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In 1931 Dr. Otto Warburg received the Nobel Prize in Physiology or Medicine for his discovery that cancer cells have a fundamentally different energy metabolism compared with healthy cells.
Many experts consider him the most important biochemist of the 20th century. Among his laboratory staff was Hans Krebs, PhD, after whom the Krebs cycle was named.
The Krebs cycle relates to oxidation-reduction pathways that occur in the mitochondria. But how does the metabolic inflexibility of cancer cells differ from healthy cells?
A cell can make energy in two ways: aerobically, in the mitochondria, or anaerobically, in the cytoplasm, the latter producing lactic acid — a toxic byproduct.
Warburg found that in the presence of oxygen cancer cells produce excessive amounts of lactic acid. This is known as the Warburg effect.
Mitochondrial energy production is far more efficient, capable of producing 18 times more energy in the form of adenosine triphosphate (ATP) than anaerobic energy production.
Warburg concluded that the primary cause of cancer is the shift of energy production from aerobic to a more primitive form of energy production, anaerobic fermentation.
He was convinced that to reverse cancer you must disrupt the energy production cycle that feeds the tumor and that restoring aerobic energy metabolism could effectively “starve” it into remission.
Although he could not conclusively prove it, he held this view until his death in 1970. One of his life goals was to discover a cure for cancer.
Sadly, as often happens in science, his theory — despite his status as a scientist — was never accepted by conventional science. That is only now changing.
The New York Times recently published a long, detailed article on the history of current cancer research, including Warburg’s theories about cancer, which are now beginning to gain broader acceptance.
Cancer is fed by sugar
An easy way to explain Warburg’s discovery is that cancer cells are driven primarily by anaerobic burning of sugar.
Without sugar most cancer cells simply lack the metabolic flexibility necessary for their survival. As noted in the New York Times article:
“It’s estimated that the Warburg effect occurs in up to 80 percent of cancers. An imaging method called positron emission tomography (PET), which has emerged as an important tool for cancer diagnosis, works on a simple principle: it detects areas in the body whose cells consume unusually large amounts of glucose.
In many cases a patient’s prognosis is worse the more glucose the tumor consumes.
Unfortunately, Warburg’s theories were quickly forgotten as scientists turned their attention to genetics.
In 1953 molecular biologists James Watson, PhD and Francis Crick, PhD discovered the DNA molecule, and ever since cancer research has focused primarily on genetics.
The gene hypothesis gained even more momentum when in 1976 Dr. Harold Varmus and Dr. Michael Bishop won the Nobel Prize for the discovery of viral oncogenes in cancer cell DNA.
Attention then turned fully to genetic mutations and the theory that cancer cells are simply distorted versions of normal cells that have begun to seize control.
The revival of Warburg
It took another 30 years for a major revision of the prevailing cancer hypothesis to occur.
In 2006 the surprising conclusion of the Cancer Genome Atlas project, which focused on identifying all mutations thought to cause cancer, was that genetic mutations are actually far less common than originally believed.
In fact they were so rare that it was literally impossible to establish a genetic origin for cancer.
Some cancer tumors even had NO mutations AT ALL!
Instead of offering the convincing evidence needed to stop cancer, the Cancer Genome Atlas revealed something that was clearly missing from the equation.
Gradually scientists began to consider whether the emergence of cancer might indeed be related to Warburg’s theory of energy metabolism. In recent years researchers realized that cancer isn’t caused by genetic defects.
Damage to the mitochondria occurs first, which then triggers genetic mutation in the nucleus. As the New York Times reports:
“There are usually many mutations in a single cancer. Limited, however, are the ways the body can make energy and support rapid growth.
Cancer cells rely on fuels in ways healthy cells do not.
Researchers leading the Warburg revival hope they will be able to slow — or even stop — tumor growth by interrupting one or several chemical reactions the cell uses to multiply, while at the same time starving cancer cells by cutting off the nutrient supply they desperately need to grow.
