Theories on the causes of cancer

There is a flood of modern chronic diseases that were little known 100 years ago. Many of these diseases have no known cause and are nothing more than a group of symptoms, lumped together, and given a name.  Diseases such as Parkinson's, ALS or Lupus with no known cause are called idiopathic. The primary focus of treatments for idiopathic diseases is to manage symptoms. One of the main principles of holistic health is to treat the root cause of disease. Treating symptoms is like trying to put out a fire by addressing only the smoke. There is little chance of success. 

The dominant theory of cancer for the better part of the 20th Century is called the somatic mutation theory of cancer, which states that cancer arises from sequential lesions to DNAs or mutations to DNA. All today's leading cancer biologists subscribe to the somatic theory. If that theory is wrong, then the focus of treatment is wrong too. Despite the billions of dollars spent in medical research, the treatment of some cancers has remained intractable. There is a good possibility that failure to develop effective treatments is the result of a misunderstanding of the root cause.

Without understanding the root cause of any disease, finding a cure is like trying to hit a target blindfolded. We present several theories of cancer below with some focus on the metabolic theory, which contrasts profoundly from the somatic theory. The metabolic theory contends that cancer is a metabolic disease, precipitated by damage to mitochondria. Mitochondria are the organs within a cell that burn fuel and create energy.

The metabolic theory contends that when a cell loses the ability to respirate or generate energy aerobically (with oxygen) through the Krebs cycle, it reverts to anaerobic energy generation or fermentation. Mitochondrial dysfunction is now indicated in many chronic diseases. This understanding may lead to many breakthroughs in medicine. The mitochondrial hypothesis may not hold true for all types of cancer, but if it is true for some cancers the implications are huge because there are many ways of improving mitochondrial function including changes to diet and lifestyle, as well as drugs and supplements that could prove extremely effective when combined properly.

The below theories are presented with the hope that the reader may glean insights and understanding that inspires action and the type of commitment to lifestyle changes, such as eliminating sugar from the diet, which is crucial to healing. While we do not endorse any of the below theories as "The Truth", we believe a thorough reading of the below information can improve the chances of survival.  

The Warburg theory of cancer postulates that the driver of tumorigenesis is insufficient cellular respiration caused by an insult to mitochondria. Mitochondria are little organs within a cell that function to burn fuel and produce energy, which is normally done through respiration (the Krebs cycle), not fermentation. In oncology, the Warburg Effect describes the observation that cancer cells exhibit glucose fermentation even when enough oxygen is present to properly respire. In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment. This is a very inefficient method of creating energy.

Warburg articulated his hypothesis in a paper entitled The Prime Cause and Prevention of Cancer which he presented in a lecture at the meeting of the Nobel-Laureates on June 30, 1966. In this speech, Warburg presented additional evidence supporting his theory that the elevated anaerobiosis seen in cancer cells was a consequence of damaged or insufficient respiration. Put in his own words, "the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar."

The body often kills damaged cells by apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells where the mitochondria are shut down. The reactivation of healthy mitochondrial function in cancer cells restarts their apoptosis program

Warburg's theory fell out of favor in modern times but has recently been experiencing a renaissance. 

 Dr Mercola interviews Dr Thomas Seyfried on the Warburg effect here. 

• All cancer cells, regardless of tissue origin, use fermentation energy for growth. They ferment lactic acid from glucose in the cytoplasm and ferment succinic acid from glutamine in the mitochondria
• Even when tumor cells appear to be making ATP and taking in oxygen, suggestive of normal respiration, their mitochondria are abnormal; hence, mitochondrial dysfunction is at the root of most cancers
• The true origin of cancer is damage to the respiratory function of your mitochondria, triggering compensatory fermentation, which is run by oncogenes. Oncogenes facilitate the entry of glucose and glutamine into the cell to replace oxidative phosphorylation
• Metastatic cancer cells are hybrid “rogue” macrophage cells — a mix of an immune system cell and a dysregulated stem cell with macrophage characteristics, which allows it to rapidly replicate and spread
• Press-pulse cancer treatment involves restricting the fermentable fuels — glucose and glutamine — in a cyclical fashion to avoid causing damage to the immune system
• A biopsy may not always be a good option as this procedure may actually cause cancer to spread or turn a potentially benign situation into a malignant one

"Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one primary cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar. All normal body cells meet their energy needs by respiration of oxygen, whereas cancer cells meet their energy needs in great part by fermentation. All normal body cells are thus obligate aerobes, whereas all cancer cells are partial anaerobes."

