Sunday, January 13, 2008

Uterine (Endometrial) Cancer

Life After Treatment: Nutritional Support and Dietary Recommendations

Nutritional factors have been estimated to contribute to 20 percent to 60 percent of cancers and to almost one third of deaths from cancer in Western countries.

Low-fat diet

A diet high in animal fat, particularly red meat, may be associated with a small to moderately increased risk of uterine cancer (Potischman N et al 1993; Terry P et al 2002). This is probably because high-fat (and sugar) diets cause increased body fat content, which in turn results in high levels of estrogens. Estrogens are known for their proliferative effects on estrogen-sensitive tissues, resulting in tumor development. There is a stronger association between dietary fat and uterine cancer in women who have high circulating levels of estrogen, such as women with a higher body mass index ( BMI ) and users of unopposed estrogens (Littman AJ et al 2001). A low-fat diet may be linked to lower estrogen levels and thereby protect against uterine cancer (Hill HA et al 1996).

Fish and flaxseed
Oily fish such as salmon, herring, mackerel, bluefin tuna, and sardines contain high levels of essential omega-3 polyunsaturated fatty acids. Omega-3 fatty acids reduce the risk of certain hormone-dependent cancers by exerting favorable effects on estrogen metabolism, such as decreasing estrogen stimulation of these tumors and competitive inhibition of omega-6 fatty acids, which are associated with cancer development (Lord RS et al 2002).

The American Heart Association recommends two servings of fatty fish per week to obtain cardiovascular benefits from omega-3 fatty acids (Kris-Etherton PM et al 2002). Two to three servings of fatty fish per week are also suggested to prevent uterine cancer (Lord RS et al 2002; Terry P et al 1999).

Other primary sources of dietary alpha-linoleic acid (which can be converted into omega-3 fatty acids) are ground flaxseed, soybeans, pumpkin seeds, and walnuts (Kris-Etherton PM et al 2002). Ground flaxseed is a good source of omega-3 fatty acids (Brooks JD et al 2004; Lucas EA et al 2002) and is “as effective as oral estrogen-progesterone to improve mild menopausal symptoms” and to lower glucose and insulin levels (Lemay A et al 2002).

Fruits and vegetables
Significant protection against uterine cancer (a 40 percent to 60 percent reduction) was found to be conferred by elevated intake of most fresh vegetables and fruits and whole-grain foods (Levi F et al 1993). Therefore, a diet rich in fruits, vegetables, whole grains, and fiber most likely will help protect against uterine cancer (Doll R 1992; La Vecchia C et al 1986; McCullough ML et al 2004; Willett WC 2005).

Various nutrients found in fruits and vegetables seem to have the ability to detoxify certain carcinogens (cancer-causing agents) (Steinmetz KA et al 1991). For example, the risk of uterine cancer is inversely related to intake of beta-carotene and fiber (La Vecchia C et al 1986). Fruits and vegetables that contain high amounts of vitamin A (Schapira DV 1992), beta-carotene (Levi F et al 1993), and vitamin C (Berstein L et al 2002) may decrease the risk of uterine cancer.

In addition, cruciferous vegetables may have favorable effects on estrogen metabolism (Terry P et al 2002) and thus reduce the risk of developing uterine cancer (Kobayashi Y et al 2003). Examples of cruciferous vegetables include cabbage, Brussels sprouts, bok choy, kale, kohlrabi, broccoli, and watercress.

Vegetables from the allium group (allium is Latin for garlic) also may reduce the risk of uterine cancer by interrupting cancer cells' reproduction cycle (Shu XO et al 1993; Tanaka S et al 2004). Examples of allium vegetables include garlic, onions, scallions, leeks, chives, and shallots.