Even James Watson, PhD, one of the founders of molecular biology, is convinced that focusing on metabolism is a more promising path in current cancer research than gene-focused approaches…
“I never thought… that I would ever have to learn the Krebs cycle,” he said, referring to the reactions… that drive the cell itself. “Now I realize I must.”
Cancer-causing genes regulate nutrient uptake in cells
The genetic component, however, did not disappear. Scientists discovered that many genes known to promote cancer by affecting cell division — including a gene called AKT — also regulate nutrient consumption in cells.
Certain genes therefore apparently do play a role in the excessive sugar consumption of cancer cells.
“Dr. Craig Thompson, president and CEO of Sloan Kettering Cancer Center, is one of the most outspoken advocates of this renewed focus on metabolism…
His research has shown that cells need instructions from other cells to take in food, just as they need instructions from other cells to divide.
Thompson hypothesized that if he could identify mutations that cause a cell to consume more sugar than it should, it would greatly help explain how the Warburg effect and cancer begin,” the New York Times wrote.
“The protein made by AKT is part of a chain of signaling proteins that is mutated in up to 80 percent of all cancers.
Thompson says that when these proteins become very active, the cell no longer pays attention to signals from other cells to take in nutrients; instead it binges on glucose.
Thompson found that a “full Warburg effect” could be induced by simply placing an activated AKT protein into a normal cell.
When that happens, Thompson says, cells do what any single-celled organism does in the presence of food: it eats as much as possible and makes as many copies of itself as it can.”
While healthy cells have a feedback mechanism that forces them to store resources for periods of food scarcity, cancer cells lack that mechanism and keep feeding constantly.
As Dr. Chi Van Dang, director of the Abramson Cancer Center at the University of Pennsylvania, noted, cancer cells are “nutrient addicted” and “when they can’t consume enough food they begin to die.”
“Nutrient addiction explains why changes in metabolic pathways are so common and tend to increase early as a cell evolves toward cancer.”
New treatment brings hope for cancer patients
Great Korean biochemist Young Hee Ko, PhD, who early in the first decade of the 21st century collaborated with Peter Pedersen, professor of biological chemistry and oncology at Johns Hopkins University, made a remarkable discovery that brings great hope to cancer patients.
Today Ko is the CEO of KODiscovery at the Biopark of the University of Maryland, where she continues her work in cellular metabolism in cancer and neurodegenerative disease.
I am convinced Ko has the answer for a large number of incurable metastatic cancers and I predict she will eventually receive a Nobel Prize for her work.
In fact, on September 23 and 24 this year I presented with Ko at a conference on fighting cancer in Orlando.
Both of the aforementioned scientists noticed that when cancer cells produce excessive lactic acid they must create more pores, called monocarboxylate transporters, to get the lactic acid out, otherwise the cancer cell dies from within.
As mentioned earlier, lactic acid is a very toxic substance. Considering the best way to exploit this difference in the functioning of normal and cancer cells, Ko remembered a compound called 3-bromopyruvate (3BP), which she had worked with before obtaining her doctorate.
This molecule looks very similar to lactic acid but is highly reactive. She thought 3BP might be able to slip into the pore that allows lactic acid to be expelled from the cancer cell, thereby preventing the acid from getting out.
Her hunch was correct. In over 100 laboratory tests 3BP outperformed all chemotherapy drugs used for comparison.
In short, 3BP “dissolves tumors by preventing lactic acid from getting out of the cancer cell and thereby killing it from within.”
Old diabetes drugs find new use in the fight against cancer
Interestingly, metformin, a drug that lowers glucose levels in diabetics, has shown anti-cancer effects — further supporting Warburg’s theory that cancer cannot survive in a glucose-poor environment. As the article states:
“In coming years (metformin) will likely be used to treat — or at least prevent — some types of cancer.
