Monday, February 7, 2011

Catabolic / metabolic states of cancer

http://www.lef.org/protocols/prtcl-029.shtml

Catabolic Wasting

 Catabolic wasting or cachexia is a clinical wasting syndrome that is characterized by unintended and progressive weight loss, weakness, and low body fat and muscle. At least 5% of body weight is lost. Cachexia is not caused by poor appetite and nutritional intake, but rather by a metabolic state in which a "breaking down" rather than a "building up" occurs in bodily tissues no matter how much nutritional intake occurs. Additionally, whether a patient receives nutrition orally or intravenously makes no difference. The patient simply cannot gain weight, so eating more is not an answer.
It is estimated that half of all cancer patients experience catabolic wasting, with a higher occurrence seen in cases of malignancies of the lung, pancreas, and gastrointestinal tract. The syndrome is equally common in AIDS patients and can also be present in bacterial and parasitic diseases, rheumatoid arthritis, and chronic diseases of the bowel, liver, lungs, and heart. It is usually associated with anorexia and can manifest as a condition in aging or as a result of physical trauma. Catabolic wasting is a symptom that diminishes the quality of life, worsens the underlying condition, and is a major cause of death.

Cachexia and Cancer
Researchers previously believed that cancer increased metabolic demand (stolen protein), produced toxins, and suppressed appetite, resulting in malnutrition. New research, however, shows that although cancer may raise resting metabolic rate, improved nutrition does not alleviate the symptoms of anorexia, chronic nausea, early satiety, and changes in taste that make even favorite foods unpalatable to some cancer patients. The view of clinicians is that bodily wasting is the result of a combined action of tumor products and host immune factors--in particular, cytokines--that lead to poor appetite, muscle wasting, and an altered metabolism. The cytokines interleukin-1 (IL-1), IL-6, interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), and brain-derived neurotrophic factor appear to increase and play a role in the progression of cachexia in cancer, as well as in other diseases associated with bodily wasting.

Other metabolic alterations associated with the syndrome are hyperglyceridemia, lipolysis, and accelerated protein turnover, all leading to a loss of fat mass and body protein. The dysregulation of metabolic processes produces a negative energy balance.

Clinicians are currently treating cancer-related catabolic wasting with a variety of interventions, including nutritional supplementation, administration of cytokine inhibitors, steroids, hormones, cannabinoids, and thalidomide. Gemcitabine, a chemotherapeutic drug, has shown clinical benefits in treating cachexia. Newer nutritional intervention with megestrol acetate derivatives, gamma-receptor agonists, amino acid manipulations, myostatin inhibitors, and uncoupling protein modifiers is currently being explored. Further research must be done to investigate gender differences in relation to pathophysiology and therapy.

There is some evidence that the drug hydrazine sulfate may help cancer patients gain weight and improve the cachectic state. The drug is by prescription and should be given by a complementary physician familiar with its use, as it can be toxic. The dose is usually 60 mg a day. Narcotic painkillers or benzodiazepine anxiety-reducing agents cannot be given concomitantly.


Fish Oil Studies
Depletion of muscle and adipose tissue in cancer cachexia appears to arise not only from decreased food intake, but also from the production of catabolic factors secreted by certain tumors such as tumor necrosis factor and other autoimmune cytokines. Experiments with a cachexia-inducing tumor in mice showed that when part of the carbohydrate calories in their diet was replaced by fish oil, host body weight loss was inhibited. The catabolic-inhibiting effect occurred without an alteration of either the total calorie consumption or nitrogen intake (Tisdale et al. 1990).