Whole grains and high-fiber foods
A diet rich in whole grains and high-fiber foods has been closely correlated with reduced uterine cancer risk (Jacobs DR Jr et al 2004; La Vecchia C et al 1986; Schapira DV 1992). These foods are rich in antioxidants, which are important in cancer prevention (Nishino H et al 2004; Potischman N et al 1993). Low levels of antioxidants within the uterus and surrounding pelvic organs may allow proliferating free radicals to cause damage and prevent optimal functioning (Khorram O et al 2002). Many of these types of foods also contain plant estrogens (phytoestrogens), which exert protective hormonal effects against hormone-related cancers such as uterine, breast, and prostate cancer (Cassidy A 2003; Goodman MT, Wilkens LR et al 1997). Examples of whole grains include brown rice, oatmeal, pearl barley, whole wheat, and whole rye. High-fiber foods include legumes, beans, seeds, and nuts.

Soy
Nutritional studies indicate that people in Asian countries consume approximately 10 times the amount of fermented soy as the average American. A diet rich in fermented soy reduces the risk of uterine cancer ( Horn-Ross PL et al 2003; Xu WH et al 2004). The consumption of soy foods also provides high amounts of fiber, which is protective against uterine cancer (Cassidy A 2003; Goodman MT, Wilkens LR et al 1997).

Fermented soy foods include miso, tempeh, and natto. Soy milk, soy flour, and textured soy protein are used to make a variety of soy-based products including soy burgers (veggie burgers), soy cheese, and soy ice cream and yogurts. However, these processed nonfermented soy foods may not be recommended for people who already have cancer; fermented soy is the preferred source for them.

Dietary Supplements
The following are some of the dietary supplements that have been found to prevent and, in some cases, treat uterine cancer.

Vitamin A and carotenoidsCarotenoids such as alpha-carotene, beta-carotene, lutein, and lycopene have been shown to be protective against uterine cancer (Hill HA et al 1996; La Vecchia C et al 1986; Levi F et al 1993; Nagpal S 2004; Nahum A et al 2001). Vitamin A inhibits uterine tumor growth (Nagpal S 2004; Petridou E et al 2002; Schapira DV 1992).

Vitamin A can be obtained from liver and yellow or orange vegetables. The Council for Responsible Nutrition ( CRN ) suggests taking 10,000 international units (IU) of vitamin A if you have a low dietary retinol intake or 5000 IU of vitamin A if you already have a high dietary retinol intake. The dosage for optimum health and for cancer prevention is not defined, but several cancer studies have shown benefits of 25,000 IU per day (Alberts DS et al 2004; Carter CA et al 1996; Kakizoe T 2003; Meyskens FL Jr et al 1995).

Vitamin C
Vitamin C is an important antioxidant and has been linked to reduced risk of uterine cancer (Berstein L et al 2002; Goodman MT, Hankin JH et al 1997; Levi F et al 1993; McCann SE et al 2000). It is believed that vitamin C works against cancer by enhancing the immune system and suppressing cancer cell growth (De Loecker W et al 1993; Lenton KJ et al 2003). In addition, vitamin C causes the formation of collagen (Golde DW 2003), which can wall off tumors (Alcain FJ et al 1994; De Loecker W et al 1993; Head KA 1998) and help block the spread of cancer (Block KI et al 2003; Tamayo C et al 2003). Vitamin C can be obtained by eating citrus fruits and dark green, leafy vegetables (Cameron E et al 1978; Gonzalez MJ et al 2005). Many people prefer to take vitamin C in the form of a dietary supplement. Clinical studies have used up to 10 grams (g) daily (10,000 milligrams [mg] per day) (Cameron E et al 1978; Gonzalez MJ et al 2005).

Melatonin
Melatonin is a hormone secreted by the pineal gland. It is responsible for sleep patterns and can enhance immunological activity (Simonneaux V et al 2003). Melatonin may help prevent cancer, especially cancers related to hormonal activity such as breast, prostate, and uterine cancers (Barrenetxe J et al 2004; Lissoni P, Chilelli M et al 2003; Lissoni P, Malugani F et al 2003; Reiter RJ 2004; Sanchez-Barcelo EJ et al 2005).

