Reprinted with permission of Life Extension®.
- Gene Mutation and Cancer
- How Cancer Cells Form
- Preventing Gene Mutation
Just a few years ago, the federal government released an optimistic report stating that the rate of cancer was leveling off or declining. In late 2002, the National Cancer Institute disclosed that the data used to prepare this report was seriously flawed. According to the National Cancer Institute, the incidences of some of the most deadly cancers are actually sharply increasing.
The American Cancer Association responded to these startling statistics by urging that more research be devoted to ascertain why prevention programs are failing. It has become strikingly apparent that the most respected cancer institutions have no explanation for why more Americans than ever before are contracting this devastating disease.
Regrettably, most cancer cases occur needlessly. Thousands of published scientific findings provide a clear road map as to what one can do to reduce their risk of developing cancer. The problem is that people are overwhelmed by the volume of cancer prevention data and have largely failed to take the necessary steps to reduce their personal risk.
In this protocol, we will reveal the fundamental factor that causes all cancers. We will then suggest relatively simple lifestyle changes that can help keep normal cells from transforming into malignant cells.GENE MUTATION AND CANCER
- What Causes Genes to Mutate
Cancer is a disease caused by genetic mutation. Most people have a difficult time grasping the molecular complexities of genes and their relationship to cancer. To bring this down to the simplest level, the following definition from the New England Journal of Medicine (Haber 2000) should enable lay persons to understand how genes are intimately involved in cancer processes: "Cancer results from the accumulation of mutations in genes that regulate cellular proliferation."
This one sentence description enlightens us to the critical importance of maintaining gene integrity if we are to prevent cancer from developing in our bodies.
Cells operate under the direction of genes located in the DNA. Our existence is dependent on the precise genetic regulation of all cellular events. Healthy young cells have nearly perfect genes. Aging and environmental factors cause genes to mutate, resulting in cellular metabolic disorder. Gene mutations can turn healthy cells into malignant cells. As gene mutations accumulate, the risk of cancer sharply increases.What Causes Genes to Mutate
Human studies show that about 70% of gene mutations are environmental and, thus, relatively controllable based on what we eat, whether we smoke, or exposure to genotoxins or radiation (Ljungquist et al. 1995; Herskind et al. 1996; Finch et al. 1997). Antioxidant supplements have become popular because they reduce gene damage inflicted by free radicals. However, it takes more than antioxidants to adequately protect genes against environmental mutation.
The most prevalent cause of environmental genetic mutation is the food we eat every day. While certain foods are particularly genotoxic, even healthy foods result in the body being exposed to small amounts of carcinogens. A consistent finding in epidemiological studies is that people who consume the most calories have significantly higher incidences of cancer (Kuska 2000; Winick 1991). There are several mechanisms that explain why overeating causes cancer, but one reason is that more gene mutations occur in response to higher food intake.
It is well known that foods cooked at high temperatures inflict massive damage to the genes. Women who eat very well cooked hamburgers have a 50% greater risk of breast cancer than women who eat rare or medium hamburgers. A nested, case-control study among 41,836 cohort members of the Iowa Women's Health Study found that women who consistently consumed well cooked beef steak, hamburgers, and bacon had a 4.62-fold increased risk of breast cancer (Zheng et al. 1998). Cooking foods at high temperatures causes the formation of gene-mutating heterocyclic amines. This is one reason why eating deep-fried foods is dangerous. Heterocyclic amines have been linked to prostate, breast, colorectal, esophageal, lung, liver, and other cancers. While health-conscious people try to avoid foods that are known carcinogens, even grilled salmon contains a potent dose of gene-mutating heterocyclic amines (Madrigal-Bujaidar et al. 1997).
While one can reduce his exposure to cancer-causing heterocylic amines, it may be impossible to prevent them from forming in the body. This is because enzymatic activities that naturally occur in the liver can inadvertently manufacture heterocyclic amines from otherwise harmless organic compounds (Guengerich et al. 1991). The carcinogenic dangers of heterocyclic amines have been thoroughly discussed in the scientific literature, yet the public is largely unaware of these dangers and continues to consume foods that inflict massive numbers of gene mutations.
Studies indicate that heterocyclic amines cause more cases of cancer than previously indicated (Terry et al. 2003; Turesky 2002). However, heterocyclic amines are not the only dietary culprit involved in gene mutation. Other mutagenic agents found in food are nitrosamine preservatives, aflatoxin molds, and pesticide/herbicide residues.
