Life Extension Final Clerance Sale

Life Extension Magazine

LE Magazine November 2000

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What's
Missing
From Multi-Vitamin Supplements?

Page 1 of 5

imageThe primary reason that people take dietary supplements is to obtain concentrated doses of beneficial nutrients that are found in fruits and vegetables.

Consuming lots of fruits and vegetables dramatically lowers the risk of degenerative disease. This fact has been documented in epidemiological studies showing that people are healthier if they incorporate more of the right kinds of plants into their diet.

In addition to the epidemiological data, researchers have evaluated the molecular effects that fruits and vegetables possess in protecting against cellular damage. These findings provide biologic mechanisms to explain why those who eat a plant-rich diet have such low incidences of chronic disease.

The problem is that few people consistently eat enough fruits and vegetables to protect against aging-related diseases such as stroke, cancer, macular degeneration and heart attack.(1) This is one reason why vitamin supplements are becoming so popular in the United States. The concern about multi-vitamin formulas, however, is that they do not provide all the vital plant components needed to maintain good health.

In 1985, The Life Extension Foundation introduced the first multi-nutrient formula that included disease-preventing extracts from plants. Over the last 15 years, an enormous amount research data has confirmed the health benefits of these types of plant extracts.

Scientists have identified new fruit and vegetable extracts that protect cells against the deleterious effects of aging. In response to these findings, the Life Extension Mix multi-nutrient formula has been upgraded to provide these new disease-preventing agents from plants.

Moving beyond vitamins

Vitamin C, carotenoids and folic acid are examples of plant-based nutrients that can be efficiently consumed in the form of dietary supplements. Researchers are now moving beyond traditional nutrients in their quest to discover additional ways of protecting against disease. One botanical extract that offers tremendous potential is called D-glucarate. This extract appears to protect against cancer and other diseases via different mechanisms than antioxidants.

D-glucarate is found in grapefruit, apples, oranges, broccoli and brussels sprouts.(2-3) Consumption of these types of fruits and vegetables confers a protective effect against cancer, and D-glucarate is a component of these foods that has scientists very excited.

The body is bombarded with carcinogens on a daily basis. These cancer-causing agents include pesticides, over-cooked food, alcohol, food additives, tobacco, fungal mutagens and industrial pollutants. While avoiding carcinogens is difficult, it may be possible to mitigate their lethal effects by providing the body with phyto-nutrients (plant extracts) that facilitate the detoxification and removal of these dangerous substances from the body.

D-glucarate is one of these phyto-nutrients that protects against cancer-causing agents in a way that is separate and apart from the beneficial effects of antioxidants (vitamins C, E, cysteine, etc,) and methylation-enhancing agents (folic acid, vitamin B12 and TMG). D-glucarate works by supporting detoxification and removal of dangerous chemicals, and also by protecting against the mutating effects that these carcinogens induce on cellular DNA.(3)

There are several mechanisms by which the body detoxifies itself. One way of protecting against toxic overload involves the use of antioxidants to inhibit the damaging effects of free radicals. Uncontrolled free radical reactions have been identified as causative or contributing factors in most human disease states. The consumption of antioxidants (vitamin E, n-acetyl-cysteine, selenium, carotenoids, etc.) are essential to protect against toxic free radical reactions. Neutralizing free radicals, however, is only one part of the detoxification process. There are additional pathways the body must use if it is to sufficiently rid itself of DNA-damaging toxins that can cause cancer and other diseases.

Another pathway of detoxification occurs when toxins or carcinogens are combined with water soluble substances, thus making them more easily removed from the body. This process is called glucuronidation. The phyto-extract D-glucarate has been shown to support this important detoxification mechanism. The following known carcinogens are removed from the body by the glucuronidation process:

- Polycyclic aromatic hydrocarbons
- Mutated sex steroid hormones
- Nitrosamines
- Heterocyclic amines
- Fungal toxins
- Aromatic amines

Note: To give you some idea about how dangerous heterocylic amines are, refer to the article in this issue entitled “Barbequer Beware!

How does D-Glucarate work?