The melatonin dosage for insomnia is normally 3 to 6 mg at bedtime (Chase JE et al 1997; Dolberg OT et al 1998). However, the majority of clinical cancer studies have used much higher doses, up to 20 mg of melatonin at bedtime (Barrenetxe J et al 2004; Lissoni P, Chilelli M et al 2003; Lissoni P, Malugani F et al 2003; Sanchez-Barcelo EJ et al 2005).

Ginseng
Ginseng is an herb that has been used in Asian medicine for thousands of years. In experimental conditions, ginseng destroys cancerous tumors by attacking them at the cellular level (Bespalov VG et al 2001) and preventing cancer spread (Fujimoto J et al 2001). Moreover, Siberian ginseng but not Asian ginseng (Panax ginseng) or North American ginseng (Panax quinquefolius) has been shown to bind to estrogen receptors (Liu J et al 2001; Pearce PT et al 1982).

Preliminary clinical trials with panaxel and bio ginseng (Panax ginseng from Siberia ) were carried out in patients with precancerous lesions of the endometrium. Bio ginseng caused regression of these precancerous lesions (adenomatous cystic hyperplasia) of the endometrium in some patients. Thus, bio ginseng appears to hold considerable promise for uterine cancer prevention (Bespalov VG et al 2001).

A multicenter cancer-prevention study of hepatocellular carcinoma (a type of liver cancer) is underway in Korea where participants take 1 g of red ginseng powder per day for 5 years in an attempt to prevent this type of liver cancer (Ginseng- HCC Chemopreventive Study Osaka Group 2001; Manusirivithaya S et al 2004).

In a randomized, multicenter, double-blind study of symptomatic postmenopausal women, a standardized ginseng extract was found to improve quality of life and overall relief of symptoms without increasing thickening of the endometrium or raising estradiol levels (Wiklund IK et al 1999).

Adverse effects of ginseng are rare, but may include nervousness, insomnia, blood-clotting problems, high blood pressure, diarrhea, and, rarely, breast tenderness and irregular menstruation in women (Yuan CS et al 2004).

Allicin
Allicin is the major ingredient in fresh crushed garlic. Allicin is also found in onions, scallions, leeks, chives, and shallots. These vegetables have been shown to reduce the risk of uterine cancer by interrupting the reproductive cycle of the cancer cells (Hirsch K et al 2000; Shu XO et al 1993; Tanaka S et al 2004).

Selenium
Because selenium is a trace mineral found in soil, the amount of selenium in plant foods relates to the quality of the soil the plants are grown in. Therefore, diet is not the best method of obtaining reliable amounts of selenium (Sundstrom H 1985).

A low concentration of selenium in the body may be a contributing factor in uterine carcinogenesis (Sundstrom H et al 1986, 1984). Selenium works against cancer cells through antioxidant activity (Zhao L et al 2001), preventing or slowing tumor growth (Lou H et al 1995). Selenium is linked to a decreased risk of developing various types of gynecological cancers (Cunzhi H et al 2003; Drozdz M et al 1989; Sundstrom H et al 1986; Sundstrom H et al 1989).

A dosage of 400 micrograms (mcg) has been proposed as a safe daily dietary selenium intake (Yang G et al 1994). High doses (more than 910 mcg/day) can result in a rare condition called selenosis, is characterized by gastrointestinal upset, hair loss, white blotchy nails, fatigue, and irritability (Kaur R et al 2003; Sundstrom H 1985).

Calcium
Daily use of calcium supplements appears to lower endometrial cancer risk (Salazar-Martinez E et al 2005), especially in women whose calcium intake is low because they do not eat dairy products (La Vecchia C et al 1986; Terry P et al 2002).

The amount of calcium supplementation varies, depending on how much calcium is consumed in the diet (Schaafsma G 1992). However, the American College of Obstetricians and Gynecologists recommends that women take 1000 mg/day of calcium if they are younger than age 50 and 1500 mg/day of calcium if they are age 50 and above (American College of Obstetricians and Gynecologists 1998; Power ML et al 1999).

For More Information
The complications of uterine cancer are related to the natural progression of the disease, or to the adverse effects of surgery, chemotherapy, or radiation. Thromboembolic disease (a tendency toward blood clots) has long been associated with uterine cancer.