Fish oil concentrate was found to inhibit tumor-induced lipolysis directly (Beck et al. 1991). The catabolic fat loss-preventing effect of fish oil arose from an inhibition of the elevation of cyclic AMP (adenosine monophosphate, a nucleotide involved in energy metabolism) in fat cells. The increased protein degradation in the skeletal muscle of catabolic animals was also inhibited by fish oil; this effect was due to the inhibition by fish oil of muscle prostaglandin E2 production in response to a tumor-produced proteolytic factor. Thus, reversal of cachexia by fish oil in this mouse model results from its capacity to interfere with tumor-produced catabolic factors (Tisdale 1996). Similar factors have been detected in human cancer cachexia.
Studies show that the DHA fraction of fish oil is the best documented supplement to suppress the inflammatory cytokines involved in the catabolic process such as TNF-a, IL-6, IL-1(b), and prostaglandin E2(Khalfoun et al. 1997; De Caterina et al. 1998, 1999; Jeyarajah et al. 1999; Kelley et al. 1999; James et al. 2000; Kremer 2000; Watanabe et al. 2000; Yano et al. 2000; Das 2001; Tepaske et al. 2001). Catabolic wasting patients should consider taking 8 capsules a day of Super GLA/DHA, a combination of gamma-linolenic acid and primarily the DHA fraction of fish oil. Both GLA and DHA significantly suppress inflammatory cytokines (Purasiri et al. 1994; Mancuso et al. 1997; Dirks et al. 1998; DeLuca et al. 1999; James et al. 2000).
Beneficial Effects of Glutamine
Glutamine has been one of the most intensively studied nutrients in the field of nutrition support in recent years. Animal studies show that glutamine is effective against catabolic stress (Millward et al. 1989; Castell et al. 1994; Ziegler et al. 1996). Glutamine supplementation was shown to improve organ function, survival, or both in most published studies. These studies also have supported the concept that glutamine is a critical nutrient for the gut mucosa and immune cells (Furst et al. 1989; Castell et al. 1994; Campos et al. 1996; Ziegler et al. 1996).

Molecular and protein chemistry studies define the basic mechanism involved in glutamine action in the gut, liver, and other cells and organs (Ziegler et al. 1996). Double-blind prospective clinical investigations suggest that glutamine-enriched diets are generally safe and effective in catabolic patients (Griffiths 1997). Intravenous glutamine has been shown to increase plasma glutamine levels; exert protein anabolic effects; improve gut structure and function; and reduce important indices of disease, including infection rates and length of hospital stay in selected patient subgroups (Sacks 1999).

Glutamine is the most abundant free amino acid in the human body. In catabolic stress situations, such as after surgical operations or trauma and during sepsis, glutamine is rapidly transported to organs and to blood cells. This results in an intracellular depletion of glutamine in the muscles and the ensuing catabolic wasting effect (Balzola et al. 1996). Increasing evidence suggests that glutamine is a crucial substrate for immunocompetent cells. Glutamine depletion decreases the proliferation of lymphocytes, possibly by arresting a critical phase of the growth cycle of the cells (Roth et al. 1996).

Glutamine is a precursor for the synthesis of glutathione and stimulates the formation of heat-shock proteins (Zhou et al. 1997). Moreover, there are suggestions that glutamine plays a crucial role in the stimulation of intracellular protein synthesis (Hankard et al. 1996). Experimental studies revealed that glutamine deficiency causes a necrotizing enterocolitis--an inflammation of the small intestine and colon, leading to cell death--and increases the mortality of animals subjected to bacterial stress (Becker et al. 2000).

A clinical human study involving bone-marrow transplant patients demonstrated, after supplementation with glutamine, a decrease in the incidence of infections and a shortening of hospital stay. In critically ill patients, parenteral glutamine reduced nitrogen loss and caused a reduction of the mortality rate (Roth et al. 1996). In surgical patients, glutamine invoked an improvement of several immunological parameters (Slotwinski et al. 2000). Moreover, glutamine exerted a nutritional (tropic) effect on the intestinal mucosa, decreased the intestinal permeability, and thus may prevent the translocation of bacteria.