Because metformin can affect a wide range of metabolic processes, the exact mechanism by which it achieves its anti-cancer effects remains under discussion. However, the results of many epidemiological studies are surprising.
It appears that diabetics taking metformin develop cancer at a significantly lower rate than diabetics who don’t take it — and their risk of death from the disease is substantially lower.
Late in his life Warburg became increasingly obsessed with his diet. He believed most cancers could be prevented and thought that tumors might be caused by chemicals added to food and used in agriculture by interfering with respiration. He stopped eating bread. He only ate bread baked at home.
He only drank milk that came from a particular herd of cows…
Warburg’s personal diet is hardly a model for prevention. However, the Warburg revival allowed scientists to hypothesize that dietary patterns related to our obesity epidemic and diabetes — specifically foods high in sugar, which can lead to chronically elevated insulin levels — may drive cells toward the Warburg effect and cancer.”
Although metformin appears to have some benefit for improving mitochondrial dysfunction, I am convinced there are far better options, since metformin is associated with vitamin B12 deficiency.
Berberine is a natural plant alkaloid that is much safer and works similarly. Both, however, will be woefully inadequate if one does not limit protein intake to less than 1 gram per kilogram of lean body mass and clean carbohydrates to less than 40 grams per day.
From my point of view, ignoring diet as a tool for prevention is at least unreasonable. Like Warburg, I am convinced most forms of cancer can be prevented with proper diet and nutrition, and that another important factor besides optimizing macronutrient ratios is avoiding exposure to toxic substances.
That is one reason I recommend eating organic foods, especially meat from animals that were pasture-raised or grass-fed, and animal products whenever possible.
The importance of diet for successful cancer treatment
The fundamental aspect to focus on is mitochondrial metabolic dysfunction, and that requires drastically reducing the amount of non-fiber carbohydrates in your diet and increasing the amount of high-quality fats.
You may need as much as 85 percent of your daily calories to come from healthy fats, along with a moderate amount of high-quality protein, because cancer can also be driven by excessive protein.
This is a real solution. If you don’t do it, other drugs, including 3BP, likely won’t work (I am convinced that when you’re on a ketogenic diet and add 3BP to it, you may be able to reverse almost any cancer. That is my current impression. I might be wrong and will correct if needed, but everything I’ve seen so far points in that direction.).
It’s important to remember that glucose is inherently a “dirty” fuel because it produces far more reactive oxygen species (ROS) than burning fat.
However, for your cells to burn fat they must be healthy and normal. Cancer cells lack the metabolic flexibility to burn fat, and that is why a diet high in healthy fats seems to be such an effective strategy against cancer.
When you switch from burning glucose as your main fuel to burning fat, cancer cells actually have to fight for survival because most of their mitochondria are dysfunctional and cannot use oxygen to burn fuel.
At the same time healthy cells receive their preferred fuel, which reduces oxidative damage and optimizes mitochondrial function.
The overall effect is that healthy cells begin to thrive and cancer cells are “starved” into oblivion.
For optimal health you need sufficient amounts of carbohydrates, fats and proteins. With the rise of processed foods and industrial agriculture, finding healthy choices has become more complicated.
There are healthy and unhealthy carbohydrates. The same goes for fats. Important considerations also apply to proteins, since excess protein can contribute to poor health.
Based on my summary of molecular biology, to optimize mitochondrial function it’s important to aim for:
- 75 to 85 percent of your total calorie intake from healthy fats
- 8 to 15 percent from carbohydrates, with fiber-containing carbs being twice as much as non-fiber (clean) carbs
- 7 to 10 percent of your calories from protein (very high-quality meat from grass-fed or pasture-raised animals and animal products)
Diet considerations: fats
Healthy fats should account for roughly 75 to 85 percent of your total calorie intake. The important word here is HEALTHY, because the fats consumed by most people are unhealthy.
Avoid all processed oils and bottled oils, with the exception of olive oils certified by a third party, because 80% of them are adulterated with vegetable oils.
