity and mortality from prostate cancer in men taking 50 mg of synthetic alpha-tocopherol daily. Subsequent testing determined gamma-tocopherol to be superior, however, to alpha-tocopherol in terms of tumor cell inhibition (Moyad et al. 1999). Men in the highest fifth of the distribution for gamma-tocopherol had a five-fold reduction in the risk of developing prostate cancer compared to those in the lowest fifth. In addition, statistically significant protection from high levels of selenium and alpha-tocopherol occurred only when gamma-tocopherol concentrations were also high (Helzlsourer et al. 2000).
- Vitamin E's mode of efficacy in regard to prostate protection: Vitamin E interferes with two proteins (the receptor for testosterone and prostate-specific antigen [PSA]). The fewer androgen receptors there are on a prostate cancer cell, the less capable the remaining receptors are of turning on genes that stimulate prostate cancer growth and progression. PSA serves as a good marker molecule for androgen receptor activity (Mercola 2002b).
- Tocotrienols, quite similar to a tocopherol (but for the addition of an unsaturated tail in its chemical structure), accumulate in adipose tissues, including mammary glands. If a cell becomes diseased, the tocotrienol is prepared for action, ready to inhibit growth and regulate aberrant cellular activity at onset. Curiously, the more cancerous the cell, the more susceptible it is to tocotrienols. Scientists apparently have been focusing upon the wrong form of vitamin E (the tocopherols), which show little protection against breast cancer. Tocotrienols appear to inhibit proliferation of human breast cancer cells by as much as 50% (Nesaretnam et al. 1998). Results suggest that tocotrienols are effective inhibitors of both estrogen receptor-negative and estrogen receptor-positive cells and that combination with tamoxifen should be considered as a possible improvement in breast cancer therapy. This strategy could significantly reduce the amount of tamoxifen required to affect the cancer (Guthrie et al. 1997).
- Cortisol (associated with poorer survival) and IL-6 (a negative marker for various cancers) were significantly lower in laboratory animals that received alpha-tocopherol before a cortisol-IL-6 challenge (Webel et al. 1998).
||Combination with Vitamin E
|47% growth inhibition
||Bleomycin, 46% tumor reduction
||5-FU, 37% tumor reduction
||Adriamycin, 58% tumor reduction
||Cisplatin, 57% tumor reduction
A suggested vitamin E dosage is from 400-1200 IU a day of alpha-tocopherol together with gamma E tocopherol. For optimal results, use 80% alpha-tocopherol and 20% gamma-tocopherol. A tocotrienol dosage is 240 mg each day. Good food sources of vitamin E are cold-pressed vegetable oils, wheat germ, eggs, dark green vegetables, nuts, brown rice, and butter.Vitamin K
--is a growth regulator, promotes apoptosis, and decreases pro-inflammatory cytokines
A novel form of vitamin K that appears extremely promising in the treatment of primary liver cancer, a type notoriously resistant to chemotherapy has been discovered by scientists at the University of Pittsburgh Cancer Institute (UPCI). The research published in the Journal of Biological Chemistry described an innovative approach to treat, and possibly prevent, cancer by triggering apoptosis (Ni et al.1998).
The UPCI team found that a vitamin K analog, Compound 5 (CPD5), causes an imbalance in the normal activity of enzymes that controls the addition or removal of small molecules (phosphate groups) from proteins inside cells. Specifically, CPD5 blocks the activity of enzymes (protein-tyrosine phosphatases) that normally remove phosphate groups from selected proteins inside liver cancer cells. CPD5, however, does not interfere with another group of enzymes called protein tyrosine-kinases, which add phosphate groups to the same proteins. The result is an excess of tyrosine-phosphorylated proteins, which triggers a variety of activities within cells, including the shutting down and subsequent death of the cell.
It may be possible to remove some individuals from liver transplant waiting lists if CPD5 is as effective in humans as it is experimentally. However, the vitamin K compound is not limited to killing liver cancer; in tissue culture the compound was also effective against melanoma and breast cancers. Although the new vitamin K is not in clinical testing at this time, clients and physicians may contact the UPCI's Cancer Information and Referral Service at (800) 237-4PCI (4724) or (412) 624-1115 for periodic updates regarding the treatment. Inquirers can also visit the university's website at http://www.upci.upmc.edu.
Vitamin K compounds inhibited IL-6 production by lipopolysaccharide-stimulated fibroblasts, which are recognized as rich sources of cytokines (Reddi et al. 1995). This finding has significant anticancer implications because over-expression of IL-6 is intricately involved in the inflammatory process, bone resorption, the activation of telomerase, and cancer proliferation. A suggested vitamin K dosage is 10 mg a day. Interesting research relating to the use of vitamin K concurrent with anticoagulant therapy (not usually a recommended practice) appears in the protocol Cardiovascular Disease: Comprehensive Analysis in the section dedicated to vitamin K.OTHER FACTORS AFFECTING PATIENT OUTCOME
What Should Cancer Patients Eat?