The bottom line is that we need to eat a certain number of calories, and this inevitably exposes us to agents that mutate our genes. Because avoiding all dietary carcinogens is impossible, identifying methods to protect genes against mutation becomes a critical part of a life extension program.HOW CANCER CELLS FORM
As quoted earlier in this text, "Cancer results from the accumulation of mutations in genes that regulate cellular proliferation" (Haber 2000). A common pathway toward cancer occurs when dietary mutagenic agents cause adducts to be formed on DNA genes. Adducts (gene alterations) are formed when a carcinogen binds to DNA. When a high enough percentage of DNA adducts form along critical gene segments, normal cells can be transformed into cancer cells (Strauss et al. 1991). Roughly 90% of DNA adducts are removed within a 24-hour period by DNA repair enzymes and other natural gene protective mechanisms (Hart et al. 1974). Humans possess the most efficient DNA repair mechanisms in the entire animal kingdom. Mice and other small mammals, on the other hand, have a 0-13% repair rate over 24 hours (which correlates with the mouse average lifespan of only 3.4 years) (Hart et al. 1974). DNA adducts represent genetic mutation. If the adducts are not repaired, this can lead to tumor formation. Preventing these adducts from forming in the first place would dramatically lower cancer risk.PREVENTING GENE MUTATION
- History of Chlorophyllin
- Detoxifying Dietary Mutagens
- When to Take Chlorophyllin
- Chlorophyllin Side Effects/Contraindications
- Choosing a Chlorophyllin Product
The first line of defense against the many carcinogens in the human diet are agents that prevent gene mutation. Many antimutagenic agents have been identified in fruits and vegetables, the most potent being the indole-3-carbinols, the chlorophylls, and chlorophyllin (Negishi et al. 1997). The traditional dietary antioxidants should be considered only as a secondary line of defense against cancer because it is more important to inactivate or neutralize carcinogens in the first place than to try to protect the cells and proteins downstream from their effects. Chlorophyllin is the modified, water-soluble form of chlorophyll that has been tested as an antimutagenic agent for more than 20 years. In one of the great ironies of natural product science, we now have a very large body of data concerning the anticancer, antimutagenic, antioxidant, and potentially life-extending benefits of chlorophyllin but much less information on the effects of natural chlorophyll itself (Negishi et al. 1997; Tsunoda et al. 1998).
For example, chlorophyllin can cross cell membranes, organelle membranes, and the blood-brain barrier while chlorophyll cannot. Chlorophyllin even enters into the mitochondria, the energy-producing organelles of the cell where 91% of oxygen reduction occurs and where the majority of free radicals are produced (Boloor et al. 2000; Kamat et al. 2000). Chlorophyllin quenches all major reactive oxygen species, such as the superoxide radical, hydrogen peroxide, singlet oxygen, and even the most dangerously reactive hydroxyl radical at very low doses (Kamat et al. 2000). Chlorophyllin has been shown to be a potent mitochondrial antioxidant that not only protects mitochondria from their own auto-oxidation (considered to be one of the major causes of aging), but also protects mitochondria from a variety of external chemical, biological, and radiation insults (Boloor et al. 2000; Kamat et al. 2000; Wei et al. 2001).History of Chlorophyllin
The Life Extension Foundation introduced its members to the antimutagenic effects of chlorophyllin in 1989. Life Extension based its recommendation to supplement with chlorophyllin on a study in the journal Mutation Research, showing that this plant extract was more effective than all other known anticancer vitamins at that time (Ong et al. 1989). An earlier study also in Mutation Research reported that chlorophyllin suppressed the mutagenic activity of carcinogens such as fried beef and pork, red wine, chewing tobacco and snuff, cigarette smoke, diesel emissions, and coal dust by more than 90% (Ong et al. 1986)! No other supplement came close to the ability of chlorophyllin to inhibit deadly gene mutations. In 1989, the cost of chlorophyllin was exorbitant, and only relatively low amounts could be used in dietary supplements. The good news is that the price of chlorophyllin has plummeted, enabling consumers to obtain high potencies at affordable prices.Detoxifying Dietary Mutagens
The great majority of studies about chlorophyllin's health benefits concern its antimutagenic and anticarcinogenic properties. Unlike other antioxidants, which merely quench free radicals, chlorophyllin traps heterocyclic hydrocarbon carcinogens by reacting with their backbone, making it impossible for them to form adducts with DNA (Dashwood et al. 1996; Hernaez et al. 1997). There are more than 50 cancer-causing agents known to occur in the human diet that chlorophyllin has been shown to protect against, including benzopyrene, dimethylbenzanthracene (DMBA), dibenzopyrene, TRP-P2, aflatoxin B-1 and aflatoxin B-2, 2-aminoanthracene, 2-nitrofluorene, 1-nitropyrene, 1-methyl-6-phenylimidazo [4,5-pyridine] (PHIP), and 2-amino-3-methylimidazo [4,5-f] quinoline (IQ). Tea epigallocatechins have no effect on the degradation rate of N-hydroxy IQ, but chlorophyllin rapidly degrades it by combining with it (Hernaez et al. 1997; Madrigal-Bujaidar et al. 1997; Negishi et al. 1997; Tang et al. 1997; Breinholt et al. 1999; Cabera et al. 2000; Chung et al. 2000; Kamat et al. 2000; Egner et al. 2001).