In conclusion, glutamine is an important metabolic substrate of rapidly proliferating cells. It influences the cellular hydration (molecular water content) state and has multiple effects on the immune system, intestinal function, and protein metabolism (Sacks 1999). In several disease states, glutamine may become an indispensable nutrient supplement. Catabolic wasting patients should consider supplementing with 2000 mg of glutamine a day.


Summary
Catabolic wasting can be counteracted by proper nutrient supplementation. A daily dose of 2000 mg of glutamine is suggested to prevent glutamine depletion in the tissues and the ensuing catabolic effect. Fish and borage oil supplementation, in the dose of 1300 mg of DHA, 500 mg of EPA, and 1200 mg of GLA a day, should be considered to suppress inflammatory cytokines and prostaglandins that can destroy tissue. Two 1000-mg CLA capsules should be taken 2 times a day to facilitate the transport of glucose into muscle cells. The intake of 30 grams a day of biologically active whey protein concentrate, 10-20 grams of arginine, 2400 mg of L-carnitine, and a branched-chain amino acid complex may produce a dramatic anticatabolic tissue-sparing effect and regulate immune system cytokines that are thought to cause cachexia.
A multinutrient formula should be given to all people with catabolic breakdown to provide the basic building blocks the body needs to start rebuilding.
A person at risk for developing catabolic wasting syndrome or who is already suffering from cachexia (tissue wasting) should consider the following supplements:
  1. Glutamine, 2000 mg a day, available in capsule or powder form.
  2. Gamma-linolenic acid (GLA) 1200 mg, eicosapentaenoic acid (EPA) 500 mg and docosahexaenoic acid (DHA) 1300 mg daily.
  3. Conjugated linoleic acid (CLA), (76%) 2000 mg 2 times a day.
  4. Biologically active whey protein concentrate, 30-60 grams a day.
  5. Arginine, 10-20 grams a day in divided doses.
  6. L-carnitine, 2400 mg a day in divided doses.
  7. Multinutrient formula daily in divided doses.
  8. Consider growth hormone, DHEA, and/or testosterone replacement therapy.
  9. Branched chain amino acids, 1200-2400 mg a day.


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http://educate-yourself.org/cancer/kellymetabolicdiet13dec02.shtml


Protein (Phase One)

We have maintained throughout this treatise that cancer is nothing more than a pancreatic enzyme deficiency. The greatest cause of this deficiency is the amount of cooked protein (mutated amino acids) fed into the body. The pancreas simply cannot manufacture enough enzymes to digest the large volumes of pasteurized milk and cheese and cooked meat we eat and have any enzymes left over to digest the foreign protein we know as cancer. If people would not eat protein after 1:00 p.m., 86% of cancer in the United States could be eliminated.

However, a cancer patient should never give up all protein, as they might be tempted to do when they first learn that too much protein in the diet prevents the pancreas from ridding the body of cancer. The pancreatic enzymes themselves consist of protein (amino acids), and unless the body is fed adequate protein, the pancreatic enzyme production will stop and the cancer tissue will make a very rapid growth. The total withdrawal from protein has been the fallacy of many cancer diets, such as the "Grape Cure." This is also the reason these diets have worked so well for the first few months — no protein — thus freeing the pancreatic enzymes to digest the cancer. Yet, over prolonged periods of total abstinence from protein, the pancreas fails. Proper balance and regulated intake is the answer.

Protein Timing

It is not only imperative that the correct kind and quantity of protein be eaten, but of equal importance, it must be taken at a specific time. We have found that regular proteins should be taken at breakfast and lunch only. When this is strictly observed the pancreatic enzymes, used in digestion of protein, are used only about 6 hours. This leaves 18 hours for production of pancreatic enzymes to digest cancer tissue.



Eggs
 
Eggs are an unusually good source of protein — well balanced and the standard by which all protein is evaluated. They have all the essential amino acids in proper proportions. The cancer patient may have two eggs (preferably raw) each day at anytime.