- What Should Cancer Patients Eat?
For a cancer patient who appreciates the importance of a properly planned diet, the task is daunting. The diversity of the population minimizes the likelihood of a universal diet; nonetheless, most diets are hyped as being nutritionally correct for everyone. This section explores dietary variables, conceding that many generalities exist, that is, eat organic when available and eat on schedule to avoid blood glucose swings. Select foods characterized by color and texture. Avoid synthetic and refined foods: white flour products and sugar as well as trans fats (those fats altered by overheating, hydrogenation, and refining). Avoiding well-done meats and exposure to heterocyclic amines (formed during high temperature cooking) eliminates another significant cancer source (Zheng et al. 1998).
Tumors are primarily obligate glucose metabolizers, meaning they require sugar for survival. Even though the brain normally uses high amounts of glucose, hepatomas (a tumor of the liver) and fibrosarcomas (a sarcoma that contains fibrous connective tissue) consume roughly as much glucose as the brain. Some Americans continuously satisfy cancer's appetite, ingesting as much as 295 pounds of sugar a year.
Nobel laureate Otto Warburg, Ph.D., discovered in 1955 that cancer cells use glucose for fuel. But glucose accomplishes another strategic maneuver that strongly favors the cancer: it immobilizes internal defenses, the actions of the immune system. A study involving 10 healthy human volunteers assessed fasting blood glucose levels and the phagocytic index of neutrophils, a type of white blood cell. Glucose, fructose, sucrose, honey, and orange juice all significantly decreased the capacity of neutrophils to engulf bacteria. A diet structured away from sugars deprives cancer of its energy and increases the reliability of the immune response.
Dr. Jeff Bland advises selecting foodstuffs low on the glycemic index to avoid gratifying the tumor's appetite. The glycemic index lists the relative speed at which different foods are digested and raise blood sugar levels. Each food is compared to the effect of the same amount of pure glucose on the body's blood sugar curve. Glucose itself has a glycemic index rating of 100. Foods that are broken down and raise blood glucose levels quickly have higher ratings. The closer to 100, the more the food resembles glucose. The lower the rating, the more gradually that food affects blood sugar levels.
Common foods have the following glycemic ratings: baked potatoes, 95; white bread, 95; mashed potatoes, 90; chocolate candy bar, 70; corn, 70; boiled potatoes, 70; bananas, 60; white pasta, 55; peas, 50; unsweetened fruit juice, 40; rye bread, 40; lentils, 30; soy, 15; green vegetables; and tomatoes, < 15.
Note: The glycemic index should not be relied upon without factoring in the glycemic load, which is the glycemic index of a food times its carbohydrate content in grams, a concept developed at Harvard School of Public Health in 1997. Carrots, for instance, have a high glycemic index, but a very low glycemic load. This means that carrots consumed in moderation usually do not present a problem. Refer to the Obesity protocol
for complete information about the glycemic index load.
An admonition, based more on folk medicine than scientific certainty, to avoid the white foods (all sugar-containing foods, as well as rice, and white flour and flour-based products) appears to have validity when applied to the glycemic index. A diet structured principally around carbohydrates that promotes hyperglycemia (high blood sugar level) and hyperinsulinemia (high blood insulin level) provides an environment that feeds the fire of cancer. High blood insulin levels drive protein tyrosine kinase (leading to cell division) and high blood glucose metabolically feeds cancer cells. On the other hand, a diet centered on fiber-, vitamin-, and mineral-rich foods that cause no blood glucose rise or insulin rush is an excellent target for healthy eating.
The diseases such as obesity and diabetes mellitus (often characterized by hyperinsulinemia) are associated with an increased risk of endometrial, colorectal, and breast cancers. The mechanisms underlying insulin-mediated neoplasias appear to include enhanced DNA synthesis (with the resultant tumor cell growth), inhibited apoptosis, and an altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may in fact account for the decreased cancer incidence observed in individuals who maintain normal glucose and insulin levels (Gupta et al. 2002). Comment: Reducing blood insulin levels may result in remarkable improvements in men with prostate disease, with a concurrent drop in PSA levels (Hsing et al 2001).
Unfortunately, glucose modulation is an under-utilized component of cancer treatment. Some aspects of traditional treatments actually contribute to higher blood levels of glucose. For example, consider hospital meals, often favoring sugar-based foodstuffs. In addition, if the patient is on an IV solution, the infusion is largely dextrose based, feeding the cancer and perpetuating its growth.