Poor oxygenation comes from a buildup of carcinogens and other toxins within and around cells, which blocks and then damages the cellular oxygen respiration mechanism. Clumping up of red blood cells slows down the bloodstream, and restricts flow into capillaries. This also causes poor oxygenation. Even lack of the proper building blocks for cell walls, Omega 3 and 6 essential fatty acids, restricts oxygen exchange.

Warburg and other scientists found that the respiratory enzymes in cells, which make energy aerobically using oxygen, die when cellular oxygen levels drop below 65%.

When the mitochondrial enzymes get destroyed, their host cell can no longer produce all its energy using oxygen. So, if the cell is to live, it must, to some degree, ferment sugar to produce energy. For a short period of time, like when running a race, this anaerobic fermentation of sugar is okay. Your legs build up lactic acid from this fermentation process and burn, and you stop running. Then your cells recover and produce energy using oxygen. 

The problem occurs when your cells cannot produce energy using oxygen because of damage to the respiratory enzymes. Then they must produce energy primarily by fermentation most of the time. This is what can cause a cell to turn cancerous. According to Warburg, cells that produce energy by fermenting sugars may turn cancerous. Warburg's contention is this...

The cells that cannot produce energy aerobically, cannot produce enough energy to maintain their ability to function properly. So they lose their ability to do whatever they need to do in the body.

Fermentation allows these cells to survive, but they can no longer perform any functions in the body or communicate effectively with the body. Consequently, these cells can only multiply and grow. And may become cancerous. Or perhaps it would be more accurate to say, they degrade into cancer cells that no longer serve your body, but live to survive.

Decades ago, two researchers at the National Cancer Institute, Dean Burn and Mark Woods, (Dean translated some of Warburg's speeches) conducted a series of experiments where they measured the fermentation rate of cancers that grew at different speeds. What they found supported Dr. Warburg's theory.

The cancers with the highest growth rates had the highest fermentation rates. The slower a cancer grew, the less it used fermentation to produce energy.

Naturally Warburg's contention about oxygen and cancer was challenged and tested by other scientists.

Some researchers claimed his theory was not valid after they had measured a particularly slow-growing cancer, and found no fermentation at all. And if cancer could grow with no fermentation, then fermentation, or lack of oxygen respiration, was not the cause of cancer. Dean Burn and Mark Woods checked those results.

Using more sophisticated equipment, they determined that the equipment these researchers used to measure fermentation levels was not accurate enough to detect fermentation at low levels. Their testing, using newer and more accurate equipment, showed that even in those very slow-growing cancer cells, fermentation was still taking place, at very low levels.

Pietro Gullino, also at the National Cancer Institute, devised a test which showed that this slow-growing cancer always produced fermentation lactic acid. Silvio Fiala, a biochemist from the University of Southern California, also confirmed that this slow-growing cancer produced lactic acid and that its oxygen respiration was reduced.

Further research into Warburg's theory showed that when oxygen levels were turned down, cells began to produce energy anaerobically. They ultimately became cancerous when levels went low enough. It took a reduction of 35% in oxygen levels for this to happen.

J. B. Kizer, a biochemist, and physicist at Gungnir Research in Portsmith, Ohio explains, "Since Warburg's discovery, this difference in respiration has remained the most fundamental (and some say, only) physiological difference consistently found between normal and cancer cells. Using cell culture studies, I decided to examine the differential responses of normal and cancer cells to changes in the oxygen environment.

"The results that I found were rather remarkable. I found that... "High 02 tensions were lethal to cancer tissue, 95 percent being very toxic, whereas in general, normal tissues were not harmed by high oxygen tensions. Indeed, some normal tissues were found to require high 02 tensions. It does seem to demonstrate the possibility that if the 02 tensions in cancer tissues can be elevated, then the cancer tissue may be able to be killed selectively, as it seems that the cancer cells are incapable of handling the 02 in a high 02 environment."

Low oxygen levels in cells may be a fundamental cause of cancer. There are several reasons cells become poorly oxygenated. An overload of toxins clogging up the cells, poor quality cell walls that don't allow nutrients into the cells, the lack of nutrients needed for respiration, poor circulation and perhaps even low levels of oxygen in the air we breathe.

Cancer cells produce excess lactic acid as they ferment energy. Lactic acid is toxic, and tends to prevent the transport of oxygen into neighboring normal cells. Over time as these cells replicate, cancer may spread if not destroyed by the immune system.