Proper preparation of eggs is of vital importance. The eggs must be heated in the shell. We bring our eggs to a temperature of 140º F. to 160º F. (which is the normal temperature of hot tap water), for five minutes before cracking them. This destroys an enzyme just inside the membrane under the shell that prevents the biotin in the egg from functioning normally. When biotin functions properly, it greatly reduces the cholesterol risks of eating eggs.

After preheating before cracking them, the eggs may then be eaten, as you prefer them. Raw and soft-boiled eggs are the most preferable, though it isn’t absolutely necessary to eat them in these forms. In keeping with the use of as much raw food as possible, a good procedure is to eat the eggs raw in a blended drink of some kind, flavored to suit one’s taste.

Liver
Liver is a wonderful energy food and cannot be surpassed as a blood builder. It is especially crucial for leukemia and lymphoma patients, as their blood is unusually weak. However, all cancer patients can benefit from the intake of raw liver before noon each day. In the mid 1960s, when Dr. Kelley was told he was in the final stages of pancreatic and liver cancer, he found that raw liver blended into carrot juice gave him strength when everything else he ate made him feel ill.

1. The liver can be sliced about ¼ inch thick, placed on a cookie sheet, and frozen. After it is frozen, it can be cut into ¼ inch cubes. One can then use plastic sandwich bags, putting 3 to 6 tablespoons of frozen cubed liver in each bag and storing them in the freezer for daily eating. This frozen liver may be chewed or swallowed whole, followed by a sip of juice if desired. Some prefer to allow the liver to thaw and then to place a spoonful at a time in the mouth and chew it or swallow it whole with a sip of juice.
2. Liver may be placed in the blender with carrot, pineapple, or tomato juice (and seasoning of one’s preference if desired), blended, strained to remove the fiber if preferred, and used as a morning "pep-up" drink. 

Meat (Cooked and Commercially Produced)
The cancer patient will want to give up cooked and commercially produced meat such as beef, pork, lamb and fowl immediately (except for raw liver — see above). Cooked meat is harmful for the cancer patient, as the very same enzymes used in its digestion are needed for fighting and digesting the cancer. All natural, self-made enzymes your body can produce should be used to fight the cancer. Commercial meat should be avoided for another reason; it has a high female sex hormone content. For commercial reasons most animals, especially beef and fowl produced in the United States have been fed large quantities of hormones. Since an overabundance of female sex hormones initiate cancer, meat of this type should be excluded from the cancer patient’s diet.

After being on Metabolic Medicine’s Cancer Cure Diet for 9 to 12 months, when the tumors are under control, one may gradually resume consumption of meat as long as one’s metabolic type requires it (see Chapter VIII, Metabolic Typing — Discovering Your Personal Nutritional Needs) and adequate enzymes and hydrochloric acid are taken to digest it.

If and when one does go back to eating meat, it will be extremely wise to make every effort to find a source that can provide meat, which has been produced without chemical feed, hormones, antibiotics, and pesticide residues.


Seeds and Sprouts
Raw seeds and sprouts are good foods for cancer patients, and may be eaten after 1:00 p.m. We freely use brown sesame, sunflower and pumpkinseeds. Many people enjoy sprouted seeds, such as alfalfa and mung beans, buckwheat, wheat and soybeans.

The most "living foods" are sprouted seeds. When seeds are soaked in water, their protective enzyme inhibitors are removed and the enzymes, which have been "asleep," become active, and in three days the nutritional values of the seeds are increased tremendously. The seeds also become much easier to digest.
For the best in nutrition, be sure to eat your sprouts raw. Eat as many as you desire.

Beans
Dry beans of all types are a good source of food for the cancer patient, and may be used two or three times a week at anytime of the day. The best way we’ve found to prepare them is to cook them at a temperature of 200º F. We place two cups of dried beans (washed) in a bean pot to which we add five cups of RO filtered or distilled water, five garlic cloves, two tablespoons of olive oil, 1 teaspoon of sea salt or kelp, and 1/8 teaspoon of cayenne pepper. We place the pot, (covered), in an oven overnight at 200º F.