Many of these carcinogens are found in ordinary broiled, boiled, baked, and otherwise high-temperature cooked foods (Guengerich et al. 1991). For instance, PHIP is considered the most abundant heterocyclic amine in fried ground beef. It causes colon cancers in F344 rats and is considered a leading cancer suspect agent in humans (Guengerich et al. 1991; Guo 1995). Chlorophyllin 0.1% in the drinking water of rats reduced aberrant crypt foci 50% in the colon when exposed to PHIP (Guo 1995). In another study with F344 rats, a diet with 2000-ppm chlorophyllin significantly protected them from diethylnitrosamine-induced liver neoplasms (Sugie 1996). Diethylnitrosamine is commonly found in many types of distilled spirits and beers (Guengerich et al. 1991).
The most notorious of all human dietary carcinogens is aflatoxin B-1. Aflatoxins occur all over the world in fungus-infected rice, wheat, rye, and other staple grains. They have also been found in a variety of U.S. crops. Aflatoxin-infected crops are more of a problem in developing countries such as China where, in certain provinces, the farmers experience the highest liver cancer rates in the world (Egner et al. 2001). In a landmark study entitled "Chlorophyllin Intervention Reduces Aflatoxin-DNA Adducts in Individuals at High Risk for Cancer," researchers demonstrated a 55% reduction in aflatoxin urinary bio-markers compared to controls by giving the farmers 100 mg of chlorophyllin 3 times a day with their meals (Egner et al. 2001).
The scientists estimated that the induction period needed for this type of cancer to develop was extended from 20-40 years by supplementing with chlorophyllin. Chlorophyllin tablets were found to be the least expensive and most cost effective means of preventing these types of cancers (Egner et al. 2000; 2001). Several studies have noted that there is a powerful relationship between dietary aflatoxin reduction, DNA adducts, and lowering of cancer rates in both humans and animals (Dashwood et al. 1998; Kensler et al. 1998; Breinholt et al. 1999; Egner et al. 2001).
The effective dose of chlorophyllin as an antimutagenic agent is far lower than teas and other antioxidants, usually in the range of 0.5-4 mg per kilogram of body weight, making chlorophyllin the most potent antimutagen available on a weight basis. The best results in animals at suppressing carcinogenesis are in the 2-4 mg per kilogram range (Madrigal-Bujaidar et al. 1997), the same as the dosage used in the human intervention trials (Egner et al. 2000, 2001). At this dose range, it protected mouse bone marrow from benzopyrene toxicity 80.9% and 77.5%, respectively.
The anticancer properties of green tea, black tea, and chlorophyllin were compared, and it was found that chlorophyllin is a far more potent antimutagenic agent, protecting against a wider range of carcinogens than tea (Hernaez et al. 1997). In one study, teas did not degrade the mutagen IQ found in cooked meat, while chlorophyllin rapidly degraded IQ.
In human breast cell studies, chlorophyllin was one of the most effective compounds protecting against DNA adduct formation. Chlorophyllin inhibited adduct formation 65% at 30 micromolar concentrations, and it was also a very effective inhibitor at 15 micromoles/L, a level obtainable in vivo in the tissues of humans (Smith et al. 2001).
In vitro studies with chlorophyllin show it to be an inhibitor of the cytochrome P-450 liver enzymes (Tachino et al. 1994). All in vivo [whole animal] studies where cytochrome P-450 enzyme activity is reduced resulted in lower cancer rates and longer life span (Guengerich et al. 1991). In Stage II liver detoxification, enzymes called glutathione transferases cause glutathione to react with the carcinogens formed from cytochrome P-450 activity to produce harmless byproducts, but this process is not very efficient (Finch et al. 1997). Chlorophyllin, however, makes this conversion more efficient by lowering cytochrome P-450 enzyme activity in the first place and by reacting with carcinogens to produce harmless complexes in a similar manner to the glutathione transferases. Thus, chlorophyllin is not an inducer of glutathione transferases but mimics glutathione transferase activity.When to Take ChlorophyllinThe primary purpose of taking chlorophyllin supplements is to neutralize dietary carcinogens before they can mutate our DNA genes.
People are exposed to more carcinogens in their diet than from cigarette smoke. It has been established that overcooked meat, fried meat, meat containing nitrosamine, and aflatoxin-contaminated plants contain known carcinogens. There are, however, mutagenic agents in virtually all foods. The benefit of eating fresh fruits and vegetables is that they often provide more antimutagenic phytochemicals (such as chlorophyll) than harmful ones.
