Pancreatic Cancer-3

Clinical Studies: Fish Oil and Pancreatic Cancer


Many clinical studies have shown that fish oil supplementation stabilizes the rate of weight loss, as well as adipose tissue and muscle mass, in pancreatic cancer patients, who often suffer from wasting (Tisdale MJ 1999).

Protein supplements enriched with EPA increased total energy expenditure and physical activity levels in advanced pancreatic cancer patients, thereby increasing their quality of life (Klek S et al 2005; Moses AW et al 2004).
Twenty pancreatic cancer patients were asked to consume two cans of a fish oil-enriched nutritional supplement daily in addition to their normal food intake. Each can contained 16.1 grams of protein and 1.09 grams of EPA. At the study’s onset, all patients were losing weight at a median rate of 2.9 kg a month. After administration of the fish oil-enriched supplement, patients had a significant weight gain at both three and seven weeks (Barber MD et al 1999).
In another study, after three weeks of consuming an EPA-enriched supplement, the body weight of cancer patients had increased, and their energy expenditure in response to feeding had risen significantly to levels no different from baseline healthy control values (Barber MD et al 2000).
In a study of 18 pancreatic cancer patients who supplemented with fish oil capsules (1 gram each containing EPA 18 percent and DHA 12 percent), patients had a median weight loss of 2.9 kg a month before supplementation; three months after beginning fish oil supplementation, patients had a median weight gain of 0.3 kg a month (Wigmore SJ et al 1996).


Food-Derived Polyphenols
Genistein prevents pancreatic cancer cell growth primarily by regulating sugar metabolism (Boros LG et al 2001). In addition, genistein inactivates NF-kappa B (Li Y et al 2005), thus sensitizing cancer cells to chemotherapeutic agents such as Gemzar® (Banerjee S et al 2005), cisplatin and docetaxel (Li Y et al 2004), and VP-16 and doxorubicin (Sato T et al 2003). In laboratory experiments, genistein has been shown to improve survival, reduce tumor blood-vessel development (Buchler P et al 2004), almost completely inhibit cancer metastasis, and increase cancer cell suicide (Buchler P et al 2003).

If the pathology report shows that the pancreatic cancer cells have a mutated p53 oncogene, or if there is no p53 detected, then high-dose genistein therapy may be appropriate (Choi YH et al 2000; Wilson LC et al 2003). If the pathology report shows a functional p53, then genistein is less effective in stopping cancer growth. The suggested dose of genistein is approximately 500 mg daily (Miltyk W et al 2003; Takimoto CH et al 2003).

Green Tea. Tea is particularly rich in polyphenols such as epigallocatechin gallate (EGCG) that act as antioxidants. Black and green tea extracts reduce pancreatic tumor cell growth by approximately 90 percent while preventing angiogenesis (Maiti TK et al 2003; Masamune A et al 2005; Roomi MW et al 2005). They also decrease the expression of the K-ras gene (Lyn-Cook BD et al 1999a) and the invasiveness of pancreatic cancer cells (Takada M et al 2002). Animal experiments of pancreatic cancer show that tea polyphenols restrain carcinogen-induced increases in oxidative DNA damage (Frei B et al 2003).

Green tea extract curbs the process of pancreatic cancer development (Lyn-Cook BD et al 1999b) and the promotion of transplanted human pancreatic cancer in animals, and also causes pancreatic cancer cell death (Hiura A et al 1997; Qanungo S et al 2005).

In humans, an inverse relationship was observed between the amount of green tea consumed and the risk of developing pancreatic cancer; the highest intake was associated with the lowest risk of cancer (Ji BT et al 1997). In clinical studies, green tea supplementation has been shown to be safe and protective (Ahn WS et al 2003; Chow HH et al 2001; Chow HH et al 2003).

Antioxidants. Free radicals can cause repeated damage to normal cells and reduce the function of injured tissues. When sufficient antioxidants are available, free radicals are removed before excess damage occurs. Antioxidant levels are reduced in pancreatic cancer compared to other pancreatic diseases and healthy pancreatic tissue, resulting in increases in reactive oxygen (Cullen JJ et al 2003) that are capable of stimulating cancer cell division (Garcea G et al 2005; Vaquero EC et al 2004).

Increased levels of some antioxidants may be useful in slowing the growth of pancreatic cancer (Weydert C et al 2003). Vitamins A, C, and E, as well as selenium, increase antioxidants in the body needed to reduce free-radical damage (Woutersen RA et al 1999).