As just discussed, glucuronidation is a process by which the body naturally detoxifies itself. As people grow older and become overly exposed to toxins, a dangerous enzyme forms in the body called beta-glucuronidase. When levels of beta-glucuronidase become too high, it reverses the glucuronidation process and releases the toxins or carcinogens back into the bloodstream. This means that harmful compounds that would normally bind to inert molecules to be removed from the body are permitted to go free and damage cells.

imageD-glucurate functions by inhibiting the dangerous beta-glucuronidase enzyme, thus protecting the critical “glucuronidation” detoxification mechanism. One example of the importance of glucuronidation can be seen in the risk factors for breast cancer. Excess levels of free estrogens and the beta-glucuronidase enzyme are associated with increased incidence of breast cancer.(4,5) The beta-glucuronidase enzyme is associated with an increase in the number of estrogen receptors. D-glucarate has been shown to lower estrogen receptors while reducing tumor growth.(6) When breast cells hyper-proliferate in response to excess estrogen stimulation, the risk of breast cancer increases. In men, excess estrogen stimulation in the prostate gland can result in benign enlargement. D-glucurate suppresses the “bad” enzyme beta-glucuronidase, thus helping to protect against the carcinogenic effects of estrogen. This discovery helps explain why those who eat certain types of vegetables and fruits have relatively low rates of cancer.

At the University of Texas M.D. Anderson Cancer Center, repeated in vitro and animal studies have demonstrated the effectiveness of D-glucarate. Oral ingestion of D-glucarate has been positively shown to inhibit the dangerous beta-glucuronidase enzyme. This means the body is better able to get rid of carcinogens and toxic waste products. In one animal study, a single dose of D-glucarate was able to suppress beta-glucuronidase activity by 57% in the blood, 44% in the liver, 39% in the intestines and 37% in the lungs.(3)

In a rat study, the administration of D-glucarate for five months inhibited the initiation stage of liver cancer after the rats had been intentionally exposed to a known carcinogen. Researchers concluded that D-glucarate has a direct effect in preventing liver cancer that was attempted to be induced by the carcinogen, diethylnitrosamine.(4)

Research studies have shown that D-glucarate inhibits mammary tumor incidence.(7-10) One study in rats who already had breast cancer showed that oral D-glucurate administration resulted in a 50% inhibition of beta-glucuronidase resulting in a 30% reduction in mammary tumor growth during the promotion stage and a four-fold reduction in the absolute number of tumors.(11)

In a study conducted in Europe, rats fed D-glucarate and a vitamin A analog drug demonstrated a 20% reduction in mammary tumor volume.(12) Another study showed a more than 70% decrease in mammary tumor development in rats exposed to carcinogens who were also administered D-glucarate.(13) Still another study looked at the effects of D-glucarate on the initiation and promotional stages of mammary cancer. The results showed a reduction of 28% during the initiation stage, while cell replication was reduced by 42% during the promotion stage.(14) Inhibition at the initiation stage is a very important part of D-glucarate’s actions since it lessens the risk that cancer will even start.

D-glucarate is being used in a Phase I human trial at Memorial Sloan-Kettering Cancer Center in women at high risk for developing breast cancer. This study is in collaboration with the National Cancer Institute and National Institutes of Health.

When mice were exposed to known carcinogens found in tobacco smoke, D-glucarate was shown to inhibit lung cancer development.(6,15) On a molecular basis, D-glucarate was shown to cause a 70% decrease in the binding of the carcinogen benzopyrene to DNA in both mouse livers and lungs.(6) Since benzopyrene is a potent carcinogen found in cigarette smoke, D-glucarate could be of particular benefit to smokers and those exposed to environmental airborne carcinogens.(6,16)

When a carcinogen known to induce intestinal cancer was given to rats, D-glucarate was shown to inhibit adenocarcinoma formation when given at the initiation stage. When administered after tumor development, D-glucarate significantly inhibited the size and metastatic potential of intestinal and colon cancers.(17) The researchers made comments suggesting that D-glucurate may be effective in the prevention and treatment of cancer by inhibiting the beta-glucuronidase enzyme and by inhibiting cancer cell proliferation induced by chemical carcinogens.

One study indicates a potential for D-glucurate to prevent bladder cancer, while two studies indicate D-glucarate may have a protective effect against skin cancer.(18-21,145,146) A preliminary study showed that orally administered D-glucarate inhibited the growth of transplanted rat prostate tumors and reduced the levels of a tumor marker for prostate cancer.(21,147)

The results of various animal studies on D-glucarate indicates that this plant extract may be effective in inhibiting cancer during the initiation, promotion and progression phases. Human studies are just now beginning to determine if the results seen in animals will also be found in people. Since D-glucarate has no known side effects when ingested in moderate doses, and is a component of fruits and vegetables that have demonstrated a powerful cancer preventative benefits, it would appear appropriate to add this plant-constituent as part of an overall program designed to lower the risk of the following cancers:

- Breast cancer
- Bladder cancer
- Lung cancer
- Skin cancer
- Colon cancer
- Prostate cancer
- Liver cancer

The new Life Extension Mix provides 200 mg of standardized D-glucarate (in the form of calcium-D-glucarate) per daily dose, in addition to the naturally occurring D-glucarate found in the new broccoli concentrate that is included in the formula.