The American Cancer Society believes that 30% of all cancer is due to inadequate consumption of vegetables and fruits. About 91% of Americans fail to achieve target recommendations, that is, 5 vegetable servings a day or 2-3 pounds a week. Asians who consume from 15-20 servings of fruits and vegetables a day have a much lower incidence of some cancers.
Vegetables of the cruciferous family isolate the anticarcinogenic constituents of Brassica plants. Glucosinolates (appearing in cruciferous vegetables) can inhibit, retard, or even reverse experimental multistage carcinogenesis (Fimognari et al. 2002). As enzymatic processes hydrolyze glucosinolates, isothiocyanates are released, including sulphoraphane. Sulphoraphane wields a strong arm against cancer, promoting apoptosis, inducing Phase II detoxification enzymes, increasing p53 and participating in the regulatory mechanisms of the cell's growth cycle. Necrosis (localized death of diseased tissues) is typically observed after prolonged exposure to elevated doses of sulphoraphane.
For the past several years, researchers at Johns Hopkins University have urged the inclusion of broccoli sprouts in the diet. According to Dr. Paul Talalay, broccoli sprouts have 20-50 times more anticancer sulphoraphanes than grown vegetables (Fahey et al. 1997). Eating a few tablespoons of sprouts daily can supply the same amount of chemoprotection as 1-2 pounds of broccoli eaten weekly (Talalay 1997).
Broccoli sprouts contain a chemical that kills H. pylori, even in antibiotic-resistant conditions. The release of anticarcinogenic chemicals from Brassica vegetables is a sequential process that occurs as the plant tissue is broken down. Indole-3-carbinol (I3C), a product of cruciferous metabolism, is referred to as a secondary metabolite, meaning it is not found in a preformed state in the vegetables. Rather, I3C is formed after myrosinase (an enzyme inherent to the plant) is exposed to a phytochemical in the vegetable (glucobrassicin), a glucosinolate that subsequently delivers indole-3-carbinol. This occurs only when vegetable cells are crushed or eaten, a process known as enzymatic hydrolysis. I3C, thus formed, is then broken down in the presence of stomach acid to various byproducts including diindolylmethane (DIM), another powerful defense against cancer (Lukaczer 2001). It appears highly possible that the breakdown products of I3C may be delivering as much protection as I3C itself (Katchamart et al. 2001; Lukaczer 2001; Lord et al. 2002).
An undesirable effect is the conversion of estrone to a carcinogenic material called 16-alpha hydroxyestrone that damages DNA and inhibits apoptosis. The ratio of 2-hydroxyestrone to 16-hydroxyestrone indicates a woman's risk for developing breast and ovarian cancer. Levels of 2-hydroxyestrone are typically higher in women who do not get cancer; 16-hydroxyestrone is higher in women with cancer. When breast cancer cells are treated with I3C (in vitro) 90% of cells undergo growth inhibition, whether the cells are estrogen positive or negative (Galland 2000).
Broccoli (500 grams for 12 days) increased the average 2-alpha-hydroxyestrone:16- alpha-hydroxyestrone ratio (Kall et al. 1997). Hence, consuming vegetables rich in indole-3-carbinol gives hope that as 2-hydroxyestrone increases, cancers will be decreased in both men and women. The ability of I3C to neutralize estrogen metabolites as well as to block aflatoxin (a mycotoxin that promotes prostate cancer) makes cruciferous vegetables equally important to men.
By inhibiting protein kinases and other growth factors, restoring p21 activity, and encouraging apoptosis, I3C appears an effective chemopreventive/therapeutic agent against many types of malignancies (Chinni et al. 2001; Roman-Gomez et al. 2002). Evidencing its benefits, I3C reduced the incidence of cervical cancer from 76 to 8% in laboratory mice (Jin et al. 1999), and administered together with tamoxifen, I3C inhibited the growth of estrogen-dependent human MCF-7 breast cancer more effectively than either agent used alone (Cover et al. 1999).
If vegetables providing I3C are in short supply in the diet, indole-3-carbinol capsules are available. For those under 120 pounds, one 200-mg capsule taken 2 times a day is suggested; those between 120-180 pounds could take 200 mg 3 times a day, while those over 180 pounds could take four 200 mg a day. If the diet generally lacks adequate amounts of vegetables, powdered vegetable extracts are available, an example is PhytoFood; a suggested dosage for cancer patients is 1-2 tbsp daily (with food).Cholesterol (Can It Be Too Low?)