Vitamins A, C, and E. In animals in which pancreatic cancer was caused by chemicals, cancer incidence was decreased by 64.3 percent by vitamin A and by 71.4 percent with vitamin C. Both vitamins increased SOD (superoxide dismutase) activity and were toxic to tumor cells but not to normal healthy cells (Wenger FA et al 2001).

An overview of 14 randomized trials (with a total of 170,525 patients) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on pancreatic cancer incidence (Bjelakovic G et al 2004).
A study of 23 pancreatic cancer patients tested retinol palmitate (vitamin A) and beta-interferon with chemotherapy. Eight patients responded and eight patients had stable disease. For all patients, median time to disease progression and survival time were 6.1 months and 11 months, respectively. Toxicity was high, but patients who had responses and disease stabilization had prolonged symptom relief (Recchia F et al 1998).
Retinoids curb the growth and adhesion of a variety of pancreatic cancer types, even those that previously have been documented to be resistant to retinoids (El-Metwally TH et al 1999). Vitamin E succinate restrained pancreatic cancer cell growth in laboratory experiments (Heisler T et al 2000).
Ascorbyl stearate, a fat-soluble form of ascorbic acid (vitamin C), markedly restrained the growth of—and even killed—pancreatic cancer cells (Naidu KA et al 2003).
Selenium. Selenium and beta-carotene were found to restrain the growth of pancreatic tumors caused by carcinogen exposure in mice (Appel MJ et al 1996). Selenium levels were found to be reduced in pancreatic cancer patients who underwent surgery to remove the upper portion of their intestine (Armstrong T et al 2002). In preclinical studies, a diet high in selenium reduced the number of carcinogen-induced pancreatic cancers significantly (Kise Y et al 1990).

Curcumin has many anticancer effects. It is a selective inhibitor of the COX-2 enzyme and may be beneficial in preventing and treating pancreatic cancer (Cuendet M et al 2000). It decreases NF-kappa B activity, which is involved in controlling the growth of pancreatic cancer cells (Li L et al 2004). It also inhibits interleukin-8 (IL-8) production, which affects invasiveness, cell growth, and tumor blood-vessel development (Hidaka H et al 2002).

Complementary Alternative Therapies
PSK (Polysaccharide K). PSK is a protein-bound polysaccharide derived from the mycelium of the mushroom Coriolus versicolor (Tsukagoshi S et al 1984). In Japan, PSK is used as a non-specific biological response modifier to enhance the immune system in cancer patients (Koda K et al 2003; Noguchi K et al 1995; Yokoe T et al 1997). PSK suppresses tumor cell invasiveness by down-regulating several invasion-related factors (Zhang H et al 2000). Also, PSK can enhance pancreatic cancer cell death induced by Taxotere® (docetaxel) (Zhang H et al 2003).

Two patients who had unresectable pancreatic cancer were treated with combined chemotherapy using cisplatin, PSK, and UFT (uracil-tegafur). During therapy, a partial response was observed, with a remarkable decrease in tumor size and no significant side effects. From the results of these two cases, this combination chemotherapy was considered to be one of the most effective therapies available for pancreatic cancer (Sohma M et al 1987). PSK has been used as adjuvant immunotherapy for cancer at a dose of 3 grams daily (Ito K et al 2004; Ohwada S et al 2004; Toge T et al 2000).

Ukrain (NSC-631570). Ukrain, a semisynthetic agent, has been used in complementary medicine for more than 20 years to treat benign and malignant tumors. In a phase II trial of advanced pancreatic cancer patients, Ukrain either alone or together with Gemzar® (gemcitabine) was found to be well-tolerated with only moderate toxicity, and doubled median survival times (Gansauge F et al 2002). In another study, Ukrain improved the quality of life of patients suffering from advanced pancreatic cancer while significantly prolonging their survival time (Zemskov V et al 2002).

For More Information
Pancreatic cancer is usually associated with weight loss (catabolic wasting) and pain. The following protocols may be useful in designing a program that will address specific needs:

Catabolic Wasting
Pain
Cancer Surgery
Complementary Adjuvant Therapies
Cancer Chemotherapy
Cancer Radiation
Diabetes


Life Extension Foundation Recommendations
Pancreatic cancer is a rapidly progressive disease with generally poor survival time. The goal of therapy is to strengthen pancreatic function, impede cancer growth and spread, and reduce the severity of symptoms. Various nutritional supplements outlined in this chapter have been shown to help pancreatic cancer patients by slowing disease progression or increasing quality of life.

Guidelines for Reducing Pancreatic Cancer Risk
Stop smoking and drinking alcohol.
Avoid or reduce exposure to toxic chemicals and petroleum products.
Maintain a healthy body weight.
Reduce dietary intake of fried foods, red meat, and meat products.
Increase intake of fresh fruit and vegetables, fiber, minerals, and vitamins.
Reduce sugar consumption (glycemic load).
Increase physical activity.
Maintain a diet suitable for diabetics that restricts simple carbohydrates such as sugar and emphasizes complex carbohydrates (fibers) and proteins (refer to the Diabetes protocol). Protein supplements such as soy and essential fatty acids such as borage and fish oils will help by altering the dietary intake ratio of carbohydrates, proteins, and fats.
If pancreatic cancer patients are to improve their odds of achieving a remission or long-term survival, they should attempt to integrate into their conventional therapy as many of the following dietary changes and supplements as possible, but only under a physician’s supervision.

Aged Garlic Extract—1200 milligram (mg) daily
Alpha-tocopherol—400 international units (IU) daily
Ascorbic acid—500 to 3000 mg daily
Beta-carotene—20 mg daily
Curcumin—2400 mg daily, two hours apart from medications
d-Limonene—7.3 to 14.4 grams (g) daily
Fiber—4 to 12 g daily before meals
Fish oil concentrate—700 to 4200 mg of EPA, 500 to 2000 mg of DHA daily
Life Extension Booster—1 capsule daily
Gamma-linolenic acid (GLA)—700 to 900 mg daily
Grape seed extract—100 mg daily
Green tea extract (EGCG)—800 mg daily
Life Extension Mix multivitamin/multi-mineral formula without copper—follow label directions
Lycopene—15 to 30 mg daily
Perillyl alcohol—2050 mg, four times daily
PSK (Coriolus versicolor)—3 grams daily
Selenium—600 micrograms (mcg) daily
Silymarin—100 to 420 mg daily
Soy extract (genistein)—656 mg daily
Vitamin A—10,000 IU daily
Zinc—45 to 50 mg daily.
Innovative Drug Strategies
The following should be used only under a physician’s supervision:

Pancreatic enzymes (by prescription)—1000 to 10,000 U lipase per kg of body weight per meal (Schibli S et al 2002). Delayed-release preparations (capsules containing enteric-coated microspheres, such as Creon®) are reportedly less susceptible to acid inactivation.
Antacids or a histamine H2-receptor antagonist (cimetidine, Tagamet®) have been used to decrease the inactivation of pancreatic enzyme activity.
Celebrex® (celecoxib)—400 mg twice daily.
Zyflo® (zileuton)—400 to 800 mg twice daily (except for those with active liver disease).
Ukrain (NSC-631570). Ukrain is supplied as a solution ready for injection. A Ukrain therapy cycle consists of 10 mg taken intravenously every other day for 20 days. A vitamin C cycle is added to the Ukrain cycle, 3 grams taken intravenously every other day, and 2.4 grams taken orally in three divided doses on the same days, for 20 days (Zemskov V et al 2002).


Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc. For ordering information, call anytime toll-free 1-800-544-4440, or visit us online at www.LifeExtension.com.

The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc. For ordering information, call anytime toll-free 1-800-208-3444, or visit us online at www.LifeExtension.com.

Pancreatic 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:

Beta-Carotene
Do not take beta-carotene if you smoke. Daily intake of 20 milligrams or more has been associated with a higher incidence of lung cancer in smokers.
Taking 30 milligrams or more daily for prolonged periods can cause carotenoderma, a yellowish skin discoloration (carotenoderma can be distinguished from jaundice because the whites of the eyes are not discolored in carotenoderma).

Curcumin
Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.
Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.
Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.
Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.
Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

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.

Fiber
Take fiber supplements with a full 8-ounce glass of water.
Drink eight 8-ounce glasses of water daily while taking fiber.
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.

Genistein
Consult your doctor before taking genistein/genistin if you have prostate cancer.
Do not take genistein/genistin if you have estrogen receptor–positive tumors.
Genistein/genistin can cause hypothyroidism in some people.

GLA
Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.
Discontinue using GLA 2 weeks before any surgical procedure.
GLA can cause gastrointestinal symptoms such as nausea and diarrhea.

Green Tea
Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.
Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.
Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

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.
Zinc

High doses of zinc (above 30 milligrams daily) can cause adverse reactions.
Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.
High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.
High doses of zinc may suppress the immune system. High doses of zinc may be immunosuppressive.