There is more to this picture than Otto Warburg understood. It turns out that approximately 85% of cancer cells use this glucose fermentation. Other cancer cells do burn oxygen for fuel. And these cells have a very interesting interaction with the cells using glucose fermentation.

Over the last few years researchers have identified a more sophisticated and accurate description of cancer cell metabolism. It is true that the majority of cells fit into this model of burning glucose to produce energy.

The Latest Research Shows...

that many cancer cells could be burning oxygen for energy, which is vastly more efficient at producing energy, but they aren't. Researchers pieced together the key to this puzzle. It is very interesting.

Cancer cells don't need a lot of energy to function, and there is plenty of energy sources available to them. What they do need is a large supply of nutrients necessary to grow and proliferate. Burning oxygen produces a lot of energy, and not much in the way of nutrients to fuel growth. Burning glucose produces little energy, but a lot of nutrients to fuel growth and proliferation.

So it may be that the fastest growing cancer cells utilize glucose fermentation to produce energy because it produces so much more of what they need, nutrients that enable them to grow fast and proliferate more rapidly.

This makes sense. Decades ago, Dean Burns and Mark Woods found that the fastest growing cancer cells had the most glucose fermentation, and the slowest growing cancer cells had the least amount of glucose fermentation.

In addition, over the past few years researchers have noted that some cancer cells burn lactase (lactic acid) and even fat ketones as additional energy sources. Lactic acid is readily available in tumors as most of the cancer cells are burning glucose for energy and producing lactic acid as a byproduct of that process.

They pump out the lactic acid to get rid of it so that it doesn't overwhelm and destroy them. Other cancer cells in the tumor that are producing energy primarily with oxygen and less with glucose, uptake this lactase, according to researchers, and metabolize it for energy. By doing so, they use less glucose which enables glucose dependent cancer cells to have more to consume.

In order to create more nutrients as a byproduct of cell metabolism, cancer cells also metabolize glutamine. It is also not an efficient source of energy to run the cell, but it supplies valuable nutrients needed by the cancer cells to grow and proliferate.

Shutting Down Cancer Cell Metabolism

Clearly, the key to fighting cancer is shut down as much of the metabolic processes as possible in cancer cells. Stopping both their production of energy, and the more limiting factor, their processing and production of nutrients needed to support the growth of cancer cells and their rapid replication.

No one really knows why a cell turns cancerous when it has low oxygen levels. Why doesn't it just run out of gas, so to speak, when it is unable to produce energy and either putter along doing what little it can, or tell itself to die as cells normally do as they age or become damaged. Why does it turn cancerous instead of this benign action?

Even if a cell has a poorly functioning metabolism resulting in energy being produced through burning sugar rather than oxygen, what makes it turn cancerous? A cancer cell is no longer acting together with the rest of the cells in the body in their mission to keep the body as healthy as possible. It has become "non-self" –– not communicating with the rest of the cells in the body. Not trying to help the body survive. This allows it to develop into a cancerous growth that is harmful to the body.

There is a cell survival mechanism that enables this to happen, that can set up the development of cancer in some circumstances. Some day researchers may be able to detail what those circumstances are precisely. Undoubtedly they are a combination of low oxygen, an inability to metabolize oxygen because of damage to the mitochondria, or other damaged caused by pathogens and toxins. These may lead to cancer though, only because of this protective mechanism for cells.

This mechanism is called the Cell Danger Response. When a cell is injured, damaged by a pathogen such as a virus, damaged by toxins whether they be environmental toxins or toxins from candida, when a cell is ill from lack of oxygen or its inability to metabolize oxygen, the Cell Danger Response is activated for that cell. This response shuts off its communication with other cells so that it can take a break from the work it does, and heal itself.

This is something like a worker at a factory being injured or falling ill and being sent to the hospital to get well. Once that worker heals, then back to work he or she goes. The cell with the activated Cell Danger Response isn't sent to the hospital to recover. It stays where it is and nutrients are brought to it to heal. Sometimes however, something goes wrong and the cell does not heal and it does not die. And it turns cancerous because it is not in communication with the rest of the body because of the Cell Danger Response. So it no longer co-operates with the rest of the cells in your body for the common good. Instead it is doing everything it can to insure its own survival.

And so cancer develops.

If the Cell Danger Response had not been activated, there would have been no cancer. The cell would still feel it is part of the body and would tell itself to die, as all cells do, when they are no longer useful. However, the Cell Danger Response is necessary for the overall health of the body. We can't be without it.