Ideally you should consume more monounsaturated than saturated fats. Limit polyunsaturated fats (PUFAs) to a maximum of 10 percent.
At higher levels you increase the concentration of PUFAs in the inner mitochondrial membrane, making it much more susceptible to oxidative damage by reactive oxygen species produced there.
And finally, do not exceed 5 percent of your calories as omega-6 fatty acids. Your total intake of omega-6 and omega-3 fatty acids should not exceed 10 percent, and the ratio of omega-6 to omega-3 fatty acids should be less than 2.
Sources of healthy fats include:
- Olives and olive oil
- Coconuts and coconut oil
- Butter made from raw organic milk and cocoa butter
- Raw nuts, e.g., organic eggs, yolks, avocado, macadamia and pecans, and seeds like black sesame, cumin, pumpkin and hemp
- Organic eggs, yolks
- Avocado
- Meat from pasture-raised animals
- Pork lard, tallow and ghee
- Animal-sourced omega-3 fatty acids such as Antarctic krill oil
Diet considerations: carbohydrates
Regarding carbohydrates, there are fiber-rich clean carbs (mainly vegetables) and non-fiber carbs (sugar and processed grains).
Ideally you need twice as many fiber-containing carbs as non-fiber (clean) carbs.
So if your total carbohydrate intake constitutes 10 percent of your daily calories, at least half of that should be fiber-containing.
Fiber is not digested and does not break down into sugar, which means it does not adversely affect your insulin, leptin and regulatory protein kinase (mTOR).
Fiber also has many other health benefits, including weight maintenance and reducing the risk of some cancers. As noted in the New York Times article, your insulin level plays a very important role in cancer.
“The insulin hypothesis can be traced to the work of Dr. Lewis Cantley. In the 1980s Cantley discovered how insulin, which is secreted by the pancreas and instructs cells to take in glucose, affects what happens inside the cell.
Cantley now refers to insulin and the closely related hormone IGF-1 (insulin-like growth factor 1) as the “champions” of metabolic triggers related to cancer.
He says he is beginning to see evidence that in some cases “it’s actually insulin itself that triggers the tumor.” One way to think about the Warburg effect, according to Cantley, is how insulin or IGF-1 signals a “corrupted pathway — the cells behave as if insulin is constantly instructing them to take in glucose and grow.”
Cantley, who largely avoids sugar, says that … the effects of a sugar-rich diet on colorectal cancer, breast cancer and other types of cancer “look very impressive” and “pretty frightening.”
The most important figure you need to watch is your clean carbs, which should be as low as possible.
Clean carbs are calculated by adding up total carbs in grams and subtracting the fiber in the food. The resulting number represents your clean carbs.
For optimal health and disease prevention I recommend keeping clean carbs under 40 or 50 grams per day.
The only way to know how much fiber and clean carbs you consume is to keep a record of what you eat.
Diet considerations: protein
Finally, there is an upper limit to the amount of protein your body can actually utilize, and when you eat more than your body needs for maintenance and growth, you will simply be supplying extra fuel to disease processes.
The ideal protein intake is about half a gram of protein per half kilogram of lean body weight.
For most people this equals about 40 to 60 grams per day, but many Americans typically exceed this amount by three to five times, which can — like excessive sugar — increase your risk of cancer.
Significant amounts of protein are found in meat, fish, eggs, dairy products, legumes, nuts and seeds.
Some vegetables also contain large amounts of protein, for example broccoli. To estimate your protein needs first determine your lean body mass.
Subtract your body fat percentage from 100. If you have, for example, 20 percent body fat, then you have 80 percent lean body mass.
Multiply this percentage (in this case the number 0.8) by your current weight and you get your lean body weight in kilograms.
Then track everything you eat for a few days and calculate the daily amount of protein from all sources you consumed. Again, your goal is to consume half a gram of protein per half kilogram of lean body weight.