The DNA protecting effects of ellagic acid

Ellagic acid is a cancer preventing compound found in red raspberries, strawberries and other fruits.(22-29) Ellagic acid acts as a detoxifying agent by binding to carcinogens and making them inactive.(30-33) Molecular studies show that ellagic acid prevents binding of carcinogens to DNA,(23,34) reduces the incidence of cancer in cultured human cells exposed to carcinogens, may circumvent carbon tetrachloride toxicity and subsequent fibrosis,(35) and has anti-mutagenic properties.(25,36-39) Epidemiological studies show that people who consume fruits high in ellagic acid have lower rates of cancer and heart disease. It has also been shown to provide protection against chromosome damage and DNA strand breaks in lymphocytes produced by radiation, in animals.(40)

European medical research also demonstrates that ellagic acid promotes wound healing, and may reduce or reverse chemically induced liver fibrosis.(35,144)

Clinical tests conducted at the Medical University of South Carolina (MUSC) show that ellagic acid may help to prevent cancer, inhibit the growth of cancer cells, and arrest the growth of cancer in persons with a genetic predisposition for the disease. These studies show that ellagic acid induces cervical cancer cells to undergo apoptosis (normal cell death).(24) Tests reveal similar results for breast, pancreas, esophageal, skin, colon and prostate cancer cells.(31,33,37,41-46) Researchers showed that ellagic acid leads to G1 arrest of cancer cells, thus inhibiting and stopping cancer cell division. Ellagic acid was also shown to prevent destruction of the P53 gene in cancer cells.(24) P53 is a regulating gene that enables cells to divide normally. Additional studies suggests that ellagic acid inhibits mutagenesis and carcinogenesis by forming adducts with DNA, thus blocking binding sites on cells that would be occupied by a mutagen or carcinogen.(22,36,43,47-50) In another study ellagic acid was protective in experimental liver injuries.(51) Ellagic acid has also been shown to provide protection against chromosome damage produced by radiation, as well as protect against radiation induced lipid peroxidation.(40,52) In animal studies it was shown to be embryoprotective.(53)

The daily dose of the new Life Extension Mix contains 130 mg of a raspberry extract that provides 38.5% ellagic acid. When ellagic acid is extracted from other fruits, the concentration is much lower.

Continued on Page 2
References on Page 5

Published studies on
ellagic acid

“Ellagic acid protects rat embryos in culture from the embryotoxic effects of N-methyl-N-nitrosourea.” Teratology 1992, Aug (2): 109-15.

“Expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells.” Cancer Letters 1999 Mar 1; 136(2):215-21.

“Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxocity.” Journal of Experimental Cancer Research; 1998 Dec; 17(4);431-4.

“Inhibitory effects of ellagic acid on the direct-acting mutagenicity of aflatoxin B1 in the Salmonella microsuspension assay.” Mutation Research; 1998 Feb 26;398(1-2); 183-7.

“Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer.” Cancer Letters; 1997 Mar 19;114(1-2):113-9.

“Structure-function relationships of the dietary anticarcinogen ellagic acid.” Carcinogenesis; 1996 Feb;17(2):265-9.

“The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro.” Nutrition and Cancer; 1995;23(2):121-30.
“Inhibition of liver fibrosis by ellagic acid.” Indian Journal of Physiology and Pharmacology;1996 Oct;40(4): 363-6.

“Ellagic acid binding to DNA as possible mechanism for its antimutagenic and anticarcinogenic action.” Cancer Letters; 1986 Mar;30:339-36.

“Ellagic acid induces NAD(P)H:quinone reductase through activation of the antioxidant responsive element of the rat NAD(p)H:quinone reducase gene.” Carcinogensis;1994 Sept; 15(9):2065-8.

“Polyphenols as cancer chemoprevention agents.” Journal of Cell Biochemistry Supplemental; 1995;22:169-80.

“Pulmonary carcinogenesis and its prevention by dietary polyphenolic compounds.” Annals of the New York Academy of Sciences; 1993 May 28; 686:177-85.

“Lung tumors in strain A mice: application for studies in cancer chemoprevention.” Journal of Cell Biochemistry Supplemental; 1993; 7F:95-103.

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