There is a considerable amount of animal research, and some human data to recommend that a 100-mg capsule of chlorophyllin should be taken with each meal or at least with meals that are known to contain a lot of carcinogens. While some people may not be able to take chlorophyllin with every meal, there would appear to be considerable benefit in taking at least a 100-mg chlorophyllin capsule with the most dangerous meal of the day, that is, the meal that contains the most carcinogens. If your dinner consists of grilled fish or barbecued steak, it might be wise to take 200-300 mg of chlorophyllin to help neutralize the heterocyclic amines and many other carcinogens formed in the cooking process. Because the main benefit of supplementing with chlorophyllin is to detoxify dietary mutagens, it should be taken with food and not wasted on an empty stomach.Chlorophyllin Side Effects/Contraindications
The only reported side effects with chlorophyllin after 40 years of experience are occasional reports of diarrhea (transient), a green color imparted to the stool, and a pale green color conferred to serum (Egner et al. 2000, 2001). When this coloring of sera was first noticed, the authors of the study noted it to be a good sign. In other words, chlorophyllin is probably acting as an antioxidant and antimutagenic agent in the bloodstream, having been shown to be an inhibitor of ascorbate-iron induced lipid peroxidation (Kamat et al. 2000). Chlorophyllin is sold as an expensive prescription drug to reduce fecal odors in nursing home patients. Some institutions mandate that the chlorophyllin drug be given to every patient to suppress unpleasant odors. When taken by healthy people, chlorophyllin has been reported to reduce fecal aroma and possibly halitosis (Ui et al. 1991; Hideshi et al. 1996).Persons who have Wilson's disease should avoid chlorophyllin supplements
. Wilson's disease is a genetic defect that causes toxic amounts of copper to accumulate in the blood because the body lacks the ability to metabolize copper. Persons with Wilson's disease should avoid any copper supplement because of the excess copper already in their bodies. Those with active cancer may also want to avoid chlorophyllin based on a current theory that copper may promote angiogenesis. Physicians who subscribe to this theory often attempt to reduce copper to extremely low levels to better enable the patient to gain control over their active cancer. Healthy people do not have this concern because most of the copper in chlorophyllin is in the bound form and is not bioavailable to the body.Choosing a Chlorophyllin Product
There are many chlorophyllin products sold on the supplement market. They can all be expected to provide benefits in reducing fecal odor and possibly halitosis (Ui et al. 1991; Hideshi et al. 1996). In order to derive the maximum antimutagenic effects of chlorophyllin, a supplement should contain standardized potencies of these specific constituents.
A 100-mg capsule of chlorophyllin should contain very little or no free copper. The copper that is naturally part of the chlorophyllin should be tightly sequestered (bound) in the chlorophyllin molecule (Meydani et al. 2002) so that it is not freely available to the body. Consumers should insist on a standardized chlorophyllin supplement that provides optimal percentages of active chlorophyll constituents and verifies that the free copper is very low. To reduce the absorption of any free copper that may be in the product, 10 mg of zinc could be taken with chlorophyllin or be included in the supplement itself.SUMMARY
The evidence presented here clearly shows that avoiding substances known to inflict gene mutations can reduce one's risk of developing cancer. Epidemiological studies document that people who expose themselves to gene-mutating toxins develop cancer far more frequently than those who follow a healthier lifestyle.
Each human cell sustains about 10,000 DNA gene mutations every day (Seo et al. 2002). If it were not for DNA repair enzymes, these mutations would quickly lead to cancer or functional cell failure. There is a limit to the cell's ability to repair these multiple DNA alterations. That is why protecting genes against mutation is so important.
Most gene mutations occur from environmental factors, the most prevalent being the food we eat (Guengerich et al. 1991; Herskind et al. 1996; Finch et al. 1997). While a healthy diet helps protect our genes, it has been established that gene mutations occur as a part of normal metabolic processes. If we live long enough, the accumulation of gene mutations can result in cancer, neurological disorders, and other degenerative diseases.
While it is possible to reduce exposure to substances that mutate genes, it is impossible to avoid them altogether. Even if one consumed the perfect diet and minimized environmental mutagen exposure, the aging process itself results in gene mutations that can lead to cancer. It, thus, becomes imperative to both detoxify dietary mutagens as well as protect one's genes against mutagenic transformation into cancer cells.
Antioxidants help to protect genes against mutation. This is one reason why humans who consume higher levels of antioxidants and other plant extracts often have lower incidences of cancer. A number of published studies show that chlorophyllin may be the most effective antimutagenic agent ever discovered.
Because the accumulation of gene mutations is the underlying cause of cancer and a host of other diseases, it appears logical to add chlorophyllin to one's supplement program. Chlorophyllin is an antioxidant that quenches a wide variety of reactive oxygen species and exhibits a multitude of anticancer effects at very low doses.
While cholorophyllin is an important nutrient to prevent excess gene mutations, there are other supplements that protect against cancer via different mechanisms.
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