Hypocholesterolemia (abnormally low levels of cholesterol) has been shown in several epidemiological studies to be related to increased mortality from human cancer. Cholesterol and triglyceride levels in 135 patients with squamous cell and small cell lung carcinoma were evaluated. All lung cancer patients had higher rates of hypocholesterolemia as well as lower triglyceride levels compared to a healthy control group. Total cholesterol concentrations were lower in both histological types, but triglyceride levels were lower only in patients with squamous cell lung cancer (Siemianowicz et al. 2000).
An article in Hematology and Oncology reported that 90% of 83 patients with acute myeloid leukemia were hypocholesterolemic (Zyada et al. 1990). Additionally, another article in the European Journal of Haemtology reported that remission in acute myelogenous leukemia was associated with a significant increase in cholesterol levels in those patients with low cholesterol concentrations or high leukocyte counts at diagnosis (Reverter et al. 1988).
Various reports have emerged showing that low cholesterol levels are associated with higher death rates (particularly among elderly people), from cancer and infection (Weverling-Rijnsburger et al. 1997; Schatz et al. 2001). These findings raise concerns regarding hypocholesterolemic drug therapy and diet manipulation to drastically lower cholesterol levels in a subset of the population.STRESS AND CANCER
Few events are as stressful as a diagnosis of cancer. As the stress level increases, the outpouring of the adrenal cortex hormone (cortisol) also increases. Women with breast cancer who had abnormal cortisol rhythms survived an average of 3.2 years, while those with normal rhythms survived an average of 4.5 years (more than a year longer). The difference in survival times began to emerge about 1 year after the cortisol testing and continued for at least 6 additional years (Richter 2000).
Animal studies, mostly involving rats, demonstrated stress as a causal factor in cancer. The onset of cancer appears similarly allied in humans, with the immune system highly responsive to emotional pitfalls. It is well established that when the individual is emotionally challenged, cancer has a significant advantage (Levy et al. 1987).
Psychobiologist Shamgar Ben-Eliyahu, Ph.D., has been working for the past decade on stress, tumor development, and the activity of NK cells (Ben-Eliyahu et al. 2000). Considering all immune system cells, NK cells show the strongest activity in preventing metastasis and the strongest response to stress. Even short-term stress decreases NK cell activity in laboratory animals, significantly increasing the risk of certain types of cancer and metastasis. Gender plays a significant role in the NK cell response to stress, with men more adversely affected than women (Irwin 2000). The stress of abdominal surgery promotes the growth of cancerous tumors in rats, a sequence thought orchestrated by NK cell suppression (Ben-Eliyahu et al. 1999).
High levels of neuropeptide-gamma are observed in the bloodstream of depressed individuals, an elevation synonymous with immune suppression (Ader et al. 1981; Scanlan et al. 2001). Macrophages (pathogen scavengers) have receptor sites that attract endorphins (mood enhancers with analgesic traits). With the right emotional programming, white blood cells swim through the bloodstream with determination; conversely, under stress, immune competence falters, and the immune attack becomes lethargic.
Breast cancer patients with the most anxiety had a weaker immune response and were less equipped to fight the disease. The following stress-associated situations and personality types are associated with breast cancer: (1) the use of denial or repression as a coping strategy, (2) an experience of separation or loss, (3) a history of stressful life experiences, (4) a tendency toward melancholy and hopelessness (this trait has, since antiquity, been associated with uterine and breast cancers), and (5) a personality type characterized by conflict avoidance. It is theorized that the genes that cause one to avoid conflict are the same genes that increase susceptibility to cancer (Goodkin et al. 1986; Darmon 1993).
Also, psychological stress induces the production of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-10 (Maes et al. 2000). Please refer to the protocol Cancer: Gene Therapies, Stem Cells, Telomeres, and Cytokines for a full discussion regarding pro-inflammatory cytokine's role in malignancies.
The effect of chronic stress on the immune system of 116 recently treated breast cancer patients found (reproducibly) that stress levels significantly predicted (1) lower NK cell activity, (2) diminished response of NK cells to interferon-gamma, and (3) decreased proliferation of lymphocytes, white blood cells considered the army of the immune system (Andersen et al. 1998). Oncologists often suggest stress management, such as meditation, yoga and breathing exercises, guided imagery, or spirituality, to help bring about calm.
Because the cells responsible for cancer surveillance work best in an environment favoring confidence and calm, it is important that the message springing from our thoughts and transmitted to cells is commensurate with healing. Fright, pessimism, and melancholy send uncertain instructions and the cells respond with a feeble effort. The enduring message (fear or assurance, despair or hopefulness, laughter or tears) reflects our hour-to-hour psyche and sets the tone for health victories or failures. Expect little more from your body than the quality of your thoughts at this very moment: "As a man thinks in his heart, so is he" (Proverbs 23:7).Continued
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