Most of the adverse effects of chemotherapeutic agents are predictable and can be lessened with adjuvant medications or by taking nutritional supplements because poor nutrition is a risk factor.

The complications related to radiation can be acute (such as low blood cell counts) and chronic (gastrointestinal, genitourinary, and pulmonary). Gastrointestinal symptoms are controlled with supportive therapy such as eating a glutamine-rich diet, drinking enough water, and avoiding high-fiber foods while symptoms persist. For further information on some of the topics outlined in this chapter, read the following chapters:

a)Cancer Surgery
b)Cancer Radiation
c)Cancer Chemotherapy
d)Obesity
e)Female Hormone Replacement
f)Breast Cancer


Life Extension Foundation Recommendations

Women who have uterine cancer should consult their physician before taking any nutritional supplements, especially if they are receiving conventional medical treatment. The Life Extension Foundation suggests:

Apple pectin—2.8 grams (g) daily, with water
Calcium—1000 to 1500 milligrams (mg) daily
Essential fatty acids—4.8 g of eicosapentaenoic acid (EPA) and 2.4 g of docosahexaenoic acid (DHA) daily
Ground flaxseed—3 tablespoons (25 to 40 g) daily, with water
Garlic—1200 mg daily
Melatonin—6 to 20 mg, 1 to 2 hours before sleeping (nighttime)
Panax ginseng (Siberian)—200 to 1000 mg daily
Soy extract containing 50 mg of isoflavones—twice daily
Vegetable extract —daily
Vitamin A—25,000 IU daily
Vitamin C—2.5 to 5 g daily
Multivitamin/multimineral supplement (without copper) containing 20 mg of beta-carotene, 15 mg of lycopene, and 200 mcg of selenium daily.


Uterine Cancer Safety Caveats
An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Calcium
Do not take calcium if you have hypercalcemia.
Do not take calcium if you form calcium-containing kidney stones.
Ingesting calcium without food can increase the risk of kidney stones in women and possibly men.
Calcium can cause gastrointestinal symptoms such as constipation, bloating, gas, and flatulence.
Large doses of calcium carbonate (12 grams or more daily or 5 grams or more of elemental calcium daily) can cause milk-alkali syndrome, nephrocalcinosis, or renal insufficiency.

EPA/DHA
Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.
Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Flaxseed
Flaxseed has blood-thinning, anticlotting properties.
Discontinue using flaxseed before any surgical procedure.
Consult your doctor before taking flaxseed if you have hemophilia or if you take warfarin (Coumadin).
Flaxseed can cause gastrointestinal symptoms such as nausea and diarrhea.

Garlic
Garlic has blood-thinning, anticlotting properties.
Discontinue using garlic before any surgical procedure.
Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.
Ingesting large amounts of garlic can cause bad breath and body odor.

Ginseng
Consult your doctor before taking ginseng if you have high blood pressure. Overuse of ginseng can increase blood pressure.
Consult your doctor before taking ginseng if you take nonsteroidal anti-inflammatory drugs (NSAIDs) and/or warfarin (Coumadin). Taking NSAIDs or warfarin with ginseng can increase the risk of bleeding.
Consult your doctor before taking ginseng if you have diabetes. Taking ginseng can cause an extreme drop in your blood glucose level.
Ginseng can cause breast pain, vaginal bleeding after menopause, insomnia, headaches, and nosebleeds.

Melatonin
Do not take melatonin if you are depressed.
Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.
Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.
Pectin

Do not take pectin if you have a gastrointestinal obstruction.
Pectin can cause gastrointestinal symptoms such as flatulence, cramps, gas, and diarrhea.
Soy

Do not take soy if you have an estrogen receptor-positive tumor.
Soy has been associated with hypothyroidism.

Selenium
High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.
High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin A
Do not take vitamin A if you have hypervitaminosis A.
Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.
Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C
Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.
Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.
For more information see the Safety Appendix


Product Availability
All the nutrients and supplements in this chapter are available through the Life Extension Foundation. For ordering information, Life Extension Products

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