Vegetable Juice and Fruit Juice (Phase Two)
Vegetable Juices (Fresh and Raw)
The second most important phase of our cancer diet is that of fresh raw juices. At least one quart of carrot and one pint of celery juice should be taken each day. As much other fresh raw vegetable juice in volume may be taken as desired. One should consider alfalfa, beet, cabbage, cucumber, dandelion, endive, lettuce, parsley, potato, spinach, and turnip juice. Vegetable juices are the builders of the body. Juice is better than the whole vegetable because so much energy is used to digest the whole vegetable. Juice has a proper balance of vitamins and minerals in a concentrated solution. We recommend that the juice be made fresh and used immediately.

Fruit and Fruit Juices (Fresh and Raw)
Fresh raw fruit and fruit juices are the cleansers of the body. The cancer patient may eat as much as desired of fresh raw fruit or fresh fruit juices. Small amounts of dried unsulfered fruit may also be taken.

Whole Grain Cereal (Phase Three)
We have found that it is desirable in building the body to eat a mixture of raw whole grain cereals for breakfast each morning. Mix together well in a large container one pound of each of the grains and nuts below. Store in refrigerator (if too large a quantity is mixed it will keep in a cool, dark pantry).

Multi-Grain Porridge
Objective: to obtain as many different nutrients as possible from as many different seed and grain gene pools as possible from as many different sources (fields) as possible.
Contents by equal weight of Organic:
Amaranth Pumpkin Seeds
Barley Rice, Brown long grain
Barley Flakes Rice, Brown short grain
Buckwheat Groats Rye Berries
Corn Meal Blue Spelt Berries
Corn Meal Yellow Sunflower seeds
Kamut Triticale Flakes
Millet Wheat, Hard Red Spring
Oat Groats Wheat, Soft Pastry
Adding Almonds, English Walnuts and Bananas makes a complete tasty meal.
Directions
Daily at bedtime:
A. Grind 1/3 Cup porridge grains in seed mill.
B. Add 1 Cup boiling water. Stir well.
C. Let soak at room temperature overnight.
D. For breakfast add fruit, concentrated fruit juice and/or unheated honey to taste.

Flax Seed Oil (Phase Four)
Take two tablespoons per day of unrefined, fresh flaxseed oil for the first month of Metabolic Medicine’s Cancer Cure Program, and one tablespoon per day from the second month of the program to completion. (Formula F provides Essential Fatty Acids — Essential Fatty Acids must be provided in the diet, as the human body cannot make them.)

Unrefined Flaxseed oil, in practice, inhibits tumor growth and is useful in the natural treatment of cancer. EFAs, from refined oil, on the other hand, help promote tumor growth (due to trans- fats present in all American commercial vegetable oil). All oils except unrefined, fresh olive and flaxseed oil are forbidden on Metabolic Medicine’s Cancer Cure Diet.

Golden Rule of Metabolic Medicine’s Cancer Cure Diet
The Golden Rule of Metabolic Medicine’s Cancer Cure Diet is:
"Take nothing into the body that has been cooked or processed except items mentioned."

When a person eats anything processed he or she is not only eating "dead food" (those in which the enzymes have been destroyed), but he or she is adding a second very destructive force to his body, the destructive force of food preservatives. This may not be too significant for a normal healthy person, but for the cancer patient it may mean life or death. The liver must detoxify, destroy, or metabolize all foreign substances from the body. When one eats foods with preservatives, it adds an extra burden upon the liver, which the cancer patient cannot accept.

Milk
The cancer patient must give up pasteurized cows’ milk forever, except in the form of raw (unpasteurized), homemade yogurt, and for a while must avoid raw milk too, except raw (unpasteurized) goats’ milk. Cows’ milk, like meat, has too high a protein content and pasteurization compounds the problem as it alters or mutates the protein. Pasteurized cows’ milk requires too many pancreatic enzymes for